Search results for "genetics [Transcriptome]"
showing 10 items of 3033 documents
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.
Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes
2019
[Background] Early life is a period of drastic epigenetic remodeling in which the epigenome is especially sensitive to extrinsic and intrinsic influence. However, the epigenome-wide dynamics of the DNA methylation changes that occur during this period have not been sufficiently characterized in longitudinal studies.
G6PD protects from oxidative damage and improves healthspan in mice
2016
S.N.-P. and P.J.F.-M. have been funded by the Spanish Association Against Cancer(aecc). Work in the laboratory of M.S. is funded by the CNIO and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund(SAF project), the European Research Council (ERC Advanced Grant), the Regional Government of Madrid co-funded by the European Social Fund (ReCaRe project), the European Union (RISK-IR project), the Botin Foundation and Banco Santander(Santander Universities Global Division), the Ramon Areces Foundation, and the AXA Foundation. Work in the laboratory of J.V. was supported by grants SAF2013-44663-R,from the Spanish Ministry of Education and Science (MEC…
Active acetylcholine receptors prevent the atrophy of skeletal muscles and favor reinnervation
2020
Denervation of skeletal muscles induces severe muscle atrophy, which is preceded by cellular alterations such as increased plasma membrane permeability, reduced resting membrane potential and accelerated protein catabolism. The factors that induce these changes remain unknown. Conversely, functional recovery following denervation depends on successful reinnervation. Here, we show that activation of nicotinic acetylcholine receptors (nAChRs) by quantal release of acetylcholine (ACh) from motoneurons is sufficient to prevent changes induced by denervation. Using in vitro assays, ACh and non-hydrolysable ACh analogs repressed the expression of connexin43 and connexin45 hemichannels, which prom…
Injured Axons Instruct Schwann Cells to Build Constricting Actin Spheres to Accelerate Axonal Disintegration
2019
Summary: After a peripheral nerve lesion, distal ends of injured axons disintegrate into small fragments that are subsequently cleared by Schwann cells and later by macrophages. Axonal debris clearing is an early step of the repair process that facilitates regeneration. We show here that Schwann cells promote distal cut axon disintegration for timely clearing. By combining cell-based and in vivo models of nerve lesion with mouse genetics, we show that this mechanism is induced by distal cut axons, which signal to Schwann cells through PlGF mediating the activation and upregulation of VEGFR1 in Schwann cells. In turn, VEGFR1 activates Pak1, leading to the formation of constricting actomyosin…
β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain
2017
Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move t…
Bi- and uniciliated ependymal cells define continuous floor-plate-derived tanycytic territories
2017
Multiciliated ependymal (E1) cells line the brain ventricles and are essential for brain homeostasis. We previously identified in the lateral ventricles a rare ependymal subpopulation (E2) with only two cilia and unique basal bodies. Here we show that E2 cells form a distinct biciliated epithelium extending along the ventral third into the fourth ventricle. In the third ventricle floor, apical profiles with only primary cilia define an additional uniciliated (E3) epithelium. E2 and E3 cells' ultrastructure, marker expression and basal processes indicate that they correspond to subtypes of tanycytes. Using sonic hedgehog lineage tracing, we show that the third and fourth ventricle E2 and E3 …
An Experimental Model of Diet-Induced Metabolic Syndrome in Rabbit: Methodological Considerations, Development, and Assessment
2018
In recent years, obesity and metabolic syndrome (MetS) have become a growing problem for public health and clinical practice, given their increased prevalence due to the rise of sedentary lifestyles and unhealthy eating habits. Thanks to animal models, basic research can investigate the mechanisms underlying pathological processes such as MetS. Here, we describe the methods used to develop an experimental rabbit model of diet-induced MetS and its assessment. After a period of acclimation, animals are fed a high-fat (10% hydrogenated coconut oil and 5% lard), high-sucrose (15% sucrose dissolved in water) diet for 28 weeks. During this period, several experimental procedures were performed to…
Neurovascular EGFL7 regulates adult neurogenesis in the subventricular zone and thereby affects olfactory perception
2016
Adult neural stem cells reside in a specialized niche in the subventricular zone (SVZ). Throughout life they give rise to adult-born neurons in the olfactory bulb (OB), thus contributing to neural plasticity and pattern discrimination. Here, we show that the neurovascular protein EGFL7 is secreted by endothelial cells and neural stem cells (NSCs) of the SVZ to shape the vascular stem-cell niche. Loss of EGFL7 causes an accumulation of activated NSCs, which display enhanced activity and re-entry into the cell cycle. EGFL7 pushes activated NSCs towards quiescence and neuronal progeny towards differentiation. This is achieved by promoting Dll4-induced Notch signalling at the blood vessel-stem …
Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle
2015
Calorie restriction (CR) retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3-15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001). HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to…