Since the documented observations of Kanner in1943, there has been great debate about the diagnoses, the sub-types, and the diagnostic threshold that relates to what is now known as autism spectrum disorder（ASD）.Re...Since the documented observations of Kanner in1943, there has been great debate about the diagnoses, the sub-types, and the diagnostic threshold that relates to what is now known as autism spectrum disorder（ASD）.Re？ecting this complicated history, there has been continual re？nement from DSM-III with ‘Infantile Autism＇ to the current DSM-V diagnosis. The disorder is now widely accepted as a complex, pervasive, heterogeneous condition with multiple etiologies, sub-types, and developmental trajectories. Diagnosis remains based on observation of atypical behaviors, with criteria of persistent de？cits in social communication and restricted and repetitive patterns of behavior. This review provides a broad overview of the history, prevalence, etiology, clinical presentation, and heterogeneity of ASD. Factors contributing to heterogeneity, including genetic variability, comorbidity, and gender are reviewed. We then explore current evidencebased pharmacological and behavioral treatments for ASD and highlight the complexities of conducting clinical trials that evaluate therapeutic ef？cacy in ASD populations.Finally, we discuss the potential of a new wave of research examining objective biomarkers to facilitate the evaluation of sub-typing, diagnosis, and treatment response in ASD.展开更多
Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases （RIPK） associated with the tumor necrosis fact...Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases （RIPK） associated with the tumor necrosis factor-alpha （TNF-a）/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and al- leviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar con- centrations. Here, we investigated whether Dabrafenib would show a similar neuroprotective effect in mice subjected to ischemic brain injury by photothrombosis. Dabrafenib administered intraperitoneally at 10 mg/ kg one hour after photothrombosis-induced focal ischemic injury significantly reduced infarct lesion size in C57BL6 mice the following day, accompanied by a markedly attenuated upregulation of TNF-u. However, subsequent lower doses （5 mg/kg/day） failed to sustain this neuroprotective effect after 4 days. Dabrafenib bl ocked lipopolysaccharides-induced activation of TNF-ct in bone marrow-derived macrophages, suggesting that Dabrafenib may attenuate TNF-ct-induced necroptotic pathway after ischemic brain injury. Since Dab- rafenib is already in clinical use for the treatment of melanoma, it might be repurposed for stroke therapy.展开更多
Various resting-state fMRI(R-fMRI) measures have been developed to characterize intrinsic brain activity. While each of these measures has gained a growing presence in the literature, questions remain regarding the co...Various resting-state fMRI(R-fMRI) measures have been developed to characterize intrinsic brain activity. While each of these measures has gained a growing presence in the literature, questions remain regarding the common and unique aspects these indices capture. The present work provided a comprehensive examination of inter-individual variation and intra-individual temporal variation for commonly used measures, including fractional amplitude of low frequency fluctuations, regional homogeneity,voxel-mirrored homotopic connectivity, network centrality and global signal correlation. Regardless of whether examining intra-individual or inter-individual variation, we found that these definitionally distinct R-fMRI indices tend to exhibit a relatively high degree of covariation, which doesn't exist in phase randomized surrogate data. As a measure of intrinsic brain function, concordance for R-fMRI indices was negatively correlated with age across individuals(i.e., concordance among functional indices decreased with age). To understand the functional significance of concordance, we noted that higher concordance was generally associated with higher strengths of R-fMRI indices, regardless of whether looking through the lens of inter-individual(i.e., high vs. low concordance participants) or intra-individual(i.e., high vs.low concordance states identified via temporal dynamic analyses) differences. We also noted a linear increase in functional concordance together with the R-fMRI indices through the scan, which may suggest a decrease in arousal. The current study demonstrated an enriched picture regarding the relationship among the R-fMRI indices, as well as provided new insights in examining dynamic states within and between individuals.展开更多
Autism Spectrum Disorder（ASD） is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors.Hetero...Autism Spectrum Disorder（ASD） is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors.Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine pro？les and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may de？ne a subgroup of ASD,or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previouslyidenti？ed immune system abnormalities in ASD, speci？-cally addressing the role of cytokines in these aberrations.The roles and identi？cation of biomarkers are also addressed, particularly with respect to cytokine pro？les in ASD.展开更多
Arabidopsis MSI1 has fundamental functions in plant development. MSI1 is a subunit of Polycomb group protein complexes and Chromatin assembly factor 1, and it interacts with the Retinoblastoma-related protein 1. Alter...Arabidopsis MSI1 has fundamental functions in plant development. MSI1 is a subunit of Polycomb group protein complexes and Chromatin assembly factor 1, and it interacts with the Retinoblastoma-related protein 1. Altered levels of MSI1 result in pleiotropic phenotypes, reflecting the complexity of MSI1 protein functions. In order to uncover additional functions of MSI1, we performed transcriptional profiling of wild-type and plants with highly reduced MSI1 levels （msil-cs）. Surprisingly, the known functions of MSI1 could only account for a minor part of the transcriptional changes in msil-cs plants. One of the most striking unexpected observations was the up-regulation of a subset of ABA-responsive genes eliciting the response to drought and salt stress. We report that MSI1 can bind to the chromatin of the drought-inducible downstream target RD20 and suggest a new role for MSI1 in the negative regulation of the Arabidopsis drought-stress response.展开更多
People with schizophrenia exhibit impaired social cognitive functions, particularly emotion regulation. Abnormal activations of the ventral medial prefrontal cortex （vMPFC） during emotional tasks have been demonstra...People with schizophrenia exhibit impaired social cognitive functions, particularly emotion regulation. Abnormal activations of the ventral medial prefrontal cortex （vMPFC） during emotional tasks have been demonstrated in schizophrenia, suggesting its important role in emotion processing in patients. We used the resting-state functional connectivity approach, setting a functionally relevant region, the vMPFC, as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients. We found hypo-connectivity between the vMPFC and the medial frontal cortex, right middle temporal lobe （MTL）, right hippocampus, parahippocampal cortex （PHC） and amygdala. Further, there was a decreased strength of the negative connectivity （or anticorrelation） between the vMPFC and the bilateral dorsal lateral prefrontal cortex （DLPFC） and pre-supplementary motor areas. Among these connectivity alterations, reduced vMPFC-DLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale, while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients. These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia. The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.展开更多
随着中国进入老龄化社会,人口生育政策逐步放开,揭示脑与行为毕生发展的一般规律和常规模式(常模)正成为公共卫生和人口健康领域的重大基础需求.本文介绍"中国彩巢计划"(Chinese Color Nest Project—CCNP)这一在全国范围内...随着中国进入老龄化社会,人口生育政策逐步放开,揭示脑与行为毕生发展的一般规律和常规模式(常模)正成为公共卫生和人口健康领域的重大基础需求.本文介绍"中国彩巢计划"(Chinese Color Nest Project—CCNP)这一在全国范围内分期分步地开展的项目规划,在10年(2013~2022年:http://zuolab.psych.ac.cn/colornest.html)内CCNP将积累毕生发展各年龄段的心理行为与脑影像样本,基于加速纵向实验设计方法建立中国人脑毕生发展的常模轨线.作为CCNP的发育项目"成长在中国"(dev CCNP:Growing Up in China)这一学龄儿童青少年脑与行为生长曲线项目,dev CCNP已经完成对重庆北碚区192名健康儿童青少年(6~18岁)的5年追踪.初步的研究结果表明,dev CCNP在实验设计、样本采集策略、数据获取和存储、初步发现和数据共享等方面具备长期实施的可行性,我国应及早部署开展儿童青少年的脑与认知生长曲线常模的大规模脑科学研究计划,提升中国在脑科学与医疗健康研究领域的国际实力和影响力,革新脑疾病临床实践.展开更多
Objective To compare the cognitive effects of guqin （the oldest Chinese instrument） music and piano music. Methods Behavioral and event-related potential （ERP） data in a standard two-stimulus auditory oddball task...Objective To compare the cognitive effects of guqin （the oldest Chinese instrument） music and piano music. Methods Behavioral and event-related potential （ERP） data in a standard two-stimulus auditory oddball task were recorded and analyzed. Results This study replicated the previous results of culture-familiar music effect on Chinese subjects： the greater P300 amplitude in frontal areas in a culture-familiar music environment. At the same time, the difference between guqin music and piano music was observed in NI and later positive complex （LPC： including P300 and P500）： a relatively higher participation of right anterior-temporal areas in Chinese subjects. Conclusion The results suggest that the special features of ERP responses to guqin music are the outcome of Chinese tonal language environments given the similarity between Guqin＇s tones and Mandarin lexical tones.展开更多
While early investigations into the physiological effects of spaceflight suggest the body’s ability to reversibly adapt,the corresponding effects of long-term spaceflight(>6months)aremuch less conclusive.Prolonged...While early investigations into the physiological effects of spaceflight suggest the body’s ability to reversibly adapt,the corresponding effects of long-term spaceflight(>6months)aremuch less conclusive.Prolonged exposure to microgravity and radiation yields profound effects on the cardiovascular system,including a massive cephalad fluid translocation and altered arterial pressure,which attenuate blood pressure regulatory mechanisms and increase cardiac output.Also,central venous pressure decreases as a result of the loss of venous compression.The stimulation of baroreceptors by the cephalad shift results in an approximately 10%–15%reduction in plasma volume,with fluid translocating from the vascular lumen to the interstitium.Despite possible increases in cardiac workload,myocyte atrophy and notable,yet unexplained,alterations in hematocrit have been observed.Atrophy is postulated to result from shunting of protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated action.While data are scarce regarding their causative agents,arrhythmias have been frequently reported,albeit sublethal,during both Russian and American expeditions,with QT interval prolongation observed in long,but not short duration,spaceflight.Exposure of the heart to the proton and heavy ion radiation of deep space has also been shown to result in coronary artery degeneration,aortic stiffness,carotid intima thickening via collagen-mediated action,accelerated atherosclerosis,and induction of a pro-inflammatory state.Upon return,long-term spaceflight frequently results in orthostatic intolerance and altered sympathetic responses,which can prove hazardous should any rapidmobilization or evacuation be required,and indicates that these cardiac risks should be especially monitored for future missions.展开更多
Human brain mapping (HBM)is increasingly becoming a multidisciplinary field where some scientific issues are fundamental for all scientists and applications of using the technology to investigate individual difference...Human brain mapping (HBM)is increasingly becoming a multidisciplinary field where some scientific issues are fundamental for all scientists and applications of using the technology to investigate individual differences.Reliability represents a significant issue for all scientific fields and has particularly been overlooked for decades by the HBM field [1].Meanwhile,recent advances in open science have offered the field big data for developing novel methodological frameworks as well as performing largescale investigations of the brain-mind associations based upon the individual differences assessed with HBM [2].A systematic investigation of reliability seems still far behind these HBM developments. It is critical that reliability is evaluated ahead of these applications, motivating the current commentary on delineation of the anatomy of reliability for future HBM.展开更多
Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because ...Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because of the large number of voxels in the brain,multiple comparison correction(MCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent MCC)is widely recommended[1].展开更多
ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosi...ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosides,sugars,and xenobiotics.Interestingly,ABC transporters are highly expressed in the brain.While their functions in the brain still need to be elucidated,several members are implicated in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and frontotemporal dementia.In this perspective,we will review current knowledge of ABC transporters in the central nervous system in terms of physiological functions and pathology in neurodegeneration.Furthermore,we will explore the possibilities of ABC transporters as potential targets in the development of therapeutics for neurodegenerative diseases.展开更多
Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebr...Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.展开更多
It is of great scientific and translational promise to formulate a normative reference for the lifespan development of human brain to precisely quantify individual differences.By aggregating more than 120,000 brain im...It is of great scientific and translational promise to formulate a normative reference for the lifespan development of human brain to precisely quantify individual differences.By aggregating more than 120,000 brain imaging scans across the world,the Lifespan Brain Chart Consortium(LBCC)recently published brain charts for the human lifespan in Nature[1].展开更多
Frontotemporal dementia(FTD) and amyotrophic lateral sclerosis(ALS) are neurodegenerative diseases that belong to the same disease spectrum,with overlapping of genetic and pathological features.Genetic mutations in TA...Frontotemporal dementia(FTD) and amyotrophic lateral sclerosis(ALS) are neurodegenerative diseases that belong to the same disease spectrum,with overlapping of genetic and pathological features.Genetic mutations in TARDBP,C9ORF72,MAPT,and GRN have been identified in these diseases.展开更多
There is an urgent need to identify new drug targets for Alzheimer's disease(AD). While new immunotherapies show promise, clinical benefit appears low, and side effects are high. A greater understanding of the dis...There is an urgent need to identify new drug targets for Alzheimer's disease(AD). While new immunotherapies show promise, clinical benefit appears low, and side effects are high. A greater understanding of the disease mechanisms driving AD is an essential factor that will facilitate the identification of new, effective drug targets.展开更多
AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulph...AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM(n = 11) at baseline and at their transition to T2 DM using Illumina Infinium Human Methylation27 Bead Chip, that enables the query of 27578 individual cytosines at Cp G loci throughout the genome, which are focused on the promoter regions of 14495 genes.RESULTS: There were 694 Cp G sites hypomethylated and 174 Cp G sites hypermethylated in progression from Pre-DM to T2 DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective Cp G sites associated with diverse genes that may reflect differences in Pre-DM compared with T2 DM. In addition, there were Cp G hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.展开更多
Stem cell-based therapies and extracellular vesicle(EV)treatment have demonstrated significant potential for neuroprotection against ischemic stroke.Although the neuroprotective mechanisms are not yet fully under-stoo...Stem cell-based therapies and extracellular vesicle(EV)treatment have demonstrated significant potential for neuroprotection against ischemic stroke.Although the neuroprotective mechanisms are not yet fully under-stood,targeting microglia is central to promoting neuroprotection.Microglia are the resident immune cells of the central nervous system.These cells are crucial in the pathogenesis of ischemic stroke.They respond rapidly to the site of injury by releasing pro-inflammatory cytokines,phagocytizing dead cells and debris,and recruiting peripheral immune cells to the ischemic area.Although these responses are essential for clearing damage and initiating tissue repair,excessive or prolonged microglial activation can exacerbate brain injury,leading to secondary neuroinflammation and neurodegeneration.Moreover,microglia exhibit a dynamic range of activation states with the so-called M1 pro-inflammatory and M2 anti-inflammatory phenotypes,representing the two ends of the spectrum.The delivery of both EVs and stem cells modulates microglial activation,suppressing pro-inflammatory genes,influencing the expression of transcription factors,and altering receptor expression,ultimately contributing to neuroprotection.These findings underscore the importance of understanding the complex and dynamic role of microglia in the development of effective neuroprotective strategies to reduce the effects of ischemic stroke.In this review,we examine the current state of knowledge regarding the role of microglia in ischemic stroke,including their molecular and cellular mechanisms,activation states,and interactions with other cells.We also discuss the multifaceted contributions of microglia to stem cell-and EV-based neuroprotection during an ischemic stroke to provide a comprehensive understanding of microglial functions and their potential implications in stroke therapies.展开更多
基金a NHMRC career development fellowship (APP1061922)a Project Grant (1043664) to Adam J. Guastella
文摘Since the documented observations of Kanner in1943, there has been great debate about the diagnoses, the sub-types, and the diagnostic threshold that relates to what is now known as autism spectrum disorder（ASD）.Re？ecting this complicated history, there has been continual re？nement from DSM-III with ‘Infantile Autism＇ to the current DSM-V diagnosis. The disorder is now widely accepted as a complex, pervasive, heterogeneous condition with multiple etiologies, sub-types, and developmental trajectories. Diagnosis remains based on observation of atypical behaviors, with criteria of persistent de？cits in social communication and restricted and repetitive patterns of behavior. This review provides a broad overview of the history, prevalence, etiology, clinical presentation, and heterogeneity of ASD. Factors contributing to heterogeneity, including genetic variability, comorbidity, and gender are reviewed. We then explore current evidencebased pharmacological and behavioral treatments for ASD and highlight the complexities of conducting clinical trials that evaluate therapeutic ef？cacy in ASD populations.Finally, we discuss the potential of a new wave of research examining objective biomarkers to facilitate the evaluation of sub-typing, diagnosis, and treatment response in ASD.
基金supported by grants from the Heart and Stroke Foundation of Canada(HHC,AFRS)the Canadian Institutes of Health Research(to HHC and AFRS)supported by a Mid-Career Investigator Award from the Heart and Stroke Foundation of Ontario
文摘Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases （RIPK） associated with the tumor necrosis factor-alpha （TNF-a）/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and al- leviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar con- centrations. Here, we investigated whether Dabrafenib would show a similar neuroprotective effect in mice subjected to ischemic brain injury by photothrombosis. Dabrafenib administered intraperitoneally at 10 mg/ kg one hour after photothrombosis-induced focal ischemic injury significantly reduced infarct lesion size in C57BL6 mice the following day, accompanied by a markedly attenuated upregulation of TNF-u. However, subsequent lower doses （5 mg/kg/day） failed to sustain this neuroprotective effect after 4 days. Dabrafenib bl ocked lipopolysaccharides-induced activation of TNF-ct in bone marrow-derived macrophages, suggesting that Dabrafenib may attenuate TNF-ct-induced necroptotic pathway after ischemic brain injury. Since Dab- rafenib is already in clinical use for the treatment of melanoma, it might be repurposed for stroke therapy.
基金supported by the National Key R&D Program of China (2017YFC1309902 to CGY)National Basic Research Program (2015CB351702 to XNZ)+4 种基金the Natural Science Foundation of China (81671774 and 81630031 to CGY, 81471740, 81220108014 to XNZ)the Hundred Talents Program of the Chinese Academy of Sciences (Y5CX072006 to CGY)Beijing Municipal Science & Technology Commission (Z161100000216152 to CGY)the National Institutes of Health (U01MH099059 to MPM)the Child Mind Institute (1FDN2012-1 to MPM)
文摘Various resting-state fMRI(R-fMRI) measures have been developed to characterize intrinsic brain activity. While each of these measures has gained a growing presence in the literature, questions remain regarding the common and unique aspects these indices capture. The present work provided a comprehensive examination of inter-individual variation and intra-individual temporal variation for commonly used measures, including fractional amplitude of low frequency fluctuations, regional homogeneity,voxel-mirrored homotopic connectivity, network centrality and global signal correlation. Regardless of whether examining intra-individual or inter-individual variation, we found that these definitionally distinct R-fMRI indices tend to exhibit a relatively high degree of covariation, which doesn't exist in phase randomized surrogate data. As a measure of intrinsic brain function, concordance for R-fMRI indices was negatively correlated with age across individuals(i.e., concordance among functional indices decreased with age). To understand the functional significance of concordance, we noted that higher concordance was generally associated with higher strengths of R-fMRI indices, regardless of whether looking through the lens of inter-individual(i.e., high vs. low concordance participants) or intra-individual(i.e., high vs.low concordance states identified via temporal dynamic analyses) differences. We also noted a linear increase in functional concordance together with the R-fMRI indices through the scan, which may suggest a decrease in arousal. The current study demonstrated an enriched picture regarding the relationship among the R-fMRI indices, as well as provided new insights in examining dynamic states within and between individuals.
基金a National Health and Medical Research Council Career Development Fellowship(APP1061922)a Project Grant(1043664)to AJG
文摘Autism Spectrum Disorder（ASD） is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors.Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine pro？les and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may de？ne a subgroup of ASD,or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previouslyidenti？ed immune system abnormalities in ASD, speci？-cally addressing the role of cytokines in these aberrations.The roles and identi？cation of biomarkers are also addressed, particularly with respect to cytokine pro？les in ASD.
文摘Arabidopsis MSI1 has fundamental functions in plant development. MSI1 is a subunit of Polycomb group protein complexes and Chromatin assembly factor 1, and it interacts with the Retinoblastoma-related protein 1. Altered levels of MSI1 result in pleiotropic phenotypes, reflecting the complexity of MSI1 protein functions. In order to uncover additional functions of MSI1, we performed transcriptional profiling of wild-type and plants with highly reduced MSI1 levels （msil-cs）. Surprisingly, the known functions of MSI1 could only account for a minor part of the transcriptional changes in msil-cs plants. One of the most striking unexpected observations was the up-regulation of a subset of ABA-responsive genes eliciting the response to drought and salt stress. We report that MSI1 can bind to the chromatin of the drought-inducible downstream target RD20 and suggest a new role for MSI1 in the negative regulation of the Arabidopsis drought-stress response.
基金supported by grants from the Beijing Municipal Science & Technology Commission(D0906001040191,D101107047810005,D101100050010051)the Beijing Natural Science Foundation(7102086)+3 种基金the Fund for Capital Medical Development and Research(2007-3059)the National Natural Science Foundation of China(81171409)Startup Foundation for Distinguished Research Professors of the Institute for Psychology(Y0CX492S03)Fund for Outstanding Talents in Beijing(2012D003034000003)
文摘People with schizophrenia exhibit impaired social cognitive functions, particularly emotion regulation. Abnormal activations of the ventral medial prefrontal cortex （vMPFC） during emotional tasks have been demonstrated in schizophrenia, suggesting its important role in emotion processing in patients. We used the resting-state functional connectivity approach, setting a functionally relevant region, the vMPFC, as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients. We found hypo-connectivity between the vMPFC and the medial frontal cortex, right middle temporal lobe （MTL）, right hippocampus, parahippocampal cortex （PHC） and amygdala. Further, there was a decreased strength of the negative connectivity （or anticorrelation） between the vMPFC and the bilateral dorsal lateral prefrontal cortex （DLPFC） and pre-supplementary motor areas. Among these connectivity alterations, reduced vMPFC-DLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale, while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients. These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia. The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.
文摘随着中国进入老龄化社会,人口生育政策逐步放开,揭示脑与行为毕生发展的一般规律和常规模式(常模)正成为公共卫生和人口健康领域的重大基础需求.本文介绍"中国彩巢计划"(Chinese Color Nest Project—CCNP)这一在全国范围内分期分步地开展的项目规划,在10年(2013~2022年:http://zuolab.psych.ac.cn/colornest.html)内CCNP将积累毕生发展各年龄段的心理行为与脑影像样本,基于加速纵向实验设计方法建立中国人脑毕生发展的常模轨线.作为CCNP的发育项目"成长在中国"(dev CCNP:Growing Up in China)这一学龄儿童青少年脑与行为生长曲线项目,dev CCNP已经完成对重庆北碚区192名健康儿童青少年(6~18岁)的5年追踪.初步的研究结果表明,dev CCNP在实验设计、样本采集策略、数据获取和存储、初步发现和数据共享等方面具备长期实施的可行性,我国应及早部署开展儿童青少年的脑与认知生长曲线常模的大规模脑科学研究计划,提升中国在脑科学与医疗健康研究领域的国际实力和影响力,革新脑疾病临床实践.
文摘Objective To compare the cognitive effects of guqin （the oldest Chinese instrument） music and piano music. Methods Behavioral and event-related potential （ERP） data in a standard two-stimulus auditory oddball task were recorded and analyzed. Results This study replicated the previous results of culture-familiar music effect on Chinese subjects： the greater P300 amplitude in frontal areas in a culture-familiar music environment. At the same time, the difference between guqin music and piano music was observed in NI and later positive complex （LPC： including P300 and P500）： a relatively higher participation of right anterior-temporal areas in Chinese subjects. Conclusion The results suggest that the special features of ERP responses to guqin music are the outcome of Chinese tonal language environments given the similarity between Guqin＇s tones and Mandarin lexical tones.
基金Thisworkwas funded byNASA(GrantNos.NNX14AH50G and NNX17AB26G)the National Institutes of Health(Grant No.R25EB020393).
文摘While early investigations into the physiological effects of spaceflight suggest the body’s ability to reversibly adapt,the corresponding effects of long-term spaceflight(>6months)aremuch less conclusive.Prolonged exposure to microgravity and radiation yields profound effects on the cardiovascular system,including a massive cephalad fluid translocation and altered arterial pressure,which attenuate blood pressure regulatory mechanisms and increase cardiac output.Also,central venous pressure decreases as a result of the loss of venous compression.The stimulation of baroreceptors by the cephalad shift results in an approximately 10%–15%reduction in plasma volume,with fluid translocating from the vascular lumen to the interstitium.Despite possible increases in cardiac workload,myocyte atrophy and notable,yet unexplained,alterations in hematocrit have been observed.Atrophy is postulated to result from shunting of protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated action.While data are scarce regarding their causative agents,arrhythmias have been frequently reported,albeit sublethal,during both Russian and American expeditions,with QT interval prolongation observed in long,but not short duration,spaceflight.Exposure of the heart to the proton and heavy ion radiation of deep space has also been shown to result in coronary artery degeneration,aortic stiffness,carotid intima thickening via collagen-mediated action,accelerated atherosclerosis,and induction of a pro-inflammatory state.Upon return,long-term spaceflight frequently results in orthostatic intolerance and altered sympathetic responses,which can prove hazardous should any rapidmobilization or evacuation be required,and indicates that these cardiac risks should be especially monitored for future missions.
基金supported by the National Basic Research (973) Program (2015CB351702)the Natural Science Foundation of China (81471740)+3 种基金Beijing Municipal Science and Tech Commission (Z161100002616023, Z171100000117012)the China – Netherlands CAS-NWO Programme (153111KYSB20160020)the Major Project of National Social Science Foundation of China (14ZDB161)the National R&D Infrastructure and Facility Development Program of China, ‘‘Fundamental Science Data Sharing Platform" (DKA2017-12-02-21)
文摘Human brain mapping (HBM)is increasingly becoming a multidisciplinary field where some scientific issues are fundamental for all scientists and applications of using the technology to investigate individual differences.Reliability represents a significant issue for all scientific fields and has particularly been overlooked for decades by the HBM field [1].Meanwhile,recent advances in open science have offered the field big data for developing novel methodological frameworks as well as performing largescale investigations of the brain-mind associations based upon the individual differences assessed with HBM [2].A systematic investigation of reliability seems still far behind these HBM developments. It is critical that reliability is evaluated ahead of these applications, motivating the current commentary on delineation of the anatomy of reliability for future HBM.
基金the National Natural Science Foundation of China(81520108016,81661148045,and 31471084 to Yu-Feng Zang81671774 and 81630031 to Chao-Gan Yan+11 种基金81571228 to Tao Wu61571047 to Xia Wu81701664 to Jian Wang,81471654 to Biao Huang81701671 to Wei-Guo Liu82001898 to Xi-Ze Jia81771820,81371519 and 81571654 to Wei Luo)Henry G Leong Endowed Professorship in Neurology to Shu-Leong Ho and Shirley YY Pang,BRC for Mental Health at South London and Maudsley NHS Foundation Trust and by the Sackler Institute to Grainne McAlonan,NIH(2R01AG006457 to Fay B.Horak1RC4NS073008-01 and P50NS062684 to Tara Madhyastha)NINDS Intramural Research Program to Mark HallettStart-up Funds for Leading Talents at Beijing Normal UniversityNational Basic Science Data Center‘‘Chinese Data-sharing Warehouse for In-vivo Imaging Brain”(NBSDC-DB-15)to Xi-Nian ZuoGrant NU20-04-00294 of the Agency for Health Research,Czech Republic to Lenka Krajcovicova and Irena Rektorova。
文摘Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because of the large number of voxels in the brain,multiple comparison correction(MCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent MCC)is widely recommended[1].
文摘ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosides,sugars,and xenobiotics.Interestingly,ABC transporters are highly expressed in the brain.While their functions in the brain still need to be elucidated,several members are implicated in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and frontotemporal dementia.In this perspective,we will review current knowledge of ABC transporters in the central nervous system in terms of physiological functions and pathology in neurodegeneration.Furthermore,we will explore the possibilities of ABC transporters as potential targets in the development of therapeutics for neurodegenerative diseases.
文摘Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.
基金supported by the STI 2030–the major project of the Brain Science and Brain-Inspired Intelligence Technology(2021ZD0200500)。
文摘It is of great scientific and translational promise to formulate a normative reference for the lifespan development of human brain to precisely quantify individual differences.By aggregating more than 120,000 brain imaging scans across the world,the Lifespan Brain Chart Consortium(LBCC)recently published brain charts for the human lifespan in Nature[1].
文摘Frontotemporal dementia(FTD) and amyotrophic lateral sclerosis(ALS) are neurodegenerative diseases that belong to the same disease spectrum,with overlapping of genetic and pathological features.Genetic mutations in TARDBP,C9ORF72,MAPT,and GRN have been identified in these diseases.
基金supported by the Bluesand FoundationTDM FoundationFaculty of Medicine and Health, University of Sydney (FMH EMCR Emerging Star Grant), NIH (P01AG060882) to ED。
文摘There is an urgent need to identify new drug targets for Alzheimer's disease(AD). While new immunotherapies show promise, clinical benefit appears low, and side effects are high. A greater understanding of the disease mechanisms driving AD is an essential factor that will facilitate the identification of new, effective drug targets.
基金Supported by The grants from the National Center for Research Resources,No.5P20RR016480-12The National Institute of General Medical Sciences of the NIH,No.8P20GM103451-12+2 种基金the partial support from the National Center for Advancing Translational Sciences of the National Institutes of Health,No.8UL1TR000041the University of New Mexico Clinical and Translational Science Centerthe cost for clinical phenotyping and payments to participants was supported under a UNM Health Sciences Center-based Cardiovascular and Metabolic Diseases Signature Program
文摘AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus(Pre-DM) subjects who transitioned to type 2 diabetes mellitus(T2DM).METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM(n = 11) at baseline and at their transition to T2 DM using Illumina Infinium Human Methylation27 Bead Chip, that enables the query of 27578 individual cytosines at Cp G loci throughout the genome, which are focused on the promoter regions of 14495 genes.RESULTS: There were 694 Cp G sites hypomethylated and 174 Cp G sites hypermethylated in progression from Pre-DM to T2 DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective Cp G sites associated with diverse genes that may reflect differences in Pre-DM compared with T2 DM. In addition, there were Cp G hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects.CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.
文摘Stem cell-based therapies and extracellular vesicle(EV)treatment have demonstrated significant potential for neuroprotection against ischemic stroke.Although the neuroprotective mechanisms are not yet fully under-stood,targeting microglia is central to promoting neuroprotection.Microglia are the resident immune cells of the central nervous system.These cells are crucial in the pathogenesis of ischemic stroke.They respond rapidly to the site of injury by releasing pro-inflammatory cytokines,phagocytizing dead cells and debris,and recruiting peripheral immune cells to the ischemic area.Although these responses are essential for clearing damage and initiating tissue repair,excessive or prolonged microglial activation can exacerbate brain injury,leading to secondary neuroinflammation and neurodegeneration.Moreover,microglia exhibit a dynamic range of activation states with the so-called M1 pro-inflammatory and M2 anti-inflammatory phenotypes,representing the two ends of the spectrum.The delivery of both EVs and stem cells modulates microglial activation,suppressing pro-inflammatory genes,influencing the expression of transcription factors,and altering receptor expression,ultimately contributing to neuroprotection.These findings underscore the importance of understanding the complex and dynamic role of microglia in the development of effective neuroprotective strategies to reduce the effects of ischemic stroke.In this review,we examine the current state of knowledge regarding the role of microglia in ischemic stroke,including their molecular and cellular mechanisms,activation states,and interactions with other cells.We also discuss the multifaceted contributions of microglia to stem cell-and EV-based neuroprotection during an ischemic stroke to provide a comprehensive understanding of microglial functions and their potential implications in stroke therapies.
