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Convergent pathways of the gut microbiota–brain axis and neurodegenerative disorders

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Gastroenterology Report 2022年第1期10卷 90-107页

作者： Carolina Gubert Juciano Gasparotto Livia H.Morais florey institute of Neuroscience and Mental Health Melbourne Brain CentreUniversity of MelbourneParkvilleVictoriaAustralia Instituto de Ciencias Biomedicas Universidade Federal de AlfenasRua Gabriel Monteiro da SilvaAlfenasMinas GeraisBrasil Division of Biology&Biological Engineering California Institute of TechnologyPasadenaCAUSA

Recent research has been uncovering the role of the gut microbiota for brain health and *** studies highlight the role of gut microbiota on regulating brain function and behavior through immune,metabolic,and neuronal *** this review we provide an overview of the gut microbiota axis pathways to lay the groundwork for upcoming sessions on the links between the gut microbiota and neurogenerative *** also discuss how the gut microbiota may act as an intermediate factor between the host and the environment to mediate disease onset and *** on the current literature,we further examine the potential for different microbiota-based therapeutic strategies to prevent,to modify,or to halt the progress of neurodegeneration.

关键词： gut microbiota-brain axis neurodegeneration inflammation microbial metabolism gut microbiota

Brain-derived neurotrophic factors increase the proliferation and differentiation of endogenous neural stem cells in mouse models of cerebral infarction

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Neural Regeneration Research 2007年第3期2卷 134-137页

作者： Dawei Zang Juan Liu Xianhua Zuo Surindar Cheema Department of Neurology Tianjin First Central Hospital Tianjin 300192 China Division of Microbiology Department of Laboratory Tianjin First Central Hospital Tianjin 300192 China howard florey institute Medical College the University of Melbourne Australia

BACKGROUND： It has been confirmed that brain-derived neurotrophic factor （BDNF） can promote the proliferation of neural stem cells （NSCs） and protect neuron-like cells in vitro. However, its effect on endogenous NSCs in vivo is still unclear. OBJECTIVE： To evaluate whether BDNF can induce the endogenous NSCs to proliferate and differentiate into the neurons in the mice model of cerebral infarction. DESIGN： A synchronal controlled observation. SETTINGS： Department of Neurology, Microbiology Division of the Department of Laboratory, Tianjin First Central Hospital; howard florey institute, Medical College, the University of Melbourne. MATERIALS： Twenty-four pure breed C57BL/6J mice at the age of 10 weeks old （12 males and 12 females） were divided into saline control group and BDNF-treated group, 6 males and 6 females in each group. METHODS： The experiments were performed at the University of Melbourne from July 2004 to February 2005. ① The left middle cerebral artery （MCA） was ligated in both groups to establish models of cerebral infarction and the Matsushita measuring method was used to monitor the blood flow of the lesioned region supplied by MCA. 75% reduction of blood flow should be reached in the lesioned region. ② At 24 hours after infarction, mice in the BDNF-treated group were administrated with BDNF, which was slowly delivered using an ALZET osmium pump design. BDNF was dissolved in saline at the dosage of 500 mg/kg and injected into the pump, which could release the solution consistently in the following 28 days. The mice in the saline control group accepted the same volume of saline at 24 hours after infarction. ③ The Rotarod function test began at 1 week preoperatively, the time stayed on Rotarod was recorded. The mice were tested once a day till the end of the experiment. At 4 weeks post cerebral infarction, double labeling of Nestin and GFAP, BIH tubulin and CNPase immunostaining was performed to observe the differentiation directions of the re-expressed

关键词： stem cells brain-derived neurotrophic factor neurons mice

Time to forge ahead:The Internet of Things for healthcare

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Digital Communications and Networks 2023年第1期9卷 223-235页

作者： Denzil Furtado Andre F.Gygax Chien Aun Chan Ashley I.Bush Melbourne Dementia Research Centre&Department of Chemical Engineering University of MelbourneVIC3010Australia Faculty of Business and Economics University of MelbourneVIC3010Australia Department of Electrical and Electronic Engineering University of MelbourneVIC3010Australia florey institute of Neuroscience and Mental Health University of MelbourneVIC3010Australia

Situated at the intersection of technology and medicine,the Internet of Things(IoT)holds the promise of addressing some of healthcare's most pressing challenges,from medical error,to chronic drug shortages,to overburdened hospital systems,to dealing with the COVID-19 ***,despite considerable recent technological advances,the pace of successful implementation of promising IoT healthcare initiatives has been *** inspire more productive collaboration,we present here a simple—but surprisingly underrated—problemoriented approach to developing healthcare *** further assist in this effort,we reviewed the various commercial,regulatory,social/cultural,and technological factors in the development of the *** propose that fog computing—a technological paradigm wherein the burden of computing is shifted from a centralized cloud server closer to the data source—offers the greatest promise for building a robust and scalable healthcare IoT *** this end,we explore the key enabling technologies that underpin the fog architecture,from the sensing layer all the way up to the *** is our hope that ongoing advances in sensing,communications,cryptography,storage,machine learning,and artificial intelligence will be leveraged in meaningful ways to generate unprecedented medical intelligence and thus drive improvements in the health of many people.

关键词： Internet of Things Healthcare Information Fog computing Artificial intelligence Machine learning Big data COVID-19 pandemic

Alexander disease:the road ahead

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Neural Regeneration Research 2023年第10期18卷 2156-2160页

作者： María A.Pajares Elena Hernández-Gerez Milos Pekny Dolores Pérez-Sala Department of Structural and Chemical Biology Centro de Investigaciones Biológicas Margarita SalasMadridSpain Laboratory of Astrocyte Biology and CNS Regeneration Center for Brain RepairDepartment of Clinical NeuroscienceInstitute of Neuroscience and PhysiologySahlgrenska Academy at the University of GothenburgGothenburgSweden University of Newcastle NewcastleNSWand the Florey Institute of Neuroscience and Mental HealthParkvilleVICAustralia

Alexander disease is a rare neurodegenerative disorder caused by mutations in the glial fibrillary acidic protein,a type III intermediate filament protein expressed in *** early(infantile or juvenile)and adult onsets of the disease are known and,in both cases,astrocytes present characteristic aggregates,named Rosenthal *** are spread along the glial fibrillary acidic protein sequence disrupting the typical filament network in a dominant *** the presence of aggregates suggests a proteostasis problem of the mutant forms,this behavior is also observed when the expression of wild-type glial fibrillary acidic protein is ***,several isoforms of glial fibrillary acidic protein have been described to date,while the impact of the mutations on their expression and proportion has not been exhaustively ***,the posttranslational modification patterns and/or the protein-protein interaction networks of the glial fibrillary acidic protein mutants may be altered,leading to functional changes that may modify the morphology,positioning,and/or the function of several organelles,in turn,impairing astrocyte normal function and subsequently affecting *** particular,mitochondrial function,redox balance and susceptibility to oxidative stress may contribute to the derangement of glial fibrillary acidic protein mutant-expressing *** study the disease and to develop putative therapeutic strategies,several experimental models have been developed,a collection that is in constant *** fact that most cases of Alexander disease can be related to glial fibrillary acidic protein mutations,together with the availability of new and more relevant experimental models,holds promise for the design and assay of novel therapeutic strategies.

关键词： astrocytes endoplasmic reticulum stress glial fibrillary acidic protein mutants metabolism misassembly misfolding neurodegeneration oxidative stress posttranslational modifications unfolded protein response

A systemic and molecular study of subcellular localization of SARS-CoV-2 proteins

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Signal Transduction and Targeted Therapy 2020年第1期5卷 252-254页

作者： Jing Zhang Ruth Cruz-cosme Meng-Wei Zhuang Dongxiao Liu Yuan Liu Shaolei Teng Pei-Hui Wang Qiyi Tang Advanced Medical Research institute Cheeloo College of MedicineShandong UniversityJinanShandong 250012China howard University College of Medicine 520 W Street NWWashingtonDC 20059USA Weill institute for Cell and Molecular Biology Cornell UniversityIthacaNYUSA Department of Biology Howard University415 College St.NWWashingtonDC 20059USA

Dear Editor,The current pandemic of beta-coronavirus(SARS-CoV-2)has exerted devastating influence on almost all countries,resulting in the disease named COVID-19.1 Coronavirus possesses the largest RNA genome among all the RNA *** genome encodes about 29 proteins(Supplementary Fig.S1).The subcellular distributions of the viral proteins have yet been reported for *** is important to investigate the viral proteins’locations in cells because the subcellular distribution information not only helps us in understanding how viruses interact with the host cells but also provides clues in fighting against the viral ***,we cloned all the genes of SARS-CoV-2 into vectors for expression in mammalian cells and used immunofluorescent assay(IFA)to examine the viral proteins’subcellular *** for the NSP11 that is only 14 aa long,we expressed all other 28 viral proteins in HEp-2 or Caco-2 cells and found a diversity of protein distribution in cells,suggesting a complicated interaction of SARSCoV-2 with host cells to achieve a successful infection.

关键词： NSP1 fighting distribution

Endovascular thrombectomy for stroke: current best practice and future goals

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Stroke & Vascular Neurology 2016年第1期1卷 16-22页

作者： Bruce C V Campbell Geoffrey A Donnan Peter J Mitchell Stephen M Davis Department of Medicine and Neurology Melbourne Brain Centre at the Royal Melbourne HospitalUniversity of MelbourneParkvilleVictoriaAustralia The florey institute of Neuroscience and Mental Health University of MelbourneParkvilleVictoriaAustralia Department of Radiology Royal Melbourne HospitalUniversity of MelbourneParkvilleVictoriaAustralia

Endovascular thrombectomy for large vessel ischaemic stroke substantially reduces disability,with recent positive randomised trials leading to guideline changes *** review discusses in detail the evidence provided by recent randomised trials and metaanalyses,the remaining areas of uncertainty and the future directions for *** data from existing trials have demonstrated the robust benefit of endovascular thrombectomy for internal carotid and proximal middle cerebral artery *** remains for more distal occlusions where the efficacy of alteplase is greater,less tissue is at risk and the safety of endovascular procedures is less *** artery occlusion was excluded from the trials,but with a dire natural history and proof of principle that rapid reperfusion is effective,it seems reasonable to continue treating these patients pending ongoing trial *** has been no evidence of heterogeneity in treatment effect in clinically defined subgroups by age,indeed,those aged>80 years have at least as great an overall reduction in disability and reduced *** there was no heterogeneity across the range of baseline stroke severities included in the *** that routine use of general anaesthesia reduces the benefit of endovascular thrombectomy is increasing and conscious sedation is generally preferred unless severe agitation or airway compromise is *** impact of time delays has become clearer with description of onset to imaging and imaging to reperfusion *** in the onset to imaging reduce the proportion of patients with salvageable brain ***,in the presence of favourable imaging,rapid treatment appears beneficial regardless of the onset to imaging time *** to reperfusion delays lead to decay in the clinical benefit achieved,particularly in those with less robust collateral *** brain imaging options to assess prognosis have various advantages and disadvan

关键词： routine epoch benefit

The olfactory circuit of the fruit fly Drosophila melanogaster

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Science China(Life Sciences) 2010年第4期53卷 472-484页

作者： LIANG Liang1,2 & LUO Liqun1 1howard Hughes Medical institute, Department of Biology 2Department of Applied Physics, Stanford University, Stanford, CA 94305, USA 1. howard Hughes Medical institute Department of Biology Stanford University Stanford CA 94305 USA2. Department of Applied Physics Stanford University Stanford CA 94305 USA

The olfactory circuit of the fruit fly Drosophila melanogaster has emerged in recent years as an excellent paradigm for studying the principles and mechanisms of information processing in neuronal circuits. We discuss here the organizational principles of the olfactory circuit that make it an attractive model for experimental manipulations, the lessons that have been learned, and future challenges.

关键词： olfactory receptor neurons projection neurons local interneurons antennal lobe mushroom body lateral horn behavior information processing

Chromodynamic Lattice Boltzmann Method for the Simulation of Drops,Erythrocytes,and other Vesicles

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Communications in Computational Physics 2023年第1期33卷 283-309页

作者： J.Spendlove X.Xu T.Schenkel J.P.Gunn I.Halliday Department of Engineering and Mathematics Sheffield Hallam UniversityHoward StreetS11WBUK Materials&Engineering Research institute Sheffield Hallam UniversityHoward StreetS11WBUK Department of Infection Immunity and Cardiovascular DiseaseThe Medical SchoolBeech Hill RoadSheffieldS102RXUK

Recently,we have validated a three-dimensional,single framework multicomponent lattice Boltzmann method,modified to generate vesicles(rather than drops)[“Three-dimensional single framework multicomponent lattice Boltzmann equation method for vesicle hydrodynamics,”*** 33,077110(2021)].This approach implements an immersed boundary force distribution,characterised by bending rigidity,surface tension,preferred curvature and conserved membrane area,in which work we successfully validated isolated vesicle flows against other methodologies and *** most immersed boundary algorithms,our method relies on numerical computation of high-order spatial derivatives and an intricate body force *** next step is to verify that it has sufficient numerical stability to address the anticipated application of high volume fraction flows of highly deformable objects in intimate *** is this in silico verification-of both the class of fluid object attainable and the stability of the later in strong,straining and shearing flows which is at issue,*** extend our method to simulate multiple variously deflated vesicles and multiple liquid droplets still within a single framework,from which our fluid objects emerge as particular *** present data from simulations containing up to four vesicles(five immiscible fluid species),which threshold verifies that simulations containing unlimited fluid objects are possible[“Modeling the flow of dense suspensions of deformable particles in three dimensions,”***.E 75,066707(2007)].These data also assure the ability of our immersed boundary forcing to preserve the character and integrity of fluid objects in interactions characterised by large local velocity gradients(intimate squeezing,shearing and elongational straining).Throughout,we take interfacial or membrane area,A,as a proxy for stability and physical veracity.

关键词： Lattice Boltzmann membranes vesicles

Ferroptosis promotes T-cell activation-induced neurodegeneration in multiple sclerosis

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Cellular & Molecular Immunology 2022年第8期19卷 913-943页

作者： Jinyuan Luoqian Wenyong Yang Xulong Ding Qing-zhang Tuo Zheng Xiang Zhaoyue Zheng Yu-jie Guo Li Li Pengbo Guan Scott Ayton Biao Dong Huiyuan Zhang Hongbo Hu Peng Lei Department of Neurology and Center for Immunology and Hematology State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityCollaborative Innovation Center for BiotherapyChengduSichuanChina Melbourne Dementia Research Centre Florey Institute of Neuroscience and Mental HealthThe University of MelbourneParkvilleVICAustralia

While many drugs are effective at reducing the relapse frequency of multiple sclerosis (MS), there is an unmet need for treatments that slow neurodegeneration resulting from secondary disease progression. The mechanism of neurodegeneration in MS has not yet been established. Here, we discovered a potential pathogenetic role of ferroptosis, an iron-dependent regulated cell death mechanism, in MS. We found that critical ferroptosis proteins (acyl-CoA synthetase long-chain family member 4, ACSL4) were altered in an existing genomic database of MS patients, and biochemical features of ferroptosis, including lipid reactive oxygen species (ROS) accumulation and mitochondrial shrinkage, were observed in the experimental autoimmune encephalitis (EAE) mouse model. Targeting ferroptosis with ferroptosis inhibitors or reducing ACSL4 expression improved the behavioral phenotypes of EAE mice, reduced neuroinflammation, and prevented neuronal death. We found that ferroptosis was an early event in EAE, which may promote T-cell activation through T-cell receptor (TCR) signaling in vitro and in vivo. These data indicate that ferroptosis may be a potential target for treating MS.

关键词： Ferroptosis Multiple sclerosis EAE Neurodegeneration ACSL4