Temperature sensitivity of potassium flux into red blood cells in the familial pseudohyperkalaemia syndrome

The temperature dependence of potassium flux into the red cells of normal and pseudohyperkalaemic individuals over the range 4-40 degrees C was measured using 86RbCl as tracer. Flux through the pump was measured as the ouabain-sensitive component (0.2 mM ouabain) and flux via Na+,K+-cotransport was measured as the decrease in the rate of K+ influx in the presence of 1 mM furosemide. The residual passive permeability of the red cell plasma membranes to K+ was that influx which was unaffected by either inhibitor. When Na+ influxes were measured, the ratio of Na+ to K+ transported via the furosemide-sensitive component was 1 over the full temperature range studied. The temperature sensitivity of K+ influx via the pump was normal as was the enzymic activity of the Na+,K+-ATPase. In contrast, the activity of the Na+,K+-cotransport system in pseudohyperkalaemics was more temperature sensitive than that of controls and affected individuals also showed a greater passive permeability to K+ at low temperatures. Red cell membranes from affected individuals have significantly increased amounts of phosphatidylcholine which are balanced, to a degree, by a decreased content of phosphatidylethanolamiane. It is proposed that in this example of familial pseudohyperkalaemia there is an alteration in the structure of the red cell plasma membrane which influences the temperature sensitivity of both its cotransport and passive permeability properties.     

Action of Interferon in Enucleated Cells

Interferon induces protection of enucleated BSC-1 cells against infectious vesicular stomatitis virus production if cells are treated before, but not after, enucleation.     

The crystalline yolk-platelet proteins and their soluble plasma precursor in an amphibian, Xenopus laevis

A single lipophosphoprotein complex, vitellogenin, was isolated and purified from the plasma of oestrogen-stimulated female toads by preparative ultracentrifugation and chromatography on TEAE-cellulose (triethylaminoethylcellulose). The protein contains 12% lipid, 1.5% phosphorus, 1.6% calcium and smaller amounts of carbohydrates and biliverdin. In amino acid composition it is identical with total yolk-platelet protein. The platelet protein, however, is fractionated on TEAE-cellulose into two components, a high-molecular-weight lipovitellin and a smaller phosvitin. Analyses of the soluble plasma vitellogenin suggest that it is a complex of two phosvitin molecules covalently bound to one lipovitellin dimer, and that it is the immediate precursor of the yolk proteins, into which it is converted by a molecular rearrangement. Uptake of vitellogenin from the plasma into the growing oocyte, and its subsequent crystallization as a yolk platelet, appear to be enhanced by gonadotrophic hormones.     

Molecular genetics of the transcription factor GLIS3 identifies its dual function in beta cells and neurons

The GLIS family zinc finger 3 isoform (GLIS3) is a risk gene for Type 1 and Type 2 diabetes, glaucoma and Alzheimer's disease endophenotype. We identified GLIS3 binding sites in insulin secreting cells (INS1) (FDR q < 0.05; enrichment range 1.40–9.11 fold) sharing the motif wrGTTCCCArTAGs, which were enriched in genes involved in neuronal function and autophagy and in risk genes for metabolic and neuro-behavioural diseases. We confirmed experimentally Glis3-mediated regulation of the expression of genes involved in autophagy and neuron function in INS1 and neuronal PC12 cells. Naturally-occurring coding polymorphisms in Glis3 in the Goto-Kakizaki rat model of type 2 diabetes were associated with increased insulin production in vitro and in vivo, suggestive alteration of autophagy in PC12 and INS1 and abnormal neurogenesis in hippocampus neurons. Our results support biological pleiotropy of GLIS3 in pathologies affecting β-cells and neurons and underline the existence of trans?nosology pathways in diabetes and its co-morbidities.     

Sex determination and optimal development in the Moorish gecko,Tarentola mauritanica

Under temperature sex determination (TSD), sex is determined by temperature during embryonic development. Depending on ecological and physiological traits and plasticity, TSD species may face demographic collapse due to climate change. In this context, asymmetry in bilateral organisms can be used as a proxy for developmental instability and, therefore, deviations from optimal incubation conditions. Using Tarentola mauritanica gecko as a model, this study aimed first to confirm TSD, its pattern and pivotal temperature, and second to assess the local adaptation of TSD and variation of asymmetry patterns across four populations under different thermal regimes. Eggs were incubated at different temperatures, and hatchlings were sexed and measured. The number of lamellae was counted in adults and hatchlings. Results were compatible with a TSD pattern with males generated at low and females at high incubation temperatures. Estimated pivotal temperature coincided with the temperature producing lower embryonic mortality, evidencing selection towards balanced sex ratios. The temperature of oviposition was conservatively selected by gravid females. Asymmetry patterns found were likely related to nest temperature fluctuations. Overall, the rigidity of TSD may compromise reproductive success, and demographic stability in this species in case thermal nest choice becomes constrained by climate change.     

Cross-talk between hematopoiesis and angiogenesis signaling pathways

The relationship between hematopoietic cells and endothelial cells has been seen as an indication that a common progenitor, the hemangioblast, gives rise to both cell types in the yolk sac, the initial site of hematopoiesis and blood vessel formation during mammalian development. The existence of angioblast-like circulating endothelial precursor cells in adults humans has recently been suggested. In this review, we have summarized the principle mechanisms involved in the cross-talk signaling pathway between hematopoiesis and angiogenesis in order to further understand how the hematopoietic and vascular systems are established during the development.     

Rapid recovery of a population of the cryptic and evolutionarily distinct Hochstetter's Frog,Leiopelma hochstetteri,in a pest‐free environment

New Zealand's native frogs (genus Leiopelma) display a very high degree of endemism and belong to a distinctive and ancient evolutionary lineage. All four extant species are considered to be threatened or endangered, but the mechanisms behind their decline are poorly understood. Many of the potential factors causing population declines are confounded for the two species living on the mainland; in particular, habitat degradation and the presence of introduced mammalian pests have been difficult to disentangle in the past. Here we present data on a population of Hochstetter's Frog (Leiopelma hochstetteri) living in a pest‐free mainland sanctuary, the 3363‐ha Maungatautari Ecological Island. Survey data from this population shows a fourfold increase in numbers between 2009 and 2012 from a very low initial density. Our results suggest that for Hochstetter's Frog at least, and possibly the other mainland species of Leiopelma, introduced mammals are a major driving factor in population declines. Given that the frog population at Maungatautari was discovered by serendipity when planning for the pest‐free sanctuary was already well underway, this also highlights the conservation value of large pest‐free areas and ecosystem‐level management.     

Involvement of Neisseria meningitidis Lipoprotein GNA2091 in the Assembly of a Subset of Outer Membrane Proteins

GNA2091 of Neisseria meningitidis is a lipoprotein of unknown function that is included in the novel 4CMenB vaccine. Here, we investigated the biological function and the subcellular localization of the protein. We demonstrate that GNA2091 functions in the assembly of outer membrane proteins (OMPs) because its absence resulted in the accumulation of misassembled OMPs. Cell fractionation and protease accessibility experiments showed that the protein is localized at the periplasmic side of the outer membrane. Pulldown experiments revealed that it is not stably associated with the β-barrel assembly machinery, the previously identified complex for OMP assembly. Thus, GNA2091 constitutes a novel outer membrane-based lipoprotein required for OMP assembly. Furthermore, its location at the inner side of the outer membrane indicates that protective immunity elicited by this antigen cannot be due to bactericidal or opsonic activity of antibodies.