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111.
Tim M. Blackburn Thomas A. A. Prowse Julie L. Lockwood Phillip Cassey 《Biological invasions》2013,15(7):1459-1469
A central paradigm in invasion biology is that more releases of higher numbers of individuals increase the likelihood that an exotic population successfully establishes and persists. Recently, however, it has been suggested that, in cases where the data are sourced from historical records of purposefully released species, the direction of causality is reversed, and that initial success leads to higher numbers being released. Here, we explore the implications of this alternative hypothesis, and derive six a priori predictions from it. We test these predictions using data on Acclimatization Society introductions of passerine bird species to New Zealand, which have previously been used to support both hypotheses for the direction of causality. All our predictions are falsified. This study reaffirms that the conventional paradigm in invasion biology is indeed the correct one for New Zealand passerine bird introductions, for which numbers released determine establishment success. Our predictions are not restricted to this fauna, however, and we keenly anticipate their application to other suitable datasets. 相似文献
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113.
Tim Hendrikx Veerle Bieghs Sofie M. A. Walenbergh Patrick J. van Gorp Fons Verheyen Mike L. J. Jeurissen Mandy M. F. Steinbusch Nathalie Vaes Christoph J. Binder Ger H. Koek Rinke Stienstra Mihai G. Netea Marten H. Hofker Ronit Shiri-Sverdlov 《PloS one》2013,8(12)
Background & Aims
While non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis combined with inflammation, the mechanisms triggering hepatic inflammation are unknown. In Ldlr-/- mice, we have previously shown that lysosomal cholesterol accumulation in Kupffer cells (KCs) correlates with hepatic inflammation and cholesterol crystallization. Previously, cholesterol crystals have been shown to induce the activation of inflammasomes. Inflammasomes are protein complexes that induce the processing and release of pro-inflammatory cytokines IL-1b and IL-18 via caspase-1 activation. Whereas caspase-1 activation is independent of caspase-11 in the canonical pathway of inflammasome activation, caspase-11 was found to trigger caspase-1-dependent IL-1b and IL-18 in response to non-canonical inflammasome activators. So far, it has not been investigated whether inflammasome activation stimulates the formation of cholesterol crystals. We hypothesized that inflammasome activation in KCs stimulates cholesterol crystallization, thereby leading to hepatic inflammation.Methods
Ldlr -/- mice were transplanted (tp) with wild-type (Wt) or caspase-1/11-/- (dKO) bone marrow and fed either regular chow or a high-fat, high-cholesterol (HFC) diet for 12 weeks. In vitro, bone marrow derived macrophages (BMDM) from wt or caspase-1/11-/- mice were incubated with oxLDL for 24h and autophagy was assessed.Results
In line with our hypothesis, caspase-1/11-/--tp mice had less severe hepatic inflammation than Wt-tp animals, as evident from liver histology and gene expression analysis in isolated KCs. Mechanistically, KCs from caspase-1/11-/--tp mice showed less cholesterol crystals, enhanced cholesterol efflux and increased autophagy. In wt BMDM, oxLDL incubation led to disturbed autophagy activity whereas BMDM from caspase-1/11-/- mice had normal autophagy activity.Conclusion
Altogether, these data suggest a vicious cycle whereby disturbed autophagy and decreased cholesterol efflux leads to newly formed cholesterol crystals and thereby maintain hepatic inflammation during NASH by further activating the inflammasome. 相似文献114.
Yang Shen Lin Zeng Aiping Zhu Tim Blanc Dipa Patel Anthony Pennello Amtul Bari Stanley Ng Kris Persaud Yun Kang Paul Balderes David Surguladze Sagit Hindi Qinwei Zhou Dale L. Ludwig Marshall Snavely 《MABS-AUSTIN》2013,5(3):418-431
Optimization of biophysical properties is a critical success factor for the developability of monoclonal antibodies with potential therapeutic applications. The inter-domain disulfide bond between light chain (Lc) and heavy chain (Hc) in human IgG1 lends structural support for antibody scaffold stability, optimal antigen binding, and normal Fc function. Recently, human IgG1λ has been suggested to exhibit significantly greater susceptibility to reduction of the inter Lc-Hc disulfide bond relative to the same disulfide bond in human IgG1κ. To understand the molecular basis for this observed difference in stability, the sequence and structure of human IgG1λ and human IgG1κ were compared. Based on this Lc comparison, three single mutations were made in the λ Lc proximal to the cysteine residue, which forms a disulfide bond with the Hc. We determined that deletion of S214 (dS) improved resistance of the association between Lc and Hc to thermal stress. In addition, deletion of this terminal serine from the Lc of IgG1λ provided further benefit, including an increase in stability at elevated pH, increased yield from transient transfection, and improved in vitro antibody dependent cell-mediated cytotoxicity (ADCC). These observations support the conclusion that the presence of the terminal serine of the λ Lc creates a weaker inter-chain disulfide bond between the Lc and Hc, leading to slightly reduced stability and a potential compromise in IgG1λ function. Our data from a human IgG1λ provide a basis for further investigation of the effects of deleting terminal serine from λLc on the stability and function of other human IgG1λ antibodies. 相似文献
115.
Hubert Kolb Kathrin Lückemeyer Tim Heise Christian Herder Nanette C. Schloot Wolfgang Koenig Lutz Heinemann Stephan Martin 《PloS one》2013,8(8)
Background
The hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics.Methods and Findings
All patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18–39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation) giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA) held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25–0.72), i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI). There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß) but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex.Conclusions
In patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and is the only mediator which correlates (positively) with residual beta cell function.Trial registration
ClinicalTrials.gov registration number: NCT00974740相似文献116.
117.
Andrew Beck Hilda Guzman Li Li Brett Ellis Robert B. Tesh Alan D. T. Barrett 《PLoS neglected tropical diseases》2013,7(3)
Yellow fever virus (YFV) is a mosquito-borne flavivirus that is a major public health problem in tropical areas of Africa and South America. There have been detailed studies on YFV ecology in West Africa and South America, but current understanding of YFV circulation on the African continent is incomplete. This inadequacy is especially notable for East and Central Africa, for which the unpredictability of human outbreaks is compounded by limitations in both historical and present surveillance efforts. Sparse availability of nucleotide sequence data makes it difficult to investigate the dispersal of YFV in these regions of the continent. To remedy this, we constructed Bayesian phylogenetic and geographic analyses utilizing 49 partial genomic sequences to infer the structure of YFV divergence across the known range of the virus on the African continent. Relaxed clock analysis demonstrated evidence for simultaneous divergence of YFV into east and west lineages, a finding that differs from previous hypotheses of YFV dispersal from reservoirs located on edges of the endemic range. Using discrete and continuous geographic diffusion models, we provide detailed structure of YFV lineage diversity. Significant transition links between extant East and West African lineages are presented, implying connection between areas of known sylvatic cycling. The results of demographic modeling reinforce the existence of a stably maintained population of YFV with spillover events into human populations occurring periodically. Geographically distinct foci of circulation are reconstructed, which have significant implications for studies of YFV ecology and emergence of human disease. We propose further incorporation of Bayesian phylogeography into formal GIS analyses to augment studies of arboviral disease. 相似文献
118.
Allison Jones Andrew E. Teschendorff Quanxi Li Jane D. Hayward Athilakshmi Kannan Tim Mould James West Michal Zikan David Cibula Heidi Fiegl Shih-Han Lee Elisabeth Wik Richard Hadwin Rupali Arora Charlotte Lemech Henna Turunen P?ivi Pakarinen Ian J. Jacobs Helga B. Salvesen Milan K. Bagchi Indrani C. Bagchi Martin Widschwendter 《PLoS medicine》2013,10(11)
119.
120.
Géraldine De Muylder Sylvie Daulouède Laurence Lecordier Pierrick Uzureau Yannick Morias Jan Van Den Abbeele Guy Caljon Michel Hérin Philippe Holzmuller Silla Semballa Pierrette Courtois Luc Vanhamme Beno?t Stijlemans Patrick De Baetselier Michael P. Barrett Jillian L. Barlow Andrew N. J. McKenzie Luke Barron Thomas A. Wynn Alain Beschin Philippe Vincendeau Etienne Pays 《PLoS pathogens》2013,9(10)