Search results for "Nuclear"
showing 10 items of 26799 documents
A Novel Micronutrient Blend Mimics Calorie Restriction Transcriptomics in Multiple Tissues of Mice and Increases Lifespan and Mobility in C. elegans
2020
Background: We previously described a novel micronutrient blend that behaves like a putative calorie restriction mimetic. The aim of this paper was to analyze the beneficial effects of our micronutrient blend in mice and C. elegans, and compare them with calorie restriction. Methods: Whole transcriptomic analysis was performed in the brain cortex, skeletal muscle and heart in three groups of mice: old controls (30 months), old + calorie restriction and old + novel micronutrient blend. Longevity and vitality were tested in C. elegans. Results: The micronutrient blend elicited transcriptomic changes in a manner similar to those in the calorie-restricted group and different from those in the c…
Estimating the Patient-Specific Relative Stiffness Between a Hepatic Lesion and the Liver Parenchyma
2017
This paper presents a novel non-invasive methodology to obtain the patient-specific relative stiffness between a hepatic lesion and the liver parenchyma in vivo. This relative stiffness can be used as a biomarker about the type of lesion. This biomarker together with the rest of pathological information can be used to plan a biopsy, an image-guide intervention or a radiation therapy. This relative stiffness is estimated by means of the finite element simulation of the breathing process, which is embedded in an optimization routine based on genetic algorithms. This routine was aimed at finding the patient-specific relative stiffness between a hepatic lesion and the liver parenchyma for the p…
Tissue microenvironment dictates the fate and tumor-suppressive function of type 3 ILCs
2017
Nussbaum et al. found that tumor suppression through innate lymphoid cells (ILCs) cannot be predicted solely based on the ILC phenotype and lineage but that their immune properties are shaped both by their ontogeny and by the tissue microenvironment they reside in.
Insulin Dissociates the Effects of Liver X Receptor on Lipogenesis, Endoplasmic Reticulum Stress, and Inflammation
2016
IF 4.258; International audience; Diabetes is characterized by increased lipogenesis as well as increased endoplasmic reticulum (ER) stress and inflammation. The nuclear hormone receptor liver X receptor (LXR) is induced by insulin and is a key regulator of lipid metabolism. It promotes lipogenesis and cholesterol efflux, but suppresses endoplasmic reticulum stress and inflammation. The goal of these studies was to dissect the effects of insulin on LXR action. We used antisense oligonucleotides to knock down Lxr alpha in mice with hepatocytespecific deletion of the insulin receptor and their controls. We found, surprisingly, that knock-out of the insulin receptor and knockdown of Lxr alpha …
T cell Polarization toward T(H)2/T(FH)2 and T(H)17/T(FH)17 in Patients with IgG4-related Disease
2017
International audience; IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease's pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocyte's subsets were analyzed by flow cytometry, with analysis of T(H)1/T(H)2/T(H)17, T-FH cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy contro…
Human Breast Milk NMR Metabolomic Profile across Specific Geographical Locations and Its Association with the Milk Microbiota
2018
The composition of human breast milk is highly variable, and it can be influenced by genetics, diet, lifestyle, and other environmental factors. This study aimed to investigate the impact of geographical location and mode of delivery on the nuclear magnetic resonance spectroscopy (NMR) metabolic profile of breast milk and its relationship with the milk microbiome. Human milk metabolic and microbiota profiles were determined using NMR and 16S rRNA gene sequencing, respectively, in 79 healthy women from Finland, Spain, South Africa, and China. Up to 68 metabolites, including amino acids, oligosaccharides, and fatty acid-associated metabolites, were identified in the milk NMR spectra. The meta…
Increased Muscleblind levels by chloroquine treatment improve myotonic dystrophy type 1 phenotypes in in vitro and in vivo models
2019
Myotonic dystrophy type 1 (DM1) is a life-threatening and chronically debilitating neuromuscular disease caused by the expansion of a CTG trinucleotide repeat in the 3′ UTR of the DMPK gene. The mutant RNA forms insoluble structures capable of sequestering RNA binding proteins of the Muscleblind-like (MBNL) family, which ultimately leads to phenotypes. In this work, we demonstrate that treatment with the antiautophagic drug chloroquine was sufficient to up-regulate MBNL1 and 2 proteins in Drosophila and mouse (HSA LR ) models and patient-derived myoblasts. Extra Muscleblind was functional at the molecular level and improved splicing events regulated by MBNLs in all disease models. In vivo,…
Discovery of Natural Products as Novel and Potent FXR Antagonists by Virtual Screening
2018
Farnesoid X receptor (FXR) is a member of nuclear receptor family involved in multiple physiological processes through regulating specific target genes. The critical role of FXR as a transcriptional regulator makes it a promising target for diverse diseases, especially those related to metabolic disorders such as diabetes and cholestasis. However, the underlying activation mechanism of FXR is still a blur owing to the absence of proper FXR modulators. To identify potential FXR modulators, an in-house natural product database (NPD) containing over 4,000 compounds was screened by structure-based virtual screening strategy and subsequent hit-based similarity searching method. After the yeast t…
Genomic and non-genomic mechanisms of action of thyroid hormones and their catabolite 3,5-diiodo-l-thyronine in Mammals
2020
Since the realization that the cellular homologs of a gene found in the retrovirus that contributes to erythroblastosis in birds (v-erbA), i.e. the proto-oncogene c-erbA encodes the nuclear receptors for thyroid hormones (THs), most of the interest for THs focalized on their ability to control gene transcription. It was found, indeed, that, by regulating gene expression in many tissues, these hormones could mediate critical events both in development and in adult organisms. Among their effects, much attention was given to their ability to increase energy expenditure, and they were early proposed as anti-obesity drugs. However, their clinical use has been strongly challenged by the concomita…
Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2
2016
We show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728–1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nM). Our NMR solution complex structure together with isothermal titration calorimetry data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure, indicating that a transient or fluctuating polyelectrostatic interaction accounts for this …