Phosphoproteome Profiling of the Receptor Tyrosine Kinase MuSK Identifies Tyrosine Phosphorylation of Rab GTPases

Muscle-specific receptor tyrosine kinase (MuSK) agonist antibodies were developed 2 decades ago to explore the benefits of receptor activation at the neuromuscular junction. Unlike agrin, the endogenous agonist of MuSK, agonist antibodies function independently of its coreceptor low-density lipoprotein receptor–related protein 4 to delay the onset of muscle denervation in mouse models of ALS. Here, we performed dose–response and time-course experiments on myotubes to systematically compare site-specific phosphorylation downstream of each agonist. Remarkably, both agonists elicited similar intracellular responses at known and newly identified MuSK signaling components. Among these was inducible tyrosine phosphorylation of multiple Rab GTPases that was blocked by MuSK inhibition. Importantly, mutation of this site in Rab10 disrupts association with its effector proteins, molecule interacting with CasL 1/3. Together, these data provide in-depth characterization of MuSK signaling, describe two novel MuSK inhibitors, and expose phosphorylation of Rab GTPases downstream of receptor tyrosine kinase activation in myotubes.     

Growth period QTL-allele constitution of global soybeans and its differential evolution changes in geographic adaptation versus maturity group extension

Soybean (Glycine max (L.) Merr.) has been disseminated globally as a photoperiod/temperature-sensitive crop with extremely diverse days to flowering (DTF) and days to maturity (DTM) values. A population with 371 global varieties covering 13 geographic regions and 13 maturity groups (MGs) was analyzed for its DTF and DTM QTL-allele constitution using restricted two-stage multi-locus genome-wide association study (RTM-GWAS). Genotypes with 20 701 genome-wide SNPLDBs (single-nucleotide polymorphism linkage disequilibrium blocks) containing 55 404 haplotypes were observed, and 52 DTF QTLs and 59 DTM QTLs (including 29 and 21 new ones) with 241 and 246 alleles (two to 13 per locus) were detected, explaining 84.8% and 74.4% of the phenotypic variance, respectively. The QTL-allele matrix characterized with all QTL-allele information of each variety in the global population was established and subsequently separated into geographic and MG set submatrices. Direct comparisons among them revealed that the genetic adaptation from the origin to geographic subpopulations was characterized by new allele/new locus emergence (mutation) but little allele exclusion (selection), while that from the primary MG set to emerged early and late MG sets was characterized by allele exclusion without allele emergence. The evolutionary changes involved mainly 72 DTF and 71 DTM alleles on 28 respective loci, 10–12 loci each with three to six alleles being most active. Further recombination potential for faster maturation (12–21 days) or slower maturation (14–56 days) supported allele convergence (recombination) as a constant genetic factor in addition to migration (inheritance). From the QTLs, 44 DTF and 36 DTM candidate genes were annotated and grouped respectively into nine biological processes, indicating multi-functional DTF/DTM genes are involved in a complex gene network. In summary, we identified QTL-alleles relatively thoroughly using RTM-GWAS for direct matrix comparisons and subsequent analysis.     

The Neural Mechanisms Underlying the Acute Effect of Cigarette Smoking on Chronic Smokers

Although previous research had related structural changes and impaired cognition to chronic cigarette smoking, recent neuroimaging studies have associated nicotine, which is a main chemical substance in cigarettes, with improvements in cognitive functions (e.g. improved attention performance). However, information about the alterations of whole-brain functional connectivity after acute cigarette smoking is limited. In this study, 22 smokers underwent resting-state functional magnetic resonance imaging (rs-fMRI) after abstaining from smoking for 12 hours (state of abstinence, SOA). Subsequently, the smokers were allowed to smoke two cigarettes (state of satisfaction, SOS) before they underwent a second rs-fMRI. Twenty non-smokers were also recruited to undergo rs-fMRI. In addition, high-resolution 3D T1-weighted images were acquired using the same magnetic resonance imaging(fMRI)scanner for all participants. The results showed that smokers had structural changes in insula, thalamus, medial frontal cortex and several regions of the default mode network (DMN) compared with non-smokers. Voxel-wise group comparisons of newly developed global brain connectivity (GBC) showed that smokers in the SOA condition had higher GBC in the insula and superior frontal gyrus compared with non-smokers. However, smokers in the SOS condition demonstrated significantly lower GBC in several regions of the DMN, as compared with smokers in the SOA condition. These results suggest that structural integrity combined with dysfunction of the DMN might be involved in relapses after a short period of time among smokers.     

Traction force-mediated B cell activation: how and why

<正>B and T lymphocytes are responsible for the acquisition of adaptive immune response, among which, B cells dominate humoral immunity. In vivo, B cells utilize surface expressed B cell receptors (BCRs) to sense antigens presented by antigen-presenting cells (APCs), and eventually mediate antibody response and immune memory. It is well recognized     

Characteristics of replication and pathogenicity of SARS-CoV-2 Alpha and Delta isolates

The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally, from B.1.17 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) to B.1.1.529 (Omicron). The emerging or reemerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics, pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 cells. We utilized both animal models of human ACE2 (hACE2) transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.     

Managed Bumblebees Outperform Honeybees in Increasing Peach Fruit Set in China: Different Limiting Processes with Different Pollinators

Peach Prunus persica (L.) Batsch is self-compatible and largely self-fertile, but under greenhouse conditions pollinators must be introduced to achieve good fruit set and quality. Because little work has been done to assess the effectiveness of different pollinators on peach trees under greenhouse conditions, we studied ‘Okubo’ peach in greenhouse tunnels near Beijing between 2012 and 2014. We measured pollen deposition, pollen-tube growth rates, ovary development, and initial fruit set after the flowers were visited by either of two managed pollinators: bumblebees, Bombus patagiatus Nylander, and honeybees, Apis mellifera L. The results show that B. patagiatus is more effective than A. mellifera as a pollinator of peach in greenhouses because of differences in two processes. First, B. patagiatus deposits more pollen grains on peach stigmas than A. mellifera, both during a single visit and during a whole day of open pollination. Second, there are differences in the fertilization performance of the pollen deposited. Half of the flowers visited by B. patagiatus are fertilized 9–11 days after bee visits, while for flowers visited by A. mellifera, half are fertilized 13–15 days after bee visits. Consequently, fruit development is also accelerated by bumblebees, showing that the different pollinators have not only different pollination efficiency, but also influence the subsequent time course of fertilization and fruit set. Flowers visited by B. patagiatus show faster ovary growth and ultimately these flowers produce more fruit. Our work shows that pollinators may influence fruit production beyond the amount of pollen delivered. We show that managed indigenous bumblebees significantly outperform introduced honeybees in increasing peach initial fruit set under greenhouse conditions.     

SSR与SRAP标记在玉米品种鉴定中的比较研究

利用SSR标记和SRAP标记对19个玉米品种及8份莱农15样品进行了分析,比较了2种标记的分辨能力及在亲缘关系和杂交种纯度鉴定中的表现.与SSR标记相比,SRAP标记用于玉米品种鉴定扩增住点数量更多,PIC值更高,具有更高的分辨率;在亲缘关系分析方面,SSR检测的遗传距离变幅更大,2种标记计算的遗传距离呈极显著正相关,分类结果基本一致;在杂交种纯度检测中,SRAP标记的期望位点在杂交种群体中检测率高于SSR标记相应位点,检测杂交种纯度结果更接近田问种植鉴定,因而准确度更高.SRAP在玉米品种鉴定中具有一定的优势,可作为SSR标记技术的有益补充,特别是在杂交种纯度鉴定中应用.