New KCNN4 Variants Associated With Anemia: Stomatocytosis Without Erythrocyte Dehydration.

The K+ channel activated by the Ca2+, KCNN4, has been shown to contribute to red blood cell dehydration in the rare hereditary hemolytic anemia, the dehydrated hereditary stomatocytosis. We report two de novo mutations on KCNN4, We reported two de novo mutations on KCNN4, V222L and H340N, characterized at the molecular, cellular and clinical levels. Whereas both mutations were shown to increase the calcium sensitivity of the K+ channel, leading to channel opening for lower calcium concentrations compared to WT KCNN4 channel, there was no obvious red blood cell dehydration in patients carrying one or the other mutation. The clinical phenotype was greatly different between carriers of the mutated gene ranging from severe anemia for one patient to a single episode of anemia for the other patient or no documented sign of anemia for the parents who also carried the mutation. These data compared to already published KCNN4 mutations question the role of KCNN4 gain-of-function mutations in hydration status and viability of red blood cells in bloodstream.

Mechanisms of radiation in a bat group from the genus Pipistrellus inferred by phylogeography, demography and population genetics.

Here, we present a study of the Pipistrellus pipistrellus species complex, a highly diversified bat group with a radiation centre in the Mediterranean biodiversity hotspot. The study sample comprised 583 animals from 118 localities representatively covering the bats' range in the western Palearctic. We used fast-evolving markers (the mitochondrial D-loop sequence and 11 nuclear microsatellites) to describe the phylogeography, demography and population structure of this model taxon and address details of its diversification. The overall pattern within this group includes a mosaic of phylogenetically basal, often morphologically distant, relatively small and mostly allopatric demes in the Mediterranean Basin, as well as two sympatric sibling species in the large continental part of the range. The southern populations exhibit constant size, whereas northern populations show a demographic trend of growth associated with range expansion during the Pleistocene climate oscillations. There is evidence of isolation by distance and female philopatry in P. pipistrellus sensu stricto. Although the northern populations are reproductively isolated, we detected introgression events among several Mediterranean lineages. This pattern implies incomplete establishment of reproductive isolating mechanisms in these populations as well as the existence of a past reinforcement stage in the continental siblings. The occurrence of reticulations in the radiation centre among morphologically and ecologically derived relict demes suggests that adaptive unequal gene exchange within hybridizing populations could play a role in speciation and adaptive radiation within this group.

Noninvasive detection of vascular dysfunction in alcoholic patients.

Vasodilation is impaired in various conditions, such as hypercholesterolemia and tobacco use. We evaluated brachial artery flow-mediated vasodilation (FMD) after blood pressure (BP) cuff occlusion using high-resolution B-mode ultrasound in 20 alcoholics, without any coexisting conditions such as smoking, hypertension, or cholesterolemia, after a 3-month period of abstinence. They were compared with a control group of 20 alcohol-free healthy subjects. We measured the diameter of the brachial artery under baseline conditions, during reactive hyperemia (with increased flow causing endothelium-dependent dilatation), and after administration of sublingual glyceryl trinitrate (GTN), an endothelium-independent dilator. We performed an echocardiographic study (Esaote Au3) according to guidelines of the American Society of Echocardiography to assess left ventricular mass (LVM), wall thickness, systolic stress, and diastolic function changes. FMD (% diameter change) was significantly less in the alcoholic patients than in the controls (6.03+/-3.67 v 13.7+/-4.65; P < .05), whereas no difference was noted after GTN administration (13.7+/-7.97 v 16.0+/-5.12, P = NS). Echocardiographic study showed no differences between the study group for LVM, wall thickness, and systolic stress; diastolic function expressed as E/A ratio inversion was significantly impaired. These data demonstrate an impairment of endothelial-dependent vasodilatation in chronic alcohol abusers, which may contribute to the excess prevalence of cardiovascular diseases in these individuals.