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71.
Cameron L. Rutt Stephen R. Midway Vitek Jirinec Jared D. Wolfe Philip C Stouffer 《Oikos》2019,128(6):798-810
Proposed mechanisms for the decline of terrestrial and understory insectivorous birds in the tropics include a related subset that together has been termed the ‘microclimate hypothesis’. One prediction from this hypothesis is that sensitivity to bright light environments discourages birds of the dimly lit rainforest interior from using edges, gaps, or disturbed forest. Using a hierarchical Bayesian framework and capture data across time and space, we tested this by first determining vulnerability based on differences in within‐species capture rates between disturbed and undisturbed forest for 64 bird species at the Biological Dynamics of Forest Fragments Project in central Amazonian Brazil. We found that 35 species (55%) were vulnerable to anthropogenic habitat degradation, whereas only four (6%) were more commonly captured in degraded forest. To infer visual sensitivity, we then examined two different characters: eye size (maximum pupil diameter) relative to body mass and the initiation time of dawn song, which presumably reflects a species’ visual capacity under low light intensities. We predicted that species with large relative eye sizes and birds with earlier dawn songs would exhibit increased vulnerability in degraded habitats with bright light. Contrary to our predictions, however, vulnerability was positively correlated with the mean start time of dawn song. This indicates that species that wait to initiate dawn song are also more vulnerable to habitat degradation. After correcting for body size, there was no effect of eye size on vulnerability. Together, our results do not provide quantitative support for the light sensitivity mechanism of the microclimate hypothesis. More sensitive experimental tests, such as behavioral assays with controlled light environments, especially in a comparative framework, are needed to rigorously evaluate the role of light sensitivity as an aspect of the microclimate hypothesis among Neotropical birds. 相似文献
72.
Andrea B. Schreuder Jana Vanikova Libor Vitek Rick Havinga Charles E. Ahlfors Christian V. Hulzebos Henkjan J. Verkade 《PloS one》2013,8(10)
Background
Severe unconjugated hyperbilirubinemia carries the risk of neurotoxicity. Phototherapy (PT) and exchange transfusion (ET) are cornerstones in the treatment of unconjugated hyperbilirubinemia. Studies to improve ET efficacy have been hampered by the low application of ET in humans and by the lack of an in vivo model. The absence of an appropriate animal model has also prevented to determine the efficacy of adjunct or alternative treatment options such as albumin (Alb) administration.Aim
To establish an in vivo model for ET and to determine the most effective treatment (combination) of ET, PT and Alb administration.Methods
Gunn rats received either PT, PT+Alb, ET, ET+PT, ET+PT+Alb or sham operation (each n = 7). ET was performed via the right jugular vein in ∼20 min. PT (18 µW/cm2/nm) was started after ET or at T0. Albumin i.p. injections (2.5 g/kg) were given after ET or before starting PT. Plasma unconjugated bilirubin (UCB), plasma free bilirubin (Bf), and brain bilirubin concentrations were determined.Results
We performed ET in 21 Gunn rats with 100% survival. At T1, ET was profoundly more effective in decreasing both UCB −44%, p<0.01) and Bf −81%, p<0.05) than either PT or PT+Alb. After 48 h, the combination of ET+PT+Alb showed the strongest hypobilirubinemic effect (−54% compared to ET).Conclusions
We optimized ET for severe unconjugated hyperbilirubinemia in the Gunn rat model. Our data indicate that ET is the most effective treatment option, in the acute as well as the follow-up situation. 相似文献73.
Ferdinando Cerciello Meena Choi Annalisa Nicastri Damaris Bausch-Fluck Annemarie Ziegler Olga Vitek Emanuela Felley-Bosco Rolf Stahel Ruedi Aebersold Bernd Wollscheid 《Clinical proteomics》2013,10(1):16
Background
Serum biomarkers can improve diagnosis and treatment of malignant pleural mesothelioma (MPM). However, the evaluation of potential new serum biomarker candidates is hampered by a lack of assay technologies for their clinical evaluation. Here we followed a hypothesis-driven targeted proteomics strategy for the identification and clinical evaluation of MPM candidate biomarkers in serum of patient cohorts.Results
Based on the hypothesis that cell surface exposed glycoproteins are prone to be released from tumor-cells to the circulatory system, we screened the surfaceome of model cell lines for potential MPM candidate biomarkers. Selected Reaction Monitoring (SRM) assay technology allowed for the direct evaluation of the newly identified candidates in serum. Our evaluation of 51 candidate biomarkers in the context of a training and an independent validation set revealed a reproducible glycopeptide signature of MPM in serum which complemented the MPM biomarker mesothelin.Conclusions
Our study shows that SRM assay technology enables the direct clinical evaluation of protein-derived candidate biomarker panels for which clinically reliable ELISA’s currently do not exist. 相似文献74.
Singh K Chaturvedi R Barry DP Coburn LA Asim M Lewis ND Piazuelo MB Washington MK Vitek MP Wilson KT 《The Journal of biological chemistry》2011,286(5):3839-3850
Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, is a source of substantial morbidity and remains difficult to treat. New strategies for beneficial anti-inflammatory therapies would be highly desirable. Apolipoprotein (apo) E has immunomodulatory effects and synthetically derived apoE-mimetic peptides are beneficial in models of sepsis and neuroinflammation. We have reported that the antennapedia-linked apoE-mimetic peptide COG112 inhibits the inflammatory response to the colitis-inducing pathogen Citrobacter rodentium in vitro by inhibiting NF-κB activation. We now determined the effect of COG112 in mouse models of colitis. Using C. rodentium as an infection model, and dextran sulfate sodium (DSS) as an injury model, mice were treated with COG112 by intraperitoneal injection. With C. rodentium, COG112 improved the clinical parameters of survival, body weight, colon weight, and histologic injury. With DSS, COG112 ameliorated the loss of body weight, reduction in colon length, and histologic injury, whether administered concurrently with induction of colitis, during induction plus recovery, or only during the recovery phase of disease. In both colitis models, COG112 inhibited colon tissue inducible nitric-oxide synthase (iNOS), KC, TNF-α, IFN-γ, and IL-17 mRNA expression, and reduced nuclear translocation of NF-κB, as determined by immunoblot and immunofluorescence confocal microscopy. IκB kinase (IKK) activity was also reduced, which is necessary for activation of the canonical NF-κB pathway. Isolated colonic epithelial cells exhibited marked attenuation of expression of iNOS and the CXC chemokines KC and MIP-2. These studies indicate that apoE-mimetic peptides such as COG112 are novel potential therapies for IBD. 相似文献
75.
76.
Ting Huang Meena Choi Manuel Tzouros Sabrina Golling Nikhil Janak Pandya Balazs Banfai Tom Dunkley Olga Vitek 《Molecular & cellular proteomics : MCP》2020,19(10):1706-1723
Highlights
- •Statistical approach for differential abundance analysis for proteomic experiments with TMT labeling.
- •Applicable to large-scale experiments with complex or unbalanced design.
- •An open-source R/Bioconductor package compatible with popular data processing tools.
77.
Lucie Muchova Katerina Vanova Jakub Suk Stanislav Micuda Eva Dolezelova Leos Fuksa Dalibor Cerny Hassan Farghali Miroslava Zelenkova Martin Lenicek Ronald J. Wong Hendrik J. Vreman Libor Vitek 《Journal of cellular and molecular medicine》2015,19(5):924-933
Estrogen‐induced cholestasis is characterized by impaired hepatic uptake and biliary bile acids secretion because of changes in hepatocyte transporter expression. The induction of heme oxygenase‐1 (HMOX1), the inducible isozyme in heme catabolism, is mediated via the Bach1/Nrf2 pathway, and protects livers from toxic, oxidative and inflammatory insults. However, its role in cholestasis remains unknown. Here, we investigated the effects of HMOX1 induction by heme on ethinylestradiol‐induced cholestasis and possible underlying mechanisms. Wistar rats were given ethinylestradiol (5 mg/kg s.c.) for 5 days. HMOX1 was induced by heme (15 μmol/kg i.p.) 24 hrs prior to ethinylestradiol. Serum cholestatic markers, hepatocyte and renal membrane transporter expression, and biliary and urinary bile acids excretion were quantified. Ethinylestradiol significantly increased cholestatic markers (P ≤ 0.01), decreased biliary bile acid excretion (39%, P = 0.01), down‐regulated hepatocyte transporters (Ntcp/Oatp1b2/Oatp1a4/Mrp2, P ≤ 0.05), and up‐regulated Mrp3 (348%, P ≤ 0.05). Heme pre‐treatment normalized cholestatic markers, increased biliary bile acid excretion (167%, P ≤ 0.05) and up‐regulated hepatocyte transporter expression. Moreover, heme induced Mrp3 expression in control (319%, P ≤ 0.05) and ethinylestradiol‐treated rats (512%, P ≤ 0.05). In primary rat hepatocytes, Nrf2 silencing completely abolished heme‐induced Mrp3 expression. Additionally, heme significantly increased urinary bile acid clearance via up‐regulation (Mrp2/Mrp4) or down‐regulation (Mrp3) of renal transporters (P ≤ 0.05). We conclude that HMOX1 induction by heme increases hepatocyte transporter expression, subsequently stimulating bile flow in cholestasis. Also, heme stimulates hepatic Mrp3 expression via a Nrf2‐dependent mechanism. Bile acids transported by Mrp3 to the plasma are highly cleared into the urine, resulting in normal plasma bile acid levels. Thus, HMOX1 induction may be a potential therapeutic strategy for the treatment of ethinylestradiol‐induced cholestasis. 相似文献
78.
Fode P Jespersgaard C Hardwick RJ Bogle H Theisen M Dodoo D Lenicek M Vitek L Vieira A Freitas J Andersen PS Hollox EJ 《PloS one》2011,6(2):e16768
Background
There have been conflicting reports in the literature on association of gene copy number with disease, including CCL3L1 and HIV susceptibility, and β-defensins and Crohn''s disease. Quantification of precise gene copy numbers is important in order to define any association of gene copy number with disease. At present, real-time quantitative PCR (QPCR) is the most commonly used method to determine gene copy number, however the Paralogue Ratio Test (PRT) is being used in more and more laboratories.Findings
In this study we compare a Pyrosequencing-based Paralogue Ratio Test (PPRT) for determining beta-defensin gene copy number with two currently used methods for gene copy number determination, QPCR and triplex PRT by typing five different cohorts (UK, Danish, Portuguese, Ghanaian and Czech) of DNA from a total of 576 healthy individuals. We found a systematic measurement bias between DNA cohorts revealed by QPCR, but not by the PRT-based methods. Using PRT, copy number ranged from 2 to 9 copies, with a modal copy number of 4 in all populations.Conclusions
QPCR is very sensitive to quality of the template DNA, generating systematic biases that could produce false-positive or negative disease associations. Both triplex PRT and PPRT do not show this systematic bias, and type copy number within the correct range, although triplex PRT appears to be a more precise and accurate method to type beta-defensin copy number. 相似文献79.
Svetlana Sarantseva Svetlana Timoshenko Olga Bolshakova Eugenia Karaseva Dmitry Rodin Alexander L. Schwarzman Michael P. Vitek 《PloS one》2009,4(12)