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17β-Estradiol up-regulates UDP-glucuronosyltransferase 1A9 expression via estrogen receptor α

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Acta Pharmaceutica Sinica B 2016年第5期6卷 504-509页

作者： Sung-joon Cho Miaoran Ning Yanyan Zhang leah h.Rubin hyunyoung Jeong Department of Biopharmaceutical Sciences College of PharmacyUniversity of Illinois at Chicago Department of Pharmacy Practice College of PharmacyUniversity of Illinois at Chicago Department of Psychiatry University of Illinois at Chicago

UDP-glucuronosyltransferase 1A9(UGT1A9) is a major phase II enzyme responsible for elimination of drugs and endogenous *** data have shown increased elimination of UGT1A9 substrates in pregnant women or oral contraceptive users,but the role of estrogen in the regulation of UGT1A9 expression remains *** this study,we investigated the effect of 17β-estradiol(E2) on UGT1A9 expression and the role of ERα in the transcriptional regulation of UGT1A9.E2 significantly increased UGT1A9 promoter activity in hep G2 cells in the presence of ERα.UGT1A9 induction by E2 was abrogated by antiestrogen ICI182,780 in hep G2 cells that constitutively express ERα.Results from transient transfection of ERα mutants into hep G2 cells demonstrated that mutation at DNA-binding domain of ERα abrogates increased UGT1A9 promoter activity by *** and mutation assays of UGT1A9 promoter revealed a putative ERE located within -2262/-1987 *** of healthy human liver tissues revealed significantly higher UGT1A9 expression in women as compared to ***,these findings provide a mechanistic basis for the previous clinical reports and may shed a light on identifying sources for inter-individual variability in UGT1A9-mediated drug metabolism.

关键词： UGT1A9 17β-Estradiol Estrogen receptor Drug metabolism Sex difference

WNK1: analysis of protein kinase structure, downstream targets, and potential roles in hypertension

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Cell Research 2005年第1期15卷 6-10页

作者： Byung-hoon LEE,Lisa LENERTZ,Charles J hEISE,Steve STIPPEC,Elizabeth J GOLDSMITh,Melanie h. cobb Department of Pharmacology University of Texas Southwestern Medical Center 5323 harry hines Blvd Dallas USA. Department of Pharmacology University of Texas Southwestern Medical Center 5323 harry hines Blvd Dallas USA. Department of Pharmacology University of Texas Southwestern Medical Center 5323 harry hines Blvd Dallas USA. Department of Pharmacology University of Texas Southwestern Medical Center 5323 harry hines Blvd Dallas USA. Department of Biochemistry University of Texas Southwestern Medical Center 5323 harry hines Blvd Dallas USA. Department of Pharmacology University of Texas Southwestern Medical Center 5323 harry hines Blvd Dallas USA.

The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis. Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type II, a disease with salt-sensitive hypertension and hyperkalemia. This review focuses on the recent evidence elucidating the structure of the kinase domain of WNK1 and functions of these kinases in normal and disease physiology. Their functions have implications for understanding the biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. The WNK kinases may be able to influence ion homeostasis through its effects on synaptotagmin function.

关键词： kinase hypertension synaptotagmin MAP3K MAP4K ERK5 RNAi.

Axial strain enhances osteotomy repair with a concomitant increase in connexin43 expression

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Bone Research 2015年第2期3卷 83-91页

作者： Rishi R Gupta hyunchul Kim Yu-Kwan Chan Carla hebert leah Gitajn David J Yoo Robert V O’Toole Adam h hsieh Joseph P Stains Department of Orthopaedics University of Maryland Fischell Department of Bioengineering University of MarylandCollege Park

The mechanical environment is known to influence fracture healing. We speculated that connexin43 （Cx43） gap junctions, which impact skeletal homeostasis, fracture healing and the osteogenic response to mechanical load, may play a role in mediating the response of the healing bone to mechanical strain. here, we used an established rat fracture model, which uses a 2 mm osteotomy gap stabilized by an external fixator, to examine the impact of various cyclical axial loading protocols （2%, 10%, and 30% strain） on osteotomy healing. We examined the presence of Cx43 in the osteotomy-healing environment and assessed how mechanical strain modulates Cx43 expression patterns in the callus. We demonstrated that increased cyclical axial strain results in increased radiographic and histologic bone formation. In addition, we show by immunohistochemistry that Cx43 is abundantly expressed in the healing callus, with the expression most robust in samples exposed to increased cyclical axial strain. These data are consistent with the concept that an increase in Cx43 expression by mechanical load may be part of the mechanisms by which mechanical forces enhances fracture healing.

关键词： connexin healing repair concomitant callus homeostasis assessed skeletal exposed stained

Differential Relationships among Facets of Alexithymia and BDNF- and Dopamine-Related Polymorphisms

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Neuroscience & Medicine 2012年第1期3卷 7-13页

作者： Nancy S. Koven leah h. Carr Program in Neuroscience Bates College Lewiston Maine USA

Alexithymia refers to a cluster of emotion-related deficits such as difficulty attending to and identifying one’s feelings. Although not a diagnosable psychiatric condition, alexithymia is considered a personality risk factor for multiple pathologies, including somatoform, substance use, eating, and mood disorders. Evidence suggests heritability, but few studies have examined the influence of specific genes on alexithymic traits. Candidate genes explored thus far include those involved in modulation of brain-derived neurotrophic factor (BDNF) and dopamine, two neurotransmitters whose functions have been implicated in human emotion processing. This study investigated the relationship between the C270T polymorphism of the BDNF gene, facets of alexithymia, and possible interactions with the COMT, DAT1, and ANKK1 genes in a sample of 130 healthy adults. Given the multidimensionality of the alexithymia construct and its overlap with the related constructs of emotional intelligence and mood awareness, we used principal components analysis to derive Clarity of Emotion and Attention to Emotion as specific facets of alexithymia. Results showed that the C270T C/C genotype group had lower Clarity of Emotion scores relative to the C/T genotype group, even after covarying for COMT, DAT1, and ANKK1 genotypes. Dopamine-related genes had no association with alexithymia dimensions, nor did they interact with the C270T polymorphism to predict Clarity of Emotion. Although the molecular mechanisms by which this polymorphism influences BDNF are unknown, this study suggests a role for BDNF in modulating aspects of alexithymia. We discuss these results in the context of BDNF’s trophic effects in the nervous system.

关键词： Brain-Derived Neurotrophic Factor Alexithymia Dopamine Polymorphism

An Overview of FAST Real-time Fast Radio Burst Searching System

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Research in Astronomy and Astrophysics 2023年第9期23卷 251-263页

作者： X.X.Zhang R.Duan V.Gajjar h.Y.Zhang P.Wang C.h.Niu D.Werthimer J.cobb S.Y.Li X.Pei Y.Zhu D.Li National Astronomical Observatories Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Department of Astronomy University of California BerkeleyBerkeleyCA94720.USA hebei Key Laboratory of Radio Astronomy Technology Shijiazhuang 050081China Space Sciences Laboratory University of California BerkeleyBerkeleyCA 94720USA Beijing Planetarium Beijing Academy of Science and TechnologyBeijing 100044China Xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China NAOC-UKZN Computational Astrophysics Centre University of KwaZulu-NatalDurban 4000South Africa

In this paper,we report a real-time Fast Radio Burst(FRB)searching system that has been successfully implemented with the 19 beam receiver of the Five-hundred-meter Aperture Spherical radio Telescope(FAST).The relatively small field of view of FAST makes the search for new FRBs challenging,but its high sensitivity significantly improves the accuracy of FRB localization and enables the detection of high-precision neutral hydrogen absorption lines generated by *** goal is to develop an FRB searching system capable of realtime detection of FRBs that allows high-time resolution spectro-temporal studies among the repeated bursts,as well as detailed investigations of these bursts and exploration of FRB progenitor *** data from each beam of the 19-beam receiver are fed into a high-performance computing node server,which performs real-time searches for pulses with a wide dispersion measure(DM)range of 20–10,000 pc cm^(-3) with step efficiency of 25%in real ***,the head node server aggregates all the candidate signals from each beam within a given time,determining their authenticity based on various criteria,including arrival time,pulse width,signal-to-noise ratio and coincidence patterns among the 19 *** the 1.05–1.45 Ghz operating bandwidth of the FAST 19beam receiver,the system achieves a frequency resolution of 122.07 khz and a time resolution of 270.336μ***,our team detected a series of bursts with a DM of 566 on 2019 August 30 confirming them as *** FRB searching system enables the 19-beam receiver of FAST to detect repeated/one-off pulses/bursts in real time.

关键词： Astronomical Instrumentation-Methods and Techniques-instrumentation spectrographs-methods miscellaneous

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GPS伪卫星理论、设计与应用

habitat productivity and pyrethroid susceptibility status of Aedes aegypti mosquitoes in Dar es Salaam,Tanzania

2005年

作者： h. Stewart cobb 耿建平等翻译

中国科学院知识创新工程重大项目资助出版:全书包含7章，对伪卫星的基本、伪卫星的种类、伪卫星的信号设计、伪卫星设计时应考虑的主要问题、使用伪卫星导航的算法、远—近问题的解决方法以及接收机的改动等进行了详细的论述。

ISBN: (纸本)7504639605

关键词：全球定位系统 GPS 基本知识

来源：汇雅图书（南通市图书馆... 评论

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Infectious Diseases of Poverty 2017年第1期6卷 921-930页

作者： leah Mathias Vito Baraka Anitha Philbert Ester Innocent Filbert Francis Gamba N.kwengulila Eliningaya J.Kweka Department of Zoology and Wildlife Conservation College of Natural and Applied SciencesUniversity of Dar es SalaamP.O.Box 35165Dar es SalaamTanzania National Institute for Medical Research Tanga Medical Research CentreP.O.Box 5004Tanga UrbanTangaTanzania Global health Institute University of AntwerpGouverneur KinsbergencentrumDoornstraat 331B-2610WilrijkBelgium Mkwawa University College of Education Private BagIringaTanzania Institute of Traditional Medicine Muhimbili University of Health and Allied SciencesP.O.Box 65001Dar es SalaamTanzania Department of Medical Parasitology and Entomology Catholic University of Health and Allied SciencesP.O.Box 1464MwanzaTanzania Division of Livestock and human Diseases Vector Control Tropical Pesticides Research InstituteNgaramtoniOff Nairobi RoadP.O.Box 3024ArushaTanzania

Background:Aedes aegypti(Diptera:Culicidae)is the main vector of the dengue virus *** vector control is mainly based on reducing the vector population through interventions,which target potential breeding ***,in Tanzania,little is known about this vector’s habitat productivity and insecticide susceptibility status to support evidence-based implementation of control *** present study aimed at assessing the productivity and susceptibility status of *** mosquitoes to pyrethroid-based insecticides in Dar es Salaam,***:An entomological assessment was conducted between January and July 2015 in six randomly selected wards in Dar es Salaam,*** productivity was determined by the number of female adult *** mosquitoes emerged per square *** susceptibility status of adult *** females after exposure to 0.05%deltamethrin,0.75%permethrin and 0.05%lambda-cyhalothrin was evaluated using the standard WhO *** rates were recorded after 24 h exposure and the knockdown effect was recorded at the time points of 10,15,20,30,40,50 and 60 min to calculate the median knockdown times(KDT50 and KDT95).Results:The results suggest that disposed tyres had the highest productivity,while water storage tanks had the lowest productivity among the breeding habitats Of *** *** sites demonstrated reduced susceptibility to deltamethrin(0.05%)within 24 h post exposure,with mortalities ranging from 86.3±1.9(mean±SD)to 96.8±0.9(mean±SD).The lowest and highest susceptibilities were recorded in Mikocheni and Sinza wards,***,all sites demonstrated reduced susceptibility permethrin(0.75%)ranging from 83.1±2.1%(mean±SD)to 96.2±0.9%(mean±SD),in Kipawa and Sinza,*** low mortality rates were observed in relation to lambda-cyhalothrin(0.05%)at all sites,ranging from 83.1±0.7(mean±SD)to 86.3±1.4(mean±SD).The median KDT_(50)for deltamethrin,permethrin and lambda-cyhalo

关键词： Culicidae Aedes aegypti Abundance Productivity Pyrethroid Knockdown effect Dar es Salaam Tanzania

5-Methylcytosine RNA Methylation in Arabidopsis Thaliana

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Molecular Plant 2017年第11期10卷 1387-1399页

作者： Xuean Cui Zhe Liang Lisha Shen Qian Zhang Shengjie Bao Yuke Geng Bin Zhang Vonny Leo leah A. Vardy Tiegang Lu Xiaofeng Gu hao Yu Biotechnology Research Institute Chinese Academy of Agricultural Sciences Beijing 100081 China Department of Biological Sciences and Temasek Life Sciences Laboratory National University of Singapore 117543 Singapore Singapore Institute of Medical Biology Agency for Science Technology and Research (A^+STAR) 8A Biomedical Grove #06-06 Immunos 138648 Singapore Singapore

5-Methylcytosine （m^5C） is a well-characterized DNA modification, and is also predominantly reported in abundant non-coding RNAs in both prokaryotes and eukaryotes. however, the distribution and biological functions of m^5C in plant mRNAs remain largely unknown. here, we report transcriptome-wide profiling of RNA m^5C in Arabidopsis thaliana by applying m^5C RNA immunoprecipitation followed by a deep- sequencing approach （m^5C-RIP-seq）. LC-MS/MS and dot blot analyses reveal a dynamic pattern of m^5C mRNA modification in various tissues and at different developmental stages, m^5C-RIP-seq analysis identified 6045 m^5C peaks in 4465 expressed genes in young seedlings. We found that m^5C is enriched in coding sequences with two peaks located immediately after start codons and before stop codons, and is associated with mRNAs with low translation activity. We further demonstrated that an RNA （cytosine-5）-methyl- transferase, tRNA-specific methyltransferase 4B （TRM4B）, exhibits m^5C RNA methyltransferase activity. Mutations in TRM4B display defects in root development and decreased m^5C peaks. TRM4B affects the transcript levels of the genes involved in root development, which is positively correlated with their mRNA stability and m^5C levels. Our results suggest that m^5C in mRNA is a new epitranscriptome marker inArabidopsis, and that regulation of this modification is an integral part of gene regulatory networks underlying plant development.

关键词： 5-methylcytosine (m^5C) Arabidopsis RNA methylation TRM4B root development

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CCIE实验指南第2卷 1