Galaxies at redshifts 5 to 6 with systematically low dust content and high [C ii] emission

星系红移5到6系统的粉尘含量低和高[ C ]发射II

The rest-frame ultraviolet properties of galaxies during the first three billion years of cosmic time (redshift z > 4) indicate a rapid evolution in the dust obscuration of such galaxies. This evolution implies a change in the average properties of the interstellar medium, but the measurements are systematically uncertain owing to untested assumptions and the inability to detect heavily obscured regions of the galaxies. Previous attempts to measure the interstellar medium directly in normal galaxies at these redshifts have failed for a number of reasons, with two notable exceptions. Here we report measurements of the forbidden C ii emission (that is, [C ii]) from gas, and the far-infrared emission from dust, in nine typical star-forming galaxies about one billion years after the Big Bang (z ≈ 5–6). We find that these galaxies have thermal emission that is less than 1/12 that of similar systems about two billion years later, and enhanced [C ii] emission relative to the far-infrared continuum, confirming a strong evolution in the properties of the interstellar medium in the early Universe. The gas is distributed over scales of one to eight kiloparsecs, and shows diverse dynamics within the sample. These results are consistent with early galaxies having significantly less dust than typical galaxies seen at z < 3 and being comparable in dust content to local low-metallicity systems.

[详细]

  • Nature 522, 7557 (2015)
  • 5年前
  • Letter

Prediction of structural features and application to outer membrane protein identification

结构特征的预测及在外膜蛋白鉴定中的应用

Protein three-dimensional (3D) structures provide insightful information in many fields of biology. One-dimensional properties derived from 3D structures such as secondary structure, residue solvent accessibility, residue depth and backbone torsion angles are helpful to protein function prediction, fold recognition and ab initio folding. Here, we predict various structural features with the assistance of neural network learning. Based on an independent test dataset, protein secondary structure prediction generates an overall Q3 accuracy of ~80%. Meanwhile, the prediction of relative solvent accessibility obtains the highest mean absolute error of 0.164, and prediction of residue depth achieves the lowest mean absolute error of 0.062. We further improve the outer membrane protein identification by including the predicted structural features in a scoring function using a simple profile-to-profile alignment. The results demonstrate that the accuracy of outer membrane protein identification can be improved by ~3% at a 1% false positive level when structural features are incorporated. Finally, our methods are available as two convenient and easy-to-use programs. One is PSSM-2-Features for predicting secondary structure, relative solvent accessibility, residue depth and backbone torsion angles, the other is PPA-OMP for identifying outer membrane proteins from proteomes.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

In situ imaging and proteome profiling indicate andrographolide is a highly promiscuous compound

原位成像和蛋白质组分析表明穿心莲内酯是高度混杂的复合

Natural products represent an enormous source of pharmacologically useful compounds, and are often used as the starting point in modern drug discovery. Many biologically interesting natural products are however not being pursued as potential drug candidates, partly due to a lack of well-defined mechanism-of-action. Traditional in vitro methods for target identification of natural products based on affinity protein enrichment from crude cellular lysates cannot faithfully recapitulate protein-drug interactions in living cells. Reported herein are dual-purpose probes inspired by the natural product andrographolide, capable of both reaction-based, real-time bioimaging and in situ proteome profiling/target identification in live mammalian cells. Our results confirm that andrographolide is a highly promiscuous compound and engaged in covalent interactions with numerous previously unknown cellular targets in cell type-specific manner. We caution its potential therapeutic effects should be further investigated in detail.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Achieving synchronization with active hybrid materials: Coupling self-oscillating gels and piezoelectric films

实现同步的主动混合材料:耦合自激振荡凝胶和压电薄膜

Lightweight, deformable materials that can sense and respond to human touch and motion can be the basis of future wearable computers, where the material itself will be capable of performing computations. To facilitate the creation of “materials that compute”, we draw from two emerging modalities for computation: chemical computing, which relies on reaction-diffusion mechanisms to perform operations, and oscillatory computing, which performs pattern recognition through synchronization of coupled oscillators. Chemical computing systems, however, suffer from the fact that the reacting species are coupled only locally; the coupling is limited by diffusion as the chemical waves propagate throughout the system. Additionally, oscillatory computing systems have not utilized a potentially wearable material. To address both these limitations, we develop the first model for coupling self-oscillating polymer gels to a piezoelectric (PZ) micro-electro-mechanical system (MEMS). The resulting transduction between chemo-mechanical and electrical energy creates signals that can be propagated quickly over long distances and thus, permits remote, non-diffusively coupled oscillators to communicate and synchronize. Moreover, the oscillators can be organized into arbitrary topologies because the electrical connections lift the limitations of diffusive coupling. Using our model, we predict the synchronization behavior that can be used for computational tasks, ultimately enabling “materials that compute”.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Hyperscape: Visualization for complex biological networks

hyperscape:复杂生物网络可视化

Motivation: Network biology has emerged as a powerful tool to uncover the organizational properties of living systems through the application of graph theoretic approaches. However, due to limitations in underlying data models and visualization software, knowledge relating to large molecular assemblies and biologically active fragments is poorly represented.

Results: Here, we demonstrate a novel hypergraph implementation that better captures hierarchical structures, using components of elastic fibers and, chromatin modification as models. These reveal unprecedented views of the biology of these systems, demonstrating the unique capacity of hypergraphs to resolve overlaps and uncover new insights into the subfunctionalization of variant complexes.

Availability: Hyperscape is available as a web application at http://www.compsysbio.org/hyperscape. Source code, examples and a tutorial are freely available under a GNU license.

Contact: john.parkinson@utoronto.ca, graham.cromar@gmail.com

Supplementary Information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 5年前
  • APPLICATIONS NOTE

Dynamic contact network between ribosomal subunits enables rapid large-scale rotation during spontaneous translocation

核糖体亚基之间的动态接触网络,使快速大范围内自发易位旋转

During ribosomal translation, the two ribosomal subunits remain associated through intersubunit bridges, despite rapid large-scale intersubunit rotation. The absence of large barriers hindering rotation is a prerequisite for rapid rotation. Here, we investigate how such a flat free-energy landscape is achieved, in particular considering the large shifts the bridges undergo at the periphery. The dynamics and energetics of the intersubunit contact network are studied using molecular dynamics simulations of the prokaryotic ribosome in intermediate states of spontaneous translocation. Based on observed occupancies of intersubunit contacts, residues were grouped into clusters. In addition to the central contact clusters, peripheral clusters were found to maintain strong steady interactions by changing contacts in the course of rotation. The peripheral B1 bridges are stabilized by a changing contact pattern of charged residues that adapts to the rotational state. In contrast, steady strong interactions of the B4 bridge are ensured by the flexible helix H34 following the movement of protein S15. The tRNAs which span the subunits contribute to the intersubunit binding enthalpy to an almost constant degree, despite their different positions in the ribosome. These mechanisms keep the intersubunit interaction strong and steady during rotation, thereby preventing dissociation and enabling rapid rotation.

[详细]

  • Nucleic Acids Research
  • 5年前
  • Computational Biology

Evidence that avian reovirus {sigma}NS is an RNA chaperone: implications for genome segment assortment

证据表明禽呼肠孤病毒{σ} NS是一个RNA基因组片段分类意义的伴侣:

Reoviruses are important human, animal and plant pathogens having 10–12 segments of double-stranded genomic RNA. The mechanisms controlling the assortment and packaging of genomic segments in these viruses, remain poorly understood. RNA–protein and RNA–RNA interactions between viral genomic segment precursors have been implicated in the process. While non-structural viral RNA-binding proteins, such as avian reovirus NS, are essential for virus replication, the mechanism by which they assist packaging is unclear. Here we demonstrate that NS assembles into stable elongated hexamers in vitro, which bind single-stranded nucleic acids with high affinity, but little sequence specificity. Using ensemble and single molecule fluorescence spectroscopy, we show that NS also binds to a partially double-stranded RNA, resulting in gradual helix unwinding. The hexamer can bind multiple RNA molecules and exhibits strand-annealing activity, thus mediating conversion of metastable, intramolecular stem-loops into more stable heteroduplexes. We demonstrate that the ARV NS acts as an RNA chaperone facilitating specific RNA–RNA interactions between genomic precursors during segment assortment and packaging.

[详细]

  • Nucleic Acids Research
  • 5年前
  • RNA

MRPrimer: a MapReduce-based method for the thorough design of valid and ranked primers for PCR

mrprimer:一个基于MapReduce的方法有效彻底的设计和排名的PCR引物

Primer design is a fundamental technique that is widely used for polymerase chain reaction (PCR). Although many methods have been proposed for primer design, they require a great deal of manual effort to generate feasible and valid primers, including homology tests on off-target sequences using BLAST-like tools. That approach is inconvenient for many target sequences of quantitative PCR (qPCR) due to considering the same stringent and allele-invariant constraints. To address this issue, we propose an entirely new method called MRPrimer that can design all feasible and valid primer pairs existing in a DNA database at once, while simultaneously checking a multitude of filtering constraints and validating primer specificity. Furthermore, MRPrimer suggests the best primer pair for each target sequence, based on a ranking method. Through qPCR analysis using 343 primer pairs and the corresponding sequencing and comparative analyses, we showed that the primer pairs designed by MRPrimer are very stable and effective for qPCR. In addition, MRPrimer is computationally efficient and scalable and therefore useful for quickly constructing an entire collection of feasible and valid primers for frequently updated databases like RefSeq. Furthermore, we suggest that MRPrimer can be utilized conveniently for experiments requiring primer design, especially real-time qPCR.

[详细]

  • Nucleic Acids Research
  • 5年前
  • Methods Online

Primase-polymerases are a functionally diverse superfamily of replication and repair enzymes

引物聚合酶功能不同家族的复制和修复酶

Until relatively recently, DNA primases were viewed simply as a class of proteins that synthesize short RNA primers requisite for the initiation of DNA replication. However, recent studies have shown that this perception of the limited activities associated with these diverse enzymes can no longer be justified. Numerous examples can now be cited demonstrating how the term ‘DNA primase’ only describes a very narrow subset of these nucleotidyltransferases, with the vast majority fulfilling multifunctional roles from DNA replication to damage tolerance and repair. This article focuses on the archaeo-eukaryotic primase (AEP) superfamily, drawing on recently characterized examples from all domains of life to highlight the functionally diverse pathways in which these enzymes are employed. The broad origins, functionalities and enzymatic capabilities of AEPs emphasizes their previous functional misannotation and supports the necessity for a reclassification of these enzymes under a category called primase-polymerases within the wider functional grouping of polymerases. Importantly, the repositioning of AEPs in this way better recognizes their broader roles in DNA metabolism and encourages the discovery of additional functions for these enzymes, aside from those highlighted here.

[详细]

  • Nucleic Acids Research
  • 5年前
  • SURVEY AND SUMMARY

High-throughput prediction of RNA, DNA and protein binding regions mediated by intrinsic disorder

本征无序介导的核酸、核酸和蛋白结合区的高通量预测

Intrinsically disordered proteins and regions (IDPs and IDRs) lack stable 3D structure under physiological conditions in-vitro, are common in eukaryotes, and facilitate interactions with RNA, DNA and proteins. Current methods for prediction of IDPs and IDRs do not provide insights into their functions, except for a handful of methods that address predictions of protein-binding regions. We report first-of-its-kind computational method DisoRDPbind for high-throughput prediction of RNA, DNA and protein binding residues located in IDRs from protein sequences. DisoRDPbind is implemented using a runtime-efficient multi-layered design that utilizes information extracted from physiochemical properties of amino acids, sequence complexity, putative secondary structure and disorder and sequence alignment. Empirical tests demonstrate that it provides accurate predictions that are competitive with other predictors of disorder-mediated protein binding regions and complementary to the methods that predict RNA- and DNA-binding residues annotated based on crystal structures. Application in Homo sapiens, Mus musculus, Caenorhabditis elegans and Drosophila melanogaster proteomes reveals that RNA- and DNA-binding proteins predicted by DisoRDPbind complement and overlap with the corresponding known binding proteins collected from several sources. Also, the number of the putative protein-binding regions predicted with DisoRDPbind correlates with the promiscuity of proteins in the corresponding protein–protein interaction networks. Webserver: http://biomine.ece.ualberta.ca/DisoRDPbind/

[详细]

  • Nucleic Acids Research
  • 5年前
  • Methods online

The architecture of the spliceosomal U4/U6.U5 tri-snRNP

的剪接U4 / u6.u5三snRNP的架构

This study determines the structure of the spliceosomal tri-snRNP complex (containing three small nuclear RNAs and more than 30 proteins) by single-particle cryo-electron microscopy; the resolution is sufficient to discern the organization of RNA and protein components involved in spliceosome activation, exon alignment and catalysis.

[详细]

  • Nature
  • 5年前
  • Article

The core spliceosome as target and effector of non-canonical ATM signalling

核心剪接体为目标和效应的非规范的ATM信令

Transcription-blocking DNA lesions result in chromatin displacement of core spliceosomes containing U2 and U5 snRNPs; consequently, R-loops containing the nascent transcript are formed, which activate ATM in a feed-forward fashion to influence spliceosome dynamics and alternative splicing.

[详细]

  • Nature
  • 5年前
  • Article

Distinct lineages of Ebola virus in Guinea during the 2014 West African epidemic

2014西非疫情在几内亚的埃博拉病毒不同的谱系

An epidemic of Ebola virus disease of unprecedented scale has been ongoing for more than a year in West Africa. As of 29 April 2015, there have been 26,277 reported total cases (of which 14,895 have been laboratory confirmed) resulting in 10,899 deaths. The source of the outbreak was traced to the prefecture of Guéckédou in the forested region of southeastern Guinea. The virus later spread to the capital, Conakry, and to the neighbouring countries of Sierra Leone, Liberia, Nigeria, Senegal and Mali. In March 2014, when the first cases were detected in Conakry, the Institut Pasteur of Dakar, Senegal, deployed a mobile laboratory in Donka hospital to provide diagnostic services to the greater Conakry urban area and other regions of Guinea. Through this process we sampled 85 Ebola viruses (EBOV) from patients infected from July to November 2014, and report their full genome sequences here. Phylogenetic analysis reveals the sustained transmission of three distinct viral lineages co-circulating in Guinea, including the urban setting of Conakry and its surroundings. One lineage is unique to Guinea and closely related to the earliest sampled viruses of the epidemic. A second lineage contains viruses probably reintroduced from neighbouring Sierra Leone on multiple occasions, while a third lineage later spread from Guinea to Mali. Each lineage is defined by multiple mutations, including non-synonymous changes in the virion protein 35 (VP35), glycoprotein (GP) and RNA-dependent RNA polymerase (L) proteins. The viral GP is characterized by a glycosylation site modification and mutations in the mucin-like domain that could modify the outer shape of the virion. These data illustrate the ongoing ability of EBOV to develop lineage-specific and potentially phenotypically important variation.

[详细]

  • Nature
  • 5年前
  • Letter

Integration of Metabolic and Quorum Sensing Signals Governing the Decision to Cooperate in a Bacterial Social Trait

代谢和群体感应信号控制决定在细菌的社会特质合作一体化

by Kerry E. Boyle, Hilary Monaco, Dave van Ditmarsch, Maxime Deforet, Joao B. Xavier

Many unicellular organisms live in multicellular communities that rely on cooperation between cells. However, cooperative traits are vulnerable to exploitation by non-cooperators (cheaters). We expand our understanding of the molecular mechanisms that allow multicellular systems to remain robust in the face of cheating by dissecting the dynamic regulation of cooperative rhamnolipids required for swarming in Pseudomonas aeruginosa. We combine mathematical modeling and experiments to quantitatively characterize the integration of metabolic and population density signals (quorum sensing) governing expression of the rhamnolipid synthesis operon rhlAB. The combined computational/experimental analysis reveals that when nutrients are abundant, rhlAB promoter activity increases gradually in a density dependent way. When growth slows down due to nutrient limitation, rhlAB promoter activity can stop abruptly, decrease gradually or even increase depending on whether the growth-limiting nutrient is the carbon source, nitrogen source or iron. Starvation by specific nutrients drives growth on intracellular nutrient pools as well as the qualitative rhlAB promoter response, which itself is modulated by quorum sensing. Our quantitative analysis suggests a supply-driven activation that integrates metabolic prudence with quorum sensing in a non-digital manner and allows P. aeruginosa cells to invest in cooperation only when the population size is large enough (quorum sensing) and individual cells have enough metabolic resources to do so (metabolic prudence). Thus, the quantitative description of rhlAB regulatory dynamics brings a greater understating to the regulation required to make swarming cooperation stable.

[详细]

  • PLOS Computational Biology
  • 5年前

Inference of Network Dynamics and Metabolic Interactions in the Gut Microbiome

在肠道菌群的网络动力学和代谢性相互作用的推理

by Steven N. Steinway, Matthew B. Biggs, Thomas P. Loughran, Jason A. Papin, Reka Albert

We present a novel methodology to construct a Boolean dynamic model from time series metagenomic information and integrate this modeling with genome-scale metabolic network reconstructions to identify metabolic underpinnings for microbial interactions. We apply this in the context of a critical health issue: clindamycin antibiotic treatment and opportunistic Clostridium difficile infection. Our model recapitulates known dynamics of clindamycin antibiotic treatment and C. difficile infection and predicts therapeutic probiotic interventions to suppress C. difficile infection. Genome-scale metabolic network reconstructions reveal metabolic differences between community members and are used to explore the role of metabolism in the observed microbial interactions. In vitro experimental data validate a key result of our computational model, that B. intestinihominis can in fact slow C. difficile growth.

[详细]

  • PLOS Computational Biology
  • 5年前

Random sampling of skewed distributions does not necessarily imply Taylor's law [Biological Sciences]

偏斜分布的随机抽样不一定意味着泰勒定律[生物学]

Cohen and Xu (1) claim that random samples of any skewed distributions with four finite moments would give rise to Taylor’s law (TL). In fact, skewed distributions do not necessarily generate data following TL. Some highly skewed distributions can generate random data rejecting the law. Here, I show examples for...

[详细]

  • PNAS
  • 5年前
  • Letter

Plausibility of the vibrational theory of olfaction [Biological Sciences]

对生物科学嗅觉[振动理论的合理性]

Block et al. (1) have written a critique of the vibrational theory of olfaction that rests on two main points: (i) they report negative results (i.e., identical responses to normal and deuterated musk isotopomers) in a cultured human embryonic kidney cell derivative line expressing heterologous olfactory receptors; and (ii) they...

[详细]

  • PNAS
  • 5年前
  • Letters

Reply to Chen: Under specified assumptions, adequate random samples of skewed distributions obey Taylor's law [Biological Sciences]

回复陈:在特定的假设,随机样本充足的偏态分布服从泰勒定律[生物学]

Chen (1) simulated random samples of beta, lognormal, and Poisson distributions with varying parameters following the method that we (2) used for fixed parameters. Chen claimed that the relationship between the supporting rate of Taylor's law (TL) and skewness is “complex and nonmonotonic,” as some random samples of some skewed...

[详细]

  • PNAS
  • 5年前
  • Letters

No time for waiting: Statistical structure reflects subjective complexity [Biological Sciences]

没有时间等待:统计结构反映主观复杂性[生物学]

Apparent inability of human observers to understand and mimic randomness has occupied researchers for a long time. According to a recent report, the special status of streaks in randomness perception reflects sensitivity to subtle statistical properties of pattern structure. In PNAS, Sun et al. (1) have highlighted one such property,...

[详细]

  • PNAS
  • 5年前
  • Letters

Reply to Aksentijevic: It is a matter of what is countable and how neurons learn [Biological Sciences]

回复阿克塞迪耶维奇:这是一个问题,什么是可数的,神经元是如何学会[生物学]

Aksentijevic (1) raises issues with our recent report (2) that bear further clarification because they reflect some fundamental confusion about the nature of random sequences. First, it is essential to distinguish statistics for individual elements (i.e., patterns of length one) vs. statistics for patterns consisting of more than one element...

[详细]

  • PNAS
  • 5年前
  • Letters

Comprehensive identification and analysis of human accelerated regulatory DNA [RESEARCH]

人类加速调节基因的综合鉴定与分析[研究]

It has long been hypothesized that changes in gene regulation have played an important role in human evolution, but regulatory DNA has been much more difficult to study compared to protein-coding regions. Recent large-scale studies have created genome-scale catalogs of DNaseI Hypersensitive Sites (DHS), which demark potentially functional regulatory DNA. To better define regulatory DNA that has been subject to human specific adaptive evolution, we performed comprehensive evolutionary and population genetics analyses on over 18 million DHS discovered in 130 cell types. We identified 524 DHS that are conserved in non-human primates, but accelerated in the human lineage (haDHS), and estimate that 70% of substitutions in haDHS are attributable to positive selection. Through extensive computational and experimental analyses, we demonstrate that haDHS are often active in brain or neuronal cell types, play an important role in regulating the expression of developmentally important genes, including many transcription factors such as SOX6, POU3F2, and HOX genes, and identify striking examples of adaptive regulatory evolution that may have contributed to human specific phenotypes. More generally, our results reveal new insights into conserved and adaptive regulatory DNA in humans, and refine the set of genomic substrates that distinguish humans from their closest living primate relatives.

[详细]

  • Genome Research
  • 5年前
  • RESEARCH

QnAs with Robert Tibshirani [QnAs]

罗伯特qnas qnas Tibshirani [ ]

In the past two decades, with the advent of the Internet, the ubiquity of data generation and collection, and the prevalence of microarray and related “-omic” technologies, Robert Tibshirani’s work developing statistical tools has gained importance. The origins of his research can be partly traced to August 1998, when Tibshirani...

[详细]

  • PNAS
  • 5年前
  • QnAs