Impact of KRAS variant rs61764370 on breast cancer morbidity

Low-penetrance gene variants and their combinations are topical study objects in breast cancer pathogenesis. Single nucleotide polymorphism rs61764370, localized in 3՛ UTR of KRAS gene, plays an important role in the development and progression of seve­ral cancers. The aim of our study was to determine the KRAS variant impact on breast cancer morbidity. Patients and Methods: 2214 patients diagnosed with breast cancer and 861 healthy controls were screened for KRAS variant by RFLP method. Available clinical data were collected and processed using statistical analysis methods. Results of present study suggest the KRAS variant impact on breast cancer development risk in premenopausal women, but it has no effect on breast cancer prognosis. We did not observe any KRAS variant effect on breast cancer patient 10-year disease-specific survival rates. Key Words: breast cancer, rs61764370, KRAS variant, predisposing factor

Temperature Dependence of Photochemical Degradation of MAPbBr3 Perovskite

The experimental results of X-ray diffraction (XRD), optical absorbance, scanning electron microscopy (SEM), and X-ray photoelectron spectra (XPS) of the core levels and valence bands of MAPbBr3 (MA-CH3NH3+) perovskite before and after exposure to visible light for 700 h at temperatures of 10 and 60 °C are presented. It reveals that the light soaking at 60 °C induces the decomposition of MAPbBr3 perovskite accompanied with the decay of organic cation and the release of a PbBr2 phase as a degradation product whereas the photochemical degradation completely disappears while the aging temperature is decreased to 10 °C. © 2022 by the authors.Russian Foundation for Basic Research, РФФИ: 21-52-52002; Ministry of Education and Science of the Russian Federation, Minobrnauka: AAAA-A18–118020190098-5, FEUZ 2020-0060; Ministry of Science and Technology, Taiwan, MOST: 110-2923-E-002-007-MY3; Russian Science Foundation, RSF: 19-73-30020I.S.Z. and A.I.K. thank the Ministry of Science and Higher Education of the Russian Federation (Ural Federal University Program of Development within the Priority-2030 Program) for support.This work was supported by the Russian Science Foundation (Project 19-73-30020) at IPCP RAS. The XPS measurements were supported by the Ministry of Science and Higher Education of the Russian Federation under the theme “Electron” No. AAAA-A18–118020190098-5 and Project FEUZ 2020-0060 as well as the Russian Foundation for Basic Research (Project No. 21-52-52002). The research fundings from the Ministry of Science and Technology in Taiwan (MOST 110-2923-E-002-007-MY3) are gratefully acknowledged

Metformin strongly affects transcriptome of peripheral blood cells in healthy individuals

Funding Information: The study was supported by the European Regional Development Fund under the project ?Investigation of interplay between multiple determinants influencing response to metformin: search for reliable predictors for efficacy of type 2 diabetes therapy? (Project No.: 1.1.1.1/16/A/091, https://ec.europa.eu/regional_policy/en/funding/ erdf/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank all the volunteers for their participation and acknowledge the Genome Database of the Latvian Population for providing biological material and data. Publisher Copyright: © 2019 Ustinova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Metformin is a commonly used antihyperglycaemic agent for the treatment of type 2 diabetes mellitus. Nevertheless, the exact mechanisms of action, underlying the various therapeutic effects of metformin, remain elusive. The goal of this study was to evaluate the alterations in longitudinal whole-blood transcriptome profiles of healthy individuals after a one-week metformin intervention in order to identify the novel molecular targets and further prompt the discovery of predictive biomarkers of metformin response. Next generation sequencing-based transcriptome analysis revealed metformin-induced differential expression of genes involved in intestinal immune network for IgA production and cytokine-cytokine receptor interaction pathways. Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin’s action. In addition to universal effects, 4 clusters of functionally related genes with a subject-specific differential expression were distinguished, including genes relevant to insulin production (HNF1B, HNF1A, HNF4A, GCK, INS, NEUROD1, PAX4, PDX1, ABCC8, KCNJ11) and cholesterol homeostasis (APOB, LDLR, PCSK9). This inter-individual variation of the metformin effect on the transcriptional regulation goes in line with well-known variability of the therapeutic response to the drug.publishersversionPeer reviewe

Integrative genetic map of repetitive DNA in the sole Solea senegalensis genome shows a Rex transposon located in a proto-sex chromosome

Repetitive sequences play an essential role in the structural and functional evolution of the genome, particularly in the sexual chromosomes. The Senegalese sole (Solea senegalensis) is a valuable flatfish in aquaculture albeit few studies have addressed the mapping and characterization of repetitive DNA families. Here we analyzed the Simple Sequence Repeats (SSRs) and Transposable elements (TEs) content from fifty-seven BAC clones (spanning 7.9 Mb) of this species, located in chromosomes by multiple fluorescence in situ hybridization (m-BAC-FISH) technique. The SSR analysis revealed an average density of 675.1 loci per Mb and a high abundance (59.69%) of dinucleotide coverage was observed, being 'AC' the most abundant. An SSR-FISH analysis using eleven probes was also carried out and seven of the 11 probes yielded positive signals. 'AC' probes were present as large clusters in almost all chromosomes, supporting the bioinformatic analysis. Regarding TEs, DNA transposons (Class II) were the most abundant. In Class I, LINE elements were the most abundant and the hAT family was the most represented in Class II. Rex/Babar subfamily, observed in two BAC clones mapping to chromosome pair 1, showed the longest match. This chromosome pair has been recently reported as a putative sexual proto-chromosome in this species, highlighting the possible role of the Rex element in the evolution of this chromosome. In the Rex1 phylogenetic tree, the Senegalese sole Rex1 retrotransposon could be associated with one of the four major ancient lineages in fish genomes, in which it is included O. latipes

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Clinical Features of Autoimmune Autonomic Ganglionopathy and the Detection of Subunit-Specific Autoantibodies to the Ganglionic Acetylcholine Receptor in Japanese Patients

Autoimmune autonomic ganglionopathy (AAG) is a rare acquired channelopathy that is characterized by pandysautonomia, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChR) may play a central role. Radioimmunoprecipitation (RIP) assays have been used for the sensitive detection of autoantibodies to gAChR in the serum of patients with AAG. Here, we developed luciferase immunoprecipitation systems (LIPS) to diagnose AAG based on IgGs to both the α3 and β4 gAChR subunits in patient serum. We reviewed the serological and clinical data of 50 Japanese patients who were diagnosed with AAG. With the LIPS testing, we detected anti-α3 and -β4 gAChR antibodies in 48% (24/50) of the patients. A gradual mode of onset was more common in the seropositive group than in the seronegative group. Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR. The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group. In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG. Our results demonstrated that the LIPS assay was a useful novel tool for detecting autoantibodies against gAChR in patients with AAG

IMPACT OF KRAS VARIANT rs61764370 ON BREAST CANCER MORBIDITY

Low-penetrance gene variants and their combinations are topical study objects in breast cancer pathogenesis. Single nucleotide polymorphism rs61764370, localized in 3՛ UTR of KRAS gene, plays an important role in the development and progression of seve­ral cancers. The aim of our study was to determine the KRAS variant impact on breast cancer morbidity. Patients and Methods: 2214 patients diagnosed with breast cancer and 861 healthy controls were screened for KRAS variant by RFLP method. Available clinical data were collected and processed using statistical analysis methods. Results of present study suggest the KRAS variant impact on breast cancer development risk in premenopausal women, but it has no effect on breast cancer prognosis. We did not observe any KRAS variant effect on breast cancer patient 10-year disease-specific survival rates. Key Words: breast cancer, rs61764370, KRAS variant, predisposing factor