There are four isoforms of the ␣ subunit (␣1-4) and three isoforms of the  subunit (1-3) of Na,K-ATPase, with distinct tissue-specific distribution and physiological functions. ␣2 is thought to play a key role in cardiac and smooth muscle contraction and be an important target of cardiac glycosides. An ␣2-selective cardiac glycoside could provide important insights into physiological and pharmacological properties of ␣2. The isoform selectivity of a large number of cardiac glycosides has been assessed utilizing ␣11, ␣21, and ␣31 isoforms of human Na,K-ATPase expressed in Pichia pastoris and the purified detergent-soluble isoform proteins. Binding affinities of the digitalis glycosides, digoxin, -methyl digoxin, and digitoxin show moderate but highly significant selectivity (up to 4-fold) for ␣2/␣3 over ␣1 (K D ␣1 > ␣2 ؍ ␣3). By contrast, ouabain shows moderate selectivity (≈2.5-fold) for ␣1 over ␣2 (K D ␣1 < ␣3 < ␣2). Binding affinities for the three isoforms of digoxigenin, digitoxigenin, and all other aglycones tested are indistinguishable (K D ␣1 ؍ ␣3 ؍ ␣2), showing that the sugar determines isoform selectivity. Selectivity patterns for inhibition of Na,K-ATPase activity of the purified isoform proteins are consistent with binding selectivities, modified somewhat by different affinities of K ؉ ions for antagonizing cardiac glycoside binding on the three isoforms. The mechanistic insight on the role of the sugars is strongly supported by a recent structure of Na,K-ATPase with bound ouabain, which implies that aglycones of cardiac glycosides cannot discriminate between isoforms. In conclusion, several digitalis glycosides, but not ouabain, are moderately ␣2-selective. This supports a major role of ␣2 in cardiac contraction and cardiotonic effects of digitalis glycosides.
HBP formula beneficially affected infant gut microbiota by increasing the Lactobacillus and bifidobacteria counts in fecal stools.
Human milk provides the optimal balanced nutrition for the growing infant in the first months after birth. The human mammary gland has evolved with unusual pathways, resulting in a specific positioning of fatty acids at the outer sn-1 and sn-3, and center sn-2 of the triacylglyceride, which is different from the triglycerides in other human tissues and plasma. The development of structured triglycerides enables mimicking the composition as well as structure of human milk fat in infant formulas. Studies conducted two decades ago, together with very recent studies, have provided increasing evidence that this unusual positioning of 16:0 in human milk triglycerides has a significant role for infant health in different directions, such as fat and calcium absorption, bone health, intestinal flora and infant comfort. This review aims to unravel the relevance of human milk triglyceride sn-2 16:0 for intestinal health and inflammatory pathways and for other post-absorption effects.
Calculations of electron inelastic mean free paths and stopping powers for several alkali halides (KF, KCl, KBr, and KI) and metal oxides (BeO, MgO, SiOZ, and A1203) have been performed in the 50 eV to 10 keV energy range. The complex dielectric formalism, improved to include the energy gap, was used for estimating the valence part of the transport characteristics, whereas the part related to electron-core interactions was evaluated according to Gryzinski's theory. An extended comparison of these calculations with the available experimental data as well as with other theoretical predictions is presented. Trends of the energy dependence of the inelastic mean free path and stopping power in alkali halides are studied. The role of the plasmon deexcitation process as a source for low-energy electrons in secondary electron emission spectra is discussed. The presented data can be used in Monte-Carlo simulations of electron transport in the considered materials.
Human alpha1 and alpha2 isoforms of Na,K-ATPase have been expressed with porcine 10*Histidine-tagged beta1 subunit in Pichia pastoris. Methanol-induced expression of alpha2 is optimal at 20 degrees C, whereas at 25 degrees C, which is optimal for expression of alpha1, alpha2 is not expressed. Detergent-soluble alpha2beta1 and alpha1beta1 complexes have been purified in a stable and functional state. alpha2beta1 shows a somewhat lower Na,K-ATPase activity and higher K0.5K compared to alpha1beta1, while values of K0.5Na and KmATP are similar. Ouabain inhibits both alpha1beta1 (K0.5 24.6 +/- 6 nM) and alpha2beta1 (K0.5 102 +/- 14 nM) with high affinity. A striking difference between the isoforms is that alpha2beta1 is unstable. Both alpha1beta1 and alpha2beta1 complexes, prepared in C12E8 with an added phosphatidyl serine, are active, but alpha2beta1 is rapidly inactivated at 0 degrees C. Addition of low concentrations of cholesterol with 1-stearoyl-2-oleoyl-sn-glycero-3-[phospho-l-serine] (SOPS) stabilizes strongly, maintaining alpha2beta1 active up to two weeks at 0 degrees C. By contrast, alpha1beta1 is stable at 0 degrees C without added cholesterol. Both alpha1beta1 and alpha2beta1 complexes are stabilized by cholesterol at 37 degrees C. Human FXYD1 spontaneously associates in vitro with either alpha1beta1 or alpha2beta1, to form alpha1beta1/FXYD1 and alpha2beta1/FXYD1 complexes. The reconstituted FXYD1 protects both alpha1beta1 and alpha2beta1 very strongly against thermal inactivation. Instability of alpha2 is attributable to suboptimal phophatidylserine-protein interactions. Residues within TM8, TM9 and TM10, near the alphabeta subunit interface, may play an important role in differential interactions of lipid with alpha1 and alpha2, and affect isoform stability. Possible physiological implications of isoform interactions with phospholipids and FXYD1 are discussed.
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