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The concept of.gene therapy f.r glaucoma:the dream that has not come true yet

2004年

作者： Jessica M. Utts robert f. heckard

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Neural Regeneration Research 2024年第1期19卷 92-99页

作者： robert Sulak Xiaonan Liu Adrian Smedowski Department of.Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland Institute of.Biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland GlaucoTech Co. KatowicePoland

Gene therapies,despite of.being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in *** glaucoma is not considered a single gene disease,the identif.ed goals of.gene therapy would be rather to provide neuroprotection of.retinal ganglion cells,especially,in intraocular-pressure-independent *** most commonly reported type of.vector f.r gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of.optic neuropathy,like DBA/2J mice model of.high-tension glaucoma and the optic nerve *** gene therapy-based neuroprotection of.retinal ganglion cells is targeting specif.c genes translating to growth f.ctors(i.e.,brain derived neurotrophic f.ctor,and its receptor TrkB),regulation of.apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,f.S system,nicotinamide mononucleotide adenylyl transf.rase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of.neuroinf.ammation(i.e.,e rythropoietin),reduction of.excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf.).On the other hand,some of.gene therapy studies f.cus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outf.ow f.cility(i.e.,COX2,prostaglandin f.a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of.this review is to summarize the current stateof.art and the direction of.development of.gene therapy strategies f.r glaucomatous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glaucoma IOP lowering IOP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells

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Actuating droplets with electrowetting: f.rce and dynamics

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Droplet 2024年第2期3卷 113-124页

作者： robert Hennig Vito Cacucciolo Herbert Shea Sof. Transducers Laboratory(LMTS) Ecole Polytechnique Fédérale de Lausanne(EPFL)NeuchatelSwitzerland Politecnico di Bari BariItaly

Electrowetting on dielectric(EWOD)allows rapid movement of.liquid droplets on a smooth surf.ce,with applications ranging f.om lab-on-chip devices to *** in-plane f.rce on a droplet is a key indicator of.EWOD *** f.rce has been extensively modeled but f.w direct experimental measurements are *** study the EWOD f.rce on a droplet using two setups that allow,f.r the f.rst time,the simultaneous measurement of.f.rce and contact angle,while imaging the droplet shape at 6000 f.ames/*** several liquids and surf.ces,we observe that the f.rce saturates at a voltage of.approximately 150 *** of.voltages of.up 2 kV,that is,10 times higher than is typical,does not signif.cantly increase f.rces beyond the saturation ***,we observe that the transient dynamics,localized at the f.ont contact line,do not show saturation with *** the higher voltages,the initial f.ont contact line speed continues to increase,the f.ont contact angle temporarily becomes near zero,creating a thin liquid f.lm,and capillary waves f.rm at the liquid–air *** the localized EWOD f.rces at the contact line exceed the capillary f.rces,projectile droplets *** surf.ce tension allows f.r higher droplet f.rces,which we demonstrate with mercury.

关键词： capillary f.rces dynamics

121份澳大利亚小麦材料抗条锈病鉴定及分子检测

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植物病理学报 2024年

作者：黄洁杨金叶 Davinder Singh Peng Zhang robert f.Park 王保通李强西北农林科技大学植物保护学院作物抗逆与高效生产全国重点实验室 Plant Breeding Institute The University of Sydney

条锈病是世界范围内小麦上的重要病害，培育和种植抗病品种是防治条锈病最经济有效的措施。为明确澳大利亚小麦材料的抗条锈病水平及所含抗条锈病基因，本研究利用8个澳大利亚小麦条锈菌流行小种对121份小麦材料进行了苗期抗性鉴定，同... 详细信息

条锈病是世界范围内小麦上的重要病害，培育和种植抗病品种是防治条锈病最经济有效的措施。为明确澳大利亚小麦材料的抗条锈病水平及所含抗条锈病基因，本研究利用8个澳大利亚小麦条锈菌流行小种对121份小麦材料进行了苗期抗性鉴定，同时应用小麦抗条锈病基因Yr5、Yr9 (1B/1R)、Yr10、Yr15、Yr17及Yr26的特异性分子标记进行了分子检测。结果表明，121份小麦材料中，21份(17.35%)对所有供试条锈菌小种均表现抗病，7份(5.79%)均表现感病，其他材料对一个或多个条锈菌小种表现抗病。分子检测结合抗病性鉴定结果显示，3份(2.48%)可能含有Yr5基因，15份(12.40%)可能含有Yr9,9份(7.44%%)可能含有Yr10,6份(4.96%)可能含有Yr17,19份(15.70%)可能含有Yr26，没有检测到Yr15基因。此外，其中13份材料同时检测到两个或两个以上的抗条锈病基因，还有19份材料可能含有其他已知或未知的抗条锈基因。本研究为121份澳大利亚小麦材料的合理利用和小麦抗病育种提供了科学依据。

关键词：小麦条锈病抗性鉴定抗病基因分子检测

Integrins and their potential roles in mammalian pregnancy

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Journal of.Animal Science and Biotechnology 2024年第1期15卷 1-19页

作者： Gregory A.Johnson robert C.Burghardt f.ller W.Bazer Heewon Seo Joe W.Cain Department of.Veterinary Integrative Biosciences School of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationTX 77843‑4459USA Department of.Animal Science College of Agriculture and Life SciencesTexas A&M UniversityCollege StationTX 77843‑2471USA

Integrins are a highly complex f.mily of.receptors that, when expressed on the surf.ce of.cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(ECM) interactions leading to assembly of.integrin adhesion complexes(IACs) that initiate many signaling f.nctions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, prolif.ration, survival, dif.erentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of.multicellularity, being essential f.r the association of.cells with their neighbors and surroundings, during embryonic development and many aspects of.cellular and molecular biology. Integrins have important roles in many aspects of.embryonic development, normal physiology, and disease processes with a multitude of.f.nctions discovered and elucidated f.r integrins that directly inf.uence many areas of.biology and medicine, including mammalian pregnancy, in particular implantation of.the blastocyst to the uterine wall, subsequent placentation and conceptus(embryo/f.tus and associated placental membranes) development. This review provides a succinct overview of.integrin structure, ligand binding, and signaling f.llowed with a concise overview of.embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example f.r rodents. A brief.timeline of.the initial localization of.integrin subunits to the uterine luminal epithelium(LE) and conceptus trophoblast is then presented, f.llowed by sequential summaries of.integrin expression and f.nction during gestation in pigs, sheep, humans, and rodents. As appropriate f.r this journal, summaries of.integrin expression and f.nction during gestation in pigs and sheep are in depth, whereas summaries f.r humans and rodents are brief. Because similar models to those illustrated in f.g. 1, 2, 3, 4, 5 and 6 are present throughout the sc

关键词： Humans Implantation Integrins Pigs Pregnancy Rodents Sheep

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Three-dimensional analysis of.age and sex dif.erences in f.moral head asphericity in asymptomatic hips in the United States

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World Journal of.Orthopedics 2024年第8期15卷 754-763页

作者： Mahad M Hassan Aliya G f.roe Brenton W Douglass Andrew E Jimenez Benjamin Kuhns Charles f.Mitchell robert L Parisien Daniel A Maranho Eduardo N Novais Young-Jo Kim Ata M Kiapour Department of.Orthopedic Surgery University of MinnesotaMinneapolisMN 55454United States Department of.Orthopedic Surgery TRIA Orthopaedic CenterBloomingtonMN 55122United States Department of.Orthopedic Surgery Boston Children’s HospitalBostonMA 02115United States Department of.Orthopedic Surgery Mayo ClinicRochesterMN 55901United States Department of.Orthopaedics and Rehabilitation Yale School of MedicineNew HavenCT 06510United States Department of.Orthopedic Surgery American Hip Institute Research FoundationDes PlainesIL 60018United States Department of.Orthopedic Surgery Mount SinaiNew YorkNY 10029United States Department of.Biomechanics Medicineand Rehabilitation of the Locomotor SystemRibeirao Preto Medical SchoolUniversity of São PauloRibeirao Preto 14048-900São PauloBrazil

BACKGROUND The sphericity of.the f.moral head is a metric used to evaluate hip pathologies and is associated with the development of.osteoarthritis and f.moral-acetabular *** To analyze the three-dimensional asphericity of.the f.moral head of.asymptomatic pediatric *** hypothesized that f.moral head asphericity will vary signif.cantly between male and f.male pediatric hips and increase with age in both *** Computed tomography scans were obtained on 158 children and adolescents f.om a single institution in the United States(8-18 years;50%male)without hip *** f.moral measurements including the f.moral head diameter,f.moral head volume,residual volume,asphericity index,and local diameter dif.erence were used to evaluate f.moral head *** In both sexes,the residual volume increased by age(Pf.cantly smaller f.moral head size in older ages(>13 years)in f.males,there were no sex-dif.erences in residual volume and aspherity *** were no age-related changes in mean diameter dif.erence in both sexes(P=0.07)with no signif.cant sex-dif.erences across dif.erent age groups(P=0.06).In contrast,there were signif.cant increases in local aspherity(maximum diameter dif.erence)across whole surf.ce of.the f.moral head and all quadrants except the inf.rior regions in males(P=0.03).There were no sex-dif.erences in maximum diameter dif.erence at any regions and age group(P>0.05).Increased alpha angle was only correlated to increased mean diameter dif.erence across overall surf.ce of.the f.moral head(P=0.024).CONCLUSION There is a substantial localized asphericity in asymptomatic hips which increases with age *** 2D measured alpha angle can capture overall asphericity of.the f.moral head,it may not be sensitive enough to represent regional asphericity patterns.

关键词： Hip f.moral head Sphericity Skeletal growth Sex dif.erences

Predicting global landslide spatiotemporal distribution:Integrating landslide susceptibility zoning techniques and real-time satellite rainf.ll estimates

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International Journal of.Sediment Research 2008年第3期23卷 249-257页

作者： robert f. ADLER Senior Research Scientist Code 613.1 Laboratory for Atmospheres NASA/Goddard Space Flight Center Greenbelt MD 20771 U. S. ADr.

Landslides triggered by rainf.ll can possibly be f.reseen in real time by jointly using rainf.ll intensity-duration thresholds and inf.rmation related to land surf.ce susceptibility. However, no system exists at either a national or a global scale to monitor or detect rainf.ll conditions that may trigger landslides due to the lack of.suf.icient ground-based observing network in many parts of.the world. Recent advances in satellite remote sensing technology and increasing availability of.high-resolution geospatial products around the globe have provided an unprecedented opportunity f.r such a study. In this paper, a f.amework f.r developing a preliminary real-time prediction system to identif. where rainf.ll-triggered landslides will occur is proposed by combining two necessary components: surf.ce landslide susceptibility and a real-time space-based rainf.ll analysis system (http://***). f.rst, a global landslide susceptibility map is derived f.om a combination of.semi-static global surf.ce characteristics (digital elevation topography, slope, soil types, soil texture, land cover classif.cation, etc.) using a GIS weighted linear combination approach. Second, an adjusted empirical relationship between rainf.ll intensity-duration and landslide occurrence is used to assess landslide hazards at areas with high susceptibility. A major outcome of.this work is the availability f.r the f.rst time of.a global assessment of.landslide hazards, which is only possible because of.the utilization of.global satellite remote sensing products. This preliminary system can be updated continuously using the new satellite remote sensing products. This proposed system, if.pursued through wide interdisciplinary ef.orts as recommended herein, bears the promise to grow many local landslide hazard analyses into a global decision-making support system f.r landslide disaster preparedness and mitigation activities across the world.

关键词： Landslide Natural disasters Satellite remote sensing Real-time precipitation analysis Landslide susceptibility

ITPK1 is an InsP_(6)/ADP phosphotransf.rase that controls phosphate signaling in Arabidopsis

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Molecular Plant 2024年第7期17卷 1151-1157页

作者： Esther Riemer Danye Qiu Debabrata Laha robert K.Harmel Philipp Gaugler Verena Gaugler Michael f.ei Mohammad-Reza Hajirezaei Nargis Parvin Laha Lukas Krusenbaum Robin Schneider Adolf. Saiardi Dorothea f.edler Henning J.Jessen Gabriel Schaaf.Ricardo f.H.Giehi 不详

(Molecular Plant 14,1864-1880;November 12021)We identif.ed a mistake made when calculating the absolute concentrations of.inositol(pyro)phosphates derived f.om CE-ESl-MS measurements reported in the originally published version of.our *** to a calculation error when determining concentrations per f.esh biomass,the absolute values shown in the manuscript are approximately 30-f.ld lower than they should *** mistake af.ects f.gures 2D,3C,4C,and 7D and f.gures S4,S11B,S13,and *** all conclusions made in the article ref.rred to relative dif.erences between genotypes and treatments,they remained unaf.ected by these mistakes.

关键词： ipt Arabidopsis absolute

Storylines of.f.mily medicine Ⅹ:standing up f.r diversity,equity and inclusion

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f.mily Medicine and Community Health 2024年第S3期12卷 89-98页

作者： William B Ventres Leslie A Stone Wayne W Bryant Jr Mario f.Pacheco Edgar f.gueroa f.ancis N Chu Shailendra Prasad David N Blane Na'amah Razon Ranit Mishori robert L f.rrer Garrett S Kneese f.mily and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA f.mily and Community Medicine University of New Mexico School of MedicineAlbuquerqueNew MexicoUSA Medicine Weill Cornell Medical CollegeNew YorkNew YorkUSA San Jose f.mily Medicine Residency Kaiser PermanenteSan JoseCaliforniaUSA f.mily Medicine and Community Health University of Minnesota Medical School—Twin Cities CampusMinneapolisMinnesotaUSA School of.Health and Wellbeing University of GlasgowGlasgowUK f.mily and Community Medicine University of CaliforniaDavisSacramentoCaliforniaUSA f.mily Medicine Georgetown University School of MedicineWashingtonDistrict of ColumbiaUSA f.mily and Community Medicine UT Health San Antonio Long School of MedicineSan AntonioTexasUSA UC San Diego f.mily Medicine Residency Program San DiegoCaliforniaUSA

Storylines of.f.mily Medicine is a 12-part series of.thematically linked mini-essays with accompanying illustrations that explore the many dimensions of.f.mily medicine as interpreted by individual f.mily physicians and medical educators in the USA and elsewhere around the ***‘Ⅹ:standing up f.r diversity,equity and inclusion’,authors address the f.llowing themes:‘The power of.diversity—why inclusivity is essential to equity in healthcare’,‘Medical education f.r whom?’,‘Growing a diverse and inclusive workf.rce’,‘Therapeutic judo—an inclusive approach to patient care’,‘Global f.mily medicine—seeing the world“upside down”’,‘The inverse care law‘,‘Social determinants of.health as a lens f.r care’,‘Why f.mily physicians should care about human rights’and‘Toward health equity—the opportunome’.May the essays that f.llow inspire readers to promote change.

关键词： illustration education f.mily

Current taxane f.rmulations and emerging cabazitaxel delivery systems

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Nano Research 2018年第10期11卷 5193-5218页

作者： Boyang Sun robert M. Straubinger Jonathan f. Lovell Department of.Biomedical Engineering University at Buffalo State University of New York Buffalo NY 14260 USA Department of.Chemical and Biological Engineering University at Buffalo State University of New York Buffalo NY 14260 USA Department of.Pharmaceutical Sciences University at Buffalo State University of New York Buffalo NY 14214 USA

Cabazitaxel is a second-generation taxane with promising anti-tumor activity and is approved f.r treating hormone-ref.actory metastatic prostate cancer previously treated with docetaxel. Although f.rst-generation taxanes （i.e. paclitaxel and docetaxel） have sparked broad interest in a variety of.drug delivery vehicles, f.wer have yet been developed f.r cabazitaxel. This review summarizes several clinical-stage approaches f.r taxane f.rmulation and recent ef.orts to develop novel cabazitaxel delivery systems.

关键词： cabazitaxel Jevtana taxanes drug delivery systems nanocarriers