Ryr3

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KEY POINTS: A population of enteroendocrine cells (EEC) are specialized mechanosensors of the gastrointestinal (GI) epithelium that respond to mechanical stimulation with the release of important signalling molecules, such as serotonin. Mechanical activation of these EECs leads to an increase in intracellular calcium (Ca2+ ) with a longer duration than the stimulus, suggesting intracellular Ca2+ signal amplification. In this study, we profiled the expression of intracellular Ca2+ store receptors and found an enriched expression of the intracellular Ca2+ receptor Ryr3, which contributed to the mechanically evoked increases in intracellular calcium, 5-HT release, and epithelial secretion...

BACKGROUND: Dyslipidemia is a major risk factor for cardiovascular disease, and diabetes impacts the lipid metabolism through multiple pathways. In addition to the standard lipid measurements, apolipoprotein concentrations provide added awareness of the burden of circulating lipoproteins. While common genetic variants modestly affect the serum lipid concentrations, rare genetic mutations can cause monogenic forms of hypercholesterolemia and other genetic disorders of lipid metabolism...

The hippocampus is a brain region implicated in synaptic plasticity and memory formation; both processes require neuronal Ca2+ signals generated by Ca2+ entry via plasma membrane Ca2+ channels and Ca2+ release from the endoplasmic reticulum (ER). Through Ca2+ -induced Ca2+ release, the ER-resident ryanodine receptor (RyR) Ca2+ channels amplify and propagate Ca2+ entry signals, leading to activation of cytoplasmic and nuclear Ca2+ -dependent signaling pathways required for synaptic plasticity and memory processes...

Slow transit constipation (STC) is the most common type of functional constipation. Drugs with good effects and few side effects are urgently needed form the treatment of STC. Cymbopogon citratus (DC.) Stapf (CC) is an important medicinal and edible spice plant. The wide range of biological activities suggested that CC may have laxative effects, but thus far, it has not been reported. In this study, the loperamide-induced STC mouse model was used to evaluate the laxative effect of the aqueous extract of CC (CCAE), and the laxative mechanism was systematically explored from the perspectives of the enteric nervous system (ENS), neurotransmitter secretion, gastrointestinal motility factors, intestinal inflammation, gut barrier and gut microbiota...

Epigenetic alterations of brain contribute to age-related cognitive decline. The challenge now is to identify these tractable epigenetic molecules working as the downstream cell-signaling nodes mediating age-related cognitive decline. Here we reported age-related loss of miR-124 in human and rat brains. To further validate these findings, knockout mice in which one of the three miR-124 genes (miR-124-3) was deleted using CRISPR/Cas9-mediated gene engineering were generated. MiR-124-3 knockout mice developed cognitive deficit phenotype...

Ca2+ signaling is altered substantially in many cancers. The ryanodine receptors (RYRs) are among the key ion channels in Ca2+ signaling. This study aimed to establish the mutational profile of RYR in cancers and investigate the correlation between RYR alterations and cancer phenotypes. The somatic mutation and clinical data of 11,000 cancer patients across 33 cancer types was downloaded from The Cancer Genome Atlas (TCGA) database. Subsequent data processing was performed with corresponding packages of the R software...

BACKGROUND: Pharmacogenetic variants impact dihydropyridine calcium channel blockers (dCCB) (i.e. amlodipine) treatment efficacy, yet evidence on clinical outcomes in routine primary care is limited. Reported associations in PharmGKB have weak supporting evidence. We aimed to estimate associations between reported pharmacogenetic variants and incident adverse events in a community-based cohort prescribed dCCB. METHODS: We analyzed up to 32,360 UK Biobank participants prescribed dCCB in primary care (from UK General Practices, 1990-2017)...

Thermal stress poses a threat to agricultural systems through increased risk to animal growth, health, and production. Exposure of poultry, especially hatchlings, to extreme temperatures can seriously affect muscle development and thus compromise subsequent meat quality. This study was designed to characterize transcriptional changes induced in turkey muscle satellite cells (SCs) cultured from commercial birds under thermal challenge to determine the applicability of previous results obtained for select research lines...

The German Longhaired Pointer (GLP) breed is a versatile pointer dog breed. In the current study, we investigated the genetic diversity of these dogs based on SNP array data and compared it to 11 other pointer setter breeds. The results show that GLPs have a relatively low level of inbreeding among these pointer breeds. In addition, with the availability of pedigree information of the GLPs, we demonstrate that the correlation between pedigree-based inbreeding and genotype-based inbreeding coefficients was high (R = 0...

Background: The ryanodine receptors ( RYRs ) have been implicated in many muscular, cardiac and neurological diseases. However, there are almost no studies so far focusing on RYR genetic alterations and its roles in cancer, especially in non-small cell lung cancer (NSCLC). Methods: The whole-exome sequencing (WES) data, demographic and clinical data of 1,052 NSCLC patients was downloaded from The Cancer Genome Atlas (TCGA) database and analyzed using the corresponding packages of the R software...

Colorectal cancer is a highly malignant cancer with poor prognosis and mortality rates. As the first biological agent approved for metastatic colorectal cancer (mCRC), bevacizumab was confirmed to exhibit good performance when combined with chemotherapy and immunotherapy. However, the efficacy of both bevacizumab and immunotherapy is highly heterogeneous across CRC patients with different stages. Thus, exploring a novel biomarker to comprehensively assess the prognosis and bevacizumab and immunotherapy response of CRC is of great significance...

We previously reported that egg activation in Japanese quail is driven by two distinct types of intracellular Ca2+ ([Ca2+ ] i ): transient elevations in [Ca2+ ] i induced by phospholipase Czeta 1 (PLCZ1) and long-lasting spiral-like Ca2+ oscillations by citrate synthase (CS) and aconitate hydratase 2 (ACO2). Although the blockade of inositol 1,4,5-trisphosphate receptors (ITPRs) before microinjections of PLCZ1, CS , and ACO2 cRNAs only prevented transient increases in [Ca2+ ] i , a microinjection of an agonist of ryanodine receptors (RYRs) induced spiral-like Ca2+ oscillations, indicating the involvement of both ITPRs and RYRs in these events...

Objective: To evaluate the clinical features of sporadic Paget's disease of bone (PDB) in China and further explore the underlying genetic abnormalities of the disease. Methods: Clinical characteristics, biochemical indices, bone turnover markers and radiographic examinations of the patients were collected. Genomic DNA was extracted from peripheral blood and whole-exome sequencing was carried out to identify the potential pathogenic genes. The pathogenicity of the variants was thereafter investigated by bioinformatics analysis...

Tight junction proteins 1-3 (TJP1-3) are components of tight junctions that can link transmembrane proteins to the actin cytoskeleton, and their incidence directly correlates to metastasis. However, the role of the TJP family in bladder cancer has not been adequately evaluated. In this study, we evaluated the genetic changes, mRNA and protein expressions of the target genes of the TJP family in bladder cancer patients using online database and immunohistochemistry, respectively. We found that TJP1 was amplified in bladder cancer tissue and that the protein expression levels were significantly associated with age (p = 0...

Sheep ( Ovis aries ) is one of the important livestock with diverse phenotypic traits. However, little is known about the molecular mechanism of diverse phenotypic traits in domestic sheep. Using the genome-wide high-density SNP data (600K) in 253 samples from 13 populations, we conducted the tests of selective sweeps (i.e., pairwise F ST and XP-CLR) associated with several important phenotypic traits (e.g., tail types, horn morphology, prolificacy, coat pigmentation, ear size, milk production, meat production, body size and wool fineness)...

Lung squamous cell carcinoma (LUSC) is a leading cause of mobidity and mortality worldwide. Recently, there was a shift in the treatment pattern of immune therapy in LUSC patients; merely a small number of patients with non-small cell lung cancer (NSCLC) at advanced stages respond well to immune checkpoint blockade (ICB) therapy, and tumor mutation burden (TMB) is a valuable independent indicator of response to immune therapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immunocytes in LUSC are still unclear...

BACKGROUND: Admixture mapping is a powerful approach for gene mapping of complex traits that leverages the diverse genetic ancestry in populations with recent admixture, such as Hispanic or Latino individuals in the United States. These individuals have an increased risk of CKD. METHODS: We performed genome-wide admixture mapping for both CKD and eGFR in a sample of 12,601 participants from the Hispanic Community Health Study/Study of Latinos, with validation in a sample of 8191 Black participants from the Women's Health Initiative (WHI)...

Background: Yeokwisan, a standardized herbal formula, has exhibited clinical benefit for patients suffering from refractory functional dyspepsia (FD) in Korea since 2016. However, data about the mechanism of action of this formula are yet not available. Aim of the study: To evaluate and explore the effects of Yeokwisan on gastric emptying, a major symptom of functional dyspepsia, and its underlying mechanisms of action using a mouse model. Materials and methods: BALB/C mice were pretreated with Yeokwisan (100, 200, and 400 mg/kg, po) or mosapride (3 mg/kg, po) for 5 days and then treated with loperamide (10 mg/kg, ip) after 20 h of fasting...

Trophoblasts are specialized epithelial cells of the placenta that are involved in invasion, communication and the exchange of materials between the mother and fetus. Cytoplasmic Ca2+ ([Ca2+ ]c ) plays critical roles in regulating such processes in other cell types, but relatively little is known about the mechanisms that control this second messenger in trophoblasts. In the current study, the presence of RyRs and their accessory proteins in placental tissues and in the BeWo choriocarcinoma, a model trophoblast cell-line, were examined using immunohistochemistry and Western immunoblotting...