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  • 401. Brasko, Csilla
    et al.
    Smith, Kevin
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Molnar, Csaba
    Farago, Nora
    Hegedus, Lili
    Balind, Arpad
    Balassa, Tamas
    Szkalisity, Abel
    Sukosd, Farkas
    Kocsis, Katalin
    Balint, Balazs
    Paavolainen, Lassi
    Enyedi, Marton Z.
    Nagy, Istvan
    Puskas, Laszlo G.
    Haracska, Lajos
    Tamas, Gabor
    Horvath, Peter
    Intelligent image-based in situ single-cell isolation2018Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, artikkel-id 226Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Quantifying heterogeneities within cell populations is important for many fields including cancer research and neurobiology; however, techniques to isolate individual cells are limited. Here, we describe a high-throughput, non-disruptive, and cost-effective isolation method that is capable of capturing individually targeted cells using widely available techniques. Using high-resolution microscopy, laser microcapture microscopy, image analysis, and machine learning, our technology enables scalable molecular genetic analysis of single cells, targetable by morphology or location within the sample.

  • 402.
    Brattsand, Göran
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Nordin, Gunnar
    Isaksson, Anders
    Bjellerup, Per
    Stridsberg, Mats
    Hård, Lena
    Ankarberg Lindgren, Carina
    Becker, Charlotte
    Gustafsson, Sven
    Larsson, Kerstin
    Equalis/SFKK rekommenderar harmonisering av enheter vid hormonbestämningar -Något också för Norden?2012Inngår i: Klinisk Biokemi i Norden, ISSN 1101-2013, Vol. 24, nr 4, s. 20-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Equalis och Svensk Förening för Klinisk Kemi (SFKK) rekommenderar att de kliniska laboratorierna i Sverige använder enhetliga måttenheter vid hormonbestämningar för ökad jämförbarhet och patientsäkerhet. Vid analys i serum eller plasma med nuvarande metoder rekommenderas följande enheter:

    • Adrenokortikotropt hormon (ACTH): pmol/L

    • Insulin: mIE/L

    • Parathormon (PTH): pmol/L

    • Prolaktin: mIE/L

    • Tillväxthormon (GH): μg/L

    • Östradiol: pmol/L

    • Aldosteron: pmol/L

    • Reninkoncentration: mIE/L

  • 403.
    Brattsand, Göran
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Nordin, Gunnar
    Isaksson, Anders
    Bjellerup, Per
    Stridsberg, Mats
    Hård, Lena
    Ankarberg-Lindgren, Carina
    Becker, Charlotte
    Gustafsson, Sven
    Larsson, Kerstin
    Equalis/SFKK rekommenderar harmonisering av enheter vid hormonbestämningar för säkrare vård2012Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 39-40, s. 1773-1773Artikkel i tidsskrift (Annet vitenskapelig)
  • 404.
    Bravo, Mayra
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Genetisk kartläggning av mygg: Artbestämning av mygg genom barcoding2011Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 405. Brazalez, Astrid Algaba
    et al.
    Manholm, Lars
    Johansson, Martin
    Quevedo-Teruel, Oscar
    Miao, Jingwei
    KTH, Skolan för elektroteknik och datavetenskap (EECS), Elektroteknisk teori och konstruktion.
    Investigation of a Ka-band Luneburg Lens Made of a Glide-Symmetric Holey Structure2017Inngår i: 2017 INTERNATIONAL SYMPOSIUM ON ANTENNAS AND PROPAGATION (ISAP 2017), IEEE , 2017Konferansepaper (Fagfellevurdert)
    Abstract [en]

    A Ka-hand 2D flat-profiled Luneburg lens antenna implemented with a glide-symmetric holey structure is presented. The required refractive index for the lens design has been investigated via an analysis of the hole depth and the gap between the two metallic layers constituting the lens. The final unit cell is described and applied to create the complete metasurface Luneburg lens showing that a plane wave is obtained when feeding at an opposite arbitrary point with a discrete source.

  • 406. Brechmann, Nils A.
    et al.
    Eriksson, Per-Olov
    Eriksson, Kristofer
    Oscarsson, Sven
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Buijs, Jos
    Shokri, Atefeh
    Hjälm, Göran
    Chotteau, Véronique
    Pilot-scale process for magnetic bead purification of antibodies directly from non-clarified CHO cell culture2019Inngår i: Biotechnology progress (Print), ISSN 8756-7938, E-ISSN 1520-6033, Vol. 35, nr 3, artikkel-id e2775Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    High capacity magnetic protein A agarose beads, LOABeads PrtA, were used in the development of a new process for affinity purification of monoclonal antibodies (mAbs) from non-clarified CHO cell broth using a pilot-scale magnetic separator. The LOABeads had a maximum binding capacity of 65 mg/mL and an adsorption capacity of 25-42 mg IgG/mL bead in suspension for an IgG concentration of 1 to 8 g/L. Pilot-scale separation was initially tested in a mAb capture step from 26 L clarified harvest. Small-scale experiments showed that similar mAb adsorptions were obtained in cell broth containing 40 x 10(6) cells/mL as in clarified supernatant. Two pilot-scale purification runs were then performed on non-clarified cell broth from fed-batch runs of 16 L, where a rapid mAb adsorption >= 96.6% was observed after 1 h. This process using 1 L of magnetic beads had an overall mAb yield of 86% and 16 times concentration factor. After this single protein A capture step, the mAb purity was similar to the one obtained by column chromatography, while the host cell protein content was very low, <10 ppm. Our results showed that this magnetic bead mAb purification process, using a dedicated pilot-scale separation device, was a highly efficient single step, which directly connected the culture to the downstream process without cell clarification. Purification of mAb directly from non-clarified cell broth without cell separation can provide significant savings in terms of resources, operation time, and equipment, compared to legacy procedure of cell separation followed by column chromatography step.

  • 407. Breimer, Lars H
    et al.
    Eriksson, Clas-Göran
    Nilsson, Torbjörn K
    Klinisk kemi, Laboratoriemedicinska länskliniken, Örebros universitetssjukhus, och Hälsoakademin, Örebro universitet, Örebro, Sverige.
    [Tomorrow's laboratory - already yesterday]2012Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 37, s. 1624-1624Artikkel i tidsskrift (Fagfellevurdert)
  • 408.
    Breimer, Lars H.
    et al.
    Fac Med & Hlth, Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Torbjorn K.
    Dept Med Biosci, Clin Chem, Umeå Univ, Umeå, Sweden.
    Is Ferrotoxicity a New Great Public Health Challenge?2015Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 61, nr 4, s. 667-668Artikkel i tidsskrift (Fagfellevurdert)
  • 409.
    Breimer, Lars H.
    et al.
    Departments of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Clinical Medicine, Biomedicine, Örebro University, Örebro, Sweden; Departments of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Has folate a role in the developing nervous system after birth and not just during embryogenesis and gestation?2012Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, nr 3, s. 185-191Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    It is now 30 years since the first publications stating that supplementation with folate could prevent neural tube defects appeared and 20 years since the definitive data, including prevention of other birth defects. Since then epidemiological studies and animal experiments have identified folate as a molecule at the crossroads of neural development. Fortification of food has greatly reduced the incidence of spina bifida. Much interest has focussed on long-term sequelae in children born to mothers severely deprived of folate (and other nutrients) such as during the Dutch Hunger Winter of 1944 and in poor parts of the world. In addition, deficiency in folate and B12 are increasingly discussed as a possible contributing factor in dementia and congenital orofacial and heart malformations. The year 2011 saw the publication of a study that implicated low folate intake in poorer school performance of adolescents as judged by school marks. This has enormous social implications but needs confirmation from other settings. This review assesses the current state of evidence and sets the data in context of whether folate has a role in the development and plasticity of the nervous system even after birth, with particular emphasis on childhood and adolescence.

  • 410. Breimer, Lars H
    et al.
    Nilsson, Torbjörn K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Is ferrotoxicity a new great public health challenge?2015Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 61, nr 4, s. 667-668Artikkel i tidsskrift (Fagfellevurdert)
  • 411. Breimer, Lars H
    et al.
    Nilsson, Torbjörn K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Shedded cell membrane proteins in plasma: pure waste, or informative biomarkers of pathophysiological processes?2015Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 75, nr 6, s. 441-443Artikkel i tidsskrift (Annet vitenskapelig)
  • 412.
    Breimer, Lars
    et al.
    Region Örebro län.
    Nilsson, T.
    Sverige bör bergunda ett utspel i PNAS: Sweden should contemplate article in PNAS2014Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 46, s. 2045-Artikkel i tidsskrift (Fagfellevurdert)
  • 413.
    Brevestedt, Emelie
    Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
    Hur exponeras barn för ftalater i sin inomhusmiljö på förskolan?2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Ftalater är ett ämne som har till syfte att verka mjukgörande i plast. Ftalater finns i flera material och produkter i vår omgivning t ex i leksaker, elektronik, textilier och i inredningsmaterial. De problem som uppkommer i samband med användandet av ftalater i produkter är att ftalaterna inte är kovalent bundna till sitt material och därmed kan dessa frigöras ut i luft och damm. Flera ftalater är klassade som hormonstörande ämnen och kan påverka flera viktiga funktioner i kroppen. Barn är en extra känslig grupp då flera av deras organ ännu inte är färdigutvecklade och är beroende av ett fungerande endokrint system.

     

    Barn spenderar en stor del av sin vardag på förskolan och det ställer krav på deras inomhusmiljö. Studier visar på att koncentrationerna av ftalater är 2-4 gånger så hög i förskolans inomhusmiljö som i hemmiljön. Med tanke på att barn har flera organsystem under utveckling är det viktigt att fasa ut onödiga källor för exponering av ftalater.

     

    Arbetets syfte är att kartlägga ftalater i inomhusmiljön på förskolor i Växjö kommun och att undersöka pedagogers medvetenhet kring ämnet. Arbetet utgår från tidigare vetenskapliga artiklar och en enkätundersökning som personal på 46 förskolor i Växjö kommun har besvarat.

     

    Studier som undersökt inomhusmiljöer visar på att det förekommer höga koncentrationer av ftalater som är begränsade enligt REACH-förordningen. Då ftalater finns i flera produkter blir det många olika exponeringskällor och det gör det viktigt att fasa ut onödiga källor för att minska koncentrationen av ftalater i luft och damm. De mest intressanta resultat som kommit fram via enkätundersökningen är att det förekommer plastgolv i de flesta lokaler, elektronik finns i de rum där barnen spenderar mest tid och att barn använder “vuxna leksaker” såsom äldre elektronik, väskor och skor. Ett resultat som visar att barn lever i en allt mer vuxen miljö med produkter som är avsedda för vuxna. Sådana produkter täcks inte in av de begränsningar som REACH-förordningen skapat och täcks inte heller av de nya leksaksdirektiven.  

    Förskolepedagogerna uppger sig vara medvetna om ämnet ftalater men ändå visar undersökningen att det finns en rad olika brister i kunskap. Det är därför viktigt att öka kunskapen och medvetenheten kring ämnet för att på så sätt fasa ut onödiga källor för exponering av ftalater. 

  • 414.
    Bridge, Eileen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Medicinsk genetik.
    Riedel, Kai-Uwe
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Medicinsk genetik.
    Johansson, Britt-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Medicinsk genetik.
    Pettersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Medicinsk genetik.
    Spliced exons of adenovirus late RNAs colocalize with snRNP in a specific nuclear domain1996Inngår i: Journal of Cell Biology, ISSN 0021-9525, E-ISSN 1540-8140, Vol. 135, nr 2, s. 303-314Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Posttranscriptional steps in the production of mRNA include well characterized polyadenylation and splicing reactions, but it is also necessary to understand how RNA is transported within the nucleus from the site of its transcription to the nuclear pore, where it is translocated to the cytoplasmic compartment. Determining the localization of RNA within the nucleus is an important aspect of understanding RNA production and may provide clues for investigating the trafficking of RNA within the nucleus and the mechanism for its export to the cytoplasm. We have previously shown that late phase adenovirus-infected cells contain large clusters of snRNP and non-snRNP splicing factors; the presence of these structures is correlated with high levels of viral late gene transcription. The snRNP clusters correspond to enlarged interchromatin granules present in late phase infected cells. Here we show that polyadenylated RNA and spliced tripartite leader exons from the viral major late transcription unit are present in these same late phase snRNP-containing structures. We find that the majority of the steady state viral RNA present in the nucleus is spliced at the tripartite leader exons. Tripartite leader exons are efficiently exported from the nucleus at a time when we detect their accumulation in interchromatin granule clusters. Since the enlarged interchromatin granules contain spliced and polyadenylated RNA, we suggest that viral RNA may accumulate in this late phase structure during an intranuclear step in RNA transport.

  • 415.
    Brinck, Jonas
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    The expression and regulation of hyaluronan synthases and their role in glycosaminoglycan synthesis2000Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The glycosaminoglycan hyaluronan is an essential component of the extracellular matrix in all higher organisms, affecting cellular processes such as migration, proliferation and differentiation. Hyaluronan is synthesized by a plasma membrane bound hyaluronan synthase (HAS) which exists in three genetic isoforms. This thesis focuses on the understanding of the hyaluronan biosynthesis by studies on the expression and regulation of the HAS proteins.

    In order to characterize the structural and functional properties of the HAS isoforms we developed a method to solubilize HAS protein(s) while retaining enzymatic activity. The partially purified HAS protein is, most likely, not asscociated covalently with other components. Cells transfected with cDNAs for HAS1, HAS2 and HAS3 were studied and all three HAS isozymes were able to synthesize high molecular weight hyaluronan chains in intact cells. The regulation of the hyaluronan chain length involves cell specific elements as well as external stimulatory factors. HAS3 transfected cells with high hyaluronan production exhibit reduced migration capacity and reduced amounts of a cell surface hyaluronan receptor molecule (CD44) compared to wild-type cells.

    The three HAS isoforms were studied and shown to be differentially expressed and regulated in response to external stimuli. Platelet derived growth factor (PDGF-BB) and transforming growth factor (TGF-β1) are important regulators of HAS at both the transcriptional and translational level. The HAS2 isoform is the isoform most susceptible to external regulation.

    The role of the UDP-glucose dehydrogenase in mammalian glycosaminoglycan biosynthesis was assessed. The enzyme is essential for hyaluronan, heparan sulfate and chondroitin sulfate biosynthesis, but does not exert a rate-limiting effect.

  • 416.
    Brinck, Kajsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Ultraljuds effekt på bakterier: Studie av ultraljuds effekt på bakterier vid olika temperaturer och frekvenser av ultraljud.2011Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 417.
    brkic, Adisa
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013).
    Litteraturstudie av senaste forskningsresultaten kring inhibition av makrofager via CSF - 1R & CCR2: - Kan det vara en möjlig väg att hämma makrofager vid cancer och därmed ge en förbättrad prognos?2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 418. Broach, James R
    et al.
    Bharatula, Vasudha
    Chereji, Razvan
    Elfving, Nils
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Björklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Morozov, Alexandre
    The Msn2 mediated stress response: Survival based on "hedging your bet" and a dynamic interplay of transcription factor binding and nucleosome occupancy2015Inngår i: Yeast, ISSN 0749-503X, E-ISSN 1097-0061, Vol. 32, nr Suppl. 1, s. S221-S222Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Yeast cell subjected to many different stresses elicit an acute transcriptional stress response mediated by the Msn2 transcription factor, which alters expression of both a stress specific-cohort of genes as well as a common cohort of genes that changes expression in a stereotypic fashion upon exposure to any of a wide variety of stresses. We have shown by dynamic single cell analysis that stresses regulate Msn2 activity through cytoplasm to nuclear relocalization but do so in an unusual way: stresses induce increased frequency of bursts of short-lived, recurrent periods of Msn2 nuclear localization with different stresses eliciting different patterns of bursts. Moreover, genetically identical cells subject to an identical stress can behave quite differently, with some cells mounting a robust nuclear occupancy of Msn2 while others show no nuclear localization at all. We have proposed that this idiosyncratic behavior allows populations of cells to “hedge their bet” as to what will be the optimum strategy for surviving the ensuing stress. We have used computational modeling and single cell analysis to determine that bursting is a consequence of noise in the stress signaling pathways amplified by the small number of Msn2 molecules in the cell. Moreover, we have applied genome wide chromatin immunoprecipitation and nucleosome profiling to address how different stresses determine where Msn2 binds under a particular stressful conditions, and thus what genes are regulated by that stress, and how that binding affects, and is affected by, nucleosome positioning and other transcription factor binding. These results provide in vivo validation of Widon's model of indirect cooperativity of transcription factor binding, mediated by partial unwinding of nucleosomes by one transcription factor to allow access for a second transcription factor to a previously occluded binding site. Finally, we have addressed the “bet hedging” hypothesis by showing that persistence of the Msn2-mediated stress response yields cell growth arrest and have identified the targets responsible for that growth arrest. We have applied experimental evolution paradigms to address the relative fitness of cells exhibiting stochastic stress responses versus those with a uniform response. In short, our results indicate that the stress response is complex and that complexity is critical for cell survival.

  • 419. Broadbent, Kate M.
    et al.
    Broadbent, Jill C.
    Ribacke, Ulf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Wirth, Dyann
    Rinn, John L.
    Sabeti, Pardis C.
    Strand-specific RNA sequencing in Plasmodium falciparum malaria identifies developmentally regulated long non-coding RNA and circular RNA2015Inngår i: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 16, artikkel-id 454Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The human malaria parasite Plasmodium falciparum has a complex and multi-stage life cycle that requires extensive and precise gene regulation to allow invasion and hijacking of host cells, transmission, and immune escape. To date, the regulatory elements orchestrating these critical parasite processes remain largely unknown. Yet it is becoming increasingly clear that long non-coding RNAs (lncRNAs) could represent a missing regulatory layer across a broad range of organisms. Results: To investigate the regulatory capacity of lncRNA in P. falciparum, we harvested fifteen samples from two time-courses. Our sample set profiled 56 h of P. falciparum blood stage development. We then developed and validated strand-specific, non-polyA-selected RNA sequencing methods, and pursued the first assembly of P. falciparum strand-specific transcript structures from RNA sequencing data. This approach enabled the annotation of over one thousand lncRNA transcript models and their comprehensive global analysis: coding prediction, periodicity, stage-specificity, correlation, GC content, length, location relative to annotated transcripts, and splicing. We validated the complete splicing structure of three lncRNAs with compelling properties. Non-polyA-selected deep sequencing also enabled the prediction of hundreds of intriguing P. falciparum circular RNAs, six of which we validated experimentally. Conclusions: We found that a subset of lncRNAs, including all subtelomeric lncRNAs, strongly peaked in expression during invasion. By contrast, antisense transcript levels significantly dropped during invasion. As compared to neighboring mRNAs, the expression of antisense-sense pairs was significantly anti-correlated during blood stage development, indicating transcriptional interference. We also validated that P. falciparum produces circRNAs, which is notable given the lack of RNA interference in the organism, and discovered that a highly expressed, five-exon antisense RNA is poised to regulate P. falciparum gametocyte development 1 (PfGDV1), a gene required for early sexual commitment events.

  • 420.
    Broberg, Annette
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Betydelse av provtagningsrör för faktorer i fibrinolysen2014Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 421.
    Brockmann, Sarah J.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Freischmidt, Axel
    Oeckl, Patrick
    Müller, Kathrin
    Ponna, Srinivas K.
    Helferich, Anika M.
    Paone, Christoph
    Reinders, Jörg
    Kojer, Kerstin
    Orth, Michael
    Jokela, Manu
    Auranen, Mari
    Udd, Bjarne
    Hermann, Andreas
    Danzer, Karin M.
    Lichtner, Peter
    Walther, Paul
    Ludolph, Albert C.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Otto, Markus
    Kursula, Petri
    Just, Steffen
    Weishaupt, Jochen H.
    CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency2018Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 27, nr 4, s. 706-715Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mutations in the mitochondrially located protein CHCHD10 cause motoneuron disease by an unknown mechanism. In this study, we investigate the mutations p. R15L and p. G66V in comparison to wild-type CHCHD10 and the non-pathogenic variant p. P34S in vitro, in patient cells as well as in the vertebrate in vivo model zebrafish. We demonstrate a reduction of CHCHD10 protein levels in p. R15L and p. G66V mutant patient cells to approximately 50%. Quantitative real-time PCR revealed that expression of CHCHD10 p. R15L, but not of CHCHD10 p. G66V, is already abrogated at the mRNA level. Altered secondary structure and rapid protein degradation are observed with regard to the CHCHD10 p. G66V mutant. In contrast, no significant differences in expression, degradation rate or secondary structure of non-pathogenic CHCHD10 p. P34S are detected when compared with wild-type protein. Knockdown of CHCHD10 expression in zebrafish to about 50% causes motoneuron pathology, abnormal myofibrillar structure and motility deficits in vivo. Thus, our data show that the CHCHD10 mutations p. R15L and p. G66V cause motoneuron disease primarily based on haploinsufficiency of CHCHD10.

  • 422.
    Brockmöller, Scarlet F.
    et al.
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Bucher, Elmar
    Medical Biotechnology, VTT Technical Research Centre of Finland, University of Turku, Turku, Finland.
    Müller, Berit M.
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Budczies, Jan
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Hilvo, Mika
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Griffin, Julian L.
    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
    Oresic, Matej
    Örebro universitet, Institutionen för medicinska vetenskaper. VTT Technical Research Centre of Finland, Espoo, Finland.
    Kallioniemi, Olli
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Iljin, Kristiina
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Loibl, Sibylle
    German Breast Group, GBG-Forschungs GmbH, Neu-Isenburg, Germany.
    Darb-Esfahani, Silvia
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Sinn, Bruno V.
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Klauschen, Frederick
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Prinzler, Judith
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Bangemann, Nikola
    Breast Cancer Center, Charité University Hospital, Berlin, Germany.
    Ismaeel, Fakher
    Department of Gynaecology and Obstetrics, DRK Kliniken Köpenick, Berlin, Germany; Department of Gynaecology and Obstetrics, Charité University Hospital, Berlin, Germany.
    Fiehn, Oliver
    Genome Center, University of California-Davis, Davis CA, United States.
    Dietel, Manfred
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Denkert, Carsten
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer-link to patient survival, hormone receptor status, and metabolic profiling2012Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 11, nr 2, s. 850-60Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Changes in lipid metabolism are an important but not well-characterized hallmark of cancer. On the basis of our recent findings of lipidomic changes in breast cancer, we investigated glycerol-3-phosphate acyltransferase (GPAM), a key enzyme in the lipid biosynthesis of triacylglycerols and phospholipids. GPAM protein expression was evaluated and linked to metabolomic and lipidomic profiles in a cohort of human breast carcinomas. In addition, GPAM mRNA expression was analyzed using the GeneSapiens in silico transcriptiomics database. High cytoplasmic GPAM expression was associated with hormone receptor negative status (p = 0.013). On the protein (p = 0.048) and mRNA (p = 0.001) levels, increased GPAM expression was associated with a better overall survival. Metabolomic analysis by GC-MS showed that sn-glycerol-3-phosphate, the substrate of GPAM, was elevated in breast cancer compared to normal breast tissue. LC-MS based lipidomic analysis identified significantly higher levels of phospholipids, especially phosphatidylcholines in GPAM protein positive tumors. In conclusion, our results suggest that GPAM is expressed in human breast cancer with associated changes in the cellular metabolism, in particular an increased synthesis of phospholipids, the major structural component of cellular membranes.

  • 423.
    Broddesson, Sandra
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Evaluation of an automated multiplex real-time RT-PCR assay for rapid detection of Influenza A and B viruses2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Influenza is a viral infection that affects global health and economy with its endemic and sometimes pandemic spread. Rapid detection of Influenza viruses enables antiviral use and can bring financial savings. It is also essential for the global surveillance of prevalent Influenza strains. RT-PCR is considered the most specific and sensitive method for detection of Influenza, but Influenza mutates at a high rate and it is therefore crucial that RT-PCR methods are updated regularly.

    In 2014, Cepheid released their Xpert Flu/RSV XC assay, which can detect Influenza A and B and RSV by multiplex RT-PCR in approximately one hour. The aim of this study was to evaluate this assay at Laboratoriemedicin Västernorrland by using the laboratory’s previous PCR assay for detection of Influenza viruses as reference method.

    Real-time RT-PCR was used to compare Xpert Flu/RSV XC to the reference method. A dilution series was performed to estimate the methods’ PCR efficiencies and precision was calculated from quadruplicates of a positive control sample. Clinical specimens (n=42) were used to evaluate the diagnostic sensitivity and specificity of Xpert Flu/RSV XC. Objective statistical analysis of PCR data was performed and discussed.

    The Xpert Flu/RSV XC was equivalent to the reference method and demonstrated high diagnostic sensitivity and specificity. Estimated PCR efficiencies were however low.

    With the introduction of Xpert Flu/RSV XC to the laboratory follows many potential benefits, primarily in form of a simplified pre analytical procedure and a shortened analysis time. The Xpert Flu/RSV XC assay enables fast diagnosis of Influenza infection.

  • 424.
    Brodin, Henrik
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik. Linköpings universitet, Tekniska högskolan.
    CCASENSE: Canonical Correlation Analysis for Estimation of Sensitivity Maps for Fast MRI2006Independent thesis Basic level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    Magnetic Resonance Imaging is an established technology for both imaging and functional studies in clinical and research environments. The field is still very research intense. Two major research areas are acquisition time and signal quality. The last decade has provided tools for more efficient possibilities of trading these factors against each other through parallel imaging. In this thesis one parallel imaging method, Sensitivity Encoding for fast MRI (SENSE) is examined. An alternative solution CCASENSE is developed. CCASENSE reduces the acquisition time by estimating the sensitivity maps required for SENSE to work instead of running a reference scan. The estimation process is done by Blind Source Separation through Canonical Correlation Analysis. It is shown that CCASENSE appears to estimate the sensitivity maps better than ICASENSE which is a similar algorithm.

  • 425.
    Broitman, Esteban
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tunnfilmsfysik. Linköpings universitet, Tekniska högskolan.
    Bojorge, C
    CINSO, Argentina.
    Elhordoy, F
    Instituto de Física & CINQUIFIMA, Uruguay.
    Kent, V.
    Instituto de Física & CINQUIFIMA, Uruguay.
    Zanini Gadioli, G
    Instituto de Física Gleb Wataghin, Brazil.
    Marotti, R.
    Instituto de Física & CINQUIFIMA, Uruguay.
    Canepa, H
    CINSO, Argentina.
    Dalchiele, E. A.
    Instituto de Física & CINQUIFIMA, Uruguay.
    Comparative study on the properties of ZnO nanowires and nanocrystalline thin films2012Inngår i: Surface & Coatings Technology, ISSN 0257-8972, E-ISSN 1879-3347, Vol. 213, s. 59-64Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The microstructural, morphological, optical and water-adsorption properties of nanocrystalline ZnO thin films and ZnO nanowires were studied and compared. The ZnO thin films were obtained by a sol–gel process, while the ZnO nanowires were electrochemically grown onto a ZnO sol–gel spin-coated seed layer. Thin films and nanowire samples were deposited onto crystalline quartz substrates covered by an Au electrode, able to be used in a quartz crystal microbalance. X-ray diffraction measurements reveal in both cases a typical diffraction pattern of ZnO wurtzite structure. Scanning electron microscopic images of nanowire samples show the presence of nanowires with hexagonal sections, with diameters ranging from 30 to 90 nm. Optical characterization reveals a bandgap energy of 3.29 eV for the nanowires and 3.35 eV for the thin films. A quartz crystal microbalance placed in a vacuum chamber was used to quantify the amount and kinetics of water adsorption onto the samples. Nanowire samples, which have higher surface areas than the thin films, adsorb significantly more water.

  • 426.
    Broitman, Esteban
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska fakulteten.
    Nedelcu, Dumitru
    Gheorghe Asachi Tech Univ Iasi, Romania.
    Special Issue on: Modern Technologies as Future Solutions for Performance Products Introduction2018Inngår i: International journal of materials & product technology, ISSN 0268-1900, E-ISSN 1741-5209, Vol. 56, nr 1-2Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 427.
    Brokvist, Helena
    Linnéuniversitetet, Fakultetsnämnden för naturvetenskap och teknik, Institutionen för naturvetenskap, NV.
    Autolyserade pneumokocker kan modulera cytokinsvaret hos humana monocyter2011Independent thesis Basic level (degree of Bachelor), 15 poäng / 22,5 hpOppgave
  • 428.
    Brolin, Ida
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Inverkan av apolipoprotein E4 vid HSV1-infektion av GMK- och SH-SY5Y-celler2019Independent thesis Basic level (professional degree), 10 poäng / 15 hpOppgave
  • 429.
    Brolin, Malin
    Örebro universitet, Institutionen för hälsovetenskaper.
    Detektion av antikroppar mot Francisella tularensis i serum med chemiluminescence och immunokromatografiskt snabbtest2017Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 430.
    Broman, Mikael
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Frenckner, Bjorn
    Bjallmark, Anna
    Broome, Michael
    Recirculation during veno-venous extra-corporeal membrane oxygenation - a simulation study2015Inngår i: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 38, nr 1, s. 23-30Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Veno-venous ECMO is indicated in reversible life-threatening respiratory failure without life-threatening circulatory failure. Recirculation of oxygenated blood in the ECMO circuit decreases efficiency of patient oxygen delivery but is difficult to measure. We seek to identify and quantify some of the factors responsible for recirculation in a simulation model and compare with clinical data. Methods: A closed-loop real-time simulation model of the cardiovascular system has been developed. ECMO is simulated with a fixed flow pump 0 to 5 l/min with various cannulation sites -1) right atrium to inferior vena cava, 2) inferior vena cava to right atrium, and 3) superior+ inferior vena cava to right atrium. Simulations are compared to data from a retrospective cohort of 11 consecutive adult veno-venous ECMO patients in our department. Results: Recirculation increases with increasing ECMO-flow, decreases with increasing cardiac output, and is highly dependent on choice of cannulation sites. A more peripheral drainage site decreases recirculation substantially. Conclusions: Simulations suggest that recirculation is a significant clinical problem in veno-venous ECMO in agreement with clinical data. Due to the difficulties in measuring recirculation and interpretation of the venous oxygen saturation in the ECMO drainage blood, flow settings and cannula positioning should rather be optimized with help of arterial oxygenation parameters. Simulation may be useful in quantification and understanding of recirculation in VV-ECMO.

  • 431.
    Broman, Natasja
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för hälsovetenskaper (from 2013).
    Validering av en realtids-PCR metod för analys av NF-κB1 mRNA-uttryck i HT29-celler2018Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 432.
    Bromée, Torun
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Sjödin, Paula
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Fredriksson, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Boswell, Tim
    Larsson, Tomas A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Salaneck, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Zoorob, Rima
    Mohell, Nina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Larhammar, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Neuropeptide Y-family receptors Y6 and Y7 in chicken: Cloning, pharmacological characterization, tissue distribution and conserved synteny with human chromosome region2006Inngår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 273, nr 9, s. 2048-2063Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The peptides of the neuropeptide Y (NPY) family exert their functions, including regulation of appetite and circadian rhythm, by binding to G-protein coupled receptors. Mammals have five subtypes, named Y1, Y2, Y4, Y5 and Y6, and recently Y7 has been discovered in fish and amphibians. In chicken we have previously characterized the first four subtypes and here we describe Y6 and Y7. The genes for Y6 and Y7 are located 1 megabase apart on chromosome 13, which displays conserved synteny with human chromosome 5 that harbours the Y6 gene. The porcine PYY radioligand bound the chicken Y6 receptor with a Kd of 0.80 ± 0.36 nm. No functional coupling was demonstrated. The Y6 mRNA is expressed in hypothalamus, gastrointestinal tract and adipose tissue. Porcine PYY bound chicken Y7 with a Kd of 0.14 ± 0.01 nm (mean ± SEM), whereas chicken PYY surprisingly had a much lower affinity, with a Ki of 41 nm, perhaps as a result of its additional amino acid at the N terminus. Truncated peptide fragments had greatly reduced affinity for Y7, in agreement with its closest relative, Y2, in chicken and fish, but in contrast to Y2 in mammals. This suggests that in mammals Y2 has only recently acquired the ability to bind truncated PYY. Chicken Y7 has a much more restricted tissue distribution than other subtypes and was only detected in adrenal gland. Y7 seems to have been lost in mammals. The physiological roles of Y6 and Y7 remain to be identified, but our phylogenetic and chromosomal analyses support the ancient origin of these Y receptor genes by chromosome duplications in an early (pregnathostome) vertebrate ancestor.

  • 433. Brosché, Mikael
    et al.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap.
    Molecular events following perception of ultraviolet-B radiation by plants2003Inngår i: Physiologia Plantarum: An International Journal for Plant Biology, ISSN 0031-9317, E-ISSN 1399-3054, Vol. 117, nr 1, s. 1-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Exposure of plants to UV-B radiation (280–320 nm) results in changes in expression of a large number of genes. Before UV-B radiation or light of other wavelengths can give rise to a cellular response, it has to be perceived by some kind of receptor, and the information transduced via a signalling pathway to the target molecules, be it proteins in the cytoplasm

    or the genetic material in the nucleus. The perception of low levels of UV-B probably occurs via a UV-B photoreceptor followed by several different signalling pathways. These pathways include second messengers such as calcium, kinases and the catalytic formation of reactive oxygen species. High levels of UV-B, on the other hand, probably cause cellular damage

    and oxidative stress, thus activating a general stress signal transduction pathway which leads to a response similar to that which occurs after pathogen attack and other stresses. Some of the genes identified so far as being regulated by UV-B encode proteins involved in the biosynthesis of protective pigments, DNA repair and antioxidative enzymes, photosynthetic genes, cell cycle genes, and stress genes induced by other types of stimuli (i.e. pathogenesis-related proteins and senescence-induced genes). In the light of the information obtained on components necessary for UV-B-induced changes in gene expression, we propose in this mini-review a working model for UV-B perception and signal transduction. This model also takes into account dosage differences for the observations, which imply a separation into UV-B-specific and more general stress signal transduction.

  • 434. Broström, Eva
    et al.
    Örtqvist, Maria
    Haglund-Åkerlind, Yvonne
    Hagelberg, Stefan
    Gutierrez-Farewik, Elena M.
    KTH, Skolan för teknikvetenskap (SCI), Mekanik.
    Trunk and center of mass movements during gait in children with juvenile idiopathic arthritis2007Inngår i: Human Movement Science, ISSN 0167-9457, E-ISSN 1872-7646, Vol. 26, nr 2, s. 296-305Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Motion of the body center of mass (CoM) can often indicate the overall effect of the strategy of forward progression used. In the present study, focus is placed on trunk movements in the sagittal, coronal, and transverse/rotation plane, as well as placement of the CoM, during gait in children with juvenile idiopathic arthritis (JIA). Seventeen children with JIA, all with polyarticular lower extremity involvement were examined before and approximately two weeks after treatment with intra-articular cortico-steroid injections. Movement was recorded with a 6-camera 3D motion analysis system in both the children with JIA and in 21 healthy controls. Trunk and center of mass movements were compared between JIA and controls, and effects of intra-articular cortico-steroid treatment were evaluated. Children with JIA were more posteriorly tilted in the trunk, contrary to the common clinical impression, and had their CoM placed more posterior and off-centred, which may have been a result of pain. With such knowledge, it might be possible to better understand the effects of their pain and involvement, and ultimately to plan a treatment strategy for improving their gait patterns.

  • 435.
    Browning, Kathryn L.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Lind, Tania
    Malmo Univ, Dept Biomed Sci & Biofilm, Malmo, Sweden.
    Maric, Selma
    Malmoe Univ, Dept Hlth & Soc, Malmo, Sweden.
    Malekkhaiat Häffner, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Fredrikson, Gunilla
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Bengtsson, Eva
    Lund Univ, Dept Clin Sci, Rochester, Sweden.
    Malmsten, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Univ Copenhagen, Dept Pharm, Copenhagen, Denmark.
    Cardenas, Marite
    Malmo Univ, Dept Biomed Sci & Biofilm, Malmo, Sweden.
    Human lipoproteins at model cell membranes: Role of the lipoprotein class on lipid dynamics2017Inngår i: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 253, artikkel-id 700Artikkel i tidsskrift (Annet vitenskapelig)
  • 436. Brownstein, Catherine A.
    et al.
    Beggs, Alan H.
    Homer, Nils
    Merriman, Barry
    Yu, Timothy W.
    Flannery, Katherine C.
    DeChene, Elizabeth T.
    Towne, Meghan C.
    Savage, Sarah K.
    Price, Emily N.
    Holm, Ingrid A.
    Luquette, Lovelace J.
    Lyon, Elaine
    Majzoub, Joseph
    Neupert, Peter
    McCallie, David, Jr.
    Szolovits, Peter
    Willard, Huntington F.
    Mendelsohn, Nancy J.
    Temme, Renee
    Finkel, Richard S.
    Yum, Sabrina W.
    Medne, Livija
    Sunyaev, Shamil R.
    Adzhubey, Ivan
    Cassa, Christopher A.
    de Bakker, Paul I. W.
    Duzkale, Hatice
    Dworzynski, Piotr
    Fairbrother, William
    Francioli, Laurent
    Funke, Birgit H.
    Giovanni, Monica A.
    Handsaker, Robert E.
    Lage, Kasper
    Lebo, Matthew S.
    Lek, Monkol
    Leshchiner, Ignaty
    MacArthur, Daniel G.
    McLaughlin, Heather M.
    Murray, Michael F.
    Pers, Tune H.
    Polak, Paz P.
    Raychaudhuri, Soumya
    Rehm, Heidi L.
    Soemedi, Rachel
    Stitziel, Nathan O.
    Vestecka, Sara
    Supper, Jochen
    Gugenmus, Claudia
    Klocke, Bernward
    Hahn, Alexander
    Schubach, Max
    Menzel, Mortiz
    Biskup, Saskia
    Freisinger, Peter
    Deng, Mario
    Braun, Martin
    Perner, Sven
    Smith, Richard J. H.
    Andorf, Janeen L.
    Huang, Jian
    Ryckman, Kelli
    Sheffield, Val C.
    Stone, Edwin M.
    Bair, Thomas
    Black-Ziegelbein, E. Ann
    Braun, Terry A.
    Darbro, Benjamin
    DeLuca, Adam P.
    Kolbe, Diana L.
    Scheetz, Todd E.
    Shearer, Aiden E.
    Sompallae, Rama
    Wang, Kai
    Bassuk, Alexander G.
    Edens, Erik
    Mathews, Katherine
    Moore, Steven A.
    Shchelochkov, Oleg A.
    Trapane, Pamela
    Bossler, Aaron
    Campbell, Colleen A.
    Heusel, Jonathan W.
    Kwitek, Anne
    Maga, Tara
    Panzer, Karin
    Wassink, Thomas
    Van Daele, Douglas
    Azaiez, Hela
    Booth, Kevin
    Meyer, Nic
    Segal, Michael M.
    Williams, Marc S.
    Tromp, Gerard
    White, Peter
    Corsmeier, Donald
    Fitzgerald-Butt, Sara
    Herman, Gail
    Lamb-Thrush, Devon
    McBride, Kim L.
    Newsom, David
    Pierson, Christopher R.
    Rakowsky, Alexander T.
    Maver, Ales
    Lovrecic, Luca
    Palandacic, Anja
    Peterlin, Borut
    Torkamani, Ali
    Wedell, Anna
    Huss, Mikael
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Alexeyenko, Andrey
    Lindvall, Jessica M.
    Magnusson, Mans
    Nilsson, Daniel
    Stranneheim, Henrik
    Taylan, Fulya
    Gilissen, Christian
    Hoischen, Alexander
    van Bon, Bregje
    Yntema, Helger
    Nelen, Marcel
    Zhang, Weidong
    Sager, Jason
    Zhang, Lu
    Blair, Kathryn
    Kural, Deniz
    Cariaso, Michael
    Lennon, Greg G.
    Javed, Asif
    Agrawal, Saloni
    Ng, Pauline C.
    Sandhu, Komal S.
    Krishna, Shuba
    Veeramachaneni, Vamsi
    Isakov, Ofer
    Halperin, Eran
    Friedman, Eitan
    Shomron, Noam
    Glusman, Gustavo
    Roach, Jared C.
    Caballero, Juan
    Cox, Hannah C.
    Mauldin, Denise
    Ament, Seth A.
    Rowen, Lee
    Richards, Daniel R.
    San Lucas, F. Anthony
    Gonzalez-Garay, Manuel L.
    Caskey, C. Thomas
    Bai, Yu
    Huang, Ying
    Fang, Fang
    Zhang, Yan
    Wang, Zhengyuan
    Barrera, Jorge
    Garcia-Lobo, Juan M.
    Gonzalez-Lamuno, Domingo
    Llorca, Javier
    Rodriguez, Maria C.
    Varela, Ignacio
    Reese, Martin G.
    De la Vega, Francisco M.
    Kiruluta, Edward
    Cargill, Michele
    Hart, Reece K.
    Sorenson, Jon M.
    Lyon, Gholson J.
    Stevenson, David A.
    Bray, Bruce E.
    Moore, Barry M.
    Eilbeck, Karen
    Yandell, Mark
    Zhao, Hongyu
    Hou, Lin
    Chen, Xiaowei
    Yan, Xiting
    Chen, Mengjie
    Li, Cong
    Yang, Can
    Gunel, Murat
    Li, Peining
    Kong, Yong
    Alexander, Austin C.
    Albertyn, Zayed I.
    Boycott, Kym M.
    Bulman, Dennis E.
    Gordon, Paul M. K.
    Innes, A. Micheil
    Knoppers, Bartha M.
    Majewski, Jacek
    Marshall, Christian R.
    Parboosingh, Jillian S.
    Sawyer, Sarah L.
    Samuels, Mark E.
    Schwartzentruber, Jeremy
    Kohane, Isaac S.
    Margulies, David M.
    An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge2014Inngår i: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 15, nr 3, artikkel-id R53Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.

  • 437.
    Brun, Anders
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatiK. Linköpings universitet, Tekniska högskolan.
    Manifold learning and representations for image analysis and visualization2006Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    We present a novel method for manifold learning, i.e. identification of the low-dimensional manifold-like structure present in a set of data points in a possibly high-dimensional space. The main idea is derived from the concept of Riemannian normal coordinates. This coordinate system is in a way a generalization of Cartesian coordinates in Euclidean space. We translate this idea to a cloud of data points in order to perform dimension reduction. Our implementation currently uses Dijkstra's algorithm for shortest paths in graphs and some basic concepts from differential geometry. We expect this approach to open up new possibilities for analysis of e.g. shape in medical imaging and signal processing of manifold-valued signals, where the coordinate system is “learned” from experimental high-dimensional data rather than defined analytically using e.g. models based on Lie-groups.

    We propose a novel post processing method for visualization of fiber traces from DT-MRI data. Using a recently proposed non-linear dimensionality reduction technique, Laplacian eigenmaps (Belkin and Niyogi, 2002), we create a mapping from a set of fiber traces to a low dimensional Euclidean space. Laplacian eigenmaps constructs this mapping so that similar traces are mapped to similar points, given a custom made pairwise similarity measure for fiber traces. We demonstrate that when the low-dimensional space is the RGB color space, this can be used to visualize fiber traces in a way which enhances the perception of fiber bundles and connectivity in the human brain.

  • 438.
    Brun, Anders
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik. Linköpings universitet, Tekniska högskolan. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Knutsson, Hans
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik. Linköpings universitet, Tekniska högskolan. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Tensor Glyph Warping - Visualizing Metric Tensor Fields using Riemannian Exponential Maps2009Inngår i: Visualization and Processing of Tensor Fields: Advances and Perspectives / [ed] Laidlaw, David H.; Weickert, Joachim, Springer Berlin/Heidelberg, 2009, s. 139-160Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    The Riemannian exponential map, and its inverse the Riemannian logarithm map, can be used to visualize metric tensor fields. In this chapter we first derive the well-known metric sphere glyph from the geodesic equations, where the tensor field to be visualized is regarded as the metric of a manifold. These glyphs capture the appearance of the tensors relative to the coordinate system of the human observer. We then introduce two new concepts for metric tensor field visualization: geodesic spheres and geodesically warped glyphs. These additions make it possible not only to visualize tensor anisotropy, but also the curvature and change in tensorshape in a local neighborhood. The framework is based on the exp maps, which can be computed by solving a second order Ordinary Differential Equation (ODE) or by manipulating the geodesic distance function. The latter can be found by solving the eikonal equation, a non-linear Partial Differential Equation (PDE), or it can be derived analytically for some manifolds. To avoid heavy calculations, we also include first and second order Taylor approximations to exp and log. In our experiments, these are shown to be sufficiently accurate to produce glyphs that visually characterize anisotropy, curvature and shape-derivatives in smooth tensor fields. 

  • 439.
    Brunette, Isabelle
    et al.
    University of Montreal, Canada.
    Alarcon, Emilio
    University of Ottawa Heart Institute, Canada.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Cornea Regeneration as an Alternative to Human Donor Transplantation2015Inngår i: European Ophthalmic Review, ISSN 1756-1795, Vol. 9, nr 2, s. 111-114Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is a need for an alternative to human donor corneas as the availability of good-quality tissues remains limited, with this situation potentially worsening as the population in many countries is progressively ageing. There have been numerous attempts to develop corneal equivalent as alternatives to donated human corneas as well as prostheses. In this short review, we focus on the efforts in bioengineering implants that promote regeneration by Canadian researchers, including our current team of authors. The examples of technologies developed that we describe include biomaterials that allow for partial regeneration of corneal tissue, self-assembled cornea constructs and cell-free corneal implants that promoted regeneration when evaluated in clinical trials in Europe.

  • 440.
    Brus, Annelie
    Karlstads universitet, Fakulteten för hälsa, natur- och teknikvetenskap (from 2013), Institutionen för hälsovetenskaper.
    Är det någon skillnad mellan odlingsplattorna för MRSA, ESBL och VRE?: Från två olika tillverkare av kromogena odlingsplattor för MRSA, ESBL och VRE.2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 441.
    Brändén, Magnus
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Electron and proton transfer in cytochrome c oxidase2003Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This doctoral thesis describes results from studies on the mechanisms by which the enzyme cytochrome c oxidase catalyses the reduction of oxygen to water. Cytochrome c oxidase is the last integral enzyme complex of the socalled respiratory chain in the mitochondrial inner membrane (plasma membrane of bacteria). The reaction catalysed by cytochrome c oxidase produces a charge separation across the membrane by two separate mechanisms. The protons and the electrons needed to reduce oxygen to water are supplied from different sides of the membrane, and the energy released in this reaction is used by cytochrome c oxidase to pump protons against the electro-chemical gradient across the membrane. Another integral enzyme, ATP-synthase, utilises this gradient for synthesis of ATP, which in turn is used in many of the energyrequiring processes of a cell. Cytochrome c oxidase holds four redox-active metal centres that mediate electron transfer to, and reduction of the O2-molecule. One part of the thesis concerns the rates of electron transfer as well as the redox equilibrium between the metal sites (papers II and IV).

    Since the oxygen chemistry takes place in the membrane-spanning part of the enzyme it is equipped with two proton-transfer pathways that lead from the bulk solution to the active site. A second part of the thesis concerns the location of the entry-point of one of these pathways as well as the role of this pathway during the catalytic cycle (papers I and III).

    The third part of the thesis concerns the mechanism by which the enzymecouples the O2-chemistry to proton pumping (paper V).

  • 442.
    Brännström, Kristoffer
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Gharibyan, Anna L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Islam, Tohidul
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Iakovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Nilsson, Lina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Lee, Cheng Choo
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Sandblad, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Pamrén, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Olofsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Scanning electron microscopy as a tool for evaluating morphology of amyloid structures formed on surface plasmon resonance chips2018Inngår i: Data in Brief, E-ISSN 2352-3409, Vol. 19, s. 1166-1170Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We demonstrate the use of Scanning Electron microscopy (SEM) in combination with Surface Plasmon Resonance (SPR) to probe and verify the formation of amyloid and its morphology on an SPR chip. SPR is a technique that measures changes in the immobilized weight on the chip surface and is frequently used to probe the formation and biophysical properties of amyloid structures. In this context it is of interest to also monitor the morphology of the formed structures. The SPR chip surface is made of a layer of gold, which represent a suitable material for direct analysis of the surface using SEM. The standard SPR chip used here (CM5-chip, GE Healthcare, Uppsala, Sweden) can easily be disassembled and directly analyzed by SEM. In order to verify the formation of amyloid fibrils in our experimental conditions we analyzed also in-solution produced structures by using Transmission Electron Microscopy (TEM). For further details and experimental findings, please refer to the article published in Journal of Molecular Biology, (Brännström K. et al., 2018) [1].

  • 443.
    Brännström, Kristoffer
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Islam, Tohidul
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sandblad, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Olofsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    The role of histidines in amyloid β fibril assembly2017Inngår i: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 591, nr 8, s. 1167-1175Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Low pH has a strong stabilising effect on the fibrillar assembly of amyloid β, which is associated with Alzheimer's disease. The stabilising effect is already pronounced at pH 6.0, suggesting that protonation of histidines might mediate this effect. Through the systematic substitution of the three native histidines in Aβ for alanines, we have evaluated their role in fibril stability. Using surface plasmon resonance, we show that at neutral pH the fibrillar forms of all His-Ala variants are destabilised by a factor of 4-12 compared to wild-type Aβ. However, none of the His-Ala Aβ variants impair the stabilising effect of the fibril at low pH.

  • 444.
    Brännström, Kristoffer
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Lindhagen Persson, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Gharabyan, A
    Vestling, M
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Morozova-Roche, Ludmilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Olofsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Design of oligomer-specific antibodiesManuskript (preprint) (Annet vitenskapelig)
  • 445.
    Brännström, Kristoffer
    et al.
    Umeå universitet, Institutionen för medicinsk kemi och biofysik.
    Lindhagen-Persson, Malin
    Umeå universitet, Institutionen för medicinsk kemi och biofysik.
    Gharibyan, Anna L.
    Umeå universitet, Institutionen för medicinsk kemi och biofysik.
    Iakovleva, Irina
    Umeå universitet, Institutionen för medicinsk kemi och biofysik.
    Vestling, Monika
    Umeå universitet, Institutionen för medicinsk kemi och biofysik.
    Sellin, Mikael E.
    Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Brännström, Thomas
    Umeå universitet, Patologi.
    Morozova-Roche, Ludmilla
    Umeå universitet, Institutionen för medicinsk kemi och biofysik.
    Forsgren, Lars
    Umeå universitet, Klinisk neurovetenskap.
    Olofsson, Anders
    Umeå universitet, Institutionen för medicinsk kemi och biofysik.
    A Generic Method for Design of Oligomer-Specific Antibodies2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 3, artikkel-id e90857Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Antibodies that preferentially and specifically target pathological oligomeric protein and peptide assemblies, as opposed to their monomeric and amyloid counterparts, provide therapeutic and diagnostic opportunities for protein misfolding diseases. Unfortunately, the molecular properties associated with oligomer-specific antibodies are not well understood, and this limits targeted design and development. We present here a generic method that enables the design and optimisation of oligomer-specific antibodies. The method takes a two-step approach where discrimination between oligomers and fibrils is first accomplished through identification of cryptic epitopes exclusively buried within the structure of the fibrillar form. The second step discriminates between monomers and oligomers based on differences in avidity. We show here that a simple divalent mode of interaction, as within e. g. the IgG isotype, can increase the binding strength of the antibody up to 1500 times compared to its monovalent counterpart. We expose how the ability to bind oligomers is affected by the monovalent affinity and the turnover rate of the binding and, importantly, also how oligomer specificity is only valid within a specific concentration range. We provide an example of the method by creating and characterising a spectrum of different monoclonal antibodies against both the A beta peptide and alpha-synuclein that are associated with Alzheimer's and Parkinson's diseases, respectively. The approach is however generic, does not require identification of oligomer-specific architectures, and is, in essence, applicable to all polypeptides that form oligomeric and fibrillar assemblies.

  • 446.
    Brännström, Kristoffer
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Lindhagen-Persson, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Gharibyan, Anna L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Iakovleva, Irina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Vestling, Monika
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sellin, Mikael E.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Morozova-Roche, Ludmilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Olofsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    A Generic Method for Design of Oligomer-Specific Antibodies2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 3, s. e90857-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Antibodies that preferentially and specifically target pathological oligomeric protein and peptide assemblies, as opposed to their monomeric and amyloid counterparts, provide therapeutic and diagnostic opportunities for protein misfolding diseases. Unfortunately, the molecular properties associated with oligomer-specific antibodies are not well understood, and this limits targeted design and development. We present here a generic method that enables the design and optimisation of oligomer-specific antibodies. The method takes a two-step approach where discrimination between oligomers and fibrils is first accomplished through identification of cryptic epitopes exclusively buried within the structure of the fibrillar form. The second step discriminates between monomers and oligomers based on differences in avidity. We show here that a simple divalent mode of interaction, as within e. g. the IgG isotype, can increase the binding strength of the antibody up to 1500 times compared to its monovalent counterpart. We expose how the ability to bind oligomers is affected by the monovalent affinity and the turnover rate of the binding and, importantly, also how oligomer specificity is only valid within a specific concentration range. We provide an example of the method by creating and characterising a spectrum of different monoclonal antibodies against both the A beta peptide and alpha-synuclein that are associated with Alzheimer's and Parkinson's diseases, respectively. The approach is however generic, does not require identification of oligomer-specific architectures, and is, in essence, applicable to all polypeptides that form oligomeric and fibrillar assemblies.

  • 447.
    Brännström, Kristoffer
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Öhman, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lindhagen-Persson, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Olofsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ca2+ enhances Aβ polymerization rate and fibrillar stability in a dynamic manner2013Inngår i: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 450, s. 189-197Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Identifying factors that affect the self-assembly of the amyloid-β peptide (Aβ) is of utmost importance in the quest to understand the molecular mechanisms causing Alzheimer's disease (AD). Ca2+ has previously been shown to accelerate both Aβ fibril nucleation and maturation, and a dysregulated Ca2+ homeostasis frequently correlates with development of AD. The mechanisms regarding Ca2+ binding as well as its effect on fibril kinetics are not fully understood. Using a polymerization assay we show that Ca2+ in a dynamic and reversible manner enhances both the elongation rate and fibrillar stability, where specifically the "dock and lock" phase mechanism is enhanced. Through NMR analysis we found that Ca2+ affects the fibrillar architecture. In addition, and unexpectedly, we found that Ca2+ does not bind the free Aβ monomer. This implies that Ca2+ binding requires an architecture adopted by assembled peptides, and consequently is mediated through intermolecular interactions between adjacent peptides. This gives a mechanistic explanation to the enhancing effect on fibril maturation and indicates structural similarities between prefibrillar structures and mature amyloid. Taken together we expose how Ca2+ levels affect the delicate equilibrium between the monomeric and assembled Aβ and how fluctuations in vivo may contribute to development and progression of the disease.

  • 448.
    Brönnestam, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Polymorphism of the human complement component C3- genetic and immunological aspects1973Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Genetic polymorphism is by definition the occurrence in the same population of two or more alleles at one locus,each with a frequency high enough not to be maintained by recurrent mutation only (1). Among the human plasmaproteins two major categories of polymorphism have been described, allotypic and electrophoretic heterogeneity. Allotypy is defined by Oudin as individual antigenic differences among proteins within a species (2). The first discovered polymorphism of this category was the Gm system of immunoglobulin G by Grubb (3). The first described electrophoretic heterogeneity in plasma proteins was theHp (haptoglobin) system discovered by Smithies (4). Sincethen genetic variants of several other human plasma proteins have been found. This dissertation is concerned with thegenetic and immunological aspects of the polymorphism of the third component of human complement, C3.

  • 449.
    Budczies, Jan
    et al.
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Denkert, Carsten
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Müller, Berit M.
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Brockmöller, Scarlet F.
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Klauschen, Frederick
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Györffy, Balazs
    Institute of Pathology, Charité University Hospital, Berlin, Germany; Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Dietel, Manfred
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Richter-Ehrenstein, Christiane
    Interdisciplinary Breast Center, Charité University Hospital, Berlin, Germany.
    Marten, Ulrike
    Institute of Pathology, DRK Kliniken Berlin, Berlin, Germany.
    Salek, Reza M.
    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
    Griffin, Julian L.
    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
    Hilvo, Mika
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Oresic, Matej
    Örebro universitet, Institutionen för medicinska vetenskaper. VTT Technical Research Centre of Finland, Espoo, Finland.
    Wohlgemuth, Gert
    Genome Center, University of California Davis, Davis CA, United States.
    Fiehn, Oliver
    Genome Center, University of California Davis, Davis CA, United States.
    Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue - a GC-TOFMS based metabolomics study2012Inngår i: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 13, nr 1, artikkel-id 334Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS) is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far.

    RESULTS: A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468 metabolite peaks could be detected; out of these 368 (79%) were significantly changed between cancer and normal tissues (p<0.05 in training and validation set). Furthermore, 13 tumor and 7 normal tissue markers were identified that separated cancer from normal tissues with a sensitivity and a specificity of >80%. Two-metabolite classifiers, constructed as ratios of the tumor and normal tissues markers, separated cancer from normal tissues with high sensitivity and specificity. Specifically, the cytidine-5-monophosphate / pentadecanoic acid metabolic ratio was the most significant discriminator between cancer and normal tissues and allowed detection of cancer with a sensitivity of 94.8% and a specificity of 93.9%.

    CONCLUSIONS: For the first time, a comprehensive metabolic map of breast cancer was constructed by GC-TOF analysis of a large cohort of breast cancer and normal tissues. Furthermore, our results demonstrate that spectrometry-based approaches have the potential to contribute to the analysis of biopsies or clinical tissue samples complementary to histopathology.

  • 450.
    Budnjo, Almir
    Högskolan i Skövde, Institutionen för biovetenskap.
    Gene expression of MAP2K1 and Cyclin D1 in BDII rat model of Endometrial cancer2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Endometrial adenocarcinoma (EAC) is the most frequently diagnosed gynecological cancer of the female genital tract in the Western world. Research studies in EC is difficult to conduct on human tumor samples due to the complex nature of tumor arousal and genetic heterogeneousness in the human population. Therefore, inbred animal models can be promising tools to use in EC research due to similar histopathology and pathogenesis as humans. Studies performed on MAP2K1 and CCND1 has shown that their altered expression play a crucial role in carcinogenesis. CCND1 has been demonstrated to have oncogenic properties when overexpressed in human neoplasias.

    The aim of this study is to investigate gene expression levels of MAP2K1 and CCND1 in BDII rat model of endometrial adenocarcinoma cells. Quantitative real-time PCR was used to analyze expression levels of MAP2K1 and CCND1 genes in BDII/Han rat model of endometrial cancer cells using TaqMan approach. The differences in gene expression levels of MAP2K1 and CCND1 between pathologically EAC malignant and nonmalignant cells showed an upregulation of MAP2K1 and CCND1 in EAC malignant cells. The analyzed data presented observable mean differences between MAP2K1 and CCND1 in several endometrial cell lines that were examined.

    Although no statistical significance was reached, an alteration in gene expression levels in malignant and nonmalignant endometrial cells could be observed. Furthermore, this present study shows observable upregulation of MAP2K1 and CCND1 in endometrial carcinoma cells vs. nonmalignant endometrium cells and encourages further investigation of the role of CCND1 and MAP2K genes in endometrial carcinogenesis.

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