scholarly journals Retinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a Focus on Neuropathological Involvement

2022 ◽  
Author(s):  
Samridhi Sharma ◽  
Ting Shen ◽  
Nitin Chitranshi ◽  
Veer Gupta ◽  
Devaraj Basavarajappa ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Critical Role ◽  
Future Research ◽  
Protective Effects ◽  
Biochemical Processes ◽  
Expression Of Genes ◽  
X Receptors ◽  
Nuclear Receptor Family ◽  
Cumulative Evidence ◽  
Neuronal Stress

AbstractRetinoid X receptors (RXRs) present a subgroup of the nuclear receptor superfamily with particularly high evolutionary conservation of ligand binding domain. The receptor exists in α, β, and γ isotypes that form homo-/heterodimeric complexes with other permissive and non-permissive receptors. While research has identified the biochemical roles of several nuclear receptor family members, the roles of RXRs in various neurological disorders remain relatively under-investigated. RXR acts as ligand-regulated transcription factor, modulating the expression of genes that plays a critical role in mediating several developmental, metabolic, and biochemical processes. Cumulative evidence indicates that abnormal RXR signalling affects neuronal stress and neuroinflammatory networks in several neuropathological conditions. Protective effects of targeting RXRs through pharmacological ligands have been established in various cell and animal models of neuronal injury including Alzheimer disease, Parkinson disease, glaucoma, multiple sclerosis, and stroke. This review summarises the existing knowledge about the roles of RXR, its interacting partners, and ligands in CNS disorders. Future research will determine the importance of structural and functional heterogeneity amongst various RXR isotypes as well as elucidate functional links between RXR homo- or heterodimers and specific physiological conditions to increase drug targeting efficiency in pathological conditions.

scholarly journals Liver X Receptors Interact with Corepressors to Regulate Gene Expression

2003 ◽  
Vol 17 (6) ◽  
pp. 1019-1026 ◽  
Author(s):  
Xiao Hu ◽  
Suzhen Li ◽  
Jun Wu ◽  
Chunsheng Xia ◽  
Deepak S. Lala
Keyword(s):  
Gene Expression ◽  
Nuclear Receptor ◽  
Target Gene ◽  
Critical Role ◽  
Cholesterol Homeostasis ◽  
Liver X Receptors ◽  
Regulate Gene Expression ◽  
Target Gene Expression ◽  
X Receptors ◽  
Regulate Gene

Abstract Liver X receptors (LXRs) are members of the nuclear receptor superfamily that regulate gene expression in response to oxysterols and play a critical role in cholesterol homeostasis by regulating genes that are involved in cholesterol transport, catabolism, and triglyceride synthesis. Oxysterols and synthetic agonists bind LXRs and activate transcription by recruiting coactivator proteins. The role of LXRs in regulating target gene expression in the absence of ligand is unknown. Here we show that LXRs interact with corepressors, N-CoR (nuclear receptor corepressor) and SMRT (silent mediator of retinoic acid receptor and thyroid receptor), which are released upon binding agonists. The LXR-corepressor interaction is isoform selective, wherein LXRα has a very strong interaction with corepressors and LXRβ only shows weak interaction. LXRs also exhibit a preference for interacting with N-CoR vs. SMRT. Similar to other nuclear receptors, mutations in the LXR helix 3 and 4 region abolish corepressor interaction. Using a transient transfection assay, we demonstrate that LXR represses transcription that can be further increased by cotransfecting N-CoR into cells. Chromatin immunoprecipitation experiments further indicated that N-CoR is recruited onto endogenous LXR target genes, and addition of LXR agonists releases N-CoR from their promoters. Collectively, these results suggest that corepressors play an important role in regulating LXR target gene expression.

scholarly journals Oxysterol Nuclear Receptor LXRβ Regulates Cholesterol Homeostasis and Contractile Function in Mouse Uterus

2006 ◽  
Vol 282 (7) ◽  
pp. 4693-4701 ◽  
Author(s):  
Kevin Mouzat ◽  
Magali Prod'Homme ◽  
David H. Volle ◽  
Benoit Sion ◽  
Pierre Déchelotte ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Nuclear Receptor ◽  
Target Genes ◽  
Contractile Function ◽  
Contractile Activity ◽  
Critical Role ◽  
Cholesterol Homeostasis ◽  
Protective Mechanism ◽  
Mouse Uterus ◽  
Expression Of Genes

The uterus is an organ where lipid distribution plays a critical role for its function. Here we show that nuclear receptor for oxysterols LXRβ prevents accumulation of cholesteryl esters in mouse myometrium by controlling expression of genes involved in cholesterol efflux and storage (abca1 and abcg1). Upon treatment with an LXR agonist that mimics activation by oxysterols, expression of these target genes was increased in wild-type mice, whereas under basal conditions, lxrα;β-/- mice exhibited a marked decrease in abcg1 accumulation. This change resulted in a phenotype of cholesteryl ester accumulation. Besides, a defect of contractile activity induced by oxytocin or PGF2α was observed in mice lacking LXRβ. These results imply that LXRβ provides a safety valve to limit cholesteryl ester levels as a basal protective mechanism in the uterus against cholesterol accumulation and is necessary for a correct induction of contractions.

Attachment Organization in Suicide Prevention Research

Crisis ◽  
2014 ◽  
Vol 35 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Amanda Venta ◽  
Carla Sharp
Keyword(s):  
Risk Factors ◽  
Suicidal Ideation ◽  
Suicide Attempt ◽  
Interpersonal Relationships ◽  
Suicide Ideation ◽  
Suicide Attempts ◽  
Critical Role ◽  
Self Report ◽  
Future Research ◽  
Self Harm

Background: Identifying risk factors for suicide-related thoughts and behaviors (SRTB) is essential among adolescents in whom SRTB remain a leading cause of death. Although many risk factors have already been identified, influential theories now suggest that the domain of interpersonal relationships may play a critical role in the emergence of SRTB. Because attachment has long been seen as the foundation of interpersonal functioning, we suggest that attachment insecurity warrants attention as a risk factor for SRTB. Aims: This study sought to explore relations between attachment organization and suicidal ideation, suicide attempts, and self-harm in an inpatient adolescent sample, controlling for demographic and psychopathological covariates. Method: We recruited 194 adolescents from an inpatient unit and assigned them to one of four attachment groups (secure, preoccupied, dismissing, or disorganized attachment). Interview and self-report measures were used to create four variables reflecting the presence or absence of suicidal ideation in the last year, single lifetime suicide attempt, multiple lifetime suicide attempts, and lifetime self-harm. Results: Chi-square and regression analyses did not reveal significant relations between attachment organization and SRTB, although findings did confirm previously established relations between psychopathology and SRTB, such that internalizing disorder was associated with increased self-harm, suicide ideation, and suicide attempt and externalizing disorder was associated with increased self-harm. Conclusion: The severity of this sample and methodological differences from previous studies may explain the nonsignificant findings. Nonsignificant findings may indicate that the relation between attachment organization and SRTB is moderated by other factors that should be explored in future research.

scholarly journals A Novel 13 bp Deletion within the NR6A1 Gene Is Significantly Associated with Growth Traits in Donkeys

Animals ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 681 ◽  
Author(s):  
Xiya Fang ◽  
Zhenyu Lai ◽  
Jie Liu ◽  
Chunlan Zhang ◽  
Shipeng Li ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Growth Traits ◽  
Polyacrylamide Gel Electrophoresis ◽  
Embryonic Stem ◽  
The Body ◽  
Economic Traits ◽  
Breeding Programs ◽  
Intron 1 ◽  
Group A ◽  
Nuclear Receptor Family

Nuclear receptor subfamily 6, group A, member 1 (NR6A1), as an important member of the nuclear receptor family, plays an important role in regulating growth, metabolism, and differentiation of embryonic stem cells. For this reason, the NR6A1 gene is considered to be a promising candidate for economic traits and was found to be associated with body size traits in many livestock. However, no studies have been conducted on NR6A1 in donkeys so far. Thus, in this research, we focused on donkeys and identified a 13 bp deletion in intron-1 of the NR6A1 gene among 408 individuals from Guanzhong and Dezhou donkeys using polyacrylamide gel electrophoresis. Three genotypes were identified, namely II, ID, and DD. The association analysis indicated that the body lengths and body heights5f genotype II individuals were significantly different to those of genotype ID in Dezhou donkeys. Conclusively, the 13 bp deletion was associated with growth traits in both Guanzhong donkeys and Dezhou donkeys, indicating that the NR6A1 gene could be a possible candidate gene in marker-assisted selection for donkey breeding programs.

scholarly journals Training may enhance early childhood educators’ self-efficacy to lead physical activity in childcare

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Brianne A. Bruijns ◽  
Andrew M. Johnson ◽  
Jennifer D. Irwin ◽  
Shauna M. Burke ◽  
Molly Driediger ◽  
...  
Keyword(s):  
Physical Activity ◽  
Early Childhood ◽  
Self Efficacy ◽  
Critical Role ◽  
Early Childhood Educators ◽  
Outdoor Play ◽  
Future Research ◽  
Intervention Component ◽  
Space Extension ◽  
The Impact

Abstract Background Early childhood educators (ECEs) play a critical role in promoting physical activity (PA) among preschoolers in childcare; thus, PA-related training for ECEs is essential. The Supporting PA in the Childcare Environment (SPACE) intervention incorporated: 1. shorter, more frequent outdoor play sessions; 2. provision of portable play equipment; and, PA training for ECEs. An extension of the SPACE intervention (the SPACE-Extension) incorporated only the shorter, more frequent outdoor play periods component of the original SPACE intervention. The purpose of this study was to explore the individual impact of these interventions on ECEs’ PA-related self-efficacy and knowledge. Methods ECEs from the SPACE (n = 83) and SPACE-Extension (n = 31) were administered surveys at all intervention time-points to assess: self-efficacy to engage preschoolers in PA (n = 6 items; scale 0 to 100); self-efficacy to implement the intervention (n = 6 items); and, knowledge of preschooler-specific PA and screen-viewing guidelines (n = 2 items). A linear mixed effects model was used to analyze the impact of each intervention on ECEs’ self-efficacy and knowledge and controlled for multiple comparison bias. Results The SPACE intervention significantly impacted ECEs’ self-efficacy to engage preschoolers in PA for 180 min/day (main effect), and when outdoor playtime was not an option (interaction effect). Further, the interaction model for ECEs’ knowledge of the total PA guideline for preschoolers approached significance when compared to the main effects model. Participants within the SPACE-Extension did not demonstrate any significant changes in self-efficacy or knowledge variables. Conclusions Findings from this study highlight the benefit of ECE training in PA with regard to fostering their PA-related self-efficacy and knowledge. Future research should explore the impact of PA training for ECEs uniquely in order to determine if this intervention component, alone, can produce meaningful changes in children’s PA behaviours at childcare.

scholarly journals A Review on Thermal Energy Modelling for Optimal Microgrids Management

Thermo ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 63-76
Author(s):  
Mengxuan Yan ◽  
Dongxiao Wang ◽  
Chun Sing Lai ◽  
Loi Lei Lai
Keyword(s):  
Energy Management ◽  
Thermal Energy ◽  
Critical Role ◽  
Distribution Networks ◽  
Energy Resources ◽  
Future Research ◽  
Renewable Energy Resources ◽  
Energy Modelling ◽  
Microgrid Energy Management ◽  
Combined Cooling

Microgrids have become increasingly popular in recent years due to technological improvements, growing recognition of their benefits, and diminishing costs. By clustering distributed energy resources, microgrids can effectively integrate renewable energy resources in distribution networks and satisfy end-user demands, thus playing a critical role in transforming the existing power grid to a future smart grid. There are many existing research and review works on microgrids. However, the thermal energy modelling in optimal microgrid management is seldom discussed in the current literature. To address this research gap, this paper presents a detailed review on the thermal energy modelling application on the optimal energy management for microgrids. This review firstly presents microgrid characteristics. Afterwards, the existing thermal energy modeling utilized in microgrids will be discussed, including the application of a combined cooling, heating and power (CCHP) and thermal comfort model to form virtual energy storage systems. Current trial programs of thermal energy modelling for microgrid energy management are analyzed and some challenges and future research directions are discussed at the end. This paper serves as a comprehensive review to the most up-to-date thermal energy modelling applications on microgrid energy management.

scholarly journals Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 414
Author(s):  
Saja Baraghithy ◽  
Yael Soae ◽  
Dekel Assaf ◽  
Liad Hinden ◽  
Shiran Udi ◽  
...  
Keyword(s):  
Bone Mass ◽  
Proximal Tubule ◽  
Bone Remodeling ◽  
Kidney Function ◽  
Bone Cells ◽  
Critical Role ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cell ◽  
Protective Effects ◽  
Cannabinoid 1 Receptor

The renal proximal tubule cells (RPTCs), well-known for maintaining glucose and mineral homeostasis, play a critical role in the regulation of kidney function and bone remodeling. Deterioration in RPTC function may therefore lead to the development of diabetic kidney disease (DKD) and osteoporosis. Previously, we have shown that the cannabinoid-1 receptor (CB1R) modulates both kidney function as well as bone remodeling and mass via its direct role in RPTCs and bone cells, respectively. Here we employed genetic and pharmacological approaches that target CB1R, and found that its specific nullification in RPTCs preserves bone mass and remodeling both under normo- and hyper-glycemic conditions, and that its chronic blockade prevents the development of diabetes-induced bone loss. These protective effects of negatively targeting CB1R specifically in RPTCs were associated with its ability to modulate erythropoietin (EPO) synthesis, a hormone known to affect bone mass and remodeling. Our findings highlight a novel molecular mechanism by which CB1R in RPTCs remotely regulates skeletal homeostasis via a kidney-to-bone axis that involves EPO.

scholarly journals The Bdkrb2 gene family provides a novel view of viviparity adaptation in Sebastes schlegelii

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jingjing Niu ◽  
Weihao Song ◽  
Rui Li ◽  
Haiyang Yu ◽  
Jian Guan ◽  
...  
Keyword(s):  
Protein Structure ◽  
Vascular System ◽  
Critical Role ◽  
Future Research ◽  
Breeding Cycle ◽  
Exterior Surface ◽  
Black Rockfish ◽  
Vascular Regulation ◽  
Sebastes Schlegelii ◽  
Ovarian Wall

Abstract Background Black rockfish (Sebastes schlegelii) is a viviparous teleost. We proposed that the rockfish ovarian wall had a similar function to the uterus of mammals previously. In the present study, the well-developed vascular system was observed in the ovarian wall and the exterior surface of the egg membrane. In gestation, adaptation of the ovary vasculature to the rising needs of the embryos occurs through both vasodilation and neovascularization. Bdkrb2, encoding a receptor for bradykinin, plays a critical role in the control of vasodilatation by regulating nitric oxide production. Results Eight Bdkrb2 genes were identified in the black rockfish genome. These genes were located on chromosome 14, which are arranged in a tandem array, forming a gene cluster spanning 50 kb. Protein structure prediction, phylogenetic analysis, and transcriptome analysis showed that eight Bdkrb2 genes evolved two kinds of protein structure and three types of tissue expression pattern. Overexpression of two Bdkrb2 genes in zebrafish indicated a role of them in blood vessel formation or remodeling, which is an important procedure for the viviparous rockfish getting prepared for fertilization and embryos implantation. Conclusions Our study characterizes eight Bdrkb2 genes in the black rockfish, which may contribute to preparation for fertilization and embryo implantation. This research provides a novel view of viviparity adaptation and lays the groundwork for future research into vascular regulation of ovarian tissue in the breeding cycle in black rockfish.

scholarly journals The Role of the Bone Marrow Microenvironment in the Response to Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Courtney B. Johnson ◽  
Jizhou Zhang ◽  
Daniel Lucas
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Immune Cells ◽  
Critical Role ◽  
Primary Source ◽  
Bone Marrow Microenvironment ◽  
Future Research ◽  
Multipotent Stem Cells ◽  
Hematopoietic Stem

Hematopoiesis in the bone marrow (BM) is the primary source of immune cells. Hematopoiesis is regulated by a diverse cellular microenvironment that supports stepwise differentiation of multipotent stem cells and progenitors into mature blood cells. Blood cell production is not static and the bone marrow has evolved to sense and respond to infection by rapidly generating immune cells that are quickly released into the circulation to replenish those that are consumed in the periphery. Unfortunately, infection also has deleterious effects injuring hematopoietic stem cells (HSC), inefficient hematopoiesis, and remodeling and destruction of the microenvironment. Despite its central role in immunity, the role of the microenvironment in the response to infection has not been systematically investigated. Here we summarize the key experimental evidence demonstrating a critical role of the bone marrow microenvironment in orchestrating the bone marrow response to infection and discuss areas of future research.

scholarly journals Role of Insulin in Health and Disease: An Update

2021 ◽  
Vol 22 (12) ◽  
pp. 6403
Author(s):  
Md Saidur Rahman ◽  
Khandkar Shaharina Hossain ◽  
Sharnali Das ◽  
Sushmita Kundu ◽  
Elikanah Olusayo Adegoke ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Basic Research ◽  
Future Research ◽  
Protective Effects ◽  
Glucose Levels ◽  
Physiological Processes ◽  
Blood Glucose Levels ◽  
Wide Range ◽  
Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

Sign in / Sign up

Export Citation Format

Share Document