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https://www.readbyqxmd.com/read/28226201/genomewide-association-study-of-alcohol-dependence-identifies-risk-loci-altering-ethanol-response-behaviors-in-model-organisms
#1
Amy E Adkins, Laura M Hack, Tim B Bigdeli, Vernell S Williamson, G Omari McMichael, Mohammed Mamdani, Alexis Edwards, Fazil Aliev, Robin F Chan, Poonam Bhandari, Richard C Raabe, Joseph T Alaimo, GinaMari G Blackwell, Arden A Moscati, Ryan S Poland, Benjamin Rood, Diana G Patterson, Dermot Walsh, John B Whitfield, Gu Zhu, Grant W Montgomery, Anjali K Henders, Nicholas G Martin, Andrew C Heath, Pamela A F Madden, Josef Frank, Monika Ridinger, Norbert Wodarz, Michael Soyka, Peter Zill, Marcus Ising, Markus M Nöthen, Falk Kiefer, Marcella Rietschel, Joel Gelernter, Richard Sherva, Ryan Koesterer, Laura Almasy, Hongyu Zhao, Henry R Kranzler, Lindsay A Farrer, Brion S Maher, Carol A Prescott, Danielle M Dick, Silviu A Bacanu, Laura D Mathies, Andrew G Davies, Vladimir I Vladimirov, Mike Grotewiel, M Scott Bowers, Jill C Bettinger, Bradley T Webb, Michael F Miles, Kenneth S Kendler, Brien P Riley
BACKGROUND: Alcohol Dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified. METHODS: We conducted a genomewide association study in 706 related AD cases and 1748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent. We used model organisms to assess the role of orthologous genes in ethanol response behaviors. We tested one primate-specific gene for expression differences in case/control post-mortem brain tissue...
February 22, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28206967/calcium-regulatory-proteins-as-modulators-of-chemotherapy-in-human-neuroblastoma
#2
Ana-Maria Florea, Elizabeth Varghese, Jennifer E McCallum, Safa Mahgoub, Irfan Helmy, Sharon Varghese, Neha Gopinath, Steffen Sass, Fabian J Theis, Guido Reifenberger, Dietrich Büsselberg
Neuroblastoma (NB) is a pediatric cancer treated with poly-chemotherapy including platinum complexes (e.g. cisplatin (CDDP), carboplatin), DNA alkylating agents, and topoisomerase I inhibitors (e.g. topotecan (TOPO)). Despite aggressive treatment, NB may become resistant to chemotherapy. We investigated whether CDDP and TOPO treatment of NB cells interacts with the expression and function of proteins involved in regulating calcium signaling. Human neuroblastoma cell lines SH-SY5Y, IMR-32 and NLF were used to investigate the effects of CDDP and TOPO on cell viability, apoptosis, calcium homeostasis, and expression of selected proteins regulating intracellular calcium concentration ([Ca2+]i)...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28111173/cardiac-expression-of-ryanodine-receptor-subtype-3-a-strategic-component-in-the-intracellular-ca-2-release-system-of-purkinje-fibers-in-large-mammalian-heart
#3
Rebecca E Daniels, Kazi T Haq, Lawson S Miller, Elizabeth W Chia, Masahito Miura, Vincenzo Sorrentino, John J McGuire, Bruno D Stuyvers
BACKGROUND: Three distinct Ca(2+) release channels were identified in dog P-cells: the ryanodine receptor subtype 2 (RyR2) was detected throughout the cell, while the ryanodine receptor subtype 3 (RyR3) and inositol phosphate sensitive Ca(2+) release channel (InsP3R) were found in the cell periphery. How each of these channels contributes to the Ca(2+) cycling of P-cells is unclear. Recent modeling of Ca(2+) mobilization in P-cells suggested that Ca(2+) sensitivity of Ca(2+)induced Ca(2+)release (CICR) was larger at the P-cell periphery...
January 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27866413/disbalance-of-calcium-regulation-related-genes-in-broiler-hearts-induced-by-selenium-deficiency
#4
Ziwei Zhang, Man Liu, Zhenqiong Guan, Jie Yang, Zhonghua Liu, Shiwen Xu
Dietary selenium (Se) deficiency may influence the calcium (Ca) homeostasis in broilers. Our objective was to investigate the effects of Se deficiency on Ca regulation-related genes in broiler hearts. In the present study, 1-day-old broilers were fed either a commercial diet (as control group) with 0.15 mg/kg Se or a Se-deficient diet (as L group) with 0.033 mg/kg Se for 35 days. We examined the mRNA expression levels of 15 Ca regulation-related genes (ITPR 1, ITPR 2, ITPR3, RyR2, RyR3, SERCA1s, SLC8A1, PMCA1, CACNA1S, TRPC1, TRPC3, stromal interacting molecule 1, ORAI1, calmodulin (CaLM) and calreticulin (CRT) in broiler hearts...
January 31, 2017: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/27866274/ryanodine-receptor-type-3-does-not-contribute-to-contractions-in-the-mouse-myometrium-regardless-of-pregnancy
#5
Katsuhito Matsuki, Masashi Takemoto, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Hiroshi Takeshima, Yuji Imaizumi
Ryanodine receptor type 3 (RyR3) is expressed in myometrial smooth muscle cells (MSMCs). The short isoform of RyR3 is a dominant negative variant (DN-RyR3) and negatively regulates the functions of RyR2 and full-length (FL)-RyR3. DN-RyR3 has been suggested to function as a major RyR3 isoform in non-pregnant (NP) mouse MSMCs, and FL-RyR3 may also be upregulated during pregnancy (P). This increase in the FL-RyR3/DN-RyR3 ratio may contribute to the strong contractions by MSMCs for parturition. In the present study, spontaneous contractions by the myometrium in NP and P mice were highly susceptible to nifedipine but were not affected by ryanodine...
November 20, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27858853/genome-wide-linkage-analysis-and-regional-fine-mapping-identified-variants-in-the-ryr3-gene-as-a-novel-quantitative-trait-locus-for-circulating-adiponectin-in-chinese-population
#6
Yi-Cheng Chang, Yen-Feng Chiu, Chih-Tsueng He, Wayne Huey-Herng Sheu, Ming-Wei Lin, Todd B Seto, Themistocles Assimes, Yuh-Shan Jou, Lynn Su, Wei-Jei Lee, Po-Chu Lee, Shu-Huei Tsai, Lee-Ming Chuang
Adiponectin is adipocyte-secreted cytokine with potent insulin-sensitizing action in peripheral tissues. The heritability of plasma adiponectin is high in Han Chinese population.To identify genetic loci influencing plasma adiponectin levels in Chinese population, we performed a genome-wide linkage scan in 1949 Chinese participants of the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study and mapped a quantitative trail locus located on chromosome 15 at 31 cM (logarithm of odds = 3...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27742266/proteomic-analysis-of-mucopolysaccharidosis-i-mouse-brain-with-two-dimensional-polyacrylamide-gel-electrophoresis
#7
Li Ou, Michael J Przybilla, Chester B Whitley
Mucopolysaccharidosis type I (MPS I) is due to deficiency of α-l-iduronidase (IDUA) and subsequent storage of undegraded glycosaminoglycans (GAG). The severe form of the disease, known as Hurler syndrome, is characterized by mental retardation and neurodegeneration of unknown etiology. To identify potential biomarkers and unveil the neuropathology mechanism of MPS I disease, two-dimensional polyacrylamide gel electrophoresis (PAGE) and nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) were applied to compare proteome profiling of brains from MPS I and control mice (5-month old)...
January 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27602096/a-polymorphism-at-the-microrna-binding-site-in-the-3-untranslated-region-of-c14orf101-is-associated-with-the-risk-of-gastric-cancer-development
#8
Cuiju Wang, Yufei Zhao, Yanming Ming, Shengnan Zhao, Zhanjun Guo
MicroRNAs (miRNAs) bind to the 3'-untranslated regions (3'-UTRs) of mRNAs, affecting translation and regulating cell differentiation, tumorigenesis and apoptosis. Genetic polymorphisms in these regions in target genes are able to affect the binding affinity between miRNA and target genes, ultimately affecting the expression of individual miRNAs. In the present case-control study, genotyping of 5 microRNA single nucleotide polymorphisms (SNPs) located at the binding site of the 3'-UTR of RYR3 (rs1044129), C14orf101 (rs4901706), KIAA0423 (rs1053667), GOLGA7 (rs11337) and KRT81 (rs3660) genes was assessed in order to investigate its role in gastric cancer (GC)...
September 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27590123/differential-effects-of-contractile-potentiators-on-action-potential-induced-ca-2-transients-of-frog-and-mouse-skeletal-muscle-fibres
#9
Caputo Carlo, Bolaños Pura, Ramos Magaly, DiFranco Marino
Muscle fibres, isolated from frog tibialis anterior and mouse flexor digitorum brevis (FDB) were loaded with the fast dye MagFluo-4 to study the effects of potentiators caffeine, nitrate, Zn(2+) and perchlorate on Ca(2+) transients elicited by single action potentials. Overall, the potentiators doubled the transients amplitude and prolonged by about 1.5-fold their decay time. In contrast, as shown here for the first time, nitrate and Zn(2+), but not caffeine, activated a late, secondary component of the transient rising phase of frog but not mouse, fibres...
September 2, 2016: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/27383122/role-of-adenylyl-cyclase-in-reduced-%C3%AE-adrenoceptor-mediated-vasorelaxation-during-maturation
#10
O A López-Canales, M C Castillo-Hernandez, H Vargas-Robles, A Rios, J S López-Canales, B Escalante
Beta-adrenergic receptor (βAR)-dependent blood vessel relaxation is impaired in older animals and G protein activation has been suggested as the causative mechanism. Here, we investigated the role of βAR subtypes (β1AR, β2AR, and β3AR) and cAMP in maturation-dependent vasorelaxation impairment. Aortic rings from 15 Sprague-Dawley male rats (3 or 9 weeks old) were harvested and left intact or denuded of the endothelium. Vascular relaxation in aortic rings from younger and older groups was compared in the presence of βAR subtype agonists and antagonists along with cAMP and cGMP antagonists...
July 4, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/27376531/from-contraction-to-gene-expression-nanojunctions-of-the-sarco-endoplasmic-reticulum-deliver-site-and-function-specific-calcium-signals
#11
REVIEW
A Mark Evans, Nicola Fameli, Oluseye A Ogunbayo, Jingxian Duan, Jorge Navarro-Dorado
Calcium signals determine, for example, smooth muscle contraction and changes in gene expression. How calcium signals select for these processes is enigmatic. We build on the "panjunctional sarcoplasmic reticulum" hypothesis, describing our view that different calcium pumps and release channels, with different kinetics and affinities for calcium, are strategically positioned within nanojunctions of the SR and help demarcate their respective cytoplasmic nanodomains. SERCA2b and RyR1 are preferentially targeted to the sarcoplasmic reticulum (SR) proximal to the plasma membrane (PM), i...
August 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27199668/mediation-of-autophagic-cell-death-by-type-3-ryanodine-receptor-ryr3-in-adult-hippocampal-neural-stem-cells
#12
Kyung Min Chung, Eun-Ji Jeong, Hyunhee Park, Hyun-Kyu An, Seong-Woon Yu
Cytoplasmic Ca(2+) actively engages in diverse intracellular processes from protein synthesis, folding and trafficking to cell survival and death. Dysregulation of intracellular Ca(2+) levels is observed in various neuropathological states including Alzheimer's and Parkinson's diseases. Ryanodine receptors (RyRs) and inositol 1,4,5-triphosphate receptors (IP3Rs), the main Ca(2+) release channels located in endoplasmic reticulum (ER) membranes, are known to direct various cellular events such as autophagy and apoptosis...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27096430/different-profile-of-mrna-expression-in-sinoatrial-node-from-streptozotocin-induced-diabetic-rat
#13
Zannatul Ferdous, Muhammad Anwar Qureshi, Petrilla Jayaprakash, Khatija Parekh, Annie John, Murat Oz, Haider Raza, Halina Dobrzynski, Thomas Edward Adrian, Frank Christopher Howarth
BACKGROUND: Experiments in isolated perfused heart have shown that heart rate is lower and sinoatrial node (SAN) action potential duration is longer in streptozotocin (STZ)-induced diabetic rat compared to controls. In sino-atrial preparations the pacemaker cycle length and sino-atrial conduction time are prolonged in STZ heart. To further clarify the molecular basis of electrical disturbances in the diabetic heart the profile of mRNA encoding a wide variety of proteins associated with the generation and transmission of electrical activity has been evaluated in the SAN of STZ-induced diabetic rat heart...
2016: PloS One
https://www.readbyqxmd.com/read/26827652/discovery-of-gene-gene-interactions-across-multiple-independent-data-sets-of-late-onset-alzheimer-disease-from-the-alzheimer-disease-genetics-consortium
#14
Timothy J Hohman, William S Bush, Lan Jiang, Kristin D Brown-Gentry, Eric S Torstenson, Scott M Dudek, Shubhabrata Mukherjee, Adam Naj, Brian W Kunkle, Marylyn D Ritchie, Eden R Martin, Gerard D Schellenberg, Richard Mayeux, Lindsay A Farrer, Margaret A Pericak-Vance, Jonathan L Haines, Tricia A Thornton-Wells
Late-onset Alzheimer disease (AD) has a complex genetic etiology, involving locus heterogeneity, polygenic inheritance, and gene-gene interactions; however, the investigation of interactions in recent genome-wide association studies has been limited. We used a biological knowledge-driven approach to evaluate gene-gene interactions for consistency across 13 data sets from the Alzheimer Disease Genetics Consortium. Fifteen single nucleotide polymorphism (SNP)-SNP pairs within 3 gene-gene combinations were identified: SIRT1 × ABCB1, PSAP × PEBP4, and GRIN2B × ADRA1A...
February 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/26309413/a-polymorphism-at-the-microrna-binding-site-in-the-3-untranslated-region-of-ryr3-is-associated-with-outcome-in-hepatocellular-carcinoma
#15
Chenxing Peng, Zhanjun Guo, Xiaoyan Wu, Xiao-Lan Zhang
OBJECTIVE: MicroRNAs can bind to the 3' untranslated regions (UTRs) of messenger RNAs, where they interfere with the translation of targeting genes, thereby regulating cell differentiation, apoptosis, and tumorigenesis. In this study, three microRNA binding site single nucleotide polymorphisms (SNPs) located in the 3' UTR of RYR3 (rs1044129), C14orf101 (rs4901706), and KIAA0423 (rs1053667) were genotyped to assess their relationships with the risks and outcomes of hepatocellular carcinoma (HCC)...
2015: OncoTargets and Therapy
https://www.readbyqxmd.com/read/26277840/chronic-fetal-exposure-to-caffeine-altered-resistance-vessel-functions-via-ryrs-bkca-down-regulation-in-rat-offspring
#16
Na Li, Yongmei Li, Qinqin Gao, Dawei Li, Jiaqi Tang, Miao Sun, Pengjie Zhang, Bailin Liu, Caiping Mao, Zhice Xu
Caffeine modifies vascular/cardiac contractility. Embryonic exposure to caffeine altered cardiac functions in offspring. This study determined chronic influence of prenatal caffeine on vessel functions in offspring. Pregnant Sprague-Dawley rats (5-month-old) were exposed to high dose of caffeine, their offspring (5-month-old) were tested for vascular functions in mesenteric arteries (MA) and ion channel activities in smooth muscle cells. Prenatal exposure to caffeine increased pressor responses and vasoconstrictions to phenylephrine, accompanied by enhanced membrane depolarization...
August 17, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26250335/mir-367-promotes-proliferation-and-stem-like-traits-in-medulloblastoma-cells
#17
Carolini Kaid, Patrícia B G Silva, Beatriz A Cortez, Carolina O Rodini, Patricia Semedo-Kuriki, Oswaldo K Okamoto
In medulloblastoma, abnormal expression of pluripotency factors such as LIN28 and OCT4 has been correlated with poor patient survival. The miR-302/367 cluster has also been shown to control self-renewal and pluripotency in human embryonic stem cells and induced pluripotent stem cells, but there is limited, mostly correlational, information about these pluripotency-related miRNA in cancer. We evaluated whether aberrant expression of such miRNA could affect tumor cell behavior and stem-like traits, thereby contributing to the aggressiveness of medulloblastoma cells...
September 2015: Cancer Science
https://www.readbyqxmd.com/read/26100948/both-ryrs-and-tpcs-are-required-for-naadp-induced-intracellular-ca%C3%A2-%C3%A2-%C2%BA-release
#18
Julia V Gerasimenko, Richard M Charlesworth, Mark W Sherwood, Pawel E Ferdek, Katsuhiko Mikoshiba, John Parrington, Ole H Petersen, Oleg V Gerasimenko
Intracellular Ca(2+) release is mostly mediated by inositol trisphosphate, but intracellular cyclic-ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are important messengers in many systems. Whereas cADPR generally activates type 2 ryanodine receptors (RyR2s), the NAADP-activated Ca(2+) release mechanism is less clear. Using knockouts and antibodies against RyRs and Two-Pore Channels (TPCs), we have compared their relative importance for NAADP-induced Ca(2+) release from two-photon permeabilized pancreatic acinar cells...
September 2015: Cell Calcium
https://www.readbyqxmd.com/read/26053858/pre-slaughter-stress-affects-ryanodine-receptor-protein-gene-expression-and-the-water-holding-capacity-in-fillets-of-the-nile-tilapia
#19
Elenice S R Goes, Jorge A F Lara, Eliane Gasparino, Ana P Del Vesco, Marcio D Goes, Luiz Alexandre Filho, Ricardo P Ribeiro
Current study evaluated the effect of pre-slaughter stress on serum cortisol levels, pH, colorimetry, water-holding capacity (WHC) and gene expression of ryanodine receptors (RyR1 and RyR3) in the Nile tilapia. A 3x4 factorial scheme experiment was conducted comprising three densities (100, 200, 400 kg/m³) with four transportation times (60, 120, 180, and 240 minutes).Transportation times alone reduced cortisol levels up to 180 minutes, followed by increased WHC and mRNA expression, RyR1 and RyR3 (200 kg/m³ density)...
2015: PloS One
https://www.readbyqxmd.com/read/26046824/the-role-of-ca-2-influx-in-spontaneous-ca-2-wave-propagation-in-interstitial-cells-of-cajal-from-the-rabbit-urethra
#20
Bernard T Drumm, Roddy J Large, Mark A Hollywood, Keith D Thornbury, Salah A Baker, Brian J Harvey, Noel G McHale, Gerard P Sergeant
Tonic contractions of rabbit urethra are associated with spontaneous electrical slow waves that are thought to originate in pacemaker cells termed interstitial cells of Cajal (ICC). ICC pacemaker activity results from their ability to generate propagating Ca(2+) waves, although the exact mechanisms of propagation are not understood. In this study, we have identified spontaneous localised Ca(2+) events for the first time in urethral ICC; these were due to Ca(2+) release from the endoplasmic reticulum (ER) via ryanodine receptors (RyRs) and, while they often remained localised, they sometimes initiated propagating Ca(2+) waves...
August 1, 2015: Journal of Physiology
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