Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA

The phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is critical for cellular growth and metabolism. Correspondingly, loss of function of PTEN, a negative regulator of PI3K, or activating mutations in AKT1, AKT2 or AKT3 have been found in distinct disorders featuring overgrowth or hypoglycemia. We performed exome sequencing of DNA from unaffected and affected cells from an individual with an unclassified syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified the cancer-associated mutation encoding p.His1047Leu in PIK3CA, the gene that encodes the p110α catalytic subunit of PI3K, only in affected cells. Sequencing of PIK3CA in ten additional individuals with overlapping syndromes identified either the p.His1047Leu alteration or a second cancer-associated alteration, p.His1047Arg, in nine cases. Affected dermal fibroblasts showed enhanced basal and epidermal growth factor (EGF)-stimulated phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) generation and concomitant activation of downstream signaling relative to their unaffected counterparts. Our findings characterize a distinct overgrowth syndrome, biochemically demonstrate activation of PI3K signaling and thereby identify a rational therapeutic target.     

河东乌麦胚芽营养麦片的研制

在系统评价河东乌麦、黑优粘米和粤引黑大豆1号主要营养成分的基础上,以河东乌麦为主要原料,配伍黑优粘米、粤引黑大豆1号等辅料,采用原料发芽处理等工艺技术,研制开发出河东乌麦胚芽营养麦片新产品,原料通过发处理可以明显提高其维生素B1、B2、C和维生素E的含量,3种主要原料的合理配比使制成的麦片营养全面、平衡,具有良好的总溶性和适口性。     

不同活性短肽对酪朊酸钠乳化特性的影响及其配比优化

比较了水解乳清蛋白、大豆肽、海洋胶原蛋白肽、玉米肽和花生肽等不同活性短肽对酪朊酸钠的乳化活性和乳化稳定性影响,并优化了其蛋白体系乳化效果较好的复配比例.结果表明,水解乳清蛋白与酪朊酸钠的复配比例大于2∶8,大豆肽和海洋胶原蛋白肽分别与酪朊酸钠的复配比例大于1∶9时,以酪朊酸钠为主体的蛋白体系的乳化活性和乳化稳定性均显著降低(p＜0.05);玉米肽和花生肽与酪朊酸钠的复配比例为1∶9时,体系的乳化活性和乳化稳定性均显著降低(p＜0.05).进一步选用水解乳清蛋白、大豆肽和海洋胶原蛋白肽复合后与酪朊酸钠复配,采用混料设计试验,确定复配体系乳化效果较好的3种活性短肽的较佳配比为水解乳清蛋白50％、大豆肽40％、海洋胶原蛋白肽10％,3种复合活性短肽与酪朊酸钠的优化复配比例为3∶7.研究结果可为高蛋白饮料中活性短肽的选择提供理论依据.     

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair

Chronic kidney disease (CKD) represents a major health burden. Its central feature of renal fibrosis is not well understood. By exome sequencing, we identified mutations in FAN1 as a cause of karyomegalic interstitial nephritis (KIN), a disorder that serves as a model for renal fibrosis. Renal histology in KIN is indistinguishable from that of nephronophthisis, except for the presence of karyomegaly. The FAN1 protein has nuclease activity and acts in DNA interstrand cross-link (ICL) repair within the Fanconi anemia DNA damage response (DDR) pathway. We show that cells from individuals with FAN1 mutations have sensitivity to the ICL-inducing agent mitomycin C but do not exhibit chromosome breakage or cell cycle arrest after diepoxybutane treatment, unlike cells from individuals with Fanconi anemia. We complemented ICL sensitivity with wild-type FAN1 but not with cDNA having mutations found in individuals with KIN. Depletion of fan1 in zebrafish caused increased DDR, apoptosis and kidney cysts. Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms contributing to renal fibrosis and CKD.     

Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.     

荔枝多糖的超声波辅助提取工艺优化研究

通过单因素试验和RSA响应面分析法优化了荔枝多糖的超声波辅助提取工艺.结果表明,超声波法提取荔枝多糖的最佳条件为:以荔枝干果肉为原料,以水为提取剂,超声波功率72W,提取时间32min,水料比12:1.在此条件下,荔枝粗多糖的提取率可达18.94%.     

籼型稻米糊化温度和直链淀粉含量一体化的半粒测定法研究

首次提出稻米碱消值－湖化温度和直链淀粉含量一体化的半粒测定法,即采用同一半粒稻米在测定了碱消值－湖化温度后,继续测定其直链淀粉含量,取远胚端粒籼稻米在质量分数为0．5％NaOH溶液中保持在30℃的恒温箱中23h,按农业部部标准米质测定方法（NY147－88）中碱消值的判断依据与方法,可以较准确地测定其碱消值－湖化温度,测定结果与农业部部标准方法的结果一致;将测定了硝消值－湖化温度后的半粒稻米及其消解液在沸水溶中继续分散,用乙酸调节pH值后,按碘蓝比色法可以进一步测定其直链淀粉含量,其结果与国家标准稻米直链淀粉含量的测定方法（GB／T15683－1995）的结果差异不显著,发芽的结果表明,近胚端半粒稻米的发芽率在90％以上,取半粒稻米一体化测定其碱消值－湖化温度和直链淀粉含量,留半粒稻米繁种,既可以提高材料的利用率,减少分析误差,又可以提高稻米品质改良的有效性。     

荔枝多糖的提取条件及含量测定

采用料水比、浸提温度、浸提时间3因素3水平的正交试验法优化了荔枝多糖的提取条件,并用硫酸-苯酚法对荔枝多糖含量进行了测定．结果表明,荔枝多糖最佳提取条件为：料水比为1：9,浸提温度为100℃,浸提时间为4h;荔枝多糖换算因子为1．45,多糖平均质量分数为4．36％,多糖含量测定相对标准偏差(RSD)为1．57％．