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https://www.readbyqxmd.com/read/29115887/effect-of-heat-stress-on-the-gene-expression-of-ion-transporters-channels-in-the-uterus-of-laying-hens-during-eggshell-formation
#1
Shahab Bahadoran, Amir Dehghani Samani, Hossein Hassanpour
Heat stress is a problem in laying hens as it decreases egg quality by decreasing eggshell mineralization. Heat stress alters gene expression, hence our aim was to investigate effects of heat stress on gene expression of ion transport elements involving in uterine mineralization (TRPV6, CALB1, ITPR3, SCNN1G, SLC4A4, KCNJ15, SLC4A9, and CLCN2) by real time quantitative PCR. Forty 23-week-old White Leghorn laying hens were housed in two rooms. The control group (n = 20) was maintained at 21-23 °C, and the heat stress group (n = 20) was exposed to 36-38 °C for 8 weeks...
November 8, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/29070411/chemical-space-big-data-challenge-for-molecular-diversity
#2
Mahendra Awale, Ricardo Visini, Daniel Probst, Josep Arús-Pous, Jean-Louis Reymond
Chemical space describes all possible molecules as well as multi-dimensional conceptual spaces representing the structural diversity of these molecules. Part of this chemical space is available in public databases ranging from thousands to billions of compounds. Exploiting these databases for drug discovery represents a typical big data problem limited by computational power, data storage and data access capacity. Here we review recent developments of our laboratory, including progress in the chemical universe databases (GDB) and the fragment subset FDB-17, tools for ligand-based virtual screening by nearest neighbor searches, such as our multi-fingerprint browser for the ZINC database to select purchasable screening compounds, and their application to discover potent and selective inhibitors for calcium channel TRPV6 and Aurora A kinase, the polypharmacology browser (PPB) for predicting off-target effects, and finally interactive 3D-chemical space visualization using our online tools WebDrugCS and WebMolCS...
October 25, 2017: Chimia
https://www.readbyqxmd.com/read/29037849/letrozole-induced-low-estrogen-levels-affected-the-expressions-of-duodenal-and-renal-calcium-processing-gene-in-laying-hens
#3
REVIEW
Qiao Li, Xingkai Zhao, Shujie Wang, Zhenlei Zhou
Estrogen regulates the calcium homeostasis in hens, but the mechanisms involved are still unclear fully. In this study, we investigated whether letrozole (LZ) induced low estrogen levels affected the calcium absorption and transport in layers. In the duodenum, we observed a significant decrease of mRNA expressions of Calbindin-28k (CaBP-28k) and plasma membrane Ca(2+)-ATPase (PMCA 1b) while CaBP-28k protein expression was declined in birds with LZ treatment, and the mRNA levels of duodenal transient receptor potential vanilloid 6 (TRPV6) and Na(+)/Ca(2+) exchanger 1 (NCX1) were not affected...
January 1, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29030554/hdx-reveals-the-conformational-dynamics-of-dna-sequence-specific-vdr-co-activator-interactions
#4
Jie Zheng, Mi Ra Chang, Ryan E Stites, Yong Wang, John B Bruning, Bruce D Pascal, Scott J Novick, Ruben D Garcia-Ordonez, Keith R Stayrook, Michael J Chalmers, Jeffrey A Dodge, Patrick R Griffin
The vitamin D receptor/retinoid X receptor-α heterodimer (VDRRXRα) regulates bone mineralization via transcriptional control of osteocalcin (BGLAP) gene and is the receptor for 1α,25-dihydroxyvitamin D3 (1,25D3). However, supra-physiological levels of 1,25D3 activates the calcium-regulating gene TRPV6 leading to hypercalcemia. An approach to attenuate this adverse effect is to develop selective VDR modulators (VDRMs) that differentially activate BGLAP but not TRPV6. Here we present structural insight for the action of a VDRM compared with agonists by employing hydrogen/deuterium exchange...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28970257/identification-and-characterization-of-hydrophobic-gate-residues-in-trp-channels
#5
Wang Zheng, Ruikun Hu, Ruiqi Cai, Laura Hofmann, Qiaolin Hu, Mohammad Fatehi, Wentong Long, Tim Kong, Jingfeng Tang, Peter Light, Veit Flockerzi, Ying Cao, Xing-Zhen Chen
Transient receptor potential (TRP) channels, subdivided into 6 subfamilies in mammals, have essential roles in sensory physiology. They respond to remarkably diverse stimuli, comprising thermal, chemical, and mechanical modalities, through opening or closing of channel gates. In this study, we systematically substituted the hydrophobic residues within the distal fragment of pore-lining helix S6 with hydrophilic residues and, based on Xenopus oocyte and mammalian cell electrophysiology and a hydrophobic gate theory, identified hydrophobic gates in TRPV6/V5/V4/C4/M8...
September 28, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28878326/swapping-of-transmembrane-domains-in-the-epithelial-calcium-channel-trpv6
#6
Appu K Singh, Kei Saotome, Alexander I Sobolevsky
Tetrameric ion channels have either swapped or non-swapped arrangements of the S1-S4 and pore domains. Here we show that mutations in the transmembrane domain of TRPV6 can result in conversion from a domain-swapped to non-swapped fold. These results reveal structural determinants of domain swapping and raise the possibility that a single ion channel subtype can fold into either arrangement in vivo, affecting its function in normal or disease states.
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28860545/1%C3%AE-20s-dihydroxyvitamin-d3-interacts-with-vitamin-d-receptor-crystal-structure-and-route-of-chemical-synthesis
#7
Zongtao Lin, Hao Chen, Anna Y Belorusova, John C Bollinger, Edith K Y Tang, Zorica Janjetovic, Tae-Kang Kim, Zhongzhi Wu, Duane D Miller, Andrzej T Slominski, Arnold E Postlethwaite, Robert C Tuckey, Natacha Rochel, Wei Li
1α,20S-Dihydroxyvitamin D3 [1,20S(OH)2D3], a natural and bioactive vitamin D3 metabolite, was chemically synthesized for the first time. X-ray crystallography analysis of intermediate 15 confirmed its 1α-OH configuration. 1,20S(OH)2D3 interacts with the vitamin D receptor (VDR), with similar potency to its native ligand, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] as illustrated by its ability to stimulate translocation of the VDR to the nucleus, stimulate VDRE-reporter activity, regulate VDR downstream genes (VDR, CYP24A1, TRPV6 and CYP27B1), and inhibit the production of inflammatory markers (IFNγ and IL1β)...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28839241/leukocyte-trp-channel-gene-expressions-in%C3%A2-patients-with-non-valvular-atrial-fibrillation
#8
Irfan V Düzen, Fethi Yavuz, Ertan Vuruskan, Erhan Saracoglu, Fatih Poyraz, Hüseyin Göksülük, Basar Candemir, Seniz Demiryürek
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a major cause of morbidity and mortality. The upregulation of TRP channels is believed to mediate the progression of electrical remodelling and the arrhythmogenesis of the diseased heart. However, there is limited data about the contribution of the TRP channels to development of AF. The aim of this study was to investigate leukocyte TRP channels gene expressions in non-valvular atrial fibrillation (NVAF) patients. The study included 47 NVAF patients and 47 sex and age matched controls...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28602864/nckx3-was-compensated-by-calcium-transporting-genes-and-bone-resorption-in-a-nckx3-ko-mouse-model
#9
Hyun Yang, Changhwan Ahn, Eun-Kyeong Shin, Ji-Sun Lee, Beum-Soo An, Eui-Bae Jeung
Gene knockout is the most powerful tool for determination of gene function or permanent modification of the phenotypic characteristics of an animal. Existing methods for gene disruption are limited by their efficiency, time required for completion and potential for confounding off-target effects. In this study, a rapid single-step approach to knockout of a targeted gene in mice using zinc-finger nucleases (ZFNs) was demonstrated for generation of mutant (knockout; KO) alleles. Specifically, ZFNs to target the sodium/calcium/potassium exchanger3 (NCKX3) gene in C57bl/6j were designed using the concept of this approach...
October 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28599589/expressions-of-trpvs-in-the-cholesteatoma-epithelium
#10
Ba Hung Do, Hiroki Koizumi, Toyoaki Ohbuchi, Rintaro Kawaguchi, Hideaki Suzuki
OBJECTIVE: We have recently proposed a hypothesis that acid leakage through the cholesteatoma epithelium mediates bone resorption in middle ear cholesteatoma. In the present study, we investigated the expressions of transient receptor potential vanilloid (TRPV) channels, which have been shown to play roles in the regulation of epidermal barrier function, in the cholesteatoma epithelium in comparison with the normal skin. METHODS: Cholesteatoma epithelium and postauricular skin were collected from 17 patients with primary acquired middle ear cholesteatoma who underwent tympanomastoidectomy...
June 9, 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28578001/1%C3%AE-25-dihydroxyvitamin-d3-enhances-trpv6-transcription-through-p38-mapk-activation-and-gadd45-expression
#11
Michiyasu Ishizawa, Daisuke Akagi, Jumpei Yamamoto, Makoto Makishima
The active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], acts as a ligand for the vitamin D receptor (VDR), and regulates various physiological processes, including calcium and bone metabolism, cellular growth and differentiation, immunity and cardiovascular function. A number of vitamin D derivatives have been synthesized for the treatment of cancer and inflammatory disease, but the adverse effect of hypercalcemic activity due to intestinal calcium absorption has limited wide clinical application...
September 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28539338/expression-of-transcellular-and-paracellular-calcium-and-magnesium-transport-proteins-in-renal-and-intestinal-epithelia-during-lactation
#12
Megan R Beggs, Ida Appel, Per Svenningsen, Karsten Skjødt, R Todd Alexander, Henrik Dimke
Significant alterations in maternal calcium (Ca(2+)) and magnesium (Mg(2+)) balance occur during lactation. Ca(2+) is the primary divalent cation mobilized into breast milk by demineralization of the skeleton and alterations in intestinal and renal Ca(2+) transport. Mg(2+) is also concentrated in breast milk, but the underlying mechanisms are not well understood. To determine the molecular alterations in Ca(2+) and Mg(2+) transport in the intestine and kidney during lactation, three groups of female mice consisting of either nonpregnant controls, lactating mice, or mice undergoing involution were examined...
September 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28501141/trpv6-from-identification-to-function
#13
REVIEW
Claudia Fecher-Trost, Ulrich Wissenbach, Petra Weissgerber
No abstract text is available yet for this article.
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/28498349/desalted-duck-egg-white-peptides-promote-calcium-uptake-and-modulate-bone-formation-in-the-retinoic-acid-induced-bone-loss-rat-and-caco-2-cell-model
#14
Tao Hou, Yanshuang Liu, Nikolai Kolba, Danjun Guo, Hui He
Desalted duck egg white peptides (DPs) have been proven to promote calcium uptake in Caco-2 cells and rats treated with a calcium-deficient diet. The retinoic acid-induced bone loss model was used to evaluate the effect of DPs on calcium absorption and bone formation. Three-month-old Wistar female rats were treated with 0.9% saline, DPs (800 mg/kg), or alendronate (5 mg/kg) for three weeks immediately after retinoic acid treatment (80 mg/kg) once daily for two weeks. The model group was significantly higher in serum bone alkaline phosphatase than the other three groups (p < 0...
May 12, 2017: Nutrients
https://www.readbyqxmd.com/read/28416203/the-s4-s5-linker-gearbox-of-trp-channel-gating
#15
REVIEW
Laura Hofmann, Hongmei Wang, Wang Zheng, Stephan E Philipp, Patricia Hidalgo, Adolfo Cavalié, Xing-Zhen Chen, Andreas Beck, Veit Flockerzi
Transient receptor potential (TRP) channels are cation channels which participate in a wide variety of physiological processes in organisms ranging from fungi to humans. They fulfill roles in body homeostasis, are sensors for noxious chemicals and temperature in the mammalian somatosensory system and are activated by light stimulated phospholipase C activity in Drosophila or by hypertonicity in yeast. The transmembrane topology of TRP channels is similar to that of voltage-gated cation channels. TRP proteins assemble as tetramers with each subunit containing six transmembrane helices (S1-S6) and intracellular N- and C-termini...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/28389981/erratum-to-first-in-human-phase-i-study-of-sor-c13-a-trpv6-calcium-channel-inhibitor-in-patients-with-advanced-solid-tumors
#16
S Fu, H Hirte, S Welch, T T Ilenchuk, T Lutes, C Rice, N Fields, A Nemet, D Dugourd, S Piha-Paul, V Subbiah, L Liu, J Gong, D Hong, J M Stewart
No abstract text is available yet for this article.
June 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28374795/a-gate-hinge-controls-the-epithelial-calcium-channel-trpv5
#17
Jenny van der Wijst, Elizabeth H Leunissen, Maxime G Blanchard, Hanka Venselaar, Sjoerd Verkaart, Candice E Paulsen, René J Bindels, Joost G Hoenderop
TRPV5 is unique within the large TRP channel family for displaying a high Ca(2+) selectivity together with Ca(2+)-dependent inactivation. Our study aims to uncover novel insights into channel gating through in-depth structure-function analysis. We identify an exceptional tryptophan (W583) at the terminus of the intracellular pore that is unique for TRPV5 (and TRPV6). A combination of site-directed mutagenesis, biochemical and electrophysiological analysis, together with homology modeling, demonstrates that W583 is part of the gate for Ca(2+) permeation...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270862/the-polypharmacology-browser-a-web-based-multi-fingerprint-target-prediction-tool-using-chembl-bioactivity-data
#18
Mahendra Awale, Jean-Louis Reymond
BACKGROUND: Several web-based tools have been reported recently which predict the possible targets of a small molecule by similarity to compounds of known bioactivity using molecular fingerprints (fps), however predictions in each case rely on similarities computed from only one or two fps. Considering that structural similarity and therefore the predicted targets strongly depend on the method used for comparison, it would be highly desirable to predict targets using a broader set of fps simultaneously...
2017: Journal of Cheminformatics
https://www.readbyqxmd.com/read/28152538/two-cases-of-mistaken-polyuria-and-nephrocalcinosis-in-infants-with-glucose-galactose-malabsorption-a-possible-role-of-1-25-oh-2d3%C3%A2
#19
Melissa Fiscaletti, Marie-Jeanne Lebel, Nathalie Alos, Geneviève Benoit, Prévost Jantchou
BACKGROUND/AIMS: Glucose-galactose malabsorption (GGM) is a rare and potentially fatal disorder. The autosomal recessive mutation of the SGLT1 gene interferes with the active glucose transport in the gut resulting in osmotic diarrhea and failure to thrive (FTT). Two nonrelated infants with GGM are presented as well as a novel mutation in SGLT1. CASE PRESENTATION: The first case consulted for FTT and presented with hypercalcemia and hypercalciuria. His mother had self-medicated with high doses of vitamin D...
2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/28150073/first-in-human-phase-i-study-of-sor-c13-a-trpv6-calcium-channel-inhibitor-in-patients-with-advanced-solid-tumors
#20
S Fu, H Hirte, S Welch, T T Ilenchuk, T Lutes, C Rice, N Fields, A Nemet, D Dugourd, S Piha-Paul, V Subbiah, L Liu, J Gong, D Hong, J M Stewart
Introduction This was an open-label, dose escalation (3 + 3 design), Phase I study of SOR-C13 in patients with advanced tumors of epithelial origin. Primary objectives were to assess safety/tolerability and pharmacokinetics. Secondary goals were to assess pharmacodynamics and efficacy of SOR-C13. Methods SOR-C13 was administered IV QD on days 1-3 and 8-10 of a 21-day cycle. Doses were 2.75 and 5.5 mg/kg (20-min infusion) and 1.375, 2.75, 4.13 and 6.2 mg/kg (90-min infusion). Toxicity was assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4...
June 2017: Investigational New Drugs
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