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Extracellular vesicles as a potential therapeutic for age-related macular degeneration

Neural Regeneration Research 2023年第9期18卷 1876-1880页

作者： lorraine l.c.chow Ben Mead School of Optometry and Vision Sciences Cardiff UniversityCardiffUK

Age-related macular degeneration is a major global cause of central visual impairment and seve re vision *** an aging population,the already immense economic burden of costly anti-vascular endothelial growth fa ctor treatment is likely to *** addition,current conventional treatment is only available for the late neovascular stage of age-related macular degeneration,and injections can come with potentially devastating complications,introducing the need for more economical and ris kfree *** recent years,exosomes,which are nano-sized extracellular vesicles of an endocytic origin,have shown immense potential as diagnostic biomarkers and in the therapeutic application,as they are bestowed with characte ristics including an expansive cargo that closely resembles their parent cell and exceptional ability of intercellular communication and targeting neighboring *** are currently undergoing clinical trials for various conditions such as type 1 diabetes and autoimmune diseases;however,exosomes as a potential therapy for seve ral retinal diseases have just begun to undergo scrutinizing investigation with little literature on age-related macular degeneration *** article will focus on the limited literature availa ble on exosome transplantation treatment in age-related macular degeneration animal models and in vitro cell cultures,as well as briefly identify future research *** literature on exosome therapy using agerelated macular degeneration rodent models includes laser retinal injury,N-methyl-N-nitrosourea,and royal college of surgeon models,which mimic inflammatory and degenerative aspects of agerelated macular *** have shown promising results in preserving retinal function and morphology,as well as protecting photoreceptors from *** from their respective cellular origins may also act by regulating the expression of various inflammatory cyto kines,mRNAs,and proteins involved in photo

关键词： age-related macular degeneration exosomes extracellular vesicles miRNA neuroprotection photoreceptors retina retinal pigment epithelium

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Downscaling future climate scenarios to fine scales for hydrologic and ecological modeling and analysis

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Ecological Processes 2012年第1期1卷 109-123页

作者： lorraine E Flint Alan l Flint U.S.Geological Survey Placer Hall6000 J St.SacramentoCA 95819USA

Introduction:Evaluating the environmental impacts of climate change on water resources and biological components of the landscape is an integral part of hydrologic and ecological investigations,and the resultant land and resource management in the twenty-first *** of both climate and simulated hydrologic parameters on ecological processes are relevant at scales that reflect the heterogeneity and complexity of *** present,simulations of climate change available from global climate models[GcMs]require downscaling for hydrologic or ecological ***:Using statistically downscaled future climate projections developed using constructed analogues,a methodology was developed to further downscale the projections spatially using a gradient-inverse-distancesquared approach for application to hydrologic modeling at 270-m spatial ***:This paper illustrates a methodology to downscale and bias-correct national GcMs to subkilometer scales that are applicable to fine-scale environmental *** scenarios were chosen to bracket the range of future emissions put forth by the Intergovernmental Panel on climate ***-scale applications of downscaled datasets of ecological and hydrologic correlations to variation in climate are ***:The methodology,which includes a sequence of rigorous analyses and calculations,is intended to reduce the addition of uncertainty to the climate data as a result of the downscaling while providing the fine-scale climate information necessary for ecological *** results in new but consistent data sets for the US at 4 km,the southwest US at 270 m,and california at 90 m and illustrates the utility of fine-scale downscaling to analyses of ecological processes influenced by topographic complexity.

关键词： downscaling climate change spatial scale scenarios

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Fine-scale hydrologic modeling for regional landscape applications:the california Basin characterization Model development and performance

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Ecological Processes 2013年第1期2卷 254-274页

作者： lorraine E Flint Alan l Flint James H Thorne Ryan Boynton Water Resources Discipline U.S.Geological SurveyPlacer Hall6000 J StreetSacramentoCA 95819-6129USA Information center for the Environment University of CaliforniaDavisCA95616USA

Introduction:Resource managers need spatially explicit models of hydrologic response to changes in key climatic drivers across variable landscape *** demonstrate the utility of a Basin characterization Model for california(cA-BcM)to integrate high-resolution data on physical watershed characteristics with historical or projected climate data to predict watershed-specific hydrologic ***:The cA-BcM applies a monthly regional water-balance model to simulate hydrologic responses to climate at the spatial resolution of a 270-m *** model has been calibrated using a total of 159 relatively unimpaired watersheds for the california ***:As a result of calibration,predicted basin discharge closely matches measured data for validation *** cA-BcM recharge and runoff estimates,combined with estimates of snowpack and timing of snowmelt,provide a basis for assessing variations in water *** important output variable,climatic water deficit,integrates the combined effects of temperature and rainfall on site-specific soil moisture,a factor that plants may respond to more directly than air temperature and precipitation *** outputs are calculated for each grid cell,allowing results to be summarized for a variety of planning units including hillslopes,watersheds,ecoregions,or political ***:The ability to confidently calculate hydrologic outputs at fine spatial scales provides a new suite of hydrologic predictor variables that can be used for a variety of purposes,such as projections of changes in water availability,environmental demand,or distribution of plants and *** we present the framework of the cA-BcM model for the california hydrologic region,a test of model performance on 159 watersheds,summary results for the region for the 1981–2010 time period,and changes since the 1951–1980 time period.

关键词： Water balance Basin models Watershed hydrology climate change Downscaling Basin characterization model

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Regulation of Parkin-dependent mitophagy by Bcl-2-associated athanogene(BAG)family members

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Neural Regeneration Research 2021年第4期16卷 684-685页

作者： Minesh Kapadia Mitchell l.De Snoo lorraine V.Kalia Suneil K.Kalia Krembil Research Institute Toronto Western HospitalUniversity Health NetworkTorontoONCanada Faculty of Medicine University of TorontoTorontoONCanada Department of laboratory Medicine and Pathobiology University of TorontoTorontoONCanada Tanz centre for Research in Neurodegenerative Diseases Division of NeurologyDepartment of MedicineUniversity of TorontoToronto Western HospitalUniversity Health NetworkTorontoONCanada Division of Neurosurgery Department of SurgeryUniversity of TorontoToronto Western HospitalUniversity Health NetworkTorontoONCanada

Mitochondria are essential organelles that play a central role in cellular metabolism and *** broad range of functions include supplying energy,regulating signaling pathways,and maintaining control of cell proliferation and *** defective mitochondria can perturb cellular homeostasis,quality control mechanisms have evolved to preserve mitochondrial fidelity in response to stress and aging(Palikaras et al.,2018).Persistent defects,however,trigger elimination of the entire organelle by an evolutionarily conserved set of cellular processes that specifically remove dysfunctional or surplus *** selective degradation of the mitochondria through autophagy,termed mitophagy,is important in fine-tuning mitochondrial number.

关键词： remove elimination metabolism

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characterizing drought in california:new drought indices and scenario-testing in support of resource management

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Ecological Processes 2018年第1期7卷 1-13页

作者： lorraine E.Flint Alan l.Flint John Mendoza Julie Kalansky F.M.Ralph U.S.Geological Survey 6000 J.StSacramentoCA 95819USA Sonoma county Water Agency 404 Aviation Dr.Santa RosaCA 95403USA Scripps Institution of Oceanography 9500 Gilman Dr.La JollaCA 92093USA

Introduction:california’s recent drought(2012–2016)has implications throughout the state for natural resource management and adaptation planning and has generated many discussions about drought characterization and *** study characterizes drought conditions with two indices describing deficits in natural water supply and increases in landscape stress developed on the basis of water balance modeling,at a fine spatial scale to assess the variation in conditions across the entire state,and provides an in-depth evaluation for the Russian River basin in northern california to address local resource management by developing extreme drought scenarios for consideration in planning and ***:We employed the USGS Basin characterization Model to characterize drought on the basis of water supply(a measure of recharge plus runoff)and landscape stress(climatic water deficit).These were applied to the state and to the Russian River basin where antecedent soil moisture conditions were evaluated and extreme drought scenarios were developed and run through a water management and reservoir operations model to further explore impacts on water ***:Drought indices indicated that as of the end of water year 2016 when reservoirs were full,additional water supply and landscape replenishment of up to three average years of precipitation in some locations was needed to return to normal *** soil conditions in the Russian River were determined to contribute to very different water supply results for different years and were necessary to understand to anticipate proper watershed response to *** drought scenarios manifested very different kinds of drought and recovery and characterization helps to guide the management response to ***:These scenarios and indices illustrate how droughts differ with regard to water supply and landscape stress and how long warm droughts recover much more slowly than short very dry dro

关键词： california drought Russian River Water supply Basin characterization Model

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Mass data processing of time series landsat imagery:pixels to data products for forest monitoring

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International Journal of Digital Earth 2016年第11期9卷 1035-1054页

作者： Txomin Hermosilla Michael A.Wulder Joanne c.White Nicholas c.coops Geordie W.Hobart lorraine B.campbella Integrated Remote Sensing Studio Department of Forest Resources ManagementUniversity of British ColumbiaVancouverBCCanada canadian Forest Service(Pacific Forestry centre) Natural Resources CanadaVictoriaBCCanada

Free and open access to the landsat archive has enabled the implementation of national and global terrestrial monitoring ***,we summarize a project characterizing the change history of canada’s forested ecosystems with a time series of data representing *** the composite2change approach,we applied spectral trend analysis to annual best-available-pixel(BAP)surface reflectance image composites produced from landsat TM and ETM+imagery.A total of 73,544 images were used to produce 29 annual image composites,generating∼400 TB of interim data products and resulting in∼25 TB of annual gap-free reflectance composites and change *** average,10%of pixels in the annual BAP composites were missing data,with 86%of pixels having data gaps in two consecutive years or *** detection overall accuracy was 89%.change attribution overall accuracy was 92%,with higher accuracy for standreplacing wildfire and *** were assigned to the correct year with an accuracy of 89%.Outcomes of this project provide baseline information and nationally consistent data source to quantify and characterize changes in forested *** methods applied and lessons learned build confidence in the products generated and empower others to develop or refine similar satellite-based monitoring projects.

关键词： Remote sensing big data forest change monitoring image processing

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High-throughput phenotyping in cotton:a review

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Journal of cotton Research 2019年第3期2卷 174-182页

作者： PABUAYON Irish lorraine B SUN Yazhou GUO Wenxuan RITcHIE Glen l Department of Plant and Soil Science Texas Tech UnivPO Box 42122LubbockTX 7909USA Texas A&M Agrilife Research and Extension center 1102 East FM 1294LubbockTX 79403USA

Recent technological advances in cotton(Gossypium hirsutum l.) phenotyping have offered tools to improve the efficiency of data collection and ***-throughput phenotyping(HTP) is a non-destructive and rapid approach of monitoring and measuring multiple phenotypic traits related to the growth,yield,and adaptation to biotic or abiotic *** have conducted extensive experiments on HTP and developed techniques including spectral,fluorescence,thermal,and three-dimensional imaging to measure the morphological,physiological,and pathological resistance traits of *** addition,ground-based and aerial-based platforms were also developed to aid in the implementation of these HTP *** review paper highlights the techniques and recent developments for HTP in cotton,reviews the potential applications according to morphological and physiological traits of cotton,and compares the advantages and limitations of these HTP systems when used in cotton cropping ***,the use of HTP has generated many opportunities to accurately and efficiently measure and analyze diverse traits of ***,because of its relative novelty,HTP has some limitations that constrains the ability to take full advantage of what it can *** challenges need to be addressed to increase the accuracy and utility of HTP,which can be done by integrating analytical techniques for big data and continuous advances in imaging.

关键词： cotton High-throughput phenotyping Remote sensing Sensors Spectral Fluorescence Thermal Platforms Aerial-based Ground-based

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cross-scale modeling of surface temperature and tree seedling establishment in mountain landscapes

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Ecological Processes 2013年第1期2卷 313-327页

作者： John R Dingman lynn c Sweet Ian Mccullough Frank W Davis Alan Flint Janet Franklin lorraine E Flint Earth Research Institute University of California Santa BarbaraSanta BarbaraCA 93106USA U.S.Geological Survey California Water Science CenterSacramentoCA 95819USA Bren School of Environmental Science&Management University of California Santa BarbaraSanta BarbaraCA93106USA School of Geographical Sciences and Urban Planning Arizona State UniversityTempeAZ85287USA

Introduction:Estimating surface temperature from above-ground field measurements is important for understanding the complex landscape patterns of plant seedling survival and establishment,processes which occur at heights of only several ***,future climate models predict temperature at 2 m above ground,leaving ground-surface microclimate not well ***:Using a network of field temperature sensors and climate models,a ground-surface temperature method was used to estimate microclimate variability of minimum and maximum *** lapse rates were derived from field temperature sensors and distributed across the landscape capturing differences in solar radiation and cold air drainages modeled at a 30-m spatial ***:The surface temperature estimation method used for this analysis successfully estimated minimum surface temperatures on north-facing,south-facing,valley,and ridgeline topographic settings,and when compared to measured temperatures yielded an R2 of 0.88,0.80,0.88,and 0.80,*** surface temperatures generally had slightly more spatial variability than minimum surface temperatures,resulting in R2 values of 0.86,0.77,0.72,and 0.79 for north-facing,south-facing,valley,and ridgeline topographic ***-Poisson regressions predicting recruitment of Quercus kelloggii(black oak)seedlings from temperature variables were significantly improved using these estimates of surface temperature compared to air temperature modeled at 2 ***:Predicting minimum and maximum ground-surface temperatures using a downscaled climate model coupled with temperature lapse rates estimated from field measurements provides a method for modeling temperature effects on plant *** methods could be applied to improve projections of species’range shifts under climate *** of complex topography can provide intricate microclimates that may allow species to redistribute locally as climate

关键词： Black oak climate change Generalized linear models Microclimate Topography Spatial scale Surface temperature

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Elucidating the Degradation Pathways of Human Insulin in the Solid State

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Journal of Analysis and Testing 2024年第3期8卷 288-299页

作者： Andrew Fagan lorraine M.Bateman Joseph P.O’Shea Abina M.crean SSPc the SFI Centre for Pharmaceutical ResearchSchool of PharmacyUniversity College CorkCork T12 YT20Ireland School of Pharmacy University College CorkCork T12 YT20Ireland Analytical and Biological chemistry Research Facility(ABcRF) University College CorkCork T12 YN60Ireland School of chemistry University College CorkCork T12 YN60Ireland

While there have been significant advances in the development of peptide oral dosage forms in recent years,highlighted by the clinical and commercial success of approved peptides such as Rybelsus®,there remain several barriers in the way of broad range applicability of this approach to peptide *** such barrier includes the poor physical and chemical stability inherent to their structures,which persists in the solid state although degradation typically occurs at different rates and via different pathways in comparison to the solution *** insulin as a model peptide,this work sought to contribute to the development of analytical techniques for investigating common insulin degradation *** denatured,deamidated and aggregated samples were prepared and used to benchmark circular dichroism spectroscopy,reverse phase HPlc and size exclusion chromatography methods for the investigation of unfolding,chemical modifications and covalent aggregation of the insulin molecule *** state degraded samples were prepared by heating insulin powder at 60°c and 75%relative humidity for 1,3,5 and 7 d,and the degradation profiles of the samples were evaluated and compared with those observed in *** no unfolding was observed to occur,significant deamidation and covalent aggregation were *** disulfide bond cleavage using dithiothreitol allowed for separation of the insulin A-and B-chains,offering a facile yet novel means of assessing the mechanisms of deamidation and covalent aggregation occurring in the solid state.

关键词： Insulin Stability Solid state Deamidation covalent aggregation Disulfide cleavage Biopharmaceutical analysis

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Giant cell arteritis: current treatment and management

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World Journal of clinical cases 2015年第6期3卷 484-494页

作者： cristina Ponte Ana Filipa Rodrigues lorraine O'Neill Raashid Ahmed luqmani Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences Botnar Research Centre University of Oxford Oxford OX1 2JD United Kingdom Department of Rheumatology Hospital de Santa Maria CHLN Lisbon Academic Medical Centre 1649-035 Lisbon Portugal Department of Internal Medicine Hospital das Caldas da Rainha Centro Hospitalar Oeste 2500-176 Caldas da Rainha Portugal Department of Rheumatology St Vincent’s University Hospital Dublin Ireland

Glucocorticoids remain the cornerstone of medicaltherapy in giant cell arteritis(GcA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Various steroid-sparing agents have been tried, but robust scientific evidence of their efficacy and safety is still lacking. Tocilizumab, a monoclonal Il-6 receptor blocker, has shown promising results in a number of case series and is now being tested in a multi-centre randomized controlled trial. Other targeted treatments, such as the use of abatacept, are also now under investigation in GcA. The need for surgical treatment is rare and should ideally be performed in a quiescent phase of the disease. Not all patients follow the same course, but there are no valid biomarkers to assess therapy response. Monitoring of disease progress still relies on assessing clinical features and measuring inflammatory markers(c-reactive protein and erythrocyte sedimentation rate). Imaging techniques(e.g., ultrasound) are clearly important screening tools for aortic aneurysms and assessing patients with largevessel involvement, but may also have an important role as biomarkers of disease activity over time or in response to therapy. Although GcA is the most common form of primary vasculitis, the optimal strategies for treatment and monitoring remain uncertain.

关键词： Giant cell arteritis Therapy Disease management Glucocorticoids Immunosuppressive agents

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