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Metabolite profile comparisons between ascending and descending colon tissue in healthy adults

World Journal of Gastroenterology 2020年第3期26卷 335-352页

作者： Bridget A Baxter Kristopher d Parker Michael J Nosler Sangeeta Rao rebecca Craig Catherine Seiler Elizabeth P Ryan department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsFort CollinsCO 80523United States University of Colorado Health Gastroenterology Clinic Fort CollinsCO 80524United States department of Clinical Sciences Colorado State UniversityFort CollinsCO 80523United States Harmony Surgery Center Fort CollinsCO 80528United States director of Clinical Operations Harmony Surgery CenterFort CollinsCO 80523United States

BACKGROUNd Obesity is a risk factor for colorectal cancer,yet metabolic distinctions between healthy right and left colon tissue,before cancer is diagnosed,remains largely *** study compared right-ascending and left-descending colon tissue metabolomes to identify differences from the stool metabolome in normal weight,overweight,and obese *** To examine right and left colon tissue metabolites according to body mass index that may serve as mechanistic targets for interventions and biomarkers for colon cancer *** Global,non-targeted metabolomics was applied to assess right-ascending and left-descending colon tissue collected from healthy adults undergoing screening colonoscopies to test the hypothesis that BMI differentially impacts colon tissue metabolite *** colon tissue and stool metabolome of healthy adults(n=24)was analyzed for metabolite signatures and metabolic pathway networks implicated in progression of colorectal *** Ascending and descending colon contained 504 host,food,and microbiotaderived metabolites from normal weight,overweight and obese adults grouped according to body mass *** acids,lipids,and nucleotides were among the chemical types that further differentiated from the stool metabolite *** weight adults had 46 significantly different metabolites between ascending and descending colon tissue locations,whereas there were 37 metabolite differences in overweight and 28 metabolite differences for obese adults(Pdults had trimethylamine N-oxide,endocannabinoids and monoacylglycerols with different relative abundances identified between ascending and descending *** and secondary bile acids,vitamins,and fatty acids also showed marked relative abundance differences in colon tissue from overweight/obese *** There were metabolite profile differences between right-ascending and leftdescending colon tissue in healthy *** lipids and other metabolites in

关键词： Colon Ascending descending Metabolomics Obesity Stool

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Identification of sumoylated targets in proliferating mouse spermatogonia and human testicular seminomas

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Asian Journal of Andrology 2020年第6期22卷 569-577页

作者： Margarita Vigodner Benjamin Lucas Stav Kemeny Tamar Schwartz rebecca Levy department of Biology Stern CollegeYeshiva UniversityNew YorkNY 10016USA department of developmental and Molecular Biology Albert Einstein College of MedicineBronxNY 10461USA

Spermatogenesis is regulated by a complex network of posttranslation ***(a modification by small ubiquiti like modifiers,or SUMO proteins)was identified as an importa nt cellular event in d iff ere nt cell *** proteins are highly expressed in the testis,and their role during spermatogenesis has begun to be *** the important role of sumoylation in the regulation of mitosis and cancer progress!on in other tissues,the aim of the current study was to identify the targets of SUMO in proliferating mouse spermatog onia and huma n semi noma tissues and to in itially exami ne the level of sumoylation in relation to the proliferative activity of the *** freshly purified spermatogonia and Cl8-4 spermatogonia cell line,mass spectrometry analysis identified several SUMO targets implicated into the proliferation of spermatogonia(such as heat shock protein 60[HSP60]and prohibitin).Tissue array and western blot approaches showed that SUMO expression is a prominent feature of human seminomas and that the proliferative activity of the tumor tissues was positively correlated with the level of SUMO *** regulation of sumoylati on with si-RNA was not sufficie nt to sign ificantly affect the proliferation of C18-4 spermatogonia;however,SUMO overexpression in creased the proliferation rate of the *** data suggest that cells are more sensitive to an elevated level of SUMO,and that this situation may lead to an upregulated cellular proliferation and,possibly,*** spectrometry analysis identified around a hundred SUMO targets in seminoma ***,many of the identified proteins(such as proliferating cell nuclear antigen[PCNA],dNA topoisomerase 2-alpha[Top2A],prohibitin,14-3-3 protein,and others)were implicated in oncogenic transformation and cancer progression.

关键词： proliferation seminoma spermatog onia sumoylation

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Epigenetic modulation in sensitizing metastatic sarcomas to therapies and overcoming resistance

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Cancer drug Resistance 2022年第1期5卷 25-35页

作者： Jeff Rytlewski Qierra R.Brockman rebecca d.dodd Mohammed Milhem Varun Monga department of Internal Medicine University of IowaIowa CityIA 52242USA Holden Comprehensive Cancer Center University of IowaIowa CityIA 52242USA

Sarcomas are a class of rare malignancies of mesenchymal origin with a heterogeneous histological *** are classically associated with poor outcomes,especially once metastasized.A path to improving clinical outcomes may be made through modifying the epigenome,where a variety of sarcomas demonstrate changes that contribute to their oncogenic *** Perspective article identifies and describes changes in the sarcoma genome,while discussing specific epigenetic changes and their effect on clinical *** attempts at modulating epigenetics in sarcoma are reviewed,as well as potential implications of these *** targets to reverse and delay chemotherapy resistance are *** directions with primary next steps are proposed to invigorate the current understanding of epigenetic biomarkers to enact targeted therapies to epigenetic phenotypes of sarcoma *** to prior studies,as well as proposed clinical steps,are also addressed.

关键词： Epigenetics sarcoma resistance metastasis

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Epidemiology andinteractions of Human Immunodeficiency Virus - 1 and Schistosoma mansoni in sub-SaharanAfrica

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Infectious diseases of Poverty 2013年第1期2卷 6-16页

作者： Humphrey d Mazigo Fred Nuwaha Shona Wilson Safari M Kinunghi domenica Morona rebecca Waihenya Jorg Heukelbach david W dunne department of Medical Parasitology and Entomology School of MedicineCathollc University of Health and Aled SclencesP.O.Box 1464MwanzaTanzanla department of Environmental Health and Communicable disease Control School of Public HealthCollege of Health SclencesMakerere UniversiyP.O.Box 7072KampalaUganda National Institute for Medical.Research Mwanza Research CentreP.Q.Box 1462MwanzaTanzanla department of Pathology University of CambidgeTennis Court RoadCambridge CB21OPUK department of Zoology Faculty of SclenceJomo Kenyatta University of Agriculture and TechnologyP.O.Box ***NairobiKenya department of Community Health School of MedicineFederal University of CearaCearaBail

Human Immunodeficiency Virus-1/AIdS and Schis tosoma mansoni are widespread in sub Saharan Africa and co-infection occurs *** the early 1990s,it has been suggested that the two infections may interact and potentiate the effects of each other within co-infected human ***,S mansoni infection has been suggested to be a risk factor for HIV transmission and progression in *** so,it would follow that mass deworming could have beneficial effects on HIV-1 transmission *** epidemiology of HIV in African countries is changing,shifting from urban to rural areas where the prevalence of Schistosoma mansoni is high and public health services are *** the other side,the consequent pathogenesis of HIV-1/*** co-infection remains *** we give an account of the epidemiology of HIV-1 and ***,discuss co-infection and possible biological causal relationships between the two infections,and the potential impact of praziquantel treatment on HIV-1 viral loads,Cd4^(+) counts and Cd4^(+)/Cd8^(+) *** review of the available literature indicates that there is evidence to support the hypothesis that *** infections can influence the replication of the HIV-1,cel-to-cell transmission,as well as increase HIV progression as measured by reduced Cd4^(+) T lymphocytes *** so,then deworming of HIV positive individuals living in endemic areas may impact on HV-1 viral loads and Cd4^(+) T lymphocyte counts.

关键词： Schitosoma mansoni HIV-1 Co-infections Immunological interactions deworming

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Improving Performance and Enhancing Introductory Statistics Using Projects

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American Journal of Computational Mathematics 2017年第1期7卷 21-28页

作者： Joy d’Andrea rebecca Wooten University of Florida Sarasota USA New College of Florida Sarasota USA

Introductory Statistics is a course taught in various community colleges, state colleges, and universities. Implementation of projects in this course has been shown to enhance students’ learning;in addition to increasing the ability of educators to assess students’ learning outcomes in detail. These projects are often inquiry-based and require a balance between flexibility and efficiency. Maintaining balance has provided the students’ opportunities through exploration and learner autonomy. In exploration, a student seeks new methods and options through experimenting. In this paper, we will discuss the benefits of exploration required by projects given in an introductory statistics course. The details of five different projects discussed in this paper—illustrate the practical influence that they could have on higher statistics courses.

关键词： Introductory Statistics Projects Inquiry-Based Learning Centered Active Learning

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Asymmetric reinforcement in Lucania killifish:assessing reproductive isolation when both sexes choose

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Current Zoology 2021年第2期67卷 215-224页

作者： Michelle E.ST.JOHN rebecca C.FULLER School of Integrative Biology University of liois Urbana-ChampaignChampaignIL 61820USA

Reinforcement can occur when maladaptive hybridization in sympatry favors the evolution of con-specific preferences and target traits that promote behav ioral isolation(BI).In many systems,enhanced BI is due to increased female preference for *** others,BI is driven by male preference,and in other systems both sexes exert *** of these patterns can be atributed to classic sex-specific costs and benefits of ***,sex differences in conspecific preference can emerge due to asymmetric postzygotic isolation(e.g.,hybrid offspring from female A × male B have lower fitness than hybrid offspring from female B × male A),which can lead to asymmetric BI(e.g.,female A and male B are less likely to mate than female B and male A).Understanding reinforcement requires understanding how conspecific preferences evolve in ***,estimating conspecific preferences can be difficult when both sexes are *** this study,we use Lucania killifish to test the hypothesis that patterns of reinforcement are driven by asymmetric postzygotic isolation between *** true,we predicted that sympatric female Lucania goodei and sympatric male *** should have lower levels of BI compared with their sympatric counterparts,as they produce hybrid offspring with the highest *** address the problem of measuring BI when both sexes are choosy,we inferred the contribution to BI of each partner using assays where one sex in the mating pair comes from an allopatric population with potentially low preference,whereas the other comes from a sympatric population with high *** one hybrid cross direction,we found that both female *** and male *** have high contributions to BI in *** the other hybrid cross direction,we found that only female *** contribute to *** male *** readily engaged in hybrid spawnings with allo-patric *** *** results indicate that both asymmetric postzygotic isolation

关键词： reinforcement behavioral isolatin female mate choice male mate choice asymmetric costs to hybridization

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The F-box-only protein 44 regulates pregnane X receptor protein level by ubiquitination and degradation

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Acta Pharmaceutica Sinica B 2023年第11期13卷 4523-4534页

作者： rebecca R.Florke Gee Andrew d.Huber Jing Wu Richa Bajpai Allister J.Loughran Shondra M.Pruett-Miller Taosheng Chen department of Chemical Biology and Therapeutics St.Jude Children's Research HospitalMemphisTN 38105USA Graduate School of Biomedical Sciences St.Jude Children's Research HospitalMemphisTN 38105USA Center for Advanced Genome Engineering and department of Cell and Molecular Biology St.Jude Children's Research HospitalMemphisTN 38105USA

Pregnane X receptor(PXR)is a ligand-activated nuclear receptor that transcriptionally upregulates drug-metabolizing enzymes[e.g.,cytochrome P4503A4(CYP3A4)]and *** the regulation of PXR target genes is well-characterized,less is known about the regulation of PXR protein *** screening an RNAi library,we identified the F-box-only protein 44(FBXO44)as a novel E3ligase for *** abundance increases upon knockdown of FBXO44,and,inversely,decreases upon overexpression of *** analysis revealed that FBXO44 interacts with PXR,leading to its ubiquitination and proteasomal degradation,and we determined that the F-box associated domain of FBXO44 and the ligand binding domain of PXR are required for the functional *** summary,FBXO44 regulates PXR protein abundance,which has downstream consequences for CYP3A4 levels and drug-drug *** results of this study provide new insight into the molecular mechanisms that regulate PXR protein level and activity and suggest the importance of considering how modulating E3ubiquitin ligase activities will affect PXR-mediated drug metabolism.

关键词： PXR FBXO44 Ubiquitination Proteasomal degradation CYP3A4 drug-drug interactions E3 ligase Nuclear receptor

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High-dose biotin neither fosters remyelination nor stimulates malonyl coenzyme A synthesis in the regenerating nerve

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Neural Regeneration Research 2023年第7期18卷 1623-1624页

作者： Fabian Szepanowski rebecca d.Steubing Cansu Güngör Jaqueline Zipfel Anne K.Mausberg Christoph Kleinschnitz Mark Stettner department of Neurology and Center for Translational Neuro-and Behavioral Sciences(C-TNBS) University Medicine EssenUniversity Duisburg-EssenEssenGermany

dear editor,dysregulated inflammatory responses primarily account for damage to the central nervous system,however,neurodegenerative processes likely contribute to the pathophysiology of progressive forms of multiple sclerosis(MS).These pathophysiological aspects include axonal energy depletion and impaired remyelination capacity(Levin et al.,2014).The clinical efficacy of most disease-modifying therapies in MS to date has been achieved by targeting functions of the adaptive immune system(Cree et al.,2019;Szepanowski et al.,2021).

关键词： system synthesis neither

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Viral hepatitis in 2021:The challenges remaining and how we should tackle them

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World Journal of Gastroenterology 2022年第1期28卷 76-95页

作者： rebecca dunn Aaron Wetten Stuart McPherson Mhairi C donnelly Gastroenterology University Hospital of North TeesStockton on Tees TS198PEUnited Kingdom Liver Unit Freeman HospitalNewcastle NE77DNUnited Kingdom Translational and Clinical Research Institute Newcastle UniversityNewcastle NE17RUUnited Kingdom

Viral hepatitis results in 1.4 million deaths *** World Health Organization(WHO)set an ambitious target to eliminate viral hepatitis by 2030,but significant challenges *** include inequalities in access to healthcare,reaching at risk populations and providing access to screening and effective *** around viral hepatitis persists and must be *** WHO goal of global elimination by 2030 is a worthy aim,but remains ambitious and the coronavirus 2019 pandemic undoubtedly has set back *** review article will focus on hepatitis A to E,highlighting problems that have been resolved in the field over the past decade,those that remain to be resolved and suggest directions for future problem solving and research.

关键词： Hepatitis A Hepatitis B Hepatitis C Hepatitis d Hepatitis E COVId-19

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Transcriptional regulation of secretory capacity by bZip transcription factors

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Frontiers in Biology 2015年第1期10卷 28-51页

作者： rebecca M. FOX deborah J. ANdREW The department of Cell Biology The Johns Hopkins University School of Medicine Baltimore MD 21205 USA

Cells of specialized secretory organs expand their secretory pathways to accommodate the increased protein load necessary for their function. The endoplasmic reticulum （ER）, the Golgi apparatus and the secretory vesicles, expand not only the membrane components but also the protein machinery required for increased protein production and transport. Increased protein load causes an ER stress response akin to the Unfolded Protein Response （UPR）. Recent work has implicated several bZip transcription factors in the regulation of protein components of the early secretory pathway necessary to alleviate this stress. Here, we highlight eight bZip transcription factors in regulating secretory pathway component genes. These include components of the three canonical branches of the UPR-ATF4, XBP1, and ATF6, as well as the five members of the Creb3 family of transcription factors. We review findings from both invertebrate and vertebrate model systems suggesting that all of these proteins increase secretory capacity in response to increased protein load. Finally, we propose that the Creb3 family of factors may have a dual role in secretory cell differentiation by also regulating the pathways necessary for cell cycle exit during terminal differentiation.

关键词： bZip transcription factors endoplasmic reticulum Golgi secretion secretory capacity secretory vesicles

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