Enterotypes of the human gut microbiome

Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.     

Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9

Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand.     

Electron pockets in the Fermi surface of hole-doped high-Tc superconductors

High-temperature superconductivity in copper oxides occurs when the materials are chemically tuned to have a carrier concentration intermediate between their metallic state at high doping and their insulating state at zero doping. The underlying evolution of the electron system in the absence of superconductivity is still unclear, and a question of central importance is whether it involves any intermediate phase with broken symmetry. The Fermi surface of the electronic states in the underdoped 'YBCO' materials YBa2Cu3O(y) and YBa2Cu4O8 was recently shown to include small pockets, in contrast with the large cylinder that characterizes the overdoped regime, pointing to a topological change in the Fermi surface. Here we report the observation of a negative Hall resistance in the magnetic-field-induced normal state of YBa2Cu3O(y) and YBa2Cu4O8, which reveals that these pockets are electron-like rather than hole-like. We propose that these electron pockets most probably arise from a reconstruction of the Fermi surface caused by the onset of a density-wave phase, as is thought to occur in the electron-doped copper oxides near the onset of antiferromagnetic order. Comparison with materials of the La2CuO4 family that exhibit spin/charge density-wave order suggests that a Fermi surface reconstruction also occurs in those materials, pointing to a generic property of high-transition-temperature (T(c)) superconductors.     

Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry

Cancer cells arise from normal cells through the acquisition of a series of mutations in oncogenes and tumour suppressor genes. Mouse models of human cancer often rely on germline alterations that activate or inactivate genes of interest. One limitation of this approach is that germline mutations might have effects other than somatic mutations, owing to developmental compensation. To model sporadic cancers associated with inactivation of the retinoblastoma (RB) tumour suppressor gene in humans, we have produced a conditional allele of the mouse Rb gene. We show here that acute loss of Rb in primary quiescent cells is sufficient for cell cycle entry and has phenotypic consequences different from germline loss of Rb function. This difference is explained in part by functional compensation by the Rb-related gene p107. We also show that acute loss of Rb in senescent cells leads to reversal of the cellular senescence programme. Thus, the use of conditional knockout strategies might refine our understanding of gene function and help to model human cancer more accurately.     

Clonal reproduction by males and females in the little fire ant

Sexual reproduction can lead to major conflicts between sexes and within genomes. Here we report an extreme case of such conflicts in the little fire ant Wasmannia auropunctata. We found that sterile workers are produced by normal sexual reproduction, whereas daughter queens are invariably clonally produced. Because males usually develop from unfertilized maternal eggs in ants and other haplodiploid species, they normally achieve direct fitness only through diploid female offspring. Hence, although the clonal production of queens increases the queen's relatedness to reproductive daughters, it potentially reduces male reproductive success to zero. In an apparent response to this conflict between sexes, genetic analyses reveal that males reproduce clonally, most likely by eliminating the maternal half of the genome in diploid eggs. As a result, all sons have nuclear genomes identical to those of their father. The obligate clonal production of males and queens from individuals of the same sex effectively results in a complete separation of the male and female gene pools. These findings show that the haplodiploid sex-determination system provides grounds for the evolution of extraordinary genetic systems and new types of sexual conflict.     

Thermochemical flows couple the Earth's inner core growth to mantle heterogeneity

Seismic waves sampling the top 100 km of the Earth's inner core reveal that the eastern hemisphere (40 degrees E-180 degrees E) is seismically faster, more isotropic and more attenuating than the western hemisphere. The origin of this hemispherical dichotomy is a challenging problem for our understanding of the Earth as a system of dynamically coupled layers. Previously, laboratory experiments have established that thermal control from the lower mantle can drastically affect fluid flow in the outer core, which in turn can induce textural heterogeneity on the inner core solidification front. The resulting texture should be consistent with other expected manifestations of thermal mantle control on the geodynamo, specifically magnetic flux concentrations in the time-average palaeomagnetic field over the past 5 Myr, and preferred eddy locations in flows imaged below the core-mantle boundary by the analysis of historical geomagnetic secular variation. Here we show that a single model of thermochemical convection and dynamo action can account for all these effects by producing a large-scale, long-term outer core flow that couples the heterogeneity of the inner core with that of the lower mantle. The main feature of this thermochemical 'wind' is a cyclonic circulation below Asia, which concentrates magnetic field on the core-mantle boundary at the observed location and locally agrees with core flow images. This wind also causes anomalously high rates of light element release in the eastern hemisphere of the inner core boundary, suggesting that lateral seismic anomalies at the top of the inner core result from mantle-induced variations in its freezing rate.     

解体好氧颗粒污泥修复

考察了加入新的活性污泥使解体好氧颗粒污泥完成修复的可行性.解体好氧颗粒污泥对新加入的活性污泥进行吸附,在各种选择压力特别是水力剪切力作用下和原有颗粒污泥形成一个有机整体.大约3周时间,解体颗粒污泥被完全修复.扫描电镜观察发现,被修复后的颗粒污泥呈现非常规则的结构,微生物相十分致密.在解体颗粒污泥逐渐被修复的过程中,颗粒平均粒径仅从最初的2.8mm增至2.9mm,说明活性污泥在颗粒污泥上的附着主要发生在颗粒的空穴.而颗粒污泥的沉降性能和强度都得到了极大的改善,颗粒沉降速率和完整性系数分别由最初的72m/h和56.8%提高到110m/h和65.8%.新加入的活性污泥除了部分用于修复解体颗粒污泥,其余在选择压力等的作用下形成了新的好氧颗粒污泥.     

Estimating the Out‐of‐Sample Predictive Ability of Trading Rules: A Robust Bootstrap Approach

In this paper, we provide a novel way to estimate the out‐of‐sample predictive ability of a trading rule. Usually, this ability is estimated using a sample‐splitting scheme, true out‐of‐sample data being rarely available. We argue that this method makes poor use of the available data and creates data‐mining possibilities. Instead, we introduce an alternative.632 bootstrap approach. This method enables building in‐sample and out‐of‐sample bootstrap datasets that do not overlap but exhibit the same time dependencies. We show in a simulation study that this technique drastically reduces the mean squared error of the estimated predictive ability. We illustrate our methodology on IBM, MSFT and DJIA stock prices, where we compare 11 trading rules specifications. For the considered datasets, two different filter rule specifications have the highest out‐of‐sample mean excess returns. However, all tested rules cannot beat a simple buy‐and‐hold strategy when trading at a daily frequency. Copyright © 2015 John Wiley & Sons, Ltd.     

Epithelial homeostasis and the underlying molecular mechanisms in the gut of the insect model <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Insects mostly develop on decaying and contaminated organic matter and often serve as vectors of biologically transmitted diseases by transporting microorganisms to the plant and animal hosts. As such, insects are constantly ingesting microorganisms, a small fraction of which reach their epithelial surfaces, mainly their digestive tract, where they can establish relationships ranging from symbiosis to mutualism or even parasitism. Understanding the tight physical, genetic, and biochemical interactions that takes place between intestinal epithelia and either resident or infectious microbes has been a long-lasting objective of the immunologist. Research in this field has recently been re-vitalized with the development of deep sequencing techniques, which allow qualitative and quantitative characterization of gut microbiota. Interestingly, the recent identification of regenerative stem cells in the Drosophila gut together with the initial characterization of Drosophila gut microbiota have opened up new avenues of study aimed at understanding the mechanisms that regulate the dialog between the Drosophila gut epithelium and its microbiota of this insect model. The fact that some of the responses are conserved across species combined with the power of Drosophila genetics could make this organism model a useful tool to further elucidate some aspects of the interaction occurring between the microbiota and the human gut.