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Toward understanding the role of genomic repeat elements in neurodegenerative diseases

Neural Regeneration Research 2025年第3期20卷 646-659页

作者： Zhengyu An Aidi Jiang Jingqi Chen Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina MOE Key Laboratory of computational neuroscience and Brain-Inspired Intelligence Fudan UniversityShanghaiChina Zhangjiang Fudan International Innovation Center ShanghaiChina

Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

关键词： Alzheimer's disease ataxia deep learning long-read sequencing neurodegeneration neurodegenerative diseases Parkinson's disease repeat element structural variant

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Dirichlet Process Gaussian Mixture Models:Choice of the Base Distribution

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Journal of Computer Science & Technology 2010年第4期25卷 653-664页

作者： Dilan Grür Carl Edward Rasmussen gatsby computational neuroscience unit University College London Department of Engineering University of Cambridge Max Planck Institute for Biological Cybernetics.D-72076 Tubingen

In the Bayesian mixture modeling framework it is possible to infer the necessary number of components to model the data and therefore it is unnecessary to explicitly restrict the number of components. Nonparametric mixture models sidestep the problem of finding the ＂correct＂ number of mixture components by assuming infinitely many components. In this paper Dirichlet process mixture （DPM） models are cast as infinite mixture models and inference using Markov chain Monte Carlo is described. The specification of the priors on the model parameters is often guided by mathematical and practical convenience. The primary goal of this paper is to compare the choice of conjugate and non-conjugate base distributions on a particular class of DPM models which is widely used in applications, the Dirichlet process Gaussian mixture model （DPGMM）. We compare computational efficiency and modeling performance of DPGMM defined using a conjugate and a conditionally conjugate base distribution. We show that better density models can result from using a wider class of priors with no or only a modest increase in computational effort.

关键词： Bayesian nonparametrics Dirichlet processes Gaussian mixtures

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Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

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Neural Regeneration Research 2025年第5期20卷 1495-1504页

作者： Yunting Xiang Xiangxin Xing Xuyun Hua Yuwen Zhang Xin Xue Jiajia Wu Mouxiong Zheng He Wang Jianguang Xu School of Rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina Department of Rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of Traumatology and Orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina Key Laboratory of computational neuroscience and Brain-Inspired Intelligence(Fudan University) Ministry of EducationShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected ***,differences among reconstruction strategies at the brain network level have not been *** study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve ***–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper ***-state brain functional magnetic resonance imaging was obtained 7 months after *** independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the *** in intra-network resting-state functional connectivity were compared among the *** muscle reinnervation was assessed by behavioral observation(elbow flexion)and *** results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural *** repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor *** thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve *** areas related to cognition and emotion were enhanced after end-to-side nerve *** study revealed important brain networks related to different nerve *** networks may be potential targets for enhancing motor recovery.

关键词： brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity

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Three-Stage Transfer Learning with AlexNet50 for MRI Image Multi-Class Classification with Optimal Learning Rate

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 155-183页

作者： Suganya Athisayamani A.Robert Singh Gyanendra Prasad Joshi Woong Cho School of Computing Sastra Deemed to be UniversityThanjavur613401India Department of computational Intelligence SRM Institute of Science and TechnologyKattankulathur603203India Department of AI and Software Engineering Kangwon National UniversitySamcheok25913Republic of Korea Department of Electronics Information and Communication EngineeringKangwon National UniversitySamcheok25913Republic of Korea

In radiology,magnetic resonance imaging(MRI)is an essential diagnostic tool that provides detailed images of a patient’s anatomical and physiological *** is particularly effective for detecting soft tissue ***,radiologists manually interpret these images,which can be labor-intensive and time-consuming due to the vast amount of *** address this challenge,machine learning,and deep learning approaches can be utilized to improve the accuracy and efficiency of anomaly detection in MRI *** manuscript presents the use of the Deep AlexNet50 model for MRI classification with discriminative learning *** are three stages for learning;in the first stage,the whole dataset is used to learn the *** the second stage,some layers of AlexNet50 are frozen with an augmented dataset,and in the third stage,AlexNet50 with an augmented dataset with the augmented *** method used three publicly available MRI classification datasets:Harvard whole brain atlas(HWBA-dataset),the School of Biomedical Engineering of Southern Medical University(SMU-dataset),and The National Institute of neuroscience and Hospitals brain MRI dataset(NINS-dataset)for *** hyperparameter optimizers like Adam,stochastic gradient descent(SGD),Root mean square propagation(RMS prop),Adamax,and AdamW have been used to compare the performance of the learning ***-dataset registers maximum classification *** evaluated the performance of the proposed classification model using several quantitative metrics,achieving an average accuracy of 98%.

关键词： MRI tumors classification AlexNet50 transfer learning hyperparameter tuning optimizer

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Could non-invasive brain-stimulation prevent neuronal degeneration upon ion channel re-distribution and ion accumulation after demyelination?

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Neural Regeneration Research 2020年第11期15卷 1977-1980页

作者： Friederike Pfeiffer Alia Benali Werner Reichardt Centre for Integrative neuroscience(CIN) University of TubingenTubingenGermany Section for computational Sensomotorics Department of Cognitive NeurologyHertie-Institute for Clinical Brain Research and Centre for Integrative NeuroscienceUniversity of TubingenTubingenGermany

Fast and efficient transmission of electrical signals in the nervous system is mediated through myelinated nerve *** neuronal diseases such as multiple sclerosis,the conduction properties of axons are disturbed by the removal of the myelin sheath,leaving nerve cells at a higher risk of *** some cases,the protective myelin sheath of axons can be rebuilt by remyelination through oligodendroglial *** any case,however,changes in the ion channel organization occur and may help to restore impulse conduction after *** the other hand,changes in ion channel distribution may increase the energy demand of axons,thereby increasing the probability of axonal *** attempts have been made or discussed in recent years to increase remyelination of affected axons in demyelinating diseases such as multiple *** approaches range from pharmacological treatments that reduce inflammatory processes or block ion channels to the modulation of neuronal activity through electrical cortical ***,these treatments either affect the entire organism(pharmacological)or exert a very local effect(electrodes).Current results show that neuronal activity is a strong regulator of oligodendroglial *** bridge the gap between global and very local treatments,non-invasive transcranial magnetic stimulation could be *** magnetic stimulation is externally applied to brain areas and experiments with repetitive transcranial magnetic stimulation show that the neuronal activity can be modulated depending on the stimulation parameters in both humans and *** this review,we discuss the possibilities of influencing ion channel distribution and increasing neuronal activity by transcranial magnetic stimulation as well as the effect of this modulation on oligodendroglial cells and their capacity to remyelinate previously demyelinated *** the physiological mechanisms underlying the effects of transcrani

关键词： ion channel multiple sclerosis neuronal activity oligodendrocyte (re-)myelination repetitive transcranial magnetic stimulation transcranial magnetic stimulation

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Can we promote neural regeneration through microbiota-targeted strategies? Introducing the new concept of neurobiotics

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Neural Regeneration Research 2022年第9期17卷 1965-1966页

作者： Celia Herrera-Rincon Julia Murciano-Brea Stefano Geuna Department of Biodiversity Ecology&Evolutionand ModelingData Analysis&Computational Tools for Biology Research GroupBiomathematics UnitComplutense University of MadridMadridSpain Department of Clinical and Biological Sciences and Cavalieri Ottolenghi Neuroscience InstituteUniversity of TurinTurinItaly

The human body is populated by a large number of microbial colonies,with an estimated 10-100 trillion *** total genome size of human microbial colonies by far overwhelms the size of the host’s *** heterogenous group of microbial colonies(primarily bacteria,but also archaea,eukaryotes and viruses)is referred to with the term microbiota,and although most of them populate the gut,microbes are also detectable in many other organs of the body,especially in the distal tracts of the genitourinary system and the *** the last years,an increasing amount of evidence has been accumulated on how the microbiota exerts a significant influence on the development and physiology of the human body.

关键词： neural organs size

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computational neuroscience:a frontier of the 21st century

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National Science Review 2020年第9期7卷 1418-1422页

作者： Xiao-Jing Wang Hailan Hu Chengcheng Huang Henry Kennedy Chengyu Tony Li Nikos Logothetis Zhong-Lin Lu Qingming Luo Mu-ming Poo Doris Tsao Si Wu Zhaohui Wu Xu Zhang Douglas Zhou Center for Neural Science New York University Center for neuroscience Key Laboratory of Medical Neurobiology of the Ministry of Health of China School of Medicine Zhejiang University Department of neuroscience and Department of Mathematics Center for the Neural Basis of Cognition University of Pittsburgh Université Claude Bernard Lyon 1 Inserm Stem Cell and Brain Research Institute U1208 Institute of neuroscience State Key Laboratory of Neuroscience Chinese Academy of SciencesCAS Center for Excellence in Brain Science and Intelligence Technology Shanghai Center for Brain Science and Brain-Inspired Technology Division of Arts and Sciences and NYU-ECNU Institute of Cognitive Neuroscience NYU Shanghai School of Biomedical Engineering Hainan University Huazhong University of Science and Technology-Suzhou Institute for Brainsmatics Division of Biology and Biological Engineering California Institute of Technology Howard Hughes Medical Institute School of Electronics Engineering and Computer Science IDG/Mc Govern Institute for Brain Research PKU-Tsinghua Center for Life SciencesPeking University College of Computer Science and Technology Zhejiang University Institute of Brain-Intelligence Science and Technology Zhangjiang Lab School of Mathematical Sciences MOE-LSCand Institute of Natural Sciences Shanghai Jiao Tong University

THEORY IN neuroscience The human brain is a biological organ,weighing about three pounds or 1.4 kg,that determines our behaviors, thoughts,emotions and consciousness. Although comprising only 2%of the total body weigh...

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The Brain Connectome for Chinese Reading

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neuroscience Bulletin 2022年第9期38卷 1097-1113页

作者： Wanwan Guo Shujie Geng Miao Cao Jianfeng Feng Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghai200433China Key Laboratory of computational neuroscience and Brain-Inspired Intelligence(Ministry of Education) Fudan UniversityShanghai200433China

Chinese,as a logographic language,fundamentally differs from alphabetic languages like *** neuroimaging studies have mainly focused on alphabetic languages,while the exploration of Chinese reading is still an emerging and fast-growing research ***,a growing number of neuroimaging studies have explored the neural circuit of Chinese ***,we summarize previous research on Chinese reading from a connectomic *** evidence indicates that the left middle frontal gyrus is a specialized hub region that connects the ventral with dorsal pathways for Chinese ***,the orthography-to-phonology and orthography-to-semantics mapping,mainly processed in the ventral pathway,are more specific during Chinese ***,in addition to the left-lateralized language-related regions,reading pathways in the right hemisphere also play an important role in Chinese ***,we comprehensively review prior findings and emphasize several challenging issues to be explored in future work.

关键词： Brain connectome Chinese reading Word recognition Reading comprehension Structural connectivity Functional connectivity

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Role of the Anterior Cingulate Cortex in Translational Pain Research

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neuroscience Bulletin 2021年第3期37卷 405-422页

作者： Xiao Xiao Ming Ding Yu-Qiu Zhang Key Laboratory of computational neuroscience and Brain-Inspired Intelligence Ministry of EducationInstitute of Science and Technology for Brain-Inspired IntelligenceBehavioral and Cognitive Neuroscience CenterFudan UniversityShanghai 200433China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Department of Translational NeuroscienceJing’an District Centre Hospital of ShanghaiInstitutes of Brain ScienceInstitute of Integrative MedicineFudan UniversityShanghai 200032China

As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and *** pain processing,noxious stimuli may activate the anterior cingulate cortex(ACC).But the function of ACC in the different pain conditions is not well *** this review,we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain,neuropathic pain,and cancer pain in the ACC,and discuss the cellular receptors and signaling molecules from animal *** further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain *** comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.

关键词： Anterior cingulate cortex Deep brain stimulation Transcranial magnetic stimulation Transcranial direct current stimulation Pathological pain Inflammatory pain Neuropathic pain Cancer pain

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Cerebellar pathology in motor neuron disease:neuroplasticity and neurodegeneration

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Neural Regeneration Research 2022年第11期17卷 2335-2341页

作者： Rangariroyashe H.Chipika Grainne Mulkerrin Pierre-François Pradat Aizuri Murad Fabrice Ango Cédric Raoul Peter Bede computational Neuroimaging Group Biomedical Sciences InstituteTrinity College DublinDublinIreland Pitié-Salpêtrière University Hospital Sorbonne UniversityParisFrance The neuroscience Institute of Montpellier(INM) INSERMCNRSMontpellierFrance

Amyotrophic lateral sclerosis is a relentlessly progressive multi-system *** clinical picture is dominated by upper and lower motor neuron degeneration,but extra-motor pathology is increasingly recognized,including cerebellar ***-mortem and neuroimaging studies primarily focus on the chara cterization of supratentorial disease,des pite emerging evidence of cerebellar degeneration in amyotrophic lateral *** clinical features of amyotrophic lateral sclerosis,such as dysarthria,dysphagia,cognitive and behavioral deficits,saccade abnormalities,gait impairment,respiratory weakness and pseudobulbar affect are likely to be exacerbated by co-existing cerebellar *** review summarizes in vivo and post mortem evidence for cerebellar degeneration in amyotrophic lateral scle *** imaging studies consistently capture cerebellar grey matter volume reductions,diffusivity studies readily detect both intra-cerebellar and cerebellar peduncle white matter alte rations and functional imaging studies commonly report increased functional connectivity with supratentorial *** functional connectivity is commonly interpreted as evidence of neuro plasticity representing compensatory processes despite the lack of post-mortem *** is a scarcity of post-mortem studies focusing on cerebellar alte rations,but these detect pTDP-43 in cerebellar *** rebellar pathology is an overloo ked facet of neurodegeneration in amyotrophic lateral sclerosis despite its contribution to a multitude of clinical symptoms,wides p read connectivity to spinal and supratentorial regions and putative role in compensating for the degeneration of primary motor regions.

关键词： amyotrophic lateral sclerosis ataxia cerebellum magnetic resonance imaging motor neuron disease neuroimaging neuroplasticity pathology primary lateral sclerosis pseudobulbar affect

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