Desmodium mottle virus, the first legumovirus (genus Begomovirus) from East Africa

A novel bipartite legumovirus (genus Begomovirus, family Geminiviridae), that naturally infects the wild leguminous plant Desmodium sp. in Uganda, was molecularly characterized and named Desmodium mottle virus. The highest nucleotide identities for DNA-A, obtained from two field-collected samples, were 79.9% and 80.1% with the legumovirus, soybean mild mottle virus. DNA-B had the highest nucleotide identities (65.4% and 66.4%) with a typical non-legumovirus Old World begomovirus, African cassava mosaic virus. This is the first report of a legumovirus in East Africa and extends the known diversity of begomoviruses found infecting wild plants in this continent

Medium-term seed storage of 50 genera of forage legumes and evidence-based genebank monitoring intervals

Genebanks maintaining seeds for long-term genetic resources conservation monitor seed lots to detect early loss in viability. Monitoring is costly and depletes valuable seed. Three decades of genebank seed germination test results of diverse forage species from 50 legume genera in the International Livestock Research Institute’s medium-term store (circa 8° C with 5 % moisture content) were analysed to determine whether advice on seed monitoring intervals could be derived. Cumulative normal distributions were fitted by probit analysis for each seed lot and compared within each genus. Six patterns of within-genus variation were identified: no detectable trend in germination test results during storage (4 genera); detectable trends, but variable (positive to negative) amongst lots (5); consistent slope of loss in viability amongst lots (17); consistent slope of increase in ability to germinate amongst lots (21); common loss in viability amongst lots (2); common increase in ability to germinate amongst lots (1). Seed lot monitoring intervals for the medium-term store were derived for each of 19 genera with consistent loss in viability across seed lots: three genera provided comparatively rapid deterioration, five met the general expectations for a medium-term store (2-10 years’ maintenance of high viability), whilst 11 provided much better survival. Moreover, 26 further genera provided no evidence as yet of seed deterioration; of these, 22 improved in ability to germinate during storage indicating confounding of hardseededness with viability in germination tests

Multisensory body representation in autoimmune diseases

Body representation has been linked to the processing and integration of multisensory signals. An outstanding example of the pivotal role played by multisensory mechanisms in body representation is the Rubber Hand Illusion (RHI). In this paradigm, multisensory stimulation induces a sense of ownership over a fake limb. Previous work has shown high interindividual differences in the susceptibility to the RHI. The origin of this variability remains largely unknown. Given the tight and bidirectional communication between the brain and the immune system, we predicted that the origin of this variability could be traced, in part, to the immune system's functioning, which is altered by several clinical conditions, including Coeliac Disease (CD). Consistent with this prediction, we found that the Rubber Hand Illusion is stronger in CD patients as compared to healthy controls. We propose a biochemical mechanism accounting for the dependency of multisensory body representation upon the Immune system. Our finding has direct implications for a range of neurological, psychiatric and immunological conditions where alterations of multisensory integration, body representation and dysfunction of the immune system co-exist

Variation in RNA Virus Mutation Rates across Host Cells

It is well established that RNA viruses exhibit higher rates of spontaneous mutation than DNA viruses and microorganisms. However, their mutation rates vary amply, from 10−6 to 10−4 substitutions per nucleotide per round of copying (s/n/r) and the causes of this variability remain poorly understood. In addition to differences in intrinsic fidelity or error correction capability, viral mutation rates may be dependent on host factors. Here, we assessed the effect of the cellular environment on the rate of spontaneous mutation of the vesicular stomatitis virus (VSV), which has a broad host range and cell tropism. Luria-Delbrück fluctuation tests and sequencing showed that VSV mutated similarly in baby hamster kidney, murine embryonic fibroblasts, colon cancer, and neuroblastoma cells (approx. 10−5 s/n/r). Cell immortalization through p53 inactivation and oxygen levels (1–21%) did not have a significant impact on viral replication fidelity. This shows that previously published mutation rates can be considered reliable despite being based on a narrow and artificial set of laboratory conditions. Interestingly, we also found that VSV mutated approximately four times more slowly in various insect cells compared with mammalian cells. This may contribute to explaining the relatively slow evolution of VSV and other arthropod-borne viruses in nature

The Pathway Coexpression Network: Revealing pathway relationships.

A goal of genomics is to understand the relationships between biological processes. Pathways contribute to functional interplay within biological processes through complex but poorly understood interactions. However, limited functional references for global pathway relationships exist. Pathways from databases such as KEGG and Reactome provide discrete annotations of biological processes. Their relationships are currently either inferred from gene set enrichment within specific experiments, or by simple overlap, linking pathway annotations that have genes in common. Here, we provide a unifying interpretation of functional interaction between pathways by systematically quantifying coexpression between 1,330 canonical pathways from the Molecular Signatures Database (MSigDB) to establish the Pathway Coexpression Network (PCxN). We estimated the correlation between canonical pathways valid in a broad context using a curated collection of 3,207 microarrays from 72 normal human tissues. PCxN accounts for shared genes between annotations to estimate significant correlations between pathways with related functions rather than with similar annotations. We demonstrate that PCxN provides novel insight into mechanisms of complex diseases using an Alzheimer's Disease (AD) case study. PCxN retrieved pathways significantly correlated with an expert curated AD gene list. These pathways have known associations with AD and were significantly enriched for genes independently associated with AD. As a further step, we show how PCxN complements the results of gene set enrichment methods by revealing relationships between enriched pathways, and by identifying additional highly correlated pathways. PCxN revealed that correlated pathways from an AD expression profiling study include functional clusters involved in cell adhesion and oxidative stress. PCxN provides expanded connections to pathways from the extracellular matrix. PCxN provides a powerful new framework for interrogation of global pathway relationships. Comprehensive exploration of PCxN can be performed at http://pcxn.org/

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2

Item does not contain fulltextBACKGROUND: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. METHODS: Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. RESULTS: An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. CONCLUSIONS AND INTERPRETATION: No evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers

Understanding the retinal basis of vision across species

The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision

Regulatory T cells and their role in rheumatic diseases: a potential target for novel therapeutic development

Regulatory T cells have an important role in limiting immune reactions and are essential regulators of self-tolerance. Among them, CD4+CD25high regulatory T cells are the best-described subset. In this article, we summarize current knowledge on the phenotype, function, and development of CD4+CD25high regulatory T cells. We also review the literature on the role of these T cells in rheumatic diseases and discuss the potential for their use in immunotherapy