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Neural Regeneration Research 2015年第5期10卷 713-714页

作者： miranda mladinic Andrea Nistri Department of Biotechnology University of Rijeka Neuroscience Department International School for Advanced Studies (SISSA)34136 TriesteItaly (Nistri 1)

One of the major problems of modern neurobiology is how to replace dead or damaged neurons in the human brain or spinal cord after injury or as a consequence of neurodegenerative dis- eases. In fact, because adult mammalian neurons are post-mi- totic cells that cannot divide to replace dead cells, loss due to lesion or disease is permanent. Furthermore, surviving neurons have modest capacity to regenerate their damaged axons and re-establish functional connections. Thus, a gradual neurode- generative scenario with certain similarities in stroke, brain or spinal cord injuries and neurological diseases like Alzheimer＇s disease is produced. These conditions represent the major disease burden of the modern world in terms of mortality, dis- ability, productivity loss and health-care costs （World Health Organization, 2008）. While much effort has been directed to understand the molecular and cellular mechanisms involved in the pathology of these diseases to set new effective treatments, many neuroprotective and regenerative approaches, although showing positive results in preclinical studies, have so far failed to provide strong benefit to patients.

关键词： stem cell ATF

Monodelphis domestica: a new source of mammalian primary neurons in vitro

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Neural Regeneration Research 2022年第8期17卷 1726-1727页

作者： Jelena Ban miranda mladinic Laboratory for Molecular Neurobiology Department of BiotechnologyUniversity of RijekaRijekaCroatia

In vi t ro mode ls have tremendously revolutionized cell biology and biomedical research,reducing the need for in vivo experiments,as well as offering the simplified models for easier investigations at molecular and cellular level(for example genetic manipulations,electrophysiological measurements,drug screening etc.).However,the major challenge is to develop long-surviving in vitro preparations of post-mitotic cells such as neurons or *** overcome the problem of neuronal inability to proliferate,the immortalized cell lines derived from neuronal tumors have been *** secondary neuronal cultures are restricted to neuroblastoma-like cells,but their biological relevance is often questionable due to genetic drift and lack of mature,differentiated neuronal phenotypes,which makes primary cultures the better *** central nervous system(CNS)in vitro primary cell cultures are mostly prepared from the late embryonic or early postnatal mice and *** mammalian species have been less used,meaning that inter-species diversity is not sufficiently investigated and that the additional comparative analyses are required to avoid misinterpretations in translating the knowledge to humans(Bonfanti and Peretto,2011).

关键词： overcome offering mostly

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose M.Santiago Samuel E.Ocasio Rivera Dina P.Bracho-Rincon Luis H.Pagan Rivera Jorge D.miranda Department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

Therapies for Tau-associated neurodegenerative disorders:targeting molecules,synapses,and cells

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Neural Regeneration Research 2023年第12期18卷 2633-2637页

作者： miranda Robbins MRC Laboratory of Molecular Biology Cambridge Biomedical CampusFrancis Crick AveTrumpingtonCambridgeUKUniversity of CambridgeDepartment of ZoologyCambridgeUK

Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers that were approved for use in Alzheimer's disease. As diagnostic screening can detect disorders at earlier time points, the field needs pre-symptomatic treatments that can prevent, or significantly delay the progression of these disorders(Koychev et al., 2019). These approaches may be different from late-stage treatments that may help to ameliorate symptoms and slow progression once symptoms have become more advanced should early diagnostic screening fail. This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders. These avenues include investigating(1) the broad class of chemicals termed “small molecules”;(2) adaptive immunity through both passive and active antibody treatments;(3) innate immunity with an emphasis on microglial modulation;(4) synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies. Although this mini-review will focus on Alzheimer's disease due to its prevalence, it will also argue the need to target other tauopathies, as through understanding Alzheimer's disease as a Tau-associated neurodegenerative disorder, we may be able to generalize treatment options. For this reason, added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.

关键词： Alzheimer's disease antibody frontotemporal dementia immunotherapy small molecules synapses tau therapeutics

On Building Practical Biocomputers for Real-world Applications： Receptacles for Culturing Slime Mould Memristors and Component Standardisation

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Journal of Bionic Engineering 2017年第1期14卷 151-162页

作者： Edward Braund Eduardo Reck miranda Interdisciplinary Centre for Computer Music Research (ICCMR) The House Plymouth University Drake Circus UK PL4 8AA

Our application of bionic engineering is novel： we are interested in developing hybrid hardware-wetware systems for music. This paper introduces receptacles for culturing Physarum polycephalum-based memristors that are highly accessible to the creative practitioner. The myxomycete Physarum polycephalum is an amorphous unicellular organism that has been found to exhibit memristive properties. Such a discovery has potential to allow us to move towards engineering electrical systems that encompass Physarum polycephalum components. To realise this potential, it is necessary to address some of the constraints associated with harnessing living biological entities in systems for real-time application. Within the paper, we present 3D printed receptacles designed to standardise both the production of components and memristive observations. Subsequent testing showed a significant decrease in growth time, increased lifespan, and superior similarity in component-to-component responses. The results indicate that our receptacle design may provide means of implementing hybrid electrical systems for music technology.

关键词： unconventional computing Physarum polycephalum computer music biological computing memristor

Development of a 3D model for particle-wall collision and induced rotation and its influence on particle trajectories

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Particuology 2024年第11期94卷 211-228页

作者： Cairen miranda John Palmore Jr. Department of Mechanical Engineering Virginia TechBlacksburg24060VAUSA Department of Mechanical Engineering University of WashingtonSeattle98195WAUSA

The present research focuses on improving the prediction of rotating particle *** particle-surface collision models do not accurately predict the particle rebound when taking rotation into *** data,such as the studies by Gorham and Kharaz(2000),Buck,Tang,Heinrich,Deen and Kuipers(2017),and Dong and Moys(2006)show that the Tsuji,Oshima and Morikawa(1985)model is inaccurate due to the incorrect tangential coefficient of restitution ***,Kuipers,Mohd Salleh,Stein,and Seville(2001)introduced a similar model to the work by Tsuji et al.(1985)which includes a tangential coefficient of restitution but is only in two dimensions and does not consider out of plane *** work re-derives the particle collision model from the impulse equations for binary collisions in 3D while considering rotating *** derived equations in this work compares well to experimental particle-surface impact *** implications of this model are seen by investigating erosion due to particle collision in a simple pipe *** is shown that Tsuji et al.(1985)over predicts the *** small differences in particle trajectories between the present model and the Tsuji et al.(1985)model will grow in complex flows with multiple close range particle impacts leading to inaccurate erosion predictions which will negatively impact the design of turbomachinery and pneumatic pipes.

关键词： Particle collisions CFD Rotation Three dimensional

Successful Large-scale Renewables Integration in Portugal:Technology and Intelligent Tools

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CSEE Journal of Power and Energy Systems 2017年第1期3卷 7-16页

作者： Vladimiro miranda Faculty of Engineering University of PortoPortugal

Portugal is seen worldwide as a case of success in the large-scale integration of renewables in its power system,especially for wind *** policies and sound management decisions are fundamental,but a sustainable process is not possible without the development of endogenous *** paper summarizes a set of models,both applied by the industry and representing actual technologic advancement,denoting the context of research and innovation in the country that helps to explain such *** arise in reliability assessment for systems with renewables,active and reactive power control,integration of wind farms,storage,electric vehicle integration,wind and solar power forecasting and distribution operation and state estimation taking advantage of smart grid *** all cases,one relevant trait is evident:the pervasive use of computational intelligence tools.

关键词： Autoencoders electric vehicles EPSO evolutionary particle swarm optimization forecasting voltage/var control large-scale integration reliability renewables smart grids solar power state estimation storage wind power

Preventing brain aging by the artificial enforcement of the unfolded protein response:future directions

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Neural Regeneration Research 2024年第2期19卷 393-394页

作者： Felipe Cabral-miranda Claudio Hetz Instituto de Ciências Biomédicas Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Center for Geroscience Brain Health and MetabolismSantiagoChile、Biomedical Neuroscience InstituteFaculty of MedicineUniversity of ChileSantiagoChile、Program of Cellular and Molecular BiologyInstitute of Biomedical SciencesFaculty of MedicineUniversity of ChileSantiagoChile、Buck Institute for Research on AgingNovatoCAUSA

As the life expectancy of the world’s population increases,age-related diseases are emerging as one of the greatest problems facing modern *** onset of dementia and neurodegenerative diseases is strictly dependent on aging as a major risk factor and has a profound impact on various aspects of the lives of individuals and their families.

关键词： diseases aging directions

Elucidating the pathological mechanisms of neurodegeneration in the lethal serpinopathy FENIB

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Neural Regeneration Research 2022年第8期17卷 1733-1734页

作者： Elena miranda Giovanna Galliciotti Department of Biology and Biotechnologies‘Charles Darwin’and Pasteur Institute-Cenci Bo-lognetti Foundation Sapienza University of RomeRomeItaly Institute of Neuropathology University Medical Center Hamburg-EppendorfHamburgGermany

The term serpinopathies was introduced to describe a family of diseases caused by point mutations in serine protease inhibitors,or *** inhibit their cognate protease by an irreversible suicide mechanism starting with the attack of the active site serine on the reactive center loop of the inhibitor,followed by formation of a covalent complex between both proteins,insertion of the reactive center loop of the serpin into its own beta-sheet A,and culminating in distortion of the active site of the serine protease and thus irreversible *** inhibitory mechanism,reminiscent of the movement of a mousetrap,requires a structural flexibility that proves to be unfavorable when the folding of the serpin is altered by mutations responsible for conformational rearrangements,allowing an intermolecular domain exchange characterized by the insertion of the C-terminal domain of a molecule into a second one,thus forming a *** of this insertion reaction leads to the formation of serpin polymers that accumulate within the endoplasmic reticulum(ER)of the cell and consequently reduces the secretion of the wild-type serpin(Greene et al.,2016).

关键词： insertion irreversible starting

Synaptopathy in CHMP2B frontotemporal dementia highlights the synaptic vesicle cycle as a therapeutic target

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Neural Regeneration Research 2023年第2期18卷 315-316页

作者： miranda Robbins Emma L.Clayton MRC Laboratory of Molecular Biology Department of Zoology University of CambridgeCambridgeUK UK Dementia Research Institute at King’s College London Department of Basic and Clinical Neuroscience Institute of PsychiatryPsychology and NeuroscienceKing’s College LondonMaurice Wohl Clinical Neuroscience InstituteLondonUK

Amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD)are both devastating neurodegenerative *** affecting different regions of the nervous system(FTD affecting primarily the frontal and temporal lobes,whilst ALS presents with motor neuron loss),there is significant overlap between these conditions in terms of genetics,pathology,and disease mechanisms,and they are therefore often grouped as a spectrum of symptoms under the heading FTD/ALS(Abramzon et al.,2020).Significantly,there is currently no cure for ALS or ***,recent mechanistic insight points to a novel pathway to target for potential therapeutic intervention.

关键词： therapeutic pathology