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Control of nuclear-cytoplasmic shuttling of Ankrd54 by PKCδ

World Journal of Biological Chemistry 2017年第3期8卷 163-174页

作者： amy l samuels Alison louw Reza Zareie Evan Ingley Cell Signalling Group Harry Perkins Institute of Medical Research and Centre for Medical Researchthe University of Western Australia Proteomics International laboratories ltd Proteowa Pty ltd SABCMurdoch University Cell Signalling Group School of Veterinary and Health SciencesMurdoch University

AIM To identify and characterize the effect of phosphorylation on the subcellular localization of *** HEK293 T cells were treated with calyculin A, staurosporin or phorbol 12-myristate 13-acetate(PMA). Cells were transfected with eG FP-tagged Ankrd54 with or without lyn tyrosine kinase(wild-type, Y397 F mutant, or Y508 F mutant). The subcellular localization was assessed by immunofluorescence imaging of cells, immunoblotting of subcellular fractionations. The phosphorylation of Ankrd54 was monitored using Phos-tagT M gel retardation. Phosphorylated peptides were analysed by multiplereaction-monitoring(MRM) proteomic *** Activation of PKC kinases using PMA promoted nuclear export of Ankrd54 and correlated with increased Ankrd54 phosphorylation, assayed using Phos-tag TM gel retardation. Co-expression of an active form of the PKCδisoform specifically promoted both phosphorylation and cytoplasmic localization of Ankrd54, while PKCδ, Akt and PKA did not. Alanine mutation of several serine residues in the amino-terminal region of Ankrd54(Ser14, Ser17, Ser18, Ser19) reduced both PMA induced cytoplasmic localization and phosphorylation of Ankrd54. Using MRM proteomic analysis, phosphorylation of the Ser18 residue of Ankrd54 was readily detectable in response to PMA stimulation. PMA stimulation of cells co-expressing Ankrd54 and lyn tyrosine kinase displayed increased coimmunoprecipitation and enhanced co-localization in the *** We identify phosphorylation by PKCδ as a major regulator of nuclear-cytoplasmic shuttling of Ankrd54, and its interaction with the tyrosine kinase lyn.

关键词： Ankrd54 PKC lyn Btk Phosphorylation

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Examining the effects of voluntary avoidance behaviour and policy-mediated behaviour change on the dynamics of SARS-CoV-2:A mathematical model

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Infectious Disease Modelling 2024年第3期9卷 701-712页

作者： Gabrielle Brankston David N.Fisman Zvonimir Poljak Ashleigh R.Tuite amy l.Greer Department of Population Medicine University of GuelphCanada Dalla lana School of Public Health University of TorontoCanada Centre for Immunization Readiness Public Health Agency of CanadaOttawaOntarioCanada

Background Throughout the SARS-CoV-2 pandemic,policymakers have had to navigate between recommending voluntary behaviour change and policy-driven behaviour change to mitigate the impact of the *** individuals will voluntarily engage in self-protective behaviour when there is an increasing infectious disease risk,the extent to which this occurs and its impact on an epidemic is not *** This paper describes a deterministic disease transmission model exploring the impact of individual avoidance behaviour and policy-mediated avoidance behaviour on epidemic outcomes during the second wave of SARS-CoV-2 infections in Ontario,Canada(September 1,2020 to February 28,2021).The model incorporates an information feedback function based on empirically derived behaviour data describing the degree to which avoidance behaviour changed in response to the number of new daily cases *** Voluntary avoidance behaviour alone was estimated to reduce the final attack rate by 23.1%,the total number of hospitalizations by 26.2%,and cumulative deaths by 27.5%over 6 months compared to a counterfactual scenario in which there were no interventions or avoidance behaviour.A provincial shutdown order issued on December 26,2020 was estimated to reduce the final attack rate by 66.7%,the total number of hospitalizations by 66.8%,and the total number of deaths by 67.2%compared to the counterfactual *** Given the dynamics of SARS-CoV-2 in a pre-vaccine era,individual avoidance behaviour in the absence of government action would have resulted in a moderate reduction in disease however,it would not have been sufficient to entirely mitigate transmission and the associated risk to the population in *** action during the second wave of the COVID-19 pandemic in Ontario reduced infections,protected hospital capacity,and saved lives.

关键词： Mathematical modelling COVID-19 SARS-CoV-2 Human behaviour

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The HIF-1α/PlOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang amy l.Strong Yuxiao Sun lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard Juhoon lee Sowmya Ramesh Aaron W.James David Hudson Kevin N.Dalby lin Xu Robert J.Tower Benjamin levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PlOD2/lOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-lOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PlOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PlOD2/lOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PlOD2/lOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

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Dairy cows inoculated with highly pathogenic avian influenza virus H5N1

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四川生理科学杂志 2024年第10期46卷 2275-2275页

作者： amy l Baker Virus and Prion Research Unit National Animal Disease Center Agricultural Research Service United States Department of Agriculture Ames Iowa USA National Veterinary Services laboratories Animal and Plant Health Inspection Service United States Department of Agriculture Ames Iowa USA Veterinary Diagnostic and Production Animal Medicine Iowa State University Ames Iowa USA

Highly pathogenic avian influenza(HPAI)H5N1 hemagglutinin clade 2.***.4.4b was detected in the United States in *** HPAI viruses caused mortality events in poultry,wild birds,and wild *** March 25,2024,HPAI H5N1 clade 2.***.4.4b was confirmed in a dairy cow in Texas in response to a multi-state investigation into milk production losses.1 Over 200 positive herds were identified in 14 *** case description included reduced feed intake and rumen motility in lactating cows,decreased milk production,and thick yellow milk.2,3 The diagnostic investigation revealed viral RNA in milk and mammary tissue with alveolar epithelial degeneration and necrosis and positive immunoreactivity of glandular epithelium.A single transmission event,likely from birds,was followed by limited local transmission and onward horizontal transmission of H5N1 clade 2.***.4.4b genotype B3.13.4 We sought to experimentally reproduce infection with genotype B3.13 in Holstein yearling heifers and lactating *** were inoculated by aerosol respiratory route and cows by intramammary *** disease was mild in heifers,but infection was confirmed by virus detection,lesions,and *** disease in lactating cows included decreased rumen motility,changes to milk appearance,and production *** was confirmed by high levels of viral RNA detected in milk,virus isolation,lesions in mammary tissue,and *** study provides the foundation to investigate additional routes of infection,pathogenesis,transmission,and intervention strategies.

关键词： H5N1 cows fir

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Storylines of family medicine Ⅳ:perspectives on practice—lenses of appreciation

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Family Medicine and Community Health 2024年第S3期12卷 33-42页

作者： William B Ventres leslie A Stone Radeeb Akhtar Jeffrey M Ring lucy M Candib Erick Messias Ronald M Epstein Marc Tunzi amy l lee Christopher P Morley Carina M Brown David Slawson Jill Konkin David G Campbell Ian Couper Susan Williams Robert Brooks lucie Walters Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family Medicine and Community Health Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA Independent Health Psychologist Los AngelesCaliforniaUSA Family Medicine and Community Health UMass Chan Medical SchoolWorcesterMassachusettsUSA Psychiatry and Behavioral Neurosciences Saint Louis University School of MedicineSaint LouisMissouriUSA Family Medicine University of Rochester Medical CenterRochesterNew YorkUSA Family Medicine Residency Program Natividad Medical CenterSalinasCaliforniaUSA Family Medicine Tufts University School of MedicineBostonMassachusettsUSA Public Health and Preventive Medicine SUNY Upstate Medical UniversitySyracuseNew YorkUSA Cone Health Family Medicine Residency The University of North Carolina School of MedicineGreensboroNorth CarolinaUSA Family Medicine Atrium HealthCharlotteNorth CarolinaUSA Family Medicine University of Alberta Faculty of Medicine&DentistryEdmontonAlbertaCanada Cunninghame Arm Medical Centre Australian College of Rural and Remote MedicineLakes EntranceQueenslandAustralia Ukwanda Centre for Rural Health Stellenbosch University Faculty of Medicine and Health SciencesCape TownWestern CapeSouth Africa Adelaide Rural Clinical School The University of AdelaideAdelaideSouth AustraliaAustralia Department of Rural Health Broken Hill UniversityBroken HillNew South WalesAustralia Adelaide Rural Clinical School The University of Adelaide Faculty of Health and Medical SciencesMount GambierSouth AustraliaAustralia

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅳ:perspectives on practice—lenses of appreciation’,authors address the following themes:‘Relational connections in the doctor–patient partnership’,‘Feminism and family medicine’,‘Positive family medicine’,‘Mindful practice’,‘The new,old ethics of family medicine’,‘Public health,prevention and populations’,‘Information mastery in family medicine’and‘Clinical courage.’May readers nurture their curiosity through these essays.

关键词： thematic illustration doctor

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Phylogeny and taxonomic revision of Thelonectria discophora(Ascomycota,Hypocreales,Nectriaceae)species complex

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Fungal Diversity 2015年第1期70卷 1-29页

作者： Catalina Salgado-Salazar amy Y.Rossman Gary J.samuels Yuuri Hirooka Romina M.Sanchez Priscila Chaverri Department of Plant Science and landscape Architecture University of Maryland2112 Plant Sciences BuildingCollege ParkMD 20742USA Systematic Mycology and Microbiology laboratory USDA-ARSBeltsvilleMD 20705USA Biodiversity(Mycology) Eastern Cereal and Oilseed Research CentreAgriculture and Agri-Food CanadaOttawaOntario K1A 0C6Canada Centro de Recursos Renovables de la Zona Semiarida-Cerzos Conicet Universidad Nacional del SurCamino La Carrindanga Km7B8000FWB Bahía BlancaProvincia de Buenos AiresArgentina Escuela de Biología Universidad de Costa RicaApartado11501-2060 San PedroSan JoséCosta Rica

Specimens regarded as Thelonectria discophora(Thelonectria,Nectriaceae,Hypocreales)constitute a conspicuous group of saprobic fungi on decaying plant material,characterized by red perithecia each with a broad mammiform(nipple-like)*** asexual state is characterized by a cylindrocarpon-like morphology,with 3–5 septate macroconidia,unicellular microconidia and chlamydospores that are rarely produced in *** the past,*** was regarded as one species with a wide geographic ***,a recent study rejected the monophyly and cosmopolitan distribution of this species,and showed the existence of at least 16 cryptic species distributed in three main *** combining the results of phylogenetic analyses of six nuclear loci and morphological studies,we revised the taxonomy of the *** species complex,resulting in the description of 12 new species and four new combinations based on historic *** though molecular phylogenetic analyses strongly support the segregation of these species,and are in agreement with previous studies,individual diagnostic morphological characters for each species could not be ***,discrete morphological traits corresponding to each of the three main groups of species were *** could be differentiated based on the average values of morphological traits as well as the presence/absence of characteristic asexual propagules and colony growth at ***,illustrations are provided for the recognized species.

关键词： New species Rubus canker Species concept Taxonomy

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Perioperative use of immunosuppressive medications in patients with Crohn’s disease in the new"biological era"

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Gastroenterology Report 2017年第3期5卷 165-177,I0001页

作者： amy l.lightner Bo Shen Division of Colon and Rectal Surgery Mayo ClinicRochesterMinnesotaMNUSA Center for Inflammatory Bowel Diseases Digestive Disease and Surgery Institutethe Cleveland Clinic FoundationClevelandOHUSA

Crohn’s disease(CD)is characterized by transmural inflammation of the gastrointestinal tract leading to inflammatory,stricturing and/or and fistulizing *** a patient develops medically refractory disease,mechanical obstruction,fistulizing disease or perforation,surgery is ***,surgery is not curative in most cases,underscoring the importance of bowel preservation and adequate perioperative medical *** many of the medications used to treat CD are immunosuppressive,the concern for postoperative infectious complications and anastomotic healing are particularly concerning;these concerns have to be balanced with preventing and treating residual or recurrent *** herein review the available literature and make recommendations regarding the preoperative,perioperative and postoperative administration of immunosuppressive medications in the current era of biological therapy for *** algorithms for perioperative medical management would greatly assist future research for optimizing surgical outcomes and preventing disease recurrence in the future.

关键词： Crohn’s disease biological therapy perioperative period medical management

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The ascent of immune checkpoint inhibitors： is the understudy ready for a leading role？

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Cancer Biology & Medicine 2017年第4期14卷 341-347页

作者： amy l. Cummings Edward B. Garon Department of Hematology and Oncology David Geffen School of Medicine at the University of California Los Angeles 90095 USA

The recent approval of pembrolizumab as second-line treatment for any solid tumor with high-level microsatellite instability or mismatch repair deficiency agnostic of tissue and origin1 has shattered a glass ceiling for immune checkpoint *** longer bound to a specific cancer diagnosis but rather a biomarker,pembrolizumab has heightened a burgeoning optimism towards the drug *** how these agents should carve out additional

关键词： PD The ascent of immune checkpoint inhibitors:is the understudy ready for a leading role PFS OS ORR IHC

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Variation in floral form of CRISPR knock-outs of the poplar homologs of lEAFY and AGAMOUS after FT heat-induced early flowering

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Horticulture Research 2023年第8期10卷 183-193页

作者： amy l.Klocko Estefania Elorriaga Cathleen Ma Steven H.Strauss Department of Biology University of Colorado Colorado SpringsColorado SpringsCO 80918USA Department of Forest Ecosystems and Society Oregon State UniversityCorvallisOR 97331USA

Plant migration and gene flow from genetically modified or exotic trees to nearby lands or by crossing with wild relatives is a major public and regulatory *** genetic strategies exist to mitigate potential gene flow;however,the long delay in onset of flow-ering is a severe constraint to research *** used heat-induced FT overexpression to speed assessment of the expected floral phenotypes after CRISPR knockout of poplar homologs of the key floral genes,lEAFY and *** selected events with previously characterized CRISPR-Cas9 induced biallelic changes then re-transformed them with the Arabidopsis thaliana FlOWERING lOCUS T(AtFT)gene under control of either a strong constitutive promoter or a heat-inducible *** successfully obtained flowering in both a male and female clone of poplar,observing a wide range of inflorescence and floral forms among flowers,ramets,and insertion ***,flowers obtained from the selected lFY and AG targeted events were consistent with what would be predicted for loss-of-function of these ***-targeted events showed small catkins with leaf-like organs,AG-targeted events had nested floral organs consistent with reduction in floral determinacy and absence of well-formed carpels or *** findings demonstrate the great developmental plasticity of Populus flowers during genetically accelerated flowering,which may be of horticultural *** also provide an informative early view of floral phenotypes and apparent sterility from knockouts of both these gene targets.

关键词： AGAMOUS flowers organs

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Preparation on the basis of Trichoderma asperellum in the system of biological protection of wheat from Fusarium ear scab

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浙江大学学报（农业与生命科学版） 2004年第4期30卷 394-395页

作者： Kolombet l V Sokolov M S Chuprina V P Schisler D A samuels G J State Research Center for Applied Microbiology Obolensk Moscow Region RussiaResearch Center of Toxicology and Hygienic Regulation of Biological Products Serpukhov RussiaAll-Russia Research Institute of Biological Plant Disease Control Krasnodar Russia USDA-ARS NCAUR Peoria Illinois USA USDA-ARS Systematic Botany and Mycology Lab. Beltsville USA

During the last century, as the area of wheat grown under advanced grain husbandry has increased worldwide, so too has the importance of Fusarium ear scab (FES) (synonym, Fusarium head blight) caused by several species of the fungus Fusarium. Yield losses due to FES can total 20%-40% and more depending on climatic conditions. During the last twenty years epidemics of FES in cereals have become chronic all over the world, including the United States and Russia. The most destructive of these were observed in 1982, 1986, 1990-1996 in USA and in the south of Russia in 1982, 1984, 1988, 1992. The harmful effect of FES is manifested not only in reduced grain yields, but also in the contamination of grains and grain products with mycotoxins, such as deoxynivalenol (DON) and its derivatives (3-alfa acetyl-DON, 15-alfa acetyl-DON), T-2 toxin and zearalenone. Standard means to control FES (cultural control methodologies, chemical pesticides, and FES resistant varieties) have little effect or are not practical and rarely reduce the accumulation of mycotoxins in grain. We have developed a new technique to reduce FES using biological preparations. The technique utilizes wheat seed pretreatment with a biofungicide “Mycol” in combination with spraying wheat plants during flowering with a yeast preparation. Technology for production of Mycol on the basis of Trichoderma asperellum strain GJS 03-35 (systematics by samuels) has been developed. This strain shows hyperparasitic activity against a wide spectrum of plant pathogens, including Fusarium graminearum, a causative agent of FES in wheat. Experiments conducted in the United States demonstrated that spraying wheat plants during flowering with the patented yeast Cryptococcus nodaensis OH 182.9 (NRRl Y-30216) reliably reduces FES development. Tests of the Mycol preparation and the yeast OH 182.9 (EOD) have been performed on the spring wheat “Ivolga” in greenhouse conditions (the Moscow region) and on the winter wheat “Kupava” in fie

关键词：曲霉素木霉素镰刀霉穗痂病小麦生物防治

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