COMPLEMENT FACTOR B IS A DETERMINANT OF BOTH METABOLIC AND CARDIOVASCULAR FEATURES OF METABOLIC SYNDROME

CFB (complement factor B) is elevated in adipose tissue and serum from patients with type 2 diabetes mellitus and cardiovascular disease, but the causal relationship to disease pathogenesis is unclear. Cfb is also elevated in adipose tissue and serum of the spontaneously hypertensive rat, a well-characterized model of metabolic syndrome. To establish the role of CFB in metabolic syndrome, we knocked out the Cfb gene in the spontaneously hypertensive rat. Cfb−/− rats showed improved glucose tolerance and insulin sensitivity, redistribution of visceral to subcutaneous fat, increased adipocyte mitochondrial respiration, and marked changes in gene expression. Cfb−/− rats also had lower blood pressure, increased ejection fraction and fractional shortening, and reduced left ventricular mass. These changes in metabolism and gene expression, in adipose tissue and left ventricle, suggest new adipose tissue-intrinsic and blood pressure-independent mechanisms for insulin resistance and cardiac hypertrophy in the spontaneously hypertensive rat. In silico analysis of the human CFB locus revealed 2 cis-regulated expression quantitative trait loci for CFB expression significantly associated with visceral fat, circulating triglycerides and hypertension in genome-wide association studies. Together, these data demonstrate a key role for CFB in the development of spontaneously hypertensive rat metabolic syndrome phenotypes and of related traits in humans and indicate the potential for CFB as a novel target for treatment of cardiometabolic disease

Chromosome contacts in activated T cells identify autoimmune disease candidate genes

BACKGROUND: Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4+ T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes. RESULTS: Within four hours, activation of CD4+ T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C (PCHi-C). By integrating PCHi-C data with genetic associations for five autoimmune diseases we prioritised 245 candidate genes with a median distance from peak signal to prioritised gene of 153 kb. Just under half (108/245) prioritised genes related to activation-sensitive interactions. This included IL2RA, where allele-specific expression analyses were consistent with its interaction-mediated regulation, illustrating the utility of the approach. CONCLUSIONS: Our systematic experimental framework offers an alternative approach to candidate causal gene identification for variants with cell state-specific functional effects, with achievable sample sizes.This work was funded by the JDRF (9-2011-253), the Wellcome Trust (089989, 091157, 107881), the UK Medical Research Council (MR/L007150/1, MC_UP_1302/5), the UK Biotechnology and Biological Sciences Research Council (BB/J004480/1) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. The research leading to these results has received funding from the European Union’s 7th Framework Programme (FP7/2007-2013) under grant agreement no. 241447 (NAIMIT). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140)

Barcodes of marine invertebrates from north Iberian ports: Native diversity and resistance to biological invasions

Ports are gateways for many marine organisms transported by ships worldwide, especially non-indigenous species (NIS). In this study carried out in North Iberian ports (Cantabrian Sea, Bay of Biscay) we have observed 38% of exotic macroinvertebrates. Four species, namely the barnacle Austrominius modestus, the tubeworm Ficopomatus enigmaticus, the Pacific oyster Crassostrea gigas and the pygmy mussel Xenostrobus securis, exhibited clear signs of invasiveness. A total of 671 barcode (cytochrome oxidase subunit I or 18S rRNA) genes were obtained and confirmed the species status of some cryptic NIS. Negative and significant correlation between diversity estimators of native biota and proportion of NIS suggests biotic resistance in ports. This could be applied to management of port biota for contributing to prevent the settlement of biopollutants in these areas which are very sensitive to biological invasions.Versión del editor2,359

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

Flotsam, an overlooked vector of alien dispersal from ports

Anthropogenic litter is considered a potential vector for the dispersal of non-indigenous species (NIS) in marine ecosystems. Using the bay of Gijon (Southwestern Bay of Biscay) as a case study, we studied the composition and potential transfer of the communities inhabiting three different environment components: 1) natural and artificial substrates from the international port of Gijon, 2) six proximate rocky beaches and 3) floating litter collected in the adjacent coast. A total of 717 organisms were morphologically identified and DNA barcoded using COI and 18S genes. In total 23 NIS were detected, six of them considered invasive in the area. The taxonomic profiles of the three environment components were significantly different, flotsam containing higher proportions of Hexanauplia and less mollusks, echinoderms and polychaetes than ports and beaches. Contrary to expectations, floating litter showed higher densities of native and exotic species than beaches or port surfaces. This and shared haplotypes between port, flotsam and beaches in some invasive species may indicate that marine litter could represent a new habitat for species to disperse into new areas.En prens