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Adiponectin signalling in bone homeostasis,with age and in disease

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Bone Research 2021年第1期9卷 15-25页

作者： Jonathan W.Lewis James R.Edwards Amy J.Naylor helen m.mcgettrick Rheumatology Research Group Institute of Inflammation and AgeingUniversity of BirminghamBirmingham B152TTUK Ageing&Regeneration Research Group Botnar Research CentreUniversity of OxfordOxford OX37LDUK

Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin *** the bone,osteoblasts and osteoclasts express the adiponectin receptors,however,there are conflicting reports on the effects of adiponectin on bone formation and *** studies have shown a pro-osteogenic role for adiponectin in in vivo murine models and in vitro:with increased osteoblast differentiation and activity,alongside lower levels of ***,human studies often demonstrate an inverse relationship between adiponectin concentration and bone ***,the presence of multiple isoforms of adiponectin and multiple receptor subtypes has the potential to lead to more complex signalling and functional *** such,we still do not fully understand the importance of the adiponectin signalling pathway in regulating bone homeostasis and repair in health,with age and in *** this review,we explore our current understanding of adiponectin bioactivity in the bone;the significance of its different isoforms;and how adiponectin biology is altered in ***,furthering our understanding of adiponectin regulation of bone biology is key to developing pharmacological and non-pharmacological(lifestyle)interventions that target adiponectin signalling to boost bone growth and repair in healthy ageing,following injury or in disease.

关键词： homeostasis metabolism consequences

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

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

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

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： Three major Quantitative Cold and Dark Natural Allelic Variation

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

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

Accuracy of genomic selection in biparental populations of flax(Linum usitatissimum L.)

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The Crop Journal 2016年第4期4卷 290-303页

作者： Frank m.You helen m.Booker Scott D.Duguid Gaofeng Jia Sylvie Cloutier morden Research and Development Centre Agriculture and Agri-Food Canada Crop Development Centre Department of Plant Sciences University of Saskatchewan Ottawa Research and Development Centre Agriculture and Agri-Food Canada

Flax is an important economic crop for seed oil and stem fiber. Phenotyping of traits such as seed yield, seed quality, stem fiber yield, and quality characteristics is expensive and time consuming. Genomic selection(GS) refers to a breeding approach aimed at selecting preferred individuals based on genomic estimated breeding values predicted by a statistical model based on the relationship between phenotypes and genome-wide genetic markers. We evaluated the prediction accuracy of GS(rmP) and the efficiency of GS relative to phenotypic selection(RE) for three GS models: ridge regression best linear unbiased prediction(RR-BLUP),Bayesian LASSO(BL), and Bayesian ridge regression(BRR), for seed yield, oil content, iodine value, linoleic, and linolenic acid content with a full and a common set of genome-wide simple sequence repeat markers in each of three biparental populations. The three GS models generated similar rmPand RE, while BRR displayed a higher coefficient of determination(R^2)of the fitted models than did RR-BLUP or BL. The mean rmPand RE varied for traits with different heritabilities and was affected by the genetic variation of the traits in the *** for seed yield generated a mean RE of 1.52 across populations and marker sets, a value significantly superior to that for direct phenotypic selection. Our empirical results provide the first validation of GS in flax and demonstrate that GS could increase genetic gain per unit time for linseed breeding. Further studies for selection of training populations and markers are warranted.

关键词： Genomic selection SSR Flax Linseed Seed yield Fatty acid composition