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The potential of bone morphogenetic protein 2 as a neurotrophic factor for Parkinson’s disease

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Neural Regeneration Research 2020年第8期15卷 1432-1436页

作者： Susan R.goulding Aideen M.Sullivan Gerard W.O’Keeffe Louise M.Collins Department of Biological Sciences Cork Institute of TechnologyCorkIreland Department of Anatomy and Neuroscience and Cork Neuroscience Centre University College CorkCorkIreland Department of Physiology University College CorkCorkIreland

Parkinson’s disease is the second most common neurodegenerative disorder;it affects 1%of the population over the age of *** number of people with Parkinson’s disease is set to rapidly increase due to changing demographics and there is an unmet clinical need for disease-modifying *** pathological hallmarks of Parkinson’s disease are the progressive degeneration of dopaminergic neurons in the substantia nigra and their axons which project to the striatum,and the aggregation ofα-synuclein;these result in a range of debilitating motor and non-motor *** application of neurotrophic factors to protect and potentially regenerate the remaining dopaminergic neurons is a major area of research ***,this strategy has had limited success to *** trials of two well-known neurotrophic factors,glial cell line-derived neurotrophic factor and neurturin,have reported limited efficacy in Parkinson’s disease patients,despite these factors showing potent neurotrophic actions in animal *** is therefore a need to identify other neurotrophic factors that can protect againstα-synuclein-induced degeneration of dopaminergic *** bone morphogenetic protein(BMP)family is the largest subgroup of the transforming growth factor-βsuperfamily of *** are naturally secreted proteins that play crucial roles throughout the developing nervous ***,many BMPs have been shown to be potent neurotrophic factors for dopaminergic *** we discuss recent work showing that transcripts for the BMP receptors and BMP2 are co-expressed with several key markers of dopaminergic neurons in the human substantia nigra,and evidence for downregulation of BMP2 expression at distinct stages of Parkinson’s *** also discuss studies that explored the effects of BMP2 treatment,in in vitro and in vivo models of Parkinson’s *** studies found potent effects of BMP2 on dopaminergic neurites,which is important given that axon deg

关键词： axon growth BMP2 dopaminergic neurons neuroprotection neurotrophic factor neuroregeneration Parkinson’s disease α-synuclein

Growth differentiation factor 5:a neurotrophic factor with neuroprotective potential in Parkinson’s disease

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Neural Regeneration Research 2022年第1期17卷 38-44页

作者： Susan R.goulding Jayanth Anantha Louise M.Collins Aideen M.Sullivan Gerard W.O’Keeffe Department of Anatomy and Neuroscience and Cork Neuroscience CentreUniversity College CorkCorkIreland Department of Physiology University College CorkCorkIreland

Parkinson’s disease is the most common movement disorder worldwide,affecting over 6 million *** is an age-related disease,occurring in 1%of people over the age of 60,and 3%of the population over 80 *** disease is characterized by the progressive loss of midbrain dopaminergic neurons from the substantia nigra,and their axons,which innervate the striatum,resulting in the characteristic motor and non-motor symptoms of Parkinson’s *** is paralleled by the intracellular accumulation ofα-synuclein in several regions of the nervous *** therapies are solely symptomatic and do not stop or slow disease *** promising disease-modifying strategy to arrest the loss of dopaminergic neurons is the targeted delivery of neurotrophic factors to the substantia nigra or striatum,to protect the remaining dopaminergic neurons of the nigrostriatal ***,clinical trials of two well-established neurotrophic factors,glial cell line-derived neurotrophic factor and neurturin,have failed to meet their primary *** failure is thought to be at least partly due to the downregulation byα-synuclein of Ret,the common co-receptor of glial cell line-derived neurorophic factor and ***/differentiation factor 5 is a member of the bone morphogenetic protein family of neurotrophic factors,that signals through the Ret-independent canonical Smad signaling ***,we review the evidence for the neurotrophic potential of growth/differentiation factor 5 in in vitro and in vivo models of Parkinson’s *** discuss new work on growth/differentiation factor 5’s mechanisms of action,as well as data showing that viral delivery of growth/differentiation factor 5 to the substantia nigra is neuroprotective in theα-synuclein rat model of Parkinson’s *** data highlight the potential for growth/differentiation factor 5 as a disease-modifying therapy for Parkinson’s disease.

关键词： adeno-associated virus bone morphogenetic protein dopaminergic neurons growth/differentiation factor 5 neurodegeneration neuroprotection neurotrophic factor Parkinson’s disease Smad signaling α-synuclein

Strategies for farmers and policy makers to control nitro-gen losses whilst maintaining crop production

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Science China(Life Sciences) 2005年第Z2期48卷 710-719页

作者： Keith W.T.goulding Agriculture and the Environment Division Rothamsted Research HarpendenHertfordshireAL5 2JQUK

The nitrogen (N) cycle is essentially 'leaky'. The losses of small amounts of nitrate to waters and of ammonia and nitrous oxide to the atmosphere are a part of the global biogeo-chemical N cycle. However, intensive agricultural production, industry and vehicle use have more than doubled the amount of 'reactive' N in the environment, resulting in eutrophication, ecosystem change and health concerns. Research has identified agricultural practices that cause large losses of N and, in some cases, developed solutions. This paper discusses the problems of maintaining productivity while reducing N losses, compares conventional with low input (integrated) and organic farming systems, and discusses wider options. It also looks at the need to integrate studies on N with other environmental impacts, set in the context of the whole farm system, to provide truly sustainable agricultural systems.

关键词： Nitrogen cycle, farm systems, best management, environmental impact, productivity.

A proteome-wide screen identifies valosin-containing protein as an essential regulator of podocyte endoplasmic reticulum stress

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Chinese Science Bulletin 2012年第20期57卷 2493-2505页

作者： HUANG ZhiYong HONG Quan XUE Peng PAUL goulding FENG Zhe WANG LiYuan MEI Yan WU LingLing CHEN XiangMei WU Di State Key Laboratory of Kidney Disease(2011DAV00088) Kidney Department&Institute of NephrologyDivision of Clinical Internal MedicineChinese People’s Liberation Army General HospitalBeijing 100853China Laboratory of Proteomics Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Nonlinear Dynamics Ltd Keel HouseGarth HeadsNewcastle upon TyneNE12JEUK

To investigate proteins expressed in the renal tissue of the passive Heymann nephritis (pHN) rat model,we prepared pHN rat models with anti-FxA1 serum and analyzed the proteins differentially expressed in the kidney tissue with label-free liquid chromatography-tandem mass *** then analyzed in depth the endoplasmic reticulum stress (ERS)-related protein using an online bioinformatics ***-one differential proteins and their annotations were *** Ontology (GO) function analysis showed that 16 proteins were involved in cellular metabolism and 22 were proteins related to catalytic activity,including protein folding or ***-GO networks indicated that VCP could interact with the ERS marker HSPa5,with both involved in a single *** inhibition of podocyte VCP by RNAi under normal conditions,the HSPa5 expression level did not change,but when the cell was subjected to ERS by tunicamycin,HSPa5 expression significantly increased with RNAi of VCP when compared with the tunicamycin-treated *** results showed that ERS plays an important role in podocyte injury of membranous nephropathy and is mediated by an HSPa5-VCP signaling pathway,in which the most predominant proteins are those related to cellular metabolism and catalytic activity.

关键词：蛋白质折叠内质网应激细胞损伤 Networks公司宽屏幕标识大鼠模型催化活性

A green eco-environment for sustainable development:framework and action

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Frontiers of Agricultural Science and Engineering 2020年第1期7卷 67-74页

作者： Xuejun LIU Wen XU Zhipeng SHA Yangyang ZHANG Zhang WEN Jingxia WANG Fusuo ZHANG Keith goulding National Academy of Agriculture Green Development College of Resources and Environmental SciencesChina Agricultural UniversityBeijing 100193China Sustainable Agricultural Sciences Department Rothamsted ResearchHarpenden AL52JQUK

Following its 40-year reform and‘Open Door’policy,China has recently proposed a new approach to green development and rural revitalization—the idea of Agriculture Green Development(AGD),with the key feature of creating a green *** this minireview we introduce the definition,theory,framework and major components of a green eco-environment as a key part of the *** define a green eco-environment as including four key elements or measures:(1)a green ecoenvironmental indicator system;(2)environmental monitoring and warning networks;(3)emission standards and environmental thresholds for key pollutants;(4)emission controls and pollution remediation *** have used Quzhou County(a typical county in the center of the North China Plain)as an example to show how detailed air,water and soil monitoring networks,as well as improved farmer practices and pollution control measures(especially ammonia emission mitigation and PM2.5 pollution reduction),can begin to create a green eco-environment in China and that AGD is *** conclude by stressing the need to improve the framework and practice for a green eco-environment,especially the importance of linking proposals and practices for a green eco-environment with the United Nations high priority Sustainable Development Goals.

关键词： monitoring networks environmental thresholds ammonia emission mitigation green ecological environment Quzhou County

Occupational injuries and burn out among orthopedic oncology surgeons

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World Journal of Orthopedics 2022年第12期13卷 1056-1063页

作者： Abdulrahman M Alaseem Robert E Turcotte Nathalie Ste-Marie Mohammad M Alzahrani Saad M Alqahtani Krista A goulding Department of Orthopedic Surgery College of MedicineKing Saud UniversityRiyadh 12372Saudi Arabia Department of Orthopedic Surgery McGill University Health CentreMontreal H4A3J1Canada Department of Orthopedic Surgery College of MedicineImam Abdulrahman Bin Faisal universityDammam 34212Saudi Arabia Department of Orthopaedic Surgery Mayo ClinicPhoenixArizona 85054USA

BACKGROUND Orthopedic oncology surgeons commonly engage in prolonged and complex surgical *** types of surgeries increase the risk of physical and psychological stressors,which may in turn make these physicians prone to workrelated occupational *** The aim of this study was to explore in orthopedic oncologists,the prevalence of work-related physical injuries and psychological *** A modified version of the physical discomfort survey was developed to assess occupational injuries among orthopedic oncology surgeon members of the Musculoskeletal Tumor Society,the Canadian Orthopedic Oncology Society and European Musculoskeletal Oncology *** survey was sent by email,and it explored musculoskeletal complaints,psychological disturbances,treatment required for these complaints and the requirement of time off *** A total of 67 surgeon responses were collected.A high number of orthopedic oncologists(84%)reported an occupational *** back pain(39%)was the most prevalent musculoskeletal condition,followed by lumbar disk herniation(16%),shoulder tendinitis(15%)and lateral epicondylitis(13%).Of the cohort,46%required surgery and 31%required time off work due to their ***-three respondents reported a psychological ***(27%),anxiety(20%)and insomnia(20%)were the most commonly *** required off work due to injury was associated with old age and years in *** Orthopedic oncology surgeons report a high prevalence of work-related *** back related injury and burnout were the most reported *** operative room ergonomics and prevention of stress related to the work environment should be areas to explore in upcoming research.

关键词： Orthopedic oncology Surgeons Occupational Musculoskeletal Injuries

Nitrogen and Sulphur Deposition to Soils and Their Impacts on Soil Processes

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Nitrogen and Sulphur Deposition to Soils and Their Impacts o...

A Modified Simulated Annealing Algorithm for Optimal Vibration Control of Flexible Structures

中国土壤学会第十一届全国会员代表大会暨第七届海峡两岸土壤肥料学术交流研讨会

作者： K.W.T.goulding Department of Soil Science Rothamsted ResearchHarpendenHertfordshire AL5 2JQUK

Human activity has greatly perturbed the nitrogen (N) and sulphur (S) cycles through combustion of fossil fuels and,for N,through increased fixation by legumes,its mobilisation from long-term storage pools (*** biomass burning and cultivation) and the Haber-Bosch process of fertilizer *** extra reactive N and S is readily transported through the en- vironment,impacting on *** of precipitation composition,made at Roth- amsted Research since 1853,show an increase of nitrate-N and ammonium-N in precipitation from 1 and 3 kg N hayr,respectively,in 1855 to a maximum of 8 and 10 kg N hayr,respec- tively,in 1980,decreasing to 4 and 5 kg N *** in precipitation increased from c 3 kg S hayrin 1855 to c 30 kg S hayrin 1980,decreasing back to c 3 kg S hayrto- *** deposition of all measured N species is c 40 kg N hayrand of S less than 10 ha *** major changes in S deposition have resulted from a marked decline in industrial produc- tion and a change from coal to natural ***,formerly reliant on S deposited from the at- mosphere now need to apply S fertiliser to all crops,especially *** of ox- ides of N in the atmosphere are declining because catalytic converters have been fitted to motor vehicles,but numbers of vehicles continue to *** emissions have not decreased greatly,so amounts of total N deposited are still large. Acidification and eutrophication resulting from the deposition of N and S have impacted on semi-natural ecosystems in the *** impacts have been quantified using the 152-year old Park Grass experiment at Rothamsted and other long-term *** N has also re- duced methane oxidation rates in soil by about 15% under arable land and 30% under woodland, and has caused N saturation of local woodland ecosystems:nitrous oxide emission rates are equal to those from arable land receiving>200 kg N hayr,and in proportion to the excess N de- posited.

关键词： Nitrogen deposition sulphur deposition nitrification trace gas fluxes

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A Modified Simulated Annealing Algorithm for Optimal Vibrati...

Practical Application of Principal Component Analysis

第十九届中国控制会议

作者： Barry Lennox Peter R goulding Andrew Y T Leung Control Technology Centre School of EngineeringThe University of ManchesterUK Control Technology Centre School of EngineeringThe University of ManchesterUK Department of Building and Construction City University of Hong KongHong Kong

＜正＞This paper presents a modified simulated annealing algorithm and applies it to the optimal control of flexible smart structures bonded with piezoelectric actuators and sensors. A performance function is initially developed, based on the integrated total energy stored in the system. Then according to this characteristic, a modified simulated annealing algorithm is presented which is capable of solving this optimization problem reliably and efficiently. The optimization algorithm that is developed for the control of flexible systems allows an integrated determination of actuator and sensor locations and feedback gains. The paper demonstrates the suitability of the proposed algorithm through its application to a collocated cantilever beam with both one and two actuators/sensors.

关键词： Active Vibration Control Optimization Piezoelectric Actuators/Sensors Simulated Annealing Algorithm

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Practical Application of Principal Component Analysis