المؤلفون: Wilcox, N., Wahlström, C., Kvist, A., Simard, J.

المصدر: Nature Genetics. 55(9):1435-1439

مصطلحات موضوعية: Exome, Exome Sequencing, Female, Humans, Mutation, Missense, Neoplasms, ATM protein, ATR protein, BRCA1 associated ring domain protein 1, BRCA1 protein, BRCA2 protein, checkpoint kinase 2, partner and localizer of BRCA2, adult, Article, breast cancer, cancer risk, cancer susceptibility, controlled study, female, gene frequency, gene identification, genetic association, genetic linkage, genetic susceptibility, genetic variability, human, lztr1 gene, major clinical study, map3k1 gene, missense mutation, oncogene, whole exome sequencing, exome, genetics, meta analysis, neoplasm, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Medicinsk genetik, Medical and Health Sciences, Basic Medicine, Medical Genetics, Klinisk medicin, Cancer och onkologi, Clinical Medicine, Cancer and Oncology

الوصف: Linkage and candidate gene studies have identified several breast cancer susceptibility genes, but the overall contribution of coding variation to breast cancer is unclear. To evaluate the role of rare coding variants more comprehensively, we performed a meta-analysis across three large whole-exome sequencing datasets, containing 26,368 female cases and 217,673 female controls. Burden tests were performed for protein-truncating and rare missense variants in 15,616 and 18,601 genes, respectively. Associations between protein-truncating variants and breast cancer were identified for the following six genes at exome-wide significance (P < 2.5 × 10−6): the five known susceptibility genes ATM, BRCA1, BRCA2, CHEK2 and PALB2, together with MAP3K1. Associations were also observed for LZTR1, ATR and BARD1 with P < 1 × 10−4. Associations between predicted deleterious rare missense or protein-truncating variants and breast cancer were additionally identified for CDKN2A at exome-wide significance. The overall contribution of coding variants in genes beyond the previously known genes is estimated to be small. © 2023, The Author(s).

الوصول الحر: https://lup.lub.lu.se/record/69c36c9b-10ee-4f40-8800-b6aec24ba791Test
http://dx.doi.org/10.1038/s41588-023-01466-zTest

المؤلفون: Mossberg, Karin, 1981, Olausson, Josefin, 1983, Fryk, Emanuel, Jern, Sverker, 1954, Jansson, Per-Anders, 1961, Brogren, Helén, 1977

المصدر: Plos One. 17(8 August)

مصطلحات موضوعية: Clinical Medicine, Klinisk medicin, messenger RNA, plasminogen activator inhibitor 1, plasminogen activator inhibitor 1 antigen, unclassified drug, plasminogen activator inhibitor 2, tissue plasminogen activator, adult, aged, antigen blood level, Article, cell level, clinical article, comparative study, controlled study, diabetes control, diabetic patient, enzyme linked immunosorbent assay, female, gene expression, human, human cell, human tissue, lean body weight, male, middle aged, non insulin dependent diabetes mellitus, obesity, polymerase chain reaction, thrombocyte, thrombocyte function, genetics, metabolism, Blood Platelets, Diabetes Mellitus, Type 2, Humans, RNA, Messenger

الوصف: Background The main inhibitor of the fibrinolytic system, Plasminogen Activator Inhibitor -1 (PAI-1), irreversibly binds tissue-type Plasminogen Activator (t-PA) and thereby inhibits the protective action of tPA against thrombus formation. Elevated levels of plasma PAI-1 are associated with an increased risk of cardiovascular events and are observed in subjects with type 2 diabetes (T2D) and obesity. Platelets contain the majority of PAI-1 present in blood and exhibit the ability to synthesis active PAI-1. Diabetic platelets are known to be hyper-reactive and larger in size; however, whether these features affect their contribution to the elevated levels of plasma PAI-1 in T2D is not established. Objectives To characterize the PAI-1 antigen content and the mRNA expression in platelets from T2D subjects compared to obese and lean control subjects, in order to elucidate the role of platelet PAI-1 in T2D. Methods Nine subjects with T2D and obesity were recruited from Primary Care Centers together with 15 healthy control subjects (8 lean subjects and 7 with obesity). PAI-1 antigen levels in plasma, serum and platelets were determined by ELISA, and PAI-1 mRNA expression was analyzed by qPCR. Results There was no significant difference in PAI-1 mRNA expression or PAI-1 antigen in platelets in T2D subject in comparison to obese and lean control subjects. An elevated level of plasma PAI-1 was seen in both T2D and obese subjects. PAI-1 gene expression was significantly higher in both obese groups compared to lean. Conclusion Similar levels of protein and mRNA expression of PAI-1 in platelets from T2D, obese and lean subjects indicate a limited role of platelets for the elevated plasma PAI-1 levels. However, an increased synthesis rate of mRNA transcripts in platelets from T2D and an increased release of PAI-1 could also result in similar mRNA and protein levels. Hence, synthesis and release rates of PAI-1 from platelets in T2D and obesity need to be investigated to further elucidate the role of platelets in obesity and T2D. © 2022 Mossberg 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.

الوصول الحر: https://gup.ub.gu.se/publication/322519Test

المؤلفون: Studahl, Marie, 1957, Hagberg, Lars, 1951, Rekabdar, E, Bergström, T

المصدر: Scandinavian journal of infectious diseases. 32(3):237-48

مصطلحات موضوعية: Clinical Medicine, Klinisk medicin, Adolescent, Adult, Aged, Central Nervous System Infections, cerebrospinal fluid, diagnosis, virology, Child, Preschool, Cytomegalovirus, genetics, DNA, Viral, Female, Herpesviridae, Herpesviridae Infections, Herpesvirus 1, Human, Herpesvirus 2, Herpesvirus 3, Herpesvirus 4, Herpesvirus 6, Humans, Infant, Newborn, Male, Middle Aged, Polymerase Chain Reaction

الوصف: To evaluate the role of 6 human herpesviruses (cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), herpes simplex virus (HSV) types 1 and 2 and varicella zoster virus (VZV)) in infections of the nervous system, cerebrospinal fluid (CSF) samples from 662 patients with suspected viral aetiology to neurological symptoms were investigated for presence of herpesviral DNA in a PCR-based study. Of the 69 patients (2 patients had 2 herpesvirus DNA detected in CSF) who had herpesvirus DNA detected in the CSF, 60 (87%) were non-immunocompromised (CMV 7; HHV-6 6; EBV 16; HSV-1 18; HSV-2 9 and VZV 6) and 9 (13%) were immunocompromised (CMV 3; HHV-6 0; EBV 5; HSV-1 0; HSV-2 1 and VZV 0). The study was performed in a retrospective/prospective manner. The HSV-1, HSV-2, VZV and CMV DNA-positive patients usually had typical clinical syndromes, such as encephalitis/myelitis and meningitis, but also other neurological conditions were associated with findings of these viruses. HHV-6 and EBV DNA were detected in patients presenting with a variety of neurological symptoms, and in some of the cases, concurrent with diagnosis of other infections of the central nervous system. Despite the overall variability of clinical conditions seen, a pattern associated with each investigated herpesvirus was discernable as regards clinical presentation.

الوصول الحر: https://gup.ub.gu.se/publication/246554Test