Rapid cloning of high-affinity human monoclonal antibodies against influenza virus

Pre-existing neutralizing antibody provides the first line of defence against pathogens in general. For influenza virus, annual vaccinations are given to maintain protective levels of antibody against the currently circulating strains. Here we report that after booster vaccination there was a rapid and robust influenza-specific IgG+ antibody-secreting plasma cell (ASC) response that peaked at approximately day 7 and accounted for up to 6% of peripheral blood B cells. These ASCs could be distinguished from influenza-specific IgG+ memory B cells that peaked 14-21 days after vaccination and averaged 1% of all B cells. Importantly, as much as 80% of ASCs purified at the peak of the response were influenza specific. This ASC response was characterized by a highly restricted B-cell receptor (BCR) repertoire that in some donors was dominated by only a few B-cell clones. This pauci-clonal response, however, showed extensive intraclonal diversification from accumulated somatic mutations. We used the immunoglobulin variable regions isolated from sorted single ASCs to produce over 50 human monoclonal antibodies (mAbs) that bound to the three influenza vaccine strains with high affinity. This strategy demonstrates that we can generate multiple high-affinity mAbs from humans within a month after vaccination. The panel of influenza-virus-specific human mAbs allowed us to address the issue of original antigenic sin (OAS): the phenomenon where the induced antibody shows higher affinity to a previously encountered influenza virus strain compared with the virus strain present in the vaccine. However, we found that most of the influenza-virus-specific mAbs showed the highest affinity for the current vaccine strain. Thus, OAS does not seem to be a common occurrence in normal, healthy adults receiving influenza vaccination.     

Ecology: avoidance of disease by social lobsters

Transmissible pathogens are the bane of social animals, so they have evolved behaviours to decrease the probability of infection. There is no record, however, of social animals avoiding diseased individuals of their own species in the wild. Here we show how healthy, normally gregarious Caribbean spiny lobsters (Panulirus argus) avoid conspecifics that are infected with a lethal virus. Early detection and avoidance of infected, though not yet infectious, individuals by healthy lobsters confers a selective advantage and highlights the importance of host behaviour in disease transmission among natural populations.     

Resveratrol improves health and survival of mice on a high-calorie diet

Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.     

多范例自动需求建模和分析: 一种基于本体的方法

提出基于组织本体的问题领域描述, 用领域用户能够理解的术语与他们交互, 引导他们提供需求. 提出以问题领域描述为起点的多范例自动建模和分析方法, 提出组织结构的合理性, 组织目标的可实现性和组织过程的可行性等三个分析准则. 分析的结果可以进一步引导领域用户补充和修改问题领域描述, 分析完成后得到的问题领域模型可以作为前期需求文档, 为进一步的软件需求建模提供依据.