Potential global stratotype sections and points in China for defining Cambrian stages and series

Three stratigraphic sections in the Cambrian of China that contain complete successions across important biohorizons having chronostratigraphic value, and that may be useful for developing Cambrian stage or series boundaries, are reviewed. The Wuliu section (Guizhou, South China), contains the FAD of Oryctocephalus indicus at 58.2 m above the base of the Kaili Formation. The Wangcun North section (Hunan, South China), contains the FADs of Ptychagnostus (or Acidusus) atavus, Ptychagnostus punctuosus, and Lejopyge laevigata at 1.2 m, 56.7 m, and 111.3 m, respectively, above the base of the Huaqiao Formation. The Xiaoyangqiao section (Jilin, Northeast China), contains the FAD of Cordylodus proavus in the Fengshan Formation at 10.89 m above the zero point of the section. A fourth potential stratotype section, the Wangcun South section (Hunan, South China), which contains the P. atavus, P. punctuosus, and L. laevigata zones, is discussed briefly.     

A graphical user interface (NWUSA) for Raman spectral processing,analysis and feature recognition

It is a practical necessity for non-professional users to interpret biologically derived Raman spectral information for obtaining accurate and reliable analytical results. An integrated Raman spectral analysis software (NWUSA) was developed for spectral processing, analysis, and feature recognition. It provides a user-friendly graphical interface to perform the following preprocessing tasks: spectral range selection, cosmic ray removal, polynomial fitting based background subtraction, Savitzky–Golay smoothing, area-under-curve normalization, mean-centered procedure, as well as multivariate analysis algorithms including principal component analysis (PCA), linear discriminant analysis, partial least squares-discriminant analysis, support vector machine (SVM), and PCA-SVM. A spectral dataset obtained from two different samples was utilized to evaluate the performance of the developed software, which demonstrated that the analysis software can quickly and accurately achieve functional requirements in spectral data processing and feature recognition. Besides, the open-source software can not only be customized with more novel functional modules to suit the specific needs, but also benefit many Raman based investigations, especially for clinical usages.     

Multiple Surface Plasmon Resonances in Compound Structure with Metallic Nanoparticle and Nanohole Arrays

The optical properties of a compound structure with metallic nanoparticle and nanohole arrays are numerically investigated by the means of finite-difference time domain method. We report on the observation of multi-valleys in the reflection spectra due to the excitation of surface plasmon (SP) resonant modes of the compound structure. Simulation results show that multiple SP resonances consist of surface plasmon polaritons on the gold film, localized surface plasmons on the nanoparticles, and coupling mode between them. These findings are important for applications utilizing multiple surface plasmon resonances.     

The gating charge pathway of an epilepsy-associated potassium channel accommodates chemical ligands

Voltage-gated potassium (Kv) channels derive their voltage sensitivity from movement of gating charges in voltage-sensor domains (VSDs). The gating charges translocate through a physical pathway in the VSD to open or close the channel. Previous studies showed that the gating charge pathways of Shaker and Kv1.2-2.1 chimeric channels are occluded, forming the structural basis for the focused electric field and gating charge transfer center. Here, we show that the gating charge pathway of the voltage-gated KCNQ2 potassium channel, activity reduction of which causes epilepsy, can accommodate various small molecule ligands. Combining mutagenesis, molecular simulation and electrophysiological recording, a binding model for the probe activator, ztz240, in the gating charge pathway was defined. This information was used to establish a docking-based virtual screening assay targeting the defined ligand-binding pocket. Nine activators with five new chemotypes were identified, and in vivo experiments showed that three ligands binding to the gating charge pathway exhibit significant anti-epilepsy activity. Identification of various novel activators by virtual screening targeting the pocket supports the presence of a ligand-binding site in the gating charge pathway. The capability of the gating charge pathway to accommodate small molecule ligands offers new insights into the gating charge pathway of the therapeutically relevant KCNQ2 channel.     

LncRNA CASC11 improves atherosclerosis by downregulating IL-9 and regulating vascular smooth muscle cell apoptosis and proliferation

LncRNA CASC11 is an oncogene in several types of cancer, while its role in atherosclerosis is unknown. In the present study we found that CASC11 was downregulated, while IL-9 was upregulated in plasma of atherosclerosis patients compared with healthy controls. Altered plasma levels of CASC11 and IL-9 distinguished atherosclerosis patients from healthy controls. CASC11 and IL-9 were significantly and inversely correlated in atherosclerosis patients but not in healthy controls. Exogenous IL-9 treatment failed to significantly affect expression levels of CASC11 in vascular smooth muscle cells (VSMC), while CASC11 overexpression resulted in the downregulation of IL-9. CASC11 overexpression also resulted in the downregulation of proliferation and promoted apoptosis of VSMC. Therefore, CASC11 may improve atherosclerosis by downregulating IL-9 and regulating VSMC apoptosis and proliferation.     

Atg7 is required for acrosome biogenesis during spermatogenesis in mice

The acrosome is a specialized organelle that covers the anterior part of the sperm nucleus and plays an essential role in the process of fertilization. The molecular mechanism underlying the biogenesis of this lysosome-related organelle (LRO) is still largely unknown. Here, we show that germ cell-specific Atg7-knockout mice were infertile due to a defect in acrosome biogenesis and displayed a phenotype similar to human globozoospermia; this reproductive defect was successfully rescued by intracytoplasmic sperm injections. Furthermore, the depletion of Atg7 in germ cells did not affect the early stages of development of germ cells, but at later stages of spermatogenesis, the proacrosomal vesicles failed to fuse into a single acrosomal vesicle during the Golgi phase, which finally resulted in irregular or nearly round-headed spermatozoa. Autophagic flux was disrupted in Atg7-depleted germ cells, finally leading to the failure of LC3 conjugation to Golgi apparatus-derived vesicles. In addition, Atg7 partially regulated another globozoospermia-related protein, Golgi-associated PDZ- and coiled-coil motif-containing protein (GOPC), during acrosome biogenesis. Finally, the injection of either autophagy or lysosome inhibitors into testis resulted in a similar phenotype to that of germ cell-specific Atg7-knockout mice. Altogether, our results uncover a new role for Atg7 in the biogenesis of the acrosome, and we provide evidence to support the autolysosome origination hypothesis for the acrosome.     

Normal frailty probit model for clustered interval‐censored failure time data

Clustered interval‐censored data commonly arise in many studies of biomedical research where the failure time of interest is subject to interval‐censoring and subjects are correlated for being in the same cluster. A new semiparametric frailty probit regression model is proposed to study covariate effects on the failure time by accounting for the intracluster dependence. Under the proposed normal frailty probit model, the marginal distribution of the failure time is a semiparametric probit model, the regression parameters can be interpreted as both the conditional covariate effects given frailty and the marginal covariate effects up to a multiplicative constant, and the intracluster association can be summarized by two nonparametric measures in simple and explicit form. A fully Bayesian estimation approach is developed based on the use of monotone splines for the unknown nondecreasing function and a data augmentation using normal latent variables. The proposed Gibbs sampler is straightforward to implement since all unknowns have standard form in their full conditional distributions. The proposed method performs very well in estimating the regression parameters as well as the intracluster association, and the method is robust to frailty distribution misspecifications as shown in our simulation studies. Two real‐life data sets are analyzed for illustration.     

广西北部湾茅尾海浮游真菌群落结构及其影响因子

浮游真菌在海洋食物网和生物地球化学循环中发挥着关键作用。【目的】为解析广西北部湾茅尾海不同季节浮游真菌群落结构及其关键环境影响因子，于2017年7月(夏季)、9月(秋季)、12月(冬季)和2018年3月(春季)期间在该海域设置7个站点，采集表层海水样品。【方法】利用内部转录间隔区(internal transcribed spacer, ITS)基因高通量测序技术，分析茅尾海浮游真菌群落结构与多样性。【结果】茅尾海海域浮游真菌隶属6个门、26个纲、71个目、167个科、282个属和374个种。主要浮游真菌类群为子囊菌门(Ascomycota, 82.14%)和担子菌门(Basidiomycota, 10.74%)，共占浮游真菌总丰度的92.88%。茅尾海浮游真菌群落Shannon指数和Simpson指数在春季最高，Chao1指数和丰富度(richness)指数在冬季最高。主坐标分析(principal coordinates analysis, PCoA)和相似性分析(analysis of similarities, ANOSIM)结果显示，不同季节浮游真菌群落的β多样性具有极显著差异(R=0.591 2, P<0.001)。通过随机森林模型分析(random forest modeling analysis, RF)，发现黄曲霉(Aspergillus flavus)、二色胶孔菌(Gloeoporus dichrous)、杂色曲霉(Aspergillus subversicolor)和微扁沃利雅炭皮菌(Whalleya microplaca)、翹鱗香菇(Lentinus squarrosulus)等20种海洋浮游真菌对环境变化敏感，可用于评估茅尾海富营养化状况。Spearman相关性分析表明，浮游真菌α多样性与海水pH、盐度和溶解氧(dissolved oxygen, DO)呈显著正相关关系(P<0.05)，与温度、叶绿素-a (chlorophyll a, Chl-a)以及总有机碳(total organic carbon, TOC)呈显著负相关关系(P<0.05)。方差分解分析(variance partitioning analysis, VPA)发现营养因子是浮游真菌群落结构的主要驱动因子。【结论】本研究可为揭示北部湾海洋浮游真菌多样性提供理论参考，并为茅尾海生态环境监测与资源利用提供科学依据。     

A high-efficiency gene silencing in plants using two-hit asymmetrical artificial MicroRNAs

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. They are produced through an enzyme-guided process called dicing and have an asymmetrical structure with two nucleotide overhangs at the 3′ ends. Artificial microRNAs (amiRNAs or amiRs) are designed to mimic the structure of miRNAs and can be used to silence specific genes of interest. Traditionally, amiRNAs are designed based on an endogenous miRNA precursor with certain mismatches at specific positions to increase their efficiency. In this study, the authors modified the highly expressed miR168a in Arabidopsis thaliana by replacing the single miR168 stem-loop/duplex with tandem asymmetrical amiRNA duplexes that follow the statistical rules of miRNA secondary structures. These tandem amiRNA duplexes, called “two-hit” amiRNAs, were shown to have a higher efficiency in silencing GFP and endogenous PDS reporter genes compared to traditional “one-hit” amiRNAs. The authors also demonstrated the effectiveness of “two-hit” amiRNAs in silencing genes involved in miRNA, tasiRNA, and hormone signalling pathways, individually or in families. Importantly, “two-hit” amiRNAs were also able to over-express endogenous miRNAs for their functions. The authors compare “two-hit” amiRNA technology with CRISPR/Cas9 and provide a web-based amiRNA designer for easy design and wide application in plants and even animals.     

Site-directed mutagenesis of epoxide hydrolase to probe catalytic amino acid residues and reaction mechanism

Epoxide hydrolase from Rhodococcus opacus catalyzes the stereospecific hydrolysis of cis-epoxysuccinate to L(+)-tartrate. It shows low but significant similarity to haloacid dehalogenase and haloacetate dehalogenase (16–23% identity). To identify catalytically important residues, we mutated 29 highly conserved charged and polar amino acid residues (except for one alanine). The replacement of D18, D193, R55, K164, H190, T22, Y170, N134 and A188 led to a significant loss in the enzyme activity, indicating their involvement in the catalysis. Single and multiple turnover reaction studies show that the enzyme reaction proceeded through the two-step mechanism involving the formation of a covalent intermediate. We discuss the roles of these residues and propose its possible reaction mechanism.