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Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension

Chronic Diseases and Translational Medicine 2024年第2期10卷 102-117页

作者： Nicholas R.Powell Tyler Shugg Jacob Leighty Matthew Martin Rolf P.Kreutz Michael T.Eadon Dongbing Lai Tao Lu todd C.Skaar Division of Clinical Pharmacology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Pharmacology and Toxicology School of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Cardiology School of MedicineKrannert Institute of CardiologyIndiana UniversityIndianapolisIndianaUSA Division of Nephrology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Medical and Molecular Genetics School of MedicineIndiana UniversityIndianapolisIndianaUSA

Background Hypertension(HTN)involves genetic variability in the renin-angiotensin system and influences antihypertensive *** previously reported that angiotensinogen(AGT)messenger RNA(mRNA)is endogenously bound by miR-122-5p and rs699 A>G decreases reporter mRNA in the microRNA functional-assay *** AGT promoter variant rs5051 C>T is in linkage disequilibrium(LD)with rs699 A>G and increases AGT *** independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C>T counterbalances AGT decreased by rs699 A>G,and when these variants occur independently,it translates to HTN-related *** We used in silico,in vitro,in vivo,and retrospective models to test this *** In silico,rs699 A>G is predicted to increase miR-122-5p binding affinity by 3%.Mir-eCLIP results show rs699 is 40–45 nucleotides from the strongest microRNA-binding site in the AGT ***,rs699 A>G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression ***-Tissue Expression(GTEx)and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A>G occurs independently from rs5051 C>***,GTEx and the in vitro experiments suggest rs699 A>G confers cell-type-specific effects on AGT mRNA abundance,and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A>G associations with *** We found that rs5051 C>T and rs699 A>G significantly associate with systolic blood pressure in Black participants in the UK Biobank,demonstrating a fourfold larger effect than in White *** studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C>T or rs699 A>*** like this will help clinicians move beyond the use of race as a surrogate for genotype.

关键词： angiotensinogen genetic and genomic medicine hypertension rs699

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Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

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World Journal of Gastroenterology 2024年第4期30卷 332-345页

作者： Yi-Jie Li Brittney O Baumert Nikos Stratakis Jesse A Goodrich Hao-Tian Wu Jing-Xuan He Yin-Qi Zhao Max T Aung Hong-Xu Wang Sandrah P Eckel Douglas I Walker Damaskini Valvi Michele A La Merrill Justin R Ryder Thomas H Inge todd Jenkins Stephanie Sisley Rohit Kohli Stavra A Xanthakos Andrea A Baccarelli Rob McConnell David V Conti Lida Chatzi Department of Population and Public Health Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90032United States Barcelona Institute of Global Health Barcelona Institute of Global HealthBarcelona 08036Spain Department of Environmental Health Sciences Mailman School of Public HealthColumbia UniversityNew YorkNY 10032United States Gangarosa Department of Environmental Health Rollins School of Public HealthEmory UniversityAtlantaGA 30329United States Department of Environmental Medicine and Public Health Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Department of Environmental Toxicology University of CaliforniaDavisCA 95616United States Department of Surgery Lurie Children’s Hospital of ChicagoChicagoIL 60611United States Northwestern University Feinberg School of Medicine Northwestern UniversityChicagoIL 60611United States Division of Biostatistics and Epidemiology Cincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States Department of Pediatrics University of Cincinnati College of MedicineCincinnatiOH 45229United States Department of Pediatrics Children’s Nutrition Research Center USDA/ARSBaylor College of MedicineHoustonTX 77030United States Department of Gastroenterology Children’s Hospital Los AngelesLos AngelesCA 90027United States Division of Gastroenterology Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and *** ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with *** microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains *** analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in *** To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with *** This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery ***-operative core liver biopsies were collected from participants and used to characterize histological features of *** samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq *** examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key *** Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of *** We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with ***,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,***,16 miRNAs were associated with two or more histological features of *** those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and posi

关键词： MicroRNA Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Liver fibrosis Lobular inflammation Ballooning degeneration

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南京天印山医院

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建筑实践 2024年第4期 152-153页

作者：曹伟孙承磊吉英雷 todd Pilgreen Roman Wittmer 舒帆东南大学建筑设计研究院有限公司晋思建筑设计事务所

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Lyapunov exponent,Liao perturbation and persistence

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Science China Mathematics 2020年第9期63卷 1913-1928页

作者： Wenxiang Sun todd Young School of Mathematical Sciences Peking UniversityBeijing 100871China Department of Mathematics Ohio UniversityAthensOH 45701USA

Consider a C1 vector eld together with an ergodic invariant probability that hasℓnonzero Lya-punov *** orthonormal moving frames along a generic orbit we construct a linear system ofℓdi erential equations which is a linearized Liao standard *** show that Lyapunov exponents of this linear system coincide with all the nonzero exponents of the given vector eld with respect to the given ergodic ***,we prove that these Lyapunov exponents have a persistence property meaning that a small perturbation to the linear system(Liao perturbation)preserves both the sign and the value of the nonzero Lyapunov exponents.

关键词： Lyapunov exponent Liao perturbation ergodic probability non-uniformly hyperbolicity

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Kinetics of Molecular Recognition Mediated Nanoparticle Self-Assembly

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Nano Research 2009年第1期2卷 78-84页

作者： Chinmay Soman todd Giorgio Interdisciplinary Program in Materials Science Vanderbilt University201 West End AvenueNashvilleTN 37240USA Department of Biomedical Engineering Vanderbilt University201 West End AvenueNashvilleTN 37240USA

Nanoscale quantum dot-antibody conjugates have been shown to self-assemble to form micron-scale aggregates in the presence of specific proteomic *** self-assembly process exhibits sigmoidal kinetics,suggesting that nucleation limits ***-assembly kinetics in this study is characterized by flow cytometric analysis of the aggregation reaction over time.A range of physiologically relevant concentrations of the protein angiopoietin-2,a candidate cancer biomarker,are incubated with quantum dots conjugated with a polyclonal mixture of anti-angiopoietin-2 *** concentration modulates the slopes and inflection times of the sigmoidal kinetics *** understanding of self-assembly kinetics in this system may lead to improvements in sensitivity and specificity of this novel proteomic biomarker detection technique and improve the screening,diagnostics,and therapy response monitoring for cancers and other *** approach to studying the kinetics of nanoparticle self-assembly may also provide a valuable tool for understanding the fundamental characteristics of nanoscale particle aggregation.

关键词： Quantum dot self-assembly kinetics proteomics diagnostics has

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New Methodological Approach to Investigation of Kinetics of REE Extraction in Nonstationary Conditions

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Journal of Rare Earths 2007年第4期25卷 385-391页

作者： Kopyrin A A Fomichev A A Afonin M A todd T A Saint-Petersburg Institute of Technology Idaho National Laboratory

The influence of periodical oscillations of the temperature on extraction and stripping processes in the extraction systems was studied. Two extraction systems were investigated：（1） 6 mol · L^-1 NaNO3-Nd（NO3）3-Pr（NO3）3-TBP kerosene and （2） [Nd（NO3）3 · 3TBP] -[ Pr（NO3）3 · 3TBP] -kerosene - 0.1 mol · L^-1 HNO3. Mathematical modeling of the nonstationary membrane extraction has been enhanced by including the dependence of the extraction rate constants on temperature. The values of activation energy for direct and reverse extraction and stripping reactions of Pr and Nd were calculated from experimental temporal dependencies of metal concentration and temperature by solving the reverse kinetics problem using the proposed mathematical model, A series of experiments with periodical oscillations of the temperature on the extraction system for the separation of rare earth elements （REE） using bulk liquid membrane between two extractors were performed. The mathematical model adequately describes the experimental data. The optimization of the extraction process for separation of REE by liquid membrane, under the influence of periodical oscillation of the temperature, was made based on the extraction rate constants and activation energies. The optimal conditions of separation by liquid membrane were found： frequency and amplitude of thermal oscillations, liquid membrane flow rate, and optimal ratio between organic and aqueous phase in extractors.

关键词： kinetics extraction non-stationary rare earths

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Distribution of Primitive λ-Roots of Composite Moduli II

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Chinese Annals of Mathematics,Series B 2006年第5期27卷 549-552页

作者： Zhiyong ZHENG todd COCHRANE Department of Mathematical Sciences Tsinghua University Beijing 100084 China Department of Mathematics Kansas State University Manhattan Kansas 66506 USA.

We improve estimates for the distribution of primitive λ-roots of a composite modulus q yielding an asymptotic formula for the number of primitive A-roots in any interval I of length ｜I｜〉〉 q^1/2＋ε Similar results are obtained for the distribution of ordered pairs （x, x^-1） with x a primitive λ-root, and for the number of primitive A-roots satisfying inequalities such as ｜x - x^-1｜≤ B.

关键词： λ-Roots Primitive roots

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Upper bounds on a two-term exponential sum

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Science China Mathematics 2001年第8期44卷 1003-1015页

作者： todd COCHRANE 郑志勇 Department of Mathematics Kansas State University Manhattan KS 66506 USA Department of Mathematics Tsinghua University Beijing 100084 China

We obtain upper bounds for mixed exponential sums of the type $S(\chi ,f,p^m ) = \sum\nolimits_{x = 1}^{p^n } {\chi (x)e} _{p^m } (ax^n + bx)$ where pm is a prime power with m? 2 and X is a multiplicative character (mod pm). If X is primitive or p?(a, b) then we obtain |S(χ,f,p m)| ?2np 2/3 m . If X is of conductor p and p?( a, b) then we get the stronger bound |S(χ,f,p m)|?np m/2.

关键词： exponential sums primitive character weil’sbound

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Between Human and Animal： A Study of New Year＇s Sacrifice, Kong YijL and Diary of a Madman

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Frontiers of Literary Studies in China-Selected Publications from Chinese Universities 2012年第3期6卷 374-392页

作者： todd Foley Department of East Asian Studies New York University New York NY 10003 USA

A subtle aspect of Lu Xun＇s writing, running through several of his works of fiction, is his animalistic portrayal of some of his most well-known characters. Scraping away their humanity as he writes, Lu Xun depicts Kong Yiji, Xianglin Sao, and the infamous Madman crawling on their hands and knees, working like draught animals, and abandoning all rational thought. In short, all three end up occupying an ambiguous space between the realms of human and animal. This paper attempts to examine how Lu Xun＇s description and situation of these characters suggests, aside from the standard agendas of May Fourth writing in general, a certain, shared metaphysical conundrum. Drawing on the work of Giorgio Agamben to take the hiatus between human and animal as an occasion for ontological possibility, I will investigate how the dehumanized portrayal of these characters situates them at the threshold of a new becoming： one which has not yet been realized, but which is also rendered impossible either through the character＇s death or return to health. Examining Lu Xun＇s works in this way not only recognizes his major emphasis on social critique, but suggests both that his thought on Chinese society pierces through to the level of metaphysical inquiry, and that the relationship between human and animal marks a productive entry point for this sort of questioning.

关键词： Lu Xun animality Agamben metaphysics Kong Yiji Xianglin Sao Madman

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Modeling endodermal organ development and diseases using human pluripotent stem cell-derived organoids

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Journal of Molecular Cell Biology 2020年第8期12卷 580-592页

作者： Fong Cheng Pan todd Evans Shuibing Chen Department of Surgery Weill Cornell Medical CollegeNew YorkNY 10065USA

Recent advances in development of protocols for directed differentiation from human pluripotent stem cells(hPSCs)to defined lineages,in combination with 3D organoid technology,have facilitated the generation of various endoderm-derived organoids for in vitro modeling of human gastrointestinal development and associated *** this review,we discuss current state-ofthe-art strategies for generating hPSC-derived endodermal organoids including stomach,liver,pancreatic,small intestine,and colonic *** also review the advantages of using this system to model various human diseases and evaluate the shortcomings of this ***,we emphasize how other technologies,such as genome editing and bioengineering,can be incorporated into the 3D hPSC-organoid models to generate even more robust and powerful platforms for understanding human organ development and disease modeling.

关键词： human pluripotent stem cells endoderm gastrointestinal development disease modeling

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