A novel human polycomb binding site acts as a functional polycomb response element in Drosophila

Polycomb group (PcG) proteins are key chromatin regulators implicated in multiple processes including embryonic development, tissue homeostasis, genomic imprinting, X-chromosome inactivation, and germ cell differentiation. The PcG proteins recognize target genomic loci through cis DNA sequences known as Polycomb Response Elements (PREs), which are well characterized in Drosophila. However, mammalian PREs have been elusive until two groups reported putative mammalian PREs recently. Consistent with the existence of mammalian PREs, here we report the identification and characterization of a potential PRE from human T cells. The putative human PRE has enriched binding of PcG proteins, and such binding is dependent on a key PcG component SUZ12. We demonstrate that the putative human PRE carries both genetic and molecular features of Drosophila PRE in transgenic flies, implying that not only the trans PcG proteins but also certain features of the cis PREs are conserved between mammals and Drosophila.     

野百合碱诱导大鼠肺动脉高压及肺源性心脏病的病理生理特征

目的:探讨野百合碱诱发肺动脉高压及肺源性心脏病模型的建立机制。方法:雄性Wistar大鼠20只,随机分为两组(n=10):正常组,模型组。模型组大鼠腹腔一次性注射野百合碱50 mg/kg,对照组注射同剂量的溶媒,28 d后测定大鼠血流动力学参数,硝酸盐还原酶法测定血清和肺组织中一氧化氮的含量;放射免疫法测定血浆中内皮素、脑钠素和肺组织中肿瘤坏死因子、内皮素的含量。结果:与对照组比较,右心室压力上升、心率和平均动脉压下降,血液和肺组织中肿瘤坏死因子、一氧化氮、内皮素-1、脑钠素含量上升,具有统计学意义。结论:野百合碱通过诱发肺血管和组织炎性损伤,升高体内肿瘤坏死因子、一氧化氮、内皮素-1的含量,建立肺动脉高压及肺源性心脏病模型。     

Prevalence and Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency at the China-Myanmar Border

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hereditary disease that predisposes red blood cells to oxidative damage. G6PD deficiency is particularly prevalent in historically malaria-endemic areas. Use of primaquine for malaria treatment may result in severe hemolysis in G6PD deficient patients. In this study, we systematically evaluated the prevalence of G6PD deficiency in the Kachin (Jingpo) ethnic group along the China-Myanmar border and determined the underlying G6PD genotypes. We surveyed G6PD deficiency in 1770 adult individuals (671 males and 1099 females) of the Kachin ethnicity using a G6PD fluorescent spot test. The overall prevalence of G6PD deficiency in the study population was 29.6% (523/1770), among which 27.9% and 30.6% were males and females, respectively. From these G6PD deficient samples, 198 unrelated individuals (147 females and 51 males) were selected for genotyping at 11 known G6PD single nucleotide polymorphisms (SNPs) in Southeast Asia (ten in exons and one in intron 11) using a multiplex SNaPshot assay. Mutations with known association to a deficient phenotype were detected in 43.9% (87/198) of cases, intronic and synonymous mutations were detected alone in 34.8% (69/198) cases and no mutation were found in 21.2% (42/198) cases. Five non-synonymous mutations, Mahidol 487G>A, Kaiping 1388G>A, Canton 1376G>T, Chinese 4 392G>T, and Viangchan 871G>A were detected. Of the 87 cases with known deficient mutations, the Mahidol variant was the most common (89.7%; 78/87), followed by the Kaiping (8.0%; 7/87) and the Viangchan (2.2%; 2/87) variants. The Canton and Chinese 4 variants were found in 1.1% of these 87 cases. Among them, two females carried the Mahidol/Viangchan and Mahidol/Kaiping double mutations, respectively. Interestingly, the silent SNPs 1311C>T and IVS11nt93T>C both occurred in the same 95 subjects with frequencies at 56.4% and 23.5% in tested females and males, respectively (P<0.05). It is noteworthy that 24 subjects carrying the Mahidol mutation and two carrying the Kaiping mutation also carried the 1311C>T/IVS11nt93T>C SNPs. Further studies are needed to determine the enzyme levels of the G6PD deficient people and presence of additional G6PD mutations in the study population.     

Chitosan nanoparticle as gene therapy vector via gastrointestinal mucosa administration: results of an in vitro and in vivo study

This study was designed to investigate the in vitro and in vivo transfection efficiency of chitosan nanoparticles used as vectors for gene therapy. Three types of chitosan nanoparticles [quaternized chitosan -60% trimethylated chitosan oligomer (TMCO-60%), C(43-45 KDa, 87%), and C(230 KDa, 90%)] were used to encapsulate plasmid DNA (pDNA) encoding green fluorescent protein (GFP) using the complex coacervation technique. The morphology, optimal chitosan-pDNA binding ratio and conditions for maximal in vitro transfection were studied. The in vivo transfection was conducted by feeding the chitosan/pDNA nanoparticles to 12 BALB/C-nu/nu nude mice. Both conventional and TMCO-60% could form stable nanoparticles with pDNA. The in vitro study showed the transfection efficiency to be in the following descending order: TMCO-60%>C(43-45 KDa, 87%)>C(230 KDa, 90%). TMCO-60% proved to be the most efficient and the optimal chitosan/pDNA ratio being 3.2:1. In vivo study showed most prominent GPF expression in the gastric and upper intestinal mucosa. GFP expression in the mucosa of the stomach and duodenum, jejunum, ileum, and large intestine were found, respectively, in 100%, 88.9%, 77.8% and 66.7% of the nude mice examined. TMCO-60%/pDNA nanoparticles had better in vitro and in vivo transfection activity than the other two, and with minimal toxicity, which made it a desirable non-viral vector for gene therapy via oral administration.     

Inhibition of polypeptide N-acetyl-α-galactosaminyltransferases is an underlying mechanism of dietary polyphenols preventing colorectal tumorigenesis

Ellagitannin-derived ellagic acid (EA) and colonic metabolite urolithins are functional dietary ingredients for cancer prevention, but the underlying mechanism need elucidation. Mucin-type O-glycosylation, initiated by polypeptide N-acetyl-α-galactosaminyltransferases (ppGalNAc-Ts), fine-tunes multiple biological processes and is closely associated with cancer progression. Herein, we aim to explore how specific tannin-based polyphenols affect tumor behavior of colorectal cancer cells (CRC) by modulating O-glycosylation. Utilizing HPLC-based enzyme assay, we find urolithin D (UroD), EA and gallic acid (GA) potently inhibit ppGalNAc-Ts. In particular, UroD inhibits ppGalNAc-T2 through a peptide/protein-competitive manner with nanomolar affinity. Computational simulations combined with site-directed mutagenesis further support the inhibitors’ mode of action. Moreover, lectin analysis and metabolic labelling reveal that UroD can reduce cell O-glycans but not N-glycans. Transwell experiments prove that UroD inhibits migration and invasion of CRC cells. Our work proves that specific tannin-based polyphenols can potently inhibit ppGalNAc-Ts activity to reduce cell O-glycosylation and lead to lowering the migration and invasion of CRC cells, suggesting that disturbance of mucin-type O-glycosylation is an important mechanism for the function of dietary polyphenols.     

胰岛素不同给药方式对妊娠期糖尿病患者围手术期血糖控制的效果研究

目的:研究胰岛素不同给药方式对妊娠期糖尿病患者围手术期血糖控制的效果与安全性。方法:选择2013年11月～2016年11月于我院接受治疗的92例妊娠期糖尿病患者,所有患者按随机数字表法分为对照组和研究组,每组46例。对照组围手术期予以皮下注射胰岛素治疗,研究组围手术期予以胰岛素泵治疗。比较两组空腹血糖(FBG),餐后2 h血糖(2hPBG),血糖达标情况,抗生素使用情况,切口愈合情况、住院时间及并发症的发生情况。结果:治疗后12 h、24 h及36 h,两组FBG、2hPBG水平均较治疗前显著下降,且研究组以上指标均低于对照组(P0.05)。研究组血糖达标、抗生素使用、切口愈合及住院时间均明显短于对照组(P0.05)。两组均有低血糖、切口感染发生,研究组并发症发生率低于对照组(P0.05)。结论:胰岛素泵输注胰岛素对妊娠期糖尿病患者围手术血糖的控制效果明显优于皮下注射胰岛素,且其安全性更高。     

Non-invasive estimation of root zone soil moisture from coarse root reflections in ground-penetrating radar images

Plant and Soil - Root zone soil moisture is an important component in water cycling through the soil-plant-atmosphere continuum. However, its measurement in the field remains a challenge,...     

棉铃虫核型多角体病毒多角体蛋白聚集体特性及与其它包涵体蛋白的血清学关系

纯化的多角体碱解释放多角体蛋白,经等电点沉淀和柱层析对多角体蛋白进行分离纯化,结合SDS-PAGE、免疫双向扩散、免疫电镜等方法,证明棉铃虫核型多角体病毒(HaNPV)的多角体蛋白以聚集体形式存在。用ELISA法检测包涵体蛋白之间的血清学关系,结果表明,与黄地老虎颗粒体病毒(AsGV)和粘虫颗粒体病毒(PsGV)颗粒体蛋白相比较,HaNPV多角体蛋白与葡萄天蛾核型多角体病毒(ArNPV)和黄地老虎核型多角体病毒(AsNPV)多角体蛋白之间的血清学关系更为密切。