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  • 1.
    Aarnio, Riina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Isacson, Isabella
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Sanner, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Gustavsson, Inger M.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Comparison of vaginal self-sampling and cervical sampling by medical professionals for the detection of HPV and CIN2+: a randomized study2021Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 148, nr 12, s. 3051-3059Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Primary screening with human papillomavirus (HPV) test is more effective in reducing cervical cancer incidence than cytology and it also offers the opportunity to self-sample. We conducted a randomized study to compare vaginal self-sampling with cervical sampling by medical professionals for HPV testing concerning prevalence of HPV and detection of cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+) in primary screening. In total, 11 951 women aged 30-60 years were randomized into two groups, 5961 for self-sampling (SS arm) and 5990 for sampling by medical professionals (SMP arm). Sampling was performed with a RoversViba-brush in the SS arm and a cytobrush in the SMP arm. All samples were applied to an indicating FTA elute card and analyzed for HPV using a clinically validated real-time PCR test (hpVIR). All HPV-positive women performed repeated sampling about 6 months later using the same procedure as used initially. All HPV-positive women in the second sampling were referred to colposcopy. The prevalence of HPV in the first test did not differ between the SS arm (6.8%, 167/2466) and the SMP arm (7.8%, 118/1519) (P = .255). The prevalence of CIN2+ per 1000 screened women was 17 (43/2466 × 1000) (95%CI 13-24) in the SS arm and 21 (32/1519 × 1000) (95%CI 15-30) in the SMP arm. For CIN3+, the prevalence per 1000 screened women was 14 (35/2466 × 1000) (95%CI 10-20) in the SS arm and 15 (23/1519 × 1000) (95%CI 10-23) in the SMP arm. In conclusion, self-sampling and sampling by medical professionals showed the same prevalence of HPV and detection rate of CIN2+ and CIN3+ in histology.

    Fulltekst (pdf)
    fulltext
  • 2.
    Aarnio, Riina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Wikström, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Gustavsson, Inger M.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Diagnostic excision of the cervix in women over 40 years with human papilloma virus persistency and normal cytology2019Inngår i: European journal of obstetrics & gynecology and reproductive biology: X, ISSN 2590-1613, Vol. 3, artikkel-id 100042Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Persistent infection with human papillomavirus (HPV) is recognized as the main risk factor of cervical cancer. Investigation via cytology and colposcopy have lower sensitivity than HPV testing in the diagnosis of high-grade cervical intraepithelial neoplasia (CIN2+). Despite normal cytology and colposcopy findings women with persistent HPV infection have an increased risk of CIN2+. The aim of the study was to evaluate the proportion of histologically confirmed CIN2+ in women with persistent HPV infection and normal Pap smears.

    Study design: From April 2013 until March 2016 we prospectively recruited 91 women over 40 years with persistent HPV infection without any abnormalities in cytology. Of these, 40 women attended a gynecological examination including an HPV test, Pap smear, endocervical cytology, colposcopy with biopsies and diagnostic loop electrosurgical excision procedure (LEEP). Biopsy and LEEP samples were subjected to histological examination.

    Results: CIN2+ was verified by histological examination of the LEEP sample in 6/40 (15%) of the women. All the cytological samples were normal and none of the biopsies confirmed CIN2+. Only 19/40 women still had a persistent HPV infection at the study visit. None of the 21/40 women who had cleared their HPV infection at the study visit had CIN2+ in histology of the LEEP sample.

    Conclusions: A persistent HPV infection needs to be monitored despite normal Pap smears, since 6/40 (15%) women older than 40 years, was revealed to have an undiagnosed CIN2+ when LEEP was performed. Counseling women regarding the risk of cervical cancer and the expected effect of an eventual LEEP can help them to make an optimal informed choice.

    Fulltekst (pdf)
    fulltext
  • 3.
    Aarnio, Riina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Östensson, Ellinor
    Karolinska Institutet.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Gustavsson, Inger M.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study2020Inngår i: BMC Cancer, E-ISSN 1471-2407, Vol. 20, nr 1, artikkel-id 645Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background

    Human papillomavirus (HPV) testing is recommended in primary cervical screening to improve cancer prevention. An advantage of HPV testing is that it can be performed on self-samples, which could increase population coverage and result in a more efficient strategy to identify women at risk of developing cervical cancer. Our objective was to assess whether repeated self-sampling for HPV testing is cost-effective in comparison with Pap smear cytology for detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) in increasing participation rate in primary cervical screening.

    Methods

    A cost-effectiveness analysis (CEA) was performed on data from a previously published randomized clinical study including 36 390 women aged 30–49 years. Participants were randomized either to perform repeated self-sampling of vaginal fluid for HPV testing (n = 17 997, HPV self-sampling arm) or to midwife-collected Pap smears for cytological analysis (n = 18 393, Pap smear arm).

    Results

    Self-sampling for HPV testing led to 1633 more screened women and 107 more histologically diagnosed CIN2+ at a lower cost vs. midwife-collected Pap smears (€ 228 642 vs. € 781 139). 

    Conclusions

    This study projected that repeated self-sampling for HPV testing increased participation and detection of CIN2+ at a lower cost than midwife-collected Pap smears in primary cervical screening. Offering women a home-based self-sampling may therefore be a more cost-effective alternative than clinic-based screening.

     

  • 4.
    Aasebo, Kristine
    et al.
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Dragomir, Anca
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.
    Sundström, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.
    Mezheyeuski, Artur
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Edqvist, Per-Henrik D
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Eide, Geir Egil
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Lifestyle Epidemiol Grp, Bergen, Norway;Haukeland Hosp, Clin Res Ctr, Bergen, Norway.
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Pfeiffer, Per
    Odense Univ Hosp, Dept Oncol, Odense, Denmark.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sorbye, Halfdan
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Oncol, Bergen, Norway.
    CDX2: A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup2020Inngår i: Frontiers in Oncology, E-ISSN 2234-943X, Vol. 10, artikkel-id 8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Survival of metastatic colorectal cancer (mCRC) patients has improved, but mainly for trial patients. New predictive and prognostic biomarkers validated in the general mCRC population are needed. Caudal-type homeobox 2 (CDX2) is an intestine-specific transcription factor with potential prognostic and predictive effect, but the importance in mCRC has not been fully investigated. Methods: Immunohistochemistry analysis of CDX2 was performed in a Scandinavian population-based cohort of mCRC (n = 796). Frequency, clinical and tumor characteristics, response rate, progression-free survival, and overall survival (OS) were estimated. Results: Loss of CDX2 expression was found in 87 (19%) of 452 stained cases, in 53% if BRAF mutated (BRAFmut) and in 9% if KRAS mutated (KRASmut). CDX2 loss was associated with microsatellite instability, BRAFmut, and poor differentiation and inversely associated with KRASmut. Patients with CDX2 loss received less first-line (53 vs. 64%, p = 0.050) and second-line (23 vs. 39%, p = 0.006) chemotherapy and secondary surgery (1 vs. 9%, p = 0.019). Median progression-free survival and OS for patients given first-line combination chemotherapy was 4 and 10 months if CDX2 loss vs. 9 and 24 months if CDX2 expressed (p = 0.001, p < 0.001). Immediate progression on first-line combination chemotherapy was seen in 35% of patients with CDX2 loss vs. 10% if CDX2 expressed (p = 0.003). Median OS in patients with BRAFmut or KRASmut and CDX2 expressed in tumor (both 21 months) was comparable to wild-type patients (27 months). However, if CDX2 loss, median OS was only 8 and 11 months in BRAFmut and KRASmut cases, respectively, and 10 months in double wild-type patients. In multivariate analysis, CDX2 loss (hazard ratio: 1.50, p = 0.027) and BRAFmut (hazard ratio: 1.62, p = 0.012) were independent poor prognostic markers for OS. Conclusion: In a population-based cohort of mCRC patients, CDX2 loss is an independent poor prognostic marker. Expression of CDX2 defines a new subgroup of BRAFmut cases with a much better prognosis. Loss of CDX2 defines a small group of KRASmut cases with a worse prognosis. Patients with CDX2 loss receive less palliative chemotherapy with less benefit and rarely reach secondary surgery.

    Fulltekst (pdf)
    FULLTEXT01
  • 5.
    Aasebö, Kristine Ö.
    et al.
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Dragomir, Anca
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Sundström, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Mezheyeuski, Artur
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Edqvist, Per-Henrik D
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Eide, Geir Egil
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Lifestyle Epidemiol Grp, Bergen, Norway;Haukeland Hosp, Ctr Clin Res, Bergen, Norway.
    Pontén, Fredrik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Pfeiffer, Per
    Odense Univ Hosp, Dept Oncol, Odense, Denmark.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Sorbye, Halfdan
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Oncol, Bergen, Norway.
    Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: A population-based cohort of metastatic colorectal cancer patients2019Inngår i: Cancer Medicine, E-ISSN 2045-7634, Vol. 8, nr 7, s. 3623-3635Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Immunotherapy for patients with microsatellite-instable (MSI-H) tumors or BRAF-inhibitors combination treatment for BRAF-mutated (mutBRAF) tumors in metastatic colorectal cancer (mCRC) is promising, but the frequency of these molecular changes in trial patients are low. Unselected population-based studies of these molecular changes are warranted.

    Methods: A population-based cohort of 798 mCRC patients in Scandinavia was studied. Patient and molecular tumor characteristics, overall survival (OS) and progression-free survival (PFS) were estimated.

    Results: Here, 40/583 (7%) tumor samples were MSI-H and 120/591 (20%) were mutBRAF; 87% of MSI-H tumors were mutBRAF (non-Lynch). Elderly (>75 years) had more often MSI-H (10% vs 6%) and MSI-H/mutBRAF (9% vs 4%) tumors. Response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first-line chemotherapy was all significantly lower in patients with MSI-H compared to patients with microsatellite stable tumors. MSI-H and mutBRAF were both independent poor prognostic predictors for OS (P = 0.049, P < 0.001) and PFS (P = 0.045, P = 0.005) after first-line chemotherapy. Patients with MSI-H tumors received less second-line chemotherapy (15% vs 37%, P = 0.005).

    Conclusions: In unselected mCRC patients, MSI-H and mutBRAF cases were more common than previously reported. Patients with MSI-H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third-line immunotherapy trial patients as they were older and most had mutBRAF tumor (non-Lynch).

    Fulltekst (pdf)
    FULLTEXT01
  • 6. Aasebø, Kristine
    et al.
    Bruun, Jarle
    Bergsland, Christian H
    Nunes, Luís
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Eide, Geir Egil
    Pfeiffer, Per
    Dahl, Olav
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lothe, Ragnhild A
    Sorbye, Halfdan
    Prognostic role of tumour-infiltrating lymphocytes and macrophages in relation to MSI, CDX2 and BRAF status: a population-based study of metastatic colorectal cancer patients2022Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 126, nr 1, s. 48-56Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Tumour-infiltrating CD3, CD8 lymphocytes and CD68 macrophages are associated with favourable prognosis in localised colorectal cancer, but the effect in metastatic colorectal cancer (mCRC) is not established.

    METHODS: A Scandinavian population-based cohort of non-resectable mCRC patients was studied. Tissue microarrays (n = 460) were stained with CD3, CD8 and CD68 using fluorescence-based multiplex immunohistochemistry. Associations with clinicopathological variables, overall survival (OS) and progression-free survival were estimated.

    RESULTS: Two-thirds of microsatellite instable (MSI) and one-fourth of microsatellite stable (MSS) tumours displayed the highest quartile density of CD8. For CD3 high vs low cases, median OS was 20 vs 16 months (HR: 0.76, 95% CI: 0.59, 0.76, p = 0.025) with 3-year OS of 27 vs 13%. For CD68 high vs low cases, median OS was 23 vs 15 months (HR: 0.69, 95% CI: 0.54, 0.88, p = 0.003) with 3-year OS of 28 vs 12%. MSI, BRAF mutation and CDX2 loss were negative prognostic markers independent of tumour immune infiltration.

    CONCLUSIONS: In mCRC, high lymphocyte infiltration was found in proportions of MSI and MSS tumours-potential subgroups of immunotherapy response. Tumour-infiltrating CD3 lymphocytes and CD68 macrophages were associated with median and long-term survival. MSI was a significant negative prognostic marker despite high immunogenicity.

  • 7.
    Abadpour, Shadab
    et al.
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Göpel, Sven O.
    AstraZeneca R&D Gothenburg, Dept CVMD Biosci, Gothenburg, Sweden..
    Schive, Simen W.
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Foss, Aksel
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Scholz, Hanne
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Glial cell-line derived neurotrophic factor protects human islets from nutrient deprivation and endoplasmic reticulum stress induced apoptosis2017Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 7, artikkel-id 1575Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    One of the key limitations to successful human islet transplantation is loss of islets due to stress responses pre- and post-transplantation. Nutrient deprivation and ER stress have been identified as important mechanisms leading to apoptosis. Glial Cell-line Derived Neurotrophic Factor (GDNF) has recently been found to promote islet survival after isolation. However, whether GDNF could rescue human islets from nutrient deprivation and ER stress-mediated apoptosis is unknown. Herein, by mimicking those conditions in vitro, we have shown that GDNF significantly improved glucose stimulated insulin secretion, reduced apoptosis and proinsulin: insulin ratio in nutrient deprived human islets. Furthermore, GDNF alleviated thapsigargin-induced ER stress evidenced by reduced expressions of IRE1 alpha and BiP and consequently apoptosis. Importantly, this was associated with an increase in phosphorylation of PI3K/AKT and GSK3B signaling pathway. Transplantation of ER stressed human islets pre- treated with GDNF under kidney capsule of diabetic mice resulted in reduced expressions of IRE1 alpha and BiP in human islet grafts with improved grafts function shown by higher levels of human C-peptide post-transplantation. We suggest that GDNF has protective and anti-apoptotic effects on nutrient deprived and ER stress activated human islets and could play a significant role in rescuing human islets from stress responses.

    Fulltekst (pdf)
    fulltext
  • 8.
    Abadpour, Shadab
    et al.
    Oslo Univ Hosp, Dept Transplant Med, Sognsvannsveien 20, Oslo 0027, Norway.;Oslo Univ Hosp, Inst Surg Res, Sognsvannsveien 20, Oslo 0027, Norway.;Univ Oslo, Inst Basic Med Sci, Ctr Excellence, Hybrid Technol Hub, Oslo, Norway..
    Tyrberg, Bjorn
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Schive, Simen W.
    Oslo Univ Hosp, Dept Transplant Med, Sognsvannsveien 20, Oslo 0027, Norway.;Oslo Univ Hosp, Inst Surg Res, Sognsvannsveien 20, Oslo 0027, Norway..
    Huldt, Charlotte Wennberg
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Gennemark, Peter
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden.;Univ Linköping, Dept Biomed Engn, Linköping, Sweden..
    Ryberg, Erik
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Ryden-Bergsten, Tina
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Smith, David M.
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden.;AstraZeneca, BioPharmaceut R&D, Discovery Sci, Hit Discovery, Cambridge, England..
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Skrtic, Stanko
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden..
    Scholz, Hanne
    Oslo Univ Hosp, Dept Transplant Med, Sognsvannsveien 20, Oslo 0027, Norway.;Oslo Univ Hosp, Inst Surg Res, Sognsvannsveien 20, Oslo 0027, Norway.;Univ Oslo, Inst Basic Med Sci, Ctr Excellence, Hybrid Technol Hub, Oslo, Norway..
    Winzell, Maria Sorhede
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Inhibition of the prostaglandin D2-GPR44/DP2 axis improves human islet survival and function2020Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 63, nr 7, s. 1355-1367Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims/hypothesis Inflammatory signals and increased prostaglandin synthesis play a role during the development of diabetes. The prostaglandin D-2 (PGD(2)) receptor, GPR44/DP2, is highly expressed in human islets and activation of the pathway results in impaired insulin secretion. The role of GPR44 activation on islet function and survival rate during chronic hyperglycaemic conditions is not known. In this study, we investigate GPR44 inhibition by using a selective GPR44 antagonist (AZ8154) in human islets both in vitro and in vivo in diabetic mice transplanted with human islets. Methods Human islets were exposed to PGD(2) or proinflammatory cytokines in vitro to investigate the effect of GPR44 inhibition on islet survival rate. In addition, the molecular mechanisms of GPR44 inhibition were investigated in human islets exposed to high concentrations of glucose (HG) and to IL-1 beta. For the in vivo part of the study, human islets were transplanted under the kidney capsule of immunodeficient diabetic mice and treated with 6, 60 or 100 mg/kg per day of a GPR44 antagonist starting from the transplantation day until day 4 (short-term study) or day 17 (long-term study) post transplantation. IVGTT was performed on mice at day 10 and day 15 post transplantation. After termination of the study, metabolic variables, circulating human proinflammatory cytokines, and hepatocyte growth factor (HGF) were analysed in the grafted human islets. Results PGD(2) or proinflammatory cytokines induced apoptosis in human islets whereas GPR44 inhibition reversed this effect. GPR44 inhibition antagonised the reduction in glucose-stimulated insulin secretion induced by HG and IL-1 beta in human islets. This was accompanied by activation of the Akt-glycogen synthase kinase 3 beta signalling pathway together with phosphorylation and inactivation of forkhead box O-1and upregulation of pancreatic and duodenal homeobox-1 and HGF. Administration of the GPR44 antagonist for up to 17 days to diabetic mice transplanted with a marginal number of human islets resulted in reduced fasting blood glucose and lower glucose excursions during IVGTT. Improved glucose regulation was supported by increased human C-peptide levels compared with the vehicle group at day 4 and throughout the treatment period. GPR44 inhibition reduced plasma levels of TNF-alpha and growth-regulated oncogene-alpha/chemokine (C-X-C motif) ligand 1 and increased the levels of HGF in human islets. Conclusions/interpretation Inhibition of GPR44 in human islets has the potential to improve islet function and survival rate under inflammatory and hyperglycaemic stress. This may have implications for better survival rate of islets following transplantation.

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  • 9.
    Abalde, Samuel
    et al.
    Swedish Museum Nat Hist, Dept Zool, Stockholm, Sweden..
    Tellgren-Roth, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Heintz, Julia
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Vinnere Pettersson, Olga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jondelius, Ulf
    Swedish Museum Nat Hist, Dept Zool, Stockholm, Sweden.;Stockholm Univ, Dept Zool, Stockholm, Sweden..
    The draft genome of the microscopic Nemertoderma westbladi sheds light on the evolution of Acoelomorpha genomes2023Inngår i: Frontiers in Genetics, E-ISSN 1664-8021, Vol. 14, artikkel-id 1244493Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Xenacoelomorpha is a marine clade of microscopic worms that is an important model system for understanding the evolution of key bilaterian novelties, such as the excretory system. Nevertheless, Xenacoelomorpha genomics has been restricted to a few species that either can be cultured in the lab or are centimetres long. Thus far, no genomes are available for Nemertodermatida, one of the group’s main clades and whose origin has been dated more than 400 million years ago.

    Methods: DNA was extracted from a single specimen and sequenced with HiFi following the PacBio Ultra-Low DNA Input protocol. After genome assembly, decontamination, and annotation, the genome quality was benchmarked using two acoel genomes and one Illumina genome as reference. The gene content of three cnidarians, three acoelomorphs, four deuterostomes, and eight protostomes was clustered in orthogroups to make inferences of gene content evolution. Finally, we focused on the genes related to the ultrafiltration excretory system to compare patterns of presence/absence and gene architecture among these clades.

    Results: We present the first nemertodermatid genome sequenced from a single specimen of Nemertoderma westbladi. Although genome contiguity remains challenging (N50: 60 kb), it is very complete (BUSCO: 80.2%, Metazoa; 88.6%, Eukaryota) and the quality of the annotation allows fine-detail analyses of genome evolution. Acoelomorph genomes seem to be relatively conserved in terms of the percentage of repeats, number of genes, number of exons per gene and intron size. In addition, a high fraction of genes present in both protostomes and deuterostomes are absent in Acoelomorpha. Interestingly, we show that all genes related to the excretory system are present in Xenacoelomorpha except Osr, a key element in the development of these organs and whose acquisition seems to be interconnected with the origin of the specialised excretory system.

    Conclusion: Overall, these analyses highlight the potential of the Ultra-Low Input DNA protocol and HiFi to generate high-quality genomes from single animals, even for relatively large genomes, making it a feasible option for sequencing challenging taxa, which will be an exciting resource for comparative genomics analyses.

    Fulltekst (pdf)
    FULLTEXT01
  • 10.
    Abalo, Xesus
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Boije: Zebrafiskens neuronala nätverk. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lagman, David
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Univ Bergen, Sars Int Ctr Marine Mol Biol, Bergen, Norway.
    Heras, Gabriel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    del Pozo, Ana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Boije: Zebrafiskens neuronala nätverk. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Eggert, Joel
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Emory Univ, Dept Med, Atlanta, GA 30322 USA.
    Larhammar, Dan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Larhammar: Farmakologi.
    Circadian regulation of phosphodiesterase 6 genes in zebrafish differs between cones and rods: Implications for photopic and scotopic vision2020Inngår i: Vision Research, ISSN 0042-6989, E-ISSN 1878-5646, Vol. 166, s. 43-51Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A correlation is known to exist between visual sensitivity and oscillations in red opsin and rhodopsin gene expression in zebrafish, both regulated by the clock gene. This indicates that an endogenous circadian clock regulates behavioural visual sensitivity, apart from the regulation exerted by the pineal organ. However, the specific mechanisms for cones (photopic vision) and rods (scotopic vision) are poorly understood. In this work, we performed gene expression, cosinor and immunohistochemical analyses to investigate other key genes involved in light perception, encoding the different subunits of phosphodiesterase pde6 and transducin G alpha(T), in constant lighting conditions and compared to normal light-dark conditions. We found that cones display prominent circadian oscillations in mRNA levels for the inhibitory subunit gene pde6ha that could contribute to the regulation of photopic sensitivity by preventing overstimulation in photopic conditions. In rods, the mRNA levels of the inhibitory subunit gene pde6ga oscillate under normal conditions and dampen down in constant light but continue oscillating in constant darkness. There is an increase in total relative expression for pde6gb in constant conditions. These observations, together with previous data, suggest a complex regulation of the scotopic sensitivity involving endogenous and non-endogenous components, possibly present also in other teleost species. The G alpha(T) genes do not display mRNA oscillations and therefore may not be essential for the circadian regulation of photosensitivity. In summary, our results support different regulation for the zebrafish photopic and scotopic sensitivities and suggest circadian regulation of pde6ha as a key factor regulating photopic sensitivity, while the regulatory mechanisms in rods appear to be more complex.

  • 11.
    Abdollahi, Maryam
    et al.
    Semnan Univ Med Sci, Canc Res Ctr, Semnan, Iran.;Semnan Univ Med Sci, Student Res Comm, Semnan, Iran..
    Mohammadlou, Maryam
    Semnan Univ Med Sci, Canc Res Ctr, Semnan, Iran.;Semnan Univ Med Sci, Student Res Comm, Semnan, Iran..
    Hemati, Maral
    Semnan Univ Med Sci, Canc Res Ctr, Semnan, Iran..
    Baharlou, Rasoul
    Semnan Univ Med Sci, Canc Res Ctr, Semnan, Iran..
    Doulabi, Ehsan Manouchehri
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ghahremanfard, Farahnaz
    Semnan Univ Med Sci, Canc Res Ctr, Semnan, Iran..
    Sarabi, Mohammad Amir
    Semnan Univ Med Sci, Canc Res Ctr, Semnan, Iran..
    Kokhaei, Parviz
    Arak Univ Med Sci, Sch Med, Dept Immunol, Arak, Iran.;Karolinska Univ Hosp Solna, Dept Oncol Pathol, BioClinicum, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Anti-tumor effect of berberine on chronic lymphocytic leukemia cells2022Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 39, nr 12, artikkel-id 217Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic lymphocytic leukemia (CLL) is a blood malignancy that is characterized by remarkable expression of CD69 and Ki67 in CLL cells. Elevated levels of Cleaved-Poly (ADP-ribose) polymerase-1 (PARP1) and microRNA-155 (MiR-155) are related to poor prognosis of disease. Berberine as a natural isoquinoline alkaloid, has shown an anti-tumor potential in tumor cells. The objective of present study was to explore some aspects of molecular mechanisms of berberine effect in CLL cells. To analyze the expression of CD69 and Ki67 using flow cytometry, 16 peripheral blood samples and seven bone marrow aspirates were collected from CLL patients. Isolated peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) were treated with 25 mu M of berberine for 24 h. The level of miR-155 expression was subsequently evaluated by real-time PCR. Furthermore, western blot was used for assessment of cleaved PARP1. Our results demonstrated a significant reduction in CD69 and Ki67 expression on CD19(+) cells when the cells were treated by berberine. Interestingly, the expression level of miR-155 was reduced after berberine treatment in compare to the control group. Furthermore, western blotting revealed an increased level of cleaved PARP1 in dose-dependently manner in CLL cells. The results confirmed the anti-tumor impact of berberine on CLL cells through reducing CD69, Ki67, and miR-155 expression and increasing cleaved PARP1 may be considered as an option for future clinical studies.

  • 12.
    Abdulla, Maysaa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Alexsson, Andrei
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Ladenvall, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Mansouri, Larry
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Lindskog, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Berglund, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Cavelier, Lucia
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Hollander, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    PD-L1 and IDO1 are potential targets for treatment in patients with primary diffuse large B-cell lymphoma of the CNS2021Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 60, nr 4, s. 531-538Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2, as well as Indoleamine 2,3-deoxygenase (IDO1) can be expressed both by tumor and microenvironmental cells and are crucial for tumor immune escape. We aimed to evaluate the role of PD-1, its ligands and IDO1 in a cohort of patients with primary diffuse large B-cell lymphoma of the CNS (PCNSL).

    Material and methods

    Tissue microarrays (TMAs) were constructed in 45 PCNSL cases. RNA extraction from whole tissue sections and RNA sequencing were successfully performed in 33 cases. Immunohistochemical stainings for PD-1, PD-L1/paired box protein 5 (PAX-5), PD-L2/PAX-5 and IDO1, and Epstein-Barr virus encoding RNA (EBER) in situ hybridization were analyzed.

    Results

    High proportions of PD-L1 and PD-L2 positive tumor cells were observed in 11% and 9% of cases, respectively. High proportions of PD-L1 and PD-L2 positive leukocytes were observed in 55% and 51% of cases, respectively. RNA sequencing revealed that gene expression of IDO1 was high in patients with high proportion of PD-L1 positive leukocytes (p = .01). Protein expression of IDO1 in leukocytes was detected in 14/45 cases, in 79% of these cases a high proportion of PD-L1 positive leukocytes was observed. Gene expression of IDO1 was high in EBER-positive cases (p = .0009) and protein expression of IDO1 was detected in five of six EBER-positive cases.

    Conclusion

    Our study shows a significant association between gene and protein expression of IDO1 and protein expression of PD-L1 in the tumor microenvironment of PCNSL, possibly of importance for prediction of response to immunotherapies.

    Fulltekst (pdf)
    fulltext
  • 13.
    Abolhassani, Hassan
    et al.
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.;Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Pediat Ctr Excellence, Childrens Med Ctr, Tehran, Iran.
    Vosughimotlagh, Ahmad
    North Khorasan Univ Med Sci, Dept Pediat, Bojnurd, Iran.
    Asano, Takaki
    Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.
    Landegren, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden.
    Boisson, Bertrand
    Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.;Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.
    Delavari, Samaneh
    Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Pediat Ctr Excellence, Childrens Med Ctr, Tehran, Iran.
    Bastard, Paul
    Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.
    Aranda-Guillen, Maribel
    Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden.
    Wang, Yating
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
    Zuo, Fanglei
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
    Sardh, Fabian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden..
    Marcotte, Harold
    Karolinska Inst, Dept Lab Med, Stockholm, Sweden.;Karolinska Univ, Hosp Huddinge, Stockholm, Sweden.
    Du, Likun
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
    Zhang, Shen-Ying
    Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.
    Zhang, Qian
    Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.
    Rezaei, Nima
    Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Pediat Ctr Excellence, Childrens Med Ctr, Tehran, Iran.
    Kampe, Olle
    Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.
    Casanova, Jean-Laurent
    Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.;Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, INSERM U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.;Howard Hughes Med Inst, New York, NY USA.
    Hammarstrom, Lennart
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
    Pan-Hammarstrom, Qiang
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
    X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia2022Inngår i: Journal of Clinical Immunology, ISSN 0271-9142, E-ISSN 1573-2592, Vol. 42, nr 1, s. 1-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk.

    Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI).

    Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry.

    Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient.

    Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.

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  • 14.
    Abousharieha, Samah
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för materialvetenskap.
    Atif, Abdul-Raouf
    Mestres, Gemma
    Tenje, Maria
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för materialvetenskap.
    A 3D-Printed Device Providing Mechanical Strain for Matrigel-Incorprated Organoids2022Konferansepaper (Annet vitenskapelig)
  • 15.
    Abouzayed, Ayman
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Borin, Jesper
    KTH Royal Inst Technol, Dept Prot Sci, S-11417 Stockholm, Sweden..
    Lundmark, Fanny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Rybina, Anastasiya
    Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Med, Tomsk 634009, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia..
    Hober, Sophia
    KTH Royal Inst Technol, Dept Prot Sci, S-11417 Stockholm, Sweden..
    Zelchan, Roman
    Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Med, Tomsk 634009, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia..
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerprecisionsmedicin.
    Chernov, Vladimir
    Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Med, Tomsk 634009, Russia..
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    The GRPR Antagonist [99mTc]Tc-maSSS-PEG2-RM26 towards Phase I Clinical Trial: Kit Preparation, Characterization and Toxicity2023Inngår i: Diagnostics, ISSN 2075-4418, Vol. 13, nr 9, artikkel-id 1611Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gastrin-releasing peptide receptors (GRPRs) are overexpressed in the majority of primary prostate tumors and in prostatic lymph node and bone metastases. Several GRPR antagonists were developed for SPECT and PET imaging of prostate cancer. We previously reported a preclinical evaluation of the GRPR antagonist [99mTc]Tc-maSSS-PEG2-RM26 (based on [D-Phe6, Sta13, Leu14-NH2]BBN(6-14)) which bound to GRPR with high affinity and had a favorable biodistribution profile in tumor-bearing animal models. In this study, we aimed to prepare and test kits for prospective use in an early-phase clinical study. The kits were prepared to allow for a one-pot single-step radiolabeling with technetium-99m pertechnetate. The kit vials were tested for sterility and labeling efficacy. The radiolabeled by using the kit GRPR antagonist was evaluated in vitro for binding specificity to GRPR on PC-3 cells (GRPR-positive). In vivo, the toxicity of the kit constituents was evaluated in rats. The labeling efficacy of the kits stored at 4 °C was monitored for 18 months. The biological properties of [99mTc]Tc-maSSS-PEG2-RM26, which were obtained after this period, were examined both in vitro and in vivo. The one-pot (gluconic acid, ethylenediaminetetraacetic acid, stannous chloride, and maSSS-PEG2-RM26) single-step radiolabeling with technetium-99m was successful with high radiochemical yields (>97%) and high molar activities (16–24 MBq/nmol). The radiolabeled peptide maintained its binding properties to GRPR. The kit constituents were sterile and non-toxic when tested in living subjects. In conclusion, the prepared kit is considered safe in animal models and can be further evaluated for use in clinics.

    Fulltekst (pdf)
    FULLTEXT01
  • 16.
    Abouzayed, Ayman
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Kanellopoulos, Panagiotis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi. NCSR Demokritos, Mol Radiopharm, INRaSTES, Athens 15310, Greece..
    Gorislav, Alisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Maina, Theodosia
    NCSR Demokritos, Mol Radiopharm, INRaSTES, Athens 15310, Greece..
    Nock, Berthold A.
    NCSR Demokritos, Mol Radiopharm, INRaSTES, Athens 15310, Greece..
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Preclinical Characterization of a Stabilized Gastrin-Releasing Peptide Receptor Antagonist for Targeted Cancer Theranostics2023Inngår i: Biomolecules, E-ISSN 2218-273X, Vol. 13, nr 7, artikkel-id 1134Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Radiolabeled gastrin-releasing peptide receptor (GRPR) antagonists have shown great promise for the theranostics of prostate cancer; however, their suboptimal metabolic stability leaves room for improvements. It was recently shown that the replacement of Gly(11) with Sar(11) in the peptidic [D-Phe(6),Leu(13)-NHEt,des-Met(14)]BBN(6-14) chain stabilized the [Tc-99m]Tc-DB15 radiotracer against neprilysin (NEP). We herein present DOTAGA-PEG(2)-(Sar(11))RM26 (AU-RM26-M1), after Gly(11) to Sar(11)-replacement. The impact of this replacement on the metabolic stability and overall biological performance of [In-111]In-AU-RM26-M1 was studied using a head-to-head comparison with the unmodified reference [In-111]In-DOTAGA-PEG(2)-RM26. In vitro, the cell uptake of [In-111]In-AU-RM26-M1 could be significantly reduced in the presence of a high-excess GRPR-blocker that demonstrated its specificity. The cell uptake of both radiolabeled GRPR antagonists increased with time and was superior for [In-111]In-AU-RM26-M1. The dissociation constant reflected strong affinities for GRPR (500 pM for [In-111]In-AU-RM26-M1). [In-111]In-AU-RM26-M1 showed significantly higher stability in peripheral mice blood at 5 min pi (88 & PLUSMN; 8% intact) than unmodified [In-111]In-DOTAGA-PEG(2)-RM26 (69 & PLUSMN; 2% intact; p < 0.0001). The administration of a NEP inhibitor had no significant impact on the Sar(11)-compound (91 & PLUSMN; 2% intact; p > 0.05). In vivo, [In-111]In-AU-RM26-M1 showed high and GRPR-mediated uptake in the PC-3 tumors (7.0 & PLUSMN; 0.7%IA/g vs. 0.9 & PLUSMN; 0.6%IA/g in blocked mice) and pancreas (2.2 & PLUSMN; 0.6%IA/g vs. 0.3 & PLUSMN; 0.2%IA/g in blocked mice) at 1 h pi, with rapid clearance from healthy tissues. The tumor uptake of [In-111]In-AU-RM26-M1 was higher than for [In-111]In-DOTAGA-PEG(2)-RM26 (at 4 h pi, 5.7 & PLUSMN; 1.8%IA/g vs. 3 & PLUSMN; 1%IA/g), concordant with its higher stability. The implanted PC-3 tumors were visualized with high contrast in mice using [In-111]In-AU-RM26-M1 SPECT/CT. The Gly(11) to Sar(11)-substitution stabilized [In-111]In-DOTAGA-PEG(2)-(Sar(11))RM26 against NEP without negatively affecting other important biological features. These results support the further evaluation of AU-RM26-M1 for prostate cancer theranostics after labeling with clinically relevant radionuclides.

    Fulltekst (pdf)
    FULLTEXT01
  • 17.
    Abouzayed, Ayman
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Rinne, Sara S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Sabahnoo, Hamideh
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Chernov, Vladimir
    Russian Acad Sci, Canc Res Inst, Dept Nucl Med, Tomsk Natl Res Med Ctr, Tomsk 634009, Russia; Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634009, Russia.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap. Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634009, Russia.
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634009, Russia.
    Preclinical Evaluation of 99mTc-Labeled GRPR Antagonists maSSS/SES-PEG2-RM26 for Imaging of Prostate Cancer2021Inngår i: Pharmaceutics, E-ISSN 1999-4923, Vol. 13, nr 2, artikkel-id 182Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Gastrin-releasing peptide receptor (GRPR) is an important target for imaging of prostate cancer. The wide availability of single-photon emission computed tomography/computed tomography (SPECT/CT) and the generator-produced 99mTc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers.

    Methods: Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG2-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PEG2-RM26 (RM26 = d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) were radiolabeled with 99mTc and characterized in vitro using PC-3 cells and in vivo, using NMRI or PC-3 tumor bearing mice. SPECT/CT imaging and dosimetry calculations were performed for [99mTc]Tc-maSSS-PEG2-RM26.

    Results: Peptides were radiolabeled with high yields (>98%), demonstrating GRPR specific binding and slow internalization in PC-3 cells. [99mTc]Tc-maSSS-PEG2-RM26 outperformed [99mTc]Tc-maSES-PEG2-RM26 in terms of GRPR affinity, with a lower dissociation constant (61 pM vs 849 pM) and demonstrating higher tumor uptake. [99mTc]Tc-maSSS-PEG2-RM26 had tumor-to-blood, tumor-to-muscle, and tumor-to-bone ratios of 97 ± 56, 188 ± 32, and 177 ± 79, respectively. SPECT/CT images of [99mTc]Tc-maSSS-PEG2-RM26 clearly visualized the GRPR-overexpressing tumors. The dosimetry estimated for [99mTc]Tc-maSSS-PEG2-RM26 showed the highest absorbed dose in the small intestine (1.65 × 10−3 mGy/MBq), and the effective dose is 3.49 × 10−3 mSv/MBq.

    Conclusion: The GRPR antagonist maSSS-PEG2-RM26 is a promising GRPR-targeting agent that can be radiolabeled through a single-step with the generator-produced 99mTc and used for imaging of GRPR-expressing prostate cancer.

    Fulltekst (pdf)
    FULLTEXT01
  • 18.
    Abouzayed, Ayman
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Seitova, Kamila
    Siberian State Med Univ, Sci & Res Lab Chem & Pharmaceut Res, Tomsk, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia..
    Lundmark, Fanny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Bodenko, Vitalina
    Siberian State Med Univ, Sci & Res Lab Chem & Pharmaceut Res, Tomsk, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia..
    Oroujeni, Maryam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Affibody AB, Solna, Sweden..
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia..
    Rosenström, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    177Lu-labeled PSMA targeting therapeutic with optimized linker for treatment of disseminated prostate cancer; evaluation of biodistribution and dosimetry2023Inngår i: Frontiers in Oncology, E-ISSN 2234-943X, Vol. 13, artikkel-id 1221103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    <bold>Introduction:</bold> Prostate specific membrane antigen (PSMA), highly expressed in metastatic castration-resistant prostate cancer (mCRPC), is an established therapeutic target. Theranostic PSMA-targeting agents are widely used in patient management and has shown improved outcomes for mCRPC patients. Earlier, we optimized a urea-based probe for radionuclide visualization of PSMA-expression in vivo using computer modeling. With the purpose to develop a targeting agent equally suitable for radionuclide imaging and therapy, the agent containing DOTA chelator was designed (BQ7876). The aim of the study was to test the hypothesis that Lu-177-labeled BQ7876 possesses target binding and biodistribution properties potentially enabling its use for radiotherapy.<bold>Methods:</bold> BQ7876 was synthesized and labeled with Lu-177. Specificity and affinity of [Lu-177]Lu-BQ7876 to PSMA-expressing PC3-pip cells was evaluated and its processing after binding to cells was studied. Animal studies in mice were performed to assess its biodistribution in vivo, target specificity and dosimetry. [Lu-177]Lu-PSMA-617 was simultaneously evaluated for comparison.<bold>Results:</bold> BQ7876 was labeled with Lu-177 with radiochemical yield >99%. Its binding to PSMA was specific in vitro and in vivo when tested in antigen saturation conditions as well as in PSMA-negative PC-3 tumors. The binding of [Lu-177]Lu-BQ7876 to living cells was characterized by rapid association, while the dissociation included a rapid and a slow phase with affinities K-D1 = 3.8 nM and K-D2 = 25 nM. The half-maximal inhibitory concentration for Lu-nat-BQ7876 was 59 nM that is equal to 61 nM for Lu-nat-PSMA-617. Cellular processing of [Lu-177]Lu-BQ7876 was accompanied by slow internalization. [Lu-177]Lu-BQ7876 was cleared from blood and normal tissues rapidly. Initial elevated uptake in kidneys decreased rapidly, and by 3 h post injection, the renal uptake (13 +/- 3%ID/g) did not differ significantly from tumor uptake (9 +/- 3%ID/g). Tumor uptake was stable between 1 and 3 h followed by a slow decline. The highest absorbed dose was in kidneys, followed by organs and tissues in abdomen.<bold>Discussion:</bold> Biodistribution studies in mice demonstrated that targeting properties of [Lu-177]Lu-BQ7876 are not inferior to properties of [Lu-177]Lu-PSMA-617, but do not offer any decisive advantages.

    Fulltekst (pdf)
    FULLTEXT01
  • 19.
    Abouzayed, Ayman
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Tano, Hanna
    KTH Royal Inst Technol, AlbaNova Univ Ctr, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden..
    Nagy, Abel
    KTH Royal Inst Technol, AlbaNova Univ Ctr, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden..
    Rinne, Sara S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Wadeea, Fadya
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Kumar, Sharmishtaa
    KTH Royal Inst Technol, AlbaNova Univ Ctr, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden..
    Westerlund, Kristina
    KTH Royal Inst Technol, AlbaNova Univ Ctr, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden..
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap. Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, Tomsk 634050, Russia.
    Eriksson Karlström, Amelie
    KTH Royal Inst Technol, AlbaNova Univ Ctr, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-10691 Stockholm, Sweden..
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Centrum Oncotheranost, Tomsk 634050, Russia..
    Preclinical Evaluation of the GRPR-Targeting Antagonist RM26 Conjugated to the Albumin-Binding Domain for GRPR-Targeting Therapy of Cancer2020Inngår i: Pharmaceutics, E-ISSN 1999-4923, Vol. 12, nr 10, artikkel-id 977Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The targeting of gastrin-releasing peptide receptors (GRPR) was recently proposed for targeted therapy, e.g., radiotherapy. Multiple and frequent injections of peptide-based therapeutic agents would be required due to rapid blood clearance. By conjugation of the GRPR antagonist RM26 (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) to an ABD (albumin-binding domain), we aimed to extend the blood circulation of peptides. The synthesized conjugate DOTA-ABD-RM26 was labelled with indium-111 and evaluated in vitro and in vivo. The labelled conjugate was stable in PBS and retained specificity and its antagonistic function against GRPR. The half-maximal inhibitory concentration (IC50) of In-nat-DOTA-ABD-RM26 in the presence of human serum albumin was 49 +/- 5 nM. [In-111]In-DOTA-ABD-RM26 had a significantly longer residence time in blood and in tumors (without a significant decrease of up to 144 h pi) than the parental RM26 peptide. We conclude that the ABD-RM26 conjugate can be used for GRPR-targeted therapy and delivery of cytotoxic drugs. However, the undesirable elevated activity uptake in kidneys abolishes its use for radionuclide therapy. This proof-of-principle study justified further optimization of the molecular design of the ABD-RM26 conjugate.

    Fulltekst (pdf)
    FULLTEXT01
  • 20.
    Abouzayed, Ayman
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Yim, Cheng-Bin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Mitran, Bogdan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Rinne, Sara S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Larhed, Mats
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
    Rosenström, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Orlova, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Synthesis and Preclinical Evaluation of Radio-Iodinated GRPR/PSMA Bispecific Heterodimers for the Theranostics Application in Prostate Cancer2019Inngår i: Pharmaceutics, E-ISSN 1999-4923, Vol. 11, nr 7, artikkel-id 358Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gastrin-releasing peptide receptor (GRPR) and prostate-specific membrane antigen (PSMA) are overexpressed in most prostate cancers. GRPR expression is higher in early stages while PSMA expression increases with progression. The possibility of targeting both markers with a single theranostics radiotracer could improve patient management. Three GRPR/PSMA-targeting bispecific heterodimers (urea derivative PSMA-617 and bombesin-based antagonist RM26 linked via X-triazolyl-Tyr-PEG2, X = PEG2 (BO530), (CH2)(8) (BO535), none (BO536)) were synthesized by solid-phase peptide synthesis. Peptides were radio-iodinated and evaluated in vitro for binding specificity, cellular retention, and affinity. In vivo specificity for all heterodimers was studied in PC-3 (GRPR-positive) and LNCaP (PSMA-positive) xenografts. [I-125]I-BO530 was evaluated in PC-3pip (GRPR/PSMA-positive) xenografts. Micro single-photon emission computed tomography/computed tomography (microSPECT/CT) scans were acquired. The heterodimers were radiolabeled with high radiochemical yields, bound specifically to both targets, and demonstrated high degree of activity retention in PC-3pip cells. Only [I-125]I-BO530 demonstrated in vivo specificity to both targets. A biodistribution study of [I-125]I-BO530 in PC-3pip xenografted mice showed high tumor activity uptake (30%-35%ID/g at 3 h post injection (pi)). Activity uptake in tumors was stable and exceeded all other organs 24 h pi. Activity uptake decreased only two-fold 72 h pi. The GRPR/PSMA-targeting heterodimer [I-125]I-BO530 is a promising agent for theranostics application in prostate cancer.

    Fulltekst (pdf)
    FULLTEXT01
  • 21.
    Abramov, Sergei
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Kazan Fed Univ, Inst Fundamental Med & Biol, Kazan, Russia.
    Kozyrev, Sergey V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Farias, Fabiana H. G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Washington Univ, Genome Inst, Sch Med, St Louis, MO USA.
    Dahlqvist, Johanna
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wilbe, Maria
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Swedish Univ Agr Sci SLU, Dept Anim Breeding & Genet, Uppsala, Sweden.
    Alexsson, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Pielberg, Gerli
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hansson-Hamlin, H.
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Uppsala, Sweden.
    Andersson, G.
    Swedish Univ Agr Sci SLU, Dept Anim Breeding & Genet, Uppsala, Sweden.
    Tandre, Karolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ronnblom, L.
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Uppsala, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    The risk allele A of rs200395694 associated with SLE in Swedish patients affects on MEF2D gene regulation and alternative splicing2018Inngår i: Human Gene Therapy, ISSN 1043-0342, E-ISSN 1557-7422, Vol. 29, nr 12, s. A44-A44Artikkel i tidsskrift (Annet vitenskapelig)
  • 22.
    Abramsson, Mia L.
    et al.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17165 Stockholm, Sweden..
    Sahin, Cagla
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17165 Stockholm, Sweden.;Univ Copenhagen, Linderstrom Lang Ctr Prot Sci, Dept Biol, DK-2200 Copenhagen, Denmark.;OMass Therapeut, SchrOdinger Bldg,Oxford Sci Pk, Oxford OX4 4GE, England..
    Hopper, Jonathan T. S.
    Univ Oxford, Dept Chem, Oxford OX1 3QZ, England..
    Branca, Rui M. M.
    Sci Life Lab, Dept Oncol Pathol, S-17165 Stockholm, Sweden.;Karolinska Inst, S-17165 Stockholm, Sweden..
    Danielsson, Jens
    Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden..
    Xu, Mingming
    Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden..
    Chandler, Shane A.
    Univ Oxford, Dept Chem, Oxford OX1 3QZ, England..
    Osterlund, Nicklas
    Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden..
    Ilag, Leopold L.
    Stockholm Univ, Dept Mat & Environm Chem, S-10691 Stockholm, Sweden..
    Leppert, Axel
    Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden..
    Costeira-Paulo, Joana
    Uppsala Univ, Dept Chem BMC, S-75123 Uppsala, Sweden..
    Lang, Lisa
    Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden..
    Teilum, Kaare
    Univ Copenhagen, Linderstrom Lang Ctr Prot Sci, Dept Biol, DK-2200 Copenhagen, Denmark..
    Laganowsky, Arthur
    Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA..
    Benesch, Justin L. P.
    Univ Oxford, Dept Chem, Oxford OX1 3QZ, England..
    Oliveberg, Mikael
    Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden..
    Robinson, Carol, V
    Univ Oxford, Dept Chem, Oxford OX1 3QZ, England..
    Marklund, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi.
    Allison, Timothy M.
    Univ Canterbury, Biomol Interact Ctr, Sch Phys & Chem Sci, Christchurch 8140, New Zealand..
    Winther, Jakob R.
    Univ Copenhagen, Linderstrom Lang Ctr Prot Sci, Dept Biol, DK-2200 Copenhagen, Denmark..
    Landreh, Michael
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17165 Stockholm, Sweden..
    Charge Engineering Reveals the Roles of Ionizable Side Chains in Electrospray Ionization Mass Spectrometry2021Inngår i: JACS Au, E-ISSN 2691-3704, Vol. 1, nr 12, s. 2385-2393Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In solution, the charge of a protein is intricately linked to its stability, but electrospray ionization distorts this connection, potentially limiting the ability of native mass spectrometry to inform about protein structure and dynamics. How the behavior of intact proteins in the gas phase depends on the presence and distribution of ionizable surface residues has been difficult to answer because multiple chargeable sites are present in virtually all proteins. Turning to protein engineering, we show that ionizable side chains are completely dispensable for charging under native conditions, but if present, they are preferential protonation sites. The absence of ionizable side chains results in identical charge state distributions under native-like and denaturing conditions, while coexisting conformers can be distinguished using ion mobility separation. An excess of ionizable side chains, on the other hand, effectively modulates protein ion stability. In fact, moving a single ionizable group can dramatically alter the gas-phase conformation of a protein ion. We conclude that although the sum of the charges is governed solely by Coulombic terms, their locations affect the stability of the protein in the gas phase.

  • 23.
    Abu Sabaa, Amal
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Mörth, Charlott
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Berglund, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Hashemi, Jamileh
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Freyhult, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg och funktionsgenomik.
    Robelius, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    T-cell Leukaemia/Lymphoma Protein 1A (TCL1A) In Diffuse Large B-cell lymphoma (DLBCL)Manuskript (preprint) (Annet vitenskapelig)
  • 24.
    Abu Sabaa, Amal
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Mörth, Charlott
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Molin, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Freyhult, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Cancerfarmakologi och beräkningsmedicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg och funktionsgenomik.
    Robelius, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancerimmunterapi.
    Plasma Protein Profiling using Multiplex Extension Assay in Diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP: A descriptive studyManuskript (preprint) (Annet vitenskapelig)
  • 25.
    Acharya, Shikha
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Odontol, Dept Oral Microbiol & Immunol, PO 450, S-40530 Gothenburg, Sweden.
    Jin, Chunsheng
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Biochem & Cell Biol, Gothenburg, Sweden.
    Bylund, Johan
    Univ Gothenburg, Sahlgrenska Acad, Inst Odontol, Dept Oral Microbiol & Immunol, PO 450, S-40530 Gothenburg, Sweden.
    Shen, Qiujin
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jontell, Mats
    Univ Gothenburg, Sahlgrenska Acad, Inst Odontol, Dept Oral Med & Pathol, Gothenburg, Sweden.
    Carlen, Anette
    Univ Gothenburg, Sahlgrenska Acad, Inst Odontol, Dept Oral Microbiol & Immunol, PO 450, S-40530 Gothenburg, Sweden.
    Karlsson, Niclas G.
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Biochem & Cell Biol, Gothenburg, Sweden.
    Reduced sialyl-Lewis(x) on salivary MUC7 from patients with burning mouth syndrome2019Inngår i: Molecular Omics, E-ISSN 2515-4184, Vol. 15, nr 5, s. 331-339Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We analysed and compared MUC7 O-glycosylation and inflammatory biomarkers in saliva from female patients with burning mouth syndrome (BMS) and gender/age-matched controls. Oligosaccharides from salivary MUC7 from BMS and controls were released. Inflammatory mediators were measured by multiplex proximity extension assay. Presence of sialyl-Lewis(x) (Si-Le(x)) epitope on MUC7 was confirmed using Western blot. MUC7 O-glycans and measured inflammatory biomarkers were found to be similar between BMS and controls. However, oligosaccharides sialyl-Lewis(x) (Si-Le(x)) was found to be reduced in samples from BMS patients. Positive correlation (combined patients and controls) was found between levels of C-C motif chemokine 19 (CCL-19) and the amount of core-2 oligosaccharides on MUC7 as well as fractalkine (CX3CL1) and level of sialylation. Patients with BMS were shown to represent a heterogeneous group in terms of inflammatory biomarkers. This indicates that BMS patients could be further stratified on the basis of low-level inflammation. The results furthermore indicate that reduced sialylation of MUC7, particularly Si-Le(x), may be an important feature in patients with BMS. However, the functional aspects and potential involvement in immune regulation of Si-Le(x) remains unclear. Our data suggests a chemokine driven alteration of MUC7 glycosylation.

    Fulltekst (pdf)
    fulltext
  • 26.
    Adams, Hieab H. H.
    et al.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands..
    Hibar, Derrek P.
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA..
    Chouraki, Vincent
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Univ Lille, RID AGE Risk Factors & Mol Determinants Aging Rel, CHU Lille, Inserm,Inst Pasteur Lille, Lille, France.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Stein, Jason L.
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA.;Univ N Carolina, Dept Genet, Chapel Hill, NC USA.;Univ N Carolina, UNC Neurosci Ctr, Chapel Hill, NC USA..
    Nyquist, Paul A.
    Johns Hopkins Univ, Dept Neurol, Dept Anesthesia Crit Care Med, Dept Neurosurg, Baltimore, MD 21218 USA..
    Renteria, Miguel E.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Arias-Vasquez, Alejandro
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Seshadri, Sudha
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Desrivieres, Sylvane
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London, England..
    Beecham, Ashley H.
    Univ Miami, Miller Sch Med, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA..
    Jahanshad, Neda
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA..
    Wittfeld, Katharine
    German Ctr Neurodegenerat Dis DZNE Rostock Greifs, Greifswald, Germany.;Univ Med Greifswald, Dept Psychiat, Greifswald, Germany..
    Van der Lee, Sven J.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Abramovic, Lucija
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Alhusaini, Saud
    McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ, Canada.;Royal Coll Surgeons Ireland, Dublin 2, Ireland..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Andersson, Micael
    Umea Univ, Dept Integrat Med Biol, Umea, Sweden.;Umea Univ, Umea Ctr Funct Brain Imaging, Umea, Sweden..
    Arfanakis, Konstantinos
    IIT, Dept Biomed Engn, Chicago, IL 60616 USA.;Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Diagnost Radiol & Nucl Med, Chicago, IL 60612 USA..
    Aribisala, Benjamin S.
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Lagos State Univ, Dept Comp Sci, Lagos, Nigeria.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland..
    Armstrong, Nicola J.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.;Murdoch Univ, Math & Stat, Perth, WA, Australia..
    Athanasiu, Lavinia
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Beiser, Alexa
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Bernard, Manon
    Univ Toronto, Hosp Sick Children, Toronto, ON, Canada..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Blanken, Laura M. E.
    Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.;Erasmus MC Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands..
    Blanton, Susan H.
    Univ Miami, Miller Sch Med, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA..
    Bohlken, Marc M.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Boks, Marco P.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Bralten, Janita
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Brickman, Adam M.
    Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA.;Columbia Univ, GH Sergievsky Ctr, Med Ctr, New York, NY USA.;Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA..
    Carmichael, Owen
    Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA..
    Chakravarty, M. Mallar
    Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Montreal, PQ, Canada.;McGill Univ, Dept Psychiat & Biomed Engn, Montreal, PQ, Canada..
    Chauhan, Ganesh
    Univ Bordeaux, INSERM Unit U1219, Bordeaux, France..
    Chen, Qiang
    Lieber Inst Brain Dev, Baltimore, MD USA..
    Ching, Christopher R. K.
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA.;Univ Calif Los Angeles, Sch Med, Interdept Neurosci Grad Program, Los Angeles, CA USA..
    Cuellar-Partida, Gabriel
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Den Braber, Anouk
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Doan, Nhat Trung
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Ehrlich, Stefan
    Tech Univ Dresden, Fac Med, Div Psychol & Social Med & Dev Neurosci, Dresden, Germany.;Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA..
    Filippi, Irina
    Univ Paris Sud, Univ Paris Descartes, NSERM Unit Neuroimaging & Psychiat 1000, Paris, France.;Hosp Cochin, AP HP, Maison Solenn Adolescent Psychopathol & Med Dept, Paris, France..
    Ge, Tian
    Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA.;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA..
    Giddaluru, Sudheer
    Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5020 Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway..
    Goldman, Aaron L.
    Lieber Inst Brain Dev, Baltimore, MD USA..
    Gottesman, Rebecca F.
    Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA..
    Greven, Corina U.
    Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands.;Kings Coll London, Med Res Council Social, Genet & Dev Psychiat Ctr, Inst Psychol Psychiat & Neurosci, London, England..
    Grimm, Oliver
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany..
    Griswold, Michael E.
    Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA..
    Guadalupe, Tulio
    Max Planck Inst Psycholinguist, Language & Genet Dept, Nijmegen, Netherlands.;Int Max Planck Res Sch Language Sci, Nijmegen, Netherlands..
    Hass, Johanna
    Tech Univ Dresden, Fac Med, Dept Child & Adolescent Psychiat, Dresden, Germany..
    Haukvik, Unn K.
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Diakonhjemmet Hosp, Dept Res & Dev, Oslo, Norway..
    Hilal, Saima
    Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore.;Natl Univ Hlth Syst, Mem Aging & Cognit Ctr, Singapore, Singapore..
    Hofer, Edith
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria.;Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria..
    Hoehn, David
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Holmes, Avram J.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Yale Univ, Dept Psychol, New Haven, CT USA..
    Hoogman, Martine
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Janowitz, Deborah
    Univ Med Greifswald, Dept Psychiat, Greifswald, Germany..
    Jia, Tianye
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London, England..
    Kasperaviciute, Dalia
    UCL, Inst Neurol, London, England.;Epilepsy Soc, Gerrards Cross, Bucks, England.;Imperial Coll London, Dept Med, London, England..
    Kim, Sungeun
    Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA.;Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA..
    Klein, Marieke
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Kraemer, Bernd
    Heidelberg Univ, Dept Gen Psychiat, Sect Expt Psychopathol & Neuroimaging, Heidelberg, Germany..
    Lee, Phil H.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA.;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA.;Harvard Med Sch, Massachusetts Gen Hosp, Lurie Ctr Autism, Lexington, MA USA..
    Liao, Jiemin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore..
    Liewald, David C. M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland..
    Lopez, Lorna M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland..
    Luciano, Michelle
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland..
    Macare, Christine
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London, England..
    Marquand, Andre
    Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Ctr Cognit Neuroimaging, Nijmegen, Netherlands..
    Matarin, Mar
    UCL, Inst Neurol, London, England.;Epilepsy Soc, Gerrards Cross, Bucks, England.;UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England..
    Mather, Karen A.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia..
    Mattheisen, Manuel
    Aarhus Univ, Dept Biomed, Aarhus, Denmark.;iPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Aarhus, Denmark.;iPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Copenhagen, Denmark.;Aarhus Univ, iSEQ, Ctr Integrated Sequencing, Aarhus, Denmark..
    Mazoyer, Bernard
    UMR5296 Univ Bordeaux, CNRS, CEA, Bordeaux, France..
    Mckay, David R.
    Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.;Olin Neuropsychiat Res Ctr, Hartford, CT USA..
    McWhirter, Rebekah
    Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia..
    Milaneschi, Yuri
    VU Univ Med Ctr GGZ Geest, EMGO Inst Hlth & Care Res, Dept Psychiat, Amsterdam, Netherlands.;VU Univ Med Ctr GGZ Geest, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Mirza-Schreiber, Nazanin
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Muetzel, Ryan L.
    Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.;Erasmus MC Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands..
    Maniega, Susana Munoz
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland..
    Nho, Kwangsik
    Indiana Univ, Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN USA.;Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA.;Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA..
    Nugent, Allison C.
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Loohuis, Loes M. Olde
    Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA..
    Oosterlaan, Jaap
    Vrije Univ Amsterdam, Dept Clin Neuropsychol, Amsterdam, Netherlands..
    Papmeyer, Martina
    Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland.;Univ Bern, Univ Hosp Psychiat, Translat Res Ctr, Div Syst Neurosci Psychopathol, CH-3012 Bern, Switzerland..
    Pappa, Irene
    Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.;Erasmus Univ, Sch Pedag & Educ Sci, Rotterdam, Netherlands..
    Pirpamer, Lukas
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria..
    Pudas, Sara
    Umea Univ, Dept Integrat Med Biol, Umea, Sweden.;Umea Univ, Umea Ctr Funct Brain Imaging, Umea, Sweden..
    Puetz, Benno
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Rajan, Kumar B.
    Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA..
    Ramasamy, Adaikalavan
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England.;Kings Coll London, Dept Med & Mol Genet, London, England.;Univ Oxford, Jenner Inst Labs, Oxford, England..
    Richards, Jennifer S.
    Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands..
    Risacher, Shannon L.
    Indiana Univ, Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN USA.;Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA..
    Roiz-Santianez, Roberto
    Univ Cantabria IDIVAL, Sch Med, Dept Med & Psychiat, Univ Hosp Marques de Valdecilla, Santander, Spain.;CIBERSAM Ctr Invest Biomed Red Salud Med, Santander, Spain..
    Rommelse, Nanda
    Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands..
    Rose, Emma J.
    Trinity Coll Dublin, Psychosis Res Grp, Dept Psychiat, Dublin, Ireland.;Trinity Coll Dublin, Trinity Translat Med Inst, Dublin, Ireland..
    Royle, Natalie A.
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland..
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth Sci, Miami, FL 33136 USA..
    Saemann, Philipp G.
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Satizabal, Claudia L.
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Schmaal, Lianne
    Orygen, Melbourne, Vic, Australia.;Univ Melbourne, Ctr Youth Mental Hlth, Melbourne, Vic, Australia.;Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Schork, Andrew J.
    Univ Calif San Diego, Dept Neurosci, Multimodal Imaging Lab, San Diego, CA 92103 USA.;Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92103 USA..
    Shen, Li
    Indiana Univ, Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN USA.;Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA.;Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA..
    Shin, Jean
    Univ Toronto, Hosp Sick Children, Toronto, ON, Canada..
    Shumskaya, Elena
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Ctr Cognit Neuroimaging, Nijmegen, Netherlands..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Sprooten, Emma
    Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.;Olin Neuropsychiat Res Ctr, Hartford, CT USA.;Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland.;Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA..
    Strike, Lachlan T.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Thomson, Russell
    Tordesillas-Gutierrez, Diana
    CIBERSAM Ctr Invest Biomed Red Salud Med, Santander, Spain.;Valdecilla Biomed Res Inst IDIVAL, Neuroimaging Unit, Technol Facil, Santander, Cantabria, Spain..
    Toro, Roberto
    Inst Pasteur, Paris, France..
    Trabzuni, Daniah
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England.;King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh, Saudi Arabia..
    Vaidya, Dhananjay
    Johns Hopkins Univ, Sch Med, Dept Med, GeneSTAR Res Ctr, Baltimore, MD 21205 USA..
    Van der Grond, Jeroen
    Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands..
    van der Meer, Dennis
    Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands..
    Van Donkelaar, Marjolein M. J.
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Van Eijk, Kristel R.
    UMC Utrecht, Human Neurogenet Unit, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Van Erp, Theo G. M.
    Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA..
    Van Rooij, Daan
    Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands..
    Walton, Esther
    Tech Univ Dresden, Fac Med, Dept Child & Adolescent Psychiat, Dresden, Germany..
    Westlye, Lars T.
    Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, Oslo, Norway.;Univ Oslo, Dept Psychol, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Whelan, Christopher D.
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA.;Royal Coll Surgeons Ireland, Dublin 2, Ireland..
    Windham, Beverly G.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Winkler, Anderson M.
    Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.;Univ Oxford, FMRIB Ctr, Oxford, England..
    Woldehawariat, Girma
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Wolf, Christiane
    Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany..
    Wolfers, Thomas
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Xu, Bing
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London, England..
    Yanek, Lisa R.
    Johns Hopkins Univ, Sch Med, Dept Med, GeneSTAR Res Ctr, Baltimore, MD 21205 USA..
    Yang, Jingyun
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA..
    Zijdenbos, Alex
    Biospect Inc, Montreal, PQ, Canada..
    Zwiers, Marcel P.
    Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Ctr Cognit Neuroimaging, Nijmegen, Netherlands..
    Agartz, Ingrid
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Diakonhjemmet Hosp, Dept Res & Dev, Oslo, Norway.;Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Aggarwal, Neelum T.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA..
    Almasy, Laura
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA.;Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Dept Biomed & Hlth Informat, Philadelphia, PA 19104 USA..
    Ames, David
    Royal Melbourne Hosp, Natl Ageing Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Acad Unit Psychiat Old Age, Melbourne, Vic, Australia..
    Amouyel, Philippe
    Univ Lille, RID AGE Risk Factors & Mol Determinants Aging Rel, CHU Lille, Inserm,Inst Pasteur Lille, Lille, France..
    Andreassen, Ole A.
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Arepalli, Sampath
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Assareh, Amelia A.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia..
    Barral, Sandra
    Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA..
    Bastin, Mark E.
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland..
    Becker, Diane M.
    Johns Hopkins Univ, Sch Med, Dept Med, GeneSTAR Res Ctr, Baltimore, MD 21205 USA..
    Becker, James T.
    Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.;Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.;Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA..
    Bennett, David A.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA..
    Blangero, John
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA..
    van Bokhoven, Hans
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Boomsma, Dorret I.
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Brodaty, Henry
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.;UNSW, Dementia Collaborat Res Ctr Assessment & Better, Sydney, NSW, Australia..
    Brouwer, Rachel M.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Brunner, Han G.
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands..
    Buckner, Randy L.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Harvard Univ, Dept Psychol, Ctr Brain Sci, 33 Kirkland St, Cambridge, MA 02138 USA..
    Buitelaar, Jan K.
    Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands..
    Bulayeva, Kazima B.
    Dagestan State Univ, Dept Evolut & Genet, Makhachkala, Dagestan, Russia..
    Cahn, Wiepke
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Calhoun, Vince D.
    Mind Res Network, Albuquerque, NM USA.;LBERI, Albuquerque, NM USA.;Univ New Mexico, Dept ECE, Albuquerque, NM 87131 USA..
    Cannon, Dara M.
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.;Natl Univ Ireland Galway, Ctr Neuroimaging & Cognit Genom NICOG, NCBES Galway Neurosci Ctr, Coll Med Nursing & Hlth Sci,Clin Neuroimaging Lab, Galway, Ireland..
    Cavalleri, Gianpiero L.
    Royal Coll Surgeons Ireland, Dublin 2, Ireland..
    Chen, Christopher
    Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore.;Natl Univ Hlth Syst, Mem Aging & Cognit Ctr, Singapore, Singapore..
    Cheng, Ching -Yu
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Duke NUS Grad Med Sch, Acad Med Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore..
    Cichon, Sven
    Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland.;Univ Bonn, Inst Human Genet, Bonn, Germany.;Res Ctr Julich, Inst Neurosci & Med INM1, Julich, Germany..
    Cookson, Mark R.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Corvin, Aiden
    Trinity Coll Dublin, Psychosis Res Grp, Dept Psychiat, Dublin, Ireland.;Trinity Coll Dublin, Trinity Translat Med Inst, Dublin, Ireland..
    Crespo-Facorro, Benedicto
    Univ Cantabria IDIVAL, Sch Med, Dept Med & Psychiat, Univ Hosp Marques de Valdecilla, Santander, Spain.;CIBERSAM Ctr Invest Biomed Red Salud Med, Santander, Spain..
    Curran, Joanne E.
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA..
    Czisch, Michael
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Dale, Anders M.
    Univ Calif San Diego, Ctr Multimodal Imaging & Genet, San Diego, CA 92103 USA.;Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.;Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA.;Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.;Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92103 USA..
    Davies, Gareth E.
    Avera Inst Human Genet, Sioux Falls, SD USA.;Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Gen, 75 Francis St, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    De Geus, Eco J. C.
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    De Jager, Philip L.
    Harvard Med Sch, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Broad Inst, Cambridge, MA USA..
    de Zubicaray, Greig I.
    Queensland Univ Technol, Fac Hlth, Brisbane, Qld, Australia.;Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia..
    Delanty, Norman
    Royal Coll Surgeons Ireland, Dublin 2, Ireland.;Beaumont Hosp, Div Neurol, Dublin 9, Ireland..
    Depondt, Chantal
    Univ Libre Bruxelles, Hop Erasme, Dept Neurol, Brussels, Belgium..
    DeStefano, Anita L.
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway..
    Dillman, Allissa
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Djurovic, Srdjan
    Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5020 Bergen, Norway.;Oslo Univ Hosp, Dept Med Genet, Oslo, Norway..
    Donohoe, Gary
    Natl Univ Ireland Galway, Cognit Genet & Cognit Therapy Grp, Neuroimaging Cognit & Genom Ctr NICOG, Galway, Ireland.;Natl Univ Ireland Galway, NCBES Galway Neurosci Ctr, Sch Psychol, Galway, Ireland.;Natl Univ Ireland Galway, Discipline Biochem, Galway, Ireland.;Trinity Coll Dublin, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 8, Ireland.;Trinity Coll Dublin, Inst Psychiat, Dublin 8, Ireland..
    Drevets, Wayne C.
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.;Janssen Res & Dev LLC, Titusville, NJ USA..
    Duggirala, Ravi
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA..
    Dyer, Thomas D.
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA..
    Erk, Susanne
    Charite, CCM, Dept Psychiat & Psychotherapy, Berlin, Germany..
    Espeseth, Thomas
    Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, Oslo, Norway.;Univ Oslo, Dept Psychol, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Evans, Denis A.
    Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA..
    Fedko, Iryna
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Fernandez, Guillen
    Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Ferrucci, Luigi
    NIA, Intramural Res Program, Baltimore, MD 21224 USA..
    Fisher, Simon E.
    Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Max Planck Inst Psycholinguist, Language & Genet Dept, Nijmegen, Netherlands..
    Fleischman, Debra A.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL 60612 USA..
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Foroud, Tatiana M.
    Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA.;Indiana Univ, Sch Med, Med & Mol Genet, Indianapolis, IN USA..
    Fox, Peter T.
    Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA..
    Francks, Clyde
    Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Max Planck Inst Psycholinguist, Language & Genet Dept, Nijmegen, Netherlands..
    Fukunaga, Masaki
    Natl Inst Physiol Sci, Div Cerebral Integrat, Aichi, Japan..
    Gibbs, J. Raphael
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England.;NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Glahn, David C.
    Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.;Olin Neuropsychiat Res Ctr, Hartford, CT USA..
    Gollub, Randy L.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA.;Harvard Med Sch, Boston, MA USA..
    Goring, Harald H. H.
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA..
    Grabe, Hans J.
    Univ Med Greifswald, Dept Psychiat, Greifswald, Germany..
    Green, Robert C.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA..
    Gruber, Oliver
    Heidelberg Univ, Dept Gen Psychiat, Sect Expt Psychopathol & Neuroimaging, Heidelberg, Germany..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Guelfi, Sebastian
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England..
    Hansell, Narelle K.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Hardy, John
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England..
    Hartman, Catharina A.
    Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands..
    Hashimoto, Ryota
    Osaka Univ, Grad Sch Med, Dept Psychiat, Osaka, Japan.;Osaka Univ, United Grad Sch Child Dev, Mol Res Ctr Childrens Mental Dev, Osaka, Japan..
    Hegenscheid, Katrin
    Univ Med Greifswald, Inst Diagnost Radiol & Neuroradiol, Greifswald, Germany..
    Heinz, Andreas
    Charite, CCM, Dept Psychiat & Psychotherapy, Berlin, Germany..
    Le Hellard, Stephanie
    Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5020 Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway..
    Hernandez, Dena G.
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England.;NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.;German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany..
    Heslenfeld, Dirk J.
    Vrije Univ Amsterdam, Dept Psychol, Amsterdam, Netherlands..
    Ho, Beng-Choon
    Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA..
    Hoekstra, Pieter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands..
    Hoffmann, Wolfgang
    German Ctr Neurodegenerat Dis DZNE Rostock Greifs, Greifswald, Germany.;Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Holsboer, Florian
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany.;HMNC Brain Hlth, Munich, Germany..
    Homuth, Georg
    Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany..
    Hosten, Norbert
    Univ Med Greifswald, Inst Diagnost Radiol & Neuroradiol, Greifswald, Germany..
    Hottenga, Jouke-Jan
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Pol, Hilleke E. Hulshoff
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Ikeda, Masashi
    Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi, Japan..
    Ikram, M. Kamran
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore.;Natl Univ Hlth Syst, Mem Aging & Cognit Ctr, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Duke NUS Grad Med Sch, Acad Med Res Inst, Singapore, Singapore..
    Jack, Clifford R., Jr.
    Mayo Clin, Dept Radiol, Rochester, MN USA..
    Jenldnson, Mark
    Univ Oxford, FMRIB Ctr, Oxford, England..
    Johnson, Robert
    Univ Maryland, Sch Med, NICHD Brain & Tissue Bank Dev Disorders, Baltimore, MD 21201 USA..
    Jonsson, Erik G.
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Univ Oxford, FMRIB Ctr, Oxford, England..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Kahn, Rene S.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Kanai, Ryota
    Univ Sussex, Sch Psychol, Brighton, E Sussex, England.;UCL, Inst Cognit Neurosci, London, England.;Araya Brain Imaging, Dept Neuroinformat, Tokyo, Japan..
    Kloszewska, Iwona
    Med Univ Lodz, Lodz, Poland..
    Knopman, David S.
    Mayo Clin, Dept Neurol, Rochester, MN USA..
    Kochunov, Peter
    Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA..
    Kwok, John B.
    Neurosci Res Australia, Sydney, NSW, Australia.;UNSW, Sch Med Sci, Sydney, NSW, Australia..
    Lawrie, Stephen M.
    Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland..
    Lemaitre, Herve
    Univ Paris Sud, Univ Paris Descartes, NSERM Unit Neuroimaging & Psychiat 1000, Paris, France.;Hosp Cochin, AP HP, Maison Solenn Adolescent Psychopathol & Med Dept, Paris, France..
    Liu, Xinmin
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.;Columbia Univ, Med Ctr, New York, NY USA..
    Longo, Dan L.
    NIA, Genet Lab, NIH, Baltimore, MD 21224 USA..
    Longstreth, W. T., Jr.
    Univ Washington, Dept Neurol, Seattle, WA 98195 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Lopez, Oscar L.
    Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.;Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA..
    Lovestone, Simon
    Univ Oxford, Dept Psychiat, Oxford, England.;Kings Coll London, NIHR Dementia Biomed Res Unit, London, England..
    Martinez, Oliver
    Univ Calif Davis, Dept Neurol, Imaging Dementia & Aging IDeA Lab, Sacramento, CA 95817 USA.;Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA..
    Martinot, Jean-Luc
    Univ Paris Sud, Univ Paris Descartes, NSERM Unit Neuroimaging & Psychiat 1000, Paris, France.;Hosp Cochin, AP HP, Maison Solenn Adolescent Psychopathol & Med Dept, Paris, France..
    Mattay, Venkata S.
    Lieber Inst Brain Dev, Baltimore, MD USA.;Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA..
    McDonald, Colm
    Natl Univ Ireland Galway, Ctr Neuroimaging & Cognit Genom NICOG, NCBES Galway Neurosci Ctr, Coll Med Nursing & Hlth Sci,Clin Neuroimaging Lab, Galway, Ireland..
    McIntosh, Andrew M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland..
    McMahon, Katie L.
    Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia..
    McMahon, Francis J.
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Mecocci, Patrizia
    Univ Perugia, Dept Med, Sect Gerontol & Geriatr, Perugia, Italy..
    Melle, Ingrid
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Meyer-Lindenberg, Andreas
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany..
    Mohnke, Sebastian
    Charite, CCM, Dept Psychiat & Psychotherapy, Berlin, Germany..
    Montgomery, Grant W.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Morris, Derek W.
    Natl Univ Ireland Galway, Cognit Genet & Cognit Therapy Grp, Neuroimaging Cognit & Genom Ctr NICOG, Galway, Ireland.;Natl Univ Ireland Galway, NCBES Galway Neurosci Ctr, Sch Psychol, Galway, Ireland.;Natl Univ Ireland Galway, Discipline Biochem, Galway, Ireland.;Trinity Coll Dublin, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 8, Ireland.;Trinity Coll Dublin, Inst Psychiat, Dublin 8, Ireland..
    Mosley, Thomas H.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Muhleisen, Thomas W.
    Natl Univ Ireland Galway, Ctr Neuroimaging & Cognit Genom NICOG, NCBES Galway Neurosci Ctr, Coll Med Nursing & Hlth Sci,Clin Neuroimaging Lab, Galway, Ireland.;Res Ctr Julich, Inst Neurosci & Med INM1, Julich, Germany..
    Mueller-Myhsok, Bertram
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany.;Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England..
    Nalls, Michael A.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Nauck, Matthias
    Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.;German Ctr Cardiovasc Res DZHK eV, Partner Site Greifswald, Berlin, Germany..
    Nichols, Thomas E.
    Univ Oxford, FMRIB Ctr, Oxford, England.;Univ Warwick, Dept Stat, Coventry, W Midlands, England.;Univ Warwick, Warwick Mfg Grp, Coventry, W Midlands, England..
    Niessen, Wiro J.
    Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands.;Erasmus MC, Dept Med Informat, Rotterdam, Netherlands.;Delft Univ Technol, Fac Sci Appl, Delft, Netherlands..
    Noethen, Markus M.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany..
    Nyberg, Lars
    Umea Univ, Dept Integrat Med Biol, Umea, Sweden.;Umea Univ, Umea Ctr Funct Brain Imaging, Umea, Sweden..
    Ohi, Kazutaka
    Osaka Univ, Grad Sch Med, Dept Psychiat, Osaka, Japan..
    Olvera, Rene L.
    Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA..
    Ophoff, Roel A.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.;Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA..
    Pandolfo, Massimo
    Univ Libre Bruxelles, Hop Erasme, Dept Neurol, Brussels, Belgium..
    Paus, Tomas
    Univ Toronto, Rotman Res Inst, Toronto, ON, Canada.;Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada.;Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A1, Canada.;Child Mind Inst, New York, NY USA..
    Pausova, Zdenka
    Univ Toronto, Hosp Sick Children, Toronto, ON, Canada.;Univ Toronto, Dept Phys, Toronto, ON, Canada.;Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada..
    Penninx, Brenda W. J. H.
    Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Pike, G. Bruce
    Univ Calgary, Dept Radiol, Calgary, AB, Canada.;Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada..
    Potkin, Steven G.
    Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA..
    Psaty, Bruce M.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Dept Med, Seattle, WA USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.;Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA..
    Reppermund, Simone
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.;UNSW Med, Sch Psychiat, Dept Dev Disabil Neuropsychiat, Kensington, NSW, Australia..
    Rietschel, Marcella
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany..
    Roffman, Joshua L.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA..
    Romanczuk-Seiferth, Nina
    Charite, CCM, Dept Psychiat & Psychotherapy, Berlin, Germany..
    Rotter, Jerome I.
    Univ Calif Los Angeles, Med Ctr, Ilnst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst & Pediat Harbor, Torrance, CA 90509 USA..
    Ryten, Mina
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England.;Kings Coll London, Dept Med & Mol Genet, London, England..
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth Sci, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Evelyn F McKnight Brain Inst, Miami, FL 33136 USA..
    Sachdev, Perminder S.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.;Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia..
    Saykin, Andrew J.
    Indiana Univ, Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN USA.;Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA.;Indiana Univ, Sch Med, Med & Mol Genet, Indianapolis, IN USA..
    Schmidt, Reinhold
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria..
    Schofield, Peter R.
    Neurosci Res Australia, Sydney, NSW, Australia.;UNSW, Sch Med Sci, Sydney, NSW, Australia..
    Sigurdsson, Sigurdur
    Iceland Heart Assoc, Kopavogur, Iceland..
    Simmons, Andy
    Kings Coll London, Inst Psychiat, Dept Neuroimaging, London, England.;Kings Coll London, Biomed Res Ctr Mental Hlth, London, England.;Kings Coll London, Biomed Res Unit Dementia, London, England..
    Singleton, Andrew
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Sisodiya, Sanjay M.
    UCL, Inst Neurol, London, England.;Epilepsy Soc, Gerrards Cross, Bucks, England..
    Smith, Colin
    Univ Edinburgh, Acad Dept Neuropathol, Ctr Clin Brain Sci, MRC Edinburgh Brain Bank, Edinburgh, Midlothian, Scotland..
    Smoller, Jordan W.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA.;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA..
    Soininen, Hindu.
    Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.;Kuopio Univ Hosp, Neuroctr Neurol, Kuopio, Finland..
    Srikanth, Velandai
    Peninsula Hlth & Monash Univ, Dept Med, Melbourne, Vic, Australia..
    Steen, Vidar M.
    Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5020 Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway..
    Stott, David J.
    Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Sussmann, Jessika E.
    Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland..
    Thalamuthu, Anbupalam
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia..
    Tiemeier, Henning
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands..
    Toga, Arthur W.
    Univ Southern Calif, Keck Sch Med, Inst Neuroimaging & Informat, Lab Neuro Imaging, Los Angeles, CA USA..
    Traynor, Bryan J.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Troncoso, Juan
    Johns Hopkins Univ, Brain Resource Ctr, Baltimore, MD USA..
    Turner, Jessica A.
    Georgia State Univ, Atlanta, GA 30303 USA..
    Tzourio, Christophe
    Univ Bordeaux, Institute Neurodegenerat Disorders, CEA, CNRS,UMR 5293, Bordeaux, France..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Hernandez, Maria C. Valdes
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland..
    Van der Brug, Marcel
    Genentech Inc, San Francisco, CA 94080 USA..
    Van der Lugt, Aad
    Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands..
    Van der Wee, Nic J. A.
    Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.;Leiden Univ, Med Ctr, Leiden Inst Brain & Cognit, Leiden, Netherlands..
    Van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Van Haren, Neeltje E. M.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Van't Ent, Dennis
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Van Tol, Marie Jose
    Univ Groningen, Univ Med Ctr Groningen, Neuroimaging Ctr, Groningen, Netherlands..
    Vardarajan, Badri N.
    Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA..
    Veltman, Dick J.
    Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Vernooij, Meike W.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands..
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Walter, Henrik
    Charite, CCM, Dept Psychiat & Psychotherapy, Berlin, Germany..
    Wardlaw, Joanna M.
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland..
    Wassink, Thomas H.
    Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA..
    Weale, Michael E.
    Kings Coll London, Dept Med & Mol Genet, London, England..
    Weinberger, Daniel R.
    Lieber Inst Brain Dev, Baltimore, MD USA.;Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA..
    Weiner, Michael W.
    Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 USA..
    Wen, Wei
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia..
    Westman, Eric
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    White, Tonya
    Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands.;Erasmus MC Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands..
    Wong, Tien Y.
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Dagestan State Univ, Dept Evolut & Genet, Makhachkala, Dagestan, Russia.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore..
    Wright, Clinton B.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth Sci, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Evelyn F McKnight Brain Inst, Miami, FL 33136 USA..
    Zielke, H. Ronald
    Univ Maryland, Sch Med, NICHD Brain & Tissue Bank Dev Disorders, Baltimore, MD 21201 USA..
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland..
    DeCarli, Charles
    Univ Calif Davis, Dept Neurol, Imaging Dementia & Aging IDeA Lab, Sacramento, CA 95817 USA.;Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA..
    Schmidt, Helena
    Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria..
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    De Craen, Anton J. M.
    Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Wright, Margaret J.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia..
    Launer, Lenore J.
    NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Schumann, Gunter
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London, England..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med & Human Genet Ctr, Houston, TX 77030 USA..
    Franke, Barbara
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Debette, Stephanie
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Lieber Inst Brain Dev, Baltimore, MD USA.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France..
    Medland, Sarah E.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands.;Erasmus MC, Dept Neurol, Rotterdam, Netherlands..
    Thompson, Paul M.
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA.;Univ Western Sydney, Sch Comp Engn & Math, Parramatta, NSW, Australia..
    Novel genetic loci underlying human intracranial volume identified through genome-wide association2016Inngår i: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 19, nr 12, s. 1569-1582Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  • 27.
    Adeyemi, Ahmed
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Bergman, Joakim
    AstraZeneca, Dept Med Chem Cardiovasc & Metab Dis, Innovat Med & Early Dev Biotech Unit, Pepparedsleden 1, S-43183 Molndal, Sweden..
    Branalt, Jonas
    AstraZeneca, Dept Med Chem Cardiovasc & Metab Dis, Innovat Med & Early Dev Biotech Unit, Pepparedsleden 1, S-43183 Molndal, Sweden..
    Sävmarker, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Larhed, Mats
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi.
    Continuous Flow Synthesis under High-Temperature/High-Pressure Conditions Using a Resistively Heated Flow Reactor2017Inngår i: Organic Process Research & Development, ISSN 1083-6160, E-ISSN 1520-586X, Vol. 21, nr 7, s. 947-955Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A cheap, easy-to-build, and effective resistively heated reactor for continuous flow synthesis at high temperature and pressure is herein presented. The reactor is rapidly heated directly using, an electric current and is capable of rapidly delivering temperatures and pressures up to 400 degrees C and 200 bar, respectively. High-temperature and high-pressure applications of this reactor were safely performed and demonstrated by selected transformations such as esterifications, transesterifications, and direct carboxylic acid to nitrile reactions using supercritical ethanol, methanol, and acetonitrile. Reaction temperatures were between 300 and 400 degrees C with excellent conversions and good to excellent isolated product yields. Examples of Diels-Alder reactions were also carried out at temperatures up to 300 degrees C in high yield. No additives or catalysts were used in the reactions.

  • 28.
    Adeyemi, Ahmed
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Wetzel, Alexander
    AstraZeneca, Dept Med Chem, Cardiovasc Renal & Metab IMED Biotech Unit, Pepparedsleden 1, S-43183 Molndal, Sweden.
    Bergman, Joakim
    AstraZeneca, Dept Med Chem, Cardiovasc Renal & Metab IMED Biotech Unit, Pepparedsleden 1, S-43183 Molndal, Sweden.
    Brånalt, Jonas
    AstraZeneca, Dept Med Chem, Cardiovasc Renal & Metab IMED Biotech Unit, Pepparedsleden 1, S-43183 Molndal, Sweden.
    Larhed, Mats
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Preparativ läkemedelskemi.
    Regio- and Stereoselective Synthesis of Spirooxindoles via Mizoroki-Heck Coupling of Aryl Iodides2019Inngår i: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, ISSN 0936-5214, E-ISSN 1437-2096, Vol. 30, nr 1, s. 82-88Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A method for highly regio- and stereoselective intramolecular Mizoroki-Heck 5- exo cyclization of aryl iodides to the corresponding spirooxindoles has been developed. Electron-rich and electron-deficient aryl iodide precursors were selectively ring-closed with high stereoselectivity and good yields. The double-bond position in the cyclopentene ring was controlled by careful choice of reaction conditions. These rare spiro compounds were further functionalized to rigidified unnatural amino acid derivatives by a subsequent gas-free Pd(0)-catalyzed alkoxycarbonylation, followed by selective O - and N -deprotections.

  • 29.
    Adl, Sina M.
    et al.
    Univ Saskatchewan, Dept Soil Sci, Coll Agr & Bioresources, 51 Campus Dr, Saskatoon, SK S7N 5A8, Canada.
    Bass, David
    Nat Hist Museum, Dept Life Sci, Cromwell Rd, London SW7 5BD, England;CEFAS, Barrack Rd, Weymouth DT4 8UB, Dorset, England.
    Lane, Christopher E.
    Univ Rhode Isl, Dept Biol Sci, Kingston, RI 02881 USA.
    Lukes, Julius
    Czech Acad Sci, Biol Ctr, Inst Parasitol, Ceske Budejovice 37005, Czech Republic;Univ South Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic.
    Schoch, Conrad L.
    Natl Inst Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20892 USA.
    Smirnov, Alexey
    St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia.
    Agatha, Sabine
    Univ Salzburg, Dept Biosci, Hellbrunnerstr 34, A-5020 Salzburg, Austria.
    Berney, Cedric
    CNRS, UMR 7144 AD2M, Grp Evolut Protistes & Ecosyst Pelag, Stn Biol Roscoff, Pl Georges Teissier, F-29680 Roscoff, France.
    Brown, Matthew W.
    Mississippi State Univ, Dept Biol Sci, Starkville, MS 39762 USA;Mississippi State Univ, Inst Genom Biocomp & Biotechnol, Starkville, MS 39762 USA.
    Burki, Fabien
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Cárdenas, Paco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Cepicka, Ivan
    Charles Univ Prague, Dept Zool, Fac Sci, Vinicna 7, CR-12844 Prague, Czech Republic.
    Chistyakova, Lyudmila
    St Petersburg State Univ, Core Facil Ctr Culture Collect Microorganisms, St Petersburg 198504, Russia.
    del Campo, Javier
    CSIC, Inst Ciencies Mar, Passeig Maritim Barceloneta 37-49, E-08003 Barcelona, Catalonia, Spain.
    Dunthorn, Micah
    Univ Kaiserslautern, Dept Ecol, Erwin Schroedinger St, D-67663 Kaiserslautern, Germany;Univ Duisburg Essen, Dept Eukaryot Microbiol, Univ Str 5, D-45141 Essen, Germany.
    Edvardsen, Bente
    Univ Oslo, Dept Biosci, POB 1066 Blindern, N-0316 Oslo, Norway.
    Eglit, Yana
    Dalhousie Univ, Dept Biol, Halifax B3H 4R2, NS, Canada.
    Guillou, Laure
    Univ Paris 06, Sorbonne Univ, Paris 6, CNRS,UMR 7144 AD2M,Stn Biol Roscoff, Pl Georges Teissier,,CS90074, F-29688 Roscoff, France.
    Hampl, Vladimir
    Charles Univ Prague, Dept Parasitol, Fac Sci, BIOCEV, Prumyslov 595, Vestec 25242, Czech Republic.
    Heiss, Aaron A.
    Amer Museum Nat Hist, Dept Invertebrate Zool, New York, NY 10024 USA.
    Hoppenrath, Mona
    DZMB German Ctr Marine Biodivers Res, D-26382 Wilhelmshaven, Germany.
    James, Timothy Y.
    Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
    Karnkowska, Anna
    Univ Warsaw, Dept Mol Phylogenet & Evolut, PL-02089 Warsaw, Poland.
    Karpov, Sergey
    St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia;RAS, Lab Parasit Worms & Protistol, Zool Inst, St Petersburg 199034, Russia.
    Kim, Eunsoo
    Amer Museum Nat Hist, Dept Invertebrate Zool, New York, NY 10024 USA.
    Kolisko, Martin
    Czech Acad Sci, Biol Ctr, Inst Parasitol, Ceske Budejovice 37005, Czech Republic.
    Kudryavtsev, Alexander
    St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia;RAS, Lab Parasit Worms & Protistol, Zool Inst, St Petersburg 199034, Russia.
    Lahr, Daniel J. G.
    Univ Sao Paulo, Dept Zool, Inst Biosci, Matao Travessa 14 Cidade Univ, BR-05508090 Sao Paulo, SP, Brazil.
    Lara, Enrique
    Univ Neuchatel, Lab Soil Biodivers, Rue Emile Argand 11, CH-2000 Neuchatel, Switzerland;CSIC, Real Jardim Bot,Plaza Murillo 2, E-28014 Madrid, Spain.
    Le Gall, Line
    Sorbonne Univ, Museum Natl Hist Nat, Inst Systemat Evolut Biodiversit, 57 Rue Cuvier,CP 39, F-75005 Paris, France.
    Lynn, Denis H.
    Univ Guelph, Dept Integrat Biol, Summerlee Sci Complex, Guelph, ON N1G 2W1, Canada;Univ British Columbia, Dept Zool, 4200-6270 Univ Blvd, Vancouver, BC V6T 1Z4, Canada.
    Mann, David G.
    Royal Bot Garden, Edinburgh EH3 5LR, Midlothian, Scotland;Inst Agrifood Res & Technol, C Poble Nou Km 5-5, E-43540 San Carlos de la Rapita, Spain.
    Massana, Ramon
    CSIC, Inst Ciencies Mar, Passeig Maritim Barceloneta 37-49, E-08003 Barcelona, Catalonia, Spain.
    Mitchell, Edward A. D.
    Univ Neuchatel, Lab Soil Biodivers, Rue Emile Argand 11, CH-2000 Neuchatel, Switzerland;Jardin Bot Neuchatel,Chemin Perthuis du Salut 58, CH-2000 Neuchatel, Switzerland.
    Morrow, Christine
    Natl Museums Northern Ireland, Dept Nat Sci, 153 Bangor Rd, Holywood BT18 0EU, England.
    Park, Jong Soo
    Kyungpook Natl Univ, Sch Earth Syst Sci, Dept Oceanog, Daegu, South Korea;Kyungpook Natl Univ, Sch Earth Syst Sci, Kyungpook Inst Oceanog, Daegu, South Korea.
    Pawlowski, Jan W.
    Univ Geneva, Dept Genet & Evolut, CH-1211 Geneva 4, Switzerland.
    Powell, Martha J.
    Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA.
    Richter, Daniel J.
    Univ Pompeu Fabra, CSIC, Inst Biol Evolut, Passeig Maritim Barceloneta 37-49, Barcelona 08003, Spain.
    Rueckert, Sonja
    Edinburgh Napier Univ, Sch Appl Sci, Edinburgh EH11 4BN, Midlothian, Scotland.
    Shadwick, Lora
    Univ Arkansas, Dept Biol Sci, Fayetteville, AR 72701 USA.
    Shimano, Satoshi
    Hosei Univ, Sci Res Ctr, Chiyoda Ku, 2-17-1 Fujimi, Tokyo, Japan.
    Spiegel, Frederick W.
    Univ Arkansas, Dept Biol Sci, Fayetteville, AR 72701 USA.
    Torruella, Guifre
    Univ Paris XI, Lab Evolut & Systemat, F-91405 Orsay, France.
    Youssef, Noha
    Oklahoma State Univ, Dept Microbiol & Mol Genet, Stillwater, OK 74074 USA.
    Zlatogursky, Vasily V.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Systematisk biologi. St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia.
    Zhang, Qianqian
    Chinese Acad Sci, Yantai Inst Coastal Zone Res, Yantai 264003, Peoples R China.
    Revisions to the Classification, Nomenclature, and Diversity of Eukaryotes2019Inngår i: Journal of Eukaryotic Microbiology, ISSN 1066-5234, E-ISSN 1550-7408, Vol. 66, nr 1, s. 4-119Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This revision of the classification of eukaryotes follows that of Adl et al., 2012 [J. Euk. Microbiol. 59(5)] and retains an emphasis on protists. Changes since have improved the resolution of many nodes in phylogenetic analyses. For some clades even families are being clearly resolved. As we had predicted, environmental sampling in the intervening years has massively increased the genetic information at hand. Consequently, we have discovered novel clades, exciting new genera and uncovered a massive species level diversity beyond the morphological species descriptions. Several clades known from environmental samples only have now found their home. Sampling soils, deeper marine waters and the deep sea will continue to fill us with surprises. The main changes in this revision are the confirmation that eukaryotes form at least two domains, the loss of monophyly in the Excavata, robust support for the Haptista and Cryptista. We provide suggested primer sets for DNA sequences from environmental samples that are effective for each clade. We have provided a guide to trophic functional guilds in an appendix, to facilitate the interpretation of environmental samples, and a standardized taxonomic guide for East Asian users.

    Fulltekst (pdf)
    fulltext
  • 30.
    Adler, Jeremy
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala Univ, Dept Immunol Genet & Pathol, BioVis, Uppsala, Sweden..
    Huang, Ainsley
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Biochem & Cell Biol, Gothenburg, Sweden..
    Parmryd, Ingela
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Biochem & Cell Biol, Gothenburg, Sweden..
    Find_plasma_membrane and measure_plasma_membrane: ImageJ macros for efficient identification of and measurements at and around the plasma membrane2023Inngår i: SoftwareX, E-ISSN 2352-7110, Vol. 24, artikkel-id 101570Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The plasma membrane that encloses cells is difficult to precisely delineate but this is often required for quantitation of fluorescence images. We have created an ImageJ macro that efficiently maps the plasma membrane based on a few imprecisely marked points as the user input, to generate a one-pixel-wide region of interest. A second macro makes measurements from the plasma membrane and optionally from additional regions of interest, offset both inwards and outwards from the plasma membrane. While we are interested in membrane order quantified by generalized polarization, any measurements from two or more channels could easily be implemented.

  • 31.
    Adler, Jeremy
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Parmryd, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Quantifying colocalization: thresholding, void voxels and the H-coef2014Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 9, nr 11, s. e111983-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A critical step in the analysis of images is identifying the area of interest e.g. nuclei. When the nuclei are brighter than the remainder of the image an intensity can be chosen to identify the nuclei. Intensity thresholding is complicated by variations in the intensity of individual nuclei and their intensity relative to their surroundings. To compensate thresholds can be based on local rather than global intensities. By testing local thresholding methods we found that the local mean performed poorly while the Phansalkar method and a new method based on identifying the local background were superior. A new colocalization coefficient, the Hcoef, highlights a number of controversial issues. (i) Are molecular interactions measurable (ii) whether to include voxels without fluorophores in calculations, and (iii) the meaning of negative correlations. Negative correlations can arise biologically (a) because the two fluorophores are in different places or (b) when high intensities of one fluorophore coincide with low intensities of a second. The cases are distinct and we argue that it is only relevant to measure correlation using pixels that contain both fluorophores and, when the fluorophores are in different places, to just report the lack of co-occurrence and omit these uninformative negative correlation. The Hcoef could report molecular interactions in a homogenous medium. But biology is not homogenous and distributions also reflect physico-chemical properties, targeted delivery and retention. The Hcoef actually measures a mix of correlation and co-occurrence, which makes its interpretation problematic and in the absence of a convincing demonstration we advise caution, favouring separate measurements of correlation and of co-occurrence.

    Fulltekst (pdf)
    fulltext
  • 32.
    Adler, Jeremy
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sintorn, Ida-Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Strand, Robin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Parmryd, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Conventional analysis of movement on non-flat surfaces like the plasma membrane makes Brownian motion appear anomalous2019Inngår i: Communications Biology, E-ISSN 2399-3642, Vol. 2, artikkel-id 12Artikkel i tidsskrift (Fagfellevurdert)
  • 33.
    Adolfsson, Päivi
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Hysing, Jennie
    City of Stockholm, Sweden..
    Ek, Pia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Dietitians’ endeavor to contribute to the nutritional health of children and youth with intellectual disability and autism2023Inngår i: International Journal of Developmental Disabilities, ISSN 2047-3869Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of the present study was to explore the experiences of registered dietitians (RD) who consult children and youth with intellectual disability (ID) and autism. Another aim was to investigate how knowledge and working methods were transferred to RDs working with adults with ID and autism. Twenty-six RDs completed a web-based study-specific questionnaire with multiple-choice and open-ended questions. The respondents’ comments and responses to the open-ended questions were analyzed using systematic text condensation. The analyses resulted in four categories: Reachability and accessibility of RDs, Clients do not comply with RDs’ dietary advice, RD finds individual solutions and Better collaboration for better knowledge. It was noteworthy that RDs’ undergraduate education did not prepare them for clients with ID and autism. Instead, they learned by doing and from other professionals at the clinic if they collaborate with them or were part in teams around the client. The RDs reported a lack of national routines for the transition process of nutrition support from young to adult.

    Fulltekst (pdf)
    fulltext
  • 34.
    Adolphe, Christelle
    et al.
    Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia..
    Millar, Amanda
    Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia..
    Kojic, Marija
    Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia..
    Barkauskas, Deborah S.
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Sundström, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Swartling, Fredrik J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hediyeh-Zadeh, Soroor
    Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic, Australia.;Univ Melbourne, Fac Med Dent & Hlth Sci, Dept Med Biol, Melbourne, Vic, Australia..
    Tan, Chin Wee
    Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic, Australia.;Univ Melbourne, Fac Med Dent & Hlth Sci, Dept Med Biol, Melbourne, Vic, Australia..
    Davis, Melissa J.
    Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic, Australia.;Univ Melbourne, Fac Med Dent & Hlth Sci, Dept Med Biol, Melbourne, Vic, Australia.;Univ Melbourne, Fac Med Dent & Hlth Sci, Dept Clin Pathol, Melbourne, Vic, Australia..
    Genovesi, Laura A.
    Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia..
    Wainwright, Brandon J.
    Univ Queensland, Univ Queensland Diamantina Inst, Woolloongabba, Qld 4102, Australia..
    SOX9 Defines Distinct Populations of Cells in SHH Medulloblastoma but Is Not Required for Math1-Driven Tumor Formation2021Inngår i: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 19, nr 11, s. 1831-1839Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Medulloblastoma is the most common malignant pediatric brain tumor and there is an urgent need for molecularly targeted and subgroup-specific therapies. The stem cell factor SOX9, has been proposed as a potential therapeutic target for the treatment of Sonic Hedgehog medulloblastoma (SHH-MB) subgroup tumors, given its role as a downstream target of Hedgehog signaling and in functionally promoting SHH-MB metastasis and treatment resistance. However, the functional requirement for SOX9 in the genesis of medulloblastoma remains to be determined. Here we report a previously undocumented level of SOX9 expression exclusively in proliferating granule cell precursors ( GCP) of the postnatal mouse cerebellum, which function as the medulloblastoma-initiating cells of SHH-MBs. Wild-type GCPs express comparatively lower levels of SOX9 than neural stem cells and mature astroglia and SOX9(low) GCP-like tumor cells constitute the bulk of both infant (Math1Cre: Ptch1(lox/lox)) and adult (Ptch1(LacZ/+)) SHH-MB mouse models. Human medulloblastoma single-cell RNA data analyses reveal three distinct SOX9 populations present in SHH-MB and noticeably absent in other medulloblastoma subgroups: SOX9(+)MATH1(+) (GCP), SOX9(+)GFAP(+) (astrocytes) and SOX9(+)MATH1(+)GFAP(+) (potential tumor-derived astrocytes). To functionally address whether SOX9 is required as a downstream effector of Hedgehog signaling in medulloblastoma tumor cells, we ablated Sox9 using a Math1Cre model system. Surprisingly, targeted ablation of Sox9 in GCPs (Math1Cre:Sox9(lox/lox)) revealed no overt phenotype and loss of Sox9 in SHH-MB (Math1Cre:Ptch1(lox/lox);Sox9(lox/lox)) does not affect tumor formation.

  • 35. Adoue, Veronique
    et al.
    Schiavi, Alicia
    Light, Nicholas
    Carlsson Almlöf, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lundmark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ge, Bing
    Kwan, Tony
    Caron, Maxime
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Wang, Chuan
    Chen, Shu-Huang
    Goodall, Alison H
    Cambien, Francois
    Deloukas, Panos
    Ouwehand, Willem H
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Pastinen, Tomi
    Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs2014Inngår i: Molecular Systems Biology, ISSN 1744-4292, E-ISSN 1744-4292, Vol. 10, nr 10, s. 754-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor-SNP interactions. By perturbing NFκB action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NFκB perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases.

    Fulltekst (pdf)
    fulltext
  • 36.
    Aerts, Jordan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Andrén, Per E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jansson, Erik T.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Electrochemically Etched Tapered-Tip Stainless-Steel Electrospray-Ionization Emitters for Capillary Electrophoresis-Mass Spectrometry2023Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 22, nr 4, s. 1377-1380Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have used household consumables to facilitate electrochemical etching of stainless-steel hypodermic tubing to produce tapered-tip emitters suitable for electrospray ionization for use in mass spectrometry. The process involves the use of 1% oxalic acid and a 5 W USB power adapter, commonly known as a phone charger. Further, our method avoids the otherwise commonly used strong acids that entail chemical hazards: concentrated HNO3 for etching stainless steel, or concentrated HF for etching fused silica. Hence, we here provide a convenient and self-inhibiting procedure with minimal chemical hazards to manufacture tapered-tip stainless-steel emitters. We show its performance in metabolomic analysis with CE-MS of a tissue homogenate where the metabolites acetylcarnitine, arginine, carnitine, creatine, homocarnosine, and valerylcarnitine were identified, all with basepeak separated electropherograms, within <6 min of separation. The mass spectrometry data are freely available through the MetaboLight public data repository via access number MTBLS7230.

    Fulltekst (pdf)
    fulltext
  • 37.
    Aerts, Jordan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala751 24, Sweden.
    Andrén, Per E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, MMS, medicinsk masspektrometri. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala751 24, Sweden;Science for Life Laboratory, Spatial Mass Spectrometry, Uppsala University, Uppsala751 24, Sweden.
    Jansson, Erik T.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala751 24, Sweden.
    Zero-Degree Celsius Capillary Electrophoresis Electrospray Ionization for Hydrogen Exchange Mass Spectrometry2023Inngår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, ISSN 0003-2700, Vol. 95, nr 2, s. 1149-1158Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Currently, fast liquid chromatographic separations at low temperatures are exclusively used for the separation of peptides generated in hydrogen deuterium exchange (HDX) workflows. However, it has been suggested that capillary electrophoresis may be a better option for use with HDX. We performed in solution HDX on peptides and bovine hemoglobin (Hb) followed by quenching, pepsin digestion, and cold capillary electrophoretic separation coupled with mass spectrometry (MS) detection for benchmarking a laboratory-built HDX–MS platform. We found that capillaries with a neutral coating to eliminate electroosmotic flow and adsorptive processes provided fast separations with upper limit peak capacities surpassing 170. In contrast, uncoated capillaries achieved 30% higher deuterium retention for an angiotensin II peptide standard owing to faster separations but with only half the peak capacity of coated capillaries. Data obtained using two different separation conditions on peptic digests of Hb showed strong agreement of the relative deuterium uptake between methods. Processed data for denatured versus native Hb after deuterium labeling for the longest timepoint in this study (50,000 s) also showed agreement with subunit interaction sites determined by crystallographic methods. All proteomic data are available under DOI: 10.6019/PXD034245.

  • 38.
    Agarwal, Prasoon
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Collier, Paul
    Fritz, Markus Hsi-Yang
    Benes, Vladimir
    Wiklund, Helena Jernberg
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Westermark, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Singh, Umashankar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    CGGBP1 mitigates cytosine methylation at repetitive DNA sequences2015Inngår i: BMC Genomics, E-ISSN 1471-2164, Vol. 16, artikkel-id 390Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: CGGBP1 is a repetitive DNA-binding transcription regulator with target sites at CpG-rich sequences such as CGG repeats and Alu-SINEs and L1-LINEs. The role of CGGBP1 as a possible mediator of CpG methylation however remains unknown. At CpG-rich sequences cytosine methylation is a major mechanism of transcriptional repression. Concordantly, gene-rich regions typically carry lower levels of CpG methylation than the repetitive elements. It is well known that at interspersed repeats Alu-SINEs and L1-LINEs high levels of CpG methylation constitute a transcriptional silencing and retrotransposon inactivating mechanism. Results: Here, we have studied genome-wide CpG methylation with or without CGGBP1-depletion. By high throughput sequencing of bisulfite-treated genomic DNA we have identified CGGBP1 to be a negative regulator of CpG methylation at repetitive DNA sequences. In addition, we have studied CpG methylation alterations on Alu and L1 retrotransposons in CGGBP1-depleted cells using a novel bisulfite-treatment and high throughput sequencing approach. Conclusions: The results clearly show that CGGBP1 is a possible bidirectional regulator of CpG methylation at Alus, and acts as a repressor of methylation at L1 retrotransposons.

    Fulltekst (pdf)
    fulltext
  • 39.
    Agarwal, Prasoon
    et al.
    Lund Univ, Dept Lab Med, Div Occupat & Environm Med, Sci Life Lab,Natl Bioinformat Infrastructure Swede, S-22362 Lund, Sweden..
    Glowacka, Aleksandra
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17165 Solna, Sweden..
    Mahmoud, Loay
    Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden..
    Bazzar, Wesam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17165 Solna, Sweden..
    Larsson, Lars-Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17165 Solna, Sweden..
    Alzrigat, Mohammad
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17165 Solna, Sweden..
    MYCN Amplification Is Associated with Reduced Expression of Genes Encoding gamma-Secretase Complex and NOTCH Signaling Components in Neuroblastoma2023Inngår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 24, nr 9, artikkel-id 8141Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amplification of the MYCN oncogene is found in similar to 20% of neuroblastoma (NB) cases and correlates with high-risk disease and poor prognosis. Despite the plethora of studies describing the role of MYCN in NB, the exact molecular mechanisms underlying MYCN's contribution to high-risk disease are not completely understood. Herein, we implemented an integrative approach combining publicly available RNA-Seq and MYCN ChIP-Seq datasets derived from human NB cell lines to define biological processes directly regulated by MYCN in NB. Our approach revealed that MYCN-amplified NB cell lines, when compared to non-MYCN-amplified cell lines, are characterized by reduced expression of genes involved in NOTCH receptor processing, axoneme assembly, and membrane protein proteolysis. More specifically, we found genes encoding members of the gamma-secretase complex, which is known for its ability to liberate several intracellular signaling molecules from membrane-bound proteins such as NOTCH receptors, to be down-regulated in MYCN-amplified NB cell lines. Analysis of MYCN ChIP-Seq data revealed an enrichment of MYCN binding at the transcription start sites of genes encoding gamma-secretase complex subunits. Notably, using publicly available gene expression data from NB primary tumors, we revealed that the expression of gamma-secretase subunits encoding genes and other components of the NOTCH signaling pathway was also reduced in MYCN-amplified tumors and correlated with worse overall survival in NB patients. Genetic or pharmacological depletion of MYCN in NB cell lines induced the expression of gamma-secretase genes and NOTCH-target genes. Chemical inhibition of gamma-secretase activity dampened the expression of NOTCH-target genes upon MYCN depletion in NB cells. In conclusion, this study defines a set of MYCN-regulated pathways that are specific to MYCN-amplified NB tumors, and it suggests a novel role for MYCN in the suppression of genes of the gamma-secretase complex, with an impact on the NOTCH-target gene expression in MYCN-amplified NB.

    Fulltekst (pdf)
    FULLTEXT01
  • 40.
    Agathangelidis, Andreas
    et al.
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece..
    Chatzidimitriou, Anastasia
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Gemenetzi, Katerina
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece.;Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece..
    Giudicelli, Veronique
    Univ Montpellier, Ctr Natl Rech Sci CNRS, Inst Genet Humaine IGH, Unite Mixte Rech UMR, Montpellier, France..
    Karypidou, Maria
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece..
    Plevova, Karla
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Ctr Mol Med, Cent European Inst Technol, Brno, Czech Republic..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Yan, Xiao-Jie
    Feinstein Inst Med Res, Northwell Hlth, Manhasset, NY USA..
    Jeromin, Sabine
    MLL Munich Leukemia Lab, Munich, Germany..
    Schneider, Christof
    Univ Hosp Med Ctr, Ulm, Germany..
    Pedersen, Lone Bredo
    Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Tschumper, Renee C.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Sutton, Lesley-Ann
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Baliakas, Panagiotis
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Scarfo, Lydia
    Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Strateg Res Program CLL,Ist Ricovero & Cura Carat, Milan, Italy..
    van Gastel, Ellen J.
    Univ Med Ctr UMC, Dept Immunol, Lab Med Immunol, Erasmus MC, Rotterdam, Netherlands..
    Armand, Marine
    Sorbonne Univ, Ctr Rech Cordeliers, Dept Biol Hematol, Hop Pitie Salpetriere,AP HP,UMR S 1138, Paris, France..
    Tausch, Eugen
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Biderman, Bella
    Natl Res Ctr Hematol, Moscow, Russia..
    Baer, Constance
    MLL Munich Leukemia Lab, Munich, Germany..
    Bagnara, Davide
    Univ Genoa, Dept Expt Med, Genoa, Italy..
    Navarro, Alba
    Ctr Invest Biomed Red Oncol CIBERONC, Madrid, Spain.;Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain..
    de Septenville, Anne Langlois
    Sorbonne Univ, Ctr Rech Cordeliers, Dept Biol Hematol, Hop Pitie Salpetriere,AP HP,UMR S 1138, Paris, France..
    Guido, Valentina
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Haematol Dept, Mol Pathol Unit, Milan, Italy..
    Mitterbauer-Hohendanner, Gerlinde
    Med Univ Vienna, Dept Lab Med, Vienna, Austria..
    Dimovski, Aleksandar
    Ss Cyril & Methodius Univ Skopje, Fac Pharm, Skopje, North Macedonia..
    Brieghel, Christian
    Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Lawless, Sarah
    Belfast City Hosp, Clin Haematol, Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland..
    Meggendorfer, Manja
    MLL Munich Leukemia Lab, Munich, Germany..
    Brazdilova, Kamila
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Ctr Mol Med, Cent European Inst Technol, Brno, Czech Republic..
    Ritgen, Matthias
    Univ Hosp Schleswig Holstein, Med Dept 2, Campus Kiel, Kiel, Germany..
    Facco, Monica
    Univ Padua, Dept Med DIMED, Hematol & Clin Immunol Unit, Padua, Italy.;Veneto Inst Mol Med, Padua, Italy..
    Tresoldi, Cristina
    Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, IRCCS, Milan, Italy..
    Visentin, Andrea
    Univ Padua, Dept Med DIMED, Hematol & Clin Immunol Unit, Padua, Italy.;Veneto Inst Mol Med, Padua, Italy..
    Patriarca, Andrea
    Univ Eastern Piedmont Osped Maggiore Carita, Dept Translat Med, Div Hematol, Novara, Italy..
    Catherwood, Mark
    Belfast City Hosp, Clin Haematol, Belfast Hlth & Social Care Trust, Belfast, Antrim, North Ireland..
    Bonello, Lisa
    Azienda Osped Univ AOU, City Hlth & Sci Turin, Gen Anatomopathol & Mol Oncogenet, Turin, Italy..
    Sudarikov, Andrey
    Natl Res Ctr Hematol, Moscow, Russia..
    Vanura, Katrina
    Med Univ Vienna, Dept Lab Med, Vienna, Austria..
    Roumelioti, Maria
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Francova, Hana Skuhrova
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic..
    Moysiadis, Theodoros
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece..
    Veronese, Silvio
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Haematol Dept, Mol Pathol Unit, Milan, Italy..
    Giannopoulos, Krzysztof
    Med Univ Lublin, Expt Hematooncol Dept, Lublin, Poland..
    Mansouri, Larry
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Karan-Djurasevic, Teodora
    Univ Belgrade, Inst Mol Genet & Genet Engn, Belgrade, Serbia..
    Sandaltzopoulos, Raphael
    Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece..
    Bodor, Csaba
    Semmelweis Univ, Dept Pathol & Expt Canc Res 1, MTA SE Momentum Mol Oncohematol Res Grp, Budapest, Hungary..
    Fais, Franco
    Univ Genoa, Dept Expt Med, Genoa, Italy.;IRCCS Osped Policlin San Martino, UO Mol Pathol, Genoa, Italy..
    Kater, Arnon
    Univ Amsterdam, Amsterdam UMC, Amsterdam Infect & Immun Inst, Dept Hematol,Canc Ctr Amsterdam, Amsterdam, Netherlands..
    Panovska, Irina
    Ss Cyril & Methodius Univ Skopje, Fac Med, Dept Hematol, Skopje, North Macedonia..
    Rossi, Davide
    Inst Southern Switzerland, Div Hematol Oncol, Bellinzona, Switzerland..
    Alshemmari, Salem
    Kuwait Univ, Fac Med, Dept Med, Kuwait, Kuwait..
    Panagiotidis, Panagiotis
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Costeas, Paul
    Ctr Study Haematol Malignancies, Nicosia, Cyprus.;Karaiskakio Fdn, Nicosia, Cyprus..
    Espinet, Blanca
    Hosp Mar, Serv Patol & Serv Hematol, Lab Citogenet Mol, Lab Citol Hematol, Barcelona, Spain..
    Antic, Darko
    Clin Ctr Serbia, Clin Hematol, Belgrade, Serbia..
    Foroni, Letizia
    Hammersmith Hosp, London, England..
    Montillo, Marco
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Haematol Dept, Mol Pathol Unit, Milan, Italy..
    Trentin, Livio
    Univ Padua, Dept Med DIMED, Hematol & Clin Immunol Unit, Padua, Italy.;Veneto Inst Mol Med, Padua, Italy..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Hematol Dept, Hematocrit HCT Unit, Thessaloniki, Greece..
    Gaidano, Gianluca
    Univ Eastern Piedmont Osped Maggiore Carita, Dept Translat Med, Div Hematol, Novara, Italy..
    di Celle, Paola Francia
    Azienda Osped Univ AOU, City Hlth & Sci Turin, Gen Anatomopathol & Mol Oncogenet, Turin, Italy..
    Niemann, Carsten
    Copenhagen Univ Hosp, Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Campo, Elias
    Ctr Invest Biomed Red Oncol CIBERONC, Madrid, Spain.;Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain.;Univ Barcelona, Hosp Clin Barcelona, Barcelona, Spain..
    Anagnostopoulos, Achilles
    Hammersmith Hosp, London, England..
    Pott, Christiane
    Univ Hosp Schleswig Holstein, Med Dept 2, Campus Kiel, Kiel, Germany..
    Fischer, Kirsten
    Univ Hosp Cologne, Cologne, Germany..
    Hallek, Michael
    Univ Cologne, Dept & Internal Med, Cologne, Germany..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Stilgenbauer, Stephan
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Haferlach, Claudia
    MLL Munich Leukemia Lab, Munich, Germany..
    Jelinek, Diane
    Mayo Clin, Dept Immunol, Scottsdale, AZ USA..
    Chiorazzi, Nicholas
    Feinstein Inst Med Res, Northwell Hlth, Manhasset, NY USA..
    Pospisilova, Sarka
    Masaryk Univ, Fac Med, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Ctr Mol Med, Cent European Inst Technol, Brno, Czech Republic..
    Lefranc, Marie-Paule
    Univ Montpellier, Ctr Natl Rech Sci CNRS, Inst Genet Humaine IGH, Unite Mixte Rech UMR, Montpellier, France..
    Kossida, Sofia
    Univ Montpellier, Ctr Natl Rech Sci CNRS, Inst Genet Humaine IGH, Unite Mixte Rech UMR, Montpellier, France..
    Langerak, Anton W.
    Univ Med Ctr UMC, Dept Immunol, Lab Med Immunol, Erasmus MC, Rotterdam, Netherlands..
    Belessi, Chrysoula
    Nikea Gen Hosp, Hematol Dept, Piraeus, Greece..
    Davi, Frederic
    Univ Med Ctr UMC, Dept Immunol, Lab Med Immunol, Erasmus MC, Rotterdam, Netherlands..
    Rosenquist, Richard
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Karolinska Univ Lab, Clin Genet, Stockholm, Sweden..
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Strateg Res Program CLL,Ist Ricovero & Cura Carat, Milan, Italy..
    Stamatopoulos, Kostas
    Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermis, Thessaloniki 57001, Greece.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL2021Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 137, nr 10, s. 1365-1376Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed "satellites," were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL.

  • 41.
    Agathangelidis, Andreas
    et al.
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Ljungström, Viktor
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Scarfo, Lydia
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Fazi, Claudia
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Gounari, Maria
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy;Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Pandzic, Tatjana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sutton, Lesley-Ann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Stamatopoulos, Kostas
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Tonon, Giovanni
    IRCCS Ist Sci San Raffaele, Funct Genom Canc Unit, Div Expt Oncol, Milan, Italy.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra-stable chronic lymphocytic leukemia with low frequency of driver mutations2018Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, nr 5, s. 865-873Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite the recent discovery of recurrent driver mutations in chronic lymphocytic leukemia, the genetic factors involved in disease onset remain largely unknown. To address this issue, we per-formed whole-genome sequencing in 11 individuals with monoclonal B-cell lymphocytosis, both of the low-count and high-count subtypes, and 5 patients with ultra-stable chronic lymphocytic leukemia (>10 years without progression from initial diagnosis). All three entities were indistinguishable at the genomic level exhibiting low genomic complexity and similar types of somatic mutations. Exonic mutations were not frequently identified in putative chronic lymphocytic leukemia driver genes in all settings, including low-count monoclonal B-cell lymphocytosis. To corroborate these findings, we also performed deep sequencing in 11 known frequently mutated genes in an extended cohort of 28 monoclonal B-cell lym phocytosis/chronic lymphocytic leukemia cases. Interestingly, shared mutations were detected between clonal B cells and paired polymorphonuclear cells, strengthening the notion that at least a fraction of somatic mutations may occur before disease onset, likely at the hematopoietic stem cell level. Finally, we identified previously unreported non-coding variants targeting pathways relevant to B-cell and chronic lymphocytic leukemia development, likely associated with the acquisition of the characteristic neoplastic phenotype typical of both monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia.

    Fulltekst (pdf)
    fulltext
  • 42.
    Agathangelidis, Andreas
    et al.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Sutton, Lesley Ann
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Hadzidimitriou, Anastasia
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Tresoldi, Cristina
    IRCCS San Raffaele Sci Inst, Div Immunol Transplantat & Infect, Milan, Italy.
    Langerak, Anton W.
    Erasmus Univ, Med Ctr, Lab Med Immunol, Dept Immunol, Rotterdam, Netherlands.
    Belessi, Chrysoula
    Nikea Gen Hosp, Hematol Dept, Piraeus, Greece.
    Davi, Frederic
    Hop La Pitie Salpetriere, AP HP, Dept Hematol, Paris, France;UPMC Univ Paris 06, UMRS 1138, Paris, France.
    Rosenquist, Richard
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Stamatopoulos, Kostas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Ghia, Paolo
    IRCCS Ist Scientifico San Raffaele, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation2018Inngår i: Journal of Visualized Experiments, E-ISSN 1940-087X, nr 141, artikkel-id e57787Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    During B cell maturation, the complex process of immunoglobulin (IG) gene V(D)J recombination coupled with somatic hypermutation (SHM) gives rise to a unique DNA sequence within each individual B cell. Since B cell malignancies result from the clonal expansion of a single cell, IG genes represent a unique molecular signature common to all the malignant cells within an individual patient; thus, IG gene rearrangements can be used as clonal markers. In addition to serving as an important clonal identifier, the IG gene sequence can act as a 'molecular timeline' since it is associated with specific developmental stages and hence reflects the history of the B cell involved in the neoplastic transformation. Moreover, for certain malignancies, in particular chronic lymphocytic leukemia (CLL), the IG gene sequence holds prognostic and potentially predictive capabilities. That said, extrapolating meaningful conclusions from IG gene sequence analysis would be impossible if robust methods and tools were not available to aid in their analysis. This article, drawing on the vast experience of the European Research Initiative on CLL (ERIC), details the technical aspects and essential requirements necessary to ensure reliable and reproducible IG gene sequence analysis in CLL, a test that is now recommended for all CLL patients prior to treatment. More specifically, the various analytical stages are described ranging from the identification of the clonotypic IG gene rearrangement and the determination of the nucleotide sequence to the accurate clinical interpretation of the IG gene sequence data.

    Fulltekst (pdf)
    fulltext
  • 43.
    Agnihotri, Sagar Narhari
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för materialvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Liu, Zhenhua
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för materialvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Barbe, Laurent
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för materialvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fornell, Anna
    Tenje, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för materialvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Droplet Acoustofluidics and Pico-injection for Long-term Cell Culture2022Konferansepaper (Annet vitenskapelig)
    Fulltekst (pdf)
    fulltext
  • 44.
    Aguilera, Katherina
    et al.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Bladh, Oscar
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Marking, Ulrika
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Publ Hlth Agcy Sweden, Östersund, Sweden..
    Norin, Nina Greilert
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Rihani, Ali
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solna, Sweden.;Karolinska Inst, Natl Pandem Ctr, Solna, Sweden..
    Ujvari, Dorina
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solna, Sweden.;Karolinska Inst, Natl Pandem Ctr, Solna, Sweden..
    Ning, Frank Chenfei
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solna, Sweden..
    Klingstroem, Jonas
    Publ Hlth Agcy Sweden, Östersund, Sweden.;Linköping Univ, Dept Biomed & Clin Sci BKV, Linköping, Sweden..
    Havervall, Sebastian
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Åberg, Mikael
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Blom, Kim
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Publ Hlth Agcy Sweden, Östersund, Sweden..
    Alm, Jessica J.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solna, Sweden..
    Thalin, Charlotte
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Prevalence of SARS-CoV-2 infections among Swedish healthcare workers on duty in December 20232024Inngår i: The Lancet Regional Health: Europe, E-ISSN 2666-7762, Vol. 38, artikkel-id 100872Artikkel i tidsskrift (Annet vitenskapelig)
    Fulltekst (pdf)
    fulltext
  • 45.
    Aguirre Rivera, Javier
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi. Uppsala Universitet.
    Larsson, Jimmy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Seefeldt, A. Carolin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi.
    Sanyal, Suparna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi.
    Johansson, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi.
    Real-time measurements of aminoglycoside effects on protein synthesis in live cellsManuskript (preprint) (Annet vitenskapelig)
  • 46.
    Aguirre Rivera, Javier
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi.
    Larsson, Jimmy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Volkov, Ivan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi.
    Seefeldt, A. Carolin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi.
    Sanyal, Suparna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi.
    Johansson, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi.
    Real-time measurements of aminoglycoside effects on protein synthesis in live cells2021Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 118, nr 9, artikkel-id e2013315118Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The spread of antibiotic resistance is turning many of the currently used antibiotics less effective against common infections. To address this public health challenge, it is critical to enhance our understanding of the mechanisms of action of these compounds. Aminoglycoside drugs bind the bacterial ribosome, and decades of results from in vitro biochemical and structural approaches suggest that these drugs disrupt protein synthesis by inhibiting the ribosome's translocation on the messenger RNA, as well as by inducing miscoding errors. So far, however, we have sparse information about the dynamic effects of these compounds on protein synthesis inside the cell. In the present study, we measured the effect of the aminoglycosides apramycin, gentamicin, and paromomycin on ongoing protein synthesis directly in live Escherichia coli cells by tracking the binding of dye-labeled transfer RNAs to ribosomes. Our results suggest that the drugs slow down translation elongation two- to fourfold in general, and the number of elongation cycles per initiation event seems to decrease to the same extent. Hence, our results imply that none of the drugs used in this study cause severe inhibition of translocation.

    Fulltekst (pdf)
    FULLTEXT01
  • 47.
    Aguirre Rivera, Javier
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär systembiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mao, Guanzhong
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Sabantsev, Anton
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Panfilov, Mikhail
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hou, Qinhan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lindell, Magnus
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Chanez, C.
    Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland..
    Ritort, F.
    Univ Barcelona, Condensed Matter Phys Dept, Small Biosyst Lab, Barcelona 08028, Spain.;Univ Barcelona, Inst Nanociencia & Nanotecnol In2UB, Barcelona 08028, Spain..
    Jinek, M.
    Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland..
    Deindl, Sebastian
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Massively parallel analysis of single-molecule dynamics on next-generation sequencing chips2024Inngår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 385, nr 6711, s. 892-898Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Single-molecule techniques are ideally poised to characterize complex dynamics but are typically limited to investigating a small number of different samples. However, a large sequence or chemical space often needs to be explored to derive a comprehensive understanding of complex biological processes. Here we describe multiplexed single-molecule characterization at the library scale (MUSCLE), a method that combines single-molecule fluorescence microscopy with next-generation sequencing to enable highly multiplexed observations of complex dynamics. We comprehensively profiled the sequence dependence of DNA hairpin properties and Cas9-induced target DNA unwinding-rewinding dynamics. The ability to explore a large sequence space for Cas9 allowed us to identify a number of target sequences with unexpected behaviors. We envision that MUSCLE will enable the mechanistic exploration of many fundamental biological processes.

  • 48.
    Ahlgren, Kerstin M
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Landegren, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Grimelius, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    von Euler, Henrik
    Sundberg, Katarina
    Lindblad-Toh, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lobell, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hedhammar, Åke
    Andersson, Göran
    Hansson-Hamlin, Helene
    Lernmark, Åke
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus2014Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 9, nr 8, s. e105473-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS/HYPOTHESIS:

    Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.

    METHODS:

    Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide.

    RESULTS:

    None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted.

    CONCLUSIONS/INTERPRETATIONS:

    Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.

    Fulltekst (pdf)
    fulltext
  • 49.
    Ahlroth Pind, Caroline
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Ställberg, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Lisspers, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Sundh, Josefin
    Kisiel, Marta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Sandelowsky, Hanna
    Nager, Anna
    Hasselgren, Mikael
    Montgomery, Scott
    Janson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Pharmacological treatment of asthma in Sweden from 2005 to 2015.2023Inngår i: Journal of Asthma, ISSN 0277-0903, E-ISSN 1532-4303, Vol. 61, nr 4, s. 313-321Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids (ICS) and overuse of short-acting β2-agonists (SABA). Our aim was to investigate longitudinal trends and associated factors in asthma treatment.

    METHODS: Two separate cohorts of adults with physician-diagnosed asthma were randomly selected from 14 hospitals and 56 primary health centers in Sweden in 2005 (n = 1182) and 2015 (n = 1225). Information about symptoms, maintenance treatment, and use of rescue medication was collected by questionnaires. Associations between treatment and sex, age, smoking, education, body mass index (BMI), physical activity, allergic asthma, and symptom control were analyzed using Pearson's chi2-test. Odds ratios (ORs) were calculated using logistic regression.

    RESULTS: Maintenance treatment with ICS together with long-acting β2-agonists (LABA) and/or montelukast increased from 39.2% to 44.2% (p = 0.012). The use of ICS + LABA as-needed increased (11.1-18.9%, p < 0.001), while SABA use decreased (46.4- 41.8%, p = 0.023). Regular treatment with ICS did not change notably (54.2-57.2%, p = 0.14). Older age, former smoking, and poor symptom control were related to treatment with ICS + LABA/montelukast. In 2015, 22.7% reported daily use of SABA. A higher step of maintenance treatment, older age, obesity, shorter education, current smoking, allergic asthma, low or very high physical activity, and a history of exacerbations were associated with daily SABA use.

    CONCLUSIONS: The use of ICS + LABA both for maintenance treatment and symptom relief has increased over time. Despite this, the problem of low use of ICS and high use of SABA remains.

  • 50. Ahlstedt, Jonas
    et al.
    Johansson, Edvin
    Sydoff, Marie
    Karlsson, Helena
    Thordarson, Eddie
    Gram, Magnus
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Antaros Medical AB, Mölndal, Sweden.
    Non-invasive imaging methodologies for assessment of Peptide Receptor Radiotherapy damage to bone marrow and kidney2020Inngår i: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 110, nr 1-2, s. 130-138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/Aims: Peptide receptor radionuclide therapy (PRRT) is becoming clinical routine for management of neuroendocrine tumours. The number of PRRT cycles is correlated with treatment effect but theoretically limited by off-target radiation damage to kidneys and bone marrow. New imaging biomarkers for assessment of PRRT tissue damage would enable evaluation of novel renal and bone marrow protective agents, as well as personalised PRRT treatment regiments. Methods: Mice treated with [177Lu]Lu-DOTA-TATE PRRT or vehicle were examined at baseline and following treatment with [18F]fluorothymidine (FLT) positron emission tomography (PET) and technetium-99m-mercapto-acetyl-tri-glycine ([99mTc]Tc-Mag3) single-photon emission tomography (SPECT) to assess dynamic changes in bone marrow proliferation and renal function, respectively. Results: Bone marrow proliferation as assessed by [18F]FLT was decreased 2 days after PRRT treatment, but not vehicle, compared to baseline (target-to-background ratio [TBRmax] baseline:1.69 ± 0.29 vs. TBRmax PRRT: 0.91 ± 0.02, p < 0.01). Renal function as assessed by [99mTc]Tc-Mag3 SPECT was similarly decreased 2 days following PRRT compared to vehicle (fractional uptake rate [FUR] vehicle: 0.030 ± 0.014 s–1 vs. FUR PRRT: 0.0051 ± 0.0028 s–1, p < 0.01). Conclusion: [18F]FLT PET and [99mTc]Tc-Mag3 SPECT are promising techniques for assessing bone marrow and renal injury from [177Lu]Lu-DOTA-TATE PRRT and may potentially improve patient management by allowing evaluation of protective interventions as well as enabling personalised PRRT treatments.

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