Rab46 integrates Ca and histamine signaling to regulate selective cargo release from Weibel-Palade bodies.

Endothelial cells selectively release cargo stored in Weibel-Palade bodies (WPBs) to regulate vascular function, but the underlying mechanisms are poorly understood. Here we show that histamine evokes the release of the proinflammatory ligand, P-selectin, while diverting WPBs carrying non-inflammatory cargo away from the plasma membrane to the microtubule organizing center. This differential trafficking is dependent on Rab46 (CRACR2A), a newly identified Ca-sensing GTPase, which localizes to a subset of P-selectin-negative WPBs.

Natural and synthetic flavonoid modulation of TRPC5 channels.

Background And Purpose: The TRPC5 proteins assemble to create calcium-permeable, non-selective, cationic channels. We sought novel modulators of these channels through studies of natural products.

Experimental Approach: Intracellular calcium measurements and patch clamp recordings were made from cell lines.

Expression of a long variant of CRACR2A that belongs to the Rab GTPase protein family in endothelial cells.

CRACR2A protein is described in T cells as an EF-hand-containing modulator of calcium-release-activated calcium (CRAC) channels. Here we sought relevance to calcium entry of endothelial cells. Unexpectedly, short interfering RNA designed to deplete CRACR2A had no effect on CRAC channels in endothelial cells but reduced the abundance of a protein with about twice the mass of CRACR2A.

Piezo1 integration of vascular architecture with physiological force.

The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca(2+)-permeable non-selective cationic channels for detection of noxious mechanical impact. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology.

Inhibition of endothelial cell Ca²⁺ entry and transient receptor potential channels by Sigma-1 receptor ligands.

Background And Purpose: The Sigma-1 receptor (Sig1R) impacts on calcium ion signalling and has a plethora of ligands. This study investigated Sig1R and its ligands in relation to endogenous calcium events of endothelial cells and transient receptor potential (TRP) channels.

Experimental Approach: Intracellular calcium and patch clamp measurements were made from human saphenous vein endothelial cells and HEK 293 cells expressing exogenous human TRPC5, TRPM2 or TRPM3.

Constitutively active TRPC channels of adipocytes confer a mechanism for sensing dietary fatty acids and regulating adiponectin.

Rationale: Calcium entry is pivotal in the heart and blood vessels, but its significance and mechanisms in adipose tissue are largely unknown. An important factor produced by adipocytes is adiponectin, which confers myocardial protection, insulin-sensitization, and antiatherosclerotic effects.

Objective: To investigate the relevance of calcium channels to adipocytes and the production of adiponectin.

Orai1 and CRAC channel dependence of VEGF-activated Ca2+ entry and endothelial tube formation.

Rationale: Orai1 and the associated calcium release-activated calcium (CRAC) channel were discovered in the immune system. Existence also in endothelial cells has been suggested, but the relevance to endothelial biology is mostly unknown.

Objective: The aim of this study was to investigate the relevance of Orai1 and CRAC channels to vascular endothelial growth factor (VEGF) and endothelial tube formation.

Rapid and contrasting effects of rosiglitazone on transient receptor potential TRPM3 and TRPC5 channels.

The aim of this study was to generate new insight into chemical regulation of transient receptor potential (TRP) channels with relevance to glucose homeostasis and the metabolic syndrome. Human TRP melastatin 2 (TRPM2), TRPM3, and TRP canonical 5 (TRPC5) were conditionally overexpressed in human embryonic kidney 293 cells and studied by using calcium-measurement and patch-clamp techniques. Rosiglitazone and other peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists were investigated.

Neuropeptide modulation of a lumbar spinal reflex: potential implications for female sexual function.

Introduction: Neuropeptides are known to modulate female receptivity. However, even though receptivity is a spinal reflex, the role of neuropeptides within the spinal cord remains to be elucidated.

Aim: The aims were to (i) investigate neuropeptides in the lumbosacral region; and (ii) determine how neuropeptides modulate glutamate release from stretch Ia fibers, touch sensation Abeta fibers and Adelta/C pain fibers.

Understanding bowel problems in older people: Part 2.

Bowel problems can be devastating for patients and those who care for them. Accurate assessment is essential in determining the cause of symptoms and deciding treatment and management strategies. Treatment can be complex, but with care and patience improvement or cure is possible.

Understanding bowel problems in older people: part 1.

Bowel problems can be devastating for patients and those who care for them. Accurate assessment is essential to determine the cause of symptoms and to decide treatment and management strategies. Treatment and management can be complex but with care and patience improvement or cure is possible.

Urinalysis.

Urine analysis is an essential component of patient assessment, which is used for screening, diagnosis and planning care. This article discusses specimen collection and reagent strip testing.

cDNA cloning, functional expression, and characterization of chicken sulfotransferases belonging to the SULT1B and SULT1C families.

A search of the chicken expressed sequence tag (EST) database identified 2 cDNA clones that appeared to represent members of the SULT1B and SULT1C enzyme families. These cDNAs were fully sequenced and found to contain full-length inserts. Phylogenetic analysis of the derived amino acid sequences clearly placed them as the first members of the chicken SULT1B and SULT1C families, respectively, to be identified, and we propose they be named SULT1B1 and SULT1C1.

Assessment of performance of laboratories in determining acrylamide in crispbread.

A proficiency testing round was undertaken to assess the performance of laboratories to measure acrylamide in a sample of crispbread. Retail samples of crispbread were ground to a fine powder and after thorough mixing were packed in 40 g units for distribution. Ten samples were selected at random and analyzed in duplicate for acrylamide by liquid chromatography/mass spectrometry (LC/MS).