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Partial epithelial-mesenchymal transition in keloid scars: regulation of keloid keratinocyte gene expression by transforming growth factor-β1

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Burns & Trauma 2016年第3期4卷 199-215页

作者： Jennifer m.Hahn Kevin L.mcFarland Kelly A.Combs dorothy m.supp Research Department Shriners Hospitals for Children-CincinnatiCincinnatiOHUSA Research Department Shriners Hospitals for Children-CincinnatiCincinnatiOHUSA Department of Surgery University of Cincinnati College of MedicineCincinnatiOHUSA

Background:Keloids are an extreme form of abnormal scarring that result from a pathological fibroproliferative wound healing *** molecular mechanisms driving keloid pathology remain incompletely understood,hindering development of targeted,effective *** studies in our laboratory demonstrated that keloid keratinocytes exhibit adhesion abnormalities and display a transcriptional signature reminiscent of cells undergoing epithelial-mesenchymal transition(EmT),suggesting a role for EmT in keloid *** the current study,we further define the EmT-like phenotype of keloid scars and investigate regulation of EmT-related genes in ***:Primary keratinocytes from keloid scar and normal skin were cultured in the presence or absence of transforming growth factor beta 1(TGF-β1)+/-inhibitors of TGF-β1 and downstream signaling *** expression was measured using quantitative polymerase chain *** was analyzed using an in vitro wound healing *** in keloid scar and normal skin sections were localized by *** analyses utilized SigmaPlot(SyStat Software,San Jose,CA)or SAS?(SAS Institute,Cary,NC).Results:In keloid and normal keratinocytes,TGF-β1 regulated expression of EmT-related genes,including hyaluronan synthase 2,vimentin,cadherin-11,wingless-type mmTV integration site family,member 5A,frizzled 7,ADAm metallopeptidase domain 19,and *** of canonical TGF-β1 signaling in keloid keratinocytes significantly inhibited expression of these genes,and TGF-β1 stimulation of normal keratinocytes increased their *** inhibition of the extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway or the p38 mitogen-activated protein kinase pathway attenuated TGF-β1-induced expression of subsets of these *** of keloid keratinocytes,previously shown to be increased compared with normal keratinocytes,was significantly reduced by inhibition of TGF-β1 or E

关键词： Keloid Keratinocyte Epithelial-mesenchymal transition Wound healing Scar Fibrosis

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Pirfenidone inhibits epithelial–mesenchymal transition in keloid keratinocytes

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Burns & Trauma 2020年第1期8卷 441-451页

作者： Latha Satish Alexander Evdokiou Eleni Geletu Jennifer m.Hahn dorothy m.supp Research Department Shriners Hospitals for Children—CincinnatiCincinnatiOH 45229 USA Department of Pathology&Laboratory medicine University of CincinnatiCincinnatiOH 45229USA Department of Surgery University of CincinnatiCincinnatiOH 45229USA

Background:Keloids are benign fibroproliferative skin lesions that are difficult to treat and become a lifetime predicament for *** treatment modalities have been put forth,but as yet no satisfactory approach to the prevention or treatment of keloids has been *** process of epithelial-to-mesenchymal transition(EmT)has been implicated in keloid scarring,as keloid keratinocytes display an EmT-like *** study investigated the potential of pirfenidone,an antifibrotic agent,to counteract EmT-like alterations in keloid keratinocytes,including gene expression,cell migratory and proliferative ***:Normal and keloid keratinocytes were isolated from discarded normal skin tissues and from resected keloid tissues,*** were quiesced for 24 h without epidermal growth factor DS-Qi1mCDigital and were exposed to transforming growth factor-beta1(TGF-β1;10 ng/mL),with or without pirfenidone(400μg/mL),for an additional 24 *** effects of pirfenidone on cytotoxicity,cell migration,cell proliferation,and on expression of genes and proteins involved in EmT were *** significance was determined by two-way ANOVA using Sigma ***:We found that pirfenidone did not elicit any cytotoxic effect at concentrations up to 1000μg/mL.A statistically significant dose-dependent decrease in basal cell proliferation rate was noted in both normal and keloid keratinocytes when exposed to pirfenidone at concentrations ranging from 200 to 1000μg/*** significantly decreased basal cell migration in both normal and keloid keratinocytes,but a significant decrease in TGF-β1-induced cell migration was seen only in keloid *** inhibition of the expression of TGF-β1-induced core EmT genes,namely hyaluronan synthase 2,vimentin,cadherin-11,and wingless-type mmTV integration site family,member 5A along with fibronectin-1,was observed in both normal and keloid keratinocytes treated with *** addi

关键词： Keloids EmT genes Cell migration Proliferation Pirfenidone Fibronectin

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Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

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World Journal of Hepatology 2024年第4期16卷 650-660页

作者： dorothy Liu mark m Youssef Josephine A Grace marie Sinclair Department of Gastroenterology Austin HealthMelbourne 3084VictoriaAustralia Victorian Liver Transplant Unit Austin HealthMelbourne 3084VictoriaAustralia Department of medicine University of MelbourneMelbourne 3084VictoriaAustralia

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant *** immunosuppression has been shown to contribute to post-transplant malignancy(PTm)*** is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of *** inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(mPA),the active metabolite of mycophenolate mofetil,may limit tumour *** transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or mPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this ***,there is limited clinical data on this subject in both LT and other solid organ transplant *** To investigate the relative carcinogenicity of tacrolimus and mPA in solid organ *** A literature search was conducted using mEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August *** terms,synonyms and explosion of meSH terms,Boolean operators and truncations were also utilised in the *** lists of retrieved articles were also reviewed to identify any additional *** duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in ***-text articles were assessed for eligibility based on pre-specified inclusion and exclusion *** A total of 6 studies were included in this *** studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol us

关键词： Immunosuppression Solid organ transplantation Liver transplantation Carcinogenicity Tacrolimus mycophenolate

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Discourse Intonation in L2. From theory and research to practice.

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丛书名： Language Learning & Language Teaching

2002年

作者： dorothy m. Chun

ISBN: (数字)9789027297525

ISBN: (纸本)9789027216915

Intonation, rhythm, and general “melody” of language are among the first aspects of speech that infants attend to and produce themselves. Yet, these same features are among the last to be mastered by adult L2 learners. Why is this, and how can L2 learners be helped? This book first presents the latest linguistic theories of intonation, in particular, how intonation functions in discourse not only to signal sentence types and attitudinal meanings but also to provide turn-taking and other conversational cues. The second part of the book examines the research in applied linguistics on the acquisition of L2 phonology and intonation. The third section offers practical applications of how to incorporate the teaching of intonation into L2 instruction, with a focus on using new speech technologies. The accompanying CD-ROm makes a unique addition in allowing for simultaneous audio playback and visual display of the pitch contours of utterances contained in the book. Users can start or stop the playback at any point in the utterance and can observe first-hand how such visual and audio representations could be useful for L2 learners.

关键词： language learn practice research intonation theory discourseWords & Language Education & Reference

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Determinants and rates of land degradation： Application of stationary time-series model to data from a semi-arid environment in Kenya

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Journal of Arid Land 2018年第1期10卷 1-11页

作者： kevin z mganga dickson m nyariki nashon k r musimba dorothy a amwata department of range and wildlife sciences south eastern kenya university170-90200 KituiKenya department of agricultural economics and agribusiness south eastern kenya university170-90200 KituiKenya school of business and economics murangáuniversity of technology75-10200 MurangaKenya

The causes of land degradation in the African drylands have been shown to vary. Some researchers consider climate to be the major contributor to degradation, with anthropogenic factors playing a minor role. Others reverse the significance of these two factors. A third group attributes land degradation to climate and anthropogenic factors equally. This study was undertaken to establish the factors influencing land degradation in a semi-arid environment in southeastern Kenya and the rate of change in vegetation types for a period of 35 years （1973-2007）. The reduction in grassland cover was used as an indicator of land degradation. Causes of land degradation were determined by a multiple regression analysis. A log-linear regression analysis was used to establish the rate of vegetation change. The multiple and log-linear regression analyses showed：（1） woody vegetation, livestock population and cultivated area to be the main contributors of reduction in grassland cover in the area, and （2） an increase in undesirable woody species, livestock population and cultivated area had a significant （P〈0.05） negative effect on grassland vegetation. Increased human population, low amounts of rainfall and drought showed no significant negative effect on grassland vegetation cover. In conclusion, human and livestock population growth and increased agricultural land have contributed to intensive crop cultivation and overgrazing in the semi-arid lands. This overuse of the semi-arid rangelands has worsened the deterioration of the natural grassland vegetation.

关键词： regression analysis land degradation grassland cover semi-arid Kenya Sub-Saharan Africa

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Quantifying the early snowmelt event of 2015 in the Cascade mountains,USA by developing and validating mODIS-based snowmelt timing maps

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Frontiers of Earth Science 2018年第4期12卷 693-710页

作者： Donal O'LEARY III dorothy HALL michael mEDLER Aquila FLOWER University of maryland Department of Geographical SciencesCollege ParkMD 20740USA Westem Washington University Department of Environmental StudiesBellinghamWA 98225USA National Aeronautics and Space Administration Goddard Space Flight CenterGreenbeltMD 20771USA Earth System Science Interdisciplinary Center University of MarylandCollege ParkMD 20740USA

Spring snowmelt serves as the major hydrological contribution to many watersheds of the US West. Since the 1970s the conterminous western USA has seen an earlier arrival of spring snowmelt. The extremely low snowpack and early melt of 2015 in the Cascade mountains may be a harbinger of winters to come, underscoring the interest in advancements in spring snowmelt monitoring. Target-of-opportunity and point measurements of snowmelt using meteorological stations or stream gauges are common sources of these data, however, there have been few attempts to identify snowmelt timing using remote sensing. In this study, we describe the creation of snowmelt timing maps (STms) which identify the day of year that each pixel of a remotely sensed image transitions from “snow-covered” to “no snow” during the spring melt season, controlling for cloud coverage and ephemeral spring snow storms. Derived from the 500 m mODerate-resolution Imaging Spectroradiometer (mODIS) standard snow map, mOD10A2, this new dataset provides annual maps of snowmelt timing, with corresponding maps of cloud interference and interannual variability in snow coverage from 2001–2015. We first show that the STms agree strongly with in-situ snow telemetry (SNOTEL) meteorological station measurements in terms of snowmelt timing. We then use the STms to investigate the early snowmelt event of 2015 in the Cascade mountains, USA, highlighting the protected areas of mt. Rainier, Crater Lake, and Lassen Volcanic National Parks. In 2015 the Cascade mountains experienced snowmelt 41 days earlier than the 2001–2015 average, with 25% of its land area melting>65 days earlier than average. The upper elevations of the Cascade mountains experienced the greatest snowmelt anomaly. Our results are relevant to land managers and biologists as they plan adaptation strategies for mitigating the effects of climate change throughout temperate mountains.

关键词： Cascade mountains snowmelt spring phenology mODIS remote sensing

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Phone skills for the Information Age / 3rd ed.

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2006年

作者： dorothy maxwell.

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Gm604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis

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Translational Neurodegeneration 2018年第1期7卷 322-345页

作者： William R.Swindell Krzysztof Bojanowski mark S.Kindy Raymond m.W.Chau dorothy Ko Heritage College of Osteopathic medicine Ohio UniversityAthensOHUSA Sunny BioDiscovery IncSanta PaulaCAUSA Department of Pharmaceutical Sciences College of PharmacyUniversity of South FloridaTampaFLUSA James A.Haley VAmC TampaFLUSA Genervon Biopharmaceuticals LLC PasadenaCAUSA

Background:Amyotrophic lateral sclerosis(ALS)is currently an incurable disease without highly effective pharmacological *** peptide drug Gm604(Gm6 or Alirinetide)was developed as a candidate ALS therapy,which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic ***6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways,but mechanisms of action are not fully ***:This study used RNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following Gm6 treatment(6,24 and 48 h).Results:We identified 2867 protein-coding genes with expression significantly altered by Gm6(FDRmponents,with increased expression of developmental genes mediating neurogenesis and axon *** Gm6 treatment(24 and 48 h)altered the expression of genes contributing to cell adhesion and the extracellular ***6 further down-regulated the expression of genes associated with mitochondria,inflammatory responses,mRNA processing and chromatin ***6-increased genes were located near GC-rich motifs interacting with C2H2 zinc finger transcription factors,whereas Gm6-decreased genes were located near AT-rich motifs associated with helix-turn-helix homeodomain *** motifs interacted with a diverse network of transcription factors encoded by Gm6-regulated genes(STAT3,HOXD11,HES7,GLI1).We identified 77 ALS-associated genes with expression significantly altered by Gm6 treatment(FDRsupport the hypothesis that Gm6 acts through developmental-stage pathways to influence neuron *** expression responses were consistent with neurotrophic effects,ECm modulation,and activation of the Notch and hedgehog neurodevelopmental *** multif

关键词： Alzheimer’s disease Amyotrophic lateral sclerosis Extracellular matrix,Hedgehog Huntington’s disease Neurodegenerative disease Notch,Parkinson’s disease RNA-seq Transcriptome

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Field Test of Optical and Electrical Fire Detectors in Simulated Fire Scenes in a Cable Tunnel

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Photonic Sensors 2014年第2期4卷 156-161页

作者： Dian FAN Hongjun DING dorothy Y. WANG Desheng JIANG National Engineering Laboratory for Fiber Optic Sensing Technology Wuhan University of Technology Wuhan430070 China Shenyang Fire Research Institute Shenyang 110034 China Center for Photonics Technology Bradley Department of Electrical and Computer Engineering Virginia PolytechnicInstitute and State University Blacksburg VA 24061 USA

这份报纸论述火察觉者的三种类型的严峻的结果：电的热察觉到电报，光纤维拉曼温度察觉到察觉者，和光纤维布拉格栅栏(FBG ) 温度察觉到察觉者，在二模仿的火，在一个电报的场面掘。在有有限热放射和没有火焰的小规模的火，火警报仅仅... 详细信息

这份报纸论述火察觉者的三种类型的严峻的结果：电的热察觉到电报，光纤维拉曼温度察觉到察觉者，和光纤维布拉格栅栏(FBG ) 温度察觉到察觉者，在二模仿的火，在一个电报的场面掘。在有有限热放射和没有火焰的小规模的火，火警报仅仅来自直接与热来源一起联系的热传感器。在有大约 5

关键词：火灾探测器电缆隧道现场测试火灾场景模拟光纤布拉格光栅 FBG传感器电气

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Knowledge, perception and practices about malaria, climate change, livelihoods and food security among rural communities of central Tanzania

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Infectious Diseases of Poverty 2015年第1期4卷 176-184页

作者： Benjamin K mayala Carolyn A Fahey dorothy Wei maria m Zinga Venera m Bwana Tabitha mlacha Susan F Rumisha Grades Stanley Elizabeth H Shayo Leonard EG mboera National Institute for medical Research Dar es SalaamTanzania Georgetown University WashingtonDCUSA Catholic University of Health and Allied Sciences-Bugando MwanzaTanzania

Background:Understanding the interactions between malaria and agriculture in Tanzania is of particular significance when considering that they are the major sources of illness and *** objective of this study was to determine knowledge,perceptions and practices as regards to malaria,climate change,livelihoods and food insecurity in a rural farming community in central ***:Using a cross-sectional design,heads of households were interviewed on their knowledge and perceptions on malaria transmission,symptoms and prevention and knowledge and practices as regards to climate change and food ***:A total of 399 individuals(mean age=39.8±15.5 years)were ***(62.41%)of them had attained primary school education and majority(91.23%)were involved in crop farming *** all(94.7%)knew that malaria is acquired through a mosquito *** quarters(73%)reported that most people get sick from malaria during the rainy *** 50%of the respondents felt that malaria had decreased during the last 10 *** household coverage of insecticide treated mosquito nets(ITN)was high(95.5%).Ninety-six percent reported to have slept under a mosquito net the previous *** one in four understood the official Kiswahili term(mabadiliko ya Tabia Nchi)for climate ***,there was a general understanding that the rain patterns have changed in the past 10 ***-two percent believed that the temperature has increased during the same *** quarters of the respondents reported that they had no sufficient production from their own farms to guarantee food security in their household for the *** quarters(73.0%)reported to having food shortages in the past five *** half said they most often experienced severe food shortage during the rainy ***:Farming communities in Kilosa District have little knowledge on climate change and its impact on malaria *** insecurity is common and comm

关键词： malaria Agriculture Climate change Food insecurity Knowledge Practice Tanzania

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