Comparison of SSRs and SNPs in assessment of genetic relatedness in maize

Advances in high-throughput SNP genotyping and genome sequencing technologies have enabled genome-wide association mapping in dissecting the genetic basis of complex quantitative traits. In this study, 82 SSRs and 884 SNPs with minor allele frequencies (MAF) over 0.20 were used to compare their ability to assess population structure, principal component analysis (PCA) and relative kinship in a maize association panel consisting of 154 inbred lines. Compared to SNPs, SSRs provided more information on genetic diversity. The expected heterozygosity (He) of SSRs and SNPs averaged 0.65 and 0.44, and the polymorphic information content of these two markers was 0.61 and 0.34 in this panel, respectively. Additionally, SSRs performed better at clustering all lines into groups using STRUCTURE and PCA approaches, and estimating relative kinship. For both marker systems, the same clusters were observed based on PCA and the first two eigenvectors accounted for similar percentage of genetic variations in this panel. The correlation coefficients of each eigenvector from SSRs and SNPs decreased sharply when the eigenvector varied from 1 to 3, but kept around 0 when the eigenvector were over 3. The kinship estimates based on SSRs and SNPs were moderately correlated (r (2)?=?0.69). All these results suggest that SSR markers with moderate density are more informative than SNPs for assessing genetic relatedness in maize association mapping panels.     

玉米C4型NADP—ME的生物信息学分析

利用生物信息学软件对GeneBank上注册的玉米C4型NADP-ME进行氨基酸组成、功能域、二级结构、疏水性、导肽、亚细胞定位、蛋白质功能及系统进化分析和预测.结果表明,NADP-ME蛋白是等电点为6.09的亲水性不稳定蛋白,包含一个结合NAD(P)的结构域和一个N-末端区域,属于裂解酶类,具有能量代谢的功能,定位于叶绿体中;α螺旋和不规则卷曲是其蛋白质二级结构的主要结构元件,β折叠和伸展链散布其中;玉米C4型NADP-ME与高粱、水稻等植物的NADP-ME基因有较高的同源性.     

Potentiating CD8+ T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling

Metabolic regulation has been proven to play a critical role in T cell antitumor immunity.However,cholesterol metabolism as a key component of this regulation remains largely unexplored.Herein,we found that the low-density lipoprotein receptor (LDLR),which has been previously identified as a transporter for cholesterol,plays a pivotal role in regulating CD8+ T cell antitumor activity.Besides the involvement of cholesterol uptake which is mediated by LDLR in T cell priming and clonal expansion,we also found a non-canonical function of LDLR in CD8+ T cells: LDLR interacts with the T-cell receptor (TCR) complex and regulates TCR recycling and signaling,thus facilitating the effector function of cytotoxic T-lymphocytes (CTLs).Furthermore,we found that the tumor microenvironment (TME) downregulates CD8+ T cell LDLR level and TCR signaling via tumor cell-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) which binds to LDLR and prevents the recycling of LDLR and TCR to the plasma membrane thus inhibits the effector function of CTLs.Moreover,genetic deletion or pharmacological inhibition of PCSK9 in tumor cells can enhance the antitumor activity of CD8+ T cells by alleviating the suppressive effect on CD8+ T cells and consequently inhibit tumor progression.While previously established as a hypercholesterolemia target,this study highlights PCSK9/LDLR as a potential target for cancer immunotherapy as well.     

Proviral Insertion in Murine Lymphomas 2 (PIM2) Oncogene Phosphorylates Pyruvate Kinase M2 (PKM2) and Promotes Glycolysis in Cancer Cells

Pyruvate kinase M2 (PKM2) is a key player in the Warburg effect of cancer cells. However, the mechanisms of regulating PKM2 are not fully elucidated. Here, we identified the protein-serine/threonine kinase PIM2, a known oncogene, as a novel binding partner of PKM2. The interaction between PIM2 and PKM2 was confirmed by multiple biochemical approaches in vitro and in cultured cells. Importantly, we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue, resulting in an increase of PKM2 protein levels. Compared with wild type, PKM2 with the phosphorylation-defective mutation displayed a reduced effect on glycolysis, co-activating HIF-1α and β-catenin, and cell proliferation, while enhancing mitochondrial respiration of cancer cells. These findings demonstrate that PIM2-dependent phosphorylation of PKM2 is critical for regulating the Warburg effect in cancer, highlighting PIM2 as a potential therapeutic target.     

人体上呼吸道口喉呼吸流涡结构演化对病毒气溶胶扩散的影响研究

揭示涡结构演化对病毒气溶胶扩散的影响作用,对于有效防治呼吸道疾病具有非常重要的意义.本文运用大涡模拟的方法,对人体在循环呼吸模式下口喉模型内的涡结构演化及气溶胶扩散进行了数值仿真研究,分析了口喉模型内涡结构演化过程以及气溶胶扩散状态.结果表明：受呼吸流涡结构演化的影响,颗粒轨迹主要分布在上气道内涡量集中的区域;受横向涡结构和纵向涡结构的共同影响,部分病毒气溶胶颗粒具备了混合有环状轨迹和波状轨迹的螺旋状轨迹.本研究从微观角度揭示了涡结构演化与气溶胶扩散行为的关系,为深入认识病毒气溶胶上呼吸道传播特点提供了新的途径.     

Temperature-Triggered Enzyme Immobilization and Release Based on Cross-Linked Gelatin Nanoparticles

A glucoamylase-immobilized system based on cross-linked gelatin nanoparticles (CLGNs) was prepared by coacervation method. This system exhibited characteristics of temperature-triggered phase transition, which could be used for enzyme immobilization and release. Their morphology and size distribution were examined by transmission electron microscopy and dynamic light scattering particle size analyzer. Their temperature-triggered glucoamylase immobilization and release features were also further investigated under different temperatures. Results showed that the CLGNs were regularly spherical with diameters of 155±5 nm. The loading efficiencies of glucoamylase immobilized by entrapment and adsorption methods were 59.9% and 24.7%, respectively. The immobilized enzyme was released when the system temperature was above 40°C and performed high activity similar to free enzyme due to the optimum temperature range for glucoamylase. On the other hand, there was no enzyme release that could be found when the system temperature was below 40°C. The efficiency of temperature-triggered release was as high as 99.3% for adsorption method, while the release of enzyme from the entrapment method was not detected. These results indicate that CLGNs are promising matrix for temperature-triggered glucoamylase immobilization and release by adsorption immobilization method.     

Mechanical activation of spike fosters SARS-CoV-2 viral infection

The outbreak of SARS-CoV-2 (SARS2) has caused a global COVID-19 pandemic. The spike protein of SARS2 (SARS2-S) recognizes host receptors, including ACE2, to initiate viral entry in a complex biomechanical environment. Here, we reveal that tensile force, generated by bending of the host cell membrane, strengthens spike recognition of ACE2 and accelerates the detachment of spike’s S1 subunit from the S2 subunit to rapidly prime the viral fusion machinery. Mechanistically, such mechano-activation is fulfilled by force-induced opening and rotation of spike’s receptor-binding domain to prolong the bond lifetime of spike/ACE2 binding, up to 4 times longer than that of SARS-S binding with ACE2 under 10 pN force application, and subsequently by force-accelerated S1/S2 detachment which is up to ~10³ times faster than that in the no-force condition. Interestingly, the SARS2-S D614G mutant, a more infectious variant, shows 3-time stronger force-dependent ACE2 binding and 35-time faster force-induced S1/S2 detachment. We also reveal that an anti-S1/S2 non-RBD-blocking antibody that was derived from convalescent COVID-19 patients with potent neutralizing capability can reduce S1/S2 detachment by 3 × 10⁶ times under force. Our study sheds light on the mechano-chemistry of spike activation and on developing a non-RBD-blocking but S1/S2-locking therapeutic strategy to prevent SARS2 invasion.Subject terms: Molecular biology, Structural biology