Expansion of the Protein Repertoire in Newly Explored Environments: Human Gut Microbiome Specific Protein Families

The microbes that inhabit particular environments must be able to perform molecular functions that provide them with a competitive advantage to thrive in those environments. As most molecular functions are performed by proteins and are conserved between related proteins, we can expect that organisms successful in a given environmental niche would contain protein families that are specific for functions that are important in that environment. For instance, the human gut is rich in polysaccharides from the diet or secreted by the host, and is dominated by Bacteroides, whose genomes contain highly expanded repertoire of protein families involved in carbohydrate metabolism. To identify other protein families that are specific to this environment, we investigated the distribution of protein families in the currently available human gut genomic and metagenomic data. Using an automated procedure, we identified a group of protein families strongly overrepresented in the human gut. These not only include many families described previously but also, interestingly, a large group of previously unrecognized protein families, which suggests that we still have much to discover about this environment. The identification and analysis of these families could provide us with new information about an environment critical to our health and well being

Bioinformatics for the human microbiome project

Microbes inhabit virtually all sites of the human body, yet we know very little about the role they play in our health. In recent years, there has been increasing interest in studying human-associated microbial communities, particularly since microbial dysbioses have now been implicated in a number of human diseases [1]–[3]. Dysbiosis, the disruption of the normal microbial community structure, however, is impossible to define without first establishing what “normal microbial community structure” means within the healthy human microbiome. Recent advances in sequencing technologies have made it feasible to perform large-scale studies of microbial communities, providing the tools necessary to begin to address this question [4], [5]. This led to the implementation of the Human Microbiome Project (HMP) in 2007, an initiative funded by the National Institutes of Health Roadmap for Biomedical Research and constructed as a large, genome-scale community research project [6]. Any such project must plan for data analysis, computational methods development, and the public availability of tools and data; here, we provide an overview of the corresponding bioinformatics organization, history, and results from the HMP (Figure 1).National Institutes of Health (U.S.) (NIH U54HG004969)National Institutes of Health (U.S.) (grant R01HG004885)National Institutes of Health (U.S.) (grant R01HG005975)National Institutes of Health (U.S.) (grant R01HG005969

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky

Molecular characterization of an arthritogenic collagen peptide interacting with I-A(r)

Collagen-induced arthritis (CIA) is an autoimmune arthritis that can be elicited by the immunization of genetically susceptible strains of mice with type II collagen (CII). We have analysed the molecular interactions that occur between an arthritogenic T-cell determinant CII (442–457) and the murine class II susceptibility allele I-A(r). To determine which amino acid residues within the CII (442–457) sequence are responsible for binding to I-A(r), a soluble I-A(r) : IgG2aFc fusion protein–peptide binding assay was developed. Various concentrations of analogue peptides were tested for their ability to compete with biotinylated CII (607–622) for binding to I-A(r), thereby establishing a relative comparison of the binding affinities among these analogues. Analogue peptides with substitutions at positions 447 (Ala → Val), 448 (Gly → Ala) and 451 (Gly → Ala) bound poorly to the I-A(r) molecule. These data suggest that positions 447, 448 and 451 on CII are the major anchor points to I-A(r) molecules. In cytokine assays, only substitutions within positions 445–454 decreased the interferon-γ production by T cells. These data narrow the core of the arthritogenic T-cell determinant to CII (445–454). Identification of the molecular interactions involved in T-cell recognition of CII should lead to antigen-specific means of inhibiting autoimmune arthritis

Ultralow viscosity of carbonate melts at high pressures

Knowledge of the occurrence and mobility of carbonate-rich melts in the Earth's mantle is important for understanding the deep carbon cycle and related geochemical and geophysical processes. However, our understanding of the mobility of carbonate-rich melts remains poor. Here we report viscosities of carbonate melts up to 6.2 GPa using a newly developed technique of ultrafast synchrotron X-ray imaging. These carbonate melts display ultralow viscosities, much lower than previously thought, in the range of 0.006-0.010 Pa s, which are ~2 to 3 orders of magnitude lower than those of basaltic melts in the upper mantle. As a result, the mobility of carbonate melts (defined as the ratio of melt-solid density contrast to melt viscosity) is ~2 to 3 orders of magnitude higher than that of basaltic melts. Such high mobility has significant influence on several magmatic processes, such as fast melt migration and effective melt extraction beneath mid-ocean ridges