Developments in FINDbase worldwide database for clinically relevant genomic variation allele frequencies

FINDbase (http://www.findbase.org) aims to document frequencies of clinically relevant genomic variations, namely causative mutations and pharmacogenomic markers, worldwide. Each database record includes the population, ethnic group or geographical region, the disorder name and the related gene, accompanied by links to any related databases and the genetic variation together with its frequency in that population. Here, we report, in addition to the regular data content updates, significant developments in FINDbase, related to data visualization and querying, data submission, interrelation with other resources and a new module for genetic disease summaries. In particular, (i) we have developed new data visualization tools that facilitate data querying and comparison among different populations, (ii) we have generated a new FINDbase module, built around Microsoft’s PivotViewer (http://www.getpivot.com) software, based on Microsoft Silverlight technology (http://www.silverlight.net), that includes 259 genetic disease summaries from five populations, systematically collected from the literature representing the documented genetic makeup of these populations and (iii) the implementation of a generic data submission tool for every module currently available in FINDbase

Genetics of Myasthenia Gravis: A Case-Control Association Study in the Hellenic Population

Myasthenia gravis (MG) is an heterogeneous autoimmune disease characterized by the production of autoantibodies against proteins of the postsynaptic membrane, in the neuromuscular junction. The contribution of genetic factors to MG susceptibility has been evaluated through family and twin studies however, the precise genetic background of the disease remains elusive. We conducted a case-control association study in 101 unrelated MG patients of Hellenic origin and 101 healthy volunteers in order to assess the involvement of common genetic variants in susceptibility to MG. We focused on three candidate genes which have been clearly associated with several autoimmune diseases, aiming to investigate their potential implication in MG pathogenesis. These are interferon regulatory factor 5 (IRF-5), TNFα-induced protein 3 (TNFAIP3), also known as A20, and interleukin-10 (IL-10), key molecules in the regulation of immune function. A statistical trend of association (P=0.068) between IL-10 promoter single nucleotide polymorphisms (SNPs) and the subgroups of early and late-onset MG patients was revealed. No statistically significant differences were observed in the rest of the variants examined. As far as we are aware, this is the first worldwide attempt to address the possible association between IRF-5 and TNFAIP3 common genetic variants and the genetic basis of MG

ETHNOS: A versatile electronic tool for the development and curation of national genetic databases

National and ethnic mutation databases (NEMDBs) are emerging online repositories, recording extensive information about the described genetic heterogeneity of an ethnic group or population. These resources facilitate the provision of genetic services and provide a comprehensive list of genomic variations among different populations. As such, they enhance awareness of the various genetic disorders. Here, we describe the features of the ETHNOS software, a simple but versatile tool based on a flat-file database that is specifically designed for the development and curation of NEMDBs. ETHNOS is a freely available softw

ETHNOS : A versatile electronic tool for the development and curation of national genetic databases.

National and ethnic mutation databases (NEMDBs) are emerging online repositories, recording extensive information about the described genetic heterogeneity of an ethnic group or population. These resources facilitate the provision of genetic services and provide a comprehensive list of genomic variations among different populations. As such, they enhance awareness of the various genetic disorders. Here, we describe the features of the ETHNOS software, a simple but versatile tool based on a flat-file database that is specifically designed for the development and curation of NEMDBs. ETHNOS is a freely available software which runs more than half of the NEMDBs currently available. Given the emerging need for NEMDB in genetic testing services and the fact that ETHNOS is the only off-the-shelf software available for NEMDB development and curation, its adoption in subsequent NEMDB development would contribute towards data content uniformity, unlike the diverse contents and quality of the available gene (locus)-specific databases. Finally, we allude to the potential applications of NEMDBs, not only as worldwide central allele frequency repositories, but also, and most importantly, as data warehouses of individual-level genomic data, hence allowing for a comprehensive ethnicity-specific documentation of genomic variation

Population Based Study of 12 Autoimmune Diseases in Sardinia, Italy: Prevalence and Comorbidity

BACKGROUND: The limited availability of prevalence data based on a representative sample of the general population, and the limited number of diseases considered in studies about co-morbidity are the critical factors in study of autoimmune diseases. This paper describes the prevalence of 12 autoimmune diseases in a representative sample of the general population in the South of Sardinia, Italy, and tests the hypothesis of an overall association among these diseases. METHODS: Data were obtained from 21 GPs. The sample included 25,885 people. Prevalence data were expressed with 95% Poisson C.I. The hypothesis of an overall association between autoimmune diseases was tested by evaluating the co-occurrence within individuals. RESULTS: Prevalence per 100,000 are: 552 rheumatoid arthritis, 124 ulcerative colitis, 15 Crohn's disease, 464 type 1 diabetes, 81 systemic lupus erythematosus, 124 celiac disease, 35 myasthenia gravis, 939 psoriasis/psoriatic arthritis, 35 systemic sclerosis, 224 multiple sclerosis, 31 Sjogren's syndrome, and 2,619 autoimmune thyroiditis. An overall association between autoimmune disorders was highlighted. CONCLUSIONS: The comparisons with prevalence reported in current literature do not show outlier values, except possibly for a few diseases like celiac disease and myasthenia gravis. People already affected by a first autoimmune disease have a higher probability of being affected by a second autoimmune disorder. In the present study, the sample size, together with the low overall prevalence of autoimmune diseases in the population, did not allow us to examine which diseases are most frequently associated with other autoimmune diseases. However, this paper makes available an adequate control population for future clinical studies aimed at exploring the co-morbidity of specific pairs of autoimmune disease

Editorial: Alternative tobacco products: Toxicology and health issues

[No abstract available

Leguminous seeds powder diet reduces the survival and development of the khapra beetle, trogoderma granarium everts (Coleoptera: Dermestidae)

Chemical storage pest control is interlinked with many challenges such as environmental pollution and toxicity to humans and animals. Alternative tools are thus being increasingly researched and applied to supplement and/or substitute old-fashioned chemical means. Entomotoxic proteins, such as the lectins of leguminous seeds, have been shown to be effective alternative control agents against many serious insect pests. The objective of this work was to evaluate the effect of the flour of three leguminous seeds, Phaseolus vulgaris L. (Fabaceae) (the common bean), Vicia faba L. (Fabaceae) (the broad bean) and Glycine max L. (Fabaceae) (the soya bean), against 4th instar larvae of Trogoderma granarium Everts (Coleoptera: Curculionidae). The flours were tested at different concentrations. They all demonstrated significant effects on larval mortality, as well as they all induced a decrease in the number of larvae reaching the pupal stage. The flours of P. vulgaris and V. faba were highly insecticidal against T. granarium larvae, especially at the highest concentrations (86.7% for PV100 and 90% for VF100). Our results enrich previous findings on the entomotoxic effect of leguminous plant lectins and highlight P. vulgaris and V. faba lectins as potential alternative control agents against T. granarium. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Nicotinic cholinergic system and covid-19: In silico identification of an interaction between sars-cov-2 and nicotinic receptors with potential therapeutic targeting implications

While SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as the receptor for cell entry, it is important to examine other potential interactions between the virus and other cell receptors. Based on the clinical observation of low prevalence of smoking among hospitalized COVID-19 patients, we examined and identified a “toxin-like” amino acid (aa) sequence in the Receptor Binding Domain of the Spike Glycoprotein of SARS-CoV-2 (aa 375–390), which is homologous to a sequence of the Neurotoxin homolog NL1, one of the many snake venom toxins that are known to interact with nicotinic acetylcholine receptors (nAChRs). We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein and the superposition of the modelled structure of the Neurotoxin homolog NL1 and the SARS-CoV-2 Spike Glycoprotein. We also performed computational molecular modelling and docking experiments using 3D structures of the SARS-CoV-2 Spike Glycoprotein and the extracellular domain of the nAChR α9 subunit. We identified a main interaction between the aa 381–386 of the SARS-CoV-2 Spike Glycoprotein and the aa 189–192 of the extracellular domain of the nAChR α9 subunit, a region which forms the core of the “toxin-binding site” of the nAChRs. The mode of interaction is very similar to the interaction between the α9 nAChR and α-bungarotoxin. A similar interaction was observed between the pentameric α7 AChR chimera and SARS-CoV-2 Spike Glycoprotein. The findings raise the possibility that SARS-CoV-2 may interact with nAChRs, supporting the hypothesis of dysregulation of the nicotinic cholinergic system being implicated in the pathophysiology of COVID-19. Nicotine and other nicotinic cholinergic agonists may protect nAChRs and thus have therapeutic value in COVID-19 patients. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Smoking prevalence among hospitalized COVID-19 patients and its association with disease severity and mortality: an expanded re-analysis of a recent publication

Background: There is a lot of debate about the effects of smoking on COVID-19. A recent fixed-effects meta-analysis found smoking to be associated with disease severity among hospitalized patients, but other studies report an unusually low prevalence of smoking among hospitalized patients. The purpose of this study was to expand the analysis by calculating the prevalence odds ratio (POR) of smoking among hospitalized COVID-19 patients, while the association between smoking and disease severity and mortality was examined by random-effects meta-analyses considering the highly heterogeneous study populations. Methods: The same studies as examined in the previous meta-analysis were analyzed (N = 22, 20 studies from China and 2 from USA). The POR relative to the expected smoking prevalence was calculated using gender and age-adjusted population smoking rates. Random-effects meta-analyses were used for all other associations. Results: A total of 7162 patients were included, with 482 being smokers. The POR was 0.24 (95%CI 0.19–0.30). Unlike the original study, the association between smoking and disease severity was not statistically significant using random-effects meta-analysis (OR 1.40, 95%CI 0.98–1.98). In agreement with the original study, no statistically significant association was found between smoking and mortality (OR 1.86, 95%CI 0.88–3.94). Conclusion: An unusually low prevalence of smoking, approximately 1/4th the expected prevalence, was observed among hospitalized COVID-19 patients. Any association between smoking and COVID-19 severity cannot be generalized but should refer to the seemingly low proportion of smokers who develop severe COVID-19 that requires hospitalization. Smokers should be advised to quit due to long-term health risks, but pharmaceutical nicotine or other nicotinic cholinergic agonists should be explored as potential therapeutic options, based on a recently presented hypothesis. © 2021, The Author(s)