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m.lecular Plant 2008年第1期1卷 145-154页

作者： Ping-Hong m.ng Audrey m.cquet Olivier Loudet Annie m.rion-Poll helen m. north Laboratoire de Biologie des Sem.nces UMR 204 INRA AgroParisTech Institut Jean-Pierre Bourgin F-78026 Versailles Cedex France Station de Genetique et Am.lioration 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 tem.erature are key external factors in the control of Arabidopsis thaliana seed germ.nation and dorm.ncy m.chanism.. Perception and response to these stim.li have to ensure that seedling em.rgence and growth occur at the m.st advantageous tim. for correct establishm.nt. Analysis of over 300 Arabidopsis accessions identified 14, from.12 different geographical locations, that were able to germ.nate to greater than 20% at 6℃ in the dark. This natural variation was exploited to identify genetic loci responsible for cold-tolerant, dark germ.nation. A quantitative trait loci approach was used on recom.inant inbred line progeny of a cross between Bay-0 and Shahdara. Six distinct quantitative trait loci were identified, three of which were m.jor loci, each responsible for 17-25% of the phenotypic variability in this trait. Parental phenotypes indicated that the m.jority of the cold-tolerant, dark-germ.nation characteristics are related to light responses. Validation of the three m.jor loci using heterogeneous inbred fam.lies confirm.d the feasibility of fine m.pping and cloning the genes at the quantitative trait loci responsible for cold-tolerant, dark germ.nation.

关键词： Three m.jor Quantitative Cold and Dark Natural Allelic Variation

The ABA-Deficiency Suppressor Locus HAS2 Encodes the PPR Protein LOI1/m.F11 Involved in m.tochondrial RNA Editing

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m.lecular Plant 2015年第4期8卷 644-656页

作者： Julien Sechet Cam.lle Roux Anne Plessis Delphine Effroy Anne Frey Francois Perreau Catherine Biniek Anja Krieger-Liszkay David m.cherel helen m. north Hakim.m.reau Annie m.rion-Poll INRA Institut Jean-Pierre Bourgin UMR 1318 ERL CNRS 3559 Saclay Plant Sciences RD10 F-78026 Versailles France AgroParisTech Institut Jean-Pierre Bourgin UMR 1318 ERL CNRS 3559 Saclay Plant Sciences RD10 F-78026 Versailles France CEA Saclay IBiTec-S CNRS UMR 8221 Serv Bioenerget Biol Struct & Mecanisme F-91191 Gif Sur Yvette France Universite d'Angers UMR IRHS 1345 INRA Agrocampus Ouest F-49045 Angers France Institut Jean-Pierre Bourgin INRA Bat 2 F-78026 Versailles Cedex France Institut Jean-Pierre Bourgin INRA Bat 7 F-78026 Versailles Cedex France Departm.nt of Biology New York University 1009 Main Building 100 Washington Square East New York NY 10003-6688 USA

The hotABA-deficiency suppressor2 （has2） m.tation increases drought tolerance and the ABA sensitivity of stom.ta closure and seed germ.nation. Here we report that the HAS2 locus encodes the m.TOCHONDRIAL EDITING FACTOR11 （m.F11）, also known as LOVASTATIN INSENSITIVE1. has21m.f11 m.tants exhibited phenotypes very sim.lar to the ABA-hypersensitive m.tant, hail-1 pp2ca-1 hab 1-1 abil-2, which is im.aired in four genes encoding type 2C protein phosphatases （PP2C） that act as upstream.negative regulators of the ABA signaling cascade. Like pp2c, m.f11 plants were m.re resistant to progressive water stress and seed germ.nation was m.re sensitive to paclobutrazol （a gibberellin biosynthesis inhibitor） as well as m.nnitol and NaCI, com.ared with the wild-type plants. Phenotypic alterations in m.f11 were associated with the lack of editing of transcripts for the m.tochondrial cytochrom. c m.turation FN2 （cCm.N2） gene, which encodes a cytochrom. c-hem. lyase subunit involved in cytochrom. c biogenesis. Although the abundance of electron transfer chain com.lexes was not affected, their dysfunction could be deduced from.increased respiration and altered production of hydrogen peroxide and nitric oxide in reef11 seeds. As m.nor defects in m.tochondrial respiration affect ABA signaling, this suggests an essential role for ABA in m.tochondrial retrograde regulation.

关键词： abscisic acid m.tochondria pentatricopeptide repeat protein RNA editing drought tolerance germ.nation

Dysregulation of RNA m.dification system. 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 m.rve Dem.rbugen ?z Adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham Departm.nt of Pharm.ceutical Toxicology Faculty of Pharmacy Ankara University

The study of m.dified RNA known as epitranscriptom.cs has becom. increasingly relevant in our understanding of disease-m.difying m.chanism.. m.thylation of N6 adenosine(m.A) and C5 cytosine(m.C) bases occur on m.NAs, tRNA, m.-tRNA, and rRNA species as well as non-coding RNAs. With em.rging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, com.s a new understanding of physiological processes controlled by these system.. Such processes when spatiotem.orally disrupted within cellular nanodom.ins in highly specialized tissues such as the brain, give rise to different form. of disease. In this review, we discuss accum.lating evidence that changes in the m.A and m.C m.thylation system. contribute to neurocognitive disorders. Early studies first identified m.tations within Fm.1 to cause intellectual disability Fragile X syndrom.s several years before Fm.1 was identified as an m.A RNA reader protein. Subsequently, fam.lial m.tations within the m.A writer gene m.TTL5, m.C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form.a protein com.lex with the m.C reader protein ALYREF, were recognized to cause intellectual developm.nt disorders. Sim.larly, differences in expression of the m.C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheim.r’s disease, individuals with a high neuropathological load or have suffered traum.tic brain injury. Likewise, an abundance of m.A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheim.r’s disease, and individuals with high cognitive reserve. m.A-m.dified RNAs are also reported significantly m.re abundant in dem.ntia with Lewy bodies brain tissue but significantly reduced in Parkinson’s disease tissue, whilst m.dified RNAs are m.splaced within diseased cells, particularly where synapses are located. In parahippocam.al brain tissue, m.A m.dification is en

关键词： 5-m.thylcytosine m.thylation Alzheim.r's disease cognitive diseases epitranscriptom.cs intellectual disability Lewy body diseases N6 adenosine RNA m.dification

P system. with array objects and array rewriting rules

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Progress in Natural Science:m.terials International 2007年第4期17卷 479-485页

作者： K.G. Subram.nian R. Saravanan m. Geethalakshm. P. helen Chandra m. m.rgenstern Departm.nt of Com.uter Science Sri Muthukumaran Institute of TechnologyChennai 600 069India Departm.nt of m.them.tics Bharath Institute of Higher Education and ResearchChennai 600 073India Departm.nt of m.them.tics Dr. MGR Janaki CollegeAdayarChennaiIndia Departm.nt of m.them.tics Jayaraj Annapackiam College for Women Periyakulam 625 601India LITA Universite Paul Verlaine-MetzIle du Saulcy57045 Metz CedexFrance

Array P system. were introduced by Paun Gh. which is linking the two areas of m.m.rane com.uting and picture gram.ars. Puzzle gram.ars were introduced by us for generating connected picture arrays in the two-dim.nsional plane, m.tivated by the problem.of tiling the plane. On the other hand, incorporating into arrays the developm.ntal type of generation used in the well-known biologically m.tivated L system., Sirom.ney and Sirom.ney proposed a very general rectangular array generating m.del, called extended controlled tabled L array system.(ECTLAS). In this paper we introduce two variations of the array P system. called BPG array P system.and parallel array P system. The form.r has in the regions array objects and basic puzzle gram.ar rules (BPG), which are a specific kind of puzzle gram.ar rules. In the latter, the regions have rectangular array objects and tables of context-free rules. We exam.ne these two types of P system. for their array generative power.

关键词： m.m.rane com.uting P system. array gram.ars.

m.lecular profiling of indolent hum.n prostate cancer： tackling technical challenges to achieve high-fidelity genom.-wide data

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Asian Journal of Andrology 2012年第3期14卷 385-392,I0005页

作者： Thom.s A. Dunn helen L. Fedor Angelo m. De m.rzo Jun Luo Departm.nt of Urology Johns Hopkins University Baltimore MD 21287 USA Departm.nt of Pathology Johns Hopkins University Baltimore MD 21287 USA

The contem.orary problem.of prostate cancer overtreatm.nt can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged m.n, and lack of sufficiently accurate risk stratification m.thods to reliably seek out m.n with indolent diseases. Since progressive acquisition and accum.lation of genom.c alterations, both genetic and epigenetic, is a defining feature of all hum.n cancers at different stages of disease progression, it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tum.rs m.y be different from.those previously characterized in the setting of clinically significant prostate cancer. Approaches capable of detecting such alterations on a genom.-wide level are the m.st prom.sing. Such analysis m.y uncover m.lecular events defining early initiating stages along the natural history of prostate cancer progression, and ultim.tely lead to rational developm.nt of risk stratification m.thods for identification of m.n who can safely forego treatm.nt. However, defining and characterizing indolent prostate cancer in a clinically relevant context rem.ins a challenge, particularly when genom.-wide approaches are em.loyed to profile form.lin-fixed paraffin-em.edded （FFPE） tissue specim.ns. Here, we provide the conceptual basis underlying the im.ortance of understanding indolent prostate cancer from.m.lecular profiling studies, identify the key hurdles in sam.le acquisition and variables that affect m.lecular data derived from.FFPE tissues, and highlight recent progresses in efforts to address these technical challenges.

关键词： active surveillance form.lin-fixed paraffin-em.edded indolent prostate cancer m.croarray m.lecular profiling prostatecancer prostate cancer progression risk stratification

Bridging the gap——Im.une cells that can repair nerves

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Cellular & m.lecular Im.unology 2021年第4期18卷 784-786页

作者： helen m.m.Gettrick Institute of Inflam.ation and Aging University of BirminghamBirminghamUK

Im.unity is critical for survival in a world plagued by *** that of m.st m.litary operations,the strategy of the im.une system.is based on acceptable losses:determ.ning the m.xim.l am.unt of dam.ge to uninfected tissues that is necessary to defeat or entrap any invading *** characteristic has devastating consequences for patients with im.une-m.diated diseases,including m.ny neurological conditions.

关键词： Im.une diseases dam.ge

Towards a m.ltiscale m.del of colorectal cancer

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

作者： Ingeborg m. van Leeuwen Carina m.Edwards m.ham.ad Ilyas helen m.Byrne Centre for m.them.tical m.dicine and Biology School of Mathematical Sciences University of Nottingham Nottingham NG7 2RD United Kingdom Centre for m.them.tical 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 docum.nting the sequential gene m.tations that underlie its developm.nt. Com.lem.ntary datasets are also being generated describing changes in protein and RNA expression, tum.ur biology and clinical outcom.. Both the quantity and the variety of inform.tion are inexorably increasing and there is now an accom.anying need to integrate these highly disparate datasets. In this article we aim.to explain why we believe that m.them.tical m.delling 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 m.tations m.them.tical m.delling Stem.cell niche Wnt signalling

The Yin and Yang of Wnt/Ryk axon guidance in developm.nt 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 em.ryo,nascent axons navigate towards their specific targets to establish the intricate network of axonal connections linking neurons within the m.ture nervous *** navigational system. com.rising repulsive and attractive guidance cues form.chem.tactic gradients along the pathway of the exploring growth ***-bound receptors detect these gradients and determ.ne the trajectory of the m.grating growth *** contrast to their benevolent role in the developing nervous system.repulsive guidance receptors are detrim.ntal to the axon’s ability to regenerate after injury in the *** this review we explore the essential and beneficial role played by the chem.repulsive Wnt receptor,Ryk/Derailed in axon navigation in the em.ryonic nervous system.the Yin function).Specifically,we focus on the role of Wnt5a/Rykm.diated guidance in the establishm.nt of two m.jor axon tracts in the m.m.alian central nervous system.the corticospinal tract and the corpus *** studies have also identified Ryk as a m.jor suppressor of axonal regeneration after spinal cord ***,we also discuss this opposing aspect of Ryk function in axonal regeneration where its activity is a m.jor im.edim.nt 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 im.airm.nts 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 Departm.nt of Psychology Boston University

Autism.spectrum.disorder(ASD) is diagnosed on the basis of core im.airm.nts in pragm.tic 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 gram.atical knowledge. The m.jority of children are verbal but im.aired in language, relative to age-m.tched peers. One hypothesis is that this subgroup has ASD and co-m.rbid specific language im.airm.nt(SLI). An experim.nt was conducted com.aring children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be im.aired in children with SLI: repetition of nonsense words. Patterns of perform.nce am.ng the children with ASD and language im.airm.nt were sim.lar to those with SLI, and contrasted with the children with ASD and no language im.airm.nt and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-m.rbid SLI. The findings are discussed in the context of brain im.ging studies that have explored the neural bases of language im.airm.nt in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.

关键词： ASD SLI language im.airm.nt com.rbidity brain im.ging

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Adult celiac disease with acetylcholine receptor antibody positive m.asthenia gravis

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

作者： Hugh J Freem.n helen R Gillett Peter m.Gillett Joel Oger Departm.nt of m.dicine (Gastroenterology and Neurology) University of British Columbia

Celiac disease has been associated with som. autoim.une disorders. A 40-year-old com.etitive strongm.n with celiac disease responded to a gluten-free diet, but developed profound and generalized m.tor weakness with acetylcholine receptor antibody positive m.asthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between m.asthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum.sam.les from.23 acetylcholine receptor antibody positive m.asthenia gravis patients with no intestinal sym.tom. were used to screen for celiac disease. Both endom.sial and tissue transglutam.nase antibodies were exam.ned. One of 23 (or, about 4.3%) was positive for both IgA-endom.sial and IgA tissue transglutam.nase antibodies. Endoscopic studies subsequently showed duodenal m.cosal scalloping and biopsies confirm.d the histopathological changes of celiac disease. Celiac disease and m.asthenia gravis m.y occur together m.re often than is currently appreciated. The presence of m.tor weakness in celiac disease m.y be a clue to occult m.asthenia gravis, even in the absence of intestinal sym.tom..

关键词： Acetylcholine receptor antibodies Celiacdisease m.asthenia gravis Transglutam.nase antibodies