Functional Consequences of a Novel Variant of PCSK1

Background

Common single nucleotide polymorphisms (SNPs) in proprotein convertase subtilisin/kexin type 1 with modest effects on PC1/3 in vitro have been associated with obesity in five genome-wide association studies and with diabetes in one genome-wide association study. We here present a novel SNP and compare its biosynthesis, secretion and catalytic activity to wild-type enzyme and to SNPs that have been linked to obesity.

Methodology/Principal Findings

A novel PC1/3 variant introducing an Arg to Gln amino acid substitution at residue 80 (within the secondary cleavage site of the prodomain) (rs1799904) was studied. This novel variant was selected for analysis from the 1000 Genomes sequencing project based on its predicted deleterious effect on enzyme function and its comparatively more frequent allele frequency. The actual existence of the R80Q (rs1799904) variant was verified by Sanger sequencing. The effects of this novel variant on the biosynthesis, secretion, and catalytic activity were determined; the previously-described obesity risk SNPs N221D (rs6232), Q665E/S690T (rs6234/rs6235), and the Q665E and S690T SNPs (analyzed separately) were included for comparative purposes. The novel R80Q (rs1799904) variant described in this study resulted in significantly detrimental effects on both the maturation and in vitro catalytic activity of PC1/3.

Conclusion/Significance

Our findings that this novel R80Q (rs1799904) variant both exhibits adverse effects on PC1/3 activity and is prevalent in the population suggests that further biochemical and genetic analysis to assess its contribution to the risk of metabolic disease within the general population is warranted.     

模拟氮沉降对东北地区兴安落叶松树干呼吸的影响

2011年的5月至2012年的12月,对兴安落叶松(Larix gmelinii)人工林进行了模拟氮沉降实验,设置了4个氮沉降水平处理,分别为:对照(0 g N m-2a-1)、低氮(5 g N m-2a-1)、中氮(5 g N m-2a-1)和高氮(15 g N m-2a-1),每个处理设置3个重复样地。所施氮肥为NH4NO3,以溶液方式在生长季内每月喷施1次。采用红外气体分析法于2012年4月底—10月份,每隔15d左右测定1次树干呼吸,共测定12次。结果表明:各个氮处理下的树干呼吸速率基本与树干温度的变化一致,均呈单峰型季节变化模式,其中7月底最高、10月底最低。氮处理均提高了落叶松的树干呼吸速率,且随着氮输入水平的增加,平均树干呼吸速率呈现逐渐增强的趋势。生长季内,对照、低氮、中氮、和高氮处理条件下的树干表面释放的CO2通量分别为67.3、72.5、78.9 g C/m2和86.5 g C/m2。树干温度与树干呼吸速率存在显著的指数函数关系,而且温度敏感性(Q10)随着氮输入的逐渐升高亦随之增强,对照、低氮、中氮、和高氮处理下的Q10值分别为1.67、1.80、2.01和2.54。另外,伴随氮输入的逐渐增加,树干的氮含量也逐渐升高,树干氮含量与树干呼吸速率之间也具有一定的相关性,能够解释树干呼吸变化的38.3%。     

Fine mapping of the Pc locus of Sorghum bicolor, a gene controlling the reaction to a fungal pathogen and its host-selective toxin

Milo disease in sorghum is caused by isolates of the soil-borne fungus Periconia circinata that produce PC-toxin. Susceptibility to milo disease is conditioned by a single, semi-dominant gene, termed Pc. The susceptible allele (Pc) converts to a resistant form (pc) spontaneously at a gametic frequency of 10⁻³ to 10⁻⁴. A high-density genetic map was constructed around the Pc locus using DNA markers, allowing the Pc gene to be delimited to a 0.9 cM region on the short arm of sorghum chromosome 9. Physically, the Pc-region was covered by a single BAC clone. Sequence analysis of this BAC revealed twelve gene candidates. Several of the predicted genes in the region are homologous to disease resistance loci, including one NBS-LRR resistance gene analogue that is present in multiple tandem copies. Analysis of pc isolines derived from Pc/Pc sorghum suggests that one or more members of this NBS-LRR gene family are the Pc genes that condition susceptibility.     

Photosynthesis Limits Carbon Sequestering in the Taiga Zone of Northeastern Europe

We analyzed the time-course of carbon accumulation in the stem wood of the basic forest-forming tree species (pine, spruce, and birch) of the taiga subzones in northeastern Europe over many years. The dynamics of annual carbon accumulation was appraised from comparing the carbon content in trees of various ages. The primary photosynthetic productivity and the coefficient of proportionality between respiratory decarboxylation and the mass of the stem wood were calculated. A noticeable decrease in the net primary photosynthetic productivity was detected with a movement from South to North (from 62 to 64° N). However, the time for reaching the climax stage did not depend on the latitude and corresponding climatic parameters. Therefore, only the heterotrophic part of tree biomass determines annual carbon losses in a forest tree population. The conclusion is that the primary photosynthetic productivity, which limits the production process, determines the dependence of the volume of the northern-taiga carbon reservoir on the latitude and climatic parameters.     

广西油茶人工林林下植物多样性区域变化规律

为揭示广西油茶林植物多样性的区域变化规律,以广西7个区域具代表性的油茶林为研究对象,采用典型抽样法,对油茶林林下植被进行了调查,并对比分析了群落物种组成、结构特征和物种多样性。结果表明:(1)油茶林林下植被灌草层科数、属数、种数最多的是三江县油茶林(SJ)、较少的是巴马县油茶林(BM)和来宾市油茶林(LB);除巴马县油茶林(BM)灌木层优势种为共有种,其他区域油茶林的灌木层、草本层优势种均为交叉种。(2)多样性指数方面灌木层仅Margalef指数差异显著,草本层Margalef指数、Simpson指数、Shannon-Wiener指数差异显著。(3)通过回归分析,纬度与灌木层(单一种数量)、草本层(科数、属数、种数、单一种数量)以及总数量(属数、种数)、年均温度与草本层(科数、属数、种数、单一种数量)、有效积温与草本层(属数、种数、单一种数量)、年均降雨量与灌木层单一种数量之间的趋势模拟呈二次曲线关系。(4)不同区域油茶林物种相似性不高,通过相似系数矩阵进行聚类分析三江县油茶林(SJ)、贺州市八步区油茶林(HZ)、岑溪市软枝油茶种子园油茶林(CX)、南宁市油茶林(NN)为一类,凤山县油...     

水稻OsMS2基因在花药发育中的功能分析

拟南芥MS2（MALE STERILITY2）是一个调控花药花粉发育的关键基因。水稻OsMS2（Os03g07140）基因与拟南芥MS2的序列具有高度同源性。利用RNA干扰技术研究OsMS2基因在水稻花药发育过程中的功能。与野生型水稻相比,转基因植株营养生长阶段正常,但雄性育性降低。转基因植株雄性育性降低与RNA干扰引起的OsMS2基因表达水平降低有关。进一步对转基因植株花药进行细胞学观察,结果表明OsMS2基因表达水平的降低导致绒毡层细胞退化延迟,小孢子壁的形成出现异常。扫描电镜观察结果显示,小孢子壁光滑,不能形成正常的外壁。以上结果表明OsMS2基因在水稻花药发育过程中起重要作用。     

Seed dispersal of three sympatric oak species by forest rodents in the Qinling Mountains, Central China

Forest rodents play an essential role as seed dispersal vectors through their caching behaviors. Using seeds of Quercus aliena, Q. glandulifera, and Cyclobalanopsis engleriana (Fagaceae), which are dominant, but poorly studied species, in the Qinling Mountains, Central China, we investigated seed predation and dispersal by forest rodents in 2010 and 2011. There were significant differences in rodent seed-eating and caching strategies among the three tree species. Seeds of Q. aliena and C. engleriana had hard coats, high nutrition contents (e.g., protein, fat, and starch), and long germination schedules (C. engleriana only). They were less frequently eaten in situ, but more likely to be eaten after removal or cached. Seeds of Q. glandulifera had soft coats and low nutrition contents and were more often eaten in situ and less likely to be eaten after removal or cached. Our findings indicated that forest rodents were primarily responsible for seed predation and dispersal of these three tree species in the Qinling Mountains, and seed traits, especially coat hardness, nutrition content, and germination schedule, were important factors influencing rodent eating and caching behaviors. In addition, seed dispersal process of each tree species differed significantly between the 2 years, reflecting the effect of mast seeding on the eating and caching strategies of forest rodents.     

Efficient in situ separation and production of l-lactic acid by Bacillus coagulans using weak basic anion-exchange resin

Bioprocess and Biosystems Engineering - To get rid of the dependence on lactic acid neutralizer, a simple and economical approach for efficient in situ separation and production of l-lactic acid...     

Impact of miRNA Sequence on miRNA Expression and Correlation between miRNA Expression and Cell Cycle Regulation in Breast Cancer Cells

The miRNAs regulate cell functions by inhibiting expression of proteins. Research on miRNAs had usually focused on identifying targets by base pairing between miRNAs and their targets. Instead of identifying targets, this paper proposed an innovative approach, namely impact significance analysis, to study the correlation between mature sequence, expression across patient samples or time and global function on cell cycle signaling of miRNAs. With three distinct types of data: The Cancer Genome Atlas miRNA expression data for 354 human breast cancer specimens, microarray of 266 miRNAs in mouse Embryonic Stem cells (ESCs), and Reverse Phase Protein Array (RPPA) transfected by 776 miRNAs in MDA-MB-231 cell line, we linked the expression and function of miRNAs by their mature sequence and discovered systematically that the similarity of miRNA expression enhances the similarity of miRNA function, which indicates the miRNA expression can be used as a supplementary factor to predict miRNA function. The results also show that both seed region and 3'' portion are associated with miRNA expression levels across human breast cancer specimens and in ESCs; miRNAs with similar seed tend to have similar 3'' portion. And we discussed that the impact of 3'' portion, including nucleotides , is not significant for miRNA function. These results provide novel insights to understand the correlation between miRNA sequence, expression and function. They can be applied to improve the prediction algorithm and the impact significance analysis can also be implemented to similar analysis for other small RNAs such as siRNAs.     

High Serum Level of Soluble Programmed Death Ligand 1 is Associated With a Poor Prognosis in Hodgkin Lymphoma

Blockade of the programmed cell death 1-programmed cell death ligand 1 pathway is a new and promising therapeutic approach in Hodgkin lymphoma (HL). To our knowledge, the impact of soluble programmed cell death ligand 1 (sPD-L1) serum levels on HL patient prognosis has not yet been investigated. In this study, the prognostic value of sPD-L1 was assessed in patients with HL. We measured serum sPD-L1 levels and identified their prognostic value in 108 newly diagnosed HL patients using an enzyme-linked immunosorbent assay (ELISA). We found higher serum sPD-L1 concentrations in HL patients than in healthy controls. The best sPD-L1 cutoff value for predicting disease progression risk was 25.1674 ng/ml. The 4-year progression-free survival (PFS) rates for the high-sPD-L1 and low-sPD-L1 groups were 78.8% and 93.3%, respectively. Multivariate survival analysis showed that advanced stage and higher sPD-L1 levels (>25.1674 ng/ml) were independent prognostic factors for shorter PFS. In addition, higher sPD-L1 levels were positively correlated with advanced stage and negatively correlated with peripheral blood monocyte number. The serum sPD-L1 level is an independent prognostic factor for PFS in HL patients and may allow identification of a subgroup of patients who require more intensive therapy and who may benefit from anti-PD-1 agents.