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Versión preprint diponible en BioRxiv (doi: 10.1101/2020.02.07.937862) http://hdl.handle.net/10261/212994, The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS-CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks., Work on DEmARC advancement and coronavirus and nidovirus taxonomies was supported by the EU Horizon 2020 EVAg 653316 project and the LUMC MoBiLe program (to A.E.G.), and on coronavirus and nidovirus taxonomies by a Mercator Fellowship by the Deutsche Forschungsgemeinschaft (to A.E.G.) in the context of the SFB1021 (A01 to J.Z.).

Biological species, including viruses, change through generations and over time in the process known as evolution. Viruses may evolve at high, uneven, and fluctuating rates among genome sites. The accumulated changes, through either mutation or recombination with other species, are first fixed in the genome of successful individuals that give rise to genetic lineages. The relationship between biological lineages related by common descent is called ‘phylogeny’. For inferring phylogeny, the differences between aligned sequences of genomes and proteins are quantified and depicted in the form of a tree, in which contemporary species and their intermediate and common ancestors occupy, respectively, the terminal nodes, internal nodes, and the root. The tree is characterized by a topology, length of branches, shape, and the root position. A complex mathematical apparatus has been developed for phylogeny inference that can evaluate inter-species differences, facilitate tree building and comparison of trees, and assess the fit between data and tree through, typically, computationally intensive calculations. A reconstructed tree is an approximation of the true phylogeny that practically remains unknown. The phylogenetic analysis is used in applied and fundamental virus research, including epidemiology, diagnostics, forensic studies, phylogeography, evolutionary studies, and virus taxonomy. It can provide an evolutionary perspective on variation of any trait that can be measured for a group of viruses.

Summary Background Many people with schizophrenia experience stigma caused by other people's knowledge, attitudes, and behaviour; this can lead to impoverishment, social marginalisation, and low quality of life. We aimed to describe the nature, direction, and severity of anticipated and experienced discrimination reported by people with schizophrenia. Methods We did a cross-sectional survey in 27 countries, in centres affiliated to the INDIGO Research Network, by use of face-to-face interviews with 732 participants with schizophrenia. Discrimination was measured with the newly validated discrimination and stigma scale (DISC), which produces three subscores: positive experienced discrimination; negative experienced discrimination; and anticipated discrimination. Findings Negative discrimination was experienced by 344 (47%) of 729 participants in making or keeping friends, by 315 (43%) of 728 from family members, by 209 (29%) of 724 in finding a job, 215 (29%) of 730 in keeping a job, and by 196 (27%) of 724 in intimate or sexual relationships. Positive experienced discrimination was rare. Anticipated discrimination affected 469 (64%) in applying for work, training, or education and 402 (55%) looking for a close relationship; 526 (72%) felt the need to conceal their diagnosis. Over a third of participants anticipated discrimination for job seeking and close personal relationships when no discrimination was experienced. Interpretation Rates of both anticipated and experienced discrimination are consistently high across countries among people with mental illness. Measures such as disability discrimination laws might, therefore, not be effective without interventions to improve self-esteem of people with mental illness. Funding South London and Maudsley NHS Foundation Trustees, UK Department of Health SHiFT programme, German Ministry of Education and Research.

This thesis combines the use of standard bioinformatics analyses with the development of new computational techniques to study the evolution and genetic diversity of picornaviruses and nidoviruses. It integrates two lines of research __ genetics-based virus classification and evolutionary dynamics of gene length __ and aims at unveiling commonalities in the biology of these and other RNA viruses as well as assisting applied research in virology.

The aim of this study was to evaluate the level of anticipated discrimination in people with schizophrenia (n = 732) from 27 countries in the International Study of Discrimination and Stigma Outcomes (INDIGO).Anticipated discrimination was assessed through four questions of Discrimination and Stigma Scale. Twenty-five individuals were identified at each site who were reasonably representative of all such treated cases within the local area.Sixty-four per cent of the participants reported that they had stopped themselves from applying for work, training or education because of anticipated discrimination. Seventy-two per cent of them reported that they felt the need to conceal their diagnosis. Expecting to be avoided by others who know about their diagnosis was highly associated with decisions to conceal their diagnosis. Those who concealed their diagnosis were younger and more educated. The participants who perceived discrimination by others were more likely to stop themselves from looking for a close relationship. Anticipated discrimination in finding and keeping work was more common in the absence than in the presence of experienced discrimination, and the similar findings applied to intimate relationships.This study shows that anticipated discrimination among people with schizophrenia is common, but is not necessarily associated with experienced discrimination.

The Polyomaviridae constitute a family of small DNA viruses infecting a variety of hosts. In humans, polyomaviruses can cause infections of the central nervous system, urinary tract, skin, and possibly the respiratory tract. Here we report the identification of a new human polyomavirus in plucked facial spines of a heart transplant patient with trichodysplasia spinulosa, a rare skin disease exclusively seen in immunocompromized patients. The trichodysplasia spinulosa-associated polyomavirus (TSV) genome was amplified through rolling-circle amplification and consists of a 5232-nucleotide circular DNA organized similarly to known polyomaviruses. Two putative "early'' (small and large T antigen) and three putative "late'' (VP1, VP2, VP3) genes were identified. The TSV large T antigen contains several domains (e. g. J-domain) and motifs (e. g. HPDKGG, pRb family-binding, zinc finger) described for other polyomaviruses and potentially involved in cellular transformation. Phylogenetic analysis revealed a close relationship of TSV with the Bornean orangutan polyomavirus and, more distantly, the Merkel cell polyomavirus that is found integrated in Merkel cell carcinomas of the skin. The presence of TSV in the affected patient's skin was confirmed by newly designed quantitative TSV-specific PCR, indicative of a viral load of 10 5 copies per cell. After topical cidofovir treatment, the lesions largely resolved coinciding with a reduction in TSV load. PCR screening demonstrated a 4% prevalence of TSV in an unrelated group of immunosuppressed transplant recipients without apparent disease. In conclusion, a new human polyomavirus was discovered and identified as the possible cause of trichodysplasia spinulosa in immunocompromized patients. The presence of TSV also in clinically unaffected individuals suggests frequent virus transmission causing subclinical, probably latent infections. Further studies have to reveal the impact of TSV infection in relation to other populations and diseases.

Nuc1p, CPS-6, EndoG and EXOG are evolutionary conserved mitochondrial nucleases from yeast, Caenorhabditis elegans and humans, respectively. These enzymes play an important role in programmed cell death as well as mitochondrial DNA-repair and recombination. Whereas a significant interest has been given to the cell biology of these proteins, in particular their recruitment during caspase-independent apoptosis, determination of their biochemical properties has lagged behind. In part, biochemical as well as structural analysis of mitochondrial nucleases has been hampered by the fact that upon cloning and overexpression in Escherichia coli these enzymes can exert considerable toxicity and tend to aggregate and form inclusion bodies. We have, therefore, established a uniform E. coli expression system allowing us to obtain these four evolutionary related nucleases in active form from the soluble as well as insoluble fractions of E. coli cell lysates. Using preparations of recombinant Nuc1p, CPS-6, EndoG and EXOG we have compared biochemical properties and the substrate specificities of these related nucleases on selected substrates in parallel. Whereas Nuc1p and EXOG in addition to their endonuclease activity exert 5'-3'- exonuclease activity, CPS-6 and EndoG predominantly are endonucleases. These findings allow speculating that the mechanisms of action of these related nucleases in cell death as well as DNA-repair and recombination differ according to their enzyme activities and substrate specificities. © 2010 Elsevier Inc. All rights reserved.

At the end of the 19th century, male suicide rates in Switzerland were as high as the respective rates in recent decades, whereas female suicide rates were distinctly lower. An age-period-cohort analysis was performed to provide more information about the genderspecific changes over the last century. Suicide mortality has been reported in Switzerland since 1876 when the standardised registration of mortality data began. The analysed data cover the period 1881-2000. The statistical analyses were based on log-linear models and data aggregated by 10-year age-intervals and 10-year periodintervals. The results indicate similar age and period effects in males and females. The estimates representing age-specific risk increase steadily with age, with intermediate plateaus in the 20s and the 50s. The period-specific estimates follow the economic cycles. The birth cohort effects are stronger in males and weaker in females. In the males' estimates, there is a peak in cohorts born around 1840 and a low in cohorts born some 60-100 years later. The estimates increased again in generations born after World War II. In females, the birth cohort estimates are low in cohorts born in the first half of the 19th century and increase until the first half of the 20th century. Birth cohort effects remain an intriguing topic in epidemiology of suicide. A better understanding of birth cohort effects might open new doors to suicide prevention

Wilson's disease is a rare genetic condition, transmitted on a recessive autosomal mode, which involves a disturbance of copper metabolism. Its prevalence is 1: 30000. It is treatable but may be lethal if not managed early and treated adequately. It is caused by the loss of function of an adenosine triphosphatase (ATP 7B), which is due to a mutation in the ATP 7B gene on chromosome 13. This leads to a decrease or absence of copper transport to the bile and its accumulation within certain organs, particularly the liver and the brain. In this article we present two cases of Wilson's disease in two young male patients. We also briefly review the pathophysiology of the illness, discuss the latest guidelines for diagnosis and treatment and outline the recent genetic discoveries.

A genomic analysis of the annual fish Nothobranchius furzeri, a vertebrate with the shortest known life span in captivity and which may provide a new model organism for aging research., Background The annual fish Nothobranchius furzeri is the vertebrate with the shortest known life span in captivity. Fish of the GRZ strain live only three to four months under optimal laboratory conditions, show explosive growth, early sexual maturation and age-dependent physiological and behavioral decline, and express aging related biomarkers. Treatment with resveratrol and low temperature significantly extends the maximum life span. These features make N. furzeri a promising new vertebrate model for age research. Results To contribute to establishing N. furzeri as a new model organism, we provide a first insight into its genome and a comparison to medaka, stickleback, tetraodon and zebrafish. The N. furzeri genome contains 19 chromosomes (2n = 38). Its genome of between 1.6 and 1.9 Gb is the largest among the analyzed fish species and has, at 45%, the highest repeat content. Remarkably, tandem repeats comprise 21%, which is 4-12 times more than in the other four fish species. In addition, G+C-rich tandem repeats preferentially localize to centromeric regions. Phylogenetic analysis based on coding sequences identifies medaka as the closest relative. Genotyping of an initial set of 27 markers and multi-locus fingerprinting of one microsatellite provides the first molecular evidence that the GRZ strain is highly inbred. Conclusions Our work presents a first basis for systematic genomic and genetic analyses aimed at understanding the mechanisms of life span determination in N. furzeri.