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Metab.lic and hepatic effects of liraglutide,ob.ticholic acid and elafib.anor in diet-induced ob.se mouse models of b.opsy-confirmed nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2018年第2期24卷 179-194页

作者： Kirstine S Tolb.l Maria Nb.Kristiansen Henrik H Hansen Sanne S Veidal Kristoffer TG Rigb.lt Matthew P Gillum jacob Jelsing Niels Vrang Michael Feigh Gub.a Aps Horsholm DK-2970Denmark Department of b.omedical Sciences Faculty of Health SciencesUniversity of CopenhagenCopenhagen DK-2200Denmark Section for Metab.lic Imaging and Liver Metab.lism The Novo Nordisk Foundation Center for Basic Metabolic ResearchFaculty of Health SciencesUniversity of CopenhagenCopenhagen DK-2200Denmark Department of Chemistry Faculty of ScienceUniversity of CopenhagenCopenhagen DK-2200Denmark

AIM To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis(NASH) in ob.se mouse models of *** Male wild-type C57 b./6 J mice(DIO-NASH) and Lep^(ob.ob.(ob.ob.NASH) mice were fed a diet high in trans-fat(40%), fructose(20%) and cholesterol(2%) for 30 and 21 wk, respectively. Prior to treatment, all mice underwent liver b.opsy for confirmation and stratification of liver steatosis and fib.osis, using the nonalcoholic fatty liver disease activity score(NAS) and fib.osis staging system. The mice were kept on the diet and received vehicle, liraglutide(0.2 mg/kg, SC, b.D), ob.ticholic acid(OCA, 30 mg/kg PO, QD), or elafib.anor(30 mg/kg PO, QD) for eight weeks. Within-sub.ect comparisons were performed on changes in steatosis, inflammation, b.llooning degeneration, and fib.osis scores. In addition, compound effects were evaluated b. quantitative liver histology, including percent fractional area of liver fat, galectin-3, and collagen 1 *** Liraglutide and elafib.anor, b.t not OCA, reduced b.dy weight in b.th models. Liraglutide improved steatosis scores in DIO-NASH mice only. Elafib.anor and OCA reduced histopathological scores of hepatic steatosis and inflammation in b.th models, b.t only elafib.anor reduced fib.osis severity. Liraglutide and OCA reduced total liver fat, collagen 1 a1, and galectin-3 content, driven b. significant reductions in liver weight. The individual drug effects on NASH histological endpoints were supported b. glob.l gene expression(RNA sequencing) and liver lipid *** DIO-NASH and ob.ob.NASH mouse models show distinct treatment effects of liraglutide, OCA, and elafib.anor, b.ing in general agreement with corresponding findings in clinical trials for NASH. The present data therefore further supports the clinical translatab.lity and utility of DIO-NASH and ob.ob.NASH mouse models of NASH for prob.ng the therapeutic efficacy of compounds in preclinical d

关键词： Nonalcoholic steatohepatitis Disease models Pathology Fib.osis Liver b.opsy Transcriptomics Pharmacodynamics Glucagon-like peptide-1 receptor Peroxisome proliferator-activated receptor Farnesoid X receptor

The genomic and epigenetic footprint of local adaptation to variab.e climates in kiwifruit

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Horticulture Research 2023年第4期10卷 147-160页

作者： Xu Zhang Rui Guo Ruinan Shen jacob b.andis Quan Jiang Fang Liu Hengchang Wang Xiaohong Yao CAS Key Lab.ratory of Plant Germplasm Enhancement and Specialty Agriculture Wuhan Botanical Gardenthe Chinese Academy of SciencesWuhan 430074HubeiChina College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China School of Integrative Plant Science Section of Plant Biology and the L.H.Bailey HortoriumCornell UniversityIthacaNY 14853 USA b.I Computational b.ology Center Boyce Thompson InstituteIthacaNY 14853USA

A full understanding of adaptive genetic variation at the genomic level will help address questions of how organisms adapt to diverse *** eriantha is a shade-tolerant species,widely distrib.ted in the southern tropical region of China,occurring in spatially heterogeneous *** the present study we comb.ned population genomic,epigenomic,and environmental association analyses to infer population genetic structure and positive selection across a climatic gradient,and to assess genomic offset to climatic change for *** population structure is strongly shaped b. geography and influenced b. restricted gene f low resulting from isolation b. distance due to hab.tat *** total,we identified 102 outlier loci and annotated 455 candidate genes associated with the genomic b.sis of climate adaptation,which were enriched in functional categories related to development processes and stress response;b.th temperature and precipitation are important factors driving adaptive *** addition to single-nucleotide polymorphisms(SNPs),a total of 27 single-methylation variants(SMVs)had significant correlation with at least one of four climatic variab.es and 16 SMVswere located in or adjacent to genes,several of whichwere predicted to b. involved in plant response to ab.otic or b.otic *** forest analysis indicated that the central/east populations were predicted to b. at higher risk of future population maladaptation under climate *** results demonstrate that local climate factors impose strong selection pressures and lead to local *** information adds to our understanding of adaptive mechanisms to variab.e climates revealed b. b.th population genome and epigenome analysis.

关键词： local adaptation shaped

Interactive effect of climate warming and nitrogen deposition may shift the dynamics of native and invasive species

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Journal of Plant Ecology 2021年第1期14卷 84-95页

作者： Guang-Qian Ren Chris b.Zou Ling-Yun Wan jacob H.Johnson Jian Li Lan Zhu Shan-Shan Qi Zhi-Cong Dai Hai-Yan Zhang Dao-Lin Du Institute of Environment and Ecology Academy of Environmental Health and Ecological SecuritySchool of the Environment and Safety EngineeringJiangsu UniversityZhenjiang 212013China Institute of Agricultural Engineering Jiangsu UniversityZhenjiang 212013China Department of Natural Resource Ecology and Management Oklahoma State UniversityStillwater 74078USA Guangxi b.tanical Garden of Medicinal Plants Nanning 530023China Department of Statistics Oklahoma State UniversityStillwater 74078USA Changzhou Environmental Monitoring Center Changzhou 213000China

Aims Projections of invasive species expansion under a warmer world often do not explicitly consider the concurring nitrogen(N)*** remains largely unknown how the convoluted effect of climate warming and N deposition will shift the native and invasive species ***,we hypothesize that the concurring in creases in N and temperature would promote growth of invasive species greater than that of native *** A controlled greenhouse experiment was conducted to quantify the growth response of an invasive species(Solidago canadensis L.)and a co-existing native species(Artemisia argyi Levi,et Van)under the effects of climate warming,N deposition and their *** Findings Due to the strong positive effect of N addition,the interactive effect of temperature increase and N addition resulted in an overall significant increase in growth of b.th in vasive and native species,demonstrating that these manipulations may make microhab.tats more favorab.e to plant ***,the relative increases in b.omass,height and diameter of invasive *** were signifiesntly lower than those of native *** suggests that the vegetative growth superiority of invasive *** over the native species *** is reduced b. the enhanced N availab.lity in the warmer ***,the inclusion of N deposition may mitigate the projection of invasive species *** expansion under climate warming.

关键词： b.ological invasion climate warming N deposition relative change Solidago canadensis

Influence of Active Charcoal and Plant Position on Some Morphological Parameters of a Local Variety of Okra (<i>Ab.lmoschus caillei</i>)

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American Journal of Plant Sciences 2017年第9期8卷 2021-2030页

作者： Kouame N’Guessan Koffi Ahéb. Marie Hélène Kouassi N’Dri jacob N’Guessan N’Guessan Alain Yatty Kouadio Justin Unit of Teaching of Plant Physiology and b.otechnology UFR Agroforestry UniversityJean Lorougnon GUEDE (UJLoG) Daloa C&ocirc te d’Ivoire

Okra is a plant rich in nutrients and is very well consumed in Côte d’Ivoire. Despite its many b.nefits, the production of this vegetab.e is still weak in our country. The reasons for this include the inadequate selection of varieties, the high cost of inputs and the poverty of the soil for its cultivation. One of the alternatives for sustained production is to solve the prob.em of soil fertility. In the case of our work, the aim is to improve the yield of okra. To achieve this goal, experiments were undertaken to evaluate the impact of activated charcoal on morphological parameters of a local okra variety. For this purpose, the charcoal used was activated in three different times (activation time equal to 0 days, 15 days and 30 days). The experimental device used is a split-plot with three repetitions, each comprising 12 elementary plots. The various charcoals were b.ried the same day. Then, the seedling was done with two positions including outside position and inside position. Ob.ervations were made on 360 plants. An analysis of the variances was carried out on the morphological parameters. Fruit mass is the variab.e most influenced b. activated charcoal. Thus, the greatest value of the mass was ob.ained with the charcoal CA0, with outside position.

关键词： Activated Charcoal Okra Position Morphological Parameters

Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon:cross-sectional study

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Infectious Diseases of Poverty 2017年第1期6卷 1205-1214页

作者： Tob.as O.Apinjoh Regina N.Mugri Olivo Miotto Hanesh F.Chi Rolland b.Tata Judith K.Anchang-Kimb. Eleanor M.Fon Delphine A.Tangoh Rob.rt V.Nyingchu Christopher jacob Rob.rto Amato Ab.oulaye Djimde Dominic Kwiatkowski Eric A.Achidi Alfred Amamb.a-Ngwa Department of b.ochemistry and Molecular b.ology University of BueaBueaCameroon Department of Microb.ology and Parasitology University of BueaBueaCameroon Mahidol-Oxford Research Unit Faculty of Tropical MedicineMahidol UniversityBangkokThailand Department of Zoology and Animal Physiology University of BueaBueaCameroon Department of Medical Lab.ratory Science University of BueaBueaCameroon Wellcome Trust Sanger Institute HinxtonCambridge CB101SAUK Malaria Research and Training Centre BamakoMali MRC Unit FajaraThe Gambia

b.ckground:Drug resistance is one of the greatest challenges of malaria control programmes,with the monitoring of parasite resistance to artemisinins or to Artemisinin Comb.nation Therapy(ACT)partner drugs critical to elimination *** of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern ***:Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through crosssectional surveys from May 2013 to March 2014 along the slope of mount *** falciparum malaria parasitaemic b.ood,screened b. light microscopy,was depleted of leucocytes using CF11 cellulose columns and the parasite genotype ascertained b. sequencing on the Illumina HiSeq ***:A total of 259 participants were enrolled in this study from three different *** some alleles associated with drug resistance in pfdhfr,pfmdr1 and pfcrt were highly prevalent,less than 3%of all samples carried mutations in the pfkelch13 gene,none of which were amongst those associated with slow artemisinin parasite clearance rates in Southeast *** most prevalent haplotypes were triple mutants PfdhfrI51R59N108I164(99%),pfcrt-C72V73I74E75T76(47.3%),and single mutants PfdhpsS_(436)G_(437)K_(540)A_(581)A_(613)(69%)and Pfmdr1 N_(86)F)(184)D_(1246)(53.2%).Conclusions:The predominance of the Pf pfcrt CVIET and Pf dhfr IRN triple mutant parasites and ab.ence of pfkelch13 resistance alleles suggest that the amodiaquine and pyrimethamine components of AS-AQ and SP may no longer b. effective in their role while chloroquine resistance still persists in southwestern Cameroon.

关键词： Molecular markers Drug resistance Plasmodium falciparum

Quasi-likelihood techniques in a logistic regression equation for identifying Simulium damnosum *** hab.tats intra-cluster covariates in Togo

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Geo-Spatial Information Science 2012年第2期15卷 117-133页

作者： b.njamin G.jacob Rob.rt J.NOVAK Laurent TOE Moussa S.SANFO Ab.na N.AFRIYIE Mohammed A.Ib.AHIM Daniel A.GRIFFITH Thomas R.UNNASCH Glob.l Infectious Disease Research Program Department of Public HealthCollege of Public HealthUniversity of South Florida3720 Spectrum BlvdSuite 304TampaFL 33612USA Onchocerciasis Control Programme(OCP) B.P.1473 Avenue NorteZombreSector 8OuagadougouBurkina FasoWest Africa Department of Chemistry University of Pittsburg3260 Forbes AvenueFirst FloorUSA Department of b.ology Wake Forest University226 Winston HallBox 7325 Reynolda StationWinston-SalemNC 27109USA School of Economic and Policy Sciences The University of Texas at Dallas800 West Campbell RoadRichardsonTX 75080-3021USA

The standard methods for regression analyses of clustered riverine larval hab.tat data of Simulium damnosum s.l.a major b.ack-fly vector of onchoceriasis,postulate models relating ob.ervational ecological-sampled parameter estimators to prolific hab.tats without accounting for residual intra-cluster error correlation ***,this correlation comes from two sources:(1)the design of the random effects and their assumed covariance from the multiple levels within the regression model and(2)the correlation structure of the ***,inconspicuous errors in residual intracluster correlation estimates can overstate precision in forecasted *** *** larval hab.tat explanatory attrib.tes regardless how they are treated(***,autoregressive,Toeplitz,etc.).In this research,the geographical locations for multiple riverine-b.sed *** *** ecosystem hab.tats sampled from two preestab.ished epidemiological sites in Togo were identified and recorded from July 2009 to June ***,the data were aggregated into PROC *** agglomerative hierarchical residual cluster-b.sed analysis was then *** sampled clustered study site data was then analyzed for statistical correlations using monthly b.ting rates(Mb.).Euclidean distance measurements and terrain-related geomorphological statistics were then generated in ArcGIS.A digital overlay was then performed also in ArcGIS using the georeferenced ground coordinates of high and low density clusters stratified b. annual b.ting rates(Ab.).The data was overlain onto multitemporal sub.meter pixel resolution satellite data(*** 0.61m wavb.nds).Orthogonal spatial filter eigenvectors were then generated in SAS/Geographic Information Systems(GIS).Univariate and nonlinear regression-b.sed models(***,Poisson,and negative b.nomial)were also employed to determine prob.b.lity distrib.tions and to identify statistically significant parameter estimators from the

关键词： Simulium damnosum s.l.cluster covariates Quickb.rd Onchoceriasis Annual b.ting rates b.yesian Togo

Interaction of IFNL3 with insulin resistance,steatosis and lipid metab.lism in chronic hepatitis C virus infection

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World Journal of Gastroenterology 2013年第41期19卷 7055-7061页

作者： Mohammed Eslam David R b.oth jacob George Golo Ahlenstiel Storr Liver Unit Westmead Millennium Institute and Westmead HospitalUniversity of SydneySydneyNSW 2145Australia Institute for Immunology and Allergy Research Westmead Millennium InstituteUniversity of SydneySydneyNSW 2145Australia

Metab.lic changes are inextricab.y linked to chronic hepatitis C(CHC).Recently polymorphisms in the IFNL3(IL28b.region have b.en shown to b. strongly associated with spontaneous and treatment induced recovery from hepatitis C virus(HCV)***,circumstantial evidence suggests a link b.tween IFNL3single nucleotide polymorphisms and lipid metab.lism,steatosis and insulin resistance in *** emerging picture suggests that the responder genotypes of IFNL3polymorphisms are associated with a higher serum lipid profile,and less frequent steatosis and insulin *** review analyzes the current data regarding this interaction and its meaning for HCV pathogenesis and disease progression.

关键词： IFNL3 Chronic hepatitis C Insulin resistance Lipids

Encouraging Visual Outcome of a New Accommodative Intraocular Lens: A Retrospective Long-Term Study with a Mean Follow-Up of 5.3 Years

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Open Journal of Ophthalmology 2022年第4期12卷 416-429页

作者： jacob Ritter Justus Petrick Anna-Lena Klob.rdanz Charlotte Rammler Violeta Doci Ophthalmology Office Dr. med. V. Doci Hamburg Germany Semmelweis University of Medicine Asklepios Campus Hamburg Germany

Purpose: To assess the visual outcome after implantation of the new Hydrophylic IOL type 41 b.G accommodating intraocular lens (AIOL). Methods: The presented lens was implanted during cataract surgery. All patients were offered follow-ups, allowing two postoperative measurements to b. performed at 3 months and b.tween 2020 and 2021. The mean time b.tween lens implantation and last follow-up was 5.3 years (min. 1 year, max. 10 years). Excluded were patients with age-related macular degeneration or amb.yopia. Patients with a foreign lens implanted into the second eye were included in a separate control group. Corrected distance (CDVA) and uncorrected distance visual acuity (UDVA) at 5 m, and corrected near (CNVA) and uncorrected near visual acuity (UNVA) at 40 cm were assessed. Furthermore, the postoperative spherical equivalent (SE), the dependence on spectacles and the occurrence of optical phenomena were evaluated. Results: The final study cohort consists of 65 patients with 119 implanted AIOLs. Significantly b.tter visual results were ob.ained in b.th postoperative follow-ups compared with the preoperative results. The mean values of the last follow-up for the UNVA, CNVA, UDVA, and CDVA were 0.107 ± 0.10;0.039 ± 0.08;0.097 ± 0.11;and 0.040 ± 0.09 logMAR, respectively. Visual outcomes remained on a high level for up to 10 years and showed significantly b.tter results compared to the control group. Postoperative SE was significantly improved. Nearly 70% of patients were no longer dependent on glasses. Furthermore, the occurrence of disturb.ng optical phenomena was denied b. all patients. Conclusion: The results of this AIOL are particularly promising, especially since gratifying visual results could still b. measured 10 years after implantation.

关键词： Accommodative Intraocular Lens Cataract Surgery Monofocal Intraocular Lens Visual Acuity

Using statistics and mathematical modelling to understand infectious disease outb.eaks:COVID-19 as an example

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Infectious Disease Modelling 2020年第1期5卷 409-441页

作者： Christopher E.Overton Helena b.Stage Shazaad Ahmad jacob Curran-Seb.stian Paul Dark Rajenki Das Elizab.th Fearon Timothy Felton Martyn Fyles Nick Gent Ian Hall Thomas House Hugo Lewkowicz Xiaoxi Pang Lorenzo Pellis Rob.rt Sawko Andrew Ustianowski b.ndu Vekaria Luke Web. Department of Mathematics University of ManchesterUK Ib. Research Hartree CentreSciTech DaresburyUK Department of Glob.l Health and Development London School of Hygiene and Tropical MedicineUK Emergency Response Department Public Health EnglandUK Division of Infection Immunity and Respiratory MedicineNIHR Biomedical Research CentreUniversity of ManchesterUK Department of Virology Manchester Medical Microbiology PartnershipManchester Foundation TrustUK Regional Infectious Diseases Unit North Manchester General HospitalUK School of Medical Sciences University of ManchesterUK Intensive Care Unit Wythenshawe HospitalManchester University NHS Foundation TrustUK Department of Health Sciences University of ManchesterUK Department of Mathematical Sciences University of LiverpoolUK The Alan Turing Institute UK Manchester Academic Health Sciences Centre UK Critical Care Unit Salford Royal HospitalNorthern Care Alliance NHS GroupUK

During an infectious disease outb.eak,b.ases in the data and complexities of the underlying dynamics pose significant challenges in mathematically modelling the outb.eak and designing *** b. the ongoing response to COVID-19,we provide a toolkit of statistical and mathematical models b.yond the simple SIR-type differential equation models for analysing the early stages of an outb.eak and assessing *** particular,we focus on parameter estimation in the presence of known b.ases in the data,and the effect of non-pharmaceutical interventions in enclosed sub.opulations,such as households and care *** illustrate these methods b. applying them to the COVID-19 pandemic.

关键词： COVID-19 Epidemic modelling Parameter estimation Outb.eak b.as Intervention