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Impaired glymphatic function in the early stages of disease in a TDP-43 mouse model of amyotrophic lateral sclerosis

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Translational Neurodegeneration 2022年第1期11卷 707-717页

作者： Akram Zamani Adam K.Walker Ben Rollo Katie L.Ayers Raysha Farah Terence j.o’brien David K.Wright Department of Neuroscience Central Clinical SchoolMonash UniversityMelbourneVIC 3004Australia Queensland Brain Institute The University of QueenslandSt LuciaQLD 4072Australia The Murdoch Children’s Research Institute The Royal Children’s HospitalParkvilleVIC 3052Australia Department of Pediatrics The University of MelbourneParkvilleVIC 3052Australia Department of Medicine The Royal Melbourne HospitalThe University of MelbourneParkvilleVIC 3052Australia

Background: Multiple lines of evidence suggest possible impairment of the glymphatic system in amyotrophic lateral sclerosis (ALS). To investigate this, we used in vivo magnetic resonance imaging (MRI) to assess glymphatic func-tion early in the course of disease in a transgenic mouse with doxycycline (Dox)-controlled expression of cytoplasmic human TDP-43 (hTDP-43ΔNLS), mimicking the key pathology implicated in ALS. Methods: Adult TDP-43 transgenic and littermate monogenic control mice underwent longitudinal multimodal MRI one and three weeks after the cessation of Dox feed, together with weekly rotarod assessments of motor per-formance. Glymphatic function was assessed using dynamic contrast-enhanced MRI to track the clearance of an MR contrast agent injected into the cisterna magna. Results: Compared to their littermate controls, TDP-43 mice exhibited progressive neurodegeneration including that within the primary motor cortex, primary somatosensory cortex and corticospinal tract, significant weight loss includ-ing gastrocnemius atrophy, and shortened telomere length. Furthermore, in the presence of this ALS-like phenotype, these mice have significantly disrupted glymphatic function. Conclusions: Although the relationship between glymphatic clearance and ALS disease progression remains to be elucidated, these changes occurred very early in the disease course. This provides initial evidence to suggest that the glymphatic system might be a potential therapeutic target in the treatment of ALS.

关键词： Magnetic resonance imaging Diffusion-weighted imaging Neurodegeneration Cerebrospinal fluid Telomere

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Numerical analysis of high‑speed railway slab tracks using calibrated and validated 3D time‑domain modelling

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Railway Engineering Science 2024年第1期32卷 36-58页

作者： A.F.Esen o.Laghrouche P.K.Woodward D.Medina‑Pineda Q.Corbisez j.Y.Shih D.P.Connolly Institute for High‑Speed Rail and System Integration University of LeedsLeeds LS29JTUK Institute for Infrastructure and Environment Heriot-Watt UniversityEdinburgh EH144ASUK Alstom Transport Saint‑OuenFrance Birmingham Centre for Railway Research and Education University of BirminghamBirmingham B152TTUK

Concrete slabs are widely used in modern railways to increase the inherent resilient quality of the tracks,provide safe and smooth rides,and reduce the maintenance *** this paper,the elastic performance of a novel slab trackform for high-speed railways is investigated using three-dimensional finite element modelling in *** is then compared to the performance of a ballasted ***,slab and ballasted track models are developed to replicate the full-scale testing of track *** the models are calibrated with the experimental results,the novel slab model is developed and compared against the calibrated slab track *** slab and ballasted track models are then extended to create linear dynamic models,considering the track geodynamics,and simulating train passages at various speeds,for which the Ledsgard documented case was used to validate the *** travelling at low and high speeds are analysed to investigate the track deflections and the wave propagation in the soil,considering the issues associated with critical *** train loading methods are discussed,and the most practical approach is retained and ***,correlations are made between the geotechnical parameters of modern high-speed rail and conventional *** is found that considering the same ground condition,the slab track deflections are considerably smaller than those of the ballasted track at high speeds,while they show similar behaviour at low speeds.

关键词： High-speed railways Slab track New ballastless track Ballasted track Critical speeds Finite element modelling Calibration of numerical models

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Assessing the utility of dissolved organic matter photoreactivity as a predictor of in situ methylmercury concentration

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journal of Environmental Sciences 2018年第6期30卷 160-168页

作者： Sara j.Klapstein Susan E.Ziegler David A.Risk Nelson j.o'Driscoll Environmental Science Program Memorial University of Newfoundland Department of Earth Sciences St. Francis Xavier University Department of Earth and Environmental Science Acadia University

Methylmercury（MeHg） bioaccumulation is a growing concern in ecosystems worldwide. The absorption of solar radiation by dissolved organic matter（DoM） and other photoreactive ligands can convert MeHg into less toxic forms of mercury through photodemethylation. In this study, spectral changes and photoreactivity of DoM were measured to assess the potential to control photoreactions and predict in situ MeHg concentration. Water samples collected from a series of lakes in southwestern Nova Scotia in june, August, and September were exposed to controlled ultraviolet-A（UV-A） radiation for up to 24 hr. Dissolved organic matter photoreactivity, measured as the loss of absorbance at 350 nm at constant UV-A irradiation, was positively dependent on the initial DoM concentration in lake waters（r^2=0.94）. This relationship was consistent over time with both DoM concentration and photoreactivity increasing from summer into fall across lakes. Lake in situ MeHg concentration was positively correlated with DoM concentration and likely catchment transport in june（r = 0.77） but not the other sampling months. Despite a consistent seasonal variation in both DoM and Fe, and their respective correlations with MeHg, no discernable seasonal trend in MeHg was observed. However, a 3-year dataset from the 6 study lakes revealed a positive correlation between DoM concentration and both Fe（r = 0.91） and MeHg concentrations（r = 0.51） suggesting a more dominant landscape mobility control on *** DoM-MeHg relationships observed in these lakes highlights the need to examine DoM photoreactivity controls on MeHg transport and availability in natural waters particularly given future climate perturbations.

关键词： Methylmercury Dissolved organic carbon Photoreactions Kejimkujik National Park Freshwater lakes

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Associations between physical activity levels and ATPase inhibitory factor 1 concentrations in older adults

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journal of Sport and Health Science 2024年第3期13卷 409-418页

作者： jérémy Raffin Yves Rolland Annelise Genoux Guillaume Combes Mikael Croyal Bertrand Perret Sophie Guyonnet Bruno Vellas Laurent o.Martinez Philipe de Souto Barreto For the MAPT/DSA Group Institut du Vieillissement Gérontopôle de ToulouseCentre Hospitalo-Universitaire de ToulouseToulouse 31000France Centre d'Epidémiologie et de Recherche en Santédes Populations UnitéMixte de Recherche 1295Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse-III-Paul-SabatierToulouse 31000France LimitAging Team Institut des Maladies Métaboliques et CardiovasculairesUnitéMixte de Recherche 1297Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse III-Paul SabatierToulouse 31432France Service de Biochimie Pôle de biologieHôpital de PurpanCentre Hospitalo-Universitaire de ToulouseToulouse 31300France L'Institut du Thorax Institut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France BioCore US16Structure Fédérative de Recherche BonamyInstitut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France Plate-forme de spectrométrie de masse Centre de Recherche en Nutrition HumaineOuestNantes 44000France 不详

Background:Adenosine triphosphatase inhibitory factor 1(IF1)is a key protein involved in energy ***1 has been linked to various agerelated diseases,although its relationship with physical activity(PA)remains ***,the apolipoprotein A-I(apoA-I),a PA-modulated lipoprotein,could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP *** examined here the associations between chronic PA and plasma IF1 concentrations among older adults,and we investigated whether apoA-I mediated these ***:In the present work,1096 healthy adults(63.8%females)aged 70 years and over who were involved in the Multidomain Alzheimer Prevention Trial study were ***1 plasma concentrations(square root of ng/mL)were measured at the 1-year visit of the Multidomain Alzheimer Prevention Trial,while PA levels(square root of metabolic equivalent task min/week)were assessed using questionnaires administered each year from baseline to the 3-year *** linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 *** analyses were conducted to examine whether apoA-I mediated these *** linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in ***:Multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations(B=0.021;SE=0.010;p=0.043).Mediation analyses revealed that about 37.7%of this relationship was mediated by apoA-I(B_(ab)=0.008;SE=0.004;p=0.023).Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years(time×IF1:B=0.148;SE=0.066;p=0.025).Conclusion:This study demonstrates that regular PA is associated with plasma IF1 concentrations,and it suggests that apoA-I partly med

关键词： Aging Apolipoprotein Bioenergetics Exerkine Mitochondria

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Mercury photoreduction and photooxidation in lakes：Effects of filtration and dissolved organic carbon concentration

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journal of Environmental Sciences 2018年第6期30卷 151-159页

作者： Nelson j.o’Driscoll Emma Vost Erin Mann Sara Klapstein Robert Tordon Matthew Lukeman Department of Earth & Environmental Science Acadia University Wolfville B4P 2R6 Nova Scotia Canada Environment Canada Dartmouth Nova Scotia Canada Department of Chemistry Acadia University Wolfville B4P 2R6 Nova Scotia Canada

Mercury is a globally distributed, environmental contaminant. Quantifying the retention and loss of mercury is integral for predicting mercury-sensitive ecosystems. There is little information on how dissolved organic carbon（DoC） concentrations and particulates affect mercury photoreaction kinetics in freshwater lakes. To address this knowledge gap,samples were collected from ten lakes in Kejimkujik National Park, Nova Scotia（DoC： 2.6–15.4 mg/L）. Filtered（0.2 μm） and unfiltered samples were analysed for gross photoreduction, gross photooxidation, and net reduction rates of mercury using pseudo first-order curves. Unfiltered samples had higher concentrations（p = 0.04） of photoreducible divalent mercury（Hg（II）RED）（mean of 754 ± 253 pg/L） than filtered samples（mean of 482 ± 206 pg/L）;however, gross photoreduction and photooxidation rate constants were not significantly different in filtered or unfiltered samples in early summer. DoC was not significantly related to gross photoreduction rate constants in filtered（R2= 0.43; p = 0.08） and unfiltered（R2= 0.02; p = 0.71） samples; DoC was also not significantly related to gross photooxidation rate constants in filtered or unfiltered samples. However, DoC was significantly negatively related with Hg（Ⅱ）RED in unfiltered（R2= 0.53; p = 0.04）, but not in filtered samples（R2= 0.04;p = 0.60）. These trends indicate that DoC is a factor in determining dissolved mercury photoreduction rates and particles partially control available Hg（Ⅱ）RED in lake water. This research also demonstrates that within these lakes gross photoreduction and photooxidation processes are close to being in balance. Changes to catchment inputs of particulate matter and DoC may alter mercury retention in these lakes and could partially explain observed increases of mercury accumulation in biota.

关键词： Mercury Photoreduction Photooxidation Dissolved organic carbon(DoC) Particulates Kejimkujik National Park

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Functional attributes of two subtropical shrubs and implications for the distribution and management of endangered bird habitat

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journal of Plant Ecology 2015年第6期8卷 578-592页

作者： Genie M.Fleming joseph M.Wunderle jr David N.Ewert joseph j.o’brien Eileen H.Helmer Puerto Rican Conservation Foundation PO Box 362495San JuanPR 00936USA International Institute of Tropical Forestry USDA Forest ServiceSabana Field Research StationHC 02 Box 6205LuquilloPR 00773-1377USA The Nature Conservancy 101 East Grand RiverLansingMI 48906USA Center for Forest Disturbance Science USDA Forest Service320 Green StAthensGA 30602USA

Aims The fruits of Erithalis fruticosa *** Lantana involucrata *** important in the diet of u federally endangered Kirtland’s Warblers(Setophaga kirtlandii)wintering in the bahamas *** two shrubs occur in tropical and subtropical dry forests,including forests that have been subjected to recent *** their importance to the endangered warbler,the disturbance ecology of these shrubs is poorly *** sought to determine,based on functional characteristics of the plants,whether their presence is favored by a particular type or regime of *** We used data from field experiments(seed broadcasting and shrub cutting)conducted on the island of Eleuthera,The bahamas to determine mechanisms of and conditions favoring establishment and persistence(‘vital attributes’)of *** and ***,which enabled categorization according to the plant functional types defined by Noble and slatyer(1980).We then compared hypothesized distributions of these plant functional types among different anthropogenic disturbance regimes to observed distribu-tions of *** and *** in order to identify distur-bance regimes most likely to produce habitat used by Kirtland’s *** Findings *** and *** were functionally categorized as widely dispersed but largely shade intolerant species capable of establishing or regenerating individuals after disturbance via both seeds and vegetative *** hypothesized and observed distribution patterns indicated the shrubs were favored by a regime of frequent disturbance producing open canopy and ground *** the anthropogenic disturbances we examined,areas of large-scale land clearing combined with subsequent goat graz-ing most often supported *** and ***,while the shrubs were relatively rare in burned *** the plant functional type framework in combination with field data to evaluate predictions of species occur

关键词： anthropogenic disturbance black torch plant functional type vital attributes wild sage

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A fine-scale assessment of the ecosystem service-disservice dichotomy in the context of urban ecosystems affected by alien plant invasions

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Forest Ecosystems 2019年第4期6卷 323-338页

作者： Luke j.Potgieter Mirijam Gaertner Patrick j.o’Farrell David M.Richardson Centre for Invasion Biology Department of Botany and ZoologyStellenbosch University

Background: Natural resources within and around urban landscapes are under increasing pressure from ongoing urbanisation, and management efforts aimed at ensuring the sustainable provision of ecosystem services(ES) are an important response. Given the limited resources available for assessing urban ES in many cities, practical approaches for integrating ES in decision-making process are ***: We apply remote sensing techniques(integrating LiDAR data with high-resolution multispectral imagery)and combined these with supplementary spatial data to develop a replicable approach for assessing the role of urban vegetation(including invasive alien plants) in providing ES and ecosystem disservices(EDS). We identify areas denoting potential management trade-offs based on the spatial distribution of ES and EDS using a local-scale case study in the city of Cape Town, South Africa. Situated within a global biodiversity hotspot, Cape Town must contend with widespread invasions of alien plants(especially trees and shrubs) along with complex socio-political challenges. This represents a useful system to examine the challenges in managing ES and EDS in the context of urban plant ***: Areas of high ES provision(for example carbon sequestration, shade and visual amenity) are characterized by the presence of large trees. However, many of these areas also result in numerous EDS due to invasions of alien trees and shrubs – particularly along rivers, in wetlands and along the urban edge where tall alien trees have established and spread into the natural vegetation(for example increased water consumption, increased fire risk and reduced soil quality). This suggests significant trade-offs regarding the management of species and the ES and EDS they ***: The approach applied here can be used to provide recommendations and to guide city planners and managers to fine-tune management interventions at local scales to maximise the provision of ES.

关键词： Biodiversity Biological invasions Ecosystem disservices Ecosystem services Remote sensing Trade-offs Tree invasions Urban plant invasions

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The effects of local variations in conditions on carbon storage and release in the continental mantle

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National Science Review 2024年第06期 22-36页

作者： stephen F.Foley Chunfei Chen Dorrit E.jacob School of Natural Sciences Macquarie University Research School of Earth Sciences Australian National University State Key Laboratory of Geological Processes and Mineral Resources School of Earth Sciences China University of Geosciences

Recent advances indicate that the amount of carbon released by gradual degassing from the mantle needs to be revised upwards, whereas the carbon supplied by plumes may have been overestimated in the *** in rock types and oxidation state may be very local and exert strong influences on carbon storage and release mechanisms. Deep subduction may be prevented by diapirism in thick sedimentary packages,whereas carbonates in thinner sequences may be subducted. Carbonates stored in the mantle transition zone will melt when they heat up, recognized by coupled stable isotope systems(e.g. Mg, Zn, Ca). There is no single ‘mantle oxygen fugacity’, particularly in the thermal boundary layer(TBL) and lowermost lithosphere, where very local mixtures of rock types coexist. Carbonate-rich melts from either subduction or melting of the uppermost asthenosphere trap carbon by redox freezing or as carbonate-rich dykes in this zone. Deeply derived, reduced melts may form further diamond reservoirs, recognized as polycrystalline diamonds associated with websteritic silicate minerals. Carbon is released by either edge-driven convection,which tears sections of the TBL and lower lithosphere down so that they melt by a mixture of heating and oxidation, or by lateral advection of solids beneath rifts. Both mechanisms operate at steps in lithosphere thickness and result in carbonate-rich melts, explaining the spatial association of craton edges and carbonate-rich magmatism. High-pressure experiments on individual rock types, and increasingly on reactions between rocks and melts, are fine-tuning our understanding of processes and turning up unexpected results that are not seen in studies of single rocks. Future research should concentrate on elucidating local variations and integrating these with the interpretation of geophysical signals. Global concepts such as average sediment compositions and a uniform mantle oxidation state are not appropriate for small-scale processes; an increa

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Effect of restricted feeding on hen performance,egg quality and organ characteristics of individual laying hens

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Animal Nutrition 2023年第3期14卷 141-151页

作者： Doreen o.Anene Yeasmin Akter Peter C.Thomson Peter Groves Cormac j.o'Shea Department of Animal Science School of BiosciencesUniversity of NottinghamLoughboroughLE125RDUnited Kingdom School of Life and Environmental Sciences Faculty of ScienceUniversity of SydneyCamdenNSW 2570Australia Sydney School of Veterinary Science Faculty of SciencePoultry Research FoundationUniversity of SydneyCamdenNSW 2570Australia Department of Bioveterinary and Microbial Sciences Technological University of the Shannon:Midlands MidwestDublin RoadAthloneCo WestmeathN37 HD68Ireland

This study was to assess the impact of permanent or temporary restricted feeding on laying hen production traits,physiology,and egg *** hundred and forty individually housed ISA Brown hens were monitored across 2 phases,assigned to 3 treatments:ad libitum feeding(ALF),temporary restricted feeding(TRF)and permanent restricted feeding(PRF),n=80 hens per *** Phase 1(P1),22 to40 weeks,the TRF and PRF hens were offered 115 g of feed *** Phase 2(P2),41 to 46 weeks,the TRF hens were transitioned to ALF status while the ALF and PRF hens remained as in *** 35 to 40 weeks,eggs were collected once weekly from 15 hens per treatment and assessed for differences in albumen,yolk,and shell *** 45 weeks,10 hens each from the ALF and PRF groups were euthanized and differences in organ characteristics were *** P1,feed intake,feed to egg conversion ratio and body weight(BW)change were lower(Poth PRF and TRF hen treatments compared to hens allocated the ALF *** P2,TRF and ALF hens had a higher egg production and egg mass than PRF(Poth ALF and PRF,while feed intake and feed conversion ratio were higher in TRF followed by ALF and least in the PRF treatment group(Pominal fat pad weight and fatty liver haemorrhagic syndrome lesion score compared to *** hens to 115 g of feed per day from point of lay restrained BW,improved feed conversion ratio and albumen quality and reduced abdominal fat pad deposition and clinical signs of fatty liver haemorrhagic syndrome in individually housed laying hens.

关键词： Restricted feeding Albumen quality Fatty liver haemorrhagic syndrome Abdominal fat Laying hen Body weight

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older Adult Compendium of Physical Activities:Energy costs of human activities in adults aged 60 and older

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journal of Sport and Health Science 2024年第1期13卷 13-17,F0003页

作者： Erik A.Willis stephen D.Herrmann Mary Hastert Chelsea L.Kracht Tiago V.Barreira john M.Schuna jr. Zhenghua Cai Minghui Quan Scott A.Conger Wendy j.Brown Barbara E.Ainsworth Center for Health Promotion and Disease Prevention University of North Carolina at Chapel HillChapel HillNC 27599USA Kansas Center for Metabolism and obesity Research The University of Kansas Medical CenterKansas CityKS 66160USA Division of Physical Activity and Weight Management Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityKS 66160USA Clinical Science Division Pennington Biomedical Research CenterBaton RougeLA 70808USA Exercise Science Department Syracuse UniversitySyracuseNY 13244USA School of Exercise&Sport Science Oregon State UniversityCorvallisOR 97331USA School of Exercise and Health Shanghai University of SportShanghai 200438China Department of Kinesiology Boise State UniversityBoiseID 83725USA School of Human Movement and Nutrition Sciences The University of QueenslandSt.LuciaQLD 4072Australia Faculty of Health Sciences and Medicine Bond UniversityGold CoastQLD 4229Australia College of Health Solutions Arizona State UniversityPhoenixAZ 85003USA

Purpose:To describe the development of a Compendium for estimating the energy costs of activities in adults>60 years(oA Compendium).Methods:Physical activities(PAs)and their metabolic equivalent of task(MET)values were obtained from a systematic search of studies published in 4 sport and exercise databases(PubMed,Embase,SPoRTDiscus(EBSCohost),and Scopus)and a review of articles included in the 2011 Adult Compendium that measured PA in older *** values were computed as the oxygen cost(Vo_(2),mL/kg/min)during PA divided by 2.7 m L/kg/min(MET_(60+))to account for the lower resting metabolic rate in older ***:We identified 68 articles and extracted energy expenditure data on 427 *** these,we derived 99 unique Specific Activity codes with corresponding MET_(60+)values for older *** developed a website to present the oA Compendium MET_(60+)values:https://***:The oA Compendium uses data collected from adults>60 years for more accurate estimation of the energy cost of PAs in older *** is an accessible resource that will allow researchers,educators,and practitioners to find MET_(60+)values for older adults for use in PA research and practice.

关键词： Energy expenditure Exercise MET older adults

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