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141.
Ira Vashisht Prashant Mishra Tarun Pal Sreekrishna Chanumolu Tiratha Raj Singh Rajinder Singh Chauhan 《Planta》2015,241(5):1269-1270
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New strains of influenza spread around the globe via the movement of infected individuals. The global dynamics of influenza are complicated by different patterns of influenza seasonality in different regions of the world. We have released an open-source stochastic mathematical model of the spread of influenza across 321 major, strategically located cities of the world. Influenza is transmitted between cities via infected airline passengers. Seasonality is simulated by increasing the transmissibility in each city at the times of the year when influenza has been observed to be most prevalent. The spatiotemporal spread of pandemic influenza can be understood through clusters of global transmission and links between them, which we identify using the epidemic percolation network (EPN) of the model. We use the model to explain the observed global pattern of spread for pandemic influenza A(H1N1) 2009-2010 (pandemic H1N1 2009) and to examine possible global patterns of spread for future pandemics depending on the origin of pandemic spread, time of year of emergence, and basic reproductive number (). We also use the model to investigate the effectiveness of a plausible global distribution of vaccine for various pandemic scenarios. For pandemic H1N1 2009, we show that the biggest impact of vaccination was in the temperate northern hemisphere. For pandemics starting in the temperate northern hemisphere in May or April, vaccination would have little effect in the temperate southern hemisphere and a small effect in the tropics. With the increasing interconnectedness of the world's population, we must take a global view of infectious disease transmission. Our open-source, computationally simple model can help public health officials plan for the next pandemic as well as deal with interpandemic influenza. 相似文献
146.
Quinlan AR Boland MJ Leibowitz ML Shumilina S Pehrson SM Baldwin KK Hall IM 《Cell Stem Cell》2011,9(4):366-373
The biomedical utility of induced pluripotent stem cells (iPSCs) will be diminished if most iPSC lines harbor deleterious genetic mutations. Recent microarray studies have shown that human iPSCs carry elevated levels of DNA copy number variation compared with those in embryonic stem cells, suggesting that these and other classes of genomic structural variation (SV), including inversions, smaller duplications and deletions, complex rearrangements, and retroelement transpositions, may frequently arise as a consequence of reprogramming. Here we employ whole-genome paired-end DNA sequencing and sensitive mapping algorithms to identify all classes of SV in three fully pluripotent mouse iPSC lines. Despite the improved scope and resolution of this study, we find few spontaneous mutations per line (one or two) and no evidence for?endogenous retroelement transposition. These results show that genome stability can persist throughout reprogramming, and argue that it is possible to generate iPSCs lacking gene-disrupting mutations using current reprogramming methods. 相似文献
147.
Wu CY Jia Z Wang W Ballou LM Jiang YP Chen B Mathias RT Cohen IS Song LS Entcheva E Lin RZ 《PloS one》2011,6(9):e24404
Background
Phosphoinositide 3-kinases (PI3Ks) regulate numerous physiological processes including some aspects of cardiac function. Although regulation of cardiac contraction by individual PI3K isoforms has been studied, little is known about the cardiac consequences of downregulating multiple PI3Ks concurrently.Methods and Results
Genetic ablation of both p110α and p110β in cardiac myocytes throughout development or in adult mice caused heart failure and death. Ventricular myocytes from double knockout animals showed transverse tubule (T-tubule) loss and disorganization, misalignment of L-type Ca2+ channels in the T-tubules with ryanodine receptors in the sarcoplasmic reticulum, and reduced Ca2+ transients and contractility. Junctophilin-2, which is thought to tether T-tubules to the sarcoplasmic reticulum, was mislocalized in the double PI3K-null myocytes without a change in expression level.Conclusions
PI3K p110α and p110β are required to maintain the organized network of T-tubules that is vital for efficient Ca2+-induced Ca2+ release and ventricular contraction. PI3Ks maintain T-tubule organization by regulating junctophilin-2 localization. These results could have important medical implications because several PI3K inhibitors that target both isoforms are being used to treat cancer patients in clinical trials. 相似文献148.
Derkow K Müller A Eickmeier I Seidel D Rust Moreira MV Kruse N Klugewitz K Mintern J Wiedenmann B Schott E 《PloS one》2011,6(7):e21847
CD4 T-cell help is required for the induction of efficient CD8 T-cells responses and the generation of memory cells. Lack of CD4 T-cell help may contribute to an exhausted CD8 phenotype and viral persistence. Little is known about priming of CD4 T-cells by liver-derived antigen. We used TF-OVA mice expressing ovalbumin in hepatocytes to investigate CD4 T-cell priming by liver-derived antigen and the impact of CD4 T-cell help on CD8 T-cell function. Naïve and effector CD4 T-cells specific for ovalbumin were transferred into TF-OVA mice alone or together with naïve ovalbumin-specific CD8 T-cells. T-cell activation and function were analyzed. CD4 T-cells ignored antigen presented by liver antigen-presenting cells (APCs) in vitro and in vivo but were primed in the liver-draining lymph node and the spleen. No priming occurred in the absence of bone-marrow derived APCs capable of presenting ovalbumin in vivo. CD4 T-cells primed in TF-OVA mice displayed defective Th1-effector function and caused no liver damage. CD4 T-cells were not required for the induction of hepatitis by CD8 T-cells. Th1-effector but not naïve CD4 T-cells augmented the severity of liver injury caused by CD8 T-cells. Our data demonstrate that CD4 T-cells fail to respond to liver-derived antigen presented by liver APCs and develop defective effector function after priming in lymph nodes and spleen. The lack of CD4 T-cell help may be responsible for insufficient CD8 T-cell function against hepatic antigens. 相似文献
149.
Strack S Petersen Y Wagner A Röder IV Albrizio M Reischl M Wacker IU Wilhelm C Rudolf R 《PloS one》2011,6(6):e20524
Background
The turnover of acetylcholine receptors at the neuromuscular junction is regulated in an activity-dependent manner. Upon denervation and under various other pathological conditions, receptor half-life is decreased.Methodology/Principal Findings
We demonstrate a novel approach to follow the kinetics of acetylcholine receptor lifetimes upon pulse labeling of mouse muscles with 125I-α-bungarotoxin in vivo. In contrast to previous assays where residual activity was measured ex vivo, in our setup the same animals are used throughout the whole measurement period, thereby permitting a dramatic reduction of animal numbers at increased data quality. We identified three stability levels of acetylcholine receptors depending on the presence or absence of innervation: one pool of receptors with a long half-life of ∼13 days, a second with an intermediate half-life of ∼8 days, and a third with a short half-life of ∼1 day. Data were highly reproducible from animal to animal and followed simple exponential terms. The principal outcomes of these measurements were reproduced by an optical pulse-labeling assay introduced recently.Conclusions/Significance
A novel assay to determine kinetics of acetylcholine receptor turnover with small animal numbers is presented. Our data show that nerve activity acts on muscle acetylcholine receptor stability by at least two different means, one shifting receptor lifetime from short to intermediate and another, which further increases receptor stability to a long lifetime. We hypothesize on possible molecular mechanisms. 相似文献150.
Insulin resistance in non-obese subjects is associated with activation of the JNK pathway and impaired insulin signaling in skeletal muscle 总被引:1,自引:0,他引:1
Masharani UB Maddux BA Li X Sakkas GK Mulligan K Schambelan M Goldfine ID Youngren JF 《PloS one》2011,6(5):e19878