Instability of hyper-compact Kerr-like objects

Viable alternatives to astrophysical black holes include hyper-compact objects without horizon, such as gravastars, boson stars, wormholes and superspinars. The authors have recently shown that typical rapidly-spinning gravastars and boson stars develop a strong instability. That analysis is extended in this paper to a wide class of horizonless objects with approximate Kerr-like geometry. A detailed investigation of wormholes and superspinars is presented, using plausible models and mirror boundary conditions at the surface. Like gravastars and boson stars, these objects are unstable with very short instability timescales. This result strengthens previous conclusions that observed hyper-compact astrophysical objects with large rotation are likely to be black holes.Comment: 15 pages, 3 figures. To be published in CQ

Role of microRNAs in arrhythmogenic cardiomyopathy: translation as biomarkers into clinical practice

Arrhythmogenic cardiomyopathy is a rare inherited entity, characterized by a progressive fibro-fatty replacement of the myocardium. It leads to malignant arrhythmias and a high risk of sudden cardiac death. Incomplete penetrance and variable expressivity are hallmarks of this arrhythmogenic cardiac disease, where the first manifestation may be syncope and sudden cardiac death, often triggered by physical exercise. Early identification of individuals at risk is crucial to adopt protective and ideally personalized measures to prevent lethal episodes. The genetic analysis identifies deleterious rare variants in nearly 70% of cases, mostly in genes encoding proteins of the desmosome. However, other factors may modulate the phenotype onset and outcome of disease, such as microRNAs. These small noncoding RNAs play a key role in gene expression regulation and the network of cellular processes. In recent years, data focused on the role of microRNAs as potential biomarkers in arrhythmogenic cardiomyopathy have progressively increased. A better understanding of the functions and interactions of microRNAs will likely have clinical implications. Herein, we propose an exhaustive review of the literature regarding these noncoding RNAs, their versatile mechanisms of gene regulation and present novel targets in arrhythmogenic cardiomyopathy

Translational Selection Is Ubiquitous in Prokaryotes

Codon usage bias in prokaryotic genomes is largely a consequence of background substitution patterns in DNA, but highly expressed genes may show a preference towards codons that enable more efficient and/or accurate translation. We introduce a novel approach based on supervised machine learning that detects effects of translational selection on genes, while controlling for local variation in nucleotide substitution patterns represented as sequence composition of intergenic DNA. A cornerstone of our method is a Random Forest classifier that outperformed previous distance measure-based approaches, such as the codon adaptation index, in the task of discerning the (highly expressed) ribosomal protein genes by their codon frequencies. Unlike previous reports, we show evidence that translational selection in prokaryotes is practically universal: in 460 of 461 examined microbial genomes, we find that a subset of genes shows a higher codon usage similarity to the ribosomal proteins than would be expected from the local sequence composition. These genes constitute a substantial part of the genome—between 5% and 33%, depending on genome size—while also exhibiting higher experimentally measured mRNA abundances and tending toward codons that match tRNA anticodons by canonical base pairing. Certain gene functional categories are generally enriched with, or depleted of codon-optimized genes, the trends of enrichment/depletion being conserved between Archaea and Bacteria. Prominent exceptions from these trends might indicate genes with alternative physiological roles; we speculate on specific examples related to detoxication of oxygen radicals and ammonia and to possible misannotations of asparaginyl–tRNA synthetases. Since the presence of codon optimizations on genes is a valid proxy for expression levels in fully sequenced genomes, we provide an example of an “adaptome” by highlighting gene functions with expression levels elevated specifically in thermophilic Bacteria and Archaea

Conserved synteny at the protein family level reveals genes underlying Shewanella species’ cold tolerance and predicts their novel phenotypes

© The Authors 2009. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Functional & Integrative Genomics 10 (2010): 97-110, doi:10.1007/s10142-009-0142-y.Bacteria of the genus Shewanella can thrive in different environments and demonstrate significant variability in their metabolic and ecophysiological capabilities including cold and salt tolerance. Genomic characteristics underlying this variability across species are largely unknown. In this study, we address the problem by a comparison of the physiological, metabolic, and genomic characteristics of 19 sequenced Shewanella species. We have employed two novel approaches based on association of a phenotypic trait with the number of the trait-specific protein families (Pfam domains) and on the conservation of synteny (order in the genome) of the trait-related genes. Our first approach is top-down and involves experimental evaluation and quantification of the species’ cold tolerance followed by identification of the correlated Pfam domains and genes with a conserved synteny. The second, a bottom-up approach, predicts novel phenotypes of the species by calculating profiles of each Pfam domain among their genomes and following pair-wise correlation of the profiles and their network clustering. Using the first approach, we find a link between cold and salt tolerance of the species and the presence in the genome of a Na+/H+ antiporter gene cluster. Other cold-tolerance-related genes include peptidases, chemotaxis sensory transducer proteins, a cysteine exporter, and helicases. Using the bottom-up approach, we found several novel phenotypes in the newly sequenced Shewanella species, including degradation of aromatic compounds by an aerobic hybrid pathway in Shewanella woodyi, degradation of ethanolamine by Shewanella benthica, and propanediol degradation by Shewanella putrefaciens CN32 and Shewanella sp. W3-18-1.This research was supported by the U.S. Department of Energy (DOE) Office of Biological and Environmental Research under the Genomics: GTL Program via the Shewanella Federation consortium

Evolution of protein domain architectures

This chapter reviews current research on how protein domain architectures evolve. We begin by summarizing work on the phylogenetic distribution of proteins, as this will directly impact which domain architectures can be formed in different species. Studies relating domain family size to occurrence have shown that they generally follow power law distributions, both within genomes and larger evolutionary groups. These findings were subsequently extended to multi-domain architectures. Genome evolution models that have been suggested to explain the shape of these distributions are reviewed, as well as evidence for selective pressure to expand certain domain families more than others. Each domain has an intrinsic combinatorial propensity, and the effects of this have been studied using measures of domain versatility or promiscuity. Next, we study the principles of protein domain architecture evolution and how these have been inferred from distributions of extant domain arrangements. Following this, we review inferences of ancestral domain architecture and the conclusions concerning domain architecture evolution mechanisms that can be drawn from these. Finally, we examine whether all known cases of a given domain architecture can be assumed to have a single common origin (monophyly) or have evolved convergently (polyphyly). We end by a discussion of some available tools for computational analysis or exploitation of protein domain architectures and their evolution

Combining modularity, conservation, and interactions of proteins significantly increases precision and coverage of protein function prediction

<p>Abstract</p> <p>Background</p> <p>While the number of newly sequenced genomes and genes is constantly increasing, elucidation of their function still is a laborious and time-consuming task. This has led to the development of a wide range of methods for predicting protein functions in silico. We report on a new method that predicts function based on a combination of information about protein interactions, orthology, and the conservation of protein networks in different species.</p> <p>Results</p> <p>We show that aggregation of these independent sources of evidence leads to a drastic increase in number and quality of predictions when compared to baselines and other methods reported in the literature. For instance, our method generates more than 12,000 novel protein functions for human with an estimated precision of ~76%, among which are 7,500 new functional annotations for 1,973 human proteins that previously had zero or only one function annotated. We also verified our predictions on a set of genes that play an important role in colorectal cancer (<it>MLH1</it>, <it>PMS2</it>, <it>EPHB4 </it>) and could confirm more than 73% of them based on evidence in the literature.</p> <p>Conclusions</p> <p>The combination of different methods into a single, comprehensive prediction method infers thousands of protein functions for every species included in the analysis at varying, yet always high levels of precision and very good coverage.</p

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

The Vein Patterning 1 (VEP1) Gene Family Laterally Spread through an Ecological Network

Lateral gene transfer (LGT) is a major evolutionary mechanism in prokaryotes. Knowledge about LGT— particularly, multicellular— eukaryotes has only recently started to accumulate. A widespread assumption sees the gene as the unit of LGT, largely because little is yet known about how LGT chances are affected by structural/functional features at the subgenic level. Here we trace the evolutionary trajectory of VEin Patterning 1, a novel gene family known to be essential for plant development and defense. At the subgenic level VEP1 encodes a dinucleotide-binding Rossmann-fold domain, in common with members of the short-chain dehydrogenase/reductase (SDR) protein family. We found: i) VEP1 likely originated in an aerobic, mesophilic and chemoorganotrophic α-proteobacterium, and was laterally propagated through nets of ecological interactions, including multiple LGTs between phylogenetically distant green plant/fungi-associated bacteria, and five independent LGTs to eukaryotes. Of these latest five transfers, three are ancient LGTs, implicating an ancestral fungus, the last common ancestor of land plants and an ancestral trebouxiophyte green alga, and two are recent LGTs to modern embryophytes. ii) VEP1's rampant LGT behavior was enabled by the robustness and broad utility of the dinucleotide-binding Rossmann-fold, which provided a platform for the evolution of two unprecedented departures from the canonical SDR catalytic triad. iii) The fate of VEP1 in eukaryotes has been different in different lineages, being ubiquitous and highly conserved in land plants, whereas fungi underwent multiple losses. And iv) VEP1-harboring bacteria include non-phytopathogenic and phytopathogenic symbionts which are non-randomly distributed with respect to the type of harbored VEP1 gene. Our findings suggest that VEP1 may have been instrumental for the evolutionary transition of green plants to land, and point to a LGT-mediated ‘Trojan Horse’ mechanism for the evolution of bacterial pathogenesis against plants. VEP1 may serve as tool for revealing microbial interactions in plant/fungi-associated environments

Immune recognition of swine vesicular disease virus structural proteins Novel antigenic regions that are not exposed in the capsid

Swine vesicular disease virus (SVDV) is an enterovirus of the Picornaviridae family that belongs to the coxsackievirus B group. A number of antigenic sites have been identified in SVDV by analysis of neutralizing monoclonal antibody-resistant mutants and shown to be exposed on the surface of the capsid. In this paper we have identified seven new immunodominant antigenic regions in SVDV capsid proteins by a peptide scanning method, using a panel of sera from infected pigs. When these antigenic regions were located in the capsid by using a computer-generated three-dimensional model of the virion, one was readily exposed on the surface of the virus and the remaining sites were located facing the inner side of the capsid shell, at subunit contacts, or in the interior of the subunit structure. (C) 2000 Academic Press

The Structure of the chiral Pt{531} surface: a combined LEED and DFT study

The structure of the chiral kinked Pt{531} surface has been determined by low-energy electron diffraction intensity-versus-energy (LEED-IV) analysis and density functional theory (DFT). Large contractions and expansions of the vertical interlayer distances with respect to the bulk-terminated surface geometry were found for the first six layers (LEED: d(12) = 0.44 angstrom, d(23) = 0.69 angstrom, d(34) = 0.49 angstrom, d(45) = 0.95 angstrom, d(56) = 0.56 angstrom; DFT: d(12) = 0.51 angstrom, d(23) = 0.55 angstrom, d(34) = 0.74 angstrom, d(45) = 0.78 angstrom, d(56) = 0.63 angstrom; d(bulk) = 0.66 angstrom). Energy-dependent cancellations of LEED spots over unusually large energy ranges, up to 100 eV, can be explained by surface roughness and reproduced by applying a model involving 0.25 ML of vacancies and adatoms in the scattering calculations. The agreement between the results from LEED and DFT is not as good as in other cases, which could be due to this roughness of the real surface