Search results for "REGION"

2018

The IgMi mouse fails to secrete antibodies or class switch its BCR from IgM. Our study reveals that other cellular compartments, including B-cell subsets, DC subsets, GC B cells and TFH cells are perturbed in the IgMi mouse, thus presenting important additional considerations when using the mouse to explore the role of secreted antibody.

HSP110 sustains chronic NF-κB signaling in activated B cell diffuse large B cell lymphoma through MyD88 stabilization

2018

International audience; Activated B cell diffuse large B cell lymphoma (ABC-DLBCL) is an aggressive lymphoproliferative disorder involving chronic NF-κB activation. Several mutations in the BCR and the MyD88 signaling pathway components, such as MyD88 L265P, are implicated in this aberrant activation. Among heat-shock proteins, HSP110 has recently been identified as a pro- survival and/or proliferation factor in many cancers but its role in ABC-DLBCL survival mechanisms remained to be established. We observed that shRNA-mediated HSP110 silencing decreased the survival of several ABC-DLBCL cell lines, decreased IgM-MyD88 co-localization and subsequent NF-κB signaling. Conversely, over-expres…

Loss-of-function and missense variants in NSD2 cause decreased methylation activity and are associated with a distinct developmental phenotype

2021

Purpose Despite a few recent reports of patients harboring truncating variants in NSD2, a gene considered critical for the Wolf–Hirschhorn syndrome (WHS) phenotype, the clinical spectrum associated with NSD2 pathogenic variants remains poorly understood. Methods We collected a comprehensive series of 18 unpublished patients carrying heterozygous missense, elongating, or truncating NSD2 variants; compared their clinical data to the typical WHS phenotype after pooling them with ten previously described patients; and assessed the underlying molecular mechanism by structural modeling and measuring methylation activity in vitro. Results The core NSD2-associated phenotype includes mostly mild dev…

Simultaneous Boron Ion‐Channel/Growth Factor Receptor Activation for Enhanced Vascularization

2018

[EN] Boron ion is essential in metabolism and its concentration is regulated by ion-channel NaBC1. NaBC1 mutations cause corneal dystrophies such as Harboyan syndrome. Here we propose a 3D molecular model for NaBC1 and show that simultaneous stimulation of NaBC1 and vascular growth factor receptors (VEGFR) promote angiogenesis in vitro and in vivo with ultra-low concentrations of VEGF. We show Human Umbilical Vein Endothelial Cells (HUVEC) organization into tubular structures indicative of vascularization potential. Enhanced cell sprouting was found only in the presence of VEGF and boron, effect abrogated after blocking NaBC1. We demonstrate that stimulated NaBC1 promotes angiogenesis via P…

Arrestin-β-1 Physically Scaffolds TSH and IGF1 Receptors to Enable Crosstalk

2019

Endogenously expressed TSH receptors (TSHRs) on orbital fibroblasts of patients with Graves ophthalmopathy (GO) use crosstalk with IGF1 receptors (IGF1R) to synergistically stimulate secretion of hyaluronan (HA), a major component of GO pathology. We previously showed crosstalk occurred upstream of mitogen-activated protein kinase (ERK) phosphorylation. Because other G protein-coupled receptors engage arrestin-β-1 (ARRB1) and ERK, we tested whether ARRB1 was a necessary component of TSHR/IGF1R crosstalk. HA secretion was stimulated by the TSHR-stimulating monoclonal antibodies M22 and KSAb1, or immunoglobulins from patients with GO (GO-Igs). Treatment with M22, as previously shown, resulted…

miR-128 Is Implicated in Stress Responses by Targeting MAFG in Skeletal Muscle Cells.

2017

MAFG (v-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog G) is a bZIP-type transcriptional regulator that belongs to the small MAF (sMAFs) protein family. By interacting with other bZIP transcription factors, sMAFs can form homo- and heterodimers governing either repressive or activating transcriptional functions. As heterodimeric partner of Nrf2, MAFG positively influences the ARE-dependent antioxidant/xenobiotic pathways, at least in condition of a correct MAFG:Nrf2 balance. MicroRNAs (miRs) participate to different regulatory networks being involved as fine-tuning regulators of gene expression. However, the connections between cellular surveillance to stresses mediated by MAFG:…

Modulation of brain PUFA content in different experimental models of mice.

2016

International audience; The relative amounts of arachidonic acid (AA) and docosahexaenoic acid (DHA) govern the different functions of the brain. Their brain levels depend on structures considered, on fatty acid dietary supply and the age of animals. To have a better overview of the different models available in the literature we here compared the brain fatty acid composition in various mice models (C57BL/6J, CD1, Fat-1, SAMP8 mice) fed with different n-3 PUFA diets (deficient, balanced, enriched) in adults and aged animals. Our results demonstrated that brain AA and DHA content is 1) structure-dependent; 2) strain-specific; 3) differently affected by dietary approaches when compared to gen…

A multidimensional network approach reveals microRNAs as determinants of the mesenchymal colorectal cancer subtype

2016

Colorectal cancer (CRC) is a heterogeneous disease posing a challenge for accurate classification and treatment of this malignancy. There is no common genetic molecular feature that would allow for the identification of patients at risk for developing recurrences and thus selecting patients who would benefit from more stringent therapies still poses a major clinical challenge. Recently, an international multicenter consortium (CRC Subtyping Consortium) was established aiming at the classification of CRC patients in biologically homogeneous CRC subtypes. Four consensus molecular subtypes (CMSs) were identified, of which the mesenchymal CMS4 presented with worse prognosis signifying the impor…

Dairy product consumption and risk of colorectal cancer in an older mediterranean population at high cardiovascular risk.

2018

Prospective studies have reported an inverse association between the consumption of total dairy products and milk and the risk of colorectal cancer (CRC). Nonetheless, there is little and inconsistent evidence regarding subtypes of dairy product and CRC risk. We assessed the associations between the consumption of total dairy products, their different subtypes and CRC risk in older Mediterranean individuals at high cardiovascular risk. We analyzed data from 7,216 men and women (55-80 years) without CRC at baseline from the PREvencion con DIeta MEDiterranea study. Individuals were recruited between 2003 and 2009 and followed up until December 2012. At baseline and yearly thereafter, consumpt…

Investigation of SOSTDC1 gene in non-syndromic patients with supernumerary teeth

2018

WOS: 000443304400005 PubMed: 30148467 Background: The etiology of supernumerary teeth is still unclear however heredity is believed to be a major factor and this idea was supported by several case reports. Recently, a relationship between supernumerary tooth formation and deficiency of Uterine Sensitization Associated Gene-1 (Usag-1), a rat gene that is expressed in sensitized endometrium, was reported in mice. The human homolog gene for Usag-1, Sclerostin Domain Containing 1 (SOSTDC1), shows 85% identity with mouse Usag-1. The present study aimed to investigate SOSTDC1 coding regions in non-syndromic patients with one or more supernumerary teeth. Material and Methods: Twenty-five non-syndr…