Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu

Human cells possess an antiviral activity that inhibits the release of retrovirus particles, and other enveloped virus particles, and is antagonized by the HIV-1 accessory protein, Vpu. This antiviral activity can be constitutively expressed or induced by interferon-alpha, and it consists of protein-based tethers, which we term 'tetherins', that cause retention of fully formed virions on infected cell surfaces. Using deductive constraints and gene expression analyses, we identify CD317 (also called BST2 or HM1.24), a membrane protein of previously unknown function, as a tetherin. Specifically, CD317 expression correlated with, and induced, a requirement for Vpu during HIV-1 and murine leukaemia virus particle release. Furthermore, in cells where HIV-1 virion release requires Vpu expression, depletion of CD317 abolished this requirement. CD317 caused retention of virions on cell surfaces and, after endocytosis, in CD317-positive compartments. Vpu co-localized with CD317 and inhibited these effects. Inhibition of Vpu function and consequent mobilization of tetherin's antiviral activity is a potential therapeutic strategy in HIV/AIDS.     

Distribution and functional impact of DNA copy number variation in the rat

The abundance and dynamics of copy number variants (CNVs) in mammalian genomes poses new challenges in the identification of their impact on natural and disease phenotypes. We used computational and experimental methods to catalog CNVs in rat and found that they share important functional characteristics with those in human. In addition, 113 one-to-one orthologous genes overlap CNVs in both human and rat, 80 of which are implicated in human disease. CNVs are nonrandomly distributed throughout the genome. Chromosome 18 is a cold spot for CNVs as well as evolutionary rearrangements and segmental duplications, suggesting stringent selective mechanisms underlying CNV genesis or maintenance. By exploiting gene expression data available for rat recombinant inbred lines, we established the functional relationship of CNVs underlying 22 expression quantitative trait loci. These characteristics make the rat an excellent model for studying phenotypic effects of structural variation in relation to human complex traits and disease.     

Group II metabotropic glutamate receptors and schizophrenia

Schizophrenia is one of the most common mental illnesses, with hereditary and environmental factors important for its etiology. All antipsychotics have in common a high affinity for monoaminergic receptors. Whereas hallucinations and delusions usually respond to typical (haloperidol-like) and atypical (clozapine-like) monoaminergic antipsychotics, their efficacy in improving negative symptoms and cognitive deficits remains inadequate. In addition, devastating side effects are a common characteristic of monoaminergic antipsychotics. Recent biochemical, preclinical and clinical findings support group II metabotropic glutamate receptors (mGluR2 and mGluR3) as a new approach to treat schizophrenia. This paper reviews the status of general knowledge of mGluR2 and mGluR3 in the psychopharmacology, genetics and neuropathology of schizophrenia     

The use of the information-theoretic entropy in thermodynamics

When considering controversial thermodynamic scenarios such as Maxwell's demon, it is often necessary to consider probabilistic mixtures of macrostates. This raises the question of how, if at all, to assign entropy to them. The information-theoretic entropy is often used in such cases; however, no general proof of the soundness of doing so has been given, and indeed some arguments against doing so have been presented. We offer a general proof of the applicability of the information-theoretic entropy to probabilistic mixtures of macrostates that is based upon a probabilistic generalisation of the Kelvin statement of the second law. We defend the latter and make clear the other assumptions on which our main result depends. We also briefly discuss the interpretation of our result.     

Book Reviews

Systemic Practice and Action Research -     

<Emphasis Type="Italic">O</Emphasis>-Mannosylation and human disease

Glycosylation of proteins is arguably the most prevalent co- and post-translational modification. It is responsible for increased heterogeneity and functional diversity of proteins. Here we discuss the importance of one type of glycosylation, specifically O-mannosylation and its relationship to a number of human diseases. The most widely studied O-mannose modified protein is alpha-dystroglycan (α-DG). Recent studies have focused intensely on α-DG due to the severity of diseases associated with its improper glycosylation. O-mannosylation of α-DG is involved in cancer metastasis, arenavirus entry, and multiple forms of congenital muscular dystrophy [1, 2]. In this review, we discuss the structural and functional characteristics of O-mannose-initiated glycan structures on α-DG, enzymes involved in the O-mannosylation pathway, and the diseases that are a direct result of disruptions within this pathway.     

Genome-wide association analysis identifies three psoriasis susceptibility loci

We carried out a meta-analysis of two recent psoriasis genome-wide association studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10?11), one at FBXL19 (rs10782001, combined P = 9 × 10?1?) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10??). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10??; rs10782001, combined P = 4 × 10??; and rs12586317, combined P = 6 × 1??) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10??; rs10782001, combined P = 2 × 10??; and rs12586317, combined P = 1 × 10??). We also replicated a recently identified association signal near RNF114 (rs495337, combined P = 2 × 10??).     

Integrative taxonomic analysis reveals a new species of Leptobrachium (Anura: Megophryidae) from north-eastern Cambodia and central Vietnam

ABSTRACT

Species boundaries within the red-eyed Leptobrachium of southern Indochina have been uncertain. Leptobrachium pullum and L. mouhoti from upper and lower elevations, respectively, of the Langbian Plateau of southern Vietnam and eastern Cambodia differ in body size but have relatively low interspecific mitochondrial DNA divergence, leading to speculation that these might represent a single species with an elevational cline in body size. The recent discovery of an allopatric high-elevation population of red-eyed Leptobrachium on the Kon Tum Plateau (= Central Highlands) of north-eastern Cambodia and central Vietnam has been referred to both species, and to a putatively undescribed species. We examine variation in morphology of adults and tadpoles, mitochondrial DNA, 11 nuclear genes and advertisement calls, and show corroborating lines of evidence for the existence of three species of red-eyed Leptobrachium in southern Indochina. Although the three species are reciprocally monophyletic in mitochondrial DNA, their shallow mitochondrial DNA divergences are not mirrored by morphology, advertisement calls, or – in part – nuclear DNA, and probably reflect past mitochondrial introgression rather than recent speciation. The Central Highlands taxon is described herein as a new species.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:CE6650AF-D9FB-40F4-8A2E-9B4E23AAC205     

意大利佛罗伦萨的地方性艺术市场——经济人类学个案研究

从地方性艺术市场的角度对意大利佛罗伦萨的当代艺术体系进行分析,可以发现,佛罗伦萨的困境在于:既要充分利用其独一无二的艺术历史,又要保持活跃的当代艺术氛围。佛罗伦萨与颇具代表性的美国密苏里州圣路易斯市的地方性艺术市场截然不同。现今佛罗伦萨艺术体系中存在的问题可以从历史和以大众旅游为中心的现有生活方式中体现出来。