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实验性兔动脉瘤氧化应激评价

中国医学科学院学报 2006年第5期28卷 707-709页

作者：李立杨新健蒋凡刘爱华吴中学 Gregory J Dusting 北京市神经外科研究所神经介入科北京100050 howard florey institute the University of MelbourneVictoria 3010Australia

目的评价氧化应激在动脉瘤发生发展中的作用。方法复制兔顶端动脉瘤模型5个和侧方动脉瘤模型8个,以6段正常血管为对照。用化学方法检测标本中丙二醛(MDA)、超氧化物歧化酶(SOD)和抗活性氧单位的水平。结果顶端动脉瘤和侧方动脉瘤标本中... 详细信息

目的评价氧化应激在动脉瘤发生发展中的作用。方法复制兔顶端动脉瘤模型5个和侧方动脉瘤模型8个,以6段正常血管为对照。用化学方法检测标本中丙二醛(MDA)、超氧化物歧化酶(SOD)和抗活性氧单位的水平。结果顶端动脉瘤和侧方动脉瘤标本中MDA含量分别为(33.85±8.66)和(27.87±5.78)nmol/mgprot,均显著高于对照组的(10.91±2.72)nmol/mgprot(P均<0.01);两种动脉瘤的SOD含量分别为(28.30±3.58)和(33.00±8.09)U/mgprot,均显著低于对照组(127.27±38.72)U/mgprot(P均<0.01);两种动脉瘤的抗活性氧单位含量分别为(47.86±5.00)和(62.64±13.87)U/mgprot,也均显著低于对照组(116.94±9.22)U/mgprot(P均<0.01)。顶端动脉瘤和侧方动脉瘤之间除抗活性氧单位具有显著差异(P=0.014)外,MDA和SOD均无统计学差异。MDA与SOD和抗活性氧单位呈显著负相关关系,相关系数分别为-0.830和-0.852(P<0.01)。结论氧化应激对血管造成的损伤可能在动脉瘤的发展过程中起重要作用。不同类型动脉瘤的氧化应激差异性不明显。

关键词：动脉瘤氧化应激自由基

Heat Shocking the Jedi Master: HSP90’s Role in Regulating Stomatal Cell Fate

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Molecular Plant 2020年第4期13卷 536-538页

作者： Aarthi Putarjunan Keiko U.Torii howard Hughes Medical institute and Department of Molecular Biosciences The University of Texas at AustinAustinTX 78712USA

Plant stomata facilitate efficient gas exchange and control water loss in plants throughout the course of their *** stomatal pores plants take in CO2 from the atmosphere for photosynthesis,resulting in O2 and H2O being released back into the atmosphere,which makes life on Earth ***,the density and distribution of stomata on the epidermis of photosynthetic organs are critical for overall plant growth and *** the rise in global warming and harsher climatic conditions that threaten food security for future generations,understanding how stomatal density and distribution can be altered may serve as a valuable tool for the generation of crops that can withstand the adverse environmental conditions such as drought,flooding,extremes in temperature,and excessive salinity(Endo and Torii,2019).Temperature fluctuations constitute a critical environmental factor affecting the spatiotemporal development of plants,and seasonal fluctuations in temperature can greatly influence crop yield and productivity of agriculturally important plant species.

关键词： distribution crops salinity

Alternative models for transgenerational epigenetic inheritance:Molecular psychiatry beyond mice and man

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World Journal of Psychiatry 2021年第10期11卷 711-735页

作者： Gary R Hime Sophie LA Stonehouse Terence Y Pang Department of Anatomy and Physiology The University of MelbourneParkville 3010VICAustralia Mental Health Theme The Florey Institute of Neuroscience and Mental HealthParkville 3052VICAustralia

Mental illness remains the greatest chronic health burden globally with few inroads having been made despite significant advances in genomic knowledge in recent *** field of psychiatry is constantly challenged to bring new approaches and tools to address and treat the needs of vulnerable individuals and subpopulations,and that has to be supported by a continuous growth in *** majority of neuropsychiatric symptoms reflect complex geneenvironment interactions,with epigenetics bridging the gap between genetic susceptibility and environmental stressors that trigger disease onset and drive the advancement of *** has more recently been demonstrated in preclinical models that epigenetics underpins the transgenerational inheritance of stressrelated behavioural phenotypes in both paternal and maternal lineages,providing further supporting evidence for heritability in ***,unbiased prospective studies of this nature are practically impossible to conduct in humans so preclinical models remain our best option for researching the molecular pathophysiologies underlying many neuropsychiatric *** rodents will remain the dominant model system for preclinical studies(especially for addressing complex behavioural phenotypes),there is scope to expand current research of the molecular and epigenetic pathologies by using invertebrate ***,we will discuss the utility and advantages of two alternative model organisms–Caenorhabditis elegans and Drosophila melanogaster-and summarise the compelling insights of the epigenetic regulation of transgenerational inheritance that are potentially relevant to human psychiatry.

关键词： Transgenerational inheritance Epigenetics Invertebrate models Caenorhabditis elegans Drosophila melanogaster Environmental stress

Glutamate transporters, EAAT1 and EAAT2, are potentially important in the pathophysiology and treatment of schizophrenia and affective disorders

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World Journal of Psychiatry 2018年第2期8卷 51-63页

作者： Georgia M Parkin Madhara Udawela Andrew Gibbons Brian Dean Molecular Psychiatry Laboratory the Florey Institute of Neuroscience and Mental Health CRC for Mental Health Research Centre for Mental Health the Faculty of Health Arts and Design Swinburne University

Glutamate is the predominant excitatory neurotransmitter in the human brain and it has been shown that prolonged activation of the glutamatergic system leads to nerve damage and cell death. Following release from the pre-synaptic neuron and synaptic transmission, glutamate is either taken up into the presynaptic neuron or neighbouring glia by transmembrane glutamate transporters. Excitatory amino acid transporter(EAAT) 1 and EAAT2 are Na+-dependant glutamate transporters expressed predominantly in glia cells of the central nervous system. As the most abundant glutamate transporters, their primary role is to modulate levels of glutamatergic excitability and prevent spill over of glutamate beyond the synapse. This role is facilitated through the binding and transportation of glutamate into astrocytes and microglia. The function of EAAT1 and EAAT2 is heavily regulated at the levels of gene expression, post-transcriptional splicing, glycosylation states and cell-surface trafficking of the protein. Both glutamatergic dysfunction and glial dysfunction have been proposed to be involved in psychiatric disorder. This review will present an overview of the roles that EAAT1 and EAAT2 play in modulating glutamatergic activity in the human brain, and mount an argument that these two transporters could be involved in the aetiologies of schizophrenia and affective disorders as well as represent potential drug targets for novel therapies for those disorders.

关键词： Glia Excitatory amino acid transporter Psychiatry Affective disorders Glutamate transporter Glutamate Schizophrenia

Muscarinic Acetylcholine Receptors in Alcohol Use Disorder

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神经药理学报 2019年第Z1期 30-31页

作者： Andrew J Lawrence florey institute of Neuroscience and Mental Health ParkvilleVictoriaFlorey Department of Neuroscience and Mental HealthUniversity of Melbourne

Background:Despite the large socioeconomic burden of alcohol use disorders(AUD),therapeutic treatment options are limited. There is a need to characterise the underlying neurochemistry driving alcohol seeking to identify and evaluate novel targets. AUDs are characterised by a transition to compulsive seeking,which is hypothesized to involve a shift from ventral to dorsal striatum and a medial to lateral dorsal striatal shift in the transition from goaldirected to habitual alcohol-seeking behaviours. Muscarinic acetylcholine receptors(mAChRs) are a potential target for AUD;they are expressed within the mesocorticolimbic reward system,including dense expression in the dorsal striatum,where they modulate dopamine and glutamate release,which may regulate reward processing. Methods:To assess the role of mAChRs in AUD,we first conducted genome-wide RNA sequencing in the caudate/putamen of 10 human alcoholics and 10 healthy controls and concurrently examined muscarinic receptor expression in the corresponding regions in rat(dorsolateral and dorsomedial striatum) following chronic alcohol consumption/withdrawal using qPCR. Next we examined the role of select muscarinic and nicotinic receptor subtypes in alcohol consumption and seeking using selective allosteric modulators. Finally,we probed the role of select muscarinic and nicotinic receptor subtypes in the dorsal striatum in alcohol consumption and seeking. Results:In human alcoholics M4 receptor expression was significantly decreased in the putamen. In line with this,M4 receptor expression was decreased in the rat dorsolateral striatum. Further,administration of VU154(30 mg·kg-1,p.o.) reduced alcohol self-administration and cue-induced relapse,without effects on natural reward consumption or sedation. We also found that a centrally active and selective negative allosteric modulator(NAM) for the rat M5 muscarinic receptor(mAChR),ML375,selectively decreases ethanol self-administration and attenuates cue-induced reinstateme

关键词： AUD Muscarinic Acetylcholine Receptors in Alcohol Use Disorder

The florey institute of Neuroscience and Mental Health,

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Journal of Translational Neuroscience 2018年第2期3卷 35-38页

作者： Geoffrey A Donnan AO The florey institute of Neuroscience and Mental Health Florey Department of Neuroscience and Mental Health the Universityof Melbourne Parkville Victoria 3052 Australia

1Early history In1963the howard florey Laboratories were first established as a component of the Department of Physiology at the University of *** laboratories quickly expanded under the founding directorship of *** Denton and the funds were obtained with the philanthropic assistance of Sir Ian Potter and *** Myer to create a new building on the south-west corner University *** enabled the building to be opened in *** Nobel laureate,Sir howard florey,well-known discoverer of the technique to mass-produce penicillin was pleased to lend his name to the new initiative,and was present at its opening with the Prime Minister,Sir Robert Menzies,and other dignitaries.

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Artificial neural network approach for rheological characteristics of coal-water slurry using microwave pre-treatment

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International Journal of Mining Science and Technology 2017年第2期27卷 379-386页

作者： B.K.Sahoo S.De B.C.Meikap Department of Chemical Engineering Indian Institute of Technology Research and Development Centre for Iron and Steel Steel Authority of India Limited Chemical Engineering School of Engineering Howard College University of Kwazulu-Natal

Detailed experimental investigations were carried out for microwave pre-treatment of high ash Indian coal at high power level(900 W) in microwave oven. The microwave exposure times were fixed at60 s and 120 s. A rheology characteristic for microwave pre-treatment of coal-water slurry(CWS) was performed in an online Bohlin viscometer. The non-Newtonian character of the slurry follows the rheological model of Ostwald de Waele. The values of n and k vary from 0.31 to 0.64 and 0.19 to 0.81 Pa·sn,respectively. This paper presents an artificial neural network(ANN) model to predict the effects of operational parameters on apparent viscosity of CWS. A 4-2-1 topology with Levenberg-Marquardt training algorithm(trainlm) was selected as the controlled ANN. Mean squared error(MSE) of 0.002 and coefficient of multiple determinations(R^2) of 0.99 were obtained for the outperforming model. The promising values of correlation coefficient further confirm the robustness and satisfactory performance of the proposed ANN model.

关键词： Microwave pre-treatment Coal-water slurry Apparent viscosity Artificial neural network Back propagation algorithm

Novel pluripotent stem cell lines for enriched grafting in Parkinson’s disease

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Neural Regeneration Research 2020年第2期15卷 255-256页

作者： Agustin Cota-Coronado Lachlan H.Thompson N.Emmanuel Diaz-Martinez Biotecnologia Medica y Farmaceutica Centro de Investigacion y Asistencia en Tecnologia y Diseno del Estado de JaliscoGuadalajaraMexico The florey institute of Neuroscience and Mental Health The University of MelbourneMelbourneAustralia

Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting 1% of the population over 55 years of age and up to 4% of the population over 80 years of age (Blesa et al., 2012). This progressive and neurodegenerative condition results from an excessive loss of dopaminergic neurons (50-70%) of the substantia nigra pars compacta, leading to a significant decrease in dopamine (DA) levels in the striatum and consequently a functional deterioration of motor circuity (Blesa et al., 2012;Nielsen et al., 2016).

关键词： Parkinson's disease striatum neurodegenerative

Characterization of tub_4^(P287L), a β-tubulin mutant,revealed new aspects of microtubule regulation in shade

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Journal of Integrative Plant Biology 2015年第9期57卷 757-769页

作者： Jie Yu Hong Qiu Xin Liu Meiling Wang Yongli Gao Joanne Chory Yi Tao School of Life Sciences Xiamen Plant Genetics Key Laboratory Xiamen University State Key Laboratory of Cellular Stress Biology Xiamen University howard Hughes Medical institute The Salk Institute for Biological Studies Plant Biology Laboratory The Salk Institute for Biological Studies

When sun plants, such as Arabidopsis thaliana, are under canopy shade, elongation of stems/petioles will be induced as one of the most prominent responses. Plant hormones mediate the elongation growth. However, how environmental and hormonal signals are translated into cell expansion activity that leads to the elongation growth remains elusive. Through forward genetic study, we identi-fied shade avoidance2 (sav2) mutant, which contains a P287L mutation in b-TUBULIN 4. Cortical microtubules (cMTs) play a key role in anisotropic cell growth. Hypocotyls of sav2 are wild type-like in white light, but are short and highly swollen in shade and dark. We showed that shade not only induces cMT rearrangement, but also affects cMT stability and dynamics of plus ends. Even though auxin and brassinosteroids are required for shade-induced hypocotyl elongation, they had little effect on shade-induced rearrangement of cMTs. Blocking auxin transport suppressed dark phenotypes of sav2, while overexpressing EB1b-GFP, a microtubule plus-end binding protein, rescued sav2 in both shade and dark, suggesting that tub4P287L represents a unique type of tubulin mutation that does not affect cMT function in supporting cell elongation, but may affect the ability of cMTs to respond properly to growth promoting stimuli.

关键词： Arabidopsis microtubules plant hormones shade