Spinal cord injury（SCI）is a devastating ailment that results in drastic life style alterations for the patients and their family members（Mc Donald and Sadowsky,2002）.Damage post injury causes necrosis,edema,hemorr...Spinal cord injury（SCI）is a devastating ailment that results in drastic life style alterations for the patients and their family members（Mc Donald and Sadowsky,2002）.Damage post injury causes necrosis,edema,hemorrhage and vasospasm.Post injury,secondary damage is caused by ischemia,展开更多
KCNB1, a voltage-gated potassium(K+) channel that conducts a major delayed rectifier current in the brain, pancreas and cardiovascular system is a key player in apoptotic programs associated with oxidative stress. As ...KCNB1, a voltage-gated potassium(K+) channel that conducts a major delayed rectifier current in the brain, pancreas and cardiovascular system is a key player in apoptotic programs associated with oxidative stress. As a result, this protein represents a bona fide drug target for limiting the toxic effects of oxygen radicals. Until recently the consensus view was that reactive oxygen species trigger a pro-apoptotic surge in KCNB1 current via phosphorylation and SNARE-dependent incorpora-tion of KCNB1 channels into the plasma membrane. However, new evidence shows that KCNB1 can be modified by oxidants and that oxidized KCNB1 channels can directly activate pro-apoptotic signaling pathways. Hence, a more articulated picture of the pro-apoptotic role of KCNB1 is emerging in which the protein induces cell's death through distinct molecular mechanisms and activation of multiple pathways. In this review article we discuss the diverse functional, toxic and protective roles that KCNB1 channels play in the major organs where they are expressed.展开更多
Understanding the role of adult neural stem cells in maintaining specific brain function is a rapidly expanding research field. Recent technological advances to culture and trace neural stem cells, such as stem cell i...Understanding the role of adult neural stem cells in maintaining specific brain function is a rapidly expanding research field. Recent technological advances to culture and trace neural stem cells, such as stem cell isolation and expansion and inducible transgenic lineage tracing mouse models, have enabled more in-depth studies into the mechanisms governing neural stem cell homeostasis and pathophysiology in the adult brain. In this review we will briefly discuss the types and locations of adult neural stem cells in the mammalian brain, recent developments in tools used to study these cells, and the translational implications.展开更多
Traumatic brain injury(TBI)is a serious condition in which trauma to the head causes damage to the brain,leading to a disruption in brain function.This is a significant health issue worldwide,with around 69 million pe...Traumatic brain injury(TBI)is a serious condition in which trauma to the head causes damage to the brain,leading to a disruption in brain function.This is a significant health issue worldwide,with around 69 million people suffering from TBI each year.Immediately following the trauma,damage occurs in the acute phase of injury that leads to the primary outcomes of the TBI.In the hours-to-days that follow,secondary damage can also occur,leading to chronic outcomes.TBIs can range in severity from mild to severe,and can be complicated by the fact that some individuals sustain multiple TBIs,a risk factor for worse long-term outcomes.Although our knowledge about the pathophysiology of TBI has increased in recent years,unfortunately this has not been translated into effective clinical therapies.The U.S.Food and Drug Administration has yet to approve any drugs for the treatment of TBI;current clinical treatment guidelines merely offer supportive care.Outcomes between individuals greatly vary,which makes the treatment for TBI so challenging.A blow of similar force can have only mild,primary outcomes in one individual and yet cause severe,chronic outcomes in another.One of the reasons that have been proposed for this differential response to TBI is the underlying genetic differences across the population.Due to this,many researchers have begun to investigate the possibility of using precision medicine techniques to address TBI treatment.In this review,we will discuss the research detailing the identification of genetic risk factors for worse outcomes after TBI,and the work investigating personalized treatments for these higher-risk individuals.We highlight the need for further research into the identification of higher-risk individuals and the development of personalized therapies for TBI.展开更多
Ion channels modulate cellular excitability by regulating ionic fluxes across biological membranes.Pathogenic mutations in ion channel genes give rise to epileptic disorders that are among the most frequent neurologic...Ion channels modulate cellular excitability by regulating ionic fluxes across biological membranes.Pathogenic mutations in ion channel genes give rise to epileptic disorders that are among the most frequent neurological diseases affecting millions of individuals worldwide.Epilepsies are trigge red by an imbalance between excitatory and inhibitory conductances.However,pathogenic mutations in the same allele can give rise to loss-of-function and/or gain-of-function va riants,all able to trigger epilepsy.Furthermore,certain alleles are associated with brain malformations even in the absence of a clear electrical phenotype.This body of evidence argues that the underlying epileptogenic mechanisms of ion channels are more diverse than originally thought.Studies focusing on ion channels in prenatal cortical development have shed light on this apparent paradox.The picture that emerges is that ion channels play crucial roles in landmark neurodevelopmental processes,including neuronal migration,neurite outgrowth,and synapse formation.Thus,pathogenic channel mutants can not only cause epileptic disorders by alte ring excitability,but further,by inducing morphological and synaptic abnormalities that are initiated during neocortex formation and may persist into the adult brain.展开更多
Optoacoustics is a promising modality for biomedical imaging,sensing,and monitoring with high resolution and contrast.In this paper,we present an overview of our studies for the last two decades on optoacoustic effect...Optoacoustics is a promising modality for biomedical imaging,sensing,and monitoring with high resolution and contrast.In this paper,we present an overview of our studies for the last two decades on optoacoustic effects in tissues and imaging capabilities of the optoacoustic technique.In our earlier optoacoustic works we studied laser ablation of tissues and tissue-like media and proposed to use optoacoustics for imaging in tissues.In mid-90s we demonstrated detection of optoacoustic signals from tissues at depths of up to several centimeters,well deeper than the optical diffusion limit.We then obtained optoacoustic images of tissues both in vitro and in vivo.In late 90s we studied optoacoustic monitoring of thermotherapy:hyperthermia,coagulation,and freezing.Then we proposed and studied optoacoustic monitoring of blood oxygenation,hemoglobin concentration,and other physiologic parameters.展开更多
Methyl-CpG-binding protein 2(MeCP2),encoded by the gene MECP2,is a transcriptional regulator and chromatinremodeling protein,which is ubiquitously expressed and plays an essential role in the development and maintenan...Methyl-CpG-binding protein 2(MeCP2),encoded by the gene MECP2,is a transcriptional regulator and chromatinremodeling protein,which is ubiquitously expressed and plays an essential role in the development and maintenance of the central nervous system(CNS).Highly enriched in post-migratory neurons,MeCP2 is needed for neuronal maturation,including dendritic arborization and the development of synapses.Loss-of-function mutations in MECP2 cause Rett syndrome(RTT),a debilitating neurodevelopmental disorder characterized by a phase of normal development,followed by the progressive loss of milestones and cognitive disability.While a great deal has been discovered about the structure,function,and regulation of MeCP2 in the time since its discovery as the genetic cause of RTT,including its involvement in a number of RTT-related syndromes that have come to be known as MeCP2-spectrum disorders,much about this multifunctional protein remains enigmatic.One unequivocal fact that has become apparent is the importance of maintaining MeCP2 protein levels within a narrow range,the limits of which may depend upon the cell type and developmental time point.As such,MeCP2 is amenable to complex,multifactorial regulation.Here,we summarize the role of the MECP23'untranslated region(UTR)in the regulation of MeCP2 protein levels and how mutations in this region contribute to autism and other non-RTT neuropsychiatric disorders.展开更多
Hunger, mostly initiated by a deficiency in energy, induces food seeking and intake. However, the drive toward food is not only regulated by physiological needs, but is motivated by the pleasure derived from ingestion...Hunger, mostly initiated by a deficiency in energy, induces food seeking and intake. However, the drive toward food is not only regulated by physiological needs, but is motivated by the pleasure derived from ingestion of food, in particular palatable foods. Therefore, feeding is viewed as an adaptive motivated behavior that involves integrated communication between homeostatic feeding circuits and reward circuits. The initiation and termination of a feeding episode are instructed by a variety of neuronal signals, and maladaptive plasticity in almost any component of the network may lead to the development of pathological eating disorders. In this review we will summarize the latest understanding of how the feeding circuits and reward circuits in the brain interact. We will emphasize communication between the hypothalamus and the mesolimbic dopamine system and highlight complexities, discrepancies, open questions and future directions for the field.展开更多
Chromosomes, the longest molecular fiber that stores genetic information in eukaryotic cells, must be orderly packaged during mitosis for their proper segregation into daughter cells. Although the morphological change...Chromosomes, the longest molecular fiber that stores genetic information in eukaryotic cells, must be orderly packaged during mitosis for their proper segregation into daughter cells. Although the morphological changes of chromosomes during mitosis have been described in detail, how mitosis progression programs the transformation of seemingly amorphous and loose interphase .展开更多
文摘Spinal cord injury（SCI）is a devastating ailment that results in drastic life style alterations for the patients and their family members（Mc Donald and Sadowsky,2002）.Damage post injury causes necrosis,edema,hemorrhage and vasospasm.Post injury,secondary damage is caused by ischemia,
基金Supported by National Science Foundation Grant to Sesti F,No.1026958
文摘KCNB1, a voltage-gated potassium(K+) channel that conducts a major delayed rectifier current in the brain, pancreas and cardiovascular system is a key player in apoptotic programs associated with oxidative stress. As a result, this protein represents a bona fide drug target for limiting the toxic effects of oxygen radicals. Until recently the consensus view was that reactive oxygen species trigger a pro-apoptotic surge in KCNB1 current via phosphorylation and SNARE-dependent incorpora-tion of KCNB1 channels into the plasma membrane. However, new evidence shows that KCNB1 can be modified by oxidants and that oxidized KCNB1 channels can directly activate pro-apoptotic signaling pathways. Hence, a more articulated picture of the pro-apoptotic role of KCNB1 is emerging in which the protein induces cell's death through distinct molecular mechanisms and activation of multiple pathways. In this review article we discuss the diverse functional, toxic and protective roles that KCNB1 channels play in the major organs where they are expressed.
文摘Understanding the role of adult neural stem cells in maintaining specific brain function is a rapidly expanding research field. Recent technological advances to culture and trace neural stem cells, such as stem cell isolation and expansion and inducible transgenic lineage tracing mouse models, have enabled more in-depth studies into the mechanisms governing neural stem cell homeostasis and pathophysiology in the adult brain. In this review we will briefly discuss the types and locations of adult neural stem cells in the mammalian brain, recent developments in tools used to study these cells, and the translational implications.
基金supported by a grant from the New Jersey Commission on Brain Injury Research(No.CBIR16FEL009).
文摘Traumatic brain injury(TBI)is a serious condition in which trauma to the head causes damage to the brain,leading to a disruption in brain function.This is a significant health issue worldwide,with around 69 million people suffering from TBI each year.Immediately following the trauma,damage occurs in the acute phase of injury that leads to the primary outcomes of the TBI.In the hours-to-days that follow,secondary damage can also occur,leading to chronic outcomes.TBIs can range in severity from mild to severe,and can be complicated by the fact that some individuals sustain multiple TBIs,a risk factor for worse long-term outcomes.Although our knowledge about the pathophysiology of TBI has increased in recent years,unfortunately this has not been translated into effective clinical therapies.The U.S.Food and Drug Administration has yet to approve any drugs for the treatment of TBI;current clinical treatment guidelines merely offer supportive care.Outcomes between individuals greatly vary,which makes the treatment for TBI so challenging.A blow of similar force can have only mild,primary outcomes in one individual and yet cause severe,chronic outcomes in another.One of the reasons that have been proposed for this differential response to TBI is the underlying genetic differences across the population.Due to this,many researchers have begun to investigate the possibility of using precision medicine techniques to address TBI treatment.In this review,we will discuss the research detailing the identification of genetic risk factors for worse outcomes after TBI,and the work investigating personalized treatments for these higher-risk individuals.We highlight the need for further research into the identification of higher-risk individuals and the development of personalized therapies for TBI.
基金NJ Governor’s Council for Medical Research and Treatment of Autism predoctoral fellowship (CAUT23AFP015) to ABNational Science Foundation grant (2030348) to FS。
文摘Ion channels modulate cellular excitability by regulating ionic fluxes across biological membranes.Pathogenic mutations in ion channel genes give rise to epileptic disorders that are among the most frequent neurological diseases affecting millions of individuals worldwide.Epilepsies are trigge red by an imbalance between excitatory and inhibitory conductances.However,pathogenic mutations in the same allele can give rise to loss-of-function and/or gain-of-function va riants,all able to trigger epilepsy.Furthermore,certain alleles are associated with brain malformations even in the absence of a clear electrical phenotype.This body of evidence argues that the underlying epileptogenic mechanisms of ion channels are more diverse than originally thought.Studies focusing on ion channels in prenatal cortical development have shed light on this apparent paradox.The picture that emerges is that ion channels play crucial roles in landmark neurodevelopmental processes,including neuronal migration,neurite outgrowth,and synapse formation.Thus,pathogenic channel mutants can not only cause epileptic disorders by alte ring excitability,but further,by inducing morphological and synaptic abnormalities that are initiated during neocortex formation and may persist into the adult brain.
基金Supported by Forgorty Fellowship from NIDA/INVEST,NIH,USAby grant of National Basic Research Program of China (2007CB512501)the “111” Project of the Ministry of Education of China
文摘Optoacoustics is a promising modality for biomedical imaging,sensing,and monitoring with high resolution and contrast.In this paper,we present an overview of our studies for the last two decades on optoacoustic effects in tissues and imaging capabilities of the optoacoustic technique.In our earlier optoacoustic works we studied laser ablation of tissues and tissue-like media and proposed to use optoacoustics for imaging in tissues.In mid-90s we demonstrated detection of optoacoustic signals from tissues at depths of up to several centimeters,well deeper than the optical diffusion limit.We then obtained optoacoustic images of tissues both in vitro and in vivo.In late 90s we studied optoacoustic monitoring of thermotherapy:hyperthermia,coagulation,and freezing.Then we proposed and studied optoacoustic monitoring of blood oxygenation,hemoglobin concentration,and other physiologic parameters.
基金We want to thank the support from NIH-NINDS F31NS084551 NRSA predoctoral fellowship and the Jérôme LeJeune Foundation.
文摘Methyl-CpG-binding protein 2(MeCP2),encoded by the gene MECP2,is a transcriptional regulator and chromatinremodeling protein,which is ubiquitously expressed and plays an essential role in the development and maintenance of the central nervous system(CNS).Highly enriched in post-migratory neurons,MeCP2 is needed for neuronal maturation,including dendritic arborization and the development of synapses.Loss-of-function mutations in MECP2 cause Rett syndrome(RTT),a debilitating neurodevelopmental disorder characterized by a phase of normal development,followed by the progressive loss of milestones and cognitive disability.While a great deal has been discovered about the structure,function,and regulation of MeCP2 in the time since its discovery as the genetic cause of RTT,including its involvement in a number of RTT-related syndromes that have come to be known as MeCP2-spectrum disorders,much about this multifunctional protein remains enigmatic.One unequivocal fact that has become apparent is the importance of maintaining MeCP2 protein levels within a narrow range,the limits of which may depend upon the cell type and developmental time point.As such,MeCP2 is amenable to complex,multifactorial regulation.Here,we summarize the role of the MECP23'untranslated region(UTR)in the regulation of MeCP2 protein levels and how mutations in this region contribute to autism and other non-RTT neuropsychiatric disorders.
文摘Hunger, mostly initiated by a deficiency in energy, induces food seeking and intake. However, the drive toward food is not only regulated by physiological needs, but is motivated by the pleasure derived from ingestion of food, in particular palatable foods. Therefore, feeding is viewed as an adaptive motivated behavior that involves integrated communication between homeostatic feeding circuits and reward circuits. The initiation and termination of a feeding episode are instructed by a variety of neuronal signals, and maladaptive plasticity in almost any component of the network may lead to the development of pathological eating disorders. In this review we will summarize the latest understanding of how the feeding circuits and reward circuits in the brain interact. We will emphasize communication between the hypothalamus and the mesolimbic dopamine system and highlight complexities, discrepancies, open questions and future directions for the field.
文摘Chromosomes, the longest molecular fiber that stores genetic information in eukaryotic cells, must be orderly packaged during mitosis for their proper segregation into daughter cells. Although the morphological changes of chromosomes during mitosis have been described in detail, how mitosis progression programs the transformation of seemingly amorphous and loose interphase .
