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Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung

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分子细胞生物学报:英文版 2015年第1期7卷 35-47页

作者： Alexander W.Lange Anusha Sridharan Yan Xu barry r.Stripp Anne-Karina Perl jeffrey A.Whitsett Division of Pulmonary biology Cindinnati Children's Hospital Medical Center and the University of Cncinnati Collel ge of MedicineCincinnatiOH 452293039USA Cedars-Sinai Medical Center Los AngelesCA 90048USA

The Hippo/Yap pathwayis a wll-conserved signaling cascade that regulates cell proliferation and dfferentiationto control organsize and stem/progenitor cell *** airway injury,Yap was dynamically regulated in regenerating airway epithelial *** *** the role ofHippo signaling in the lung,the mammalian Hippo kinases,Mst1 and Mst2,were deleted in epithelial cells ofthe embry-onic and mature mouse ***1/2 deletion in the fetal lung enhanced proliferation and inhibited sacculation and epithelial cell *** transcriptional inhibition of cell proliferation and activation of differentiation during normal perinatal lung maturation were inversely regulated followving embryonic Mst1/2 *** of Mst1/2 from bronchiolar epithelial cells in the adult lung caused airway hyperplasia and altered *** Yap phosphorylation was decreased and Yap nuclear localization and transcriptional targets were increased after Mst1/2 deletion,consistent with canonical Hippo/Yap *** potentiated cell prolif-eration and inhibited dfferentiation of human bronchial epithelial cells in *** of Mst1/2 and expression ofYAP regulated transcrip-tional targets controlling cell proliferation and diferentiation,including Ajuba LIM *** was required forthe effects ofYAP oncell proliferation in ***/Yapsignaling regulates Ajuba and controls proliferation and diferentiation oflung epithelial progenitor cells.

关键词： Hippo/Yap pathway lung Ajuba proliferation dfferetiation

Dietary fatty acids and bioactive fatty acid metabolites in alcoholic liver disease

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Liver research 2019年第3期3卷 206-217页

作者： Kara H.Zirnheld Dennis r.Warner jeffrey b.Warner Josiah E.Hardesty Craig J.McClain Irina A.Kirpich Division of Gastroenterology Hepatologyand NutritionDepartment of MedicineUniversity of Louisville School of MedicineLouisvilleKYUSA Department of Pharmacology and Toxicology University of Louisville School of MedicineLouisvilleKYUSA University of Louisville Alcohol Center University of Louisville School of MedicineLouisvilleKYUSA robley rex Veterans Medical Center LouisvilleKYUSA

Alcoholic liver disease(ALD)comprises a spectrum of liver pathology,including steatosis,steatohepatitis,and *** work from our group and others suggests that dietary fat,both the amount and composition,plays a pivotal role in ALD development and progression;however,the impact of specific dietary fatty acids on ALD pathogenesis is not fully *** rodent models of ALD revealed the deleterious effects of omega-6 polyunsaturated fatty acids(n-6 PUFAs),specifically linoleic acid(LA),and this may be partially attributed to the increased levels of pro-inflammatory oxidized LA *** is limited understanding regarding the role of omega-3 polyunsaturated fatty acids(n-3 PUFAs,such as alpha-linolenic acid,eicosapentaenoic acid,and docosahexaenoic acid),and bioactive n-3 PUFAderived lipid molecules in *** that majority of n-6 and n-3 PUFAs-derived metabolites are potent endogenous signaling molecules,knowledge regarding the changes in these lipid mediators may shed new light on the mechanisms contributing to ALD pathogenesis and reveal novel therapeutic targets and biomarkers of this *** current review summarizes relevant scientific literature regarding the role of dietary fat,distinct fatty acids,and bioactive fatty acid metabolites in ALD,and highlights recent advances in the field.

关键词： Dietary fatty acids bioactive fatty acid metabolites Alcoholic liver disease(ALD) Omega-6 polyunsaturated fatty acids(n-6 PUFAs) Omega-3 polyunsaturated fatty acids(n-3 PUFAs)

Abscisic Acid Signal off the STArTing block

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Molecular Plant 2011年第4期4卷 562-580页

作者： Archana Joshi-Saha Christiane Valon jeffrey Leung Institut des Sciences du Vegetal Centre National de la Recherche Scientifique UPR2355 1 Avenue de la Terrasse Bat. 23 91198 Gif-sur-Yvette France

The year 2009 marked a real turnaround in our understanding of the mode of abscisic acid （AbA） action. Nearly 25 years had elapsed since the first biochemical detection of AbA-binding proteins in the plasmalemma of Vicia guard cells was reported. This recent--and laudable--achievement is owed largely to the discovery of the soluble AbA receptors whose major interacting proteins happen to be some of the most well-established components of earliest steps in AbA signaling. These soluble receptors, with the double name of PYrAbACTIN rESISTANCE （PYr） or rEGULATOrY COMPONENT OF AbA rECEPTOr （rCAr）, are a family of Arabidopsis proteins of about 150-200 amino acids that share a conserved STArT domain. The AbA signal transduction circuitry under non-stress conditions is muted by the clade A protein phosphatases 2C （PP2C）（notably HAb1, AbI1, and AbI2）. During the initial steps of AbA signaling, the binding of the hormone to the receptor induces a conformational change in the latter that allows it to sequester the PP2Cs. This excludes them from the negative regulation of the downstream AbA-activated kinases （OST1/SnrK2.6/SrK2E, SnrK2.2, and SnrK2.3）, thus unleashing the pathway by freeing them to phosphorylate downstream targets that now include several b-ZIP transcription factors, ion channels （SLAC1, KAT1）, and a NADPH oxidase （AtrbohF）. The discovery of this family of soluble receptors and the rich insight already gained from structural studies of their complexes with different isoforms of AbA, PP2C, and the synthetic agonist pyrabactin lay the foundation towards rational design of chemical switches that can bolster drought hardiness in plants.

关键词： Abiotic/environmental stress hormone biology signal transduction.

randomized controlled trials in frontotemporal dementia: cognitive and behavioral outcomes

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Translational Neurodegeneration 2014年第1期3卷 89-97页

作者： Justin b Miller Sarah J banks Gabriel C Léger jeffrey L Cummings Cleveland Clinic Lou Ruvo Center for Brain Health888 W.Bonneville AveLas VegasNevada 89106USA

Progress has been made in understanding the genetics and molecular biology of frontotemporal dementia(FTD).Targets for intervention have been identified,therapies are being developed,and clinical trials are advancing.A major challenge for FTD research is that multiple underlying pathologies can be associated with heterogeneous *** neuropsychological profiles associated with FTD spectrum disorders often include executive dysfunction,language impairments and behavioral *** variant FTD is characterized by an initial presentation of changes in personality,behavior and/or emotion,which are often difficult to objectively capture using traditional neuropsychological *** two principal language variants of FTD are Progressive Nonfluent Aphasia(PNFA)with predominant agrammatic/non-fluent impairments and Semantic Dementia(SD)with semantic impairments and visual *** of appropriate endpoints for clinical trials is critical to ensure that the measures are adequately sensitive to detect change,yet specific enough to isolate signal from noise,and acceptable to regulatory *** the anticipated potential for small effect sizes,measures must be able to identify small incremental changes over *** is also imperative that the measures provide adequate coverage of the constructs or behaviors of *** outcome measures should be suitable for repeat administration,yet relatively robust to practice effects to ensure that observed changes reflect true signal variance and not residual effects due to repeated measurement or poor *** facilitate widespread adoption as an endpoint,measures should be readily *** provide several examples of potential global,composite,and individual cognitive measures,as well as behavioral measures promising for FTD *** and application of appropriate trial outcomes is critically important to success in advancing new treatments for FTD patients.

关键词： Frontotemporal dementia Primary endpoints Secondary endpoints randomized controlled trial Methods

Variation in female aggression in 2 three-spined stickleback populations with female throat and spine coloration

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Current Zoology 2018年第3期64卷 345-350页

作者： Lengxob YONG brittney LEE jeffrey S. MCKINNON Department of biology East Carolina University Greenville NC 27858 USA

Despite growing interest in female ornament evolution, we still have a rudimentary understanding of female display traits relative to similar traits in males. Under one popular adaptive scenario, female ornaments are hypothesized to function in female-female competition and serve as badges of status, such that their expression is linked with elevated aggression in some cases. In this study, we investigated the relationship between 2 female ornaments--male-like red throat color and red spine coloration--and female aggression in 2 independently derived stream-resident populations of three-spined stickleback Gasterosteus aculeatus. Using simulated intrusions, we tested whether females with redder ornaments were generally more aggressive, and for variation in aggressive and social behaviors between the 2 populations. We found that the red intensity of the throat and spine did not predict aggression levels in either population, suggesting a limited role for both female ornaments during female-female interaction. The 2 populations exhibited different levels of aggressive behaviors, unrelated to the color patches. Our results suggest that variation in selective pressures between populations may promote interpopulation variance in aggressive behavior but not the correlation between female ornamentation and aggression, and raise the possibility that red coloration may have evolved through different mechanisms or processes in the 2 populations.

关键词： aggression animal coloration female ornaments Gasterosteus aculeatus stickleback.

Sam68 is a regulator of Toll-like receptor signaling

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Cellular & Molecular Immunology 2017年第1期14卷 107-117页

作者： jeffrey A Tomalka Tristan J de Jesus Parameswaran ramakrishnan Department of Pathology School of Medicine Case Western Reserve University and University Hospitals Case Medical Center Cleveland OH 44106 USA

recognition of pathogens by Toll-like receptors （TLr） activate multiple signaling cascades and expression of genes tailored to mount a primary immune response, inflammation, cell survival and apoptosis. Although TLr-induced activation of pathways, such as nuclear factor kappab （NF-κb） and mitogen-activated protein kinases （MAPK）, has been well studied, molecular entities controlling quantitative regulation of these pathways during an immune response remain poorly defined. We identified Sam68 as a novel regulator of TLr-induced NF-κb and MAPK activation. We found that TLr2 and TLr3 are totally dependent, whereas TLr4 is only partially dependent on Sam68 to induce the activation of NF-Kb c-rel. Absence of Sam68 greatly decreased TLr2- and TLr3-induced NF-κb p65 activation, whereas TLr4- induced p65 activation in a Sam68-independent manner. In contrast, Sam68 appeared to be a negative regulator of MAPK pathways because absence of Sam68 enhanced TLr2-induced activation of extracellular signal-regulated kinases （ErK） and c-Jun N-terminal kinases （JNK）. Interestingly, TLr2- and TLr3-induced gene expression showed a differential requirement of Sam68. Absence of Sam68 impaired TLr2-induced gene expression, suggesting that Sam68 has a critical role in myeloid differentiation primary response gene 88-dependent TLr2 signaling. TLr3-induced gene expression that utilize Toll/Interleukin-1 receptor-domain-containing adapter-inducing beta interferon pathway, depend only partially on Sam68. Our findings suggest that Sam68 may function as an immune rheostat that balances the activation of NF-κb p65 and c-rel, as well as MAPK, revealing a potential novel target to manipulate TLr signaling.

关键词： innate immunity MAP kinase NF-kappab Sam68 TLr

This work was supported by the European research Council Advanced Grant(ETAP-742985 to *** J.F.)and by the Ministry of Science and Technology(grant 110-2636-b-005-001 to K.-J.L.).

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Plant Communications 2024年第1期5卷 130-147页

作者： Yu Zhang Yuan Fu Wenfei Xian Xiuli Li Yong Feng Fengjiao bu Yan Shi Shiyu Chen robin van Velzen Kai battenberg Alison M.berry Marco G.Salgado Hui Liu Tingshuang Yi Pascale Fournier Nicole Alloisio Petar Pujic Hasna boubakri M.Eric Schranz Pierre-Marc Delaux Gane Ka-Shu Wong Valerie Hocher Sergio Svistoonoff Hassen Gherbi Ertao Wang Wouter Kohlen Luis G.Wall Martin Parniske Katharina Pawlowski Philippe Normand jeffrey J.Doyle Shifeng Cheng Shenzhen branch Guangdong Laboratory for Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518124China biosystematics Group Department of Plant SciencesWageningen University6708PB Wageningenthe Netherlands Department of Plant Sciences University of CaliforniaDavisDavisCA 95616USA Department of Ecology Environment and Plant SciencesStockholm University10691 StockholmSweden Germplasm bank of Wild Species Kunming Institute of BotanyChinese Academy of SciencesLanhei RoadKunming 650201China Universite´de Lyon Universite´Lyon 1CNRSUMR5557Ecologie MicrobienneINRAUMR 141843 bd du 11 novembre 191869622 VilleurbanneFrance Laboratoire de recherche en Sciences Ve´ge´tales(LrSV) Universite´de ToulouseCNRSUPS24 chemin de Borde RougeAuzevilleBP4261731326 Castanet TolosanFrance Department of biological Sciences University of AlbertaEdmontonAB T6G 2E9Canada French National research Institute for Sustainable Development(IrD) UMR LSTM(IRD/CIRAD/INRAe/Montpellier University/Supagro)-Campus International BaillarguetTA A-82/J34398 Montpellier Cedex 5France National Key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesInstitute of Plant Physiology and EcologySIBSChinese Academy of SciencesShanghaiChina Laboratory of Molecular biology Department of Plant SciencesWageningen University6708PB Wageningenthe Netherlands Laboratory of biochemistry Microbiology and Soil Biological InteractionsDepartment of Science and TechnologyNational University of QuilmesCONICETBernalArgentina Faculty of biology GeneticsLMU MunichGroßhaderner Strasse 2-482152 MartinsriedGermany School of Integrative Plant Science Sections of Plant Biology and Plant Breeding&GeneticsCornell UniversityIthacaNY 14853USA State Key Laboratory of Systematic and Evolutionary botany Institute of BotanyChinese Academy of SciencesBeijing 100093China Univer

Plant root-nodule symbiosis(rNS)with mutualistic nitrogen-fixing bacteria is restricted to a single clade of angiosperms,the Nitrogen-Fixing Nodulation Clade(NFNC),and is best understood in the legume *** species share many commonalities,explained either by divergence from a common ancestor over 100 million years ago or by convergence following independent origins over that same time ***,comparative analyses of diverse nodulation syndromes can provide insights into constraints on nodulation—what must be acquired or cannot be lost for a functional symbiosis—and the latitude for Plant Communications Genomic landscape of nodulation variation in the ***,much remains to be learned about nodulation,especially outside of ***,we employed a large-scale phylogenomic analysis across 88 species,complemented by 151 rNA-seq libraries,to elucidate the evolution of *** phylogenomic analyses further emphasize the uniqueness of the transcription factor NIN as a master regulator of nodulation and identify key muta-tions that affect its function across the *** transcriptomic assessment revealed nodule-specific upregulated genes across diverse nodulating plants,while also identifying nodule-specific and nitrogen-response *** 70%of symbiosis-related genes are highly conserved in the four representative species,whereas defense-related and host-range restriction genes tend to be lineage *** study also identified over 900000 conserved non-coding elements(CNEs),over 300000 of which are unique to sampled NFNC ***-specific CNEs are enriched with the active H3K9ac mark and are correlated with accessible chromatin regions,thus representing a pool of candidate regula-tory elements for genes involved in ***,our results provide novel insights into the evolution of nodulation and lay a foundation for engineering of rNS traits in agriculturally important crops.

关键词： nitrogen-fixing root-nodule symbiosis two competing hypotheses phylogenomics phylotranscrip-tomics conserved non-coding elements convergence deep homology

refractive outcomes among glaucoma patients undergoing phacoemulsification cataract extraction with and without Kahook Dual blade goniotomy

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Eye and Vision 2019年第1期6卷 236-241页

作者： Erin G.Sieck Cara E.Capitena Young rebecca S.Epstein jeffrey r.SooHoo Mina b.Pantcheva Jennifer L.Patnaik Anne M.Lynch Malik Y.Kahook Leonard K.Seibold Department of Ophthalmology University of Colorado School of Medicine1675 Aurora Court F731AuroraCO 80045USA

background:Glaucoma patients undergoing phacoemulsification alone have a higher rate of refractive surprise compared to patients without *** risk is further increased with combined filtering ***,there are few and conflicting reports on the effect of combined phacoemulsification and micro-invasive glaucoma surgery(MIGS).Here,we look at refractive outcomes of glaucoma patients undergoing phacoemulsification with and without Kahook Dual blade(KDb)***:retrospective chart review of 385 glaucomatous eyes of 281 patients,which underwent either phacoemulsification alone(n=309)or phacoemulsification with KDb goniotomy(n=76,phaco-KDb)at the University of *** main outcome was refractive surprise defined as the difference in target and postoperative refraction spherical equivalent greater than±0.5 Diopter(D).results:refractive surprise greater than±0.5 D occurred in 26.3%of eyes in the phaco-KDb group and 36.2%in the phacoemulsification group(p=0.11).refractive surprise greater than±1.0 D occurred in 6.6%for the phacoKDb group and 9.7%for the phacoemulsification group(p=0.08).There was no significant difference in risk of refractive surprise when pre-operative IOP,axial length,keratometry or performance of KDb goniotomy were assessed in univariate ***:There was no difference between refractive outcomes of glaucomatous patients undergoing phacoemulsification with or without KDb goniotomy.

关键词： Kahook Dual blade goniotomy refractive surprise glaucoma cataract

美国麻醉患者安全发展史是否对中国麻醉有借鉴作用？

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中华麻醉学杂志 2017年第8期37卷 897-901页

作者： jeffrey b. Cooper 麻省总医院麻醉-危重症-疼痛科美国波士顿02129

麻醉学主要关注患者安全问题，无论在美国还是中国，麻醉医生都将“无一例患者受到麻醉伤害”作为奋力追求的终极目标。本文简要介绍了美国患者麻醉安全发展史及经验和思路，通过抛砖引玉，引发中国麻醉医生进一步思考和关注麻醉患者安... 详细信息

麻醉学主要关注患者安全问题，无论在美国还是中国，麻醉医生都将“无一例患者受到麻醉伤害”作为奋力追求的终极目标。本文简要介绍了美国患者麻醉安全发展史及经验和思路，通过抛砖引玉，引发中国麻醉医生进一步思考和关注麻醉患者安全问题，从而有益于患者围术期转归和麻醉学科发展。本文主要围绕5个方面展开述评：阐述美国麻醉学界如何深刻认识患者安全的重要性；介绍有利于麻醉患者安全的措施；介绍近期美国及其他地区有关麻醉患者安全的提议；列举加强围术期护理文化理念的其他措施；特别就每位麻醉医生如何直接提高患者安全给出了一些建议。

关键词：麻醉学安全管理