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| Open AccessEmbryonic vitamin D deficiency programs hematopoietic stem cells to induce type 2 diabetes
Environmental conditions during pregnancy contribute to offspring metabolic disease. Here, the authors show that immune cells reprogrammed in utero by maternal vitamin D deficiency increase lifetime diabetes risk in the offspring and are sufficient to transplant diabetes.
- Jisu Oh
- , Amy E. Riek
- & Carlos Bernal-Mizrachi
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Article
| Open AccessClinical and molecular correlation defines activity of physiological pathways in life-sustaining kidney xenotransplantation
Porcine kidney xenotransplantation is accelerating towards clinical testing. Here the authors present preclinical results examining xenograft growth and participation in renal endocrine pathways that can be used to inform clinical study design.
- Daniel J. Firl
- , Grace Lassiter
- & Katherine C. Hall
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Article
| Open AccessCavβ1 regulates T cell expansion and apoptosis independently of voltage-gated Ca2+ channel function
The function of voltage-gated calcium channels in T cells is not well understood and controversial. Here the authors report that a regulatory beta subunit of voltage-gated calcium channels regulates T cell function despite no evidence that these channels were functional within T cells during activation.
- Serap Erdogmus
- , Axel R. Concepcion
- & Stefan Feske
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Article
| Open AccessLsm12 is an NAADP receptor and a two-pore channel regulatory protein required for calcium mobilization from acidic organelles
Nicotinic acid adenine dinucleotide phosphate (NAADP) potent Ca2+ mobilizing second messenger which uniquely triggers Ca2+ release from acidic endolysosomal organelles. Here the authors identify Lsm12 as an NAADP receptor essential for NAADP-evoked Ca2+ release from lysosomes via NAADP binding on its Lsm domain.
- Jiyuan Zhang
- , Xin Guan
- & Jiusheng Yan
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Article
| Open AccessCytosolic sequestration of the vitamin D receptor as a therapeutic option for vitamin D-induced hypercalcemia
Current therapeutic strategies for vitamin D-induced hypercalcemia are poorly efficient. Here the authors identify a new interaction between the vitamin D receptor (VDR) and WBP4 controlling the subcellular localization of VDR and show that ZK168281, a VDR antagonist, enhances the interaction between VDR and WBP4 blunting VDR signalling and normalizing calcium levels in vitamin D-intoxicated mice.
- Daniela Rovito
- , Anna Y. Belorusova
- & Daniel Metzger
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Article
| Open AccessGenome-wide association study identifies 143 loci associated with 25 hydroxyvitamin D concentration
Vitamin D is a precursor of the steroid hormone 1,25-dihydroxyvitamin D3, and its deficiency is associated with many adverse health outcomes. Here, Revez et al. perform a genome-wide association study for circulating 25-hydroxyvitamin D in 417,580 individuals and test for potential causal relationships with other traits using Mendelian randomization.
- Joana A. Revez
- , Tian Lin
- & John J. McGrath
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Article
| Open AccessGenetic variants of calcium and vitamin D metabolism in kidney stone disease
Kidney stones form in the presence of overabundance of crystal-forming substances such as Ca2+ and oxalate. Here, the authors report genome-wide association analyses for kidney stone disease, report seven previously unknown loci and find that some of these loci also associate with Ca2+ concentration and excretion.
- Sarah A. Howles
- , Akira Wiberg
- & Dominic Furniss
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Article
| Open AccessPhosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion
Elevated inorganic phosphate levels promote excessive parathyroid hormone secretion, which contributes to the aetiology of secondary hyperparathyroidism. Here, the authors show that phosphate directly inhibits the calcium-sensing receptor, the main regulator of parathyroid hormone secretion.
- Patricia P. Centeno
- , Amanda Herberger
- & Donald T. Ward