Common variants at 12q14 and 12q24 are associated with hippocampal volume

Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7). In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10(-11)) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10(-11)). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10(-7)) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10(-7)); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.     

Transient receptor potential canonical channels in angiogenesis and axon guidance

Wiring of vascular and neural networks requires precise guidance of growing blood vessels and axons, respectively, to reach their targets during development. Both of the processes share common molecular signaling pathways. Transient receptor potential canonical (TRPC) channels are calcium-permeable cation channels and gated via receptor- or store-operated mechanisms. Recent studies have revealed the requirement of TRPC channels in mediating guidance cue-induced calcium influx and their essential roles in regulating axon navigation and angiogenesis. Dissecting TRPC functions in these physiological processes may provide therapeutic implications for suppressing pathological angiogenesis and improving nerve regeneration.     

新型手性抗肿瘤药物德氮吡格（TNBG）体外抗肿瘤活性初步研究

目的观察手性旋光异构体德氮吡格（TNBG）对6株人体肿瘤细胞增殖的影响,初步探讨其抗肿瘤作用机制。方法运用MTT法检测手性TNBG对6株肿瘤细胞生长抑制情况;油红O染色法观察QGY-7701细胞中脂质聚集情况;流式细胞仪检测手性TNBG对人肝癌细胞株QGY-7701细胞周期分布和凋亡影响。结果手性TNBG能不同程度抑制肿瘤细胞增殖,且呈剂量依赖性;油红O染色提取显示QGY-7701细胞内脂质量与给药剂量呈正相关;流式细胞仪检测到有s期细胞增加,并且手性TNBG还能诱导QGY-7701细胞发生凋亡。结论手性TNBG在体外具有良好的抗肿瘤活性,其抗肿瘤作用机制可能是通过促使肿瘤细胞产生脂质聚集,抑制肿瘤细胞增殖、诱导其凋亡从而达到抗肿瘤效应。总体看（＋）TNBG体外抗肿瘤活性比（-）TNBG更强。     

隧道围岩施工监测及位移动态模拟分析

为了研究不同支护结构参数和不同开挖方法对围岩位移的影响,以百勺洋隧道为研究对象,通过现场实测、回归分析和数值模拟的技术手段,以大型非线性有限元软件ADINA为研究工具,建立有限元模型。通过改变锚杆支护相关参数和开挖方法,进行大量模拟运算。运算结果表明,随着锚杆长度的增加,地表点下沉量不断减小,隧道的底鼓幅度也逐渐减小,边墙的收敛量也逐渐减小;随着锚杆间距的增加,顶端最大下沉点的竖直方向沉降值增大,边墙收敛值也增大;开挖方法不同时,随着开挖步数的减少,地表下沉值增加,隧道底鼓现象也越明显。开挖步数越多,洞周收敛值越小。     

供应链产品质量检查策略的比较研究

研究由一个供应商和一个零售商组成的供应链,建立存在质量不确定与检查错误下的报童模型,比较分析全检、抽检、分批抽检以及组合策略在分散式与集中式供应链中对零售商订购决策与质量控制效率的影响.结果表明,次品率的增加会降低零售商订购产品的动因,但会增加组合策略下零售商的订购量与利润,同时对集中式供应链中全检策略下的零售商有利;比较策略可知,在分散式供应链中,若次品率较低,则分批抽检策略最优,而随着次品率的提高,组合策略会更优,而在集中式供应链中,全检策略最优;此外零售商质量控制策略的选择受到检查精度、责任成本、次品率阈值、抽检数量以及分批次数等诸多因素的影响,最优策略不尽相同,但不会改变零售商利润随次品率变化的趋势.     

Nine new species of the subgenus Stegana (Oxyphortica) from the Oriental region,with morphological and molecular evidence based on Chinese species (Diptera: Drosophilidae)

Nine new species of the subgenus Stegana (Oxyphortica) have been discovered from the Oriental Region: S. (O.) chuanjiangi Zhang and Chen, sp. nov., S (O.) dainuo Wang and Chen, sp. nov., S. (O.) dawa Zhang and Chen, sp. nov., S. (O.) laohlie Zhang and Chen, sp. nov., S. (O.) luchun Wang and Chen, sp. nov., S. (O.) mengwan Wang and Chen, sp. nov., S. (O.) triodonta Cheng and Chen, sp. nov. from southern China; S. (O.) dehiscens Cheng and Chen, sp. nov. and S. (O.) spinosa Cheng and Chen, sp. nov. from eastern Malaysia. One newly recorded species from China: S. (O.) maichouensis Sidorenko is re-described. The DNA sequences of the mitochondrial COI gene with BOLD Process ID and GenBank accession numbers are provided for the above seven new species and five known species from China: S. (O.) acutipenis Xu, Gao and Chen, S. (O.) adentata Toda and Peng, S. (O.) hirtipenis Xu, Gao and Chen, S. (O.) latipenis Xu, Gao and Chen, and S. (O.) maichouensis Sidorenko. Intra- and interspecific pairwise K-2P distances among these species are summarized and the phylogenetic relationships are reconstructed based on the neighbour-joining (NJ) analyses.

www.zoobank.org/urn:lsid:zoobank.org:pub:2FA403F6-5535-40A4-9FD0-ADB9913EDE83.     

Putting a brake on synaptic vesicle endocytosis

In chemical synapses, action potentials evoke synaptic vesicle fusion with the presynaptic membrane at the active zone to release neurotransmitter. Synaptic vesicle endocytosis (SVE) then follows exocytosis to recapture vesicle proteins and lipid components for recycling and the maintenance of membrane homeostasis. Therefore, SVE plays an essential role during neurotransmission and is one of the most precisely regulated biological processes. Four modes of SVE have been characterized and both positive and negative regulators have been identified. However, our understanding of SVE regulation remains unclear, especially the identity of negative regulators and their mechanisms of action. Here, we review the current knowledge of proteins that function as inhibitors of SVE and their modes of action in different forms of endocytosis. We also propose possible physiological roles of such negative regulation. We believe that a better understanding of SVE regulation, especially the inhibitory mechanisms, will shed light on neurotransmission in health and disease.     

Earlier and broader roles of Mesp1 in cardiovascular development

Mesoderm posterior 1 is one of earliest markers of the nascent mesoderm. Its best-known function is driving the onset of the cardiovascular system. In the past decade, new evidence supports that Mesp1 acts earlier with greater breadth in cell fate decisions, and through cell-autonomous and cell non-autonomous mechanisms. This review summarizes these new aspects, with an emphasis on the upstream and downstream regulation around Mesp1 and how they may guide cell fate reprogramming.