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Neurodegenerative diseases:a hotbed for splicing defects and the potential therapies

Translational Neurodegeneration 2021年第2期10卷 195-212页

作者： Dunhui Li Craig Stewart McIntosh Frank Louis Mastaglia Steve Donald Wilton May Thandar Aung-Htut Centre for Molecular Medicine and Innovative Therapeutics Health Futures InstituteMurdoch UniversityPerthWestern AustraliaAustralia Perron Institute for Neurological and Translational Science Centre for Neuromuscular and Neurological DisordersThe University of Western AustraliaPerthWestern AustraliaAustralia

Precursor messenger RNA(pre-mRNA)splicing is a fundamental step in eukaryotic gene expression that systematically removes non-coding regions(introns)and ligates coding regions(exons)into a continuous message(mature mRNA).This process is highly regulated and can be highly flexible through a process known as alternative splicing,which allows for several transcripts to arise from a single gene,thereby greatly increasing genetic plasticity and the diversity of proteome.Alternative splicing is particularly prevalent in neuronal cells,where the splicing patterns are continuously changing to maintain cellular homeostasis and promote neurogenesis,migration and synaptic function.The continuous changes in splicing patterns and a high demand on many cis-and trans-splicing factors contribute to the susceptibility of neuronal tissues to splicing defects.The resultant neurodegenerative diseases are a large group of disorders defined by a gradual loss of neurons and a progressive impairment in neuronal function.Several of the most common neurodegenerative diseases involve some form of splicing defect(s),such as Alzheimer’s disease,Parkinson’s disease and spinal muscular atrophy.Our growing understanding of RNA splicing has led to the explosion of research in the field of splice-switching antisense oligonucleotide therapeutics.Here we review our current understanding of the effects alternative splicing has on neuronal differentiation,neuronal migration,synaptic maturation and regulation,as well as the impact on neurodegenerative diseases.We will also review the current landscape of splice-switching antisense oligonucleotides as a therapeutic strategy for a number of common neurodegenerative disorders.

关键词： Neurodegenerative diseases Parkinson’s disease Alzheimer’s disease Alternative splicing Splicing defects Antisense oligonucleotides Splice-switching Disease-modifying treatment

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Adjusting to climate:Acclimation,adaptation and developmental plasticity in physiological traits of a tropical rainforest lizard

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Integrative Zoology 2018年第4期13卷 411-427页

作者： John LLEWELYN stewart L.MACDONALD craig MORITZ Felipe MARTINS AmberleeHATCHER Ben L.PHILLIPS Centre for Tropical Biodiversity and Climate Change James Cook UniversityTownsvilleQueenslandAustralia CSIRO Land and Water TownsvilleQueenslandAustralia Centre for Biodiversity Analysis Australian National UniversityCanberraAustralia School of BioSciences University of MelbourneMelbourneAustralia

The impact of climate change may be felt most keenly by tropical ectotherms.In these taxa,it is argued,thermal specialization means a given shift in temperature will have a larger effect on fitness.For species with limited dispersal ability,the impact of climate change depends on the capacity for their climate-relevant traits to shift.Such shifts can occur through genetic adaptation,various forms of plasticity,or a combination of these processes.Here we assess the extent and causes of shifts in 7 physiological traits in a tropical lizard,the rainforest sunskink(Lampropholis coggeri).Two populations were sampled that differ from each other in both climate and physiological traits.We compared trait values in each animal soon after field collection versus following acclimation to laboratory conditions.We also compared trait values between populations in:(i)recently field-collected animals;(ii)the same animals following laboratory acclimation;and(iii)the laboratory-reared offspring of these animals.Our results reveal high trait lability,driven primarily by acclimation and local adaptation.By contrast,developmental plasticity,resulting from incubation temperature,had little to no effect on most traits.These results suggest that,while specialized,tropical ectotherms may be capable of rapid shifts in climate-relevant traits.

关键词： acclimation adaptation climate change ectotherm reptile

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A crash to ice

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疯狂英语（新读写） 2018年第2期 23-23页

作者： craig mcintosh

Did you see American figure skater,Jeremy Abbott,crash to the ice during the short program at the Sochi 2014 Winter Olympics,rolling into the wall,clutching his side in pain.Ten seconds later,he got up and continued h... 详细信息

关键词：英语阅读阅读资料中国英语学习

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Retroperitoneal germ cell tumor diagnosed by endoscopic ultrasound-guided fine needle aspiration

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World Journal of Gastrointestinal Oncology 2010年第12期2卷 443-445页

作者： craig M Womeldorph Mark M Zalupski stewart M Knoepp Mohammad Soltani B Joseph Elmunzer Division of Gastroenterology University of Michigan Medical CenterAnn ArborMI 48109United States Division of Hematology and Oncology University of Michigan Medical CenterAnn ArborMI 48109United States Department of Pathology University of Michigan Medical CenteAnn ArborMI 48109United States

Isolated extragonadal germ cell tumors can be primary in nature or metastatic from a burned out testicular cancer.Accurate diagnosis is critical as appropriate therapy can be highly curative.We present the case of an isolated extragonadal germ cell tumor in the retroperitoneum diagnosed by endoscopic ultrasound-guided fi ne needle aspiration.This case underscores the importance of considering germ cell tumors in the differential diagnosis of an unexplained retroperitoneal mass,particularly since immunophenotypic staining may be necessary to establish the diagnosis.2010 Baishideng.All rights reserved.

关键词： Germ cell tumor Endoscopic ultrasound Fine needle aspiration

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Identifying the impediments and enablers of ecohealth for a case study on health and environmental sanitation in Hà Nam, Vietnam

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Infectious Diseases of Poverty 2014年第1期3卷 325-337页

作者： Vi Nguyen Hung Nguyen-Viet Phuc Pham-Duc craig Stephen Scott A McEwen Department of Population Medicine Ontario Veterinary CollegeUniversity of Guelph2509 Stewart Building(#45)Guelph N1G 2W1ONCanada Public Health Risk Sciences Division Laboratory for Foodborne ZoonosesPublic Health Agency of Canada160 Research LaneUnit 206GuelphON N1G 5B2Canada Center for Public Health and Ecosystem Research Hanoi School of Public Health(HSPH)138 Giang Vo StreetHanoiVietnam Swiss Tropical and Public Health Institute(Swiss TPH) and International Livestock Research Institute(ILRI)Socinstrasse 57CH-4002 BaselSwitzerland and HanoiVietnam Swiss Federal Institute of Aquatic Science and Technology(ESWAG) Sandec–Department of Water and Sanitation in Developing CountriesP.O.BoxCH-8600DübendorfSwitzerland Department of Ecosystem and Public Health Faculty of Veterinary MedicineUniversity of CalgaryTRW 2D263280 Hospital DriveNWCalgaryAlberta T2N 4Z6Canada Centre for Coastal Health 900 Fifth StreetNanaimoBritish Columbia V9R 5S5Canada

Background:To date,research has shown an increasing use of the term“ecohealth”in literature,but few researchers have explicitly described how it has been used.We investigated a project on health and environmental sanitation(the conceptual framework of which included the pillars of ecohealth)to identify the impediments and enablers of ecohealth and investigate how it can move from concept to practice.Methods:A case study approach was used.The interview questions were centred on the nature of interactions and the sharing of information between stakeholders.Results:The analysis identified nine impediments and 15 enablers of ecohealth.Three themes relating to impediments,in particular-integration is not clear,don’t understand,and limited participation-related more directly to the challenges in applying the ecohealth pillars of transdisciplinarity and participation.The themes relating to enablers-awareness and understanding,capacity development,and interactions-facilitated usage of the research results.By extracting information on the environmental,social,economic,and health aspects of environmental sanitation,we found that the issue spanned multiple scales and sectors.Conclusion:The challenge of how to integrate these aspects should be considered at the design stage and throughout the research process.We recommend that ecohealth research teams include a self-investigation of their processes in order to facilitate a comparison of moving from concept to practice,which may offer insights into how to evaluate the process.

关键词： Ecohealth Evaluation Health Sanitation Case study Vietnam

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