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Cytoplasmic dynein:a key player in neurodegenerative and neurodevelopmental diseases

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Science China(Life Sciences) 2014年第4期57卷 372-377页

作者： CHEN Xiang-Jun XU Huan cooper helen m LIU Yaobo Department of Neurology Huashan Hospital Fudan University Queensland Brain Institute The University of QueenslandBrisbane Institute of Neuroscience Soochow University

Cytoplasmic dynein is the most important molecular motor driving the movement of a wide range of cargoes towards the minus ends of *** a molecular motor protein,dynein performs a variety of basic cellular functions including organelle transport and centrosome *** the nervous system,dynein has been demonstrated to be responsible for axonal retrograde *** studies have revealed direct or indirect evidence of dynein in neurodegenerative diseases such as amyotrophic lateral sclerosis,Charcot-marie-Tooth disease,Alzheimer’s disease,Parkinson’s disease and Huntington’s *** them,a number of mutant proteins involved in various neurodegenerative diseases interact with *** transport disruption is presented as a common feature occurring in neurodegenerative *** heavy chain mutant mice also show features of neurodegenerative ***,defects of dynein-dependent processes such as autophagy or clearance of aggregation-prone proteins are found in most of these *** of evidence have also shown that dynein is associated with neurodevelopmental *** this review,we focus on dynein involvement in different neurological diseases and discuss potential underlying mechanisms.

关键词： dynein retrograde transport pathogenesis neurodegenerative diseases neurodevelopmental diseases

Bridging the gap——Immune cells that can repair nerves

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Cellular & molecular Immunology 2021年第4期18卷 784-786页

作者： helen m.mcGettrick Institute of Inflammation and Aging University of BirminghamBirminghamUK

Immunity is critical for survival in a world plagued by *** that of most military operations,the strategy of the immune system is based on acceptable losses:determining the maximal amount of damage to uninfected tissues that is necessary to defeat or entrap any invading *** characteristic has devastating consequences for patients with immune-mediated diseases,including many neurological conditions.

关键词： Immune diseases damage

The third cleavage geometry of Xenopus embryos is altered in a hypogeomagnetic field

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The third cleavage geometry of Xenopus embryos is altered in...

Immunological roulette: Luck or something more? Considering the connections between host and environment in TB

2011年空间生命与生命起源暨航天医学工程学术研讨会

作者： helen m.cooper The Queensland Brain Institute The University of Queensland

＜正＞The hypogeomagnetic field（HGmF,or magnetic fields＜200 nT）is one of the fundamental environmental factors of ***,the effect of HGmF exposure on living systems remains *** this paper,we examine the biological effects of HGmF on the embryonic development of Xenopus laevis（an African clawed frog）. Decrease of horizontal third cleavage furrows and abnormal morphogenesis were

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Cellular & molecular Immunology 2018年第3期15卷 226-232页

作者： John E Pearl mrinal Das Andrea m cooper Department of Infection Immunity and Inflammation Leicester Tuberculosis Research Group(LTBRG)University of LeicesterUniversity RoadLeicesterLE17RHUK

Accurate prediction of which patient will progress from a sub-clinical mycobacterium tuberculosis infection to active tuberculosis represents an elusive,yet critical,clinical research *** the individual perspective,progression can be considered to be the product of a series of unfortunate events or even a run of bad ***,we identify the subtle physiological relationships that can influence the odds of progression to active TB and how this progression may reflect directed dysbiosis in a number of interrelated *** infected individuals who progress to disease have apparently good immune responses,but these responses are,at times,compromised by either local or systemic environmental *** disease promoting processes,such as tissue-damaging granulomata,usually manifest in the lung,but illness is *** apparent dichotomy between local and systemic reflects a clear need to define the factors that promote progression to active disease within the context of the body as a physiological *** discuss aspects of the host environment that can impact expression of immunity,including the microbiome,glucocorticoid-mediated regulation,catecholamines and interaction between the gut,liver and *** suggest the importance of integrating precision medicine into our analyses of experimental outcomes such that apparently conflicting results are not contentious,but rather reflect the impact of these subtle relationships with our environment and microbiota.

关键词： gut-liver-lung axis microbiome tuberculosis

Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

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Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： helen m.Knight merve DemirbugenÖz Adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular GeneticsSchool of Life SciencesUniversity of NottinghamNottinghamUK Department of Pharmaceutical Toxicology Faculty of PharmacyAnkara UniversityAnkaraTurkey

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying *** of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding *** emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these *** processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of *** this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive *** studies first identified mutations within FmR1 to cause intellectual disability Fragile X syndromes several years before FmR1 was identified as an m^(6)A RNA reader ***,familial mutations within the m^(6)A writer gene mETTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development ***,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain ***,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are *** parahippocampal brain tissue,m^(6)A modification is enri

关键词： 5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

Towards a multiscale model of colorectal cancer

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World Journal of Gastroenterology 2007年第9期13卷 1399-1407页

作者： Ingeborg mm van Leeuwen Carina m Edwards mohammad Ilyas helen m Byrne Centre for mathematical medicine and Biology School of Mathematical Sciences University of Nottingham Nottingham NG7 2RD United Kingdom Centre for mathematical Biology Oxford Centre for Industrial and Applied Mathematics Mathematical Institute University of Oxford Oxford OX1 3LB United Kingdom Division of Pathology School of Molecular Medical SciencesQueen’s Medical Centre University of Nottingham Nottingham NG7 2UHUnited Kingdom

Colorectal cancer (CRC) is one of the best characterised cancers, with extensive data documenting the sequential gene mutations that underlie its development. Complementary datasets are also being generated describing changes in protein and RNA expression, tumour biology and clinical outcome. Both the quantity and the variety of information are inexorably increasing and there is now an accompanying need to integrate these highly disparate datasets. In this article we aim to explain why we believe that mathematical modelling represents a natural tool or language with which to integrate these data and, in so doing, to provide insight into CRC.

关键词： Intestinal epithelium Crypt fission APC mutations mathematical modelling Stem cell niche Wnt signalling

Clinical results of linezolid in arthroplasty and trauma related infections

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World Journal of Orthopedics 2014年第2期5卷 151-157页

作者： James Joel Simon matthew Graham Adam Peckham-cooper Nectarios Korres helen Tsouchnica Eleftherios Tsiridis Academic Orthopaedic and Trauma Unit Leeds Teaching Hospitals Leeds School of Medicine Leeds LS1 3EX United Kingdom Royal Liverpool University Hospital Liverpool L7 8XP United Kingdom Academic Orthopaedics and Trauma Unit Division of Surgery Aristotle University Medical School University Campus 54 124 Thessaloniki Greece

AIm: To analyse the management of patients treated with linezolid for orthopaedic ***: Twenty-two patients with orthopaedic related infections receiving a course of linezolid were reviewed retrospectively. Patients were classified into either post trauma, post arthroplasty and non trauma related infections. A diagnosis of infection was based on clinical findings, positive microbiological specimens, and positive signs of infection on radiological imaging and raised inflammatory markers. Pathogens isolated, inflammatory markers both at presentation and at final follow up, length of linezolid treatment, adverse drug reactions, concomitant anti-microbial therapy, length of hospital stay and any surgical interventions were ***: Infections were classified as post arthroplasty(n = 10), post trauma surgery(n = 8) or nontrauma related infections(n = 4). Twenty patients(91%) underwent surgical intervention as part of their treatment. The number of required surgical procedures ranged from 1 to 6(mean = 2.56). mean total length of stay per admission was 28.5 d(range 1-160 d). Furthermore, the mean duration of treatment with linezolid of patients who had resolution of symptoms was 31 d(range 10-84 d). All patients within this group were discharged on oral linezolid. Pathogens isolated included methicillin resistant Staphylococcus aureus, coagulase negative staphylococci, coliforms, enterococcus, Staphylococcus epidermidis, streptococcus viridans, Escherichia coli, group B streptococcus and pseudomonas. An overall 77% of patients demonstrated resolution of infections at follow-up, with mean C-reactive protein reducing from 123 mg/L to 13.2 mg/***: This study demonstrates that the use of linezolid offers excellent efficacy in orthopaedic related infections when used alongside appropriate surgical management.

关键词： Antibiotic resistance Linezolid Orthopaedic infections Osteomyelitis Periprosthetic joint infection

Defining language impairments in a subgroup of children with autism spectrum disorder

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Science China(Life Sciences) 2015年第10期58卷 1044-1052页

作者： helen TAGER-FLUSBERG Department of Psychology Boston University

Autism spectrum disorder(ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment(SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.

关键词： ASD SLI language impairment comorbidity brain imaging

Efficient training of ANN potentials by including atomic forces via Taylor expansion and application to water and a transition-metal oxide

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npj Computational materials 2020年第1期6卷 1205-1218页

作者： April m.cooper Johannes Kästner Alexander Urban Nongnuch Artrith School of Chemistry University of St AndrewsSt AndrewsUK Institute for Theoretical Chemistry University of StuttgartStuttgartGermany Department of Chemical Engineering Columbia UniversityNew YorkNYUSA

Artificial neural network(ANN)potentials enable the efficient large-scale atomistic modeling of complex materials with near firstprinciples *** molecular dynamics simulations,accurate energies and interatomic forces are a prerequisite,but training ANN potentials simultaneously on energies and forces from electronic structure calculations is computationally ***,we introduce an efficient alternative method for the training of ANN potentials on energy and force information,based on an extrapolation of the total energy via a Taylor *** translating the force information to approximate energies,the quadratic scaling with the number of atoms exhibited by conventional force-training methods can be avoided,which enables the training on reference datasets containing complex atomic structures.

关键词： forces enable atomic