Pathogenesis of hypertension in a mouse model for human CLCN2 related hyperaldosteronism

Human primary aldosteronism (PA) can be caused by mutations in several ion channel genes but mouse models replicating this condition are lacking. We now show that almost all known PA-associated CLCN2 mutations markedly increase ClC-2 chloride currents and generate knock-in mice expressing a constitutively open ClC-2 Cl(−) channel as mouse model for PA. The Clcn2(op) allele strongly increases the chloride conductance of zona glomerulosa cells, provoking a strong depolarization and increasing cytoplasmic Ca(2+) concentration. Clcn2(op) mice display typical features of human PA, including high serum aldosterone in the presence of low renin activity, marked hypertension and hypokalemia. These symptoms are more pronounced in homozygous Clcn2(op/op) than in heterozygous Clcn2+/op mice. This difference is attributed to the unexpected finding that only ~50 % of Clcn2(+/op) zona glomerulosa cells are depolarized. By reproducing essential features of human PA, Clcn2(op) mice are a valuable model to study the pathological mechanisms underlying this disease

Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction

Defects in the astrocytic membrane protein MLC1, the adhesion molecule GlialCAM or the chloride channel ClC-2 underlie human leukoencephalopathies. Whereas GlialCAM binds ClC-2 and MLC1, and modifies ClC-2 currents in vitro, no functional connections between MLC1 and ClC-2 are known. Here we investigate this by generating loss-of-function Glialcam and Mlc1 mouse models manifesting myelin vacuolization. We find that ClC-2 is unnecessary for MLC1 and GlialCAM localization in brain, whereas GlialCAM is important for targeting MLC1 and ClC-2 to specialized glial domains in vivo and for modifying ClC-2's biophysical properties specifically in oligodendrocytes (OLs), the cells chiefly affected by vacuolization. Unexpectedly, MLC1 is crucial for proper localization of GlialCAM and ClC-2, and for changing ClC-2 currents. Our data unmask an unforeseen functional relationship between MLC1 and ClC-2 in vivo, which is probably mediated by GlialCAM, and suggest that ClC-2 participates in the pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Effect of a phytostimulant blend as feed additive on the performance of the lactating saanen goat

The aim of the present trial was to assess an herbal blend as additive on the performance and in vivo digestibility of producing Saanen goats. In the trial nine goats in the middle of production, individually caged were used to evaluate the effect of the addition of an herbal mixture (Fortimax8 0, 0.5 and 1.0kg ton 1) to the concentrate. The herbal mix increased the daily feed intake as well as the milk yield (plus 36.7'4 and 24% with 0.5 and 1kg ton 1);p&lt;0.05) with no effect on milk nutrient concentration (p&gt;0.05) but slightly affected their daily yield. On the other hand, the nutrients total tract digestibility was no affected (p&gt;0.05). Therefore, it can be concluded that with the addition of an herbal blend to the concentrate there is an improvement on the productivity of the dairy goat without affecting digestibility. © Medwell Journals, 2014

Quail egg yield and quality of the Coturnix coturnix response to the addition level of agave inulin to the drinking water

To assess the effect of agave inulin addition to drinking water, one hundred (65 days old) Coturnix coturnix japonica hens were divided randomly into four groups with five birds per cage. Twenty five birds were assigned to each of the following treatments: i) control; addition of agave inulin in the drinking water at; ii) 2.0% (w/w), iii) 4.0%; and iv) 6%. The feeding trial lasted for six weeks. Inulin increased (P0.05). The egg weight was similar among treatments (average 12.70 g) and varied slightly with the inulin level (P=0.0537). The egg shell (percentage of the egg) was not influenced by the inulin. But, the calcium concentration in the eggshell of the present trial varied with the level on the agave inulin in the drinking water (P0.05). Then, the agave inulin addition to the drinking water increases the egg yield of Japanese quails. © L.J. Pérez de la Mora et al

Quantum correlations support probabilistic pure state cloning

To assess the effect of agave inulin addition to drinking water, one hundred (65 days old) Coturnix coturnix japonica hens were divided randomly into four groups with five birds per cage. Twenty five birds were assigned to each of the following treatments: i) control; addition of agave inulin in the drinking water at; ii) 2.0% (w/w), iii) 4.0%; and iv) 6%. The feeding trial lasted for six weeks. Inulin increased (P0.05). The egg weight was similar among treatments (average 12.70 g) and varied slightly with the inulin level (P=0.0537). The egg shell (percentage of the egg) was not influenced by the inulin. But, the calcium concentration in the eggshell of the present trial varied with the level on the agave inulin in the drinking water (P0.05). Then, the agave inulin addition to the drinking water increases the egg yield of Japanese quails. " L.J. Pérez de la Mora et al.",,,,,,"10.4081/ijas.2014.2981",,,"http://hdl.handle.net/20.500.12104/43978","http://www.scopus.com/inward/record.url?eid=2-s2.0-84901640087&partnerID=40&md5=e84ca863c8009182019213ff094dc437",,,,,,"2",,"Italian Journal of Animal Science",,"12