A Multitrait Locus Regulates Sarbecovirus Pathogenesis

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genomewide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans

The COVID-19 pandemic and its global effects on dental practice. An international survey

Objectives: A multicentre survey was designed to evaluate the impact of COVID-19 outbreak on dental practice worldwide, estimate the COVID-19 related symptoms/signs, work attitudes and behaviour and the routine use of protective measures and Personal Protective Equipment (PPE). Methods: A global survey using a standardized questionnaire with research groups from 36 countries was designed. The questionnaire was developed and pretested during April 2020 and contained three domains: 1) Personal data; 2) COVID-19 positive rate and symptoms/signs presumably related to the coronavirus; 3) Working conditions and PPE adopted after the outbreak. Countries’ data were grouped by the Country Positive Rate (CPR) during the survey period and by Gross-National-Income per capita. An ordinal multinomial logistic regression model was carried out with COVID-19 self-reported rate referred by dental professionals as dependent variable to assess the association with questionnaire items. Results: A total of 52,491 questionnaires were returned with a male/female ratio of 0.63. Out of the total respondents, 7,859 dental professionals (15%) reported symptoms/signs compatible with COVID-19. More than half of the sample (n = 27,818; 53%) stated to use FFP2/N95 masks, while 21,558 (41.07%) used eye protection. In the bivariate analysis, CPR and N95/FFP2 were significantly associated (OR = 1.80 95%CI = 1.60/2.82 and OR = 5.20 95%CI = 1.44/18.80, respectively), while Gross-National-Income was not statistically associated with CPR (OR = 1.09 95%CI = 0.97/1.60). The same significant associations were observed in the multivariate analysis. Conclusions: Oral health service provision has not been significantly affected by COVID-19, although access to routine dental care was reduced due to country-specific temporary lockdown periods. While the dental profession has been identified at high-risk, the reported rates of COVID-19 for dental professionals were not significantly different to those reported for the general population in each country. These findings may help to better plan oral health care for future pandemic events

Optimization of a rapid method for studying the cellular location of β-glucosidase activity in wine yeasts

Aims: To improve a method for determining β-glucosidase activity and to apply it in yeasts isolated from wine ecosystems from 'La Mancha' region and to know its cellular location. Methods and Results: A total of 82 wine yeasts were identified (PCR/RFLP) and evaluated for their β-glucosidase activity. First, they were qualitatively evaluated by growth on YNB cellobiose, the activity was quantified using different culture media, under aerobic and anaerobic conditions and cells after 24-72 h of growth. To study the location activity, five fractions were obtained (supernatant, whole cell, cell wall, cytosol and cell membrane). The enzymatic assays were optimized, being: growth in YP cellobiose for 72 h in aeration conditions and, after cell removing, enzyme analysis with 128 g 1-1 of cellobiose as substrate, for 30 min at 30°C. The genus that displayed the greatest activity were Pichia, Hanseniaspora and Rhodotorula, and the activity was intracellular. Conclusions: The study showed that β-glucosidase activity was induced by the carbon source and was aerobic dependent. The non-Saccharomyces species displayed the greatest activity, which was intracellular and strain-dependent. Significance and Impact of the Study: This study developed a reliable method for screening β-glucosidase activity in yeasts isolated from wine ecosystems. This activity is very important in the release of monoterpenols from glycoside precursors for the enhancement of wine aromas. © 2005 The Society for Applied Microbiology.Articl

Marine ecosystems'responses to climatic and anthropogenic forcings in the Mediterranean

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