Aggregation and vesiculation of membrane proteins by curvature-mediated interactions

Membrane remodelling plays an important role in cellular tasks such as endocytosis, vesiculation and protein sorting, and in the biogenesis of organelles such as the endoplasmic reticulum or the Golgi apparatus. It is well established that the remodelling process is aided by specialized proteins that can sense as well as create membrane curvature, and trigger tubulation when added to synthetic liposomes. Because the energy needed for such large-scale changes in membrane geometry significantly exceeds the binding energy between individual proteins and between protein and membrane, cooperative action is essential. It has recently been suggested that curvature-mediated attractive interactions could aid cooperation and complement the effects of specific binding events on membrane remodelling. But it is difficult to experimentally isolate curvature-mediated interactions from direct attractions between proteins. Moreover, approximate theories predict repulsion between isotropically curving proteins. Here we use coarse-grained membrane simulations to show that curvature-inducing model proteins adsorbed on lipid bilayer membranes can experience attractive interactions that arise purely as a result of membrane curvature. We find that once a minimal local bending is realized, the effect robustly drives protein cluster formation and subsequent transformation into vesicles with radii that correlate with the local curvature imprint. Owing to its universal nature, curvature-mediated attraction can operate even between proteins lacking any specific interactions, such as newly synthesized and still immature membrane proteins in the endoplasmic reticulum.     

Evolution of cooperation in a finite homogeneous graph

Recent theoretical studies of selection in finite structured populations have worked with one of two measures of selective advantage of an allele: fixation probability and inclusive fitness. Each approach has its own analytical strengths, but given certain assumptions they provide equivalent results. In most instances the structure of the population can be specified by a network of nodes connected by edges (that is, a graph), and much of the work here has focused on a continuous-time model of evolution, first described by ref. 11. Working in this context, we provide an inclusive fitness analysis to derive a surprisingly simple analytical condition for the selective advantage of a cooperative allele in any graph for which the structure satisfies a general symmetry condition ('bi-transitivity'). Our results hold for a broad class of population structures, including most of those analysed previously, as well as some for which a direct calculation of fixation probability has appeared intractable. Notably, under some forms of population regulation, the ability of a cooperative allele to invade is seen to be independent of the nature of population structure (and in particular of how game partnerships are specified) and is identical to that for an unstructured population. For other types of population regulation our results reveal that cooperation can invade if players choose partners along relatively 'high-weight' edges.     

Developmental reprogramming after chromosome transfer into mitotic mouse zygotes

Until now, animal cloning and the production of embryonic stem cell lines by somatic cell nuclear transfer have relied on introducing nuclei into meiotic oocytes. In contrast, attempts at somatic cell nuclear transfer into fertilized interphase zygotes have failed. As a result, it has generally been assumed that unfertilized human oocytes will be required for the generation of tailored human embryonic stem cell lines from patients by somatic cell nuclear transfer. Here we report, however, that, unlike interphase zygotes, mouse zygotes temporarily arrested in mitosis can support somatic cell reprogramming, the production of embryonic stem cell lines and the full-term development of cloned animals. Thus, human zygotes and perhaps human embryonic blastomeres may be useful supplements to human oocytes for the creation of patient-derived human embryonic stem cells.     

欠阻尼二阶线性系统中的随机共振及其抑噪应用

在乘性噪声背景下,研究欠阻尼二阶线性系统中的随机共振及其抑噪应用.当二阶线性系统的阻尼系数和固有频率均受高斯白噪声干扰下,欠阻尼二阶线性系统中存在随机共振现象.研究表明,该系统的平均输出幅度增益呈现非单调变化,不仅在一定条件下大于无噪声时的增益,而且调节适当的系统参数和噪声强度能够提高幅度增益.因而只要使系统处于共振区域,就会使夹杂在噪声中的被测信号突现出来,从而实现弱信号的检测.因而,采用可视化仿真软件SIMULINK对此进行了实例模拟.仿真证实该方法检测弱信号的可行性和有效性.     

回收废铑催化剂的预处理工艺研究

通过将定量的废铑催化剂与定量的添加剂在坩埚中均匀混合,在一定的程序升温条件下于电阻炉中进行焚烧,冷却后将焚烧残渣研细得到铑灰,将所得铑灰用盐酸进行溶解制得含铑的水溶液,考察了添加剂种类、添加剂用量、灰化温度、溶解温度、溶解时间和溶剂用量等工艺条件对铑的液相回收率的影响.结果表明:灰化温度和溶解温度对铑的回收率的影响显得尤为明显,较佳的工艺条件为:添加剂为Ca(OH)2,Ca(OH)2添加量为原料量与Ca(OH)2的质量比为1∶1,灰化温度为320℃,溶解温度为35℃,溶解时间为8 h,溶剂用量为6 mL HCl/g铑灰.在上述实验条件下,铑的液相回收率较为理想,可达到96.5%.     

Genome sequence and analysis of the tuber crop potato

Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop.     

Ebola virus entry requires the cholesterol transporter Niemann-Pick C1

Infections by the Ebola and Marburg filoviruses cause a rapidly fatal haemorrhagic fever in humans for which no approved antivirals are available. Filovirus entry is mediated by the viral spike glycoprotein (GP), which attaches viral particles to the cell surface, delivers them to endosomes and catalyses fusion between viral and endosomal membranes. Additional host factors in the endosomal compartment are probably required for viral membrane fusion; however, despite considerable efforts, these critical host factors have defied molecular identification. Here we describe a genome-wide haploid genetic screen in human cells to identify host factors required for Ebola virus entry. Our screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes, and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann-Pick C1 (NPC1). Cells defective for the HOPS complex or NPC1 function, including primary fibroblasts derived from human Niemann-Pick type C1 disease patients, are resistant to infection by Ebola virus and Marburg virus, but remain fully susceptible to a suite of unrelated viruses. We show that membrane fusion mediated by filovirus glycoproteins and viral escape from the vesicular compartment require the NPC1 protein, independent of its known function in cholesterol transport. Our findings uncover unique features of the entry pathway used by filoviruses and indicate potential antiviral strategies to combat these deadly agents.