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Carbonylation of proteins is an irreversible oxidative damage that increases during both chronological and replicative yeast aging. In the latter, a spatial protein quality control system that relies on Sir2 is responsible for the asymmetrical damage segregation in the mother cells. Proper localization of Sir2 on chromatin depends on the deubiquitinating enzyme Ubp10, whose loss of function deeply
Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics s
The RAI gene is also known as iASPP and PPP1R13L. Recent investigations have shown that the region encompassing RAI is important for the development of cancer in young and middle-aged persons. It has been speculated that the RAI product induces apoptosis by blocking NF-kappaB or inhibits apoptosis by blocking p53. Either way the gene could influence the survival of precancerous lesions. Here we re
Calcium, as an integral part of a large number of cellular regulatory pathways, is selective in the control of specific cell functions like the start of G1 phase in cell cycle. Cell proliferation has been suggested to depend on increasing intracellular calcium levels. A major regulatory pathway for intracellular calcium is the calcium influx into the cell via voltage-gated calcium channels. T-type
Cancer-associated fibroblasts (CAFs) regulate tumour growth, metastasis and response to treatment. Recent studies indicate the existence of functionally distinct CAF subsets. Suggested mechanisms whereby CAFs can impact on treatment response include paracrine signaling affecting cancer cell drug sensitivity and effects on tumour drug uptake. PDGFRβ is an important regulator of fibroblasts. Experim
UNLABELLED: To clarify the role of the TNFRSF11B gene encoding osteoprotegerin (OPG), in Paget's disease of bone (PDB) we studied TNFRSF11B polymorphisms in an association study of 690 UK subjects and in a worldwide familial study of 66 kindreds. We found that the G1181 allele of TNFRSF11B, encoding lysine at codon 3 of the OPG protein, predisposes to both sporadic and familial PDB.INTRODUCTION: P
The detailed mechanisms of progressive intensification of seizures often occurring in epilepsy are not well understood. Animal models of kindling, with progressive intensification of stimulation-induced seizures, have been previously used to investigate alterations in neuronal networks, but has been obscured by limited recording capabilities during electrical stimulations. Remote networks in kindl
The effect of amphetamine on striatal acetylcholine (ACh) release was studied by an in vivo intrastriatal microdialysis technique. Although we expected systemic amphetamine to inhibit baseline striatal ACh release, the opposite was found. In addition, we found that the amphetamine-induced striatal ACh release did not depend on nigrostriatal DA since 6-hydroxydopamine (6-OHDA) lesions had no effect
Testicular germ cell cancer is preceded by a pre-invasive stage called carcinoma-in-situ (CIS). The majority, if not all cases of CIS will progress into invasive cancer. Today, the only reliable way of diagnosing CIS is by performing open testicular biopsy. There is an ongoing search for non-invasive techniques for diagnosing early testicular neoplasia. The possibility of using ultrasound of the t
Post-translational modifications of proteins can generate antigenic conformations that may cause autoimmune diseases in persons with specific HLA-haplotypes. Monocytes and macrophages, attracted to an inflamed site, can release post-translationally acting enzymes, such as transglutaminases and peptidylarginine deiminases. In vivo, the activation of these enzymes is crucial for the further course o
We investigated whether: (1) liver X receptor (LXR)-driven induction of high-density lipoprotein cholesterol (HDL-C) and other LXR-mediated effects on cholesterol metabolism depend on intestinal cholesterol absorption; and (2) combined treatment with the LXR agonist GW3965 and the cholesterol absorption inhibitor ezetimibe results in synergistic effects on cholesterol metabolism that could be bene
ApoM is mainly associated with HDL. Nevertheless, we have consistently observed positive correlations of apoM with plasma LDL cholesterol in humans. Moreover, LDL receptor deficiency is associated with increased plasma apoM in mice. Here, we tested the idea that plasma apoM concentrations are affected by the rate of LDL receptor-mediated clearance of apoB-containing particles. We measured apoM in
Organohalogen compounds constitute one of the important groups of persistent organic pollutants (POPs). Among them, due to their long-term health effects, one should pay attention on organochlorine pesticides, polychlorinated biphenyls (PCBs) and perfluoroalkylated substances (PFASs). This paper is an attempt to answer the question about relation between the fact of cohabitation by couples expecti
Neurogenin 2 (Ngn2) is a proneural gene involved in neuronal differentiation and subtype specification in various regions of the nervous system. In the ventral midbrain, Ngn2 is expressed in a spatiotemporal pattern that correlates with the generation of mesencephalic dopaminergic (mesDA) neurons. We show here that lack of Ngn2 impairs the development of mesDA neurons, such that less than half of
Hypertension has been associated with raised plasma levels of complement factor 3 and 4 (C3 and C4). The nature of this association is unclear. This population-based longitudinal study explored whether C3 or C4 is associated with development of hypertension. Blood pressure and plasma levels of C3 and C4 were determined in 2178 healthy men, aged 35-50 years, initially without treatment for hyperten
