Structural and functional analysis of a potent human neutralizing antibody against enterovirus A71

Science China Life Sciences - Enterovirus A71 (EV-A71) causes major outbreaks of hand, foot, and mouth disease (HFMD) in many countries, most frequently affecting children, and a small proportion...     

Long-term,multidomain analyses to identify the breed and allelic effects in MSTN-edited pigs to overcome lameness and sustainably improve nutritional meat production

Science China Life Sciences - Beef and mutton production has been aided by breeding to integrate allelic diversity for myostatin (MSTN), but a lack of diversity in the MSTN germplasm has limited...     

吴茱萸碱抑制破骨细胞分化延缓骨丢失的研究

目的探讨吴茱萸碱对破骨细胞分化与骨吸收功能的调控及对骨质疏松症的治疗作用。 方法取小鼠原代骨髓来源巨噬细胞分别给予0、10、20、50、100、200 μmol/L吴茱萸碱处理,CCK8检测细胞活力;然后利用原代骨髓来源巨噬细胞给予小鼠重组可溶性核因子κB受体活化因子配体与集落刺激因子行破骨细胞分化诱导,分别给予20与50 μmol/L吴茱萸碱干预。抗酒石酸酸性磷酸酶（TRAP）染色检测破骨细胞形成能力,荧光定量PCR分析破骨细胞分化相关基因表达,免疫荧光检测F肌动蛋白（F-actin）形成,扫描电镜观察破骨细胞骨吸收能力。7月龄C57BL/6小鼠灌胃给予100与200 mg/kg吴茱萸碱,给药3个月后Micro-CT检测小鼠骨密度与骨质量。采用单因素方差分析和t检验进行统计学分析。 结果CCK8结果显示,与对照组相比,给予10、20、50、100 μmol/L吴茱萸碱处理后细胞活力无明显变化,差异无统计学意义（P > 0.05）;而给予200 μmol/L吴茱萸碱的细胞活力下降（100.64±0.18比47.54±5.58）,差异具有统计学意义（P < 0.01）。与对照组相比,20 μmol/L吴茱萸碱的TRAP染色阳性细胞数[（200.57±28.35）比（142.29±19.21）个]、Trap （1.00±0.13比0.55±0.16）、组织蛋白酶K（Ctsk） （1.01±0.17比0.59±0.11）mRNA水平、骨吸收面积比（1.00±0.15比0.79±0.19）均减少,差异有统计学意义（P < 0.05）。与对照组相比,50 μmol/L吴茱萸碱的TRAP阳性细胞数[（200.57±28.35）比（112.71±12.18）个]、Trap （1.00±0.13比0.46±0.17）、Ctsk（1.01±0.17比0.49±0.12）、树突状细胞-特异性跨膜蛋白（DC- Stamp） （1.00±0.10比0.55±0.14）、c-Fos （1.01±0.10比0.58±0.14）、活化T细胞核因子c1 （Nfatc1） （1.00±0.10比0.59±0.14）、H+转运ATP酶v0亚基d2 （Atp6v0d2）的mRNA表达（1.00±0.10比0.59±0.18）、F-actin数量[（165.00± 18.50）比（98.33±21.15）个]和骨吸收面积比（1.00±0.15比0.62±0.10）均降低,差异有统计学意义（P < 0.05）。Micro-CT结果显示,与生理盐水组相比,100 mg/kg吴茱萸碱组小鼠骨密度有一定升高[（0.19±0.03）比（0.21±0.01）g/cm³],但差异无统计学意义（P > 0.05）;与生理盐水组相比,200 mg/kg吴茱萸碱组小鼠胫骨的骨密度[（0.19±0.03）比（0.23±0.01）g/cm³]、骨体积比[（9.79±1.39）﹪比（11.62±1.18）﹪]、骨小梁数量[（2.43±0.29）比（3.08±0.43）/mm]上升,骨小梁分离度[（0.44±0.06）比（0.27±0.05）mm]下降,差异具有统计学意义（P < 0.05）。 结论吴茱萸碱通过抑制破骨细胞分化与骨吸收功能延缓小鼠骨量丢失。     

MALE STERILITY 3 encodes a plant homeodomain-finger protein for male fertility in soybean

Male-sterile plants are used in hybrid breeding to improve yield in soybean (Glycine max (L.) Merr.). Developing the capability to alter fertility under different environmental conditions could broaden germplasm resources and simplify hybrid production. However, molecular mechanisms potentially underlying such a system in soybean were unclear. Here, using positional cloning, we identified a gene, MALE STERILITY 3 (MS3), which encodes a nuclear-localized protein containing a plant homeodomain (PHD)-finger domain. A spontaneous mutation in ms3 causing premature termination of MS3 translation and partial loss of the PHD-finger. Transgenetic analysis indicated that MS3 knockout resulted in nonfunctional pollen and no self-pollinated pods, and RNA-seq analysis revealed that MS3 affects the expression of genes associated with carbohydrate metabolism. Strikingly, the fertility of mutant ms3 can restore under long-dconditions. The mutant could thus be used to create a new, more stable photoperiod-sensitive genic male sterility line for two-line hybrid seed production, with significant impact on hybrid breeding and production.     

Structural basis for histone H3 recognition by NASP in Arabidopsis

The structural basis for histone recognition by the histone chaperone nuclear autoantigenic sperm protein (NASP) remains largely unclear. Here, we showed that Arabidopsis thaliana AtNASP is a monomer and displays robust nucleosome assembly activity in vitro. Examining the structure of AtNASP complexed with a histone H3 α3 peptide revealed a binding mode that is conserved in human NASP. AtNASP recognizes the H3 N-terminal region distinct from human NASP. Moreover, AtNASP forms a co-chaperone complex with ANTI-SILENCING FUNCTION 1 (ASF1) by binding to the H3 N-terminal region. Therefore, we deciphered the structure of AtNASP and the basis of the AtNASP–H3 interaction.     

分子即时检测(POCT)技术及其在新发传染病中的应用*

分子即时检测(point-of-care testing,POCT)技术具有灵敏度高、分析速度快、体积小、检测成本低廉等特点,在分子诊断领域受到广泛关注。近年来,分子POCT技术的发展与应用在应对新发、突发传染病,保护人类生命健康方面具有重大意义。介绍近五年来新兴的分子POCT技术,总结新兴分子POCT技术的最新研究进展及应用前景,分析POCT技术的优势与面临的挑战,探讨提高其检测灵敏度和选择性的技术策略。     

中亚热带4种林分类型土壤微生物生物量碳氮特征及季节变化

以中亚热带常绿阔叶林及由其改造而来的闽楠、毛竹及杉木人工林为研究对象,采用氯仿熏蒸浸提法测定了4种林分类型表层(0～10 cm)和深层(40～60 cm)土壤微生物生物量碳(MBC)和氮(MBN),并分析了其季节变化及与土壤理化性质之间的关系.结果表明: 4种林分类型表层土壤MBC和MBN均以常绿阔叶林最高,其次为闽楠人工林、毛竹人工林和杉木人工林,且前三者显著高于后者;各林分深层土壤MBC和MBN无显著差异.4种林分类型的表层土壤MBC和MBN均显著高于深层土壤,且各土层MBC和MBN均具有明显的季节变化,总体呈现出“夏高冬低”单峰曲线变化模式.相关分析表明,4种林分类型土壤MBC和MBN与土壤有机碳、全氮及土壤温度呈显著正相关关系,与土壤容重呈显著负相关关系.表明常绿阔叶林改造成人工林30多年后,表层土壤MBC和MBN呈下降趋势,其中杉木人工林下降幅度最大(分别下降39.0%和49.8%),而对深层土壤MBC和MBN的影响较小.凋落物数量和质量、土壤有机碳和总氮含量及土壤温度是导致各林分类型土壤微生物生物量碳氮差异和季节变化的主要因素.     

Design,synthesis and bioevaluation of 3-oxo-6-aryl-2,3-dihydropyridazine-4-carbohydrazide derivatives as novel xanthine oxidase inhibitors

In view of expanding the structure activity relationship of xanthine oxidase inhibitors, a series of 3-oxo-6-aryl-2,3-dihydropyridazine-4-carbohydrazide/carboxylic acid derivatives were designed by molecular docking and synthesized. All the target compounds were evaluated for their in vitro XO inhibition by using febuxostat and allopurinol as the standard controls. Most of the hydrazide derivatives exhibited potency levels in the micromolar range. From the view of docking study, hydrazide derivatives bind to the active site of XO through a novel interaction mode, which is different from that of febuxostat bearing a carboxyl group. The most promising compound 8b was further subjected to kinetic analysis to deduce their modes of inhibition.     

Extensive allele‐level remodeling of histone methylation modification in reciprocal F1 hybrids of rice subspecies

Epigenetic mechanisms play a major role in heterosis, partly as a result of the remodeling of epigenetic modifications in F₁ hybrids. Based on chromatin immunoprecipitation‐sequencing (ChIP‐Seq) analyses, we show that at the allele level extensive histone methylation remodeling occurred for a subset of genomic loci in reciprocal F₁ hybrids of Oryza sativa (rice) cultivars Nipponbare and 93‐11, representing the two subspecies japonica and indica. Globally, the allele modification‐altered loci in leaf or root of the reciprocal F₁ hybrids involved ?12–43% or more of the genomic regions carrying either of two typical histone methylation markers, H3K4me3 (>21 000 genomic regions) and H3K27me3 (>11 000 genomic regions). Nevertheless, at the total modification level, the majority (from ?43 to >90%) of the modification‐altered alleles lay within the range of parental additivity in the hybrids because of concerted alteration in opposite directions, consistent with an overall attenuation of allelic differences in the modifications. Importantly, of the genomic regions that did show non‐additivity in total modification level by either marker in the two tissues of hybrids, >80% manifested transgressivity, which involved genes enriched in specific functional categories. Extensive allele‐level alteration of H3K4me3 alone was positively correlated with genome‐wide changes in allele‐level gene expression, whereas at the total level, both H3K4me3 and H3K27me3 remodeling, although affecting just a small number of genes, contributes to the overall non‐additive gene expression to variable extents, depending on tissue/marker combinations. Our results emphasize the importance of allele‐level analysis in hybrids to assess the remodeling of epigenetic modifications and their relation to changes in gene expression.     

基于多端元光谱混合分析方法的大兴安岭火后植被盖度恢复研究

火干扰是北方针叶林结构、功能及动态的主要调节因子之一。研究火后植被恢复对理解火干扰和生态系统的交互作用具有重要意义。火烧迹地通常由植被与基质混合组成,在中低分辨率（ > 10 m）遥感影像中表现为混合像元,因此研究亚像元尺度上植被的恢复是精确量化植被恢复的关键。本研究以2000年大兴安岭呼中自然保护区中8700 hm²火烧迹地为研究区,以两期（2014年6月1日和2010年6月22日）中分辨率Landsat ETM+影像（30 m）为基础数据,比较多端元光谱混合分析（Multiple Endmember Spectral Mixture Analysis,MESMA）和归一化植被指数（Normalized Difference Vegetation Index,NDVI）获得的植被盖度,以高分辨率（2 m）WorldView-2影像（2014年7月1日）为验证数据,对两种方法计算的植被盖度精度进行比较。结果表明,MESMA方法获得的植被盖度（R²=0.691）与传统的NDVI获得的植被盖度（R²=0.700）精度无统计差异,中烈度下获得的植被覆盖精度高于低、高火烧烈度。为验证同一端元能否运用到不同时相的Landsat影像中,本研究将从2014年影像中获取的最佳端元运用到2010年影像中获得植被盖度图,结果表明2014年与2010年得到的RMSE（均方根误差）均值分别为0.0015和0.0065,说明最佳端元可用于不同时相的影像分解。本研究表明MESMA方法可有效监测北方针叶林中火后植被盖度恢复,并可运用于时间序列遥感影像监测植被恢复动态。