A role for the cystic fibrosis transmembrane conductance regulator in the nitric oxide-dependent release of Cl \u3csup\u3e–\u3c/sup\u3e from acidic organelles in amacrine cells

© 2017 the American Physiological Society. γ-Amino butyric acid (GABA) and glycine typically mediate synaptic inhibition because their ligandgated ion channels support the influx of Cl – . However, the electrochemical gradient for Cl – across the postsynaptic plasma membrane determines the voltage response of the postsynaptic cell. Typically, low cytosolic Cl – levels support inhibition, whereas higher levels of cytosolic Cl – can suppress inhibition or promote depolarization. We previously reported that nitric oxide (NO) releases Cl – from acidic organelles and transiently elevates cytosolic Cl – , making the response to GABA and glycine excitatory. In this study, we test the hypothesis that the cystic fibrosis transmembrane conductance regulator (CFTR) is involved in the NO-dependent efflux of organellar Cl – . We first establish the mRNA and protein expression of CFTR in our model system, cultured chick retinal amacrine cells. Using whole cell voltage- clamp recordings of currents through GABA-gated Cl – channels, we examine the effects of pharmacological inhibition of CFTR on the NO-dependent release of internal Cl – . To interfere with the expression of CFTR, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing. We find that both pharmacological inhibition and CRISPR/Cas9-mediated knockdown of CFTR block the ability of NO to release Cl – from internal stores. These results demonstrate that CFTR is required for the NO-dependent efflux of Cl – from acidic organelles. NEW & NOTEWORTHY Although CFTR function has been studied extensively in the context of epithelia, relatively little is known about its function in neurons. We show that CFTR is involved in an NO-dependent release of Cl – from acidic organelles. This internal function of CFTR is particularly relevant to neuronal physiology because postsynaptic cytosolic Cl – levels determine the outcome of GABA- and glycinergic synaptic signaling. Thus the CFTR may play a role in regulating synaptic transmission

Cystic lymphangioma of the breast in an infant successfully managed with intralesional bleomycin: a case report with relevant review of the literature

Cystic hygromas, also known as lymphangiomas, are unusual congenital malformations of the lymphatic system and commonly involve the head and neck region or axilla. Involvement of other sites such as breasts is very rare. The preferred mode of treatment for lymphangioma of the breast in adults or children is surgery. We report a case of breast lymphangioma in a 3-month-old male child, which was managed successfully by intralesional bleomycin.Keywords: breast, bleomycin, intralesional sclerosing agent, macrocystic lymphangiom

Protective and susceptibility effects of hSKCa3 allelic variants on juvenile myoclonic epilepsy

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Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing

Altres ajuts: Ambry Genetics, Myriad Genetics, Novartis (I), Pfizer (I)Massively parallel sequencing allows simultaneous testing of multiple genes associated with cancer susceptibility. Guidelines are available for variant classification; however, interpretation of these guidelines by laboratories and providers may differ and lead to conflicting reporting and, potentially, to inappropriate medical management. We describe conflicting variant interpretations between Clinical Laboratory Improvement Amendments-approved commercial clinical laboratories, as reported to the Prospective Registry of Multiplex Testing (PROMPT), an online genetic registry. Clinical data and genetic testing results were gathered from 1,191 individuals tested for inherited cancer susceptibility and self-enrolled in PROMPT between September 2014 and October 2015. Overall, 518 participants (603 genetic variants) had a result interpreted by more than one laboratory, including at least one submitted to ClinVar, and these were used as the final cohort for the current analysis. Of the 603 variants, 221 (37%) were classified as a variant of uncertain significance (VUS), 191 (32%) as pathogenic, and 34 (6%) as benign. The interpretation differed among reporting laboratories for 155 (26%). Conflicting interpretations were most frequently reported for CHEK2 and ATM, followed by RAD51C, PALB2, BARD1, NBN, and BRIP1. Among all participants, 56 of 518 (11%) had a variant with conflicting interpretations ranging from pathogenic/likely pathogenic to VUS, a discrepancy that may alter medical management. Conflicting interpretation of genetic findings from multiplex panel testing used in clinical practice is frequent and may have implications for medical management decisions

World squid fisheries

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Chemoprotective Effect of Sobatum against Lithium-Induced Oxidative Damage in Rats

Lithium therapy mainly used in curing some psychiatric diseases responsible for numerous undesirable side effects on different organs in humans. The present study explores the beneficial effect of sobatum, a purified compound of Solanum trilobatum, on lithium carbonate (Li2CO3)-induced multiple organ toxicity in rats. Li2CO3 (150 mg/kg body weight) was administered orally in drinking water for a period of 30 days to induce toxicity in rats. Li2CO3 could induce lipid peroxidation to a significant extent that was accompanied by marked reduction in reduced glutathione, SOD, CAT, GST, GPX activities, and parallel decline in ATP in tissues. Toxicity resulted in abnormal elevation of lipids such as cholesterol, triglycerides, phospholipids, and fatty acids in liver tissues. Treatment with sobatum affords substantial protection in liver and heart by altering all the parameters to near normal levels that were further confirmed by histological examination. Sobatum prevents Li2CO3-induced oxidative damage of DNA by reducing DNA fragmentation indicating its block on cell death. However, these results demonstrated that sobatum has the ability to suppress the drug-induced toxicity