Structural basis for the subunit assembly of the anaphase-promoting complex

The anaphase-promoting complex or cyclosome (APC/C) is an unusually large E3 ubiquitin ligase responsible for regulating defined cell cycle transitions. Information on how its 13 constituent proteins are assembled, and how they interact with co-activators, substrates and regulatory proteins is limited. Here, we describe a recombinant expression system that allows the reconstitution of holo APC/C and its sub-complexes that, when combined with electron microscopy, mass spectrometry and docking of crystallographic and homology-derived coordinates, provides a precise definition of the organization and structure of all essential APC/C subunits, resulting in a pseudo-atomic model for 70% of the APC/C. A lattice-like appearance of the APC/C is generated by multiple repeat motifs of most APC/C subunits. Three conserved tetratricopeptide repeat (TPR) subunits (Cdc16, Cdc23 and Cdc27) share related superhelical homo-dimeric architectures that assemble to generate a quasi-symmetrical structure. Our structure explains how this TPR sub-complex, together with additional scaffolding subunits (Apc1, Apc4 and Apc5), coordinate the juxtaposition of the catalytic and substrate recognition module (Apc2, Apc11 and Apc10 (also known as Doc1)), and TPR-phosphorylation sites, relative to co-activator, regulatory proteins and substrates.     

Ecology drives a global network of gene exchange connecting the human microbiome

Horizontal gene transfer (HGT), the acquisition of genetic material from non-parental lineages, is known to be important in bacterial evolution. In particular, HGT provides rapid access to genetic innovations, allowing traits such as virulence, antibiotic resistance and xenobiotic metabolism to spread through the human microbiome. Recent anecdotal studies providing snapshots of active gene flow on the human body have highlighted the need to determine the frequency of such recent transfers and the forces that govern these events. Here we report the discovery and characterization of a vast, human-associated network of gene exchange, large enough to directly compare the principal forces shaping HGT. We show that this network of 10,770 unique, recently transferred (more than 99% nucleotide identity) genes found in 2,235 full bacterial genomes, is shaped principally by ecology rather than geography or phylogeny, with most gene exchange occurring between isolates from ecologically similar, but geographically separated, environments. For example, we observe 25-fold more HGT between human-associated bacteria than among ecologically diverse non-human isolates (P = 3.0 × 10(-270)). We show that within the human microbiome this ecological architecture continues across multiple spatial scales, functional classes and ecological niches with transfer further enriched among bacteria that inhabit the same body site, have the same oxygen tolerance or have the same ability to cause disease. This structure offers a window into the molecular traits that define ecological niches, insight that we use to uncover sources of antibiotic resistance and identify genes associated with the pathology of meningitis and other diseases.     

独立激励评估法在车身功能测试中的应用

车辆硬件在环仿真测试时,目前使用预先定义的测试结构,即测试结构将特定的测试激励与单独的测试步骤耦合到固定的、预先定义的测试体系中,测试后给出通过或不通过的结果。此方法中的每项测试都有其特定的功能测试重点,但无法适用于多项功能同时测试。未来的测试方法需要尽可能地完成全面性功能评估,并使评估资源得到有效利用,即应该在独立激励和现实环境中可同时对多项功能进行评估,因此,需要采用与之前不同的方法在独立激励的情况下进行测试。由于测试环境事先无法确定激励序列,因而也无法对每个测试步骤进行单独验证。激励的确切序列在测试运行开始时是未知的,从而可模拟出一个尽可能真实的现实环境,为此介绍一种独立激励的测试方法。该方法将组合法与基于模型法相结合,与相应功能测试要求联系起来,用于车身领域的系统性功能评估。该方法同样也支持现有的方法,并实现了比普通测试方法更广泛、更深入的评估覆盖面。该方法将在一家德国汽车制造商的车辆硬件在环舒适性功能测试中得到验证。     

Severe weather event attribution: Why values won't go away

We start by reviewing the complicated situation in methods of scientific attribution of climate change to extreme weather events. We emphasize the social values involved in using both so-called ″storyline″ and ordinary probabilistic or ″risk-based″ methods, noting that one important virtue claimed by the storyline approach is that it features a reduction in false negative results, which has much social and ethical merit, according to its advocates. This merit is critiqued by the probabilistic, risk-based, opponents, who claim the high ground; the usual probabilistic approach is claimed to be more objective and more ″scientific″, under the grounds that it reduces false positive error. We examine this mostly-implicit debate about error, which apparently mirrors the old Jeffrey-Rudner debate. We also argue that there is an overlooked component to the role of values in science: that of second-order inductive risk, and that it makes the relative role of values in the two methods different from what it first appears to be. In fact, neither method helps us to escape social values, and be more scientifically ″objective″ in the sense of being removed or detached from human values and interests. The probabilistic approach does not succeed in doing so, contrary to the claims of its proponents. This is important to understand, because neither method is, fundamentally, a successful strategy for climate scientists to avoid making value judgments.     

Biogeographic significance of low-elevation records for Neotoma cinerea from the northern Bonneville Basin, Utah

The existence of low-elevation populations of Neotoma cinera in the northern Bonneville Basin shows either that these mammals can survive thousands of years in xeric habitats or that they can move across xeric lowlands far more readily than has been appreciated, or both. Current models of Great Basin small mammal biogeography are far too static to encompass properly the interaction of the wide range of geographical and biological variability that has produced the modern distribution of those mammals that have, for several decades, been treated as ""montane"" within the Great Basin.     

Populations and habitat relationships of Piute ground squirrels in southwestern Idaho

Piute ground squirrels ( Spermophilus mollis idahoensis ) are normally above ground from late January until late June or early July in the Snake River Birds of Prey National Conservation Area in southwestern Idaho. In 2002 they were rarely seen above ground after early May. Because of the ecological importance of ground squirrels for nesting raptors and other species, we sought to determine the reasons for their early disappearance. We sampled 12 sites from January 2003 through March 2003 to determine if a population crash had occurred in 2002. Tests indicated that Piute ground squirrels had not been exposed to plague within the past year. The presence of yearlings in the population indicated that squirrels reproduced in 2002 and that at least some yearlings survived the winter. Both yearling and adult squirrels appeared to be reproducing at or above normal rates in 2003. The most plausible explanation for the early disappearance of Piute ground squirrels in 2002 is that squirrels entered seasonal torpor early in response to a late spring drought. In addition, the breeding chronology of squirrels may have shifted during the past 2 decades in response to climate change and/or habitat alteration. Shrub habitats provide a more favorable and stable environment for squirrels than grass habitats. Squirrel abundance was higher on live-trapping grids with sagebrush than on grids dominated by grass, and squirrel masses were higher at sites dominated by shrubs and Sandberg bluegrass ( Poa secunda ). Densities in big sagebrush ( Artemisia tridentata ) were within the ranges reported for earlier years, but densities in grass were lower than previously reported. Low densities at grassland sites in 2003 support other findings that drought affects squirrels in altered grass communities more than those in native shrub habitats. Long-term shifts in ground squirrel breeding chronology may have implications for raptors that depend on them for food.     

Evaluation of brood detection techniques: recommendations for estimating Greater Sage-Grouse productivity

Obtaining timely and accurate assessment of sage-grouse ( Centrocercus spp.) chick survival and recruitment is an important component of species management and conservation. We compared the effectiveness of walking, spotlight, and pointing-dog surveys to detect radio-marked and unmarked chicks within broods of radio-marked hens in Utah. Walking surveys detected 72% of marked chicks, while spotlight and pointing-dog surveys detected 100% and 96%, respectively. We found no difference between spotlight and pointing-dog counts in number of marked and unmarked chicks detected ( P = 0.57). Spotlight counts were slightly more time efficient than pointing-dog surveys. However, spotlight surveys were nocturnal searches and perceived to be more technically arduous than diurnal pointing-dog surveys. Pointing-dog surveys may offer greater utility in terms of area searched per unit effort and an increased ability to detect unmarked hens and broods.     

Density, biomass, and diversity of grasshoppers (Orthoptera: Acrididae) in a California native grassland

A native California perennial grassland was sampled for grasshopper populations. The grassland is managed for the preservation of the native perennial bunchgrass, Nassella pulchra Hitch. Grasshopper density, biomass, diversity, and richness were measured from July 1993 to October 1994. Average density of all grasshoppers was 2.30 hoppers/m 2 (0.66 s ) for 1994 (June through August). Overall forage consumed for 1994 was 140 kg/ha, suggesting that grasshopper populations exist at economically damaging levels. Grasshoppers do not appear in the grasslands until late spring, after annual grasses have set seed. Biomass of grasshoppers peaks in July when adults are predominant. Both grasshopper density and biomass were higher in 1993 than in 1994, and a total of 5 species were found throughout the study. Melanoplus sanguinipes Fabricus dominated the acridid communities and accounted for more than 95% of the individuals.