Search results for "alternative"
showing 10 items of 1466 documents
Autoregulation of NFATc1/A Expression Facilitates Effector T Cells to Escape from Rapid Apoptosis
2002
AbstractThreshold levels of individual NFAT factors appear to be critical for apoptosis induction in effector T cells. In these cells, the short isoform A of NFATc1 is induced to high levels due to the autoregulation of the NFATc1 promoter P1 by NFATs. P1 is located within a CpG island in front of exon 1, represents a DNase I hypersensitive chromatin site, and harbors several sites for binding of inducible transcription factors, including a tandemly arranged NFAT site. A second promoter, P2, before exon 2, is not controlled by NFATs and directs synthesis of the longer NFATc1/B+C isoforms. Contrary to other NFATs, NFATc1/A is unable to promote apoptosis, suggesting that NFATc1/A enhances eff…
PTHrP in differentiating human mesenchymal stem cells: Transcript isoform expression, promoter methylation, and protein accumulation
2013
Human PTHrP gene displays a complex organization with nine exons producing diverse mRNA variants due to alternative splicing at 5' and 3' ends and the existence of three different transcriptional promoters (P1, P2 and P3), two of which (P2 and P3) contain CpG islands. It is known that the expression of PTHrP isoforms may be differentially regulated in a developmental stage- and tissue-specific manner. To search for novel molecular markers of stemness/differentiation, here we have examined isoform expression in fat-derived mesenchymal stem cells both maintained in stem conditions and induced toward adipo- and osteogenesis. In addition, the expression of the splicing isoforms derived from P2 …
Expression of the Acetylcholine Receptor α-Subunit Gene is Associated with Paraneoplastic Myasthenia Gravis in Mixed Thymoma
2000
Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction [1]. The muscular AChR has been extensively characterized [2], but the etiology of MG is still obscure. Whether the muscular AChR or another (auto)antigen plays a role during the initiation of MG is unknown [3]. The muscular AChR is a pentameric ion channel composed of four different subunits. The α-subunit contains the acetylcholine binding site and the main epitopes recognized by MG autoantibodies [2]. The human muscle AChR α-subunit exists as two isoforms, P3A- and P3A+ [4]. This is a result of alternative splicing of the P3A exon located betwee…
Expression of fibronectin splice variants and oncofetal glycosylated fibronectin in the synovial membranes of patients with rheumatoid arthritis and …
2002
The aim of this study was to define and compare the expression of fibronectin (Fn) isoforms in synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA).Using monoclonal antibodies specific for total Fn, extra domain (ED)-A Fn, ED-B Fn, and oncofetal glycosylated Fn, we studied the expression of the Fn isoforms in synovium. Furthermore, in situ hybridization for the detection of ED-B Fn mRNA including a double labeling technique for the detection of cell type was applied.Strong expression of total Fn, ED-A Fn, oncofetal glycosylated Fn and, to a lesser extent, ED-B Fn could be demonstrated in the synovial lining layer in both RA and OA. Stromal and vessel expression…
Violation of the equivalence principle from light scalar dark matter
2018
In this paper, we study the local observational consequences of a violation of the Einstein Equivalence Principle induced by models of light scalar Dark Matter (DM). We focus on two different models where the scalar field couples linearly or quadratically to the standard model of matter fields. For both these cases, we derive the solutions of the scalar field. We also derive from first principles the expressions for two types of observables: (i) the local comparison of two atomic sensors that are differently sensitive to the constants of Nature and (ii) the local differential acceleration between two test-masses with different compositions. For the linear coupling, we recover that the signa…
Dynamical environments of relativistic binaries: The phenomenon of resonance shifting
2019
In this article, we explore both numerically and analytically how the dynamical environments of mildly relativistic binaries evolve with increasing the general relativity factor $\gamma$ (the normalized inverse of the binary size measured in the units of the gravitational radius corresponding to the total mass of the system). Analytically, we reveal a phenomenon of the relativistic shifting of mean-motion resonances: on increasing $\gamma$, the resonances between the test particle and the central binary shift, due to the relativistic variation of the mean motions of the primary and secondary binaries and the relativistic advance of the tertiary's pericenter. To exhibit the circumbinary dyna…
CD45 and multiple sclerosis: the exon 4 C77G polymorphism (additional studies and meta-analysis) and new markers
2003
We re-evaluated the association with multiple sclerosis (MS) of the C77G splicing regulatory variation in the CD45 gene and screened for new mutations the three alternatively spliced exons (#4, 5 and 6). No association with C77G was detected in two groups of patients (total=448) and controls (total=559) from Northern and Southern Italy. When excluding the first published study indicating a positive association, a meta-analysis of the five further studies conducted to date (including the present one) led to a non-significant combined odds ratio (OR) of 1.11. None of the four newly identified nucleotide substitutions, namely C77T (Pro59Pro) in exon 4, G69C (Asp121His) in exon 5, T127A (Ile187…
Cutting Edge: IL-6–Driven Immune Dysregulation Is Strictly Dependent on IL-6R α-Chain Expression
2020
Abstract IL-6 binds to the IL-6R α-chain (IL-6Rα) and signals via the signal transducer gp130. Recently, IL-6 was found to also bind to the cell surface glycoprotein CD5, which would then engage gp130 in the absence of IL-6Rα. However, the biological relevance of this alternative pathway is under debate. In this study, we developed a mouse model, in which murine IL-6 is overexpressed in a CD11c-Cre–dependent manner. Transgenic mice developed a lethal immune dysregulation syndrome with increased numbers of Ly-6G+ neutrophils and Ly-6Chi monocytes/macrophages. IL-6 overexpression promoted activation of CD4+ T cells while suppressing CD5+ B-1a cell development. However, additional ablation of …
Lurasidone in the Treatment of Bipolar Depression: Systematic Review of Systematic Reviews
2017
Introduction. A burgeoning number of systematic reviews considering lurasidone in the treatment of bipolar depression have occurred since its Food and Drug Administration extended approval in 2013. While a paucity of available quantitative evidence still precludes preliminary meta-analysis on the matter, the present quality assessment of systematic review of systematic reviews, nonetheless, aims at highlighting current essential information on the topic. Methods. Both published and unpublished systematic reviews about lurasidone mono- or adjunctive therapy in the treatment of bipolar depression were searched by two independent authors inquiring PubMed/Cochrane/Embase/Scopus from inception u…
Alterations of pre-mRNA splicing in cancer
2005
Recent genomewide analyses of alternative splicing (AS) indicate that up to 70% of human genes may have alternative splice forms, suggesting that AS together with various posttranslational modifications plays a major role in the production of proteome complexity. Splice-site selection under normal physiological conditions is regulated in the developmental stage in a tissue type-specific manner by changing the concentrations and the activity of splicing regulatory proteins. Whereas spliceosomal errors resulting in the production of aberrant transcripts rarely occur in normal cells, they seem to be an intrinsic property of cancer cells. Changes in splice-site selection have been observed in v…