No abstract

No abstract

The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.

Photosynthetic light harvesting in excess light is regulated by a process known as feedback deexcitation. Femtosecond transient absorption measurements on thylakoid membranes show selective formation of a carotenoid radical cation upon excitation of chlorophyll under conditions of maximum, steady-state feedback deexcitation. Studies on transgenic Arabidopsis thaliana plants confirmed that this carotenoid radical cation formation is correlated with feedback deexcitation and requires the presence of zeaxanthin, the specific carotenoid synthesized during high light exposure. These results indicate that energy transfer from chlorophyll molecules to a chlorophyllzeaxanthin heterodimer, which then undergoes charge separation, is the mechanism for excess energy dissipation during feedback deexcitation.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle weakness and early death resulting from dystrophin deficiency. Loss of dystrophin results in disruption of a large dystrophin glycoprotein complex (DGC) leading to pathologic calcium (Ca2+)-dependent signals that damage muscle cells 1–5. We have identified a structural and functional defect in the sarcoplasmic reticulum (SR) Ca2+ release channel/ryanodine receptor (RyR1) in the mdx mouse model of muscular dystrophy that may contribute to altered Ca2+ homeostasis in dystrophic muscles. RyR1 isolated from mdx skeletal muscle exhibited an age-dependent increase in S-nitrosylation coincident with dystrophic changes in the muscle. RyR1 S-nitrosylation depleted the channel complex of FKBP12 (or “calstabin1” for calcium channel stabilizing binding protein) resulting in “leaky” channels. Preventing calstabin1 depletion from RyR1 using S107, a compound that binds to the RyR1 channel and enhances the binding affinity of calstabin1 to the nitrosylated channel, inhibited SR Ca2+ leak, reduced biochemical and histologic evidence of muscle damage, improved muscle function and increased exercise performance in mdx mice. Thus, SR Ca2+ leak via RyR1 due to S-nitrosylation of the channel and calstabin1 depletion likely contributes to muscle weakness in muscular dystrophy and preventing the RyR1-mediated SR Ca2+ leak may provide a novel therapeutic approach.

Discovery of novel topological orders of condensed matters is of a significant interest in bothfundamental and applied physics due to the associated quantum conductance behaviors and unique symmetry-protected backscattering-immune propagation against defects, which inspired similar fantastic effects in classical waves system, leading to the revolution of the manipulation of wave propagation. To date, however, only few theoretical models were proposed to realize acoustic topological states. Here, we theoretically and experimentally demonstrate a two dimensional acoustic topological insulators with acoustic analogue of quantum spin Hall Effect. Due to the band inversion mechanism near the double Dirac cones, acoustic one-way pseudospin dependent

We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies.

Feedback de-excitation (qE) regulates light harvesting in plants to prevent inhibition of photosynthesis when light absorption exceeds photosynthetic capacity. Although the mechanism of qE is not completely understood, it is known to require a low thylakoid lumen pH, de-epoxidized xanthophylls, and the photosystem II protein PsbS. During a short-term 4-h exposure to excess light, three PsbS-and qE-deficient Arabidopsis thaliana mutants that differed in xanthophyll composition were more photoinhibited than the wild type. The extent of photoinhibition was the same in all of the mutants, suggesting that qE capacity rather than xanthophyll composition is critical for photoprotection in short-term high light, in contrast to longer-term high light conditions (days) when additional antioxidant roles of specific xanthophylls are evident. Plants with a 2-fold increase in qE capacity were generated by overexpression of PsbS, demonstrating that the level of PsbS limits the qE capacity in wild-type Arabidopsis. These results are consistent with the idea that variations in PsbS expression are responsible for species-specific and environmentally induced differences in qE capacity observed in nature. Furthermore, plants with higher qE capacity were more resistant to photoinhibition than the wild type. Increased qE was associated with decreased photosystem II excitation pressure and changes in the fractional areas of chlorophyll a fluorescence lifetime distributions, but not the lifetime centers, suggesting that qE protects from photoinhibition by preventing overreduction of photosystem II electron acceptors. Engineering of qE capacity by PsbS overexpression could potentially yield crop plants that are more resistant to environmental stress. P lants experience fluctuations in light intensity in nature, with quantitative changes occurring over several orders of magnitude and on time scales ranging from seconds to seasons. Because of these fluctuations, imbalances between light harvesting and utilization of absorbed light energy in photosynthesis occur frequently for most plants. Absorption of light in excess of a plant's capacity for CO 2 fixation has the potential to increase production of reactive intermediates and reactive oxygen species that can cause an inhibition of photosynthesis. To prevent this photoinhibition, plants and algae have evolved several regulatory mechanisms and antioxidant systems (1).In excess light, photosynthetic light harvesting is regulated by feedback de-excitation of singlet excited chlorophyll molecules in photosystem (PS) II. Feedback de-excitation, which can be measured as the qE component of nonphotochemical quenching of chlorophyll fluorescence (NPQ), is a nearly ubiquitous phenomenon in plants and eukaryotic algae that results in harmless thermal dissipation of excess absorbed light energy (reviewed in refs. 2 and 3). Induction and relaxation of qE occur rapidly (time scale of seconds to minutes), and qE has been considered to represent a protective mechanism that prevents PS II photoinhibition...