Endre søk
Begrens søket
6768697071 3451 - 3500 of 3514
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 3451.
    Zeller, Kathrin Stephanie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Riaz, Anjum
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Sarve, Hamid
    SLU, Centrum för bildanalys.
    Li, Jia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Tengholm, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Johansson, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    The role of mechanical force and ROS in integrin-dependent signals2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 5, artikkel-id e64897Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cells are exposed to several types of integrin stimuli, which generate responses generally referred to as "integrin signals", but the specific responses to different integrin stimuli are poorly defined. In this study, signals induced byintegrin ligation during cell attachment, mechanical force from intracellular contraction, or cell stretching by external force were compared. The elevated phosphorylation levels of several proteins during the early phase of cell attachment and spreading of fibroblast cell lines were not affected by inhibition ofROCK and myosin II activity, i.e. the reactions occurred independently ofintracellular contractile force acting on the adhesion sites. The contraction-independent phosphorylation sites included ERK1/2 T202/Y204, AKT S473, p130CAS Y410, and cofilin S3. In contrast to cell attachment, cyclic stretching ofthe adherent cells induced a robust phosphorylation only of ERK1/2 and thephosphorylation levels of the other investigated proteins were not or only moderately affected by stretching. No major differences between signaling via alpha 5 beta 1 or alpha v beta 3 integrins were detected. The importance ofmitochondrial ROS for the integrin-induced signaling pathways was investigated using rotenone, a specific inhibitor of complex I in the respiratory chain. While rotenone only moderately reduced ATP levels and hardly affected the signalsinduced by cyclic cell stretching, it abolished the activation of AKT and reduced theactin polymerization rate in response to attachment in both cell lines. In contrast, scavenging of extracellular ROS with catalase or the vitamin C analog Asc-2P did not significantly influence the attachment-derived signaling, but caused a selective and pronounced enhancement of ERK1/2 phosphorylation in response to stretching. In conclusion, the results showed that "integrin signals" are composedof separate sets of reactions triggered by different types of integrin stimulation. Mitochondrial ROS and extracellular ROS had specific and distinct effects on theintegrin signals induced by cell attachment and mechanical stretching.

  • 3452.
    Zepeda Mendoza, Marie Lisandra
    et al.
    Natural History Museum of Denmark.
    Lundberg, Johannes
    Naturhistoriska riksmuseet, Enheten för botanik.
    Ivarsson, Magnus
    Naturhistoriska riksmuseet, Enheten för paleobiologi. Nordic Center for Earth Evolution (NordCEE).
    Campos, Paula
    University of Copenhagen.
    Nylander, Johan A. A.
    Naturhistoriska riksmuseet, Enheten för bioinformatik och genetik.
    Sallstedt, Thereese
    Naturhistoriska riksmuseet, Enheten för paleobiologi. Nordic Center for Earth Evolution (NordCEE).
    Dalén, Love
    Naturhistoriska riksmuseet, Enheten för bioinformatik och genetik.
    Metagenomic Analysis from the Interior of a Speleothem in Tjuv-Ante's Cave, Northern Sweden2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 3, s. 1-23, artikkel-id e015177Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Speleothems are secondary mineral deposits normally formed by water supersaturated with calcium carbonate percolating into underground caves, and are often associated with low-nutrient and mostly non-phototrophic conditions. Tjuv-Ante’s cave is a shallow-depth cave formed by the action of waves, with granite and dolerite as major components, and opal-A and calcite as part of the speleothems, making it a rare kind of cave. We generated two DNA shotgun sequencing metagenomic datasets from the interior of a speleothem from Tjuv-Ante’s cave representing areas of old and relatively recent speleothem formation. We used these datasets to perform i) an evaluation of the use of these speleothems as past biodiversity archives, ii) functional and taxonomic profiling of the speleothem’s different formation periods, and iii) taxonomic comparison of the metagenomic results to previous microscopic analyses from a nearby speleothem of the same cave. Our analyses confirm the abundance of Actinobacteria and fungi as previously reported by microscopic analyses on this cave, however we also discovered a larger biodiversity. Interestingly, we identified photosynthetic genes, as well as genes related to iron and sulphur metabolism, suggesting the presence of chemoautotrophs. Furthermore, we identified taxa and functions related to biomineralization. However, we could not confidently establish the use of this type of speleothems as biological paleoarchives due to the potential leaching from the outside of the cave and the DNA damage that we propose has been caused by the fungal chemical etching.

  • 3453.
    Zetterberg, Camilla
    et al.
    Högskolan i Gävle, Akademin för hälsa och arbetsliv, Avdelningen för arbets- och folkhälsovetenskap, Arbetshälsovetenskap. Högskolan i Gävle, Centrum för belastningsskadeforskning. Uppsala universitet, Arbets- och miljömedicin.
    Forsman, Mikael
    Institutet för miljömedicin, Karolinska Institutet, Stockholm, Sverige.
    Richter, Hans O.
    Högskolan i Gävle, Akademin för hälsa och arbetsliv, Avdelningen för arbets- och folkhälsovetenskap, Arbetshälsovetenskap. Högskolan i Gävle, Centrum för belastningsskadeforskning.
    Neck/shoulder discomfort due to visually demanding near work is influenced by previous neck pain, task duration, astigmatism, eye discomfort and accommodation2017Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 8, artikkel-id e0182439Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Visually demanding near work can cause eye discomfort, and eye and neck/shoulder discomfort during, e.g., computer work are associated. Here, to investigate direct effects of experimental near work on eye and neck/shoulder discomfort, 33 individuals with chronic neck pain and 33 healthy control subjects performed four visual tasks, rating eye and neck/shoulder discomfort at baseline and after each task. The cumulative performance time (reflected in the temporal order of the tasks), astigmatism, concurrent eye discomfort, and extent of accommodation all aggravated neck/shoulder discomfort. There was an interaction effect between the temporal order and eye discomfort: participants with a greater mean increase in eye discomfort also developed more neck/shoulder discomfort with time. Since moderate musculoskeletal symptoms are a risk factor for more severe symptoms, it is important to ensure a good visual environment in occupations involving visually demanding near work.

  • 3454.
    Zetterberg, Camilla
    et al.
    Högskolan i Gävle, Akademin för hälsa och arbetsliv, Avdelningen för arbets- och folkhälsovetenskap, Arbetshälsovetenskap. Högskolan i Gävle, Centrum för belastningsskadeforskning. Department of Medical Sciences, Section of Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden..
    Richter, Hans
    Högskolan i Gävle, Akademin för hälsa och arbetsliv, Avdelningen för arbets- och folkhälsovetenskap, Arbetshälsovetenskap. Högskolan i Gävle, Centrum för belastningsskadeforskning.
    Forsman, Mikael
    Högskolan i Gävle, Akademin för hälsa och arbetsliv, Avdelningen för arbets- och folkhälsovetenskap, Arbetshälsovetenskap. Högskolan i Gävle, Centrum för belastningsskadeforskning. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Temporal co-variation between eye lens accommodation and trapezius muscle activity during a dynamic near-far visual task2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 5, artikkel-id e0126578Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Near work is associated with increased activity in the neck and shoulder muscles, but the underlying mechanism is still unknown. This study was designed to determine whether a dynamic change in focus, alternating between a nearby and a more distant visual target, produces a direct parallel change in trapezius muscle activity. Fourteen healthy controls and 12 patients with a history of visual and neck/shoulder symptoms performed a Near-Far visual task under three different viewing conditions; one neutral condition with no trial lenses, one condition with negative trial lenses to create increased accommodation, and one condition with positive trial lenses to create decreased accommodation. Eye lens accommodation and trapezius muscle activity were continuously recorded. The trapezius muscle activity was significantly higher during Near than during Far focusing periods for both groups within the neutral viewing condition, and there was a significant co-variation in time between accommodation and trapezius muscle activity within the neutral and positive viewing conditions for the control group. In conclusion, these results reveal a connection between Near focusing and increased muscle activity during dynamic changes in focus between a nearby and a far target. A direct link, from the accommodation/vergence system to the trapezius muscles cannot be ruled out, but the connection may also be explained by an increased need for eye-neck (head) stabilization when focusing on a nearby target as compared to a more distant target.

  • 3455.
    Zetterberg, Camilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin. University of Gävle, Department of Occupational and Public Health Sciences, Centre for Musculoskeletal Research.
    Richter, Hans O.
    Forsman, Mikael
    Temporal Co-Variation between Eye Lens Accommodation and Trapezius Muscle Activity during a Dynamic Near-Far Visual Task2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 5, artikkel-id e0126578Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Near work is associated with increased activity in the neck and shoulder muscles, but the underlying mechanismis still unknown. This study was designed to determine whether a dynamic change in focus, alternating between a nearby and a more distant visual target, produces a direct parallel change in trapezius muscle activity. Fourteen healthy controls and 12 patients with a history of visual and neck/shoulder symptoms performed a Near-Far visual task under three different viewing conditions; one neutral condition with no trial lenses, one condition with negative trial lenses to create increased accommodation, and one condition with positive trial lenses to create decreased accommodation. Eye lens accommodation and trapeziusmuscle activity were continuously recorded. The trapezius muscle activity was significantly higher during Near than during Far focusing periods for both groups within the neutral viewing condition, and there was a significant co-variation in time between accommodation and trapezius muscle activity within the neutral and positive viewing conditions for the control group. In conclusion, these results reveal a connection between Near focusing and increased muscle activity during dynamic changes in focus between a nearby and a far target. A direct link, from the accommodation/vergence system to the trapezius muscles cannot be ruled out, but the connection may also be explained by an increased need for eye-neck (head) stabilization when focusing on a nearby target as compared to a more distant target.

  • 3456. Zetterberg, Henrik
    et al.
    Mörtberg, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Song, Linan
    Chang, Lei
    Provuncher, Gail K
    Patel, Purvish P
    Ferrell, Evan
    Fournier, David R
    Kan, Cheuk W
    Campbell, Todd G
    Meyer, Ray
    Rivnak, Andrew J
    Pink, Brian A
    Minnehan, Kaitlin A
    Piech, Tomasz
    Rissin, David M
    Duffy, David C
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wilson, David H
    Blennow, Kaj
    Hypoxia Due to Cardiac Arrest Induces a Time-Dependent Increase in Serum Amyloid β Levels in Humans2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 12, s. e28263-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3-10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD.

  • 3457.
    Zetterling, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Berhane, Luwam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Jakola, Asgeir S
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Prognostic markers for survival in patients with oligodendroglial tumors; a single-institution review of 214 cases2017Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 11, artikkel-id e0188419Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In the 2016 WHO classification, the diagnosis of oligodendroglioma has been restricted to IDH mutated, 1p19q codeleted tumors (IDHmut-codel). IDHmut oligoastrocytoma is now classified either as oligodendroglioma or astrocytoma based on presence of 1p19q codeletion. There is growing evidence that this molecular classification more closely reflects patient outcome. Due to the strong association between IDHmut-codel with oligodendroglial morphology, the additional impact of these markers on prognostic accuracy is largely unknown. Our aim was to assess the prognostic impact of IDHmut-codel in an unselected cohort of morphologically classified oligodendroglial tumors.

    METHODS: We performed a retrospective chart review of oligodendroglial tumors (WHO grade II and III) operated since 1983. A total of 214 tumors were included, and molecular information was available for 96 tumors. The prognostic impact of IDHmut-codel together with clinical parameters was analyzed by multivariate Cox regression.

    RESULTS: IDHmut-codel was registered in 64 tumors while for 150 tumors the molecular profile was negative for IDHmut-codel, unknown or incomplete. Comparison between the two groups showed that patients with IDHmut-codel tumors were younger (42 vs. 48 years), had more frequent frontal tumor location (48 vs. 33%) and presented more often with seizures (72 vs. 51%) and no signs of neurological impairment (14 vs. 30%) than patients harboring tumors with unknown or incomplete molecular profile. Multivariate survival analysis identified young age (HR 1.78 ≥ 40 years), the absence of neurological deficits or personality changes (HR 0.57), frontal tumor location (HR 0.64) and the presence of IDHmut-codel (HR 0.50) as independent predictors for longer survival, whereas tumor grade was not.

    CONCLUSION: In this unselected single-institution cohort, the presence of IDHmut-codel was associated with more beneficial clinical parameters and was identified as an independent prognostic factor. We conclude that the classical oligodendroglioma genotype provides additional prognostic data beyond clinical characteristics, morphology and tumor grade.

  • 3458.
    Zetterström, Caroline E.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Hasselgren, Jenny
    Creative Antibiotics Sweden AB, Umeå, Sweden .
    Salin, Olli
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Davis, Rohan A.
    Eskitis Institute, Griffith University, Brisbane, Australia.
    Quinn, Ronald J.
    Eskitis Institute, Griffith University, Brisbane, Australia.
    Sundin, Charlotta
    Creative Antibiotics Sweden AB, Umeå, Sweden .
    Elofsson, Mikael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    The Resveratrol Tetramer (-)-Hopeaphenol Inhibits Type III Secretion in the Gram-Negative Pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 12, artikkel-id e81969Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Society faces huge challenges, as a large number of bacteria have developed resistance towards many or all of the antibiotics currently available. Novel strategies that can help solve this problem are urgently needed. One such strategy is to target bacterial virulence, the ability to cause disease e.g., by inhibition of type III secretion systems (T3SSs) utilized by many clinically relevant gram-negative pathogens. Many of the antibiotics used today originate from natural sources. In contrast, most virulence-blocking compounds towards the T3SS identified so far are small organic molecules. A recent high-throughput screening of a prefractionated natural product library identified the resveratrol tetramer (-)-hopeaphenol as an inhibitor of the T3SS in Yersinia pseudotuberculosis. In this study we have investigated the virulence blocking properties of (-)-hopeaphenol in three different gram-negative bacteria. (-)- Hopeaphenol was found to have micromolar activity towards the T3SSs in Yersinia pseudotuberculosis and Pseudomonas aeruginosa in cell-based infection models. In addition (-)-hopeaphenol reduced cell entry and subsequent intracellular growth of Chlamydia trachomatis.

  • 3459.
    Zha, Yinghua
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Limnologi.
    Berga, Mercè
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Limnologi.
    Comte, Jérôme
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Limnologi.
    Langenheder, Silke
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Limnologi.
    Effects of Dispersal and Initial Diversity on the Composition and Functional Performance of Bacterial Communities2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 5, artikkel-id e0155239Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Natural communities are open systems and consequently dispersal can play an important role for the diversity, composition and functioning of communities at the local scale. It is, however, still unclear how effects of dispersal differ depending on the initial diversity of local communities. Here we implemented an experiment where we manipulated the initial diversity of natural freshwater bacterioplankton communities using a dilution-to-extinction approach as well as dispersal from a regional species pool. The aim was further to test whether dispersal effects on bacterial abundance and functional parameters (average community growth rates, respiration rates, substrate utilisation ability) differ in dependence of the initial diversity of the communities. First of all, we found that both initial diversity and dispersal rates had an effect on the recruitment of taxa from a regional source, which was higher in communities with low initial diversity and at higher rates of dispersal. Higher initial diversity and dispersal also promoted higher levels of richness and evenness in local communities and affected, both, separately or interactively, the functional performance of communities. Our study therefore suggests that dispersal can influence the diversity, composition and functioning of bacterial communities and that this effect may be enhanced if the initial diversity of communities is depleted.

  • 3460.
    Zhang, Ce
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Liu, Yonggang
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    van der Maarel, Johan RC
    MRP14 (S100A9) protein interacts with alzheimer beta-amyloid peptide and induces its fibrillization2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 3, s. e32953-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Increasing evidence supports the contribution of local inflammation to the development of Alzheimer's disease (AD) pathology, although the precise mechanisms are not clear. In this study, we demonstrate that the pro-inflammatory protein S100A9 interacts with the A beta 1-40 peptide and promotes the formation of fibrillar beta-amyloid structures. This interaction also results in reduced S100A9 cytotoxicity by the binding of S100A9 toxic species to A beta 1-40 amyloid structures. These results suggest that secretion of S100A9 during inflammation promotes the formation of amyloid plaques. By acting as a sink for toxic species, plaque formation may be the result of a protective response within the brain of AD patients, in part mediated by S100A9.

  • 3461.
    Zhang, Dan
    et al.
    Sichuan University, Chengdu, Sichuan Province, China.
    Zhou, Bin
    Sichuan University, Chengdu, Sichuan Province, China.
    Li, Yuan
    Sichuan University, Chengdu, Sichuan Province, China.
    Wang, Mojin
    Sichuan University, Chengdu, Sichuan Province, China.
    Wang, Cun
    Sichuan University, Chengdu, Sichuan Province, China.
    Zhou, Zongguang
    Sichuan University, Chengdu, Sichuan Province, China.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Polymorphisms of Glucose-Regulated Protein 78 and Risk of Colorectal Cancer: A Case-Control Study in Southwest China2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum chaperone, up-regulation serves as an efficient mechanism to promote malignant transformation of colorectal cancer (CRC) and protect CRC cells against apoptosis. Recently, the analysis of GRP78 polymorphisms has already determined that GRP78 rs391957 polymorphism could predict clinical outcome in CRC patients. Thus, we tested whether GRP78 polymorphisms are related to the risk of CRC. In this study, we detected two GRP78 polymorphisms (rs391957 (C>T) and rs430397 (G>A)) in 414 CRC cases and 502 hospital-based cancer-free healthy controls in Southwest China using a polymerase chain reaction–restriction fragment length polymorphism technique. Compared with the CC genotype, carriers of CT and TT genotypes of rs391957 polymorphism had higher risks of CRC (odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.06–1.83 for CT genotype and OR = 2.10, 95% CI = 1.06–4.14 for TT genotype, respectively). In CRC cases, the variant T allele was significantly associated with tumor invasion stage (P = 0.030), but not with status of lymph nodes metastasis (P = 0.052). Compared with the GG genotype, carriers of GA and AA genotypes of rs430397 polymorphism had higher risks of CRC (OR = 1.63, 95% CI = 1.23–2.15 for GA genotype and OR = 2.92, 95% CI = 1.23–6.94 for AA genotype, respectively). The rs430397 polymorphism was not associated with the clinicopathological characteristics of CRC. These data provide the first evidence that GRP78 rs391957 and rs430397 polymorphisms could serve as markers to predict the risk of CRC.

  • 3462. Zhang, Ding
    et al.
    Liu, Jingying
    Gao, Jianfeng
    Shahzad, Muhammad
    Han, Zhaoqing
    Wang, Zhi
    Li, Jiakui
    Sjölinder, Hong
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Zinc Supplementation Protects against Cadmium Accumulation and Cytotoxicity in Madin-Darby Bovine Kidney Cells2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 8, s. e103427-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cadmium ions (Cd2+) have been reported to accumulate in bovine tissues, although Cd2+ cytotoxicity has not been investigated thoroughly in this species. Zinc ions (Zn2+) have been shown to antagonize the toxic effects of heavy metals such as Cd2+ in some systems. The present study investigated Cd2+ cytotoxicity in Madin-Darby bovine kidney (MDBK) epithelial cells, and explored whether this was modified by Zn2+. Exposure to Cd2+ led to a dose-and time-dependent increase in apoptotic cell death, with increased intracellular levels of reactive oxygen species and mitochondrial damage. Zn2+ supplementation alleviated Cd2+-induced cytotoxicity and this protective effect was more obvious when cells were exposed to a lower concentration of Cd2+ (10 mu M), as compared to 50 mu M Cd2+. This indicated that high levels of Cd2+ accumulation might induce irreversible damage in bovine kidney cells. Metallothioneins (MTs) are metal-binding proteins that play an essential role in heavy metal ion detoxification. We found that co-exposure to Zn2+ and Cd2+ synergistically enhanced RNA and protein expression of MT-1, MT-2, and the metal-regulatory transcription factor 1 in MDBK cells. Notably, addition of Zn2+ reduced the amounts of cytosolic Cd2+ detected following MDBK exposure to 10 mu M Cd2+. These findings revealed a protective role of Zn2+ in counteracting Cd2+ uptake and toxicity in MDBK cells, indicating that this approach may provide a means to protect livestock from excessive Cd2+ accumulation.

  • 3463. Zhang, Jian
    et al.
    Xie, Penghui
    Lascoux, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Meagher, Thomas R.
    Liu, Jianquan
    Rapidly Evolving Genes and Stress Adaptation of Two Desert Poplars, Populus euphratica and P. pruinosa2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 6, s. e66370-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Understanding which genes have evolved rapidly with the recent tree speciation in arid habitats can provide valuable insights into different adaptation mechanisms. We employed a comparative evolutionary analysis of expressed sequence tags (ESTs) from two desert poplars, Populus pruinosa and P. euphratica, which diverged in the recent past. Following an approach taken previously with P. euphratica, we conducted a deep transcriptomic analysis of P. pruinosa. To maximize representation of conditional transcripts, mRNA was obtained from living tissues of two types of callus and desert-grown trees. De novo assembly generated 114,866 high-quality unique sequences using Solexa sequence data. Following assembly we were able to identify, with high confidence, 2859 orthologous sequence pairs between the two species. Based on the ratio of nonsynonymous (Ka) to synonymous (Ks) substitutions, we identified a total of 84 (2.9%) ortholog pairs exhibiting rapid evolution with signs of strong selection (Ka/Ks>1). Genes homologous to these ortholog pairs in model species are mainly involved in 'responses to stress', 'ubiquitin-dependent protein catabolic processes', and 'biological regulation'. Finally, we examined the expression patterns of candidate genes with rapid evolution in response to salt stress. Only one pair of orthologs up-regulated their expression in both species while three and four genes were found to up-regulated in P. pruinosa and in P. euphratica respectively. Our findings together suggest that the genes at the same category or network but with differentiated expressions or functions may have evolved rapidly during adaptive divergence of the two species to differentiated salty desert habitats.

  • 3464. Zhang, Lifang
    et al.
    Selao, Tiago Toscano
    Selstam, Eva
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Norling, Birgitta
    Subcellular Localization of Carotenoid Biosynthesis in Synechocystis sp PCC 68032015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 6, artikkel-id e0130904Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The biosynthesis pathway of carotenoids in cyanobacteria is partly described. However, the subcellular localization of individual steps is so far unknown. Carotenoid analysis of different membrane subfractions in Synechocystis sp. PCC6803 shows that "light" plasma membranes have a high carotenoid/protein ratio, when compared to "heavier" plasma membranes or thylakoids. The localization of CrtQ and CrtO, two well-defined carotenoid synthesis pathway enzymes in Synechocystis, was studied by epitope tagging and western blots. Both enzymes are locally more abundant in plasma membranes than in thylakoids, implying that the plasma membrane has higher synthesis rates of beta-carotene precursor molecules and echinenone.

  • 3465. Zhang, Ling-Ling
    et al.
    Dalal, Koustuv
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Wang, Shu-Mei
    Injury related risk behaviour: a health belief model-based study of primary school students in a safe community in Shanghai2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 8, artikkel-id e70563Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim

    To explore the relationship between Health belief model (HBM) and children and adolescents' unintentional injury risk behavior, to add some useful information for injury prevention.

    Methodology

    We investigated injury related health risk behavior and health belief status of students at primary schools grade 3 to 4, in a Safe Community, in Shanghai. Self-administered injury questionnaires were used to investigate risk behavior of students and HBM factors.

    Principal Findings

    The prevalence of risk behavior among students reported in this community was high. HBM scores showed differences between two groups of students classified by whether they had risk behavior or not. Self-efficacy was highly related with the status of socio-psychological behavior.

    Significance

    HBM has been widely used in explaining the disease-related behavior; however, it has been seldom used in injury-related behavior. The study demonstrated important relation of HBM to students' injury issues, and HBM could explain injury related behavior as well, especially for traffic injury-related behavior. When developing injury prevention strategies, we can take it into account.

  • 3466.
    Zhang, Ling-ling
    et al.
    Key Laboratory of Public Health Safety, School of Public Health, Ministry of Education, Fudan University, Shanghai, China.
    Dalal, Koustuv
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Yin, Ming-min
    Key Laboratory of Public Health Safety, School of Public Health, Ministry of Education, Fudan University, Shanghai, China.
    Yuan, De-guo
    Key Laboratory of Public Health Safety, School of Public Health, Ministry of Education, Fudan University, Shanghai, China.
    Andrews, Johanna Yvonne
    Tufts University, Somerville MA, United States of America.
    Wang, Shu-mei
    Key Laboratory of Public Health Safety, School of Public Health, Ministry of Education, Fudan University, Shanghai, China.
    The KAP evaluation of intervention on fall-induced injuries among elders in a safe community in Shanghai, China2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 3, artikkel-id e32848Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: To evaluate the effect of an intervention on fall induced injuries of elderly people in a safe-community in Shanghai and to discuss an intervention model that is proper for the community to generalize.

    Methodology/Principal Findings: Five neighborhood areas in a Safe Community were purposively selected. All individuals aged 60 years or over in five neighborhoods were prospective participants. From randomly selected prospective households with elders, 2,889 (pre intervention) and 3,021 (post intervention) elderly people were included in the study.

    Knowledge, Attitude and Practice Model (KAP) questionnaires were used at the pre- and post-intervention phase for fall-induced injury prevention in the community. Descriptive statistics and chi-square tests were used. After the intervention, knowledge about the prevention of fall-induced injuries increased, as did attitudes, beliefs and good behaviors for fall prevention. Behavior modification was most notable with many behavior items changing significantly (p value<0.0001).

    Conclusions/Significance: The integrated program for reducing fall-related injuries in the community was effective in improving fall prevention among the elderly, but the intervention still needs further improvement.

  • 3467.
    Zhang, Renyun
    et al.
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för tillämpad naturvetenskap och design.
    Hummelgård, Magnus
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för tillämpad naturvetenskap och design.
    Olin, Håkan
    Mittuniversitetet, Fakulteten för naturvetenskap, teknik och medier, Institutionen för tillämpad naturvetenskap och design.
    Simple Fabrication of Gold Nanobelts and Patterns2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 1, s. Art. no. e30469-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gold nanobelts are of interest in several areas; however, there are only few methods available to produce these belts. We report here on a simple evaporation induced self-assembly (EISA) method to produce porous gold nanobelts with dimensions that scale across nanometer (thickness ~80 nm) and micrometer (width ~20 μm), to decimeter (length ~0.15 m). The gold nanobelts are well packed on the beaker wall and can be easily made to float on the surface of the solution for depositing onto other substrates. Microscopy showed that gold nanobelts had a different structure on the two sides of the belt; the density of gold nanowires on one side was greater than on the other side. Electrical measurements showed that these nanobelts were sensitive to compressive or tensile forces, indicating a potential use as a strain sensor. The patterned nanobelts were further used as a template to grow ZnO nanowires for potential use in applications such as piezo-electronics. © 2012 Zhang et al.

  • 3468. Zhang, Xin
    et al.
    Li, Fan
    Zhang, Li
    Zhao, Zhuohui
    Norbäck, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    A Longitudinal Study of Sick Building Syndrome (SBS) among Pupils in Relation to SO2, NO2, O-3 and PM10 in Schools in China2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 11, s. e112933-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There are fewer longitudinal studies from China on symptoms as described for the sick building syndrome (SBS). Here, we performed a two-year prospective study and investigated associations between environmental parameters such as room temperature, relative air humidity (RH), carbon dioxide (CO2), nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O-3), particulate matter (PM10), and health outcomes including prevalence, incidence and remission of SBS symptoms in junior high schools in Taiyuan, China. Totally 2134 pupils participated at baseline, and 1325 stayed in the same classrooms during the study period (2010-2012). The prevalence of mucosal symptoms, general symptoms and symptoms improved when away from school (school-related symptoms) was 22.7%, 20.4% and 39.2%, respectively, at baseline, and the prevalence increased during follow-up (P<0.001). At baseline, both indoor and outdoor SO2 were found positively associated with prevalence of school-related symptoms. Indoor O-3 was shown to be positively associated with prevalence of skin symptoms. At follow-up, indoor PM10 was found to be positively associated with new onset of skin, mucosal and general symptoms. CO2 and RH were positively associated with new onset of mucosal, general and school-related symptoms. Outdoor SO2 was positively associated with new onset of skin symptoms, while outdoor NO2 was positively associated with new onset of skin, general and mucosal symptoms. Outdoor PM10 was found to be positively associated with new onset of skin, general and mucosal symptoms as well as school-related symptoms. In conclusion, symptoms as described for SBS were commonly found in school children in Taiyuan City, China, and increased during the two-year follow-up period. Environmental pollution, including PM10, SO2 and NO2, could increase the prevalence and incidence of SBS and decrease the remission rate. Moreover, parental asthma and allergy (heredity) and pollen or pet allergy (atopy) can be risk factors for SBS.

  • 3469. Zhao, Charlie W.
    et al.
    Daley, Mark J.
    Pruszynski, J. Andrew
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Dept. of Computer Science, Western University, London, Ontario, Canada; Brain and Mind Institute, Western University, London, Ontario, Canada; Dept. of Physiology and Pharmacology, Western University, London, Ontario, Canada; Dept. of Psychology, Western University, London, Ontario, Canada; Robarts Research Institute, Western University, London, Ontario, Canada.
    Neural network models of the tactile system develop first-order units with spatially complex receptive fields2018Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 6, artikkel-id e0199196Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    First-order tactile neurons have spatially complex receptive fields. Here we use machine-learning tools to show that such complexity arises for a wide range of training sets and network architectures. Moreover, we demonstrate that this complexity benefits network performance, especially on more difficult tasks and in the presence of noise. Our work suggests that spatially complex receptive fields are normatively good given the biological constraints of the tactile periphery.

  • 3470.
    Zhao, Jing
    et al.
    Department of Mathematics, Logistical Engineering University, Chongqing, China.
    Yang, Ting-Hong
    Department of Mathematics, Logistical Engineering University, Chongqing, China.
    Huang, Yongxu
    Department of Health Policy & Management, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
    Holme, Petter
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Ranking candidate disease genes from gene expression and protein interaction: a katz-centrality based approach2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 9, s. e24306-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many diseases have complex genetic causes, where a set of alleles can affect the propensity of getting the disease. The identification of such disease genes is important to understand the mechanistic and evolutionary aspects of pathogenesis, improve diagnosis and treatment of the disease, and aid in drug discovery. Current genetic studies typically identify chromosomal regions associated specific diseases. But picking out an unknown disease gene from hundreds of candidates located on the same genomic interval is still challenging. In this study, we propose an approach to prioritize candidate genes by integrating data of gene expression level, protein-protein interaction strength and known disease genes. Our method is based only on two, simple, biologically motivated assumptions—that a gene is a good disease-gene candidate if it is differentially expressed in cases and controls, or that it is close to other disease-gene candidates in its protein interaction network. We tested our method on 40 diseases in 58 gene expression datasets of the NCBI Gene Expression Omnibus database. On these datasets our method is able to predict unknown disease genes as well as identifying pleiotropic genes involved in the physiological cellular processes of many diseases. Our study not only provides an effective algorithm for prioritizing candidate disease genes but is also a way to discover phenotypic interdependency, cooccurrence and shared pathophysiology between different disorders.

  • 3471.
    Zhao, Tao
    et al.
    KTH, Skolan för kemivetenskap (CHE), Kemi, Organisk kemi.
    Krokene, Paal
    Hu, Jiang
    KTH, Skolan för kemivetenskap (CHE), Kemi, Organisk kemi.
    Christiansen, Erik
    Björklund, Niklas
    Långström, Bo
    Solheim, Halvor
    Borg-Karlson, Anna-Karin
    KTH, Skolan för kemivetenskap (CHE), Kemi, Organisk kemi.
    Induced Terpene Accumulation in Norway Spruce Inhibits Bark Beetle Colonization in a Dose-Dependent Manner2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 10, s. e26649-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Tree-killing bark beetles (Coleoptera, Scolytinae) are among the most economically and ecologically important forest pests in the northern hemisphere. Induction of terpenoid-based oleoresin has long been considered important in conifer defense against bark beetles, but it has been difficult to demonstrate a direct correlation between terpene levels and resistance to bark beetle colonization. Methods: To test for inhibitory effects of induced terpenes on colonization by the spruce bark beetle Ips typographus (L.) we inoculated 20 mature Norway spruce Picea abies (L.) Karsten trees with a virulent fungus associated with the beetle, Ceratocystis polonica (Siem.) C. Moreau, and investigated induced terpene levels and beetle colonization in the bark. Results: Fungal inoculation induced very strong and highly variable terpene accumulation 35 days after inoculation. Trees with high induced terpene levels (n = 7) had only 4.9% as many beetle attacks (5.1 vs. 103.5 attacks m(-2)) and 2.6% as much gallery length (0.029 m m(-2) vs. 1.11 m m(-2)) as trees with low terpene levels (n = 6). There was a highly significant rank correlation between terpene levels at day 35 and beetle colonization in individual trees. The relationship between induced terpene levels and beetle colonization was not linear but thresholded: above a low threshold concentration of similar to 100 mg terpene g(-1) dry phloem trees suffered only moderate beetle colonization, and above a high threshold of similar to 200 mg terpene g(-1) dry phloem trees were virtually unattacked. Conclusion/Significance: This is the first study demonstrating a dose-dependent relationship between induced terpenes and tree resistance to bark beetle colonization under field conditions, indicating that terpene induction may be instrumental in tree resistance. This knowledge could be useful for developing management strategies that decrease the impact of tree-killing bark beetles.

  • 3472.
    Zhao, Yelin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Wang, Hui
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Gustafsson, Mika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Muraro, Antonella
    University of Padua, Italy .
    Bruhn, Sören
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Benson, Mikael
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Combined Multivariate and Pathway Analyses Show That Allergen-Induced Gene Expression Changes in CD4(+) T Cells Are Reversed by Glucocorticoids2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Glucocorticoids (GCs) play a key role in the treatment of allergy. However, the genome-wide effects of GCs on gene expression in allergen-challenged CD4(+) T cells have not been described. The aim of this study was to perform a genome-wide analysis to investigate whether allergen-induced gene expression changes in CD4(+) T cells could be reversed by GCs. Methodology/Principal Findings: Gene expression microarray analysis was performed to profile gene expression in diluent( D), allergen- (A), and allergen + hydrocortisone- (T) challenged CD4(+) T cells from patients with seasonal allergic rhinitis. Principal component analysis (PCA) showed good separation of the three groups. To identify the correlation between changes in gene expression in allergen-challenged CD4(+) T cells before and after GC treatment, we performed orthogonal partial least squares discriminant analysis (OPLS-DA) followed by Pearson correlation analysis. This revealed that allergen-induced genes were widely reversed by GC treatment (r = -0.77, Pless than0.0001). We extracted 547 genes reversed by GC treatment from OPLS-DA models based on their high contribution to the discrimination and found that those genes belonged to several different inflammatory pathways including TNFR2 Signalling, Interferon Signalling, Glucocorticoid Receptor Signalling and T Helper Cell Differentiation. The results were supported by gene expression microarray analyses of two independent materials. Conclusions/Significance: Allergen-induced gene expression changes in CD4(+) T cells were reversed by treatment with glucocorticoids. The top allergen-induced genes that reversed by GC treatment belonged to several inflammatory pathways and genes of known or potential relevance for allergy.

  • 3473.
    Zheleznyakova, Galina Yu
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Nilsson, Emil K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Kiselev, Anton V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Maretina, Marianna A.
    Tishchenko, Lyudmila I.
    Fredriksson, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Baranov, Vladislav S.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Methylation Levels of SLC23A2 and NCOR2 Genes Correlate with Spinal Muscular Atrophy Severity2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 3, artikkel-id e0121964Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Spinal muscular atrophy (SMA) is a monogenic neurodegenerative disorder subdivided into four different types. Whole genome methylation analysis revealed 40 CpG sites associated with genes that are significantly differentially methylated between SMA patients and healthy individuals of the same age. To investigate the contribution of methylation changes to SMA severity, we compared the methylation level of found CpG sites, designed as "targets", as well as the nearest CpG sites in regulatory regions of ARHGAP22, CDK2AP1, CHML, NCOR2, SLC23A2 and RPL9 in three groups of SMA patients. Of notable interest, compared to type I SMA male patients, the methylation level of a target CpG site and one nearby CpG site belonging to the 5'UTR of SLC23A2 were significantly hypomethylated 19-22% in type III-IV patients. In contrast to type I SMA male patients, type III-IV patients demonstrated a 16% decrease in the methylation levels of a target CpG site, belonging to the 5'UTR of NCOR2. To conclude, this study validates the data of our previous study and confirms significant methylation changes in the SLC23A2 and NCOR2 regulatory regions correlates with SMA severity.

  • 3474. Zheng, Weiwen
    et al.
    Rasmussen, Ulla
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och botanik.
    Zheng, Siping
    Bao, Xiaodong
    Chen, Bin
    Gao, Yuan
    Guan, Xiong
    Larsson, John
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och botanik.
    Bergman, Birgitta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och botanik.
    Multiple Modes of Cell Death Discovered in a Prokaryotic (Cyanobacterial) Endosymbiont2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 6, s. e66147-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Programmed cell death (PCD) is a genetically-based cell death mechanism with vital roles in eukaryotes. Although there is limited consensus on similar death mode programs in prokaryotes, emerging evidence suggest that PCD events are operative. Here we present cell death events in a cyanobacterium living endophytically in the fern Azolla microphylla, suggestive of PCD. This symbiosis is characterized by some unique traits such as a synchronized development, a vertical transfer of the cyanobacterium between plant generations, and a highly eroding cyanobacterial genome. A combination of methods was used to identify cell death modes in the cyanobacterium. Light- and electron microscopy analyses showed that the proportion of cells undergoing cell death peaked at 53.6% (average 20%) of the total cell population, depending on the cell type and host developmental stage. Biochemical markers used for early and late programmed cell death events related to apoptosis (Annexin V-EGFP and TUNEL staining assays), together with visualization of cytoskeleton alterations (FITC-phalloidin staining), showed that all cyanobacterial cell categories were affected by cell death. Transmission electron microscopy revealed four modes of cell death: apoptotic-like, autophagic-like, necrotic-like and autolytic-like. Abiotic stresses further enhanced cell death in a dose and time dependent manner. The data also suggest that dynamic changes in the peptidoglycan cell wall layer and in the cytoskeleton distribution patterns may act as markers for the various cell death modes. The presence of a metacaspase homolog (domain p20) further suggests that the death modes are genetically programmed. It is therefore concluded that multiple, likely genetically programmed, cell death modes exist in cyanobacteria, a finding that may be connected with the evolution of cell death in the plant kingdom.

  • 3475. Zheng, Zongli
    et al.
    Andersson, Anders F.
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Ye, Weimin
    Nyrén, Olof
    Normark, Staffan
    Engstrand, Lars
    A Method for Metagenomics of Helicobacter pylori from Archived Formalin-Fixed Gastric Biopsies Permitting Longitudinal Studies of Carcinogenic Risk2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 10, s. e26442-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The human microbiota has come into focus in the search for component causes of chronic diseases, such as gastrointestinal cancers. Presumably long induction periods and altered local environments after disease onset call for the development of methods for characterization of microorganisms colonizing the host decades before disease onset. Sequencing of microbial genomes in old formalin-fixed and paraffin-embedded (FFPE) gastrointestinal biopsies provides a means for such studies but is still challenging. Here we report a method based on laser capture micro-dissection and modified Roche 454 high-throughput pyrosequencing to obtain metagenomic profiles of Helicobacter pylori. We applied this method to two 15 year old FFPE biopsies from two patients. Frozen homogenized biopsies from the same gastroscopy sessions were also available for comparison after re-culture of H. pylori. For both patients, H. pylori DNA dissected from FFPE sections had similar to 96.4% identity with culture DNA from the same patients, while only similar to 92.5% identity with GenBank reference genomes, and with culture DNA from the other patient. About 82% and 60% of the predicted genes in the two genomes were captured by at least a single sequencing read. Along with sequences displaying high similarity to known H. pylori genes, novel and highly variant H. pylori sequences were identified in the FFPE sections by our physical enrichment approach, which would likely not have been detected by a sequence capture approach. The study demonstrates the feasibility of longitudinal metagenomic studies of H. pylori using decade-preserved FFPE biopsies.

  • 3476.
    Zheng, Z.Z.
    et al.
    Queen's University.
    MacDonald, E.
    Queen's University.
    Munhall, K.
    Queen's University.
    Johnsrude, Ingrid
    Queen's University.
    Perceiving a stranger's voice as being one's own:  a 'rubber voice' illusion?2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 4, s. e18655-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We describe an illusion in which a stranger's voice, when presented as the auditory concomitant of a participant's own speech, is perceived as a modified version of their own voice. When the congruence between utterance and feedback breaks down, the illusion is also broken. Compared to a baseline condition in which participants heard their own voice as feedback, hearing a stranger's voice induced robust changes in the fundamental frequency (F0) of their production. Moreover, the shift in F0 appears to be feedback dependent, since shift patterns depended reliably on the relationship between the participant's own F0 and the stranger-voice F0. The shift in F0 was evident both when the illusion was present and after it was broken, suggesting that auditory feedback from production may be used separately for self-recognition and for vocal motor control. Our findings indicate that self-recognition of voices, like other body attributes, is malleable and context dependent.

  • 3477. Zhou, Xiaohong
    et al.
    Wang, Ke
    Lv, Dongwen
    Wu, Cheng Jun
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Li, Jiarui
    Zhao, Pei
    Lin, Zhishan
    Du, Lipu
    Yan, Yueming
    Ye, Xingguo
    Global Analysis of Differentially Expressed Genes and Proteins in the Wheat Callus Infected by Agrobacterium tumefaciens2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 11, s. e79390-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Agrobacterium-mediated plant transformation is an extremely complex and evolved process involving genetic determinants of both the bacteria and the host plant cells. However, the mechanism of the determinants remains obscure, especially in some cereal crops such as wheat, which is recalcitrant for Agrobacterium-mediated transformation. In this study, differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were analyzed in wheat callus cells co-cultured with Agrobacterium by using RNA sequencing (RNA-seq) and two-dimensional electrophoresis (2-DE) in conjunction with mass spectrometry (MS). A set of 4,889 DEGs and 90 DEPs were identified, respectively. Most of them are related to metabolism, chromatin assembly or disassembly and immune defense. After comparative analysis, 24 of the 90 DEPs were detected in RNA-seq and proteomics datasets simultaneously. In addition, real-time RT-PCR experiments were performed to check the differential expression of the 24 genes, and the results were consistent with the RNA-seq data. According to gene ontology (GO) analysis, we found that a big part of these differentially expressed genes were related to the process of stress or immunity response. Several putative determinants and candidate effectors responsive to Agrobacterium mediated transformation of wheat cells were discussed. We speculate that some of these genes are possibly related to Agrobacterium infection. Our results will help to understand the interaction between Agrobacterium and host cells, and may facilitate developing efficient transformation strategies in cereal crops.

  • 3478.
    Zhou, Yuye
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Kemi, Tillämpad fysikalisk kemi.
    Romson, Joakim
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Kemi, Tillämpad fysikalisk kemi.
    Emmer, Åsa
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Kemi, Tillämpad fysikalisk kemi.
    An antibody-free sample pretreatment method for osteopontin combined with MALDI-TOF MS/MS analysis2019Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 3, artikkel-id e0213405Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Osteopontin is an osteoblast-secreted protein with an aspartic acid-rich, highly phosphorylated, and glycosylated structure. Osteopontin can easily bind to integrins, tumor cells, extracellular matrix and calcium, and is related to bone diseases, various cancers, inflammation etc. Here, DEAE-Cibacron blue 3GA was used to extract recombinant osteopontin from human plasma, and to deplete abundant plasma proteins with an antibody-free method. Using selected buffer systems, osteopontin and human serum albumin could be bound to DEAE-Cibacron blue 3GA, while immunoglobulin G was excluded. The bound osteopontin could then be separated from albumin by using different sequential elution buffers. By this method, 1 μg/mL recombinant osteopontin could be separated from the major part of the most abundant proteins in human plasma. After trypsin digestion, the extracted osteopontin could be successfully detected and identified by MALDI-TOF MS/MS using the m/z 1854.898 peptide and its fragments.

  • 3479. Zhu, Egui
    et al.
    Fors, Uno
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Smedberg, Åsa
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Exploring the needs and possibilities of physicians' continuing professional development - An explorative qualitative study in a Chinese primary care context2018Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 8, artikkel-id e0202635Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background One component of the 2009 Chinese health care reform plan is to train general practitioners to improve the delivery of primary care services. This continuing professional development is expected to further improve the physicians' competencies to be general practitioners in primary care. Augmented reality +/- a combination of virtual information and the real environment +/- may enhance general practitioners' continuing professional development by allowing their learning experiences to overlap with their workplace practice. Objective To explore the needs, opportunities, and challenges involved in continuing professional development for Chinese physicians becoming competent general practitioners within primary care, with a special focus on the possibilities of applying augmented reality. Methods This study used a qualitative approach with semi-structured face-to-face interviews. Two managers and thirteen physicians (from four community health centers and stations) participated. The data were analyzed using a thematic inductive analysis approach. Results Based on our interviews, most of the physicians were not fully trained as general practitioners but still assumed the duties of that position; they were supposed to eventually become fully trained in line with the reforms of the Chinese primary care system. However, they reported a lack of in-service training opportunities to fulfill this goal. Even those who said that they had such opportunities perceived the efficacy of that training as being poor. The managers and most of the physicians reacted positively to the idea of using augmented reality in continuing professional development, and they suggested antibiotics treatment, surgery, and emergency care as learning areas in which augmented reality could be applied. Conclusions Due to the Chinese reforms of the primary care system, both managers and the physicians themselves expect general practitioners to become qualified by engaging in continuing professional development. Both groups also regarded augmented reality as a potentially useful tool.

  • 3480.
    Zhu, Jianwei
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Orthopedics, Shandong Provincial Hospital, Shandong University, Jinan, China.
    Lu, Donghao
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sveinsson, Olafur
    Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Wirdefeldt, Karin
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fall, Katja
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Piehl, Fredrik
    Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Valdimarsdóttir, Unnur
    Center of Public Health, University of Iceland, Reykjavík, Iceland.
    Fang, Fang
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Is a cancer diagnosis associated with subsequent risk of transient global amnesia?2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 4, artikkel-id e0122960Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Psychological stress has been associated with transient global amnesia (TGA). Whether a cancer diagnosis, a severely stressful life event, is associated with subsequent risk of TGA has not been studied.

    Methods: Based on the Swedish Cancer Register and Patient Register, we conducted a prospective cohort study including 5,365,608 Swedes at age 30 and above during 2001-2009 to examine the relative risk of TGA among cancer patients, as compared to cancer-free individuals. Incidence rate ratios (IRRs) and their 95% confidence intervals (CIs) derived from Poisson regression were used as estimates of the association between cancer diagnosis and the risk of TGA.

    Results: During the study 322,558 individuals (6.01%) received a first diagnosis of cancer. We identified 210 cases of TGA among the cancer patients (incidence rate, 0.22 per 1000 person-years) and 4,887 TGA cases among the cancer-free individuals (incidence rate, 0.12 per 1000 person-years). Overall, after adjustment for age, sex, calendar year, socioeconomic status, education and civil status, cancer patients had no increased risk of TGA than the cancer-free individuals (IRR, 0.99; 95% CI, 0.86-1.13). The IRRs did not differ over time since cancer diagnosis or across individual cancer types. The null association was neither modified by sex, calendar period or age.

    Conclusion: Our study did not provide support for the hypothesis that patients with a new diagnosis of cancer display a higher risk of TGA than cancer-free individuals.

  • 3481. Zhu, Min
    et al.
    Yu, Xiaobo
    Choo, Brian
    Qu, Qingming
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Evolution och utvecklingsbiologi.
    Jia, Liantao
    Zhao, Wenjin
    Qiao, Tuo
    Lu, Jing
    Fossil Fishes from China Provide First Evidence of Dermal Pelvic Girdles in Osteichthyans2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 4, s. e35103-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The pectoral and pelvic girdles support paired fins and limbs, and have transformed significantly in the diversification of gnathostomes or jawed vertebrates (including osteichthyans, chondrichthyans, acanthodians and placoderms). For instance, changes in the pectoral and pelvic girdles accompanied the transition of fins to limbs as some osteichthyans (a clade that contains the vast majority of vertebrates - bony fishes and tetrapods) ventured from aquatic to terrestrial environments. The fossil record shows that the pectoral girdles of early osteichthyans (e. g., Lophosteus, Andreolepis, Psarolepis and Guiyu) retained part of the primitive gnathostome pectoral girdle condition with spines and/or other dermal components. However, very little is known about the condition of the pelvic girdle in the earliest osteichthyans. Living osteichthyans, like chondrichthyans (cartilaginous fishes), have exclusively endoskeletal pelvic girdles, while dermal pelvic girdle components (plates and/or spines) have so far been found only in some extinct placoderms and acanthodians. Consequently, whether the pectoral and pelvic girdles are primitively similar in osteichthyans cannot be adequately evaluated, and phylogeny-based inferences regarding the primitive pelvic girdle condition in osteichthyans cannot be tested against available fossil evidence.

    Methodology/Principal Findings: Here we report the first discovery of spine-bearing dermal pelvic girdles in early osteichthyans, based on a new articulated specimen of Guiyu oneiros from the Late Ludlow (Silurian) Kuanti Formation, Yunnan, as well as a re-examination of the previously described holotype. We also describe disarticulated pelvic girdles of Psarolepis romeri from the Lochkovian (Early Devonian) Xitun Formation, Yunnan, which resemble the previously reported pectoral girdles in having integrated dermal and endoskeletal components with polybasal fin articulation.

    Conclusions/Significance: The new findings reveal hitherto unknown similarity in pectoral and pelvic girdles among early osteichthyans, and provide critical information for studying the evolution of pelvic girdles in osteichthyans and other gnathostomes.

  • 3482.
    Zhu, Zhaolong
    et al.
    College of Material Science and Engineering, Nanjing Forestry University, Nanjing, Jiangsu, China.
    Buck, Dietrich
    Luleå tekniska universitet, Institutionen för teknikvetenskap och matematik, Träteknik.
    Guo, Xiaolei
    College of Material Science and Engineering, Nanjing Forestry University, Nanjing, Jiangsu, China.
    Ekevad, Mats
    Luleå tekniska universitet, Institutionen för teknikvetenskap och matematik, Träteknik.
    Pingxiang, Cao
    College of Material Science and Engineering, Nanjing Forestry University, Nanjing, Jiangsu, China.
    Wu, Zhenzeng
    Department of Material Engineering, Fujian Agriculture and Forestry University, Fujian, China.
    Machinability investigation in turning of high density fiberboard2018Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 9, s. 1-13, artikkel-id e0203838Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A series of experiments were conducted to assess the machinability of high density fiberboardusing cemented carbide cutting tools. The objective of this work was to investigate theinfluence of two cutting parameters, spindle speed and feed per turn, on cutting forces, chipformation and cutting quality. The results are as follows: cutting forces and chip-breakinglength decrease with increasing spindle speed and decreasing feed per turn. In contrast,surface roughness increases with decrease of spindle speed and increase in feed perturn. Chips were divided into four categories based on their shape: dust, particle, splinter,and semicontinuous chips. Chip-breaking length had a similar tendency to the varianceof cutting forces with respect to average roughness and mean peak-to-valley height: anincrease in the variance of cutting forces resulted in increased average roughness andmean peak-to-valley height. Thus, high cutting speed and low feed rate are parameters suitablefor high-quality HDF processing and will improve not only machining quality, but productionefficiency.

  • 3483.
    Ziaei, Shirin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Internationell mödra- och barnhälsovård (IMCH).
    Frith, Amy Lynn
    thaca Coll, Sch Hlth Sci & Human Performance, Ithaca, NY 14850 USA.
    Ekström, Eva-Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Internationell mödra- och barnhälsovård (IMCH).
    Naved, Ruchira Tabassum
    Int Ctr Diarrhoeal Dis Res ICDDR B, Dhaka, Bangladesh.
    Experiencing Lifetime Domestic Violence: Associations with Mental Health and Stress among Pregnant Women in Rural Bangladesh: The MINIMat Randomized Trial2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 12, artikkel-id e0168103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Experience of domestic violence has negative mental health consequences for women. The association of cumulative and specific forms of domestic violence, particularly emotional violence and controlling behavior, with common mental disorders and stress has rarely been studied in pregnant women. The aim of this study is to evaluate associations of specific and multiple forms of lifetime domestic violence and controlling behavior with distress and cortisol level during pregnancy in rural Bangladeshi women.

    METHODS AND FINDINGS: In this observational sub-study of larger MINIMat trial, 3504 pregnant women were interviewed using a shortened Conflict Tactic Scale about their lifetime experience of domestic violence including physical, sexual, emotional domestic violence and controlling behavior. Women's levels of emotional distress were assessed using the self-reported questionnaire (SRQ-20) developed by WHO, and levels of morning salivary cortisol were measured in a subsample (n = 1300) of women during week 28-32 of pregnancy. Regression analyses were used to estimate the associations of lifetime physical, sexual, emotional domestic violence and controlling behavior with levels of distress and cortisol during pregnancy. The prevalence of lifetime domestic violence was 57% and emotional distress was 35% in these pregnant women. All forms of domestic violence were associated with higher levels of emotional distress. Women who experienced either emotional violence or controlling behavior had the highest levels of emotional distress. There was a dose-response relationship between cumulative number of the different forms of domestic violence and women's levels of emotional distress. There was no association between women's experience of domestic violence and level of morning salivary cortisol.

    CONCLUSION: Including emotional violence and controlling behavior as major types of violence in future research and health interventions is warranted. Furthermore, the extent of the negative impacts of domestic violence on pregnant women, multiple forms of violence and their cumulative effects need to be investigated.

  • 3484.
    Ziegler, Ingrid
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Fagerström, Anna
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden .
    Strålin, Kristoffer
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Mölling, Paula
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Evaluation of a Commercial Multiplex PCR Assay for Detection of Pathogen DNA in Blood from Patients with Suspected Sepsis2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 12, artikkel-id e0167883Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Magicplex Sepsis Real-time Test (MST) is a commercial multiplex PCR that can detect more than 90 different pathogens in blood, with an analysis time of six hours. The aim of the present study was to evaluate this method for the detection of bloodstream infection (BSI). An EDTA whole blood sample for MST was collected together with blood cultures (BC) from patients with suspected sepsis at the Emergency Department of a university hospital. Among 696 study patients, 322 (46%) patients were positive with at least one method; 128 (18%) were BC positive and 268 (38%) were MST positive. Considering BC to be the gold standard, MST had an overall sensitivity of 47%, specificity of 66%, positive predictive value (PPV) of 23%, and a negative predictive value of 87%. Among the MST positive samples with a negative BC, coagulase-negative staphylococci (CoNS) and species that rarely cause community-acquired BSI were frequently noted. However, the quantification cycle (Cq) values of the MST+/BC- results were often high. We thus hypothesized that the performance of the MST test could be improved if the Cq cut-off level was adjusted downwards. With a lower Cq cut-off value, i.e. 6.0 for Staphylococcus species and 9.0 for all other species, the number of MST positive cases decreased to 83 (12%) and the overall sensitivity decreased to 38%. However, the PPV increased to 59% and the specificity increased to 96%, as many MST positive results for CoNS and bacteria that rarely cause community-acquired BSI turned MST negative. In conclusion, our study shows that with a lower Cq cut-off value, the MST will detect less contaminants and findings with unclear relevance, but to the cost of a lower sensitivity. Consequently, we consider that a positive MST results with a Cq value above the adjusted cut-off should be interpreted with caution, as the result might be clinically irrelevant. In a correspondent way, quantitative results could probably be useful in the interpretation of positive results from other molecular assays for the detection of BSI.

  • 3485. Zielinski, Brian L.
    et al.
    Allen, Andrew E.
    Carpenter, Edward J.
    Coles, Victoria J.
    Crump, Byron C.
    Doherty, Mary
    Foster, Rachel A.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och botanik. University of California, USA.
    Goes, Joaquim I.
    Gomes, Helga R.
    Hood, Raleigh R.
    McCrow, John P.
    Montoya, Joseph P.
    Moustafa, Ahmed
    Satinsky, Brandon M.
    Sharma, Shalabh
    Smith, Christa B.
    Yager, Patricia L.
    Paul, John H.
    Patterns of Transcript Abundance of Eukaryotic Biogeochemically-Relevant Genes in the Amazon River Plume2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 9, artikkel-id e0160929Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Amazon River has the largest discharge of all rivers on Earth, and its complex plume system fuels a wide array of biogeochemical processes, across a large area of the western tropical North Atlantic. The plume thus stimulates microbial processes affecting carbon sequestration and nutrient cycles at a global scale. Chromosomal gene expression patterns of the 2.0 to 156 mu m size-fraction eukaryotic microbial community were investigated in the Amazon River Plume, generating a robust dataset (more than 100 million mRNA sequences) that depicts the metabolic capabilities and interactions among the eukaryotic microbes. Combining classical oceanographic field measurements with metatranscriptomics yielded characterization of the hydrographic conditions simultaneous with a quantification of transcriptional activity and identity of the community. We highlight the patterns of eukaryotic gene expression for 31 biogeochemically significant gene targets hypothesized to be valuable within forecasting models. An advantage to this targeted approach is that the database of reference sequences used to identify the target genes was selectively constructed and highly curated optimizing taxonomic coverage, throughput, and the accuracy of annotations. A coastal diatom bloom highly expressed nitrate transporters and carbonic anhydrase presumably to support high growth rates and enhance uptake of low levels of dissolved nitrate and CO2. Diatom-diazotroph association (DDA: diatoms with nitrogen fixing symbionts) blooms were common when surface salinity was mesohaline and dissolved nitrate concentrations were below detection, and hence did not show evidence of nitrate utilization, suggesting they relied on ammonium transporters to aquire recently fixed nitrogen. These DDA blooms in the outer plume had rapid turnover of the photosystem D1 protein presumably caused by photodegradation under increased light penetration in clearer waters, and increased expression of silicon transporters as silicon became limiting. Expression of these genes, including carbonic anhydrase and transporters for nitrate and phosphate, were found to reflect the physiological status and biogeochemistry of river plume environments. These relatively stable patterns of eukaryotic transcript abundance occurred over modest spatiotemporal scales, with similarity observed in sample duplicates collected up to 2.45 km in space and 120 minutes in time. These results confirm the use of metatranscriptomics as a valuable tool to understand and predict microbial community function.

  • 3486. Zijnge, Vincent
    et al.
    Kieselbach, Thomas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Oscarsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral mikrobiologi.
    Proteomics of protein secretion by aggregatibacter actinomycetemcomitans2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 7, s. e41662-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The extracellular proteome (secretome) of periodontitis-associated bacteria may constitute a major link between periodontitis and systemic diseases. To obtain an overview of the virulence potential of Aggregatibacter actinomycetemcomitans, an oral and systemic human pathogen implicated in aggressive periodontitis, we used a combined LC-MS/MS and bioinformatics approach to characterize the secretome and protein secretion pathways of the rough-colony serotype a strain D7S. LC-MS/MS revealed 179 proteins secreted during biofilm growth. Further to confirming the release of established virulence factors (e.g. cytolethal distending toxin [CDT], and leukotoxin [LtxA]), we identified additional putative virulence determinants in the secretome. These included DegQ, fHbp, LppC, Macrophage infectivity protein (MIP), NlpB, Pcp, PotD, TolB, and TolC. This finding indicates that the number of extracellular virulence-related proteins is much larger than previously demonstrated, which was also supported by in silico analysis of the strain D7S genome. Moreover, our LC-MS/MS and in silico data revealed that at least Type I, II, and V secretion are actively used to excrete proteins directly into the extracellular space, or via two-step pathways involving the Sec/Tat systems for transport across the inner membrane, and outer membrane factors, secretins and auto-transporters, respectively for delivery across the outer membrane. Taken together, our results provide a molecular basis for further elucidating the role of A. actinomycetemcomitans in periodontal and systemic diseases.

  • 3487.
    Zinner, Christoph
    et al.
    Univ Wurzburg, Dept Sport Sci, D-97070 Wurzburg, Germany.;Mid Sweden Univ, Dept Hlth Sci, Swedish Winter Sports Res Ctr, Ostersund, Sweden..
    Hauser, Anna
    Swiss Fed Inst Sport, Sect Elite Sport, Magglingen, Switzerland..
    Born, Dennis-Peter
    Univ Wurzburg, Dept Sport Sci, D-97070 Wurzburg, Germany..
    Wehrlin, Jon P.
    Swiss Fed Inst Sport, Sect Elite Sport, Magglingen, Switzerland..
    Holmberg, Hans-Christer
    Mittuniversitetet, Fakulteten för humanvetenskap, Avdelningen för hälsovetenskap.
    Sperlich, Billy
    Mittuniversitetet, Fakulteten för humanvetenskap, Avdelningen för hälsovetenskap. Univ Wurzburg, Dept Sport Sci, D-97070 Wurzburg, Germany..
    Influence of Hypoxic Interval Training and Hyperoxic Recovery on Muscle Activation and Oxygenation in Connection with Double-Poling Exercise2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 10, artikkel-id e0140616Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here, we evaluated the influence of breathing oxygen at different partial pressures during recovery from exercise on performance at sea-level and a simulated altitude of 1800 m, as reflected in activation of different upper body muscles, and oxygenation of the m. triceps brachii. Ten well-trained, male endurance athletes (25.3 +/- 4.1 yrs; 179.2 +/- 4.5 cm; 74.2 +/- 3.4 kg) performed four test trials, each involving three 3-min sessions on a double-poling ergometer with 3-min intervals of recovery. One trial was conducted entirely under normoxic (No) and another under hypoxic conditions (Ho; FiO2 = 0.165). In the third and fourth trials, the exercise was performed in normoxia and hypoxia, respectively, with hyperoxic recovery (HOX; FiO2 = 1.00) in both cases. Arterial hemoglobin saturation was higher under the two HOX conditions than without HOX (p<0.05). Integrated muscle electrical activity was not influenced by the oxygen content (best d = 0.51). Furthermore, the only difference in tissue saturation index measured via near-infrared spectroscopy observed was between the recovery periods during the NoNo and HoHOX interventions (P<0.05, d = 0.93). In the case of HoHo the athletes' P-mean declined from the first to the third interval (P < 0.05), whereas P-mean was unaltered under the HoHOX, NoHOX and NoNo conditions. We conclude that the less pronounced decline in P-mean during 3 x 3-min double-poling sprints in normoxia and hypoxia with hyperoxic recovery is not related to changes inmuscle activity or oxygenation. Moreover, we conclude that hyperoxia (FiO2 = 1.00) used in conjunction with hypoxic or normoxic work intervals may serve as an effective aid when inhaled during the subsequent recovery intervals.

  • 3488. Zins, Marie
    et al.
    Guéguen, Alice
    Kivimäki, Mika
    Singh-Manoux, Archana
    Leclerc, Annette
    Vahtera, Jussi
    Westerlund, Hugo
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Ferrie, Jane E
    Goldberg, Marcel
    Effect of retirement on alcohol consumption: longitudinal evidence from the French gazel cohort study2011Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 10, s. e26531-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Little is known about the effect of retirement on alcohol consumption. The objectives were to examine changes in alcohol consumption following retirement, and whether these patterns differ by gender and socioeconomic status.

    METHODS AND FINDINGS: We assessed alcohol consumption annually from 5 years before to 5 years after retirement among 10,023 men and 2,361 women of the French Gazel study. Data were analyzed separately for men and women, using repeated-measures logistic regression analysis with generalized estimating equations. Five years prior to retirement, the prevalence of heavy drinking was about 16% among men, and not patterned by socioeconomic status. Among women, this prevalence was 19.5% in managers, 14.7% in intermediate occupations, and 12.8% in clerical workers. Around retirement, the estimated prevalence of heavy drinking increased in both sexes. In men, this increase was 3.1 percentage points for managers, 3.2 in intermediate occupations, 4.6 in clerical workers, and 1.3 in manual workers. In women, this increase was 6.6 percentage points among managers, 4.3 in intermediate occupations, and 3.3 among clerical workers. In men the increase around retirement was followed by a decrease over the following four years, not significant among manual workers; among women such a decrease was also observed in the non-managerial occupations. It is difficult to assess the extent to which the results observed in this cohort would hold for other working populations, other conditions of employment, or in other cultural settings. A plausible explanation for the increase in heavy drinking around retirement could be that increased leisure time after retirement provides more opportunities for drinking, and not having to work during the day after may decrease constraints on drinking.

    CONCLUSIONS: Our findings of increased consumption around retirement suggest that information about negative effects of alcohol consumption should be included in pre-retirement planning programs.

  • 3489.
    Zoerner, Frank
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Miclescu, Adriana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Martijn, Cecile
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Therapeutic hypothermia activates the endothelin and nitric oxide systems after cardiac arrest in a pig model of cardiopulmonary resuscitation2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 5, s. e64792-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Post-cardiac arrest myocardial dysfunction is a major cause of mortality in patients receiving successful cardiopulmonary resuscitation (CPR). Mild therapeutic hypothermia (MTH) is the recommended treatment after resuscitation from cardiac arrest (CA) and is known to exert neuroprotective effects and improve short-term survival. Yet its cytoprotective mechanisms are not fully understood. In this study, our aim was to determine the possible effect of MTH on vasoactive mediators belonging to the endothelin/nitric oxide axis in our porcine model of CA and CPR. Pigs underwent either untreated CA or CA with subsequent CPR. After state-of-the-art resuscitation, the animals were either left untreated, cooled between 32-34°C after ROSC or treated with a bolus injection of S-PBN (sodium 4-[(tert-butylimino) methyl]benzene-3-sulfonate N-oxide) until 180 min after ROSC, respectively. The expression of endothelin 1 (ET-1), endothelin converting enzyme 1 (ECE-1), and endothelin A and B receptors (ETAR and ETBR) transcripts were measured using quantitative real-time PCR while protein levels for the ETAR, ETBR and nitric oxide synthases (NOS) were assessed using immunohistochemistry and Western Blot. Our results indicated that the endothelin system was not upregulated at 30, 60 and 180 min after ROSC in untreated postcardiac arrest syndrome. Post-resuscitative 3 hour-long treatments either with MTH or S-PBN stimulated ET-1, ECE-1, ETAR and ETBR as well as neuronal NOS and endothelial NOS in left ventricular cardiomyocytes. Our data suggests that the endothelin and nitric oxide pathways are activated by MTH in the heart.

  • 3490.
    Zurek, Birte
    et al.
    University of Cologne, Germany .
    Schoultz, Ida
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Neerincx, Andreas
    University of Cologne, Germany .
    Napolitano, Luisa M
    Telethon Institute Genet and Med, Italy Cluster Biomed CBM, Italy .
    Birkner, Katharina
    University of Cologne, Germany .
    Bennek, Eveline
    University Hospital Aachen, Germany .
    Sellge, Gernot
    University Hospital Aachen, Germany .
    Lerm, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Meroni, Germana
    Cluster Biomed CBM, Italy .
    Söderholm, Johan D
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken i Östergötland.
    Kufer, Thomas A
    University of Cologne, Germany .
    TRIM27 Negatively Regulates NOD2 by Ubiquitination and Proteasomal Degradation2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    NOD2, the nucleotide-binding domain and leucine-rich repeat containing gene family (NLR) member 2 is involved in mediating antimicrobial responses. Dysfunctional NOD2 activity can lead to severe inflammatory disorders, but the regulation of NOD2 is still poorly understood. Recently, proteins of the tripartite motif (TRIM) protein family have emerged as regulators of innate immune responses by acting as E3 ubiquitin ligases. We identified TRIM27 as a new specific binding partner for NOD2. We show that NOD2 physically interacts with TRIM27 via the nucleotide-binding domain, and that NOD2 activation enhances this interaction. Dependent on functional TRIM27, ectopically expressed NOD2 is ubiquitinated with K48-linked ubiquitin chains followed by proteasomal degradation. Accordingly, TRIM27 affects NOD2-mediated pro-inflammatory responses. NOD2 mutations are linked to susceptibility to Crohns disease. We found that TRIM27 expression is increased in Crohns disease patients, underscoring a physiological role of TRIM27 in regulating NOD2 signaling. In HeLa cells, TRIM27 is partially localized in the nucleus. We revealed that ectopically expressed NOD2 can shuttle to the nucleus in a Walker A dependent manner, suggesting that NOD2 and TRIM27 might functionally cooperate in the nucleus. We conclude that TRIM27 negatively regulates NOD2-mediated signaling by degradation of NOD2 and suggest that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases.

  • 3491.
    Zurek, Birte
    et al.
    Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
    Schoultz, Ida
    Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Neerincx, Andreas
    Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
    Napolitano, Luisa M.
    Cluster in Biomedicine (CBM), AREA Science Park, Trieste, Italy; Telethon Institute of Genetics and Medicine, Naples, Italy.
    Birkner, Katharina
    Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
    Bennek, Eveline
    Department of Medicine III, University Hospital Aachen, Aachen, Germany.
    Sellge, Gernot
    Department of Medicine III, University Hospital Aachen, Aachen, Germany.
    Lerm, Maria
    Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Meroni, Germana
    Cluster in Biomedicine (CBM), AREA Science Park, Trieste, Italy.
    Söderholm, Johan D.
    Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Kufer, Thomas A.
    Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
    TRIM27 negatively regulates NOD2 by ubiquitination and proteasomal degradation2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 7, artikkel-id e41255Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    NOD2, the nucleotide-binding domain and leucine-rich repeat containing gene family (NLR) member 2 is involved in mediating antimicrobial responses. Dysfunctional NOD2 activity can lead to severe inflammatory disorders, but the regulation of NOD2 is still poorly understood. Recently, proteins of the tripartite motif (TRIM) protein family have emerged as regulators of innate immune responses by acting as E3 ubiquitin ligases. We identified TRIM27 as a new specific binding partner for NOD2. We show that NOD2 physically interacts with TRIM27 via the nucleotide-binding domain, and that NOD2 activation enhances this interaction. Dependent on functional TRIM27, ectopically expressed NOD2 is ubiquitinated with K48-linked ubiquitin chains followed by proteasomal degradation. Accordingly, TRIM27 affects NOD2-mediated pro-inflammatory responses. NOD2 mutations are linked to susceptibility to Crohn's disease. We found that TRIM27 expression is increased in Crohn's disease patients, underscoring a physiological role of TRIM27 in regulating NOD2 signaling. In HeLa cells, TRIM27 is partially localized in the nucleus. We revealed that ectopically expressed NOD2 can shuttle to the nucleus in a Walker A dependent manner, suggesting that NOD2 and TRIM27 might functionally cooperate in the nucleus.We conclude that TRIM27 negatively regulates NOD2-mediated signaling by degradation of NOD2 and suggest that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases.

  • 3492. Zybailov, Boris
    et al.
    Rutschow, Heidi
    Friso, Giulia
    Rudella, Andrea
    Emanuelsson, Olof
    Stockholms universitet.
    Sun, Qi
    van Wijk, Klaas J.
    Sorting signals, N-terminal modifications and abundance of the chloroplast proteome2008Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 3, nr 4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Characterization of the chloroplast proteome is needed to understand the essential contribution of the chloroplast to plant growth and development. Here we present a large scale analysis by nanoLC-Q-TOF and nanoLC-LTQ-Orbitrap mass spectrometry (MS) of ten independent chloroplast preparations from Arabidopsis thaliana which unambiguously identified 1325 proteins. Novel proteins include various kinases and putative nucleotide binding proteins. Based on repeated and independent MS based protein identifications requiring multiple matched peptide sequences, as well as literature, 916 nuclear-encoded proteins were assigned with high confidence to the plastid, of which 86% had a predicted chloroplast transit peptide (cTP). The protein abundance of soluble stromal proteins was calculated from normalized spectral counts from LTQ-Obitrap analysis and was found to cover four orders of magnitude. Comparison to gel-based quantification demonstrates that 'spectral counting' can provide large scale protein quantification for Arabidopsis. This quantitative information was used to determine possible biases for protein targeting prediction by TargetP and also to understand the significance of protein contaminants. The abundance data for 550 stromal proteins was used to understand abundance of metabolic pathways and chloroplast processes. We highlight the abundance of 48 stromal proteins involved in post-translational proteome homeostasis (including aminopeptidases, proteases, deformylases, chaperones, protein sorting components) and discuss the biological implications. N-terminal modifications were identified for a subset of nuclear- and chloroplast-encoded proteins and a novel N-terminal acetylation motif was discovered. Analysis of cTPs and their cleavage sites of Arabidopsis chloroplast proteins, as well as their predicted rice homologues, identified new species-dependent features, which will facilitate improved subcellular localization prediction. No evidence was found for suggested targeting via the secretory system. This study provides the most comprehensive chloroplast proteome analysis to date and an expanded Plant Proteome Database (PPDB) in which all MS data are projected on identified gene models.

  • 3493. Zygmunt, Peter M.
    et al.
    Ermund, Anna
    Movahed, Pouya
    Andersson, David A.
    Simonsen, Charlotte
    Jonsson, Bo A. G.
    Blomgren, Anders
    Birnir, Bryndis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Bevan, Stuart
    Eschalier, Alain
    Mallet, Christophe
    Gomis, Ana
    Hogestatt, Edward D.
    Monoacylglycerols Activate TRPV1-A Link between Phospholipase C and TRPV12013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 12, s. e81618-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate generates diacylglycerol, inositol 1,4,5-trisphosphate and protons, all of which can regulate TRPV1 activity via different mechanisms. Here we explored the possibility that the diacylglycerol metabolites 2-arachidonoylglycerol and 1-arachidonoylglycerol, and not metabolites of these monoacylglycerols, activate TRPV1 and contribute to this signaling cascade. 2-Arachidonoylglycerol and 1-arachidonoylglycerol activated native TRPV1 on vascular sensory nerve fibers and heterologously expressed TRPV1 in whole cells and inside-out membrane patches. The monoacylglycerol lipase inhibitors methylarachidonoyl-fluorophosphonate and JZL184 prevented the metabolism of deuterium-labeled 2-arachidonoylglycerol and deuterium-labeled 1-arachidonoylglycerol in arterial homogenates, and enhanced TRPV1-mediated vasodilator responses to both monoacylglycerols. In mesenteric arteries from TRPV1 knock-out mice, vasodilator responses to 2-arachidonoylglycerol were minor. Bradykinin and adenosine triphosphate, ligands of phospholipase C-coupled membrane receptors, increased the content of 2-arachidonoylglycerol in dorsal root ganglia. In HEK293 cells expressing the phospholipase C-coupled histamine H-1 receptor, exposure to histamine stimulated the formation of 2-AG, and this effect was augmented in the presence of JZL184. These effects were prevented by the diacylglycerol lipase inhibitor tetrahydrolipstatin. Histamine induced large whole cell currents in HEK293 cells co-expressing TRPV1 and the histamine H-1 receptor, and the TRPV1 antagonist capsazepine abolished these currents. JZL184 increased the histamine-induced currents and tetrahydrolipstatin prevented this effect. The calcineurin inhibitor ciclosporin and the endogenous "entourage'' compound palmitoylethanolamide potentiated the vasodilator response to 2-arachidonoylglycerol, disclosing TRPV1 activation of this monoacylglycerol at nanomolar concentrations. Furthermore, intracerebroventricular injection of JZL184 produced TRPV1-dependent antinociception in the mouse formalin test. Our results show that intact 2-arachidonoylglycerol and 1-arachidonoylglycerol are endogenous TRPV1 activators, contributing to phospholipase C-dependent TRPV1 channel activation and TRPV1-mediated antinociceptive signaling in the brain.

  • 3494.
    Zysk, Marlena
    et al.
    Med Univ Gdansk, Dept Lab Med, Gdansk, Poland.
    Gapys, Beata
    Med Univ Gdansk, Dept Lab Med, Gdansk, Poland.
    Ronowska, Anna
    Med Univ Gdansk, Dept Lab Med, Gdansk, Poland.
    Gul-Hinc, Sylwia
    Med Univ Gdansk, Dept Lab Med, Gdansk, Poland.
    Erlandsson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Iwanicki, Adam
    Univ Gdansk, Dept Mol Bacteriol, Gdansk, Poland;Med Univ Gdansk, Gdansk, Poland.
    Sakowicz-Burkiewicz, Monika
    Med Univ Gdansk, Dept Mol Med, Gdansk, Poland.
    Szutowicz, Andrzej
    Med Univ Gdansk, Dept Lab Med, Gdansk, Poland.
    Bielarczyk, Hanna
    Med Univ Gdansk, Dept Lab Med, Gdansk, Poland.
    Protective effects of voltage-gated calcium channel antagonists against zinc toxicity in SN56 neuroblastoma cholinergic cells2018Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 12, artikkel-id e0209363Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    One of the pathological site effects in excitotoxic activation is Zn2+ overload to postsynaptic neurons. Such an effect is considered to be equivalent to the glutamate component of excitotoxicity. Excessive uptake of Zn2+ by active voltage-dependent transport systems in these neurons may lead to significant neurotoxicity. The aim of this study was to investigate whether and which antagonists of the voltage gated calcium channels (VGCC) might modify this Zn2+-induced neurotoxicity in neuronal cells. Our data demonstrates that depolarized SN56 neuronal cells may take up large amounts of Zn2+ and store these in cytoplasmic and mitochondrial sub-fractions. The mitochondrial Zn2+ excess suppressed pyruvate uptake and oxidation. Such suppression was caused by inhibition of pyruvate dehydrogenase complex, aconitase and NADP-isocitrate dehydrogenase activities, resulting in the yielding of acetyl-CoA and ATP shortages. Moreover, incoming Zn2+ increased both oxidized glutathione and malondialdehyde levels, known parameters of oxidative stress. In depolarized SN56 cells, nifedipine treatment (L-type VGCC antagonist) reduced Zn2+ uptake and oxidative stress. The treatment applied prevented the activities of PDHC, aconitase and NADP-IDH enzymes, and also yielded the maintenance of acetyl-CoA and ATP levels. Apart from suppression of oxidative stress, N- and P/Q-type VGCCs presented a similar, but weaker protective influence. In conclusion, our data shows that in the course of excitotoxity, impairment to calcium homeostasis is tightly linked with an excessive neuronal Zn2+ uptake. Hence, the VGCCs types L, N and P/Q share responsibility for neuronal Zn2+ overload followed by significant energy-dependent neurotoxicity. Moreover, Zn2+ affects the target tricarboxylic acid cycle enzymes, yields acetyl-CoA and energy deficits as well.

  • 3495.
    Zötterman, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Mirdell, Robin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Horsten, Sandra
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Farnebo, Simon
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Tesselaar, Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Methodological concerns with laser speckle contrast imaging in clinical evaluation of microcirculation2017Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 3, artikkel-id e0174703Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Laser Speckle Contrast Imaging (LSCI) is a non-invasive and fast technique for measuring microvascular blood flow that recently has found clinical use for burn assessment and evaluation of flaps. Tissue motion caused by for example breathing or patient movements may however affect the measurements in these clinical applications, as may distance between the camera and the skin and tissue curvature. Therefore, the aims of this study were to investigate the effect of frame rate, number of frames/image, movement of the tissue, measuring distance and tissue curvature on the measured perfusion. Methods Methyl nicotinate-induced vasodilation in the forearm skin was measured using LSCI during controlled motion at different speeds, using different combinations of frame rate and number of frames/image, and at varying camera angles and distances. Experiments were made on healthy volunteers and on a cloth soaked in a colloidal suspension of polystyrene microspheres. Results Measured perfusion increased with tissue motion speed. The relation was independent of the absolute perfusion in the skin and of frame rate and number of frames/image. The measured perfusion decreased with increasing angles (16% at 60, p = 0.01). Measured perfusion did not vary significantly between measurement distances from 15 to 40 cm (p = 0.77, %CV 0.9%). Conclusion Tissue motion increases and measurement angles beyond 45 decrease the measured perfusion in LSCI. These findings have to be taken into account when LSCI is used to assess moving or curved tissue surfaces, which is common in clinical applications.

  • 3496.
    Åkerman, Linda
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Casas, Rosaura
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Ludvigsson, Johnny
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Tavira Iglesias, Beatriz
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Skoglund, Camilla
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Serum miRNA levels are related to glucose homeostasis and islet autoantibodies in children with high risk for type 1 diabetes2018Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 1, artikkel-id e0191067Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Micro RNAs (miRNAs) are promising disease biomarkers due to their high stability. Their expression in serum is altered in type 1 diabetes, but whether deviations exist in individuals with high risk for type 1 diabetes remains unexplored. We therefore assessed serum miRNAs in high-risk individuals (n = 21) positive for multiple islet autoantibodies, age-matched healthy children (n = 17) and recent-onset type 1 diabetes patients (n = 8), using Serum/Plasma Focus microRNA PCR Panels from Exiqon. The miRNA levels in the high-risk group were similar to healthy controls, and no specific miRNA profile was identified for the high-risk group. However, serum miRNAs appeared to reflect glycemic status and ongoing islet auto-immunity in high-risk individuals, since several miRNAs were associated to glucose homeostasis and autoantibody titers. High-risk individuals progressing to clinical disease after the sampling could not be clearly distinguished from non-progressors, while miRNA expression in the type 1 diabetes group deviated significantly from high-risk individuals and healthy controls, perhaps explained by major metabolic disturbances around the time of diagnosis.

  • 3497.
    Åkerström, Tobias
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Crona, Joakim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Verdugo, Alberto Delgado
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Starker, Lee F.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Cupisti, Kenko
    Willenberg, Holger S.
    Knoefel, Wolfram T.
    Saeger, Wolfgang
    Feller, Alfred
    Ip, Julian
    Soon, Patsy
    Anlauf, Martin
    Alesina, Pier F.
    Schmid, Kurt W.
    Decaussin, Myriam
    Levillain, Pierre
    Wangberg, Bo
    Peix, Jean-Louis
    Robinson, Bruce
    Zedenius, Jan
    Backdahl, Martin
    Caramuta, Stefano
    Iwen, K. Alexander
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Kraimps, Jean-Louis
    Dralle, Henning
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Sidhu, Stan
    Westin, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Lehnert, Hendrik
    Walz, Martin K.
    Åkerström, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Carling, Tobias
    Choi, Murim
    Lifton, Richard P.
    Björklund, Peyman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Experimentell kirurgi.
    Comprehensive Re-Sequencing of Adrenal Aldosterone Producing Lesions Reveal Three Somatic Mutations near the KCNJ5 Potassium Channel Selectivity Filter2012Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 7, s. e41926-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or L168R) was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na+ conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a Mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined.

    Materials and Methods: The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers.

    Results: G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%). Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p < 0.005) and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p < 0.005).

    Discussion: Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing lesions. These findings provide new insight into the pathogenesis of primary aldosteronism.

  • 3498.
    Ångström-Brännström, Charlotte
    et al.
    Department of Nursing, Umeå University, Umeå, Sweden.
    Engvall, Gunn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Mullaney, Tara
    Umeå Institute of Design, Umeå University, Umeå, Sweden.
    Nilsson, Kristina
    Section of Oncology, Department of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, Uppsala, Sweden.
    Wickart-Johansson, Gun
    Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden.
    Svärd, Anna-Maja
    Department of Radiation Sciences, Umeå University, Umeå, Sweden.
    Nyholm, Tufve
    Department of Radiation Sciences, Umeå University, Umeå, Sweden.
    Lindh, Jack
    Department of Radiation Sciences, Umeå University, Umeå, Sweden.
    Lindh, Viveca
    Department of Nursing, Umeå University, Umeå, Sweden.
    Children Undergoing Radiotherapy: Swedish Parents' Experiences and Suggestions for Improvement.2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 10, artikkel-id e0141086Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Approximately 300 children, from 0 to 18 years old, are diagnosed with cancer in Sweden every year. Of these children, 80-90 of them undergo radiotherapy treatment for their cancer. Although radiotherapy is an encounter with advanced technology, few studies have investigated the child's and the parent's view of the procedure. As part of an ongoing multicenter study aimed to improve patient preparation and the care environment in pediatric radiotherapy, this article reports the findings from interviews with parents at baseline. The aim of the present study was twofold: to describe parents' experience when their child undergoes radiotherapy treatment, and to report parents' suggestions for improvements during radiotherapy for their children. Sixteen mothers and sixteen fathers of children between 2-16 years old with various cancer diagnoses were interviewed. Data were analyzed using content analysis. The findings showed that cancer and treatment turns people's lives upside down, affecting the entire family. Further, the parents experience the child's suffering and must cope with intense feelings. Radiotherapy treatment includes preparation by skilled and empathetic staff. The parents gradually find that they can deal with the process; and lastly, parents have suggestions for improvements during the radiotherapy treatment. An overarching theme emerged: that despair gradually turns to a sense of security, with a sustained focus on and close interaction with the child. In conclusion, an extreme burden was experienced around the start of radiotherapy, though parents gradually coped with the process.

  • 3499.
    Ångström-Brännström, Charlotte
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Engvall, Gunn
    Mullaney, Tara
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Designhögskolan vid Umeå universitet.
    Nilsson, Kristina
    Wickart-Johansson, Gun
    Svärd, Anna-Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nyholm, Tufve
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Lindh, Jack
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Lindh, Viveca
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Children Undergoing Radiotherapy: Swedish Parents' Experiences and Suggestions for Improvement2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 10, artikkel-id e0141086Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Approximately 300 children, from 0 to 18 years old, are diagnosed with cancer in Sweden every year. Of these children, 80-90 of them undergo radiotherapy treatment for their cancer. Although radiotherapy is an encounter with advanced technology, few studies have investigated the child's and the parent's view of the procedure. As part of an ongoing multi-center study aimed to improve patient preparation and the care environment in pediatric radiotherapy, this article reports the findings from interviews with parents at baseline. The aim of the present study was twofold: to describe parents' experience when their child undergoes radiotherapy treatment, and to report parents' suggestions for improvements during radiotherapy for their children. Sixteen mothers and sixteen fathers of children between 2-16 years old with various cancer diagnoses were interviewed. Data were analyzed using content analysis. The findings showed that cancer and treatment turns people's lives upside down, affecting the entire family. Further, the parents experience the child's suffering and must cope with intense feelings. Radiotherapy treatment includes preparation by skilled and empathetic staff. The parents gradually find that they can deal with the process; and lastly, parents have suggestions for improvements during the radiotherapy treatment. An overarching theme emerged: that despair gradually turns to a sense of security, with a sustained focus on and close interaction with the child. In conclusion, an extreme burden was experienced around the start of radiotherapy, though parents gradually coped with the process.

  • 3500.
    Åsberg, M
    et al.
    Karolinska Institutet.
    Nygren, A
    Karolinska Institutet.
    Leopardi, Rosario
    Karolinska Institutet.
    Rylander, Gunnar
    Peterson, Ulla
    Wilczek, Lukas
    Karolinska Institutet.
    Källmén, Håkan
    Ekstedt, Mirjam
    Karolinska Institutet.
    Åkerstedt, Torbjörn
    Karolinska Institutet.
    Lekander, Mats
    Karolinska Institutet.
    Ekman, Rolf
    Novel biochemical markers of psychosocial stress in women2009Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, nr 1, s. e3590-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women.

    METHODS: Plasma concentrations of interleukin (IL) 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women.

    RESULTS: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill.

    CONCLUSIONS: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.

6768697071 3451 - 3500 of 3514
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf