Search results for "DOMAIN"

T helper cell polarisation in coeliac disease: any (T-)bet ?

2004

Recent data strongly support the view that coeliac disease is a Th1 mediated inflammatory disease as both interferon γ production and T-bet levels in gut infiltrating cells are upregulated The puzzling observation on high interferon γ (IFN-γ) but low interleukin (IL)-12 levels in coeliac disease (CD) has resulted in questions about the underlying principles of T helper cell polarisation. In this issue of G ut ,1 the molecular basis of T helper cell polarisation in CD has been illuminated by the finding that T-bet, the master transcription factor of T helper cell type 1 (Th1) cells, is upregulated in this disease [see page 1090] . The past decade has witnessed a dramatic improvement in our p…

The mitochondrial protein TCAIM regulates activation of T cells and thereby promotes tolerance induction of allogeneic transplants.

2013

Primary T cell activation and effector cell differentiation is required for rejection of allogeneic grafts in naive recipients. It has become evident, that mitochondria play an important role for T cell activation. Expression of several mitochondrial proteins such as TCAIM (T cell activation inhibitor, mitochondrial) is down-regulated upon T cell receptor triggering. Here we report that TCAIM inhibited spontaneous development of memory and effector T cells. CD4(+) T cells from Tcaim knock-in (KI) mice showed reduced activation, cytokine secretion and proliferation in vitro. Tcaim KI T cells tolerated allogeneic skin grafts upon transfer into Rag-1 KO mice. CD4(+) and CD8(+) T cells from the…

Diacylglycerol-containing oleic acid induces increases in [Ca(2+)](i) via TRPC3/6 channels in human T-cells.

2011

Though most of the studies have focused on the effects of free fatty acids on T-cell activation, fatty acids incorporated into plasma membrane phospholipids may also affect cell signaling via diacylglycerol (DAG), generally produced by phospholipid hydrolysis. In the present study, we have synthesized a DAG-containing oleic acid and studied its implication in the modulation of calcium signaling in human Jurkat T-cells. 1-palmitoyl-2-oleoyl-sn-glycerol (POG) induced a dose-dependent increase in [Ca(2+)](i). This effect was due to the presence of oleic acid at the sn-2 position as no differences were observed between POG and 1-stearoly-2-oleoyl-sn-glycerol (SOG). However, the substitution of …

In silico characterization of an Iroquois family-related homeodomain protein.

2005

Homeobox genes have been demonstrated to play important roles during cancer differentiation and embryonic development. The subset of Iroquois-related homeobox genes (IRXs) have furthermore been. demonstrated to be involved in several embryonic developmental processes such as patterning of the anterior-posterior and dorso-ventral axis, as well as specific regions of the central nervous system, and differentiation of the otic vesicle, branchial epithelium, and limbs. We have characterized a novel homeodomain protein and corresponding gene by means of computational biology. Since the protein sequence displayed high similarity to the human IRX proteins, the newly identified homeodomain protein …

Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet.

2002

Human asthma is associated with airway infiltration by T helper 2 (TH2) lymphocytes. We observed reduced expression of the TH1 transcription factor, T-bet, in T cells from airways of patients with asthma compared with that in T cells from airways of nonasthmatic patients, suggesting that loss of T-bet might be associated with asthma. Mice with a targeted deletion of the T-bet gene and severe combined immunodeficient mice receiving CD4+cells from T-bet knockout mice spontaneously demonstrated multiple physiological and inflammatory features characteristic of asthma. Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic h…

Using Machine Learning to Characterize Atrial Fibrotic Substrate From Intracardiac Signals With a Hybrid in silico and in vivo Dataset

2021

[EN] In patients with atrial fibrillation, intracardiac electrogram signal amplitude is known to decrease with increased structural tissue remodeling, referred to as fibrosis. In addition to the isolation of the pulmonary veins, fibrotic sites are considered a suitable target for catheter ablation. However, it remains an open challenge to find fibrotic areas and to differentiate their density and transmurality. This study aims to identify the volume fraction and transmurality of fibrosis in the atrial substrate. Simulated cardiac electrograms, combined with a generalized model of clinical noise, reproduce clinically measured signals. Our hybrid dataset approach combines in silico and clinic…

Dependence of Terahertz Emission and Detection in Photoconductive Antennas on Laser Parameters

In this study, we employ a standard Terahertz time-domain spectroscopy (THz-TDS) setup based on two photoconductive antennas (PCAs) for THz radiation generation and detection. The characterization of the emission and detection performance as a function of the input pulse wavelength and bandwidth is performed.

Strategies to Target ADAM17 in Disease: From Its Discovery to the iRhom Revolution

2021

For decades, disintegrin and metalloproteinase 17 (ADAM17) has been the object of deep investigation. Since its discovery as the tumor necrosis factor convertase, it has been considered a major drug target, especially in the context of inflammatory diseases and cancer. Nevertheless, the development of drugs targeting ADAM17 has been harder than expected. This has generally been due to its multifunctionality, with over 80 different transmembrane proteins other than tumor necrosis factor α (TNF) being released by ADAM17, and its structural similarity to other metalloproteinases. This review provides an overview of the different roles of ADAM17 in disease and the effects of its ablation in a n…

Design & Optimization of Large Cylindrical Radomes with Subcell and Non-Orthogonal FDTD Meshes Combined with Genetic Algorithms

2021

The word radome is a contraction of radar and dome. The function of radomes is to protect antennas from atmospheric agents. Radomes are closed structures that protect the antennas from environmental factors such as wind, rain, ice, sand, and ultraviolet rays, among others. The radomes are passive structures that introduce return losses, and whose proper design would relax the requirement of complex front-end elements such as amplifiers. The radome consists mostly in a thin dielectric curved shape cover and sometimes needs to be tuned using metal inserts to cancel the capacitive performance of the dielectric. Radomes are in the near field region of the antennas and a full wave analysis of th…

Binding properties and stability of the Ras-association domain of Rap1-GTP interacting adapter molecule (RIAM).

2012

The Rap1-GTP interacting adapter protein (RIAM) is an important protein in Rap1-mediated integrin activation. By binding to both Rap1 GTPase and talin, RIAM recruits talin to the cell membrane, thus facilitating talin-dependent integrin activation. In this article, we studied the role of the RIAM Ras-association (RA) and pleckstrin-homology (PH) domains in the interaction with Rap1. We found that the RA domain was sufficient for GTP-dependent interaction with Rap1B, and the addition of the PH domain did not change the binding affinity. We also detected GTP-independent interaction of Rap1B with the N-terminus of RIAM. In addition, we found that the PH domain stabilized the RA domain both in …