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Tailoring minimalist self-assembling peptides for localized viral vector aene deliverv

作者： D.R.·安德森 david R.·anderson

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Nano Research 2016年第3期9卷 674-684页

作者： Alexandra L. Rodriguez Ting-Yi Wang Kiara f. Bruggeman Rui Li Richard J. Williams Clare L. Parish david R. Nisbet Research School of Engineering The Australian National University Canberra ACT2601 Australia florey Institute ofNeuroscience & Men tal Health The University of Melbourne Parkville VIC 3010 Australia Cen tre for Chemistry and Biotechnology Deakin University Waurn Ponds VIC 3217 Australia School of Aerospace Mechanical and Manufacturing Engineering and the Health Innovations Research Institute RMIT University Melbourne VIC 300 I Australia

Viral vector gene delivery is a promising technique for the therapeutic administra- tion of proteins to damaged tissue for the improvement of regeneration outcomes in various disease settings including brain and spinal cord injury, as well as autoimmune diseases. Though promising results have been demonstrated, limitations of viral vectors, including spread of the virus to distant sites, neutralization by the host immune system, and low transduction efficiencies have stimulated the investigation of biomaterials as gene delivery vehicles for improved protein expression at an injury site. Here, we show how N- fluorenylmethyloxycarbonyl （fmoc） self-assembling peptide （SAP） hydrogels, designed for tissue-specific central nervous system （CNS） applications via incorporation of the laminin peptide sequence isoleucine-lysine-valine-alanine- valine （IKVAV）, are effective as biocompatible, localized viral vector gene delivery vehicles in vivo. Through the addition of a C-terminal lysine （K） residue, we show that increased electrostatic interactions, provided by the additional amine side chain, allow effective immobilization of lentiviral vector particles, thereby limiting their activity exclusively to the site of injection and enabling focal gene delivery in vivo in a tissue-specific manner. When the C-terminal lysine was absent, no difference was observed between the number of transfected cells, the volume of tissue transfected, or the transfection efficiency with and without the fmoc-SAP. Importantly, immobilization of the virus only affected transfection cell number and volume, with no impact observed on transfection efficiency. This hydrogel allows the sustained and targeted delivery of growth factors post injury. We have established fmoc-SAPs as a versatile platform for enhanced biomaterial design for a range of tissue engineering applications.

关键词： viral vectors gene therapy self-assembling peptides biomaterials

Statistics for Business and Economics, Tenth Edition 10th ed.

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Scientific evidence is just the starting point: A generalizable process for developing sports injury prevention interventions

2008年

作者： david R. anderson Dennis J. Sweeney Thomas A. Williams

Includes bibliographical references and index.

ISBN: (纸本)9780324365054

Includes bibliographical references and index.

关键词： Commercial statistics Economics Statistics.

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Journal of Sport and Health Science 2016年第3期5卷 334-341页

作者： Alex Donaldson david G.Lloyd Belinda J.Gabbe Jill Cook Warren Young Peta White Caroline f.finch Australian Centre for Research into Injury in Sport and its Prevention (ACRISP) Federation University Australia Centre for Musculoskeletal Research Griffith Health Institute Griffith University Department of Epidemiology and Preventive Medicine Monash University La Trobe Sport and Exercise Medicine Research Centre La Trobe University School of Health Sciences Federation University Australia

Background: The 2 most cited sports injury prevention research frameworks incorporate intervention development, yet little guidance is available in the sports science literature on how to undertake this complex process. This paper presents a generalizable process for developing implementable sports injury prevention interventions, including a case study applying the process to develop a lower limb injury prevention exercise training program(footy first) for community Australian ***: The intervention development process is underpinned by 2 complementary premises:(1) that evidence-based practice integrates the best available scientific evidence with practitioner expertise and end user values and(2) that research evidence alone is insufficient to develop implementable ***: The generalizable 6-step intervention development process involves(1) compiling research evidence, clinical experience, and knowledge of the implementation context;(2) consulting with experts;(3) engaging with end users;(4) testing the intervention;(5) using theory; and(6)obtaining feedback from early implementers. following each step, intervention content and presentation should be revised to ensure that the final intervention includes evidence-informed content that is likely to be adopted, properly implemented, and sustained over time by the targeted intervention deliverers. for footy first, this process involved establishing a multidisciplinary intervention development group, conducting 2targeted literature reviews, undertaking an online expert consensus process, conducting focus groups with program end users, testing the program multiple times in different contexts, and obtaining feedback from early implementers of the ***: This systematic yet pragmatic and iterative intervention development process is potentially applicable to any injury prevention topic across all sports settings and levels. It will guide researchers wishing to undertake interventio

关键词： Australian football Implementation Intervention development Lower limb injuries Research-to-practice Sports injury prevention Translation

Phylogenetically Distinct Cellulose Synthase Genes Support Secondary Wall Thickening in Arabidopsis Shoot Trichomes and Cotton fiber

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Journal of Integrative Plant Biology 2010年第2期52卷 205-220页

作者： Lissete Betancur Bir Singh Ryan A.Rapp Jonathan f.Wendel M. david Marks Alison W.Roberts Candace H.Haigler Department of Plant Biology North Carolina State University Department of Crop Science North Carolina State University EEOB Department Iowa State University Department of Plant Biology University of Minnesota Department of Biological Sciences CBLSUniversity of Rhode Island

Through exploring potential analogies between cotton seed trichomes （or cotton fiber） and arabidopsis shoot trichomes we discovered that CesAs from either the primary or secondary wall phylogenetic clades can support secondary wall thickening. CesA genes that typically support primary wall synthesis, AtCesA 1,2,3,5, and 6, underpin expansion and secondary wall thickening of arabidopsis shoot trichomes. In contrast, apparent orthologs of CesA genes that support secondary wall synthesis in arabidopsis xylem, AtCesA4,7, and 8, are up-regulated for cotton fiber secondary wall deposition. These conclusions arose from：（a） analyzing the expression of CesA genes in arabidopsis shoot trichomes; （b） observing birefringent secondary walls in arabidopsis shoot trichomes with mutations in AtCesA4, 7, or 8; （c） assaying up-regulated genes during different stages of cotton fiber development; and （d） comparing genes that were *** with primary or secondary wall CesAs in arabidopsis with genes up- regulated in arabidopsis trichomes, arabidopsis secondary xylem, or cotton fiber during primary or secondary wall deposition. Cumulatively, the data show that：（a） the xylem of arabidopsis provides the best model for secondary wall cellulose synthesis in cotton fiber; and （b） CesA genes within a ＂cell wall toolbox＂ are used in diverse ways for the construction of particular specialized cell walls.

关键词： Phylogenetically Distinct Cellulose Synthase Genes Support Secondary Wall Thickening in Arabidopsis Shoot Trichomes and Cotton fiber GUS

A gain-of-function mutation in Msl10 triggers cell death and wound-induced hyperaccumulation of jasmonic acid in Arabidopsis

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Journal of Integrative Plant Biology 2016年第6期58卷 600-609页

作者： Yan Zou Satya Chintamanani Ping He Hirotada fukushige Liping Yu Meiyu Shao Lihuang Zhu david f.Hildebrand Xiaoyan Tang Jian-Min Zhou School of Life Science and Technology Shanghai Tech University Syngenta Biotechnology Inc.Slater Department of Biochemistry and Biophysics Institute for Plant Genomics and Biotechnology Texas A&M University Department of Agronomy Agricultural Sciences Center-Noth University of Kentucky State Key Laboratory of Plant Genomics Institute of Genetics and Developmental Biology Chinese Academy of Sciences School of Life Sciences Capital Normal University

Jasmonates（JAs） are rapidly induced after wounding and act as key regulators for wound induced signaling pathway. However, what perceives the wound signal and how that triggers JA biosynthesis remains poorly understood. To identify components involved in Arabidopsis wound and JA signaling pathway, we screened for mutants with abnormal expression of a luciferase reporter, which is under the control of a wound-responsive promoter of an ethylene response factor（ERf） transcription factor gene, RAP2.6（Related to APetala 2.6）.The rea1（RAP2.6 expresser in shoot apex） mutant constitutively expressed the RAP2.6-LUC reporter gene in young *** with the typical JA phenotypes including shorter petioles,loss of apical dominance, accumulation of anthocyanin pigments and constitutive expression of JA response gene, rea1 plants also displayed cell death and accumulated high levels of JA in response to wounding. The phenotype of rea1 mutant is caused by a gain-of-function mutation in the C-terminus of a mechanosensitive ion channel MscS-like 10（MSL10）. MSL10 is localized in the plasma membrane and is expressed predominantly in root tip, shoot apex and vascular tissues. These results suggest that MSL10 is involved in the wound-triggered early signal transduction pathway and possibly in regulating the positive feedback synthesis of JA.

关键词： Arabidopsis cell death jasmonates mechanosensitive ion channel wound

Application of light sheet microscopy for qualitative and quantitative analysis of bronchus-associated lymphoid tissue in mice

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Cellular & Molecular Immunology 2018年第10期15卷 875-887页

作者： david Twapokera Mzinza Henrike fleige Kristin Laarmann Stefanie Willenzon Jasmin Ristenpart Julia Spanier Gerd Sutter Ulrich Kalinke Peter Valentin-Weigand Reinhold förster Institute of Immunology Hannover Medical SchoolHannoverGermany Institute for Microbiology University of Veterinary Medicine HannoverHannoverGermany Institute for Experimental Infection Research TWINCORECentre for Experimental and Clinical Infection Researcha joint venture between the Helmholtz-Centre for Infection Research and the Hannover Medical SchoolHannoverGermany Institute for Infectious Diseases and Zoonoses University of Munich LMUMunichGermany

Bronchus-associated lymphoid tissue(BALT)develops at unpredictable locations around lung bronchi following pulmonary *** formation and composition of BALT have primarily been investigated by immunohistology that,due to the size of the invested organ,is usually restricted to a limited number of histological *** assess the entire BALT of the lung,other approaches are urgently ***,we introduce a novel light sheet microscopy-based approach for assessing lymphoid tissue in the *** antibody staining of whole lung lobes and optical clearing by organic solvents,we present a method that allows in-depth visualization of the entire bronchial tree,the lymphatic vasculature and the immune cell composition of the induced ***,three-dimensional analysis of the entire lung allows the qualitative and quantitative enumeration of the induced *** this approach,we show that a single intranasal application of the replication-deficient poxvirus MVA induces BALT that constitutes up to 8%of the entire lung volume in mice deficient in CCR7,in contrast to wild type mice(WT).furthermore,BALT induced by heat-inactivated *** is dominated by a pronounced T cell infiltration in Cxcr5-deficient mice,in contrast to WT mice.

关键词： Lung BALT light sheet microscopy E.coli MVA

Hypolipidemic and anti-atherosclerogenic effects of aqueous extract of Ipomoea batatas leaves in diet-induced hypercholesterolemic rats

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Journal of Integrative Medicine 2021年第3期19卷 243-250页

作者： fidele Ntchapda fernand C.Tchatchouang david Miaffo Barthelemy Maidadi Lorella Vecchio Rodrigue E.Talla Christian Bonabe Paul f.Seke Etet Theophile Dimo Department of Biological Sciences University of NgaoundereNgaoundereAdamawa RegionCameroon Department of Life and Earth Sciences Higher Teachers’Training CollegeUniversity of MarouaExtreme North RegionCameroon Center for Sustainable Health and Development GarouaNorth RegionCameroon Department of Physiological Sciences and Biochemistry Faculty of Medicine and Biomedical SciencesUniversity of NgaoundereGarouaNorth RegionCameroon Department of Animal Biology and Physiology University of Yaoundé1YaoundeCentre RegionCameroon

Objective:Ipomoea batatas(L.)*** a food plant used in African traditional medicine to treat cardiovascular diseases and related *** assessed the hypolipidemic and anti-atherosclerogenic properties of the aqueous extract of *** leaves in a rat model of diet-induced ***:Hypercholesterolemia was induced in male Wistar rats by exclusive feeding with a cholesterolenriched(1%)standard diet for four ***,rats were treated once daily(per os)with *** extract at doses of 400,500 and 600 mg/kg or with atorvastatin(2 mg/kg),for four *** treatment,animals were observed for another four weeks and then *** were excised and processed for histopathological studies,and blood glucose level and lipid profile were ***:Hypercholesterolemic animals experienced a 21.5%faster increase in body weight,significant increases in blood glucose and blood lipids(148.94%triglycerides,196.97%high-density lipoprotein cholesterol,773.04%low-density lipoprotein cholesterol,148.93%very low-density lipoprotein cholesterol and 210.42%total cholesterol),and increases in aorta thickness and atherosclerotic plaque sizes compared to rats fed standard *** of hypercholesterolemic rats with the extract mitigated these alterations and restored blood glucose and blood lipid levels to normocholesterolemic ***:Our findings suggest that *** leaves have hypolipidemic and anti-atherosclerogenic properties and justify their use in traditional medicine.

关键词： Hypercholesterolemic rat Ipomoea batatas Atherosclerotic plaques High-density lipoprotein cholesterol Low-density lipoprotein cholesterol Very low-density lipoprotein cholesterol

Cardiorespiratory fitness,white blood cell count,and mortality in men and women

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Journal of Sport and Health Science 2022年第5期11卷 605-612页

作者： Stephen W.farrell david Leonard Kerem Shuval Laura f.Defina Carolyn E.Barlow Andjelka Pavlovic William L.Haskell Research Division The Cooper InstituteDallasTX 75230USA Department of Medicine Stanford UniversityPalo AltoCA 94305USA

Background:We examined the associations of cardiorespiratory fitness(CRf) and white blood cell count(WBC) with mortality ***: A total of 52,056 apparently healthy adults completed a comprehensive health examination,including a maximal treadmill test and blood chemistry *** was categorized as high,moderate,or low by age and sex;WBC was categorized as sex-specific ***:During 17.8± 9.5 years(mean± SD) of follow-up,a total of 4088 deaths *** regressed jointly,significantly decreased allcause mortality across CRf categories was observed within each quartile of WBC in *** WBC Quartile 1,all-cause mortality hazard ratios(HRs) with a 95% confidence interval(95%CI) were 1.0(referent),1.29(95%CI:1.06-1.57),and 2.03(95%CI:1.42-2.92) for high,moderate,and low CRf categories,respectively(p for trend f cardiovascular disease(CVD) mortality within Quartile 1(p for trend=0.743),there were also similar trends across CRf categories within WBC quartiles in men for both CVD and cancer mortality(p for trend for all).for women,there were no significant trends across CRf categories for mortality outcomes within Quartiles ***,we observed significantly decreased all-cause mortality across CRf categories within WBC Quartile 4(HR=1.05(95%CI:0.76-1.44),HR=1.63(95%CI:1.20-2.21),and HR=1.87(95%CI:1.29-2.69) for high,moderate,and low CRf,respectively(p for trend=0.002)).Similar trends in women were observed for CVD and cancer mortality within WBC Quartile 4 ***:There are strong joint associations between CRf,WBC,and all-cause,CVD,and cancer mortality in men;these associations are less consistent in women.

关键词： Complete blood count Epidemiology Inflammation Physical fitness

High-throughput quantification of microbial birth and death dynamics using fluorescence microscopy

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frontiers of Electrical and Electronic Engineering in China 2019年第1期7卷 69-81页

作者： Samuel f. M. Hart david Skelding Adam J. Waite Justin C. Burton Wenying Shou fred Hutchinson Cancer Research Center SeattleWA 98109USA

Background: Microbes live in dynamic environments where nutrient concentrations fluctuate. Quantifying fitness in terms of birth rate and death rate in a wide range of environments is critical for understanding microbial evolution and ecology. Methods^ Here, using high-throughput time-lapse microscopy, we have quantified how Saccharomyces cerevisiae mutants incapable of synthesizing an essential metabolite (auxotrophs) grow or die in various concentrations of the required metabolite. We establish that cells normally expressing fluorescent proteins lose fluorescence upon death and that the total fluorescence in an imaging frame is proportional to the number of live cells even when cells form multiple layers. We validate our microscopy approach of measuring birth and death rates using flow cytometry, cell counting, and chemostat culturing. Results: for lysine-requiring cells, very low concentrations of lysine are not detectably consumed and do not support cell birth, but delay the onset of death phase and reduce the death rate compared to no lysine. In contrast, in low hypoxanthine, hypoxanthine-requiring cells can produce new cells, yet also die faster than in the absence of hypoxanthine. for both strains, birth rates under various metabolite concentrations are better described by the sigmoidal-shaped Moser model than the well-known Monod model, while death rates can vary with metabolite concentration and time. Conclusions: Our work reveals how time-lapse microscopy can be used to discover non-intuitive microbial birth and death dynamics and to quantify growth rates in many environments.

关键词： Saccharomyces cerevisiae fluorescence microscopy microbial growth birth rate death rate