160 research outputs found

    Evolutionary history of tuberculosis shaped by conserved mutations in the PhoPR virulence regulator

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    Although the bovine tuberculosis (TB) agent, Mycobacterium bovis, may infect humans and cause disease, long-term epidemiological data indicate that humans represent a spill-over host in which infection with M. bovis is not self-maintaining. Indeed, human-to-human transmission of M. bovis strains and other members of the animal lineage of the tubercle bacilli is very rare. Here, we report on three mutations affecting the two-component virulence regulation system PhoP/PhoR (PhoPR) in M. bovis and in the closely linked Mycobacterium africanum lineage 6 (L6) that likely account for this discrepancy. Genetic transfer of these mutations into the human TB agent, Mycobacterium tuberculosis, resulted in down-regulation of the PhoP regulon, with loss of biologically active lipids, reduced secretion of the 6-kDa early antigenic target (ESAT-6), and lower virulence. Remarkably, the deleterious effects of the phoPR mutations were partly compensated by a deletion, specific to the animal-adapted and M. africanum L6 lineages, that restores ESAT-6 secretion by a PhoPR-independent mechanism. Similarly, we also observed that insertion of an IS6110 element upstream of the phoPR locus may completely revert the phoPR-bovis–associated fitness loss, which is the case for an exceptional M. bovis human outbreak strain from Spain. Our findings ultimately explain the long-term epidemiological data, suggesting that M. bovis and related phoPR-mutated strains pose a lower risk for progression to overt human TB, with major impact on the evolutionary history of TB

    Kang-Redner Anomaly in Cluster-Cluster Aggregation

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    The large time, small mass, asymptotic behavior of the average mass distribution \pb is studied in a dd-dimensional system of diffusing aggregating particles for 1≀d≀21\leq d \leq 2. By means of both a renormalization group computation as well as a direct re-summation of leading terms in the small reaction-rate expansion of the average mass distribution, it is shown that \pb \sim \frac{1}{t^d} (\frac{m^{1/d}}{\sqrt{t}})^{e_{KR}} for mâ‰Ștd/2m \ll t^{d/2}, where eKR=Ï”+O(Ï”2)e_{KR}=\epsilon +O(\epsilon ^2) and Ï”=2−d\epsilon =2-d. In two dimensions, it is shown that \pb \sim \frac{\ln(m) \ln(t)}{t^2} for mâ‰Șt/ln⁥(t) m \ll t/ \ln(t). Numerical simulations in two dimensions supporting the analytical results are also presented.Comment: 11 pages, 6 figures, Revtex

    Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects

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    In gravitational-wave detection, special emphasis is put onto searches that focus on cosmic events detected by other types of astrophysical observatories. The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical telescopes and neutrino observatories, provide a trigger time for analyzing gravitational wave data coincident with the event. In certain cases the expected frequency range, source energetics, directional and progenitor information is also available. Beyond allowing the recognition of gravitational waveforms with amplitudes closer to the noise floor of the detector, these triggered searches should also lead to rich science results even before the onset of Advanced LIGO. In this paper we provide a broad review of LIGO's astrophysically triggered searches and the sources they target

    Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

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    © Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

    Cluster illumination differentially affects growth of fruits along their ontogeny in highbush blueberry (Vaccinium corymbosum L.).

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    Shading highbush blueberry plants generally leads to a delayed fruit development. Experiments have been performed to study the effects of light on fruit growth independently from the rest of the canopy. Clusters were shaded during different fruit growth periods. The equatorial diameter of the fruits as a function of days after full bloom followed a double-sigmoidal growth pattern, being fitted using a Gompertz II nonlinear mixed model, and absolute growth rates were obtained from each fitted model. Both whole-cycle shaded and second-stage shaded fruits showed a delayed peak in absolute growth curves with respect to both first-stage shaded and whole-cycle unshaded controls. Our results suggest that deficiency of light during the last stage of highbush blueberry fruits may lead to a substantial delay (of about 10–16 days) in harvest as compared with well-illuminated fruits. In order to estimate the contribution of intrinsic fruit photosynthesis to its own growth at different stages, clusters were subjected to girdling on their peduncles at different times. Girdling just before the second-stage resulted in fruits gaining between 35 and 40% of dry weight in comparison with the controls. This suggests that fruit photosynthesis may play a relevant role in fruit growth during the second sigmoidal stage, which in turn may contribute to explain the delayed growth observed in shaded fruits

    Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

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    The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & NemĂ©sio 2007; Donegan 2008, 2009; NemĂ©sio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

    The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

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    The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article
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