Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme

Protein phosphatase 2A (PP2A) is a principal Ser/Thr phosphatase, the deregulation of which is associated with multiple human cancers, Alzheimer's disease and increased susceptibility to pathogen infections. How PP2A is structurally organized and functionally regulated remains unclear. Here we report the crystal structure of an AB'C heterotrimeric PP2A holoenzyme. The structure reveals that the HEAT repeats of the scaffold A subunit form a horseshoe-shaped fold, holding the catalytic C and regulatory B' subunits together on the same side. The regulatory B' subunit forms pseudo-HEAT repeats and interacts with the C subunit near the active site, thereby defining substrate specificity. The methylated carboxy-terminal tail of the C subunit interacts with a highly negatively charged region at the interface between A and B' subunits, suggesting that the C-terminal carboxyl methylation of the C subunit promotes B' subunit recruitment by neutralizing charge repulsion. Together, our structural results establish a crucial foundation for understanding PP2A assembly, substrate recruitment and regulation.     

The effect of nicotine on ethanol-induced gastric ulcers in rats

Summary Nicotine, in concentrations of 5 and 25 g/ml drinking water, given ad libitum for 10 days, dose-dependently increased lesion formation and worsened ethanol-induced ulceration in rat stomachs. Daily fluid intake and b.wt gain were not adversely affected by nicotine pretreatment.The authors are grateful to Mr C.T. Luk for his skilled technical assistance.     

Difference in direct charge-parity violation between charged and neutral B meson decays

Equal amounts of matter and antimatter are predicted to have been produced in the Big Bang, but our observable Universe is clearly matter-dominated. One of the prerequisites for understanding this elimination of antimatter is the nonconservation of charge-parity (CP) symmetry. So far, two types of CP violation have been observed in the neutral K meson (K(0)) and B meson (B(0)) systems: CP violation involving the mixing between K(0) and its antiparticle (and likewise for B(0) and ), and direct CP violation in the decay of each meson. The observed effects for both types of CP violation are substantially larger for the B(0) meson system. However, they are still consistent with the standard model of particle physics, which has a unique source of CP violation that is known to be too small to account for the matter-dominated Universe. Here we report that the direct CP violation in charged B(+/-)-->K(+/-)pi(0) decay is different from that in the neutral B(0) counterpart. The direct CP-violating decay rate asymmetry, (that is, the difference between the number of observed B(-)-->K(-)pi(0) event versus B(+)-->K(+) pi(0) events, normalized to the sum of these events) is measured to be about +7%, with an uncertainty that is reduced by a factor of 1.7 from a previous measurement. However, the asymmetry for versus B(0)-->K(+)pi(-) is at the -10% level. Although it is susceptible to strong interaction effects that need further clarification, this large deviation in direct CP violation between charged and neutral B meson decays could be an indication of new sources of CP violation-which would help to explain the dominance of matter in the Universe.     

Effect of TiO2 on the viscosity and structure of low-fluoride slag used for electroslag remelting of Ti-containing steels

The viscosity of CaF2–CaO–Al2O3–MgO–(TiO2) slag was measured using a rotating crucible viscometer. Raman spectroscopy analysis was performed to correlate the viscosity to slag structure. The viscosity of the slag was found to decrease with increasing TiO2 con-tent in the slag from 0 to 9.73wt%. The activation energy decreased from 95.16 kJ/mol to 79.40 kJ/mol with increasing TiO2 content in the slag. The introduction of TiO2 into the slag played a destructive role in Al–O–Al structural units and Q4 units by forming simpler structural units of Q2 and426TiO- chain. The amount of Al–O–Al significantly decreased with increasing TiO2 content. The relative fraction of4Q units in the [AlO4]5?-tetrahedral units shows a decreasing trend, whereas the relative fraction of2Q units and426TiO- chain increases with increasing TiO2 content accordingly. Consequently, the polymerization degree of the slag decreases with increasing TiO2 content. The varia-tion in slag structure is consistent with the change in measured viscosity.     

Antibiotics in early life alter the murine colonic microbiome and adiposity

Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we proposed that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy to young mice and evaluated changes in the composition and capabilities of the gut microbiome. Administration of subtherapeutic antibiotic therapy increased adiposity in young mice and increased hormone levels related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids, increases in colonic short-chain fatty acid levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation.     

Raman injection laser

Stimulated Raman scattering is a nonlinear optical process that, in a broad variety of materials, enables the generation of optical gain at a frequency that is shifted from that of the incident radiation by an amount corresponding to the frequency of an internal oscillation of the material. This effect is the basis for a broad class of tunable sources known as Raman lasers. In general, these sources have only small gain (approximately 10(-9) cm W(-1)) and therefore require external pumping with powerful lasers, which limits their applications. Here we report the realization of a semiconductor injection Raman laser designed to circumvent these limitations. The physics underlying our device differs in a fundamental way from existing Raman lasers: it is based on triply resonant stimulated Raman scattering between quantum-confined states within the active region of a quantum cascade laser that serves as an internal optical pump--the device is driven electrically and no external laser pump is required. This leads to an enhancement of orders of magnitude in the Raman gain, high conversion efficiency and low threshold. Our lasers combine the advantages of nonlinear optical devices and of semiconductor injection lasers, and could lead to a new class of compact and wavelength-agile mid-and far-infrared light sources.