Search results for "script"
showing 10 items of 5143 documents
Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metab…
2021
Gut: first published.
Drug-induced chromatin accessibility changes associate with sensitivity to liver tumor promotion
2019
This work explores quantitative chromatin accessibility, transcriptional and cis-acting gene regulatory variations underlying mouse strain–specific differences in drug-induced liver tumor promotion sensitivity.
Disruption of the ATXN1-CIC complex causes a spectrum of neurobehavioral phenotypes in mice and humans
2017
International audience; Gain-of-function mutations in some genes underlie neurodegenerative conditions, whereas loss-of-function mutations in the same genes have distinct phenotypes. This appears to be the case with the protein ataxin 1 (ATXN1), which forms a transcriptional repressor complex with capicua (CIC). Gain of function of the complex leads to neurodegeneration, but ATXN1-CIC is also essential for survival. We set out to understand the functions of the ATXN1-CIC complex in the developing forebrain and found that losing this complex results in hyperactivity, impaired learning and memory, and abnormal maturation and maintenance of upper-layer cortical neurons. We also found that CIC …
How miR-31-5p and miR-33a-5p Regulates SP1/CX43 Expression in Osteoarthritis Disease: Preliminary Insights
2021
Osteoarthritis (OA) is a degenerative bone disease that involved micro and macro-environment of joints. To date, there are no radical curative treatments for OA and novel therapies are mandatory. Recent evidence suggests the role of miRNAs in OA progression. In our previous studies, we demonstrated the role of miR-31-5p and miR-33a families in different bone regeneration signaling. Here, we investigated the role of miR-31-5p and miR-33a-5p in OA progression. A different expression of miR-31-5p and miR-33a-5p into osteoblasts and chondrocytes isolated from joint tissues of OA patients classified in based on different Kellgren and Lawrence (KL) grading was highlighted
Evidence for PTGER4 ,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level
2018
Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine-mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 x 10(-04)) and on chromosome …
The STAT3 Inhibitor Galiellalactone Reduces IL6-Mediated AR Activity in Benign and Malignant Prostate Models
2018
IL6/STAT3 signaling is associated with endocrine therapy resistance in prostate cancer, but therapies targeting this pathway in prostate cancer were unsuccessful in clinical trials so far. The mechanistic explanation for this phenomenon is currently unclear; however, IL6 has pleiotropic effects on a number of signaling pathways, including the androgen receptor (AR). Therefore, we investigated IL6-mediated AR activation in prostate cancer cell lines and ex vivo primary prostate tissue cultures in order to gain a better understanding on how to inhibit this process for future clinical trials. IL6 significantly increased androgen-dependent AR activity in LNCaP cells but importantly did not infl…
Variant recurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense var…
2019
Next-generation sequencing has revealed the major impact of de novo variants (DNVs) in developmental disorders (DD) such as intellectual disability, autism, and epilepsy. However, a substantial fraction of these predicted pathogenic DNVs remains challenging to distinguish from background DNVs, notably the missense variants acting via nonhaploinsufficient mechanisms on specific amino acid residues. We hypothesized that the detection of the same missense variation in at least two unrelated individuals presenting with a similar phenotype could be a powerful approach to reveal novel pathogenic variants. We looked for variations independently present in both our database of >1200 solo exomes and…
Novel Mutations in the NKX2.1 gene and the PAX8 gene in a Boy with Brain-Lung-Thyroid Syndrome
2017
Abstract Objective To elucidate the molecular mechanism which causes thyroid dysgenesis (TD) in a boy with brain-lung-thyroid syndrome. Design, patients, measurements We describe a patient with TD, respiratory disease and cerebral palsy who is heterozygous for mutations in two different genes, the PAX8 (p.E234K) and the NKX2.1 (p.A329GfsX108). In vitro studies were performed to functionally characterize these mutations. Congenital hypothyroidism (CH) was identified by neonatal screening associated with a hypoplastic thyroid gland. Postpartum he developed a brain-lung-thyroid syndrome with severe respiratory failure, symptomatic epilepsy and a considerable psychomotor retardation. The DNA-bi…
Systemic blockade of ACVR2B ligands attenuates muscle wasting in ischemic heart failure without compromising cardiac function
2020
Signaling through activin receptors regulates skeletal muscle mass and activin receptor 2B (ACVR2B) ligands are also suggested to participate in myocardial infarction (MI) pathology in the heart. In this study, we determined the effect of systemic blockade of ACVR2B ligands on cardiac function in experimental MI, and defined its efficacy to revert muscle wasting in ischemic heart failure (HF). Mice were treated with soluble ACVR2B decoy receptor (ACVR2B-Fc) to study its effect on post-MI cardiac remodeling and on later HF. Cardiac function was determined with echocardiography, and myocardium analyzed with histological and biochemical methods for hypertrophy and fibrosis. Pharmacological blo…
LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells
2015
Elevated lactate dehydrogenase A (LDHA) expression is associated with poor outcome in tumor patients. Here we show that LDHA-associated lactic acid accumulation in melanomas inhibits tumor surveillance by T and NK cells. In immunocompetent C57BL/6 mice, tumors with reduced lactic acid production (Ldhalow) developed significantly slower than control tumors and showed increased infiltration with IFN-γ-producing T and NK cells. However, in Rag2-/-γc-/- mice, lacking lymphocytes and NK cells, and in Ifng-/- mice, Ldhalow and control cells formed tumors at similar rates. Pathophysiological concentrations of lactic acid prevented upregulation of nuclear factor of activated T cells (NFAT) in T and…