An association study between polymorphism of alcohol dehydrogenase (ADH1B), aldehyde dehydrogenase (ALDH2), cytochrome (CYP4502E1), Catechol-OMethyltransferase (COMT) and 5-hydroxytryptamine transporter (5-HTT)...

Full Title: An association study between polymorphism of alcohol dehydrogenase (ADH1B), aldehyde dehydrogenase (ALDH2), cytochrome (CYP4502E1), Catechol-OMethyltransferase (COMT) and 5-hydroxytryptamine transporter (5-HTT) genes in Yunnan Han population with alcohol dependenceAbstact: Alcohol dependence (AD) is a complex disease resulting from the inheritance of several susceptible genes and multiple environmental determinants. The aim of this study was to identify the genetic risk factors which include alcohol metabolizing genes and neurotransmitter related genes for alcoholism in Yunnan Han population. Eight allelic variants of five genes were genotyped from 332 Yunnan Han individuals (including 118 alcohol-dependent patients (DSM-IV criteria) and 214 controls) using PCRRFLP method. Those polymorphic sites included alcohol dehydrogenase (ADH1B), aldehyde dehydrogenase (ALDH2), cytochrome P-4502E1 (CYP2E1) PstI, Catechol-O-Methyltransferase (COMT) rs2075507 (5’region), rs737865 (intron1), rs4680 (Val158Met), rs165599 (3’region) and serotonin transporter (5-HTTLPR). Both genotype and allele frequencies of ALDH2 and CYP4502E1 as well as the allele frequency of ADH1B gene differed significantly between AD group and control group. The proportion of ALDH2 *1/*2 genotype and *2 allele was significantly smaller in patients than that in controls (X2 = 6.554, p = 0.038; X2 = 4.906, p = 0.027), while the proportion of c2 allele of CYP4502E1 was significantly higher (X2 = 4.410, p = 0.036). Compared with the controls, the frequencies of the 5-HTTLPR L/L genotype and COMT rs737865 C/C genotype were significantly lower in AD group. Twelve COMT haplotypes (rs2075507, rs737865, rs4680 and rs165599) defined as H1 to H12 were obtained in this major minority population. The prevalence of the haplotype H1 ‘‘A-C-A-A’’ was significantly greater in alcoholics than the prevalence in their respective control group. There were no significant differences in the genotype frequencies of the COMT rs2075507, rs4680 and rs165599 polymorphisms between alcoholics and controls. COMT rs2075507 and rs737865 polymorphisms were in complete linkage disequilibrium in Han population of Yunnan Province. This study indicates that polymorphisms of ADH1B, ALDH2, CYP4502E1, COMT and 5-HTT were significantly associated with AD in Han majority. The ADH1B *2, ALDH2 *2 alleles, 5-HTTLPR L/L genotype and C/C genotype of the COMT rs737865 polymorphism had an important role in reducing the risk of AD while the c2 allele of CYP4502E1 increased the risk of AD. Therefore, the A-C-A-A haplotype may be a dangerous factor leading to AD.Key words: Yunnan Han population, polymorphism, alcohol dependence, genetic risk factor

Contrasting sensitivity of weathering proxies to Quaternary climate and sea-level fluctuations on the southern slope of the South China Sea

Tropical marginal seas host important sedimentary archives that may be exploited to reveal past changes in continental erosion, chemical weathering, and ocean dynamics. However, these records can be challenging to interpret due to the complex interactions between climate and particulate transport across ocean margins. For the southern South China Sea over the last 90 Kyr, we observe a contrasting temporal relationship between the deposition of clay minerals and magnetic minerals, which were associated with two different hydrodynamic modes. Fine-grained clay minerals can be carried in suspension by ocean currents, leading to a rapid response to regional climate-driven inputs. In contrast, changes in magnetic mineralogy were linked to glacial-interglacial sea level variability, from which we infer a control by bedload transport and resuspension. Overall, this study indicates that the transfer pathways and mechanisms imparted by varying hydrodynamic conditions exert a substantial influence on the distribution of terrigenous material in continental margin sediments

Quantum size effects on the perpendicular upper critical field in ultra-thin lead films

We report the thickness-dependent (in terms of atomic layers) oscillation behavior of the perpendicular upper critical field $H_{c2\perp}$ in the ultra-thin lead films at the reduced temperature ($t=T/T_c$). Distinct oscillations of the normal-state resistivity as a function of film thickness have also been observed. Compared with the $T_c$ oscillation, the $H_{c2\perp}$ shows a considerable large oscillation amplitude and a $\pi$ phase shift. The oscillatory mean free path caused by quantum size effect plays a role in $H_{c2\perp}$ oscillation.Comment: 4 pages, 4 figure

Modulation of Tumor Immune Microenvironment and Prognostic Value of Ferroptosis-Related Genes, and Candidate Target Drugs in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most common type of malignant brain tumor, among which IDH1-wild type GBM has a poor prognosis. Recent studies have shown that ferroptosis-related genes (FRGs) are correlated with the development and progression of cancer. In GBM, the role of FRGs associated with IDH1 status as biological indicators and therapeutic targets remains to be clarified. Ten of FRGs (STEAP3, HSPB1, MAP1LC3A, SOCS1, LOX, CAPG, CP, GDF15, CDKN1A, and CD44) associated with IDH1 status in GBM were identified as key genes through screening by survival analysis and Random Forest using The Cancer Genome Atlas (TCGA) datasets, and the protein expressions of key genes were verified. Transwell and qPCR results showed that ferroptosis promoted the migration of glioblastoma cells and affected the expression of key genes. Our study established the ferroptosis-related prognostic model for GBM patients based on ten key genes by a different modeling method from previous study, the GSVA algorithm. Further, we took the methods of functional enrichment analysis, clinical characteristics, immune cell infiltration, immunomodulator, ESTIMATE and single nucleotide variant (SNV) analysis to study the molecular mechanisms of prognostic model and key genes. The results showed that ten key genes were strongly associated with immune-related factors and were significantly involved in the p53 signaling pathway, senescence and autophagy in cancer, and in the negative regulation of protein kinase activity. Moreover, potential therapeutic drugs were identified by Virtual Screening and Molecular Docking. Our study indicated that the novel ferrotosis-related prognostic model for GBM patients and key genes possessed the prognostic and therapeutic values

Generation of Human Liver Chimeric Mice with Hepatocytes from Familial Hypercholesterolemia Induced Pluripotent Stem Cells

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HCV 6a Prevalence in Guangdong Province Had the Origin from Vietnam and Recent Dissemination to Other Regions of China: Phylogeographic Analyses

Recently in China, HCV 6a infection has shown a fast increase among patients and blood donors, possibly due to IDU linked transmission.We recruited 210 drug users in Shanwei city, Guangdong province. Among them, HCV RNA was detected in 150 (71.4%), both E1 and NS5B genes were sequenced in 136, and 6a genotyped in 70. Of the 6a sequences, most were grouped into three clusters while 23% represent emerging strains. For coalescent analysis, additional 6a sequences were determined among 21 blood donors from Vietnam, 22 donors from 12 provinces of China, and 36 IDUs from Liuzhou City in Guangxi Province. Phylogeographic analyses indicated that Vietnam could be the origin of 6a in China. The Guangxi Province, which borders Vietnam, could be the first region to accept 6a for circulation. Migration from Yunnan, which also borders Vietnam, might be equally important, but it was only detected among IDUs in limited regions. From Guangxi, 6a could have further spread to Guangdong, Yunnan, Hainan, and Hubei provinces. However, evidence showed that only in Guangdong has 6a become a local epidemic, making Guangdong the second source region to disseminate 6a to the other 12 provinces. With a rate of 2.737×10⁻³ (95% CI: 1.792×10⁻³ to 3.745×10⁻³), a Bayesian Skyline Plot was portrayed. It revealed an exponential 6a growth during 1994-1998, while before and after 1994-1998 slow 6a growths were maintained. Concurrently, 1994-1998 corresponded to a period when contaminated blood transfusion was common, which caused many people being infected with HIV and HCV, until the Chinese government outlawed the use of paid blood donations in 1998.With an origin from Vietnam, 6a has become a local epidemic in Guangdong Province, where an increasing prevalence has subsequently led to 6a spread to many other regions of China

Revealing histological and morphological features of female reproductive system in tree shrew (Tupaia belangeri)

The tree shrew has been used as a primate animal model in neuroscience studies but it has only rarely been employed in the study of reproductive systems. This is mainly because we know very little about the histological features of reproductive organs of the tree shrew. In this study, we have systematically analyzed the histology of reproductive organs of tree shrew, in comparison with human organs. The uterus of female tree shrew is uterus biomes unicolis, which is connected with an enveloped ovary through a thin fallopian tube. Histologically, the fallopian tube consists of folded mucosa, muscularis and serosa. Like other mammalian animals, the different developmental stages (primordial, primary, secondary and Graafian follicles) of ovarian follicles including inner oocyte and outer granulosa cells are embedded in the cortex. The luminal endometrium, middle muscular myometrium and serosa constitute the wall of uterus of tree shrew. The uterine endometrium contains simple columnar ciliated cells and goblet cells, and there are rich uterine glands in underlying stroma. Furthermore, these glands of tree shrew are round and smaller during anestrus, and become much longer when they are in estrus. The uterine endometrium in younger animals was less developed when compared to a mature tree shrew. Compared to human uterine endometrium, the histological features of tree shrew are very similar, indicating that it could potentially be good primate animal model for studying the diseases in reproductive system

Microwave-assisted synthesis of water-dispersed CdTe/CdSe core/shell type II quantum dots

A facile synthesis of mercaptanacid-capped CdTe/CdSe (core/shell) type II quantum dots in aqueous solution by means of a microwave-assisted approach is reported. The results of X-ray diffraction and high-resolution transmission electron microscopy revealed that the as-prepared CdTe/CdSe quantum dots had a core/shell structure with high crystallinity. The core/shell quantum dots exhibit tunable fluorescence emissions by controlling the thickness of the CdSe shell. The photoluminescent properties were dramatically improved through UV-illuminated treatment, and the time-resolved fluorescence spectra showed that there is a gradual increase of decay lifetime with the thickness of CdSe shell

PRMT1 promotes neuroblastoma cell survival through ATF5

Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number of cancers, making PRMTs potential therapeutic targets. But it remains not well understood how PRMTs impact specific oncogenic pathways. We previously identified PRMTs as important regulators of cell growth in neuroblastoma, a deadly childhood tumor of the sympathetic nervous system. Here, we demonstrate a critical role for PRMT1 in neuroblastoma cell survival. PRMT1 depletion decreased the ability of murine neuroblastoma sphere cells to grow and form spheres, and suppressed proliferation and induced apoptosis of human neuroblastoma cells. Mechanistic studies reveal the prosurvival factor, activating transcription factor 5 (ATF5) as a downstream effector of PRMT1-mediated survival signaling. Furthermore, a diamidine class of PRMT1 inhibitors exhibited anti-neuroblastoma efficacy both in vitro and in vivo. Importantly, overexpression of ATF5 rescued cell apoptosis triggered by PRMT1 inhibition genetically or pharmacologically. Taken together, our findings shed new insights into PRMT1 signaling pathway, and provide evidence for PRMT1 as an actionable therapeutic target in neuroblastoma