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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

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

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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

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Penetrating ectopic peptic ulcer in the absence of meckel's diverticulum ultimately presenting as small bowel obstruction

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World Journal of Gastroenterology 2007年第46期13卷 6281-6283页

作者： Hilary Hurley Ronan A Cahill Paul Ryan Ashraf I morcos Henry P Redmond helen m.kiely Department of Surgery Cork University HospitalCorkIreland Department of Pathology Cork University HospitalCorkIreland Department of Gastroenterology Mercy University HospitalCorkIreland

We report here how a heterotopic penetrating peptic ulcer progressed to cause small bowel obstruction in a pa- tient with multiple previous negative investigations. The clinical presentation, radiographic features and patho- logical findings of this case are described, along with the salient lessons learnt. The added value of wireless cap- sule endoscopy （WCE） in such circumstances is debated.

关键词： Non-meckelean ectopic peptic ulcer Bowel obstruction

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Changes in ecosystem carbon stocks in a grassland ash (Fraxinus excelsior) afforestation chronosequence in Ireland

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Journal of Plant Ecology 2014年第5期7卷 429-438页

作者： michael L.Wellock Rashad Rafique Christina m.LaPerle matthias Peichl Gerard kiely Centre for Hydrology Micrometeorology and Climate ChangeDepartment of Civil and Environmental EngineeringUniversity College CorkCorkIreland Department of microbiology and Plant Biology University of OklahomaNormanOK 73019USA Department of Forest Ecology and management Swedish University of Agricultural SciencesUmeåSweden

Aims Government policy in Ireland is to increase the national forest cover from the current 10%to 18%of the total land area by *** represents a major land use change that is expected to impact on the national carbon(C)*** the C stocks of ecosystem bio-mass and soils of Irish grasslands and coniferous forests have been quantified,little work has been done to assess the impact of broad-leaf afforestation on C *** In this study,we sampled a chronosequence of ash(Fraxinus excel-sior)forests aged 12,20,27,40 and 47 years on brown earth soils.A grassland site,representative of the pre-afforestation land use,was sampled as a *** Findings Our results show that there was a significant decline(Pm)following afforestation from the grassland(90.2 mg C ha^(−1))to the 27-year-old forest(66.7 mg C ha^(−1)).Subsequently,the forest soils switched from being a C source to a C sink and began to sequester C to 71.3 mg C ha^(−1) at the 47-year-old *** found the amount of C stored in the above-and belowground biomass increased with age of the forest stands and offset the amount of C lost from the *** amount of C stored in the above-and belowground biomass increased on average by 1.83 mg C ha^(−1) year^(−1).The increased storage of C in the biomass led to an increase in the total ecosystem C,from 90.2 mg C ha^(−1) at the grassland site to 162.6 mg C ha^(−1) at the 47-year-old *** a national scale,projected rates of ash afforestation to the year 2020 may cause a loss of 290752 mg C from the soil compared to 2525936 mg C sequestered into the tree *** effects of harvesting and reforestation may further modify the development of ecosystem C stocks over an entire ash rotation.

关键词： ash(Fraxinus excelsior L.) chronosequence soil biomass carbon ecosystem

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The Yin and Yang of Wnt/Ryk axon guidance in development and regeneration

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Science China(Life Sciences) 2014年第4期57卷 366-371页

作者： CLARK Charlotte EJ LIU Yaobo COOPER helen m Queensland Brain Institute The University of QueenslandBrisbane Institute of Neuroscience Soochow University

In the developing embryo,nascent axons navigate towards their specific targets to establish the intricate network of axonal connections linking neurons within the mature nervous *** navigational systems comprising repulsive and attractive guidance cues form chemotactic gradients along the pathway of the exploring growth ***-bound receptors detect these gradients and determine the trajectory of the migrating growth *** contrast to their benevolent role in the developing nervous system,repulsive guidance receptors are detrimental to the axon’s ability to regenerate after injury in the *** this review we explore the essential and beneficial role played by the chemorepulsive Wnt receptor,Ryk/Derailed in axon navigation in the embryonic nervous system(the Yin function).Specifically,we focus on the role of Wnt5a/Rykmediated guidance in the establishment of two major axon tracts in the mammalian central nervous system,the corticospinal tract and the corpus *** studies have also identified Ryk as a major suppressor of axonal regeneration after spinal cord ***,we also discuss this opposing aspect of Ryk function in axonal regeneration where its activity is a major impediment to axon regrowth(the Yang function).

关键词： Ryk Derailed Wnt Wnt signalling axon guidance axonal regeneration spinal cord injury

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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

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Analysis of Natural Allelic Variation Controlling Arabidopsis thaliana Seed Germinability in Response to Cold and Dark： Identification of Three major Quantitative Trait Loci

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molecular Plant 2008年第1期1卷 145-154页

作者： Ping-Hong meng Audrey macquet Olivier Loudet Annie marion-Poll helen m. North Laboratoire de Biologie des Semences UMR 204 INRA AgroParisTech Institut Jean-Pierre Bourgin F-78026 Versailles Cedex France Station de Genetique et Amelioration des Plantes INRA Institut Jean-Pierre Bourgin F-78026 Versailles Cedex France Present address: Institute of Horticulture Guizhou Academy of Agricultural Sciences GuiYang Guizhou Province 550006 RR. China

Light and temperature are key external factors in the control of Arabidopsis thaliana seed germination and dormancy mechanisms. Perception and response to these stimuli have to ensure that seedling emergence and growth occur at the most advantageous time for correct establishment. Analysis of over 300 Arabidopsis accessions identified 14, from 12 different geographical locations, that were able to germinate to greater than 20% at 6℃ in the dark. This natural variation was exploited to identify genetic loci responsible for cold-tolerant, dark germination. A quantitative trait loci approach was used on recombinant inbred line progeny of a cross between Bay-0 and Shahdara. Six distinct quantitative trait loci were identified, three of which were major loci, each responsible for 17-25% of the phenotypic variability in this trait. Parental phenotypes indicated that the majority of the cold-tolerant, dark-germination characteristics are related to light responses. Validation of the three major loci using heterogeneous inbred families confirmed the feasibility of fine mapping and cloning the genes at the quantitative trait loci responsible for cold-tolerant, dark germination.

关键词： .Arabidopsis accessions Seed Germinability Cold and Dark Shahdara

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Seasonal exports of phosphorus from intensively fertilised nested grassland catchments

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Journal of Environmental Sciences 2013年第9期25卷 1847-1857页

作者： Ciaran Lewis Rashad Rafique Nelius Foley Paul Leahy Gerard morgan John Albertson Sandeep Kumar Gerard kiely Department of Civil and Environmental Engineering University College Cork Department of microbiology and Plant Biology University of Oklahoma Environmental Research Institute University College Cork Aquatic Services Unit Environmental Research Institute University College Cork Department of Civil and Environmental Engineering Duke University Department of Plant Science South Dakota State University

We carried out a one year （2002） study of phosphorus （P） loss from soil to water in three nested grassland catchments with known P input in chemical fertilizer and animal liquid slurry applications. Chemical fertilizer was applied to the grasslands between march and September and animal slurry was applied over the twelve months. The annual chemical P fertilizer applications for the 17 and 211 ha catchments were 16.4 and 23.7 kg P/ha respectively and the annual slurry applications were 10.7 and 14.0 kg P/ha, respectively. The annual total phosphorus （TP） export in stream-flow was 2.61, 2.48 and 1.61 kg P/ha for the 17, 211 and 1524 ha catchments, respectively, compared with a maximum permissible （by regulation） annual export of ca. 0.35 kg P/ha. The export rate （ratio of P export to P in land applications） was 9.6% and 6.6% from the 17 and 211 ha catchments, respectively. On average, 70% of stream flow and 85% of the P export occurred during the five wet months （October to February） indicating that when precipitation is much greater than evaporation, the hydrological conditions are most favourable for P export. However the soil quality and land use history may vary the results. Particulate P made up 22%, 43% and 37% of the TP export at the 17, 211 and 1524 ha catchment areas, respectively. As the chemical fertilizer was spread during the grass growth months （march to September）, it has less immediate impact on stream water quality than the slurry applications. We also show that as the catchment scale increases, the P concentrations and P export decrease, confirming dilution due to increasing rural catchment size. In the longer term, the excess P from fertilizer maintains high soil P levels, an antecedent condition favourable to P loss from soil to water. This study confirms the significant negative water quality impact of excess P applications, particularly liquid animal slurry applications in wet winter months. The findings suggest that restricted P application in w

关键词： phosphorus fertilizer slurry exports grassland land management water quality eutrophication

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Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis

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World Journal of Gastroenterology 2009年第38期15卷 4741-4744页

作者： Hugh J Freeman helen R Gillett Peter m Gillett Joel Oger Department of medicine (Gastroenterology and Neurology) University of British Columbia

Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a gluten-free diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum samples from 23 acetylcholine receptor antibody positive myasthenia gravis patients with no intestinal symptoms were used to screen for celiac disease. Both endomysial and tissue transglutaminase antibodies were examined. One of 23 (or, about 4.3%) was positive for both IgA-endomysial and IgA tissue transglutaminase antibodies. Endoscopic studies subsequently showed duodenal mucosal scalloping and biopsies confirmed the histopathological changes of celiac disease. Celiac disease and myasthenia gravis may occur together more often than is currently appreciated. The presence of motor weakness in celiac disease may be a clue to occult myasthenia gravis, even in the absence of intestinal symptoms.

关键词： Acetylcholine receptor antibodies Celiacdisease myasthenia gravis Transglutaminase antibodies

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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

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