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Association between Exposure to Metals during Pregnancy,Childhood Gut Microbiome,and Risk of Intestinal Inflammation in Late Childhood

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Environment & Health 2024年第10期2卷 739-749页

作者： Vishal Midya Manasi Agrawal Jamil M.Lane Chris Gennings Leonid Tarassishin Libni A.Torres-Olascoaga Joseph Eggers Jill K.Gregory Mellissa Picker Inga Peter Jeremiah J.Faith Manish Arora Martha M.Tellez-Rojo robert O.Wright Jean-Frederic Colombel Shoshannah Eggers Department of Environmental Medicine and Climate Science Icahn School of Medicine at Mount SinaiNew York 10029-6574New YorkUnited States Division of Gastroenterology Icahn School of Medicine at Mount SinaiNew York 10029-6574New YorkUnited States Center for Molecular Prediction of Inflammatory Bowel Disease(PREDICT) Department of Clinical MedicineAalborg UniversityCopenhagen 9220Denmark Department of Genetics and Genomic Sciences Icahn School of MedicineNew York 10029-6574New YorkUnited States Center for Research on Nutrition and Health National Institute of Public HealthCuernavaca 62508Mexico Department of Immunology and Immunotherapy Icahn School of Medicine at Mount SinaiNew York 10029-6574New YorkUnited States Department of Epidemiology University of Iowa College of Public HealthIowa City 52242 IowaUnited States Instructional Technology Group Icahn School of Medicine at Mount SinaiNew York 10029-6574New YorkUnited States

Alterations to the gut microbiome and exposure to metals during pregnancy have been suggested to impact inflammatory bowel ***,how prenatal exposure to metals eventually results in long-term effects on the gut microbiome,leading to subclinical intestinal inflammation,particularly during late childhood,has not been *** is also unknown whether such an interactive effect drives a specific subgroup of children toward elevated susceptibility to intestinal *** used an amalgamation of machine-learning techniques with a regression-based framework to explore if children with distinct sets of gut microbes and certain patterns of exposure to metals during pregnancy(metal−microbial clique signature)had a higher likelihood of intestinal inflammation,measured based on fecal calprotectin(FC)in late *** obtained samples from a well-characterized longitudinal birth cohort from Mexico City(n=108),*** the second and third trimesters of pregnancy,11 metals were measured in whole *** microbial abundances and FC were measured in stool samples from children 9−11 years of *** FC was defined as having FC above 100μg/g of *** identified subgroups of children in whom microbial and metal−microbial clique signatures were associated with elevated FC(false discovery rate(FDR)0.05).In particular,we found two metal−microbial clique signatures significantly associated with elevated FC:(1)low cesium(Cs)and copper(Cu)in the third trimester and low relative abundance of Eubacterium ventriosum(OR[95%CI]:10.27[3.57,29.52],FDR0.001)and(2)low Cu in the third trimester and high relative abundances of Roseburia inulinivorans and Ruminococcus torques(OR[95%CI]:7.21[1.81,28.77],FDR0.05).This exploratory study demonstrates that children with specific gut microbes and specific exposure patterns to metals during pregnancy may have higher fecal calprotectin levels in late childhood,denoting an elevated risk of intestinal inflammation.

关键词： exposome metals machine learning microbiome environmental epidemiology intestinal inflammation

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World Journal of Gastroenterology 2012年第38期18卷 5397-5403页

作者： Sietze T van Turenhout Leo gm van Rossum Frank A Oort robert JF Laheij Anne F van Rijn Jochim S Terhaar sive Droste Paul Fockens René WM van der Hulst Anneke A Bouman Jan BMJ Jansen Gerrit A Meijer Evelien Dekker Chris JJ Mulder Department of Gastroenterology and Hepatology VU University Medical Center1081 HV Amsterdam The Netherlands Department of Epidemiology Biostatistics and HTA Radboud University Nijmegen Medical Center6500 HB Nijmegen The Netherlands Department of Gastroenterology and Hepatology Radboud University Nijmegen Medical Center6500 HB Nijmegen The Netherlands Department of Gastroenterology and Hepatology Academic Medical Center1105 AZ Amsterdam The Netherlands Department of Gastroenterology and Hepatology Kennemer Gasthuis 2035 RC Haarlem The Netherlands Clinical Chemistry VU University Medical Center 1081 HV Amsterdam The Netherlands Department of Gastroenterology and Hepatology Radboud University Nijmegen Medical Center 6500 HB Nijmegen The Netherlands Department of Pathology VU University Medical Center 1081 HV Amsterdam The Netherlands Department of Gastroenterology and Hepatology Academic Medical Center 1105 AZ Amsterdam The Netherlands Department of Gastroenterology and Hepatology VU University Medical Center 1081 HV Amsterdam The Netherlands

AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mLvs 613 ± 368 ng/mL,P = 0.02). Tissue tumor stage (T stage) distribution was dif-ferent between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mLvs 870 ± 258 ng/mL,P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION

关键词： Screening population Referral cohort Fecal immunochemical test Tumor stage distribution Colorectal cancer

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New developments in Western blot technology

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Chinese Chemical Letters 2015年第4期26卷 416-418页

作者： Shi Jin robert T.Kennedy Department of Chemistry University of Michigan

Western blotting is a highly valued method for protein identification and relative quantitation in complex samples. It combines size-based electrophoretic separation with immunoaffinity to identify specific proteins. This technique remains popular and has become a workhorse in biochemical research and clinical laboratories. Despite its utility and popularity, this method has many limitations including slow analysis, incompatibility with limited sample application, low throughput and low information content. Recently there has been significant success in improving different aspects of Western blotting. In this review, we provide an overview of the developments in the area of improving conventional Western blotting methods with a focus on recent developments in microfluidic Western blotting. We overview different separation platforms, and discuss studies on protein transfer methods as well as protein immobilization methods and chemistries. We also describe integrated miniaturized platforms that can perform rapid separations and immunodetections.

关键词： Western blotMicrofluidicGel electrophoresislmmunoassay

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Viscoelastic Immersed Boundary Methods for Zero Reynolds Number Flow

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Communications in Computational Physics 2012年第7期12卷 462-478页

作者： Wanda Strychalski robert D.Guy Department of Mathematics University of CaliforniaDavis CA 95616USA

The immersed boundary method has been extensively used to simulate the motion of elastic structures immersed in a viscous *** some applications,such as modeling biological materials,capturing internal boundary viscosity is *** present numerical methods for simulating Kelvin-Voigt and standard linear viscoelastic structures immersed in zero Reynolds number *** find that the explicit time immersed boundary update is unconditionally unstable above a critical boundary to fluid viscosity ratio for a Kelvin-Voigt *** also show there is a severe time step restriction when simulating a standard linear boundary with a small relaxation time scale using the same explicit update.A stable implicit method is presented to overcome these computation challenges.

关键词： Stokes flow viscoelastic structures fluid-structure interaction numerical instability

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The heterogeneity of store-operated calcium entry in melanoma

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Science China(Life Sciences) 2016年第8期59卷 764-769页

作者： robert Hooper M.Raza Zaidi Jonathan Soboloff Fels Institute for Cancer Research and Molecular Biology Lewis Katz School of Medicine at Temple University Department of Medical Genetics & Molecular Biochemistry Lewis Katz School of Medicine at Temple University

Calcium is a key regulator of many physiological processes that are perturbed in cancer, such as migration, proliferation and apoptosis. The proteins STIM and Orai mediate store-operated calcium entry(SOCE), the main pathway for calcium entry in non-excitable cells. Changes in the expression and function of STIM and Orai have been found in a range of cancer types and thus implicated in disease progression. Here we discuss the role of STIM, Orai and the SOCE pathway in the progression of melanoma and explore how the heterogeneous nature of melanoma may explain the lack of consensus in the field regarding the role of SOCE in the progression of this disease.

关键词： melanoma STIM1 Orail metastasis

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More forks on the road to replication stress recovery

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分子细胞生物学报:英文版 2011年第1期3卷 4-12页

作者： Chris Allen Amanda K.Ashley robert Hromas Jac A.Nickoloff Department of Environmental and Radiological Health Sciences Colorado State UniversityFt CollinsCO 80523USA University of New Mexico Cancer Center and Department of Internal Medicine University of New Mexico School of MedicineAlbuquerqueNM 87131USA

High-fidelity replication of DNA,and its accurate segregation to daughter cells,is critical for maintaining genome stability and suppressing *** replication forks are stalled by many DNA lesions,activating checkpoint proteins that stabilize stalled *** forks may eventually collapse,producing a broken DNA *** restart is typically mediated by proteins initially identified by their roles in homologous recombination repair of DNA double-strand breaks(DSBs).In recent years,several proteins involved in DSB repair by non-homologous end joining(NHEJ)have been implicated in the replication stress response,including DNA-PKcs,Ku,DNA Ligase IV-XRCC4,Artemis,XLF and *** is currently unclear whether NHEJ proteins are involved in the replication stress response through indirect(signaling)roles,and/or direct roles involving DNA end *** complexity in the replication stress response centers around RPA,which undergoes significant post-translational modification after stress,and RAD52,a conserved HR protein whose role in DSB repair may have shifted to another protein in higher eukaryotes,such as BRCA2,but retained its role in fork *** cancer therapeutic strategies create DNA replication ***,it is imperative to gain a better under-standing of replication stress response proteins and pathways to improve cancer therapy.

关键词： DNA repair genome instability cancer therapy

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Bacterial communities in paddy soils changed by milk vetch as green manure: A study conducted across six provinces in South China

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Pedosphere 2021年第4期31卷 521-530页

作者： Songjuan GAO Weidong CAO Guopeng ZHOU robert M.REES College of Resources and Environmental Sciences Nanjing Agricultural UniversityNanjing 210095(China) Key Laboratory of Plant Nutrition and Fertilizer Ministry of Agriculture and Rural Affairs/Institute of Agricultural Resources and Regional PlanningChinese Academy of Agricultural SciencesBeijing 100081(China) Scotland’s Rural College(SRUC) West Mains RoadEdinburgh EH93JG(UK)

The use of green manures contributes to sustainable soil and nutrient management in agriculture;however, the responses of soil microbial communities to different fertilization regimes at the regional scale are uncertain. A study was undertaken across multiple sites and years in Hunan, Jiangxi, Anhui, Henan,Hubei, and Fujian provinces of South China to investigate the effects of green manuring on the structure and function of soil bacterial communities in rice-green manure cropping systems. The study included four treatments: winter fallow with no chemical fertilizer as a control(NF), milk vetch as green manure without chemical fertilizer(gm), winter fallow and chemical fertilizer(CF), and a combination of chemical fertilizer and milk vetch(gmCF).Significant differences were found in the responses of soil microbial communities at different sites, with sampling sites explaining 72.33%(F = 36.59,P = 0.001) of the community composition variation. The bacterial communities in the soils from Anhui, Henan, and Hubei were broadly similar, while those from Hunan were distinctly different from other locations. The analysis of Weighted UniFrac distances showed that milk vetch changed soil microbial communities compared with winter fallow. Proteobacteria and Chloroflexi predominated in these paddy soils;however, the application of green manures increased the relative abundance of Actinobacteria. There was evidence showing that the functional microbes which play important roles in the cycling of soil carbon, nitrogen(N), and sulfur(S) changed after several years of milk vetch utilization(linear discriminant analysis score > 2). The abundance of methane-oxidizing bacteria and S-reducing bacteria increased, and microbes involved in N fixation, nitrification, and denitrification also increased in some provinces. We concluded that the application of milk vetch changed the bacterial community structure and affected the functional groups related to nutrient transformation in soils at

关键词： alpha diversity bacterial composition functional group operational taxonomic unit soil fertility Weighted UniFrac distance

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Tightening up the structure, lighting up the pathway:application of molecular constraints and light to manipulate protein folding, self-assembly and function

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Science China Chemistry 2014年第12期57卷 1615-1624页

作者： MARKIEWICZ Beatrice N. CULIK robert M. GAI Feng Department of Chemistry University of Pennsylvania Department of Biochemistry and Biophysics University of Pennsylvania

Chemical cross-linking provides an effective avenue to reduce the conformational entropy of polypeptide chains and hence has become a popular method to induce or force structural formation in peptides and ***,other types of molecular constraints,especially photoresponsive linkers and functional groups,have also found increased use in a wide variety of ***,we provide a concise review of using various forms of molecular strategies to constrain proteins,thereby stabilizing their native states,gaining insight into their folding mechanisms,and/or providing a handle to trigger a conformational process of interest with *** applications discussed here cover a wide range of topics,ranging from delineating the details of the protein folding energy landscape to controlling protein assembly and function.

关键词： protein folding aggregation self-assembly cross-linker phototrigger light-activation

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Dimethyl pyrazine ethylamine hydrochloride disaggregates platelets in vivo by stimulating prostacyclin synthesis.

Dimethyl pyrazine ethylamine hydrochloride disaggregates pla...

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第十五届国际药理学大会

作者： Omogbai EKI Smith gm Durham DG School of Pharmacy the Robert Gordon University Schoolhill Aberdeen Scotland AB10 1FR U. K. School of Pharmacy the Robert Gordon University Schoolhill Aberdeen Scotland AB10 1FR U. K. School of Pharmacy the Robert Gordon University Schoolhill Aberdeen Scotland AB10 1FR U. K.

＜正＞ Dimethyl ethylamine hydrochloride （DPEH） induces vascular smooth muscle contractility by acting as a calcium *** study investigated the effect of DPEH on in vivo platelet reactivity. Platelet aggregation was monitored in pento-barbital anaesthetized wistar rats using the Technicon Autocounter. Plasma levels and in vitro synthesis of PGI2 were measured by radioimmunoassay. A bolus dose of DPEH （5 mg·kg-1） i.v. caused a rapid rise in circulating platelet count with a peak increase of 20.7±3.2% in 5 to 7 min. Indomethacin significantly reduced but did not abolish DPEH-induced rise in platelet count. DPEH reduced collagen-induced fall in platelet count from 17.8±2.5% to 12.5±3.2% . The basal plasma level of 6-keto-PGF1α of 26.2±5.1 fg·ml-1 was significantly increased by DPEH（5 mg·kg-1） to 102.7±7.3 pg·ml-1. The basal level of 6-keto-PGF1α synthesis by rat aortic rings was 12.5±1.5 ng·mg-1·hr-1. DPEH caused a dose-dependent increase in aortic ring PGI2 synthesis with Emax50 of 4.5×10-5M and 68.1±2.3 ng·mg-1·hr-1 at 10-4 M. DPEH stimulates PG12 synthesis and increases the number of circulating platelets without its direct pressor effect being abolished.

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Genetically modified foods:A critical review of their promise and problems

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Food Science and Human Wellness 2016年第3期5卷 116-123页

作者： Chen Zhang robert Wohlhueter Han Zhang Department of Gene and Signaling Expression La Jolla Institute for Allergy and ImmunologyLa JollaCA 92037United States Department of Chemistry Georgia State UniversityAtlantaGA 30303United States Department of Microbiology and Immunology School of MedicineEmory UniversityAtlantaGA 30322United States

The term“genetic modified organisms(gmO)”has become a controversial topic as its benefits for both food producers and consumers are companied by potential biomedical risks and environmental side *** concerns from the public about gmO,particularly in the form of genetic modified(gm)foods,are aimed at the short-and long-lasting health problems that may result from this advanced *** studies are being carried out around the world independently to evaluate the advantages and disadvantages of gm *** this paper,we attempt to summarize up-to-date knowledge about the benefits and potential problems of gm *** also introduce some recent technological developments in gm foods and their impact in the field.

关键词： modified problems critical

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