Production of Ds0∗(2317)D^*_{s0}(2317) and Ds1(2460)D_{s1}(2460) in BB decays as D(∗)KD^{(*)}K and Ds(∗)ηD^{(*)}_s\eta molecules

The molecular nature of $D_{s0}^{\ast}(2317)$ and $D_{s1}(2460)$ have been extensively studied from the perspective of their masses, decay properties, and production rates. In this work, we study the weak decays of $B \to \bar{D}^{(\ast)}D_{s0}^{*}(2317)$ and $B \to \bar{D}^{(\ast)}D_{s1}(2460)$ by invoking triangle diagrams where the $B$ meson first decays weakly into $\bar{D}^{(\ast)}D_{s}^{(\ast)}$ and $J/\psi K$($\eta_{c}K$), and then the $D_{s0}^{\ast}(2317)$ and $D_{s1}(2460)$ are dynamically generated by the final-state interactions of $D_{s}^{(\ast)}\eta$ and $D^{(\ast)}K$ via exchanges of $\eta$ and $D^{(\ast)}$ mesons. The obtained absolute branching fractions of Br$[B \to \bar{D}^{(\ast)}D_{s0}^{*}(2317)]$ are in reasonable agreement with the experimental data, while the branching fractions of Br$[B \to \bar{D}^{(\ast)}D_{s1}(2460)]$ are smaller than the experimental central values by almost a factor of two to three. We tentatively attribute such a discrepancy to either reaction mechanisms missing in the present work or the likely existence of a relatively larger $c\bar{s}$ component in the $D_{s1}(2460)$ wave function.Comment: 17 pages, 4 figure

Characterization of a New M13 Metallopeptidase from Deep-Sea Shewanella sp. E525-6 and Mechanistic Insight into Its Catalysis

Bacterial extracellular peptidases are important for bacterial nutrition and organic nitrogen degradation in the ocean. While many peptidases of the M13 family from terrestrial animals and bacteria are studied, there has been no report on M13 peptidases from marine bacteria. Here, we characterized an M13 peptidase, PepS, from the deep-sea sedimentary strain Shewanella sp. E525-6, and investigated its substrate specificity and catalytic mechanism. The gene pepS cloned from strain E525-6 contains 2085 bp and encodes an M13 metallopeptidase. PepS was expressed in Escherichia coli and purified. Among the characterized M13 peptidases, PepS shares the highest sequence identity (47%) with Zmp1 from Mycobacterium tuberculosis, indicating that PepS is a new member of the M13 family. PepS had the highest activity at 30°C and pH 8.0. It retained 15% activity at 0°C. Its half life at 40°C was only 4 min. These properties indicate that PepS is a cold-adapted enzyme. The smallest substrate for PepS is pentapeptide, and it is probably unable to cleave peptides of more than 30 residues. PepS prefers to hydrolyze peptide bonds with P1’ hydrophobic residues. Structural and mutational analyses suggested that His531, His535 and Glu592 coordinate the catalytic zinc ion in PepS, Glu532 acts as a nucleophile, and His654 is probably involved in the transition state stabilization. Asp538 and Asp596 can stablize the orientations of His531 and His535, and Arg660 can stablize the orientation of Asp596. These results help in understanding marine bacterial peptidases and organic nitrogen degradation

Structural mechanism for bacterial oxidation of oceanic trimethylamine into trimethylamine N -oxide

Trimethylamine (TMA) and trimethylamine N-oxide (TMAO) are widespread in the ocean and are important nitrogen source for bacteria. TMA monooxygenase (Tmm), a bacterial flavin-containing monooxygenase (FMO), is found widespread in marine bacteria and is responsible for converting TMA to TMAO. However, the molecular mechanism of TMA oxygenation by Tmm has not been explained. Here, we determined the crystal structures of two reaction intermediates of a marine bacterial Tmm (RnTmm) and elucidated the catalytic mechanism of TMA oxidation by RnTmm. The catalytic process of Tmm consists of a reductive half-reaction and an oxidative half-reaction. In the reductive half-reaction, FAD is reduced and a C4a-hydroperoxyflavin intermediate forms. In the oxidative half-reaction, this intermediate attracts TMA through electronic interactions. After TMA binding, NADP+ bends and interacts with D317, shutting off the entrance to create a protected micro-environment for catalysis and exposing C4a-hydroperoxyflavin to TMA for oxidation. Sequence analysis suggests that the proposed catalytic mechanism is common for bacterial Tmms. These findings reveal the catalytic process of TMA oxidation by marine bacterial Tmm and first show that NADP+ undergoes a conformational change in the oxidative half-reaction of FMOs

Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate

人类遗传学家James V. Neel在1962年首次提出了“节俭基因”这一概念，认为现今人类导致包括肥胖症、糖尿病和高血压等代谢障碍的基因是因为生理系统为了适应远古环境食物富足和食物缺乏的周期性改变而筛选出的，可以让远古人类在食物富足的短暂时期中快速增肥，以应对随时将到来的食物缺乏时期。这类基因在当时环境下有很大的优越性，但对于当今食物富足的社会则截然相反。这篇论文中林圣彩教授团队揭示了乙酰转移酶TIP60通过乙酰化脂肪合成途径的代谢酶lipin 1并促进其向内质网转运，从而提高脂肪合成速率，揭示了TIP60作为一个“节俭基因”的功能和作用机制。该研究阐明了脂肪合成途径中首个受蛋白质乙酰化修饰调控的途径，揭示了TIP60作为经典转录调控因子之外的又一重要生物学功能，为开发防治肥胖症及其相关代谢紊乱疾病提供了新的药物作用靶点。博士后李阳、博士生宋林涛和硕士生孙玉是该论文的共同第一作者。【Abstract】Obesity is characterized by excessive fatty acid conversion to triacylglycerols (TAGs) in adipose tissues. However, how signaling networks sense fatty acids and connect to the stimulation of lipid synthesis remains elusive. Here, we show that homozygous knock-in mice carrying a point mutation at the Ser86 phosphorylation site of acetyltransferase Tip60 (Tip60SA/SA) display remarkably reduced body fat mass, and Tip60SA/SA females fail to nurture pups to adulthood due to severely reduced milk TAGs. Mechanistically, fatty acids stimulate Tip60-dependent acetylation and endoplasmic reticulum translocation of phosphatidic acid phosphatase lipin 1 to generate diacylglycerol for TAG synthesis, which is repressed by deacetylase Sirt1. Inhibition of Tip60 activity strongly blocks fatty acid-induced TAG synthesis while Sirt1 suppression leads to increased adiposity. Genetic analysis of loss-of-function mutants in Saccharomyces cerevisiae reveals a requirement of ESA1, yeast ortholog of Tip60, in TAG accumulation. These findings uncover a conserved mechanism linking fatty acid sensing to fat synthesis.This work was supported by grants from the National Natural Science Foundation of China (#31690101, #31430094, #31600961 and #31571214) and National Key Research and Development Project of China (2016YFA0502001). 该研究受到了国家自然科学基金和中国国家重点研发计划项目的资助

Relationship between Serum Levels of OPG and TGF- β

The objective of this study was to investigate the relationship between serum levels of OPG, TGF-β1, and TGF-β2 and BMD decrease rate (BDR) in native Chinese women. This cross-sectional study was performed on 465 healthy native Chinese women aged 35–80 years. Serum levels of OPG, TGF-β1, and TGF-β2 were determined. BDR was measured by DXA at the posteroanterior spine, hip, and distal forearm. At all skeletal sites tested, there was a negative correlation between BDR and serum levels of both OPG (r=−0.122 to –0.230, all P = 0.007–0.000) and TGF-β2 (r=−0.100 to –0.173, all P = 0.029–0.000) and a positive correlation between BDR and serum TGF-β1 (r=0.245−0.365, all P=0.000). After adjustment for age and BMI, there were no statistically significant correlations between serum levels of OPG or TGF-β2 and BDR. However, statistically significant correlations between serum TGF-β1 and BDR at the lumbar spine and ultradistal forearm remained. Multiple linear regression stepwise analysis showed that serum OPG could explain 1.4–3.7% of BDR variation. Serum TGF-β1 was a positive determinant of BDR and could explain 5.3–13.3% of BDR variation

Expression Profile Matrix of Arabidopsis Transcription Factor Genes Suggests Their Putative Functions in Response to Environmental Stresses

Numerous studies have shown that transcription factors are important in regulating plant responses to environmental stress. However, specific functions for most of the genes encoding transcription factors are unclear. In this study, we used mRNA profiles generated from microarray experiments to deduce the functions of genes encoding known and putative Arabidopsis transcription factors. The mRNA levels of 402 distinct transcription factor genes were examined at different developmental stages and under various stress conditions. Transcription factors potentially controlling downstream gene expression in stress signal transduction pathways were identified by observed activation and repression of the genes after certain stress treatments. The mRNA levels of a number of previously characterized transcription factor genes were changed significantly in connection with other regulatory pathways, suggesting their multifunctional nature. The expression of 74 transcription factor genes responsive to bacterial pathogen infection was reduced or abolished in mutants that have defects in salicylic acid, jasmonic acid, or ethylene signaling. This observation indicates that the regulation of these genes is mediated at least partly by these plant hormones and suggests that the transcription factor genes are involved in the regulation of additional downstream responses mediated by these hormones. Among the 43 transcription factor genes that are induced during senescence, 28 of them also are induced by stress treatment, suggesting extensive overlap responses to these stresses. Statistical analysis of the promoter regions of the genes responsive to cold stress indicated unambiguous enrichment of known conserved transcription factor binding sites for the responses. A highly conserved novel promoter motif was identified in genes responding to a broad set of pathogen infection treatments. This observation strongly suggests that the corresponding transcription factors play general and crucial roles in the coordinated regulation of these specific regulons. Although further validation is needed, these correlative results provide a vast amount of information that can guide hypothesis-driven research to elucidate the molecular mechanisms involved in transcriptional regulation and signaling networks in plants

Secreted Phospholipase A2 Involvement in Neurodegeneration: Differential Testing of Prosurvival and Anti-Inflammatory Effects of Enzyme Inhibition

There is increased interest in the contribution of secreted phospholipase A2 (sPLA2) enzymes to neurodegenerative diseases. Systemic treatment with the nonapeptide CHEC-9, a broad spectrum uncompetitive inhibitor of sPLA2, has been shown previously to inhibit neuron death and aspects of the inflammatory response in several models of neurodegeneration. A persistent question in studies of sPLA2 inhibitors, as for several other anti-inflammatory and neuroprotective compounds, is whether the cell protection is direct or due to slowing of the toxic aspects of the inflammatory response. To further explore this issue, we developed assays using SY5Y (neuronal cells) and HL-60 (monocytes) cell lines and examined the effects of sPLA2 inhibition on these homogeneous cell types in vitro. We found that the peptide inhibited sPLA2 enzyme activity in both SY5Y and HL-60 cultures. This inhibition provided direct protection to SY5Y neuronal cells and their processes in response to several forms of stress including exposure to conditioned medium from HL-60 cells. In cultures of HL-60 cells, sPLA2 inhibition had no effect on survival of the cells but attenuated their differentiation into macrophages, with regard to process development, phagocytic ability, and the expression of differentiation marker CD36, as well as the secretion of proinflammatory cytokines TNF-α and IL-6. These results suggest that sPLA2 enzyme activity organizes a cascade of changes comprising both cell degeneration and inflammation, processes that could theoretically operate independently during neurodegenerative conditions. The effectiveness of sPLA2 inhibitor CHEC-9 may be due to its ability to affect both processes in isolation. Testing potential anti-inflammatory/neuroprotective compounds with these human cell lines and their conditioned media may provide a useful screening tool prior to in vivo therapeutic applications

Low-Temperature Preparation of Superparamagnetic CoFe2O4 Microspheres with High Saturation Magnetization

Based on a low-temperature route, monodispersed CoFe2O4 microspheres (MSs) were fabricated through aggregation of primary nanoparticles. The microstructural and magnetic characteristics of the as-prepared MSs were characterized by X-ray diffraction/photoelectron spectroscopy, scanning/transmitting electron microscopy, and vibrating sample magnetometer. The results indicate that the diameters of CoFe2O4 MSs with narrow size distribution can be tuned from over 200 to ~330 nm. Magnetic measurements reveal these MSs exhibit superparamagnetic behavior at room temperature with high saturation magnetization. Furthermore, the mechanism of formation of the monodispersed CoFe2O4 MSs was discussed on the basis of time-dependent experiments, in which hydrophilic PVP plays a crucial role