Search results for "Research"
showing 10 items of 25967 documents
On the role of cystatin C in cancer progression
2018
Cystatin C (Cyst C) is an endogenous inhibitor of lysosomal cysteine proteinases, which has been shown to play a role in several normal and pathological processes. Interestingly, a growing number of experimental and clinical studies suggest that this inhibitor also appears to be implicated in the malignant progression of various human tumors. However, the role of Cyst C in malignant diseases is still controversial as these studies have highlighted that this protein may function either as tumor suppressor or tumor promoter. The specific mechanisms underlying these opposing effects at present remain murky and are the subject of many current investigations. On the other hand, a complete knowle…
Apoptotic Activity of MeCP2 Is Enhanced by C-Terminal Truncating Mutations.
2016
Methyl-CpG binding protein 2 (MeCP2) is a widely abundant, multifunctional protein most highly expressed in post-mitotic neurons. Mutations causing Rett syndrome and related neurodevelopmental disorders have been identified along the entire MECP2 locus, but symptoms vary depending on mutation type and location. C-terminal mutations are prevalent, but little is known about the function of the MeCP2 C-terminus. We employ the genetic efficiency of Drosophila to provide evidence that expression of p.Arg294* (more commonly identified as R294X), a human MECP2 E2 mutant allele causing truncation of the C-terminal domains, promotes apoptosis of identified neurons in vivo. We confirm this novel find…
IL-34–Dependent Intrarenal and Systemic Mechanisms Promote Lupus Nephritis in MRL-Faslpr Mice
2019
Background In people with SLE and in the MRL- Fas lpr lupus mouse model, macrophages and autoantibodies are central to lupus nephritis. IL-34 mediates macrophage survival and proliferation, is expressed by tubular epithelial cells (TECs), and binds to the cFMS receptor on macrophages and to a newly identified second receptor, PTPRZ. Methods To investigate whether IL-34–dependent intrarenal and systemic mechanisms promote lupus nephritis, we compared lupus nephritis and systemic illness in MRL- Fas lpr mice expressing IL-34 and IL-34 knockout (KO) MRL- Fas lpr mice. We also assessed expression of IL-34 and the cFMS and PTPRZ receptors in patients with lupus nephritis. Results Intrarenal IL-3…
Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns.
2018
BackgroundMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition involving multiple organ systems and characterized by persistent/relapsing debilitating fatigue, immune dysfunction, neurological problems, and other symptoms not curable for at least 6 months. Disruption of DNA methylation patterns has been tied to various immune and neurological diseases; however, its status in ME/CFS remains uncertain. Our study aimed at identifying changes in the DNA methylation patterns that associate with ME/CFS.MethodsWe extracted genomic DNA from peripheral blood mononuclear cells from 13 ME/CFS study subjects and 12 healthy controls and measured global DNA methylation by EL…
Towards development of a statistical framework to evaluate myotonic dystrophy type 1 mRNA biomarkers in the context of a clinical trial
2020
AbstractMyotonic dystrophy type 1 (DM1) is a rare genetic disorder, characterised by muscular dystrophy, myotonia, and other symptoms. DM1 is caused by the expansion of a CTG repeat in the 3’-untranslated region of DMPK. Longer CTG expansions are associated with greater symptom severity and earlier age at onset. The primary mechanism of pathogenesis is thought to be mediated by a gain of function of the CUG-containing RNA, that leads to trans-dysregulation of RNA metabolism of many other genes. Specifically, the alternative splicing (AS) and alternative polyadenylation (APA) of many genes is known to be disrupted. In the context of clinical trials of emerging DM1 treatments, it is important…
Common genes associated with antidepressant response in mouse and man identify key role of glucocorticoid receptor sensitivity.
2017
Response to antidepressant treatment in major depressive disorder (MDD) cannot be predicted currently, leading to uncertainty in medication selection, increasing costs, and prolonged suffering for many patients. Despite tremendous efforts in identifying response-associated genes in large genome-wide association studies, the results have been fairly modest, underlining the need to establish conceptually novel strategies. For the identification of transcriptome signatures that can distinguish between treatment responders and nonresponders, we herein submit a novel animal experimental approach focusing on extreme phenotypes. We utilized the large variance in response to antidepressant treatmen…
Methanotrophy under Versatile Conditions in the Water Column of the Ferruginous Meromictic Lake La Cruz (Spain)
2016
Lakes represent a considerable natural source of methane to the atmosphere compared to their small global surface area. Methanotrophs in sediments and in the water column largely control methane fluxes from these systems, yet the diversity, electron accepting capacity, and nutrient requirements of these microorganisms have only been partially identified. Here, we investigated the role of electron acceptors alternative to oxygen and sulfate in microbial methane oxidation at the oxycline and in anoxic waters of the ferruginous meromictic Lake La Cruz, Spain. Active methane turnover in a zone extending well below the oxycline was evidenced by stable carbon isotope-based rate measurements. We o…
Corrigendum: Phylogeny of Vibrio vulnificus From the Analysis of the Core-Genome: Implications for Intra-Species Taxonomy
2018
Vibrio vulnificus (Vv) is a multi-host pathogenic species currently subdivided into three biotypes (Bts). The three Bts are human-pathogens, but only Bt2 is also a fish-pathogen, an ability that is conferred by a transferable virulence-plasmid (pVvbt2). Here we present a phylogenomic analysis from the core genome of 80 Vv strains belonging to the three Bts recovered from a wide range of geographical and ecological sources. We have identified five well-supported phylogenetic groups or lineages (L). LI comprises a mixture of clinical and environmental Bt1 strains, most of them involved in human clinical cases related to raw seafood ingestion. LII is linked to the aquaculture industry and incl…
Evaluation of a rapid antigen test (Panbio™ COVID-19 Ag rapid test device) for SARS-CoV-2 detection in asymptomatic close contacts of COVID-19 patien…
2021
Objectives There is limited information on the performance of rapid antigen detection (RAD) tests to identify SARS-CoV-2-infected asymptomatic individuals. In this field study, we evaluated the Panbio™ COVID-19 Ag Rapid Test Device (Abbott Diagnostics, Jena, Germany) for this purpose. Methods A total of 634 individuals (355 female; median age, 37 years; range, 9–87) were enrolled. Two nasopharyngeal swabs were collected from household (n = 338) and non-household contacts (n = 296) of COVID-19 cases. RAD testing was carried out at the point of care. The RT-PCR test used was the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, MA, USA). Results Household contacts were tested at a median …
Lactic Acid Bacteria With Antioxidant Activities Alleviating Oxidized Oil Induced Hepatic Injury in Mice
2018
In order to screening new Lactic acid bacteria (LAB) strains to alleviating liver injury induced by oxidized oil, we isolated and screened LAB from Chinese fermented foods. Lactobacillus plantarum AR113, Pediococcus pentosaceus AR243, and Lactobacillus plantarum AR501 showed higher scavenging activity of α, α-Diphenyl-β-Picrylhydrazyl (DPPH) free radical and hydrogen radical, stronger inhibition of lipid peroxidation, and better protective effect on yeast cells in vitro. In vivo, oral administration of L. plantarum AR501 improved the antioxidant status of injury mice induced by oxidized oil including decreasing lipid peroxidation, recovering activities of antioxidant enzymes. Meanwhile, the…