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LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu elizabeth R.Davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.marshall David Hancock Tim Wallis Julian Downward Rob M.ewing Donna e.Davies Mark G.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely *** previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(eMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine ***,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces eMT as a *** IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast ***,these data suggest that reduced autophagy caused by LKB1 inhibition can induce eMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk eMT LKB1 Pulmonary fibrosis

Genetics of inflammatory bowel disease: The role of the HLA complex

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World Journal of Gastroenterology 2006年第23期12卷 3628-3635页

作者： Tariq Ahmad Sara e marshall Derek Jewell Gastroenterology Unit University of OxfordGibson LaboratoriesRadcliffe Infirmary Woodstock RoadOxford United Kingdom Department of Immunology Wright-Fleming InstituteImperial CollegeLondonUnited Kingdom Gastroenterology Unit University of OxfordGibson LaboratoriesRadcliffe InfirmaryWoodstock RoadOxfordUnited Kingdom

The human leucocyte antigen （HLA） complex on chromosome 6p21.3 is the most extensively studied genetic region in Inflammatory bowel disease （IBD）. Consistent evidence of linkage to IBD3 （6p21.1-23）, an area which encompasses the HLA complex, has been demonstrated for both Crohn＇s disease and ulcerative colitis, and a number of replicated associations with disease susceptibility and phenotype have recently emerged. However, despite these efforts the HLA susceptibility gene （s） for IBD remain elusive, a consequence of strong linkage disequilibrium, extensive polymorphism and high gene density across this region. This article reviews current knowledge of the role of HLA complex genes in IBD susceptibility and phenotype, and discusses the factors currently limiting the translation of this knowledge to clinical practice.

关键词： Inflammatory bowel disease Human leucocyte antigen complex Crohn's disease Ulcerative colitis Genetics

A diagnosis with a twist:Ultrasonographic sensitivity and predictors of pediatric ovarian torsion within a large pediatric hospital

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World Journal of emergency Medicine 2022年第3期13卷 229-231页

作者： Mark K.Hewitt Jesse e.marshall-Sheppard April J.Kam Department of Medicine Division of Emergency MedicineMcMaster UniversityHamilton L8S 4L8Canada Department of Family Medicine University of TorontoToronto M5S1A1Canada Department of Pediatrics Division of Pediatric Emergency MedicineMcMaster UniversityHamilton 8S 4L8Canada

The diagnosis of ovarian torsion(OT)in girls is challenging compared to that of testicular torsion in boys for many reasons,but it behooves the medical community to continue to strive to better identify this uncommon but clinically important pathology^([1]) OT occurs when the ovary and associated structures rotate around its vascular pedicle,leading to eventually irreversible necrosis.^([2,3])Studies attempting to identify clinical features for early diagnosis have not reached a consensus on the best clinical predictors of this condition,making radiographic imaging of the ovaries even more crucial.^([4,5])

关键词： diagnosis pediatric torsion

On the design and selection of vehicle coordination policies for underground mine production ramps

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International Journal of Mining Science and Technology 2016年第4期26卷 623-627页

作者： Michal Pasternak Joshua A.marshall Mining Systems Laboratory The Robert M.Buchan Department of MiningQueen's University

Traffic management in underground mines,especially on production ramps,is a difficult problem to optimize and *** operations use one of a few common policies;e.g.,the so-called ‘‘lock-out" and‘‘loaded-vehicle-priority" *** work presented in this paper uses discrete-event simulation to study the efficiency of multiple *** on simulation results,an improvement to the common lock-out policy is *** new policy utilizes the rules of the lock-out policy but integrates an option that allows a group of vehicles to be given temporary priority in a certain direction of *** results are provided and,based on these,a systematic technique for ramp design that aims to optimize the efficiency of underground mine ramp traffic flow is described.

关键词： Underground mining Fleet managementRamp design equipment selection Discrete-event simulation

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World Journal of Gastrointestinal Oncology 2013年第11期5卷 198-203页

作者： Osama e Rahma Mauricio Burotto Luisa Matos Do Canto Alexandre A Germanos Bassem R Haddad John L marshall Medical Oncology Branch National Cancer Institute the Lombardi Comprehensive Cancer Center Georgetown University Medical Center Whitman College the Ruesch Center for the Cure of GI Cancers Georgetown University Medical Center

We are reporting the longest disease-free interval ever published for colorectal cancer, using gene profiling to confirm the linkage of the primary and metastasis. This rare case reports on a patient with late recurrence of colorectal cancer in the lung 19 years after its initial diagnosis. We used high-resolution array CGH(aCGH) to analyze the genetic aberrations of both the primary rectal and the recurrent metastatic lung lesions. Interestingly, we found striking similarities between the two lesions, despite the 19 years disease-free *** addition, most of the genes that were previously reported to be associated with a high recurrence score showed copy number gains by aCGH in one or both lesions. Our findings suggest that aCGH may be a helpful tool in analyzing the origin of metastatic lesions and reflect the need for a better understanding of the characteristics of the rectal tumors with a late recurrence potential.

关键词： Colorectal cancer Genetic aberrations Delayed Recurrence High-resolution array CGH

Model-based estimation of above-ground biomass in the miombo ecoregion of Zambia

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Forest ecosystems 2016年第4期3卷 258-274页

作者： James Halperin Valerie LeMay emmanuel Chidumayo Louis Verchot Peter marshall Department of Forest Resources Management The University of British Columbia 2424 Main Mall Vancouver BC V6T 1Z4 Canada Makeni Savanna Research Project P.O. Box 50323 Ridgeway Lusaka Zambia International Center for Tropical Agriculture Km 17 Recta Cali-Palmira Apartado Aereo 6713 Cali 763537. Colombia

Background：Information on above-ground biomass（AGB） is important for managing forest resource use at local levels,land management planning at regional levels,and carbon emissions reporting at national and international *** many tropical developing countries,this information may be unreliable or at a scale too coarse for use at local *** is a vital need to provide estimates of AGB with quantifiable uncertainty that can facilitate land use management and policy development ***-based methods provide an efficient framework to estimate ***：Using National Forest Inventory（NFI） data for a^1,000,000 ha study area in the miombo ecoregion,Zambia,we estimated AGB using predicted canopy cover,environmental data,disturbance data,and Landsat 8 OLI satellite *** assessed different combinations of these datasets using three models,a semiparametric generalized additive model（GAM） and two nonlinear models（sigmoidal and exponential）,employing a genetic algorithm for variable selection that minimized root mean square prediction error（RMSPe）,calculated through *** compared model fit statistics to a null model as a baseline estimation *** bootstrap resampling methods,we calculated 95% confidence intervals for each model and compared results to a simple estimate of mean AGB from the NFI ground plot ***：Canopy cover,soil moisture,and vegetation indices were consistently selected as predictor *** sigmoidal model and the GAM performed similarly;for both models the RMSPe was -36.8 tonnes per hectare（i.e.,57% of the mean）.However,the sigmoidal model was approximately 30% more efficient than the GAM,assessed using bootstrapped variance estimates relative to a null *** selecting the sigmoidal model,we estimated total AGB for the study area at 64,526,209 tonnes（＋/- 477,730）,with a confidence interval 20 times more precise than a simple designbased ***：Our findings demonstrate that NFI

关键词： National Forest Inventory Above-ground biomass Miombo ReDD+ Generalized additive model Nonlinear model Landsat 8 OLI

Depletion of BBS Protein LZTFL1 Affects Growth and Causes Retinal Degeneration in Mice

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Journal of Genetics and Genomics 2016年第6期43卷 381-391页

作者： Jiangsong Jiang Kanyarat Promchan Hong Jiang Parirokh Awasthi Heather marshall Adam Harned Ven Natarajan Laboratory of Molecular Cell Biology Leidos Biomedical ResearchInc.Frederick National Laboratory for Cancer ResearchFrederickMD 21702USA Transgenic Mouse Model Laboratory Leidos Biomedical ResearchInc.Frederick National Laboratory for Cancer ResearchFrederickMD 21702USA electron Microscopy Laboratory Leidos Biomedical ResearehInc.Frederick National Laboratory for Cancer ResearchFrederickMD 21702USA

Bardet-Biedl syndrome（BBS） is a heterogeneous disease characterized by deficiencies in various organs that are caused by defects in genes involved in the genesis, structural maintenance, and protein trafficking of cilia. Leucine zipper transcription factor-like 1（LZTFL1）has been identified as a BBS protein（BBS17）, because patients with mutations in this gene exhibit the common BBS phenotypes. In this study, we generated a knockout mouse model to investigate the effects of LZTFL1 depletion. Lztfl1 knockout mice were born with low birth weight, reached similar weight to those of wild-type mice at 10 weeks of age, and later gained more weight than their wild-type counterparts. LZTFL1 was localized to the primary cilium of kidney cells, and the absence of LZTFL1 increased the ciliary localization of BBS9. Moreover, in the retinas of Lztfl1 knockout mice, the photoreceptor outer segment was shortened, the distal axoneme of photoreceptor connecting cilium was significantly enlarged, and rhodopsin was targeted to the outer nuclear layer. TUNeL assay showed that many of these abnormal photoreceptor cells in Lztfl1 knockout mice underwent apoptosis. Interestingly, the absence of LZTFL1 caused an abnormal increase of the adaptor protein complex 1（AP1） in some photoreceptor cells. Based on these data, we conclude that LZTFL1 is a cilium protein and regulates animal weight and photoreceptor connecting cilium function probably by controlling microtubule assembly and protein trafficking in cilia.

关键词： LZTFL1 Cilium BBSome BBS17 Retina AP-1

Walking for health during pregnancy:A literature review and considerations for future research

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Journal of Sport and Health Science 2019年第5期8卷 401-411页

作者： Christopher P.Connolly Scott A.Conger Alexander H.K.Montoye Mallory R.marshall Rebecca A.Schlaff Sylvia e.Badon James M.Pivarnik Kinesiology Program Washington State UniversityPullmanWA 99164-1410USA Department of Kinesiology Boise State UniversityBoiseID 83725USA Department of Integrative Physiology and Health Science Alma CollegeAlmaMI 48801USA Department of Kinesiology Samford UniversityBirminghamAL 35229USA Department of Kinesiology Saginaw Valley State UniversityUniversity CenterMI 48710USA Division of Research Kaiser Permanente Northern CaliforniaOaklandCA 94612USA Department of Kinesiology Michigan State UniversityEast LansingMI 48824-1034USA

Walking is the most commonly chosen type of physical activity(PA)during pregnancy and provides several health benefits to both mother and *** initiatives have promoted the importance of walking in general,but little emphasis is directed toward pregnant women,the majority of whom are insufficiently *** women face a variety of dynamic barriers to a physically active lifestyle,some of which are more commonly experienced during specific times throughout the pregnancy *** is unique in that it appears resistant to a number of these barriers that limit other types of PA participation,and it can be meaningfully integrated into some transportation and occupational activities when leisure-time options are *** intervention work suggests that walking programs can be effectively adopted into a typical pregnancy ***,a great deal of work remains to administer successful pregnancy walking interventions,including developing and using validated methods of PA and walking *** narrative review discusses the unique advantages of walking during pregnancy,provides recommendations for future intervention work,and outlines the need for pregnancy-focused community walking *** search procedures were followed to determine sources from the literature specific to walking during pregnancy for use in each section of this review.

关键词： Ambulatory activity exercise behavior Maternal-fetal health Pregnant women

Resting metabolic rates increase with elevation in a mountain-dwelling lizard

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Integrative Zoology 2020年第5期15卷 363-374页

作者： Melissa PLASMAN Amando BAUTISTA marshall D.McCUe Aníbal H.DÍAZ De LA VeGA-PÉReZ Centro Tlaxcala de Biología de la Conducta Universidad Autónoma de TlaxcalaTlaxcalaMéxico Sable Systems International Las VegasNevadaUSA Consejo Nacional de Ciencia y Tecnología–Centro Tlaxcala de Biología de la Conducta Universidad Autónoma de TlaxcalaTlaxcalaMéxico

ndividuals that inhabit broad elevational ranges may experience unique environmental *** temperature decreases with increased elevation,the ectotherms living at high elevations have to manage limited activity time and high thermoregulatory *** resting metabolic rate(RMR)of a postabsorptive animal is related to its total energy requirements as well as many other fitness *** lizards(Sceloporus grammicus)living on La Malinche Volcano,Mexico,inhabit a wide elevational range with some populations apparently thriving above the tree *** measured the RMR of lizards from different elevations(i.e.,2,600,3,200,and 4,100 m)at four ecologically relevant temperatures(i.e.,15,25,30,and 35°C)and found that RMR of mesquite lizards increased with temperature and body *** importantly,lizards from the high-elevation population had mass specific RMR that was higher at all *** the higher RMRs of high-elevation populations imply higher metabolic costs at a given temperature these lizards were also *** of these traits may allow these high elevation populations to thrive in the face of the thermal challenges imposed by their environment.

关键词： altitudinal gradient energetics reptile Sceloporus temperature