Recognition of different base tetrads by RHAU (DHX36): X-ray crystal structure of the G4 recognition motif bound to the 3′-end tetrad of a DNA G-quadruplex

G-quadruplexes (G4) are secondary structures of nucleic acids that can form in cells and have diverse biological functions. Several biologically important proteins interact with G-quadruplexes, of which RHAU (or DHX36) – a helicase from the DEAH-box superfamily, was shown to bind and unwind G-quadruplexes efficiently. We report a X-ray co-crystal structure at 1.5 Å resolution of an N-terminal fragment of RHAU bound to an exposed tetrad of a parallel-stranded G-quadruplex. The RHAU peptide folds into an L-shaped α-helix, and binds to a G-quadruplex through π-stacking and electrostatic interactions. X-ray crystal structure of our complex identified key amino acid residues important for G-quadruplex-peptide binding interaction at the 3′-end G•G•G•G tetrad. Together with previous solution and crystal structures of RHAU bound to the 5′-end G•G•G•G and G•G•A•T tetrads, our crystal structure highlights the occurrence of a robust G-quadruplex recognition motif within RHAU that can adapt to different accessible tetrads.     

Using the tools of genetic epidemiology to understand sex differences in neuropsychiatric disorders

Many neuropsychiatric disorders exhibit differences in prevalence, age of onset, symptoms or course of illness between males and females. For the most part, the origins of these differences are not well understood. In this article, we provide an overview of sex differences in psychiatric disorders including autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), anxiety, depression, alcohol and substance abuse, schizophrenia, eating disorders and risk of suicide. We discuss both genetic and nongenetic mechanisms that have been hypothesized to underlie these differences, including ascertainment bias, environmental stressors, X‐ or Y‐linked risk loci, and differential liability thresholds in males and females. We then review the use of twin, family and genome‐wide association approaches to study potential genetic mechanisms of sex differences and the extent to which these designs have been employed in studies of psychiatric disorders. We describe the utility of genetic epidemiologic study designs, including classical twin and family studies, large‐scale studies of population registries, derived recurrence risks, and molecular genetic analyses of genome‐wide variation that may enhance our understanding sex differences in neuropsychiatric disorders.     

Transmembrane adaptor protein WBP1L regulates CXCR4 signalling and murine haematopoiesis

WW domain binding protein 1‐like (WBP1L), also known as outcome predictor of acute leukaemia 1 (OPAL1), is a transmembrane adaptor protein, expression of which correlates with ETV6‐RUNX1 (t(12;21)(p13;q22)) translocation and favourable prognosis in childhood leukaemia. It has a broad expression pattern in haematopoietic and in non‐haematopoietic cells. However, its physiological function has been unknown. Here, we show that WBP1L negatively regulates signalling through a critical chemokine receptor CXCR4 in multiple leucocyte subsets and cell lines. We also show that WBP1L interacts with NEDD4‐family ubiquitin ligases and regulates CXCR4 ubiquitination and expression. Moreover, analysis of Wbp1l‐deficient mice revealed alterations in B cell development and enhanced efficiency of bone marrow cell transplantation. Collectively, our data show that WBP1L is a novel regulator of CXCR4 signalling and haematopoiesis.     

赛黑桦不同半同胞家系种子活力比较

种子活力能够预测幼苗的生长势和适应性,可作为评价采种母树的重要指标。赛黑桦作为东北林区木质坚硬的树种之一,关于其种子活力研究尚未见报道。比较不同家系赛黑桦种子活力,对赛黑桦采种母树进行初步评价,可为赛黑桦优良家系的选择提供参考。本研究以赛黑桦蛟河、集安和珲春3个采种地共30个半同胞家系为试材,对采种地及家系间种子千粒重、发芽率、发芽势、发芽指数、活力指数、出苗率和幼苗健壮率等7个性状进行了方差分析、遗传力估算、多重比较、相关性分析,并利用主成分分析法对参试家系进行了综合评价。结果表明,赛黑桦种子活力指数和幼苗健壮率在不同采种地间的差异达到了显著或极显著水平;7个性状在不同家系间的差异均达到显著或极显著水平;除出苗率和幼苗健壮率外,各性状的家系遗传力均高于0.68;7个性状间均呈现显著或极显著的正相关;采用主成分分析法选择JH6、JA1、JA7、JH10、JH3、HC1和HC10等7个家系为优良家系,这些家系的种子千粒重、发芽率、发芽势、发芽指数、活力指数、出苗率和幼苗健壮率的平均值分别比总平均值高3.87%、30.29%、30.22%、31.99%、58.22%、11.88%和30.60%。初步认为这些优良家系的母树是赛黑桦采种的首选母树。     

Goose parents lead migration V

Many migratory animals travel in large social groups. Large, avian migrants that fly in V-formations were proposed do so for energy saving by the use of up-wash by following individuals and regularly change leadership. As groups have been rather homogeneous in previous work, we aimed to explore leadership and its flight mechanics consequences in an extremely heterogeneous case of social migration, namely in spring migration of goose families. In families the experience of group members differs strongly and inclusive fitness may be important. We successfully collected overlapping spring migration tracking data of a complete family of greater white-fronted geese Anser a. albifrons and extracted leadership, flapping frequency and wind conditions in flight. Our data revealed V-formations where one parent was flying in front at all times. Although the father led the family group most of the time, he did not flap at higher frequency while doing so. In contrast, the mother flapped faster when leading, possibly because she experienced less supportive wind conditions than when the father led. We argue that in heterogeneous, social groups leadership might be fixed and not costly if supportive environmental conditions like wind can be used.     

Crystal structure of Nsp15 endoribonuclease NendoU from SARS‐CoV‐2

Severe Acute Respiratory Syndrome coronavirus 2 (SARS‐CoV‐2) is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS‐CoVs and Middle East Respiratory Syndrome coronavirus (MERS‐CoVs), the detailed information about SARS‐CoV‐2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies, and antivirals. We applied high‐throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS‐CoV‐2 proteins and structures. Here we report two high‐resolution crystal structures of endoribonuclease Nsp15/NendoU. We compare these structures with previously reported homologs from SARS and MERS coronaviruses.     

Coordinated regulation of anthranilate metabolism and bacterial virulence by the GntR family regulator MpaR in Pseudomonas aeruginosa

The GntR family regulators are widely distributed in bacteria and play critical roles in metabolic processes and bacterial pathogenicity. In this study, we describe a GntR family protein encoded by PA4132 that we named MpaR (M vfR-mediated P QS and a nthranilate r egulator) for its regulation of Pseudomonas quinolone signal (PQS) production and anthranilate metabolism in Pseudomonas aeruginosa. The deletion of mpaR increased biofilm formation and reduced pyocyanin production. RNA sequencing analysis revealed that the mRNA levels of antABC encoding enzymes for the synthesis of catechol from anthranilate, a precursor of the PQS, were most affected by mpaR deletion. Data showed that MpaR directly activates the expression of mvfR, a master regulator of pqs system, and subsequently promotes PQS production. Accordingly, deletion of mpaR activates the expression of antABC genes, and thus, increases catechol production. We also demonstrated that MpaR represses the rhl quorum-sensing (QS) system, which has been shown to control antABC activity. These results suggested that MpaR function is integrated into the QS regulatory network. Moreover, mutation of mpaR promotes bacterial survival in a mouse model of acute pneumonia infection. Collectively, this study identified a novel regulator of pqs system, which coordinately controls anthranilate metabolism and bacterial virulence in P. aeruginosa.     

秦岭蕨类植物新记录科——肠蕨科

报道了秦岭蕨类植物新记录科——肠蕨科,其新记录种为川黔肠蕨,该科也是陕西省新记录。文中提供了形态描述和野外照片及植株局部照片,并对其生境特点进行了简要分析。凭证标本藏于陕西理工大学植物标本馆。