TTLL11 gene is associated with sustained attention performance and brain networks: A genome-wide association study of a healthy Chinese sample

Genetic studies on attention have mainly focused on children with attention-deficit/hyperactivity disorder (ADHD), so little systematic research has been conducted on genetic correlates of attention performance and their potential brain mechanisms among healthy individuals. The current study included a genome-wide association study (GWAS, N = 1145 healthy young adults) aimed to identify genes associated with sustained attention and an imaging genetics study (an independent sample of 483 healthy young adults) to examine any identified genes' influences on brain function. The GWAS found that TTLL11 showed genome-wide significant associations with sustained attention, with rs13298112 as the most significant SNP and the GG homozygotes showing more impulsive but also more focused responses than the A allele carriers. A retrospective examination of previously published ADHD GWAS results confirmed an un-reported, small but statistically significant effect of TTLL11 on ADHD. The imaging genetics study replicated this association and showed that the TTLL11 gene was associated with resting state activity and connectivity of the somatomoter network, and can be predicted by dorsal attention network connectivity. Specifically, the GG homozygotes showed lower brain activity, weaker brain network connectivity, and non-significant brain-attention association compared to the A allele carriers. Expression database showed that expression of this gene is enriched in the brain and that the G allele is associated with lower expression level than the A allele. These results suggest that TTLL11 may play a major role in healthy individuals' attention performance and may also contribute to the etiology of ADHD.     

Research Progress on Anti-Inflammatory Mechanisms of Black Ginseng

In recent years, black ginseng, a new type of processed ginseng product, has attracted the attention of scholars globally. Ginsenoside and ginseng polysaccharide, the main active substances of black ginseng, have been shown to carry curative effects for many diseases. This article focuses on the mechanism of their action in anti-inflammatory response, which is mainly divided into three aspects: activation of immune cells to exert immune regulatory response; participation in inflammatory response-related pathways and regulation of the expression level of inflammatory factors; effect on the metabolic activity of intestinal flora. This study identifies active anti-inflammatory components and an action mechanism of black ginseng showing multi-component, multi-target, and multi-channel characteristics, providing ideas and a basis for a follow-up in-depth study of its specific mechanism.     

高原人体左心室舒张功能和顺应性的改变

应用同步描记心电图、心音图、颈动脉搏动图和心尖搏动图以测定高原人体的左心室舒张功能和顺应性。在4个不同海拔高度进行实验,即76m(海平对照)、2161m、3270m和4179m,每一高度40名健康男性青年,高原3组世居、移居各20名。结果显示:随着海拔增高,主动舒张时间指数(TRTI)有减小趋势,RF波相对振幅(F/H)逐渐降低,A波相对振幅(A/D)则渐趋增大,3270m以上增大明显(p<0.05),舒张振幅时间指数(DATI)逐渐降低,3270m以上差异极显著(p<0.001)。高原世居与移居者相比,在海拔4179m出现明显差别,移居组TRTI、DATI、F/H较低而A/D较高(D<0.05)。测定射血前期与左室射血时间比值(PEP/LVET)、射血分数(EF)及左室周径纤维平均缩短速度(mVcf)3项指标作对照,显示在此高度左室收缩功能仍能保持。高原慢性心肌缺氧可能是导致左室舒张功能和顺应性轻度降低的原因。     

油菜FBA基因克隆、表达分析及其与抗旱性的关系

为了解果糖-1,6-二磷酸醛缩酶(fructose-1,6-bisphosphate aldolase,FBA)在油菜抗旱中的作用,揭示油菜干旱胁迫下FBA基因表达量、光合指标、产量等之间的关系,为油菜等作物抗旱性鉴定和抗旱性改良提供依据。以抗旱性强的甘蓝型油菜94005为材料,在初花期进行干旱胁迫处理,以正常浇水作为对照;测定叶片光合参数和FBA酶活性,通过实时荧光定量PCR(RT-qPCR)分析FBA基因的表达量;采用RACE方法对FBA基因进行全长克隆,并对测序结果进行生物信息学分析;复水后生长至成熟期测定产量,分析产量、光合指标、FBA基因表达量等之间的关系。结果表明,随着干旱的加剧,油菜叶片的净光合速率(Pn)、气孔导度(Gs)、蒸腾速率(Tr)、产量均下降,FBA活性和FBA基因的表达量上升。在轻度、中度和重度干旱胁迫下,油菜叶片胞间CO_2浓度(Ci)显著下降,水分利用率(WUE)上升;极度胁迫下,Ci上升,WUE下降;油菜产量、净光合速率与FBA活性和FBA表达量呈显著负相关。FBA基因全长序列1440bp,ORF(开放阅读框)位于60—1172区域,编码370个氨基酸;蛋白分子量为38.51 KDa,等电点6.92;同源性对比显示,甘蓝型油菜FBA基因与拟南芥FBA基因的一致性在87%以上。二级结构预测结果表明FBA蛋白由α-螺旋、无规则卷曲、延伸链以及β-转角组成,4种二级结构元件所占比例分别为43.85%、31.28%、17.60%、7.26%。因此,干旱胁迫下油菜的净光合速率下降、产量降低,随着胁迫的加剧,降低幅度增大。FBA基因与干旱胁迫密切相关,干旱胁迫下,FBA基因主要通过抑制光合、降低蒸腾、促进糖酵解和有氧呼吸等途径来提高植物对干旱胁迫的适应性。     

LRP6 downregulation promotes cardiomyocyte proliferation and heart regeneration

The adult mammalian heart is thought to be a terminally differentiated organ given the postmitotic nature of cardiomyocytes. Consequently, the potential for cardiac repair through cardiomyocyte proliferation is extremely limited. Low-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor that is required for embryonic heart development. In this study we investigated the role of LRP6 in heart repair through regulation of cardiomyocyte proliferation. Lrp6 deficiency increased cardiomyocyte cell cycle activity in neonatal, juvenile and adult mice. Cardiomyocyte-specific deletion of Lrp6 in the mouse heart induced a robust regenerative response after myocardial infarction (MI), led to reduced MI area and improvement in left ventricular systolic function. In vivo genetic lineage tracing revealed that the newly formed cardiomyocytes in Lrp6-deficient mouse hearts after MI were mainly derived from resident cardiomyocytes. Furthermore, we found that the pro-proliferative effect of Lrp6 deficiency was mediated by the ING5/P21 signaling pathway. Gene therapy using the adeno-associated virus (AAV)9 miRNAi-Lrp6 construct promoted the repair of heart injury in mice. Lrp6 deficiency also induced the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our study identifies LRP6 as a critical regulator of cardiomyocyte proliferation, which may lead to the development of a novel molecular strategy to promote myocardial regeneration and repair.Subject terms: Cell-cycle exit, Cytokinesis     

piR-823 inhibits cell apoptosis via modulating mitophagy by binding to PINK1 in colorectal cancer

Mitophagy plays a vital role in the maintenance of mitochondrial homeostasis and tumorigenesis. Noncoding RNA piR-823 contributes to colorectal tumorigenesis. In this study, we aim to evaluate piR-823-mediated mitophagy and its mechanistic association with colorectal cancer (CRC). Digital gene expression analysis was performed to explore the potential functions of piR-823. A piR-823 antagomir (Ant-823) was used to inhibit piR-823 expression, and piR-823 mimics (mimics-823) were used to increase piR-823 expression. Mitophagy was measured in vivo and in vitro by immunofluorescence and western blot analysis. JC-1 staining, ATP production, real-time PCR, and western blot analysis were used to measure changes in mitochondrial quality and number. siRNA transfection was used to inhibit mitophagy, and CCCP was used to induce mitophagy. RNA pull-down assays and RNA-binding protein immunoprecipitation assays were conducted to investigate the molecular mechanisms. Here, we found that CRC cells transfected with Ant-823 presented an altered expression of autophagic and mitophagy genes by Digital gene expression analysis. Ant-823 could promote Parkin activation and mitophagy in vitro and in vivo, followed by mitochondrial loss and dysfunction of some mitochondria, whereas mimics-823 exerted the opposite effects in CRC cells. The inhibition of mitophagy by siParkin alleviated Ant-823-induced mitochondrial loss and dysfunction, as well as apoptosis to a certain extent. Furthermore, piR-823 was found to interact with PINK1 and promote its ubiquitination and proteasome-dependent degradation, thus alleviating mitophagy. Finally, these findings were verifed in samples obtained by patients affected by colorectal cancer. In conclusion, we identify a novel mechanism by which piR-823 regulates mitophagy during CRC tumorigenesis by increasing PINK1 degradation. Subject terms: Colorectal cancer, Gastrointestinal cancer     

Cryo-EM structure of the fatty acid reductase LuxC–LuxE complex provides insights into bacterial bioluminescence

The discovery of reduced flavin mononucleotide and fatty aldehydes as essential factors of light emission facilitated study of bacterial luminescence. Although the molecular mechanisms underlying bacterial luminescence have been studied for more than 60 years, the structure of the bacterial fatty acid reductase complex remains unclear. Here, we report the cryo-EM structure of the Photobacterium phosphoreum fatty acid reductase complex LuxC–LuxE to a resolution of 2.79 Å. We show that the active site Lys238/Arg355 pair of LuxE is >30 Å from the active site Cys296 of LuxC, implying that catalysis relies on a large conformational change. Furthermore, mutagenesis and biochemical experiments support that the L-shaped cleft inside LuxC plays an important role in substrate binding and reaction. We obtained a series of mutants with significantly improved activity as measured by in vitro bioluminescence assays and demonstrated that the double mutant W111A/F483K displayed the highest activity (370% of the WT). Our results indicated that the activity of LuxC significantly affects the bacterial bioluminescence reaction. Finally, we expressed this mutated lux operon in Escherichia coli but observed that the in vivo concentrations of ATP and NADPH limited the enzyme activity; thus, we conclude that the luminous intensity mainly depends on the level of metabolic energy.     

流行性出血热地鼠肾细胞灭活疫苗人体试用细胞免疫反应观察

观察了20位志愿者在接种试验性流行性出血热(EHF)地鼠肾细胞(GHKC)双价灭活疫苗后的细胞免疫反应,并以其体液免疫反应作对照观察。用淋巴细胞转化试验测定细胞免疫水平。结果首针疫苗接种后42天和56天,特异性刺激指数(SSI)和非特异性刺激指数(NSI)均较免疫前显著增高(P_(SSI)<0.001;P_(NSI)<0.02),免疫后SSI累计阳转率为100％,NSI累计阳转率为60％,免疫后6个月二者均降低至正常水平。免疫后56天测定抗体,荧光抗体阳转率为100％;微量感染性中和试验表明,针对家鼠型病毒L99株中和抗体阳转率为95％,而针对野鼠型病毒JR株阳转率为65％。     

基于可见光波段包络线去除的湿地植物叶片叶绿素估算

研究采用芦苇和香蒲叶片光谱及实测叶绿素含量数据,选取波段谱带范围为可见光波段400—760nm(为了避免近红外波段受叶片水分含量的影响,降低构建模型的稳定性),利用相关分析与逐步回归分析的统计学分析方法,建立叶面尺度下不同包络线去除衍生转换光谱:BD(band depth)、CRDR(continuum-removed derivative reflectance)、BDR(band depth ratio)、NBDI(normalized band depth index)与叶绿素含量估算模型。通过对入选波段的统计表明在550—750nm,特别是700—750nm(红边)波段范围内产生了较多的有效波段,是今后进行生物参量反演的重点波段范围。舍一交叉验证结果表明芦苇、香蒲和混合样本绿素含量估测的最佳模型分别为BD、CRDR和NBDI模型,其交叉验证决定系数依次为0.87、0.83和0.81,交叉验证均方根误差RMSE依次为0.16、0.15和0.33。并在此基础上利用独立样本非参数检验和多因子方差分析,探讨相关因素对于叶绿素含量估算模型精度的影响。结果表明物种差异、数据类型差异对于叶绿素回归模型的影响较大,而光谱类型差异及光谱数据与数据类型交互作用对于回归模型精度的影响较小。     

胜利河连续系统中蜉蝣优势种的生产量动态和营养基础

大型底栖动物在河流生态系统中发挥着重要作用, 2009 年3月至2010 年3月间对长江中游支流巴河流域的胜利河大型底栖动物群落优势种类的生产力进行为期1 周年的调查研究, 结果表明, 主要蜉蝣优势种扁蜉、等蜉和红斑蜉的生活史为3代/年、3代/年和 2代/年。现存量呈现出1-3级河流增加,而4级又较3级有所下降的趋势。采用龄期频率法( instar-frequency method) 测算的平均周年生产量分别为扁蜉, 200.13 g/(m².a) , P/B 为23.69; 等蜉, 82.06 g/(m².a), P/B 为18.12;红斑蜉, 12.30 g/(m².a), P/B 为8.78。三种蜉蝣的生产量动态在时间上与现存量动态较一致,但彼此各不相同。扁蜉的日均产量于2009年3月在二级河流中达到最大(363.56 mg/m².d),等蜉于2010年3月在三级河流中到达最大(282.76 mg/m².d),而红斑蜉于2009年3月在一级河流中到达最大(33.36 mg/m².d)。生产量的营养基础分析结果表明,扁蜉前肠内含物中无形态碎屑、动物组织、植物纤维、丝状藻类、硅藻所占平均比例为74.37%,4.19%,17.11%,4.29%,0.04%,对生产量的贡献率分别为77.15%,11.27%,6.57%,4.95% ,0.04%;等蜉前肠内含物中无形态碎屑、动物组织、植物纤维、真菌、丝状藻类和硅藻所占平均比例为65.64%,6.17%,23.04%,0.54%,4.53%,对生产量的贡献率分别为: 68.16%,16.61%,8.86%,1.03%,5.23%,0.09%,0.10%;红斑蜉前肠内含物中,无形态碎屑、动物组织、植物纤维、真菌、丝状藻类和硅藻所占平均比例为41.14%,5.96%,38.04%,1.34%,11.21%,2.31%,对生产量的贡献率分别为46.67%,17.52%,15.98%,2.81%,14.13%,2.91%。这与我们在黑竹冲和叹气沟的研究结果存在一定差异,可能与这些溪流自身环境和地区分布有关。