Search results for "Hom"

Complex Destabilization in the Mitochondrial Chaperonin Hsp60 Leads to Disease.

2020

Several neurological disorders have been linked to mutations in chaperonin genes and more specifically to the HSPD1 gene. In humans, HSPD1 encodes for the mitochondrial Heat Shock Protein 60 (mtHsp60) chaperonin, which carries out essential protein refolding reactions that help maintain mitochondrial and cellular homeostasis. It functions as a macromolecular complex that provides client proteins an environment that favors proper folding in an ATP dependent manner. It has been established that mtHsp60 plays a crucial role in the proper folding of mitochondrial proteins involved in ATP producing pathways. Recently, various single-point mutations in the mtHsp60 encoding gene have been directly…

Redox Regulation by HGF/c-Met in Liver Disease

2017

Reactive oxygen species (ROS) have gained considerable attention in recent years because of their direct involvement in the regulation of multiple physiological and pathological processes. Under normal conditions, ROS have an important role in cell signaling and function as essential mediators of cell homeostasis. However, imbalance between ROS and antioxidant systems induces oxidative stress, which leads to cell and tissue damage. The cellular redox modulation by hepatocyte growth factor (HGF) and its receptor c-Met in the liver has been studied extensively in the past. The generation of liver-specific c-Met–knockout mice has allowed to demonstrate the fundamental importance of HGF/c-Met i…

T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes

2021

Simple Summary T-cells defend the human body from pathogenic invasion via specific recognition by T-cell receptors (TCRs). The TCR genes undergo recombination (rearrangement) in a myriad of possible ways to generate different TCRs that can recognize a wide diversity of foreign antigens. However, in patients with T-cell lymphoma (TCL), a particular T-cell becomes malignant and proliferates, resulting in a population of genetically identical cells with same TCR rearrangement pattern. To help diagnose patients with TCL, a polymerase chain reaction (PCR)-based assay is currently used to determine if neoplastic cells in patient samples are of T-cell origin and bear identical (monoclonal) TCR rea…

SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

2017

AbstractBiogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we…

Activation of Mevalonate Pathway Via LKB1 is Essential for Stability of Treg Cells

2019

Summary: The function of regulatory T (Treg) cells depends on lipid oxidation. However, the molecular mechanism by which Treg cells maintain lipid metabolism after activation remains elusive. Liver kinase B1 (LKB1) acts as a coordinator by linking cellular metabolism to substrate AMP-activated protein kinase (AMPK). We show that deletion of LKB1 in Treg cells exhibited reduced suppressive activity and developed fatal autoimmune inflammation. Mechanistically, LKB1 induced activation of the mevalonate pathway by upregulating mevalonate genes, which was essential for Treg cell functional competency and stability by inducing Treg cell proliferation and suppressing interferon-gamma and interleuk…

Methylophaga and Hyphomicrobium can be used as target genera in monitoring saline water methanol-utilizing denitrification.

2016

Abstract Which bacterial taxonomic groups can be used in monitoring saline water methanol-utilizing denitrification and whether nitrate is transformed into N2 in the process are unclear. Therefore, methylotrophic bacterial communities of two efficiently functioning (nitrate/nitrite reduction was 63–96 %) tropical and cool seawater reactors at a public aquarium were investigated with clone library analysis and 454 pyrosequencing of the 16S rRNA genes. Transformation of nitrate into N2 was confirmed using 15N labeling in incubation of carrier material from the tropical reactor. Combining the data with previous study results, Methylophaga and Hyphomicrobium were determined to be suitable targe…

Intra-tumour heterogeneity of diffuse large B-cell lymphoma involves the induction of diversified stroma-tumour interfaces

2020

Abstract Background Intra-tumour heterogeneity in lymphoid malignancies encompasses selection of genetic events and epigenetic regulation of transcriptional programs. Clonal-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-specific mesenchymal cells impact on the diversification of aggressive lymphoma clones is still unknown. Methods Combining in situ quantitative immunophenotypical analyses and RNA sequencing we investigated the intra-tumour heterogeneity and the specific mesenchymal modifications that are associated with A20 diffuse large B-cell lymphoma (DLBCL) cells seeding of d…

Coincident Activation of Glutamate Receptors Enhances GABAA Receptor-Induced Ionic Plasticity of the Intracellular Cl−-Concentration in Dissociated N…

2019

Massive activation of γ-amino butyric acid A (GABAA) receptors during pathophysiological activity induces an increase in the intracellular Cl−-concentration ([Cl−]i), which is sufficient to render GABAergic responses excitatory. However, to what extent physiological levels of GABAergic activity can influence [Cl−]i is not known. Aim of the present study is to reveal whether moderate activation of GABAA receptors mediates functionally relevant [Cl−]i changes and whether these changes can be augmented by coincident glutamatergic activity. To address these questions, we used whole-cell patch-clamp recordings from cultured cortical neurons [at days in vitro (DIV) 6–22] to determine changes in t…

2020

<b><i>Introduction:</i></b> Individuals suffering from overweight or obesity frequently experience weight-based stigmatization. The widespread belief that weight is a matter of personal will and self-control results in various weight-based stereotypes (e.g., laziness, lack of self-discipline, or neglect). <b><i>Objective:</i></b> Based on the modified version of the Weight Bias Internalization Scale (WBIS-M), a short form for the economic assessment of weight bias internalization in the general population was compiled and validated. <b><i>Methods:</i></b> A three-item short form (WBIS-3) was derived based on data from a…

Cryptotanshinone deregulates unfolded protein response and eukaryotic initiation factor signaling in acute lymphoblastic leukemia cells.

2015

Abstract Background: Unfolded protein responses (UPR) determine cell fate and are recognized as anticancer targets. In a previous research, we reported that cryptotanshinone (CPT) exerted cytotoxic effects toward acute lymphoblastic leukemia cells through mitochondria-mediated apoptosis. Purpose: In the present study, we further investigated the role of UPR in CPT-induced cytotoxicity on acute lymphoblastic leukemia cells by applying tools of pharmacogenomics and bioinformatics. Methods: Gene expression profiling was performed by mRNA microarray hybridization. Potential transcription factor binding motifs were identified in the promoter regions of the deregulated genes by Cistrome software.…