Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands

Potassium channels are essential for maintaining a normal ionic balance across cell membranes. Central to this function is the ability of such channels to support transmembrane ion conduction at nearly diffusion-limited rates while discriminating for K+ over Na+ by more than a thousand-fold. This selectivity arises because the transfer of the K+ ion into the channel pore is energetically favoured, a feature commonly attributed to a structurally precise fit between the K+ ion and carbonyl groups lining the rigid and narrow pore. But proteins are relatively flexible structures that undergo rapid thermal atomic fluctuations larger than the small difference in ionic radius between K+ and Na+. Here we present molecular dynamics simulations for the potassium channel KcsA, which show that the carbonyl groups coordinating the ion in the narrow pore are indeed very dynamic ('liquid-like') and that their intrinsic electrostatic properties control ion selectivity. This finding highlights the importance of the classical concept of field strength. Selectivity for K+ is seen to emerge as a robust feature of a flexible fluctuating pore lined by carbonyl groups.     

Oxydation der Zucker durch Süssmandelemulsin (Rohferment nachHelferich)

Summary Emulsin (Rohferment ofHelferich) and similar enzyme preparations ofRosaceae-Amygdaloideae seeds have been found to exhibit a low but definite oxidizing activity towards aldohexoses in concentrated sugar solutions used for transglycosylation experiments.     

Release by sympathetic stimulation of α-methylnoradrenaline stored in the heart after administration of α-methyldopa

Résumé Dans les curs de lapins traités par l'-méthyldopa, la déplétion de la noradrénaline s'accompagne d'une fixation importante d'-méthylnoradrénaline. Sous l'effet de stimulation sympathique ou d'iodure de diméthylphényl-pipérazinium, ces curs libèrent conjointement de la noradrénaline et de l'-méthylnoradrénaline.Les quantités respectives de noradrénaline et d'-méthylnoradrénaline libérées par stimulation sympathique sont les mêmes que celles libérées par l'iodure de diméthyl-phényl-pipérazinium et que celles trouvées dans le myocarde lui-même.     

β-Fructofuranosidase activity in pea seeds

Zusammenfassung In trockenen Erbsensamen wurde alkalische-Fruktofuranosidase mit Transferaseaktivität gefunden. Ein angereichertes Enzympräparat, durchL-Cystein, 2-Merkaptoethanol und Glutathion aktiviert und durchp-Chlormerkuribenzoat, Iodoacetamid,N-Ethylmaleimide undL-Cystin inhibiert, wurde hergestellt.     

Small-scale structure of the geodynamo inferred from Oersted and Magsat satellite data

The 'geodynamo' in the Earth's liquid outer core produces a magnetic field that dominates the large and medium length scales of the magnetic field observed at the Earth's surface. Here we use data from the currently operating Danish Oersted satellite, and from the US Magsat satellite that operated in 1979/80, to identify and interpret variations in the magnetic field over the past 20 years, down to length scales previously inaccessible. Projected down to the surface of the Earth's core, we found these variations to be small below the Pacific Ocean, and large at polar latitudes and in a region centred below southern Africa. The flow pattern at the surface of the core that we calculate to account for these changes is characterized by a westward flow concentrated in retrograde polar vortices and an asymmetric ring where prograde vortices are correlated with highs (and retrograde vortices with lows) in the historical (400-year average) magnetic field. This pattern is analogous to those seen in a large class of numerical dynamo simulations, except for its longitudinal asymmetry. If this asymmetric state was reached often in the past, it might account for several persistent patterns observed in the palaeomagnetic field. We postulate that it might also be a state in which the geodynamo operates before reversing.     

Metabolic implications in the elevation of serum activity of intestinal alkaline phosphatase in chronic renal failure

Summary The activity of intestinal isoenzyme of serum alkaline phosphatase was evaluated in 21 non-dialyzed patients with advanced renal failure and in 52 patients on regular hemodialysis. In patients without hepatopathy, a significant inverse correlation was found between the enzyme activity and serum calcium levels. Hepatopathy was the most significant variable influencing the enzyme activity in patients on dialysis. Secondary hyperparathyroidism and a decreased rate in enzyme elimination should be assessed for the above-normal activities of intestinal ALP in serum in chronic renal failure.     

Neuroendocrine dysplasia in mice lacking protein tyrosine phosphatase sigma

Protein tyrosine phosphatase sigma (PTP-sigma, encoded by the Ptprs gene) is a member of the LAR subfamily of receptor-like protein tyrosine phosphatases that is highly expressed during mammalian embryonic development in the germinal cell layer lining the lateral ventricles of the developing brain, dorsal root ganglia, Rathke's pouch, olfactory epithelium, retina and developing lung and heart. On the basis of its expression and homology with the Drosophila melanogasterorthologues DPTP99 and DPTP100A (refs 5,6), which have roles in the targeting of axonal growth cones, we hypothesized that PTP-sigma may also have a modulating function in cell-cell interactions, as well as in axon guidance during mammalian embryogenesis. To investigate its function in vivo, we generated Ptprs-deficient mice. The resulting Ptprs-/-animals display retarded growth, increased neonatal mortality, hyposmia and hypofecundity. Anatomical and histological analyses showed a decrease in overall brain size with a severe depletion of luteinizing hormone-releasing hormone (LHRH)-immunoreactive cells in Ptprs-/- hypothalamus. Ptprs-/- mice have an enlarged intermediate pituitary lobe, but smaller anterior and posterior lobes. These results suggest that tyrosine phosphorylation-dependent signalling pathways regulated by PTP-sigma influence the proliferation and/or adhesiveness of various cell types in the developing hypothalamo-pituitary axis.     

Colossal cages in zeolitic imidazolate frameworks as selective carbon dioxide reservoirs

Zeolitic imidazolate frameworks (ZIFs) are porous crystalline materials with tetrahedral networks that resemble those of zeolites: transition metals (Zn, Co) replace tetrahedrally coordinated atoms (for example, Si), and imidazolate links replace oxygen bridges. A striking feature of these materials is that the structure adopted by a given ZIF is determined by link-link interactions, rather than by the structure directing agents used in zeolite synthesis. As a result, systematic variations of linker substituents have yielded many different ZIFs that exhibit known or predicted zeolite topologies. The materials are chemically and thermally stable, yet have the long-sought-after design flexibility offered by functionalized organic links and a high density of transition metal ions. Here we report the synthesis and characterization of two porous ZIFs-ZIF-95 and ZIF-100-with structures of a scale and complexity previously unknown in zeolites. The materials have complex cages that contain up to 264 vertices, and are constructed from as many as 7,524 atoms. As expected from the adsorption selectivity recently documented for other members of this materials family, both ZIFs selectively capture carbon dioxide from several different gas mixtures at room temperature, with ZIF-100 capable of storing 28 litres per litre of material at standard temperature and pressure. These characteristics, combined with their high thermal and chemical stability and ease of fabrication, make ZIFs promising candidate materials for strategies aimed at ameliorating increasing atmospheric carbon dioxide levels.     

Study of Single Plated Principle on Large Diameter Circular Weft Knitting Machine

A new theory and method that differs from the tradition-al single plated weft - knitting theory and method hasbeen expounded after theoretical analyzing and experi-mental proving. If the new method is used when platingstitch is knitted on large diameter weft knitting machine,the thorny problem of long standing that ground yarn iseasy to appear on the face side of fabric is solved. Thenew method, i.e, the production of physical ability oftraining uniform for serviceman has been used.     

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes

Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 × 10(-9), odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin.