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Sample records for adult human neural

  1. Adult human neural stem cell therapeutics: Currentdevelopmental status and prospect

    Institute of Scientific and Technical Information of China (English)

    Hyun Nam; Kee-Hang Lee; Do-Hyun Nam; Kyeung Min Joo

    2015-01-01

    Over the past two decades, regenerative therapies usingstem cell technologies have been developed for variousneurological diseases. Although stem cell therapy is anattractive option to reverse neural tissue damage and torecover neurological deficits, it is still under developmentso as not to show significant treatment effects in clinicalsettings. In this review, we discuss the scientific andclinical basics of adult neural stem cells (aNSCs), andtheir current developmental status as cell therapeuticsfor neurological disease. Compared with other typesof stem cells, aNSCs have clinical advantages, suchas limited proliferation, inborn differentiation potentialinto functional neural cells, and no ethical issues. Inspite of the merits of aNSCs, difficulties in the isolationfrom the normal brain, and in the in vitro expansion,have blocked preclinical and clinical study using aNSCs.However, several groups have recently developed noveltechniques to isolate and expand aNSCs from normaladult brains, and showed successful applications ofaNSCs to neurological diseases. With new technologiesfor aNSCs and their clinical strengths, previous hurdlesin stem cell therapies for neurological diseases could beovercome, to realize clinically efficacious regenerativestem cell therapeutics.

  2. Human-derived neural progenitors functionally replace astrocytes in adult mice

    OpenAIRE

    Chen, Hong; Qian, Kun; Chen, Wei; Hu, Baoyang; Blackbourn, Lisle W.; Du, Zhongwei; Ma, Lixiang; Liu, Huisheng; Knobel, Karla M.; Ayala, Melvin; Zhang, Su-Chun

    2015-01-01

    Astrocytes are integral components of the homeostatic neural network as well as active participants in pathogenesis of and recovery from nearly all neurological conditions. Evolutionarily, compared with lower vertebrates and nonhuman primates, humans have an increased astrocyte-to-neuron ratio; however, a lack of effective models has hindered the study of the complex roles of human astrocytes in intact adult animals. Here, we demonstrated that after transplantation into the cervical spinal co...

  3. Human-derived neural progenitors functionally replace astrocytes in adult mice

    Science.gov (United States)

    Chen, Hong; Qian, Kun; Chen, Wei; Hu, Baoyang; Blackbourn, Lisle W.; Du, Zhongwei; Ma, Lixiang; Liu, Huisheng; Knobel, Karla M.; Ayala, Melvin; Zhang, Su-Chun

    2015-01-01

    Astrocytes are integral components of the homeostatic neural network as well as active participants in pathogenesis of and recovery from nearly all neurological conditions. Evolutionarily, compared with lower vertebrates and nonhuman primates, humans have an increased astrocyte-to-neuron ratio; however, a lack of effective models has hindered the study of the complex roles of human astrocytes in intact adult animals. Here, we demonstrated that after transplantation into the cervical spinal cords of adult mice with severe combined immunodeficiency (SCID), human pluripotent stem cell–derived (PSC-derived) neural progenitors migrate a long distance and differentiate to astrocytes that nearly replace their mouse counterparts over a 9-month period. The human PSC-derived astrocytes formed networks through their processes, encircled endogenous neurons, and extended end feet that wrapped around blood vessels without altering locomotion behaviors, suggesting structural, and potentially functional, integration into the adult mouse spinal cord. Furthermore, in SCID mice transplanted with neural progenitors derived from induced PSCs from patients with ALS, astrocytes were generated and distributed to a similar degree as that seen in mice transplanted with healthy progenitors; however, these mice exhibited motor deficit, highlighting functional integration of the human-derived astrocytes. Together, these results indicate that this chimeric animal model has potential for further investigating the roles of human astrocytes in disease pathogenesis and repair. PMID:25642771

  4. Adult human neural stem cells : Properties in vitro and as xenografts in the spinal cord

    OpenAIRE

    Westerlund, Ulf

    2005-01-01

    Though the presence of stem cells in the adult human brain has been presented earlier, much has yet to be discovered about these cells. However, the mere potential of these cells has had a significant impact of how we today evaluate the regenerative capacity of the central nervous system and, importantly, on the possible means for science to provide insights in neural repair. In this thesis a series of in vitro studies, based on the formation of neurospheres, was used to...

  5. Expression of nestin by neural cells in the adult rat and human brain.

    Directory of Open Access Journals (Sweden)

    Michael L Hendrickson

    Full Text Available Neurons and glial cells in the developing brain arise from neural progenitor cells (NPCs. Nestin, an intermediate filament protein, is thought to be expressed exclusively by NPCs in the normal brain, and is replaced by the expression of proteins specific for neurons or glia in differentiated cells. Nestin expressing NPCs are found in the adult brain in the subventricular zone (SVZ of the lateral ventricle and the subgranular zone (SGZ of the dentate gyrus. While significant attention has been paid to studying NPCs in the SVZ and SGZ in the adult brain, relatively little attention has been paid to determining whether nestin-expressing neural cells (NECs exist outside of the SVZ and SGZ. We therefore stained sections immunocytochemically from the adult rat and human brain for NECs, observed four distinct classes of these cells, and present here the first comprehensive report on these cells. Class I cells are among the smallest neural cells in the brain and are widely distributed. Class II cells are located in the walls of the aqueduct and third ventricle. Class IV cells are found throughout the forebrain and typically reside immediately adjacent to a neuron. Class III cells are observed only in the basal forebrain and closely related areas such as the hippocampus and corpus striatum. Class III cells resemble neurons structurally and co-express markers associated exclusively with neurons. Cell proliferation experiments demonstrate that Class III cells are not recently born. Instead, these cells appear to be mature neurons in the adult brain that express nestin. Neurons that express nestin are not supposed to exist in the brain at any stage of development. That these unique neurons are found only in brain regions involved in higher order cognitive function suggests that they may be remodeling their cytoskeleton in supporting the neural plasticity required for these functions.

  6. Reprogramming of adult human neural stem cells into induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    XIE Li-qian; SUN Hua-ping; WANG Tian; TANG Hai-liang; WANG Pu; ZHU Jian-hong; YAO Zheng-wei

    2013-01-01

    Background Since an effective method for generating induced pluripotent stem cells (iPSCs) from human neural stem cells (hNSCs) can offer us a promising tool for studying brain diseases,here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors.Methods NSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients.When combined with four factors (OCT3/4,SOX2,KLF4,and c-MYC),iPSCs colonies were successfully obtained.Results Morphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties,which include the ability to differentiate into all three germ layers both in vitro and in vivo.Conclusion Our method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.

  7. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    Energy Technology Data Exchange (ETDEWEB)

    Manceur, Aziza P. [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Michael [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Holowacz, Tamara [Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Department of Otolaryngology, Head and Neck Surgery, University of Toronto, ON (Canada); Weksberg, Rosanna [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); McCurdy, Richard D. [The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); Warsh, Jerry J. [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Audet, Julie, E-mail: julie.audet@utoronto.ca [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada)

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  8. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    International Nuclear Information System (INIS)

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  9. Adult human neural stem cell therapeutics: Current developmental status and prospect

    OpenAIRE

    Nam, Hyun; Lee, Kee-Hang; Nam, Do-Hyun; Joo, Kyeung Min

    2015-01-01

    Over the past two decades, regenerative therapies using stem cell technologies have been developed for various neurological diseases. Although stem cell therapy is an attractive option to reverse neural tissue damage and to recover neurological deficits, it is still under development so as not to show significant treatment effects in clinical settings. In this review, we discuss the scientific and clinical basics of adult neural stem cells (aNSCs), and their current developmental status as ce...

  10. Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction

    Science.gov (United States)

    Jeong, Da Eun; Kim, Sung Soo; Song, Hye Jin; Pyeon, Hee Jang; Kang, Kyeongjin; Hong, Seung-Cheol; Nam, Do-Hyun; Joo, Kyeung Min

    2016-01-01

    Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs) immortalized by the human telomerase reverse transcriptase (hTERT) gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM) cells were injected into adult (4–6-week-old) Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1–2-week-old) NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL) were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL), they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases. PMID:27391353

  11. Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells

    Science.gov (United States)

    Lopes, Carla; Aubert, Sophie; Bourgois-Rocha, Fany; Barnat, Monia; Rego, Ana Cristina; Déglon, Nicole

    2016-01-01

    Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington’s disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions. PMID:26863614

  12. Rapid and Efficient Direct Conversion of Human Adult Somatic Cells into Neural Stem Cells by HMGA2/let-7b

    Directory of Open Access Journals (Sweden)

    Kyung-Rok Yu

    2015-01-01

    Full Text Available A recent study has suggested that fibroblasts can be converted into mouse-induced neural stem cells (miNSCs through the expression of defined factors. However, successful generation of human iNSCs (hiNSCs has proven challenging to achieve. Here, using microRNA (miRNA expression profile analyses, we showed that let-7 microRNA has critical roles for the formation of PAX6/NESTIN-positive colonies from human adult fibroblasts and the proliferation and self-renewal of hiNSCs. HMGA2, a let-7-targeting gene, enables induction of hiNSCs that displayed morphological/molecular features and in vitro/in vivo differentiation potential similar to H9-derived NSCs. Interestingly, HMGA2 facilitated the efficient conversion of senescent somatic cells or blood CD34+ cells into hiNSCs through an interaction with SOX2, whereas other combinations or SOX2 alone showed a limited conversion ability. Taken together, these findings suggest that HMGA2/let-7 facilitates direct reprogramming toward hiNSCs in minimal conditions and maintains hiNSC self-renewal, providing a strategy for the clinical treatment of neurological diseases.

  13. Culture bag systems for clinical applications of adult human neural crest-derived stem cells

    OpenAIRE

    Greiner, Johannes F. W.; Grunwald, Lena-Marie; Müller, Janine; Sudhoff, Holger; Widera, Darius; Kaltschmidt, Christian; Kaltschmidt, Barbara

    2014-01-01

    Introduction Facing the challenging treatment of neurodegenerative diseases as well as complex craniofacial injuries such as those common after cancer therapy, the field of regenerative medicine increasingly relies on stem cell transplantation strategies. Here, neural crest-derived stem cells (NCSCs) offer many promising applications, although scale up of clinical-grade processes prior to potential transplantations is currently limiting. In this study, we aimed to establish a clinical-grad...

  14. Menstrual cycle-dependent neural plasticity in the adult human brain is hormone, task, and region specific.

    NARCIS (Netherlands)

    Fernandez, G.S.E.; Weis, S.; Stoffel-Wagner, B.; Tendolkar, I.; Reuber, M.; Beyenburg, S.; Klaver, P.; Fell, J.; Greiff, A. de; Ruhlmann, J.; Reul, J.; Elger, C.E.

    2003-01-01

    In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle phase-depe

  15. Menstrual cycle-dependent neural plasticity in the adult human brain is hormone, task, and region specific.

    OpenAIRE

    Fernandez, G.S.E.; Weis, S.; Stoffel-Wagner, B.; Tendolkar, I.; Reuber, M; Beyenburg, S; Klaver, P.; Fell, J.; Greiff, A. de; Ruhlmann, J; Reul, J.; Elger, C E

    2003-01-01

    In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle phase-dependent differences in cognitive performance have almost exclusively been found in tasks probing lateralized neuronal domains, i.e., cognitive domains such as language, which are predominantly execut...

  16. Long-Term, Stable Differentiation Of Human Embryonic Stem Cell-Derived Neural Precursors Grafted Into The Adult Mammalian Neostriatum

    OpenAIRE

    Nasonkin, I; Mahairaki, V.; Xu, L.; Hatfield, G.; Cummings, B.J.; Eberhart, C.; Ryugo, D.; Maric, D; Bar, E; Koliatsos, V E

    2009-01-01

    Stem-cell grafts have been advocated as experimental treatments for neurological diseases by virtue of their ability to offer trophic support for injured neurons and, theoretically, to replace dead neurons. Human embryonic stem cells (HESCs) are a rich source of neural precursors (NPs) for grafting, but have been questioned for their tendency to form tumors. Here we studied the ability of HESC-derived NP grafts optimized for cell number and differentiation stage prior to transplantation, to s...

  17. Immunological control of adult neural stem cells

    OpenAIRE

    Gonzalez-Perez, Oscar; Quiñones-Hinojosa, Alfredo; Garcia-Verdugo, Jose Manuel

    2010-01-01

    Adult neurogenesis occurs only in discrete regions of adult central nervous system: the subventricular zone and the subgranular zone. These areas are populated by adult neural stem cells (aNSC) that are regulated by a number of molecules and signaling pathways, which control their cell fate choices, survival and proliferation rates. For a long time, it was believed that the immune system did not exert any control on neural proliferative niches. However, it has been observed that many patholog...

  18. Adult neural stem cells in the mammalian central nervous system

    Institute of Scientific and Technical Information of China (English)

    Dengke K Ma; Michael A Bonaguidi; Guo-li Ming; Hongjun Song

    2009-01-01

    Neural stem cells (NSCs) are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, in-cluding topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.

  19. Interaction of adult human neural crest-derived stem cells with a nanoporous titanium surface is sufficient to induce their osteogenic differentiation

    Directory of Open Access Journals (Sweden)

    Matthias Schürmann

    2014-07-01

    Full Text Available Osteogenic differentiation of various adult stem cell populations such as neural crest-derived stem cells is of great interest in the context of bone regeneration. Ideally, exogenous differentiation should mimic an endogenous differentiation process, which is partly mediated by topological cues. To elucidate the osteoinductive potential of porous substrates with different pore diameters (30 nm, 100 nm, human neural crest-derived stem cells isolated from the inferior nasal turbinate were cultivated on the surface of nanoporous titanium covered membranes without additional chemical or biological osteoinductive cues. As controls, flat titanium without any topological features and osteogenic medium was used. Cultivation of human neural crest-derived stem cells on 30 nm pores resulted in osteogenic differentiation as demonstrated by alkaline phosphatase activity after seven days as well as by calcium deposition after 3 weeks of cultivation. In contrast, cultivation on flat titanium and on membranes equipped with 100 nm pores was not sufficient to induce osteogenic differentiation. Moreover, we demonstrate an increase of osteogenic transcripts including Osterix, Osteocalcin and up-regulation of Integrin β1 and α2 in the 30 nm pore approach only. Thus, transplantation of stem cells pre-cultivated on nanostructured implants might improve the clinical outcome by support of the graft adherence and acceleration of the regeneration process.

  20. Skeletal myogenic potential of human and mouse neural stem cells.

    Science.gov (United States)

    Galli, R; Borello, U; Gritti, A; Minasi, M G; Bjornson, C; Coletta, M; Mora, M; De Angelis, M G; Fiocco, R; Cossu, G; Vescovi, A L

    2000-10-01

    Distinct cell lineages established early in development are usually maintained throughout adulthood. Thus, adult stem cells have been thought to generate differentiated cells specific to the tissue in which they reside. This view has been challenged; for example, neural stem cells can generate cells that normally originate from a different germ layer. Here we show that acutely isolated and clonally derived neural stem cells from mice and humans could produce skeletal myotubes in vitro and in vivo, the latter following transplantation into adult animals. Myogenic conversion in vitro required direct exposure to myoblasts, and was blocked if neural cells were clustered. Thus, a community effect between neural cells may override such myogenic induction. We conclude that neural stem cells, which generate neurons, glia and blood cells, can also produce skeletal muscle cells, and can undergo various patterns of differentiation depending on exposure to appropriate epigenetic signals in mature tissues. PMID:11017170

  1. Neural plasticity in adults with amblyopia.

    OpenAIRE

    Levi, D M; U. Polat

    1996-01-01

    Amblyopia is a neuronal abnormality of vision that is often considered irreversible in adults. We found strong and significant improvement of Vernier acuity in human adults with naturally occurring amblyopia following practice. Learning was strongest at the trained orientation and did not transfer to an untrained task (detection), but it did transfer partially to the untrained eye (primarily at the trained orientation). We conclude that this perceptual learning reflects alterations in early n...

  2. Human Metapneumovirus in Adults

    OpenAIRE

    Haas, Lenneke E. M.; Steven F. T. Thijsen; Leontine van Elden; Heemstra, Karen A.

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children ...

  3. Diversity of Neural Precursors in the Adult Mammalian Brain.

    Science.gov (United States)

    Bonaguidi, Michael A; Stadel, Ryan P; Berg, Daniel A; Sun, Jiaqi; Ming, Guo-Li; Song, Hongjun

    2016-01-01

    Aided by advances in technology, recent studies of neural precursor identity and regulation have revealed various cell types as contributors to ongoing cell genesis in the adult mammalian brain. Here, we use stem-cell biology as a framework to highlight the diversity of adult neural precursor populations and emphasize their hierarchy, organization, and plasticity under physiological and pathological conditions. PMID:26988967

  4. Adult neural stem cells-Functional potential and therapeutic applications

    Institute of Scientific and Technical Information of China (English)

    YANG Lin; ZHU Jianhong

    2004-01-01

    The adult brain has been thought traditionally as a structure with a very limited regenerative capacity. It is now evident that neurogenesis in adult mammalian brain is a prevailing phenomenon. Neural stem cells with the ability to self-renew, differentiate into neurons, astrocytes and oligodendrocytes reside in some regions of the adult brain. Adult neurogenesis can be stimulated by many physiological factors including pregnancy. More strikingly, newborn neurons in hippocampus integrally function with local neurons, thus neural stem cells might play important roles in memory and learning function. It seems that neural stem cells could transdifferentiate into other tissues, such as blood cells and muscles. Although there are some impediments in this field, some attempts have been made to employ adult neural stem cells in the cell replacement therapy for traumatic and ischemic brain injuries.

  5. Human aging alters the neural computation and representation of space.

    Science.gov (United States)

    Schuck, Nicolas W; Doeller, Christian F; Polk, Thad A; Lindenberger, Ulman; Li, Shu-Chen

    2015-08-15

    The hippocampus and striatum are core neural circuits involved in spatial learning and memory. Although both neural systems support spatial navigation, experimental and theoretical evidence indicate that they play different roles. In particular, whereas hippocampal place cells generate allocentric neural representations of space that are sensitive to geometric information, striatum-dependent learning is influenced by local landmarks. How human aging affects these different neural representations, however, is still not well understood. In this paper, we combined virtual reality, computational modeling, and neuroimaging to investigate the effects of age upon the neural computation and representation of space in humans. We manipulated the geometry and local landmarks of a virtual environment and examined the effects on memory performance and brain activity during spatial learning. In younger adults, both behavior and brain activity in the medial-temporal lobe were consistent with predictions of a computational model of hippocampus-dependent boundary processing. In contrast, older adults' behavior and medial-temporal lobe activity were primarily influenced by local cue information, and spatial learning was more associated with activity in the caudate nucleus rather than the hippocampus. Together these results point to altered spatial representations and information processing in the hippocampal-striatal circuitry with advancing adult age, which may contribute to spatial learning and memory deficits associated with normal and pathological aging. PMID:26003855

  6. Development of neural stem cell in the adult brain

    OpenAIRE

    Duan, Xin; Kang, Eunchai; Liu, Cindy Y.; Ming, Guo-li; Song, Hongjun

    2008-01-01

    New neurons are continuously generated in the dentate gyrus of the mammalian hippocampus and in the subventricular zone of the lateral ventricles throughout life. The origin of these new neurons is believed to be from multipotent adult neural stem cells. Aided by new methodologies, significant progress has been made in the characterization of neural stem cells and their development in the adult brain. Recent studies have also begun to reveal essential extrinsic and intrinsic molecular mechani...

  7. Angiogenic factors stimulate growth of adult neural stem cells.

    Directory of Open Access Journals (Sweden)

    Andreas Androutsellis-Theotokis

    Full Text Available BACKGROUND: The ability to grow a uniform cell type from the adult central nervous system (CNS is valuable for developing cell therapies and new strategies for drug discovery. The adult mammalian brain is a source of neural stem cells (NSC found in both neurogenic and non-neurogenic zones but difficulties in culturing these hinders their use as research tools. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that NSCs can be efficiently grown in adherent cell cultures when angiogenic signals are included in the medium. These signals include both anti-angiogenic factors (the soluble form of the Notch receptor ligand, Dll4 and pro-angiogenic factors (the Tie-2 receptor ligand, Angiopoietin 2. These treatments support the self renewal state of cultured NSCs and expression of the transcription factor Hes3, which also identifies the cancer stem cell population in human tumors. In an organotypic slice model, angiogenic factors maintain vascular structure and increase the density of dopamine neuron processes. CONCLUSIONS/SIGNIFICANCE: We demonstrate new properties of adult NSCs and a method to generate efficient adult NSC cultures from various central nervous system areas. These findings will help establish cellular models relevant to cancer and regeneration.

  8. Neural differentiation of human embryonic stem cells

    OpenAIRE

    Dhara, Sujoy K.; Stice, Steven L.

    2008-01-01

    Availability of human embryonic stem cells (hESC) has enhanced human neural differentiation research. The derivation of neural progenitor (NP) cells from hESC facilitates the integration of human embryonic development through the generation of neuronal subtypes and supporting glial cells. These cells will likely lead to new and novel drug screening and cell therapy uses. This review will discuss the current status of derivation, maintenance and further differentiation of NP cells with special...

  9. Human Metapneumovirus in Adults

    Directory of Open Access Journals (Sweden)

    Lenneke E. M. Haas

    2013-01-01

    Full Text Available Human metapneumovirus (HMPV is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination.

  10. Human metapneumovirus in adults.

    Science.gov (United States)

    Haas, Lenneke E M; Thijsen, Steven F T; van Elden, Leontine; Heemstra, Karen A

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  11. Molecular Diversity Subdivides the Adult Forebrain Neural Stem Cell Population

    Science.gov (United States)

    Giachino, Claudio; Basak, Onur; Lugert, Sebastian; Knuckles, Philip; Obernier, Kirsten; Fiorelli, Roberto; Frank, Stephan; Raineteau, Olivier; Alvarez–Buylla, Arturo; Taylor, Verdon

    2014-01-01

    Neural stem cells (NSCs) in the ventricular domain of the subventricular zone (V-SVZ) of rodents produce neurons throughout life while those in humans become largely inactive or may be lost during infancy. Most adult NSCs are quiescent, express glial markers, and depend on Notch signaling for their self-renewal and the generation of neurons. Using genetic markers and lineage tracing, we identified subpopulations of adult V-SVZ NSCs (type 1, 2, and 3) indicating a striking heterogeneity including activated, brain lipid binding protein (BLBP, FABP7) expressing stem cells. BLBP+ NSCs are mitotically active components of pinwheel structures in the lateral ventricle walls and persistently generate neurons in adulthood. BLBP+ NSCs express epidermal growth factor (EGF) receptor, proliferate in response to EGF, and are a major clonogenic population in the SVZ. We also find BLBP expressed by proliferative ventricular and sub-ventricular progenitors in the fetal and postnatal human brain. Loss of BLBP+ stem/progenitor cells correlates with reduced neurogenesis in aging rodents and postnatal humans. These findings of molecular heterogeneity and proliferative differences subdivide the NSC population and have implications for neurogenesis in the forebrain of mammals during aging. PMID:23964022

  12. Differentiation of embryonic versus adult rat neural stem cells into dopaminergic neurons in vitro

    Institute of Scientific and Technical Information of China (English)

    Chunlong Ke; Baili Chen; Shaolei Guo; Chao Yang

    2008-01-01

    BACKGROUND: It has been reported that the conversion of neural stem cells into dopaminergic neurons in vitro can be increased through specific cytokine combinations. Such neural stem cell-derived dopaminergic neurons could be used for the treatment of Parkinson's disease. However, little is known about the differences in dopaminergic differentiation between neural stem cells derived from adult and embryonic rats.OBJECTIVE: To study the ability of rat adult and embryonic-derived neural stem cells to differentiate into dopaminergic neurons in vitro.DESIGN: Randomized grouping design.SETTING: Department of Neurosurgery in the First Affiliated Hospital of Sun Yat-sen University.MATERIALS: This experiment was performed at the Surgical Laboratory in the First Affiliated Hospital of Sun Yat-scn University (Guangzhou, Guangdong, China) from June to December 2007. Eight, adult, male,Sprague Dawley rats and eight, pregnant, Sprague Dawley rats (embryonic day 14 or 15) were provided by the Experimental Animal Center of Sun Yat-sen University.METHODS: Neural stem cells derived from adult and embryonic rats were respectively cultivated in serum-free culture medium containing epidermal growth factor and basic fibroblast growth factor. After passaging, neural stem cells were differentiated in medium containing interleukin-1 ct, interleukin-11, human leukemia inhibition factor, and glial cell line-derived neurotrophic factor. Six days later, cells were analyzed by immunocytochemistry and flow cytometry.MAIN OUTCOME MEASURES: Alterations in cellular morphology after differentiation of neural stem cells derived from adult and embryonic rats; and percentage of tyrosine hydroxylase-positive neurons in the differentiated cells.RESULTS: Neural stem cells derived from adult and embryonic rats were cultivated in differentiation medium. Six days later, differentiated cells were immunoreactive for tyrosine hydroxylasc. The percentage of tyrosine hydroxylase positive neurons was (5.6 ± 2

  13. Human Immunodeficiency Virus Type 1 Infection of Neural Xenografts

    Science.gov (United States)

    Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; del Cerro, Coca; Gendelman, Howard E.; del Cerro, Manuel; Epstein, Leon G.

    1992-06-01

    Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.

  14. Neural correlates of fluid reasoning in children and adults

    Directory of Open Access Journals (Sweden)

    Samantha B Wright

    2008-03-01

    Full Text Available Fluid reasoning, or the capacity to think logically and solve novel problems, is central to the development of human cognition, but little is known about the underlying neural changes. During the acquisition of event-related fMRI data, children aged 6-13 (N = 16 and young adults (N = 17 performed a task in which they were asked to identify semantic relationships between drawings of common objects. On semantic problems, participants indicated which of fi ve objects was most closely semantically related to a cued object. On analogy problems, participants solved a visual propositional analogy (e.g., shoe is to foot as glove is to…µ by indicating which of four objects would complete the problem; these problems required integration of two semantic relations, or relational integration. Our prior research on analogical reasoning in adults implicated left anterior ventrolateral prefrontal cortex (VLPFC in the controlled retrieval of individual semantic relationships, and rostrolateral prefrontal cortex (RLPFC in relational integration. In this study, age-related changes in the recruitment of VLPFC, temporal cortex, and other cortical regions were observed during the retrieval of individual semantic relations. In contrast, agerelated changes in RLPFC function were observed during relational integration. Children aged 6-13 engage RLPFC too late in the analogy trials to infl uence their behavioral responses, suggesting that important changes in RLPFC function take place during adolescence.

  15. Adult Human Neurogenesis: from Microscopy to Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    AmandaSierra

    2011-04-01

    Full Text Available Neural stem cells reside in well-defined areas of the adult human brain and are capable of gene-rating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases.

  16. Neural representation of dynamic frequency is degraded in older adults.

    Science.gov (United States)

    Clinard, Christopher G; Cotter, Caitlin M

    2015-05-01

    Older adults, even with clinically normal hearing sensitivity, often report difficulty understanding speech in the presence of background noise. Part of this difficulty may be related to age-related degradations in the neural representation of speech sounds, such as formant transitions. Frequency-following responses (FFRs), which are dependent on phase-locked neural activity, were elicited using sounds consisting of linear frequency sweeps, which may be viewed as simple models of formant transitions. Eighteen adults (ten younger, 22-24 years old, and nine older, 51-67 years old) were tested. FFRs were elicited by tonal sweeps in six conditions. Two directions of frequency change, rising or falling, were used for each of three rates of frequency change. Stimulus-to-response cross correlations revealed that older adults had significantly poorer representation of the tonal sweeps, and that FFRs became poorer for faster rates of change. An additional FFR signal-to-noise ratio analysis based on time windows revealed that across the FFR waveforms and rates of frequency change, older adults had smaller (poorer) signal-to-noise ratios. These results indicate that older adults, even with clinically-normal hearing sensitivity, have degraded phase-locked neural representations of dynamic frequency. PMID:25724819

  17. Embryonic and adult neural stem cell research in China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Neural stem cells(NSCs) are one specific type of multipotential stem cells that have the ability to proliferate for a long time and to differentiate into neural cells,including neurons,astrocytes and oligodendrocytes.These NSCs exist in both the embryonic and adult central nervous system(CNS) of all mammalian species.Progress has been made in the understanding of the developmental regulation of NSCs and their function in neurogenesis.This review discusses recent progress in this area,with emphasis on work done by investigators in China.

  18. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

    Directory of Open Access Journals (Sweden)

    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  19. Application of adult stem cells in neural tissue engineering

    Institute of Scientific and Technical Information of China (English)

    Lihong Piao; Wei Wang

    2006-01-01

    OBJECTTIVE:To investigate the progress in finding,isolation and culture.proliferation and differentiation,and application in neural tissue engineering of adult stem cells(ASCs).DATA SOURCES:Using the terms"adult stem cells,nerve,tissue engineering".we searched the PubMed for adult stem ceils-related studies published in English from January 2001 to August 2006.Meanwhile,we also performed a China National Knowledge Infrastructure(CNKI)search for homochronous correlative literatures on the computer by inputting the terms"adult stem cells,nerve,tissue engineering"in Chinese.texts were searched for.Inclusive criteria:①Literatures about the sources,distribution,culture.proliferation and differentiation.and application in the repair of neural ASCs by tissue engineering.②Articles recommended either by randomized.blind or by other methods were not excluded.Exclusive criteria:①Embryonic stem cells.②Review,repetitive study,case report,Meta analysis. DATA EXTRACTION:Totally 1 278 articles related to ASCs were collected,32 were involved and the other 1 246 were excluded. DATA SYNTHESIS:Adult stem cell has the ability of self-renewal.unceasing proliferation and transdifferentiation.It has wide source,which does not involved in ethical problems.It has advantages over embryonic stem cell.Studies on the isolation and culture,induction and differentiation and application in neural ASCs by tissue engineering contribute to obtaining considerable ASCs,so as to provide experimental and theoretical bases for CONCLUSION:ASCs play a very important role in neural tissue engineering.

  20. Experience-dependent neural plasticity in the adult damaged brain

    OpenAIRE

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper extremity (hand and arm) impairments. A prolonged and widespread process of repair and reorganization of surviving neural circuits is instigated by in...

  1. Neural basis for recognition confidence in younger and older adults

    OpenAIRE

    Chua, Elizabeth F.; Schacter, Daniel L.; Sperling, Reisa A.

    2009-01-01

    Although several studies have examined the neural basis for age-related changes in objective memory performance, less is known about how the process of memory monitoring changes with aging. We used fMRI to examine retrospective confidence in memory performance in aging. During low confidence, both younger and older adults showed behavioral evidence that they were guessing during recognition, and that they were aware they were guessing when making confidence judgments. Similarly, both younger ...

  2. Neural stem cells and the regulation of adult neurogenesis

    Directory of Open Access Journals (Sweden)

    Conover Joanne C

    2003-11-01

    Full Text Available Abstract Presumably, the 'hard-wired' neuronal circuitry of the adult brain dissuades addition of new neurons, which could potentially disrupt existing circuits. This is borne out by the fact that, in general, new neurons are not produced in the mature brain. However, recent studies have established that the adult brain does maintain discrete regions of neurogenesis from which new neurons migrate and become incorporated into the functional circuitry of the brain. These neurogenic zones appear to be vestiges of the original developmental program that initiates brain formation. The largest of these germinal regions in the adult brain is the subventricular zone (SVZ, which lines the lateral walls of the lateral ventricles. Neural stem cells produce neuroblasts that migrate from the SVZ along a discrete pathway, the rostral migratory stream, into the olfactory bulb where they form mature neurons involved in the sense of smell. The subgranular layer (SGL of the hippocampal dentate gyrus is another neurogenic region; new SGL neurons migrate only a short distance and differentiate into hippocampal granule cells. Here, we discuss the surprising finding of neural stem cells in the adult brain and the molecular mechanisms that regulate adult neurogenesis.

  3. Neural network plasticity in the human brain

    OpenAIRE

    Rizk, Sviatlana

    2013-01-01

    The human brain is highly organized within networks. Functionally related neural-assemblies communicate by oscillating synchronously. Intrinsic brain activity contains information on healthy and damaged brain functioning. This thesis investigated the relationship between functional networks and behavior. Furthermore, we assessed functional network plasticity after brain damage and as a result of brain stimulation. In different groups of patients we observed reduced functional connectivity bet...

  4. Clinical translation of human neural stem cells.

    Science.gov (United States)

    Tsukamoto, Ann; Uchida, Nobuko; Capela, Alexandra; Gorba, Thorsten; Huhn, Stephen

    2013-01-01

    Human neural stem cell transplants have potential as therapeutic candidates to treat a vast number of disorders of the central nervous system (CNS). StemCells, Inc. has purified human neural stem cells and developed culture conditions for expansion and banking that preserve their unique biological properties. The biological activity of these human central nervous system stem cells (HuCNS-SC®) has been analyzed extensively in vitro and in vivo. When formulated for transplantation, the expanded and cryopreserved banked cells maintain their stem cell phenotype, self-renew and generate mature oligodendrocytes, neurons and astrocytes, cells normally found in the CNS. In this overview, the rationale and supporting data for pursuing neuroprotective strategies and clinical translation in the three components of the CNS (brain, spinal cord and eye) are described. A phase I trial for a rare myelin disorder and phase I/II trial for spinal cord injury are providing intriguing data relevant to the biological properties of neural stem cells, and the early clinical outcomes compel further development. PMID:23987648

  5. Adult neural stem cells: The promise of the future

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2007-01-01

    Full Text Available Philippe TaupinNational Neuroscience Institute, National University of SingaporeAbstract: Stem cells are self-renewing undifferentiated cells that give rise to multiple types of specialized cells of the body. In the adult, stem cells are multipotents and contribute to homeostasis of the tissues and regeneration after injury. Until recently, it was believed that the adult brain was devoid of stem cells, hence unable to make new neurons and regenerate. With the recent evidences that neurogenesis occurs in the adult brain and neural stem cells (NSCs reside in the adult central nervous system (CNS, the adult brain has the potential to regenerate and may be amenable to repair. The function(s of NSCs in the adult CNS remains the source of intense research and debates. The promise of the future of adult NSCs is to redefine the functioning and physiopathology of the CNS, as well as to treat a broad range of CNS diseases and injuries.Keywords: neurogenesis, transdifferentiation, plasticity, cellular therapy

  6. Moderate traumatic brain injury promotes proliferation of quiescent neural progenitors in the adult hippocampus

    OpenAIRE

    Gao, Xiang; Enikolopov, Grigori; Chen, Jinhui

    2009-01-01

    Recent evidence shows that traumatic brain injury (TBI) regulates proliferation of neural stem/progenitor cells in the dentate gyrus (DG) of adult hippocampus. There are distinct classes of neural stem/progenitor cells in the adult DG, including quiescent neural progenitors (QNPs), which carry stem cell properties, and their progeny, amplifying neural progenitors (ANPs). The response of each class of progenitors to TBI is not clear. We here used a transgenic reporter Nestin-GFP mouse line, in...

  7. Variability of neural activation during walking in humans: short heels and big calves

    OpenAIRE

    Ahn, A. N.; Kang, J. K.; Quitt, M. A.; Davidson, B. C.; Nguyen, C. T.

    2011-01-01

    People come in different shapes and sizes. In particular, calf muscle size in humans varies considerably. One possible cause for the different shapes of calf muscles is the inherent difference in neural signals sent to these muscles during walking. In sedentary adults, the variability in neural control of the calf muscles was examined with muscle size, walking kinematics and limb morphometrics. Half the subjects walked while activating their medial gastrocnemius (MG) muscles more strongly tha...

  8. Feeder-free Derivation of Neural Crest Progenitor Cells from Human Pluripotent Stem Cells

    OpenAIRE

    Zeltner, Nadja; Lafaille, Fabien G.; Fattahi, Faranak; Studer, Lorenz

    2014-01-01

    Human pluripotent stem cells (hPSCs) have great potential for studying human embryonic development, for modeling human diseases in the dish and as a source of transplantable cells for regenerative applications after disease or accidents. Neural crest (NC) cells are the precursors for a large variety of adult somatic cells, such as cells from the peripheral nervous system and glia, melanocytes and mesenchymal cells. They are a valuable source of cells to study aspects of human embryonic develo...

  9. TRIM32-dependent transcription in adult neural progenitor cells regulates neuronal differentiation

    OpenAIRE

    Hillje, Anna-Lena; Pavlou, Maria Angeliki; Beckmann, Elisabeth; Worlitzer, Maik; Bahnassawy, Lamiaa; Lewejohann, Lars; Palm, Thomas; Schwamborn, Jens Christian

    2013-01-01

    In the adult mammalian brain, neural stem cells in the subventricular zone continuously generate new neurons for the olfactory bulb. Cell fate commitment in these adult neural stem cells is regulated by cell fate-determining proteins. Here, we show that the cell fate-determinant TRIM32 is upregulated during differentiation of adult neural stem cells into olfactory bulb neurons. We further demonstrate that TRIM32 is necessary for the correct induction of neuronal differentiation in these cells...

  10. Intraoperative Neural Response Telemetry and Neural Recovery Function: a Comparative Study between Adults and Children

    Science.gov (United States)

    Carvalho, Bettina; Hamerschmidt, Rogerio; Wiemes, Gislaine

    2014-01-01

    Introduction Neural response telemetry (NRT) is a method of capturing the action potential of the distal portion of the auditory nerve in cochlear implant (CI) users, using the CI itself to elicit and record the answers. In addition, it can also measure the recovery function of the auditory nerve (REC), that is, the refractory properties of the nerve. It is not clear in the literature whether the responses from adults are the same as those from children. Objective To compare the results of NRT and REC between adults and children undergoing CI surgery. Methods Cross-sectional, descriptive, and retrospective study of the results of NRT and REC for patients undergoing IC at our service. The NRT is assessed by the level of amplitude (microvolts) and REC as a function of three parameters: A (saturation level, in microvolts), t0 (absolute refractory period, in seconds), and tau (curve of the model function), measured in three electrodes (apical, medial, and basal). Results Fifty-two patients were evaluated with intraoperative NRT (26 adults and 26 children), and 24 with REC (12 adults and 12 children). No statistically significant difference was found between intraoperative responses of adults and children for NRT or for REC's three parameters, except for parameter A of the basal electrode. Conclusion The results of intraoperative NRT and REC were not different between adults and children, except for parameter A of the basal electrode. PMID:25992145

  11. A neural mediator of human anxiety sensitivity.

    Science.gov (United States)

    Harrison, Ben J; Fullana, Miquel A; Soriano-Mas, Carles; Via, Esther; Pujol, Jesus; Martínez-Zalacaín, Ignacio; Tinoco-Gonzalez, Daniella; Davey, Christopher G; López-Solà, Marina; Pérez Sola, Victor; Menchón, José M; Cardoner, Narcís

    2015-10-01

    Advances in the neuroscientific understanding of bodily autonomic awareness, or interoception, have led to the hypothesis that human trait anxiety sensitivity (AS)-the fear of bodily autonomic arousal-is primarily mediated by the anterior insular cortex. Despite broad appeal, few experimental studies have comprehensively addressed this hypothesis. We recruited 55 individuals exhibiting a range of AS and assessed them with functional magnetic resonance imaging (fMRI) during aversive fear conditioning. For each participant, three primary measures of interest were derived: a trait Anxiety Sensitivity Index score; an in-scanner rating of elevated bodily anxiety sensations during fear conditioning; and a corresponding estimate of whole-brain functional activation to the conditioned versus nonconditioned stimuli. Using a voxel-wise mediation analysis framework, we formally tested for 'neural mediators' of the predicted association between trait AS score and in-scanner anxiety sensations during fear conditioning. Contrary to the anterior insular hypothesis, no evidence of significant mediation was observed for this brain region, which was instead linked to perceived anxiety sensations independently from AS. Evidence for significant mediation was obtained for the dorsal anterior cingulate cortex-a finding that we argue is more consistent with the hypothesized role of human cingulofrontal cortex in conscious threat appraisal processes, including threat-overestimation. This study offers an important neurobiological validation of the AS construct and identifies a specific neural substrate that may underlie high AS clinical phenotypes, including but not limited to panic disorder. PMID:26147233

  12. Promotion of Cortical Neurogenesis from the Neural Stem Cells in the Adult Mouse Subcallosal Zone.

    Science.gov (United States)

    Kim, Joo Yeon; Choi, Kyuhyun; Shaker, Mohammed R; Lee, Ju-Hyun; Lee, Boram; Lee, Eunsoo; Park, Jae-Yong; Lim, Mi-Sun; Park, Chang-Hwan; Shin, Ki Soon; Kim, Hyun; Geum, Dongho; Sun, Woong

    2016-04-01

    Neurogenesis occurs spontaneously in the subventricular zone (SVZ) of the lateral ventricle in adult rodent brain, but it has long been debated whether there is sufficient adult neurogenesis in human SVZ. Subcallosal zone (SCZ), a posterior continuum of SVZ closely associated with posterior regions of cortical white matter, has also been reported to contain adult neural stem cells (aNSCs) in both rodents and humans. However, little is known whether SCZ-derived aNSC (SCZ-aNSCs) can produce cortical neurons following brain injury. We found that SCZ-aNSCs exhibited limited neuronal differentiation potential in culture and after transplantation in mice. Neuroblasts derived from SCZ initially migrated toward injured cortex regions following brain injury, but later exhibited apoptosis. Overexpression of anti-apoptotic bcl-xL in the SCZ by retroviral infection rescued neuroblasts from cell death in the injured cortex, but neuronal maturation was still limited, resulting in atrophy. In combination with Bcl-xL, infusion of brain-derived neurotropic factor rescued atrophy, and importantly, a subset of such SCZ-aNSCs differentiated and attained morphological and physiological characteristics of mature, excitatory neurons. These results suggest that the combination of anti-apoptotic and neurotrophic factors might enable the use of aNSCs derived from the SCZ in cortical neurogenesis for neural replacement therapy. Stem Cells 2016;34:888-901. PMID:26701067

  13. Dopaminerge Differenzierung adulter humaner hippocampaler Stammzellen

    OpenAIRE

    Türk, Matthias

    2013-01-01

    Hintergrund und Ziele: Nachdem seit der ersten Hälfte des letzten Jahrhunderts durch mehrere Experimente adulte Neurogenese schließlich nachgewiesen und somit Cajals Dogma widerlegt werden konnte, erlebten die Neurowissenschaften durch die Möglichkeit zur Isolation adulter neuraler Stammzellen ein exponentielles Wachstum. Gleichzeitig mit der basiswissenschaftlichen Aufarbeitung der adulten Neurogenese sowohl im Tier, als auch im Menschen, kam die Idee der therapeutischen Verwendung dieser, v...

  14. Regenerative medicine using adult neural stem cells: the potential for diabetes therapy and other pharmaceutical applications

    Institute of Scientific and Technical Information of China (English)

    Tomoko Kuwabara; Makoto Asashima

    2012-01-01

    Neural stem cells (NSCs),which are responsible for continuous neurogenesis during the adult stage,are present in human adults.The typical neurogenic regions are the hippocampus and the subventricular zone; recent studies have revealed that NSCs also exist in the olfactory bulb.Olfactory bulb-derived neural stem cells (OB NSCs) have the potential to be used in therapeutic applications and can be easily harvested without harm to the patient.Through the combined influence of extrinsic cues and innate programming,adult neurogenesis is a finely regulated process occurring in a specialized cellular environment,a niche.Understanding the regulatory mechanisms of adult NSCs and their cellular niche is not only important to understand the physiological roles of neurogenesis in adulthood,but also to provide the knowledge necessary for developing new therapeutic applications using adult NSCs in other organs with similar regulatory environments.Diabetes is a devastating disease affecting more than 200 million people worldwide.Numerous diabetic patients suffer increased symptom severity after the onset,involving complications such as retinopathy and nephropathy.Therefore,the development of treatments for fundamental diabetes is important.The utilization of autologous cells from patients with diabetes may address challenges regarding the compatibility of donor tissues as well as provide the means to naturally and safely restore function,reducing future risks while also providing a long-term cure.Here,we review recent findings regarding the use of adult OB NSCs as a potential diabetes cure,and discuss the potential of OB NSC-based pharmaceutical applications for neuronal diseases and mental disorders.

  15. The neural basis of human tool use

    Directory of Open Access Journals (Sweden)

    FaustoCaruana

    2014-04-01

    Full Text Available In this review, we propose that the neural basis for the spontaneous, diversified human tool use is an area devoted to the execution and observation of tool actions, located in the left anterior supramarginal gyrus (aSMG. The aSMG activation elicited by observing tool use is typical of human subjects, as macaques show no similar activation, even after an extensive training to use tools. The execution of tool actions, as well as their observation, requires the convergence upon aSMG of inputs from different parts of the dorsal and ventral visual streams. Non semantic features of the target object may be provided by the posterior parietal cortex (PPC for tool-object interaction, paralleling the well-known PPC input to AIP for hand-object interaction. Semantic information regarding tool identity, and knowledge of the typical manner of handling the tool, could be provided by inferior and middle regions of the temporal lobe. Somatosensory feedback and technical reasoning, as well as motor and intentional constraints also play roles during the planning of tool actions and consequently their signals likewise converge upon aSMG.We further propose that aSMG may have arisen though duplication of monkey AIP and invasion of the duplicate area by afferents from PPC providing distinct signals depending on the kinematics of the manipulative action. This duplication may have occurred when Homo Habilis or Homo Erectus emerged, generating the Oldowan or Acheulean Industrial complexes respectively. Hence tool use may have emerged during hominid evolution between bipedalism and language.We conclude that humans have two parietal systems involved in tool behavior: a biological circuit for grasping objects, including tools, and an artifactual system devoted specifically to tool use. Only the latter allows humans to understand the causal relationship between tool use and obtaining the goal, and is likely to be the basis of all technological developments.

  16. Characterization of TLX Expression in Neural Stem Cells and Progenitor Cells in Adult Brains

    OpenAIRE

    Shengxiu Li; Guoqiang Sun; Kiyohito Murai; Peng Ye; Yanhong Shi

    2012-01-01

    TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analo...

  17. Evolution of Neural Controllers for Robot Navigation in Human Environments

    Directory of Open Access Journals (Sweden)

    Genci Capi

    2010-01-01

    Full Text Available Problem statement: In this study, we presented a novel vision-based learning approach for autonomous robot navigation. Approach: In our method, we converted the captured image in a binary one, which after the partition is used as the input of the neural controller. Results: The neural control system, which maps the visual information to motor commands, is evolved online using real robots. Conclusion/Recommendations: We showed that evolved neural networks performed well in indoor human environments. Furthermore, we compared the performance of neural controllers with an algorithmic vision based control method.

  18. Metformin Acts on Two Different Molecular Pathways to Enhance Adult Neural Precursor Proliferation/Self-Renewal and Differentiation

    OpenAIRE

    Michael Fatt; Karolynn Hsu; Ling He; Fredric Wondisford; Freda D. Miller; David R. Kaplan; Jing Wang

    2015-01-01

    Summary The recruitment of endogenous adult neural stem cells for brain repair is a promising regenerative therapeutic strategy. This strategy involves stimulation of multiple stages of adult neural stem cell development, including proliferation, self-renewal, and differentiation. Currently, there is a lack of a single therapeutic approach that can act on these multiple stages of adult neural stem cell development to enhance neural regeneration. Here we show that metformin, an FDA-approved di...

  19. Differential neural network configuration during human path integration

    Directory of Open Access Journals (Sweden)

    Aiden EGF Arnold

    2014-04-01

    Full Text Available Path integration is a fundamental skill for navigation in both humans and animals. Despite recent advances in unravelling the neural basis of path integration in animal models, relatively little is known about how path integration operates at a neural level in humans. Previous attempts to characterize the neural mechanisms used by humans to visually path integrate have suggested a central role of the hippocampus in allowing accurate performance, broadly resembling results from animal data. However, in recent years both the central role of the hippocampus and the perspective that animals and humans share similar neural mechanisms for path integration has come into question. The present study uses a data driven analysis to investigate the neural systems engaged during visual path integration in humans, allowing for an unbiased estimate of neural activity across the entire brain. Our results suggest that humans employ common task control, attention and spatial working memory systems across a frontoparietal network during path integration. However, individuals differed in how these systems are configured into functional networks. High performing individuals were found to more broadly express spatial working memory systems in prefrontal cortex, while low performing individuals engaged an allocentric memory system based primarily in the medial occipito-temporal region. These findings suggest that visual path integration in humans over short distances can operate through a spatial working memory system engaging primarily the prefrontal cortex and that the differential configuration of memory systems recruited by task control networks may help explain individual biases in spatial learning strategies.

  20. Data defining markers of human neural stem cell lineage potential.

    Science.gov (United States)

    Oikari, Lotta E; Okolicsanyi, Rachel K; Griffiths, Lyn R; Haupt, Larisa M

    2016-06-01

    Neural stem cells (NSCs) and neural progenitor cells (NPCs) are self-renewing and multipotent cells, however, NPCs are considered to be more lineage-restricted with a reduced self-renewing capacity. We present data comparing the expression of 21 markers encompassing pluripotency, self-renewal (NSC) as well as neuronal and glial (astrocyte and oligodendrocyte) lineage specification and 28 extracellular proteoglycan (PG) genes and their regulatory enzymes between embryonic stem cell (ESC)-derived human NSCs (hNSC H9 cells, Thermo Fisher) and human cortex-derived normal human NPCs (nhNPCs, Lonza). The data demonstrates expression differences of multiple lineage and proteoglycan-associated genes between hNSC H9 cells and nhNPCs. Data interpretation of markers and proteoglycans defining NSC and neural cell lineage characterisation can be found in "Cell surface heparan sulfate proteoglycans as novel markers of human neural stem cell fate determination" (Oikari et al. 2015) [1]. PMID:26958640

  1. Neural networks for perception human and machine perception

    CERN Document Server

    Wechsler, Harry

    1991-01-01

    Neural Networks for Perception, Volume 1: Human and Machine Perception focuses on models for understanding human perception in terms of distributed computation and examples of PDP models for machine perception. This book addresses both theoretical and practical issues related to the feasibility of both explaining human perception and implementing machine perception in terms of neural network models. The book is organized into two parts. The first part focuses on human perception. Topics on network model ofobject recognition in human vision, the self-organization of functional architecture in t

  2. Know Your Place: Neural Processing of Social Hierarchy in Humans

    OpenAIRE

    Zink, Caroline F.; Tong, Yunxia; Chen, Qiang; Bassett, Danielle S; Stein, Jason L; Meyer-Lindenberg, Andreas

    2008-01-01

    Social hierarchies guide behavior in many species, including humans, where status also has an enormous impact on motivation and health. However, little is known about the underlying neural representation of social hierarchies in humans. In the present study, we identify dissociable neural responses to perceived social rank using functional magnetic resonance imaging (fMRI) in an interactive simulated social context. In both stable and unstable social hierarchies, viewing a superior individual...

  3. Neural correlates of executive attention in adults born very preterm

    Science.gov (United States)

    Daamen, Marcel; Bäuml, Josef G.; Scheef, Lukas; Meng, Chun; Jurcoane, Alina; Jaekel, Julia; Sorg, Christian; Busch, Barbara; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter; Wohlschläger, Afra; Boecker, Henning

    2015-01-01

    Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing. PMID:26640769

  4. CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells.

    Science.gov (United States)

    Pfenninger, Cosima V; Roschupkina, Teona; Hertwig, Falk; Kottwitz, Denise; Englund, Elisabet; Bengzon, Johan; Jacobsen, Sten Eirik; Nuber, Ulrike A

    2007-06-15

    Human brain tumor stem cells have been enriched using antibodies against the surface protein CD133. An antibody recognizing CD133 also served to isolate normal neural stem cells from fetal human brain, suggesting a possible lineage relationship between normal neural and brain tumor stem cells. Whether CD133-positive brain tumor stem cells can be derived from CD133-positive neural stem or progenitor cells still requires direct experimental evidence, and an important step toward such investigations is the identification and characterization of normal CD133-presenting cells in neurogenic regions of the embryonic and adult brain. Here, we present evidence that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in the adult subventricular zone. Our findings suggest two principal possibilities for the origin of brain tumor stem cells: a derivation from CD133-expressing cells, which are normally not present in the adult brain (embryonic neural stem cells and an early postnatal intermediate radial glial/ependymal cell type), or from CD133-positive ependymal cells in the adult brain, which are, however, generally regarded as postmitotic. Alternatively, brain tumor stem cells could be derived from proliferative but CD133-negative neurogenic astrocytes in the adult brain. In the latter case, brain tumor development would involve the production of CD133. PMID:17575139

  5. Bi-parental care contributes to sexually dimorphic neural cell genesis in the adult mammalian brain.

    Directory of Open Access Journals (Sweden)

    Gloria K Mak

    Full Text Available Early life events can modulate brain development to produce persistent physiological and behavioural phenotypes that are transmissible across generations. However, whether neural precursor cells are altered by early life events, to produce persistent and transmissible behavioural changes, is unknown. Here, we show that bi-parental care, in early life, increases neural cell genesis in the adult rodent brain in a sexually dimorphic manner. Bi-parentally raised male mice display enhanced adult dentate gyrus neurogenesis, which improves hippocampal neurogenesis-dependent learning and memory. Female mice display enhanced adult white matter oligodendrocyte production, which increases proficiency in bilateral motor coordination and preference for social investigation. Surprisingly, single parent-raised male and female offspring, whose fathers and mothers received bi-parental care, respectively, display a similar enhancement in adult neural cell genesis and phenotypic behaviour. Therefore, neural plasticity and behavioural effects due to bi-parental care persist throughout life and are transmitted to the next generation.

  6. Artificial Neural Network in Prognosticating Human Personality from Social Networks

    Directory of Open Access Journals (Sweden)

    Harish Kumar V

    2013-10-01

    Full Text Available The analysis of text in the form of tweets, chat or posts can be an interesting as well as challenging area of research. In this paper, such an analysis provides information about the human behavior as positive, negative or neutral. For simplicity, tweets from social networking site, Twitter, are extracted for analyzing human personality. Various concepts from natural language processing, text mining and neural networks are used to establish the final outcome of the application. For analyzing text, Neural Networks are implemented which are so modeled that they predict the Human behavior as positive, negative or neutral based on extracted and preprocessed data. Using Neural Networks, the particular pattern is identified and weights are provided to words based on the extracted pattern.Neural networks have an added advantage of adaptive learning. This application can be immensely useful for politics, medical science, sports, matrimonial purposes etc.The results so obtained are quite promising.

  7. Neural differentiation of human placenta-derived mesenchymal stem cells following neural cell co-culture

    Institute of Scientific and Technical Information of China (English)

    Nailong Yang; Hongyan Zhang; Xiaojuan Sun; Lili Xu

    2011-01-01

    We induced human placenta-derived mesenchymal stem cells (hPMSCs) to differentiate into neural cells by adding chemical reagents,despite the fact that toxic chemicals induce cell shrinkage or cytoskeletal formation,which does not represent a proper cell differentiation process.The present study established a co-culture system with hPMSCs and neural cells and analyzed the influence of neural cells on hPMSC differentiation in a co-culture system.hPMSCs were isolated and purified from human full-term placenta using collagenase digestion.Fetal neural cells were co-cultured with hPMSCs for 48 hours using the Transwell co-culture system.hPMSCs co-cultured with neural cells exhibited a slender morphology with a filament.After 96 hours,hPMSCs expressed neuron-specific enolase,which suggested that co-culture of hPMSCs and neural cells induced neural differentiation of hPMSCs.

  8. Flexible neural mechanisms of cognitive control within human prefrontal cortex.

    Science.gov (United States)

    Braver, Todd S; Paxton, Jessica L; Locke, Hannah S; Barch, Deanna M

    2009-05-01

    A major challenge in research on executive control is to reveal its functional decomposition into underlying neural mechanisms. A typical assumption is that this decomposition occurs solely through anatomically based dissociations. Here we tested an alternative hypothesis that different cognitive control processes may be implemented within the same brain regions, with fractionation and dissociation occurring on the basis of temporal dynamics. Regions within lateral prefrontal cortex (PFC) were examined that, in a prior study, exhibited contrasting temporal dynamics between older and younger adults during performance of the AX-CPT cognitive control task. The temporal dynamics in younger adults fit a proactive control pattern (primarily cue-based activation), whereas in older adults a reactive control pattern was found (primarily probe-based activation). In the current study, we found that following a period of task-strategy training, these older adults exhibited a proactive shift within a subset of the PFC regions, normalizing their activity dynamics toward young adult patterns. Conversely, under conditions of penalty-based monetary incentives, the younger adults exhibited a reactive shift some of the same regions, altering their temporal dynamics toward the older adult baseline pattern. These experimentally induced crossover patterns of temporal dynamics provide strong support for dual modes of cognitive control that can be flexibly shifted within PFC regions, via modulation of neural responses to changing task conditions or behavioral goals. PMID:19380750

  9. Human Face Recognition Using Convolutional Neural Networks

    Directory of Open Access Journals (Sweden)

    Răzvan-Daniel Albu

    2009-10-01

    Full Text Available In this paper, I present a novel hybrid face recognition approach based on a convolutional neural architecture, designed to robustly detect highly variable face patterns. The convolutional network extracts successively larger features in a hierarchical set of layers. With the weights of the trained neural networks there are created kernel windows used for feature extraction in a 3-stage algorithm. I present experimental results illustrating the efficiency of the proposed approach. I use a database of 796 images of 159 individuals from Reims University which contains quite a high degree of variability in expression, pose, and facial details.

  10. High Accuracy Human Activity Monitoring using Neural network

    CERN Document Server

    Sharma, Annapurna; Chung, Wan-Young

    2011-01-01

    This paper presents the designing of a neural network for the classification of Human activity. A Triaxial accelerometer sensor, housed in a chest worn sensor unit, has been used for capturing the acceleration of the movements associated. All the three axis acceleration data were collected at a base station PC via a CC2420 2.4GHz ISM band radio (zigbee wireless compliant), processed and classified using MATLAB. A neural network approach for classification was used with an eye on theoretical and empirical facts. The work shows a detailed description of the designing steps for the classification of human body acceleration data. A 4-layer back propagation neural network, with Levenberg-marquardt algorithm for training, showed best performance among the other neural network training algorithms.

  11. DIFFERENCE FEATURE NEURAL NETWORK IN RECOGNITION OF HUMAN FACES

    Institute of Scientific and Technical Information of China (English)

    Chen Gang; Qi Feihu

    2001-01-01

    This article discusses vision recognition process and finds out that human recognizes objects not by their isolated features, but by their main difference features which people get by contrasting them. According to the resolving character of difference features for vision recognition, the difference feature neural network(DFNN) which is the improved auto-associative neural network is proposed.Using ORL database, the comparative experiment for face recognition with face images and the ones added Gaussian noise is performed, and the result shows that DFNN is better than the auto-associative neural network and it proves DFNN is more efficient.

  12. Neural correlates of the contents of visual awareness in humans

    OpenAIRE

    Rees, G.

    2007-01-01

    The immediacy and directness of our subjective visual experience belies the complexity of the neural mechanisms involved, which remain incompletely understood. This review focuses on how the subjective contents of human visual awareness are encoded in neural activity. Empirical evidence to date suggests that no single brain area is both necessary and sufficient for consciousness. Instead, necessary and sufficient conditions appear to involve both activation of a distributed representation of ...

  13. Intraspinal transplantation of mouse and human neural precursor cells

    OpenAIRE

    Weinger, Jason G.; Chen, Lu; Coleman, Ronald; Leang, Ronika; Plaisted, Warren C.; Loring, Jeanne F.; Lane, Thomas E

    2013-01-01

    This unit describes the preparation and transplantation of human neural precursor cells (hNPCs) and mouse neural precursor cells (mNPCs) into the thoracic region of the mouse spinal cord. The techniques in this unit also describe how to prepare the mouse for surgery by performing a laminectomy to expose the spinal cord for transplantation. Here we show NPCs genetically labeled with eGFP transplanted into the spinal cord of a mouse following viralmediated demyelination can efficiently be detec...

  14. Static human face recognition using artificial neural networks

    International Nuclear Information System (INIS)

    This paper presents a novel method of human face recognition using digital computers. A digital PC camera is used to take the BMP images of the human faces. An artificial neural network using Back Propagation Algorithm is developed as a recognition engine. The BMP images of the faces serve as the input patterns for this engine. A software 'Face Recognition' has been developed to recognize the human faces for which it is trained. Once the neural network is trained for patterns of the faces, the software is able to detect and recognize them with success rate of about 97%. (author)

  15. Comparison between human fetal and adult skin

    OpenAIRE

    Coolen, N.A.; Schouten, K.C.; Middelkoop, E.; Ulrich, M.

    2009-01-01

    Healing of early-gestation fetal wounds results in scarless healing. Since the capacity for regeneration is probably inherent to the fetal skin itself, knowledge of the fetal skin composition may contribute to the understanding of fetal wound healing. The aim of this study was to analyze the expression profiles of different epidermal and dermal components in the human fetal and adult skin. In the human fetal skin (ranging from 13 to 22 weeks’ gestation) and adult skin biopsies, the expression...

  16. Finding the beat: a neural perspective across humans and non-human primates

    OpenAIRE

    Merchant, Hugo; Grahn, Jessica; Trainor, Laurel; Rohrmeier, Martin; Fitch, W. Tecumseh

    2015-01-01

    Humans possess an ability to perceive and synchronize movements to the beat in music (‘beat perception and synchronization’), and recent neuroscientific data have offered new insights into this beat-finding capacity at multiple neural levels. Here, we review and compare behavioural and neural data on temporal and sequential processing during beat perception and entrainment tasks in macaques (including direct neural recording and local field potential (LFP)) and humans (including fMRI, EEG and...

  17. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Jinah Han

    2015-02-01

    Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

  18. Repair of acutely injured spinal cord through constructing tissue-engineered neural complex in adult rats

    Institute of Scientific and Technical Information of China (English)

    PU Yu; GUO Qing-shan; WANG Ai-min; WU Si-yu; XING Shu-xing; ZHANG Zhong-rong

    2007-01-01

    Objective: To construct tissue-engineered neural complex in vitro and study its effect in repairing acutely injured spinal cord in adult rats. Methods: Neural stem cells were harvested from the spinal cord of embryo rats and propagated in vitro. Then the neural stem cells were seeded into polyglycolic acid scaffolds and co-cultured with extract of embryonic spinal cord in vitro. Immunofluorescence histochemistry and scanning electron microscope were used to observe the microstructure of this complex. Animal model of spine semi-transection was made and tissue-engineered neural complex was implanted by surgical intervention. Six weeks after transplantation, functional evaluation and histochemistry were applied to evaluate the functional recovery and anatomic reconstruction. Results: The tissue-engineered neural complex had a distinct structure, which contained neonatal neurons, oligodendrocytes and astrocytes. After tissue-engineered neural complex was implanted into the injured spinal cord, the cell components such as neurons, astrocytes and oligodendrocytes, could survive and keep on developing. The adult rats suffering from spinal cord injury got an obvious neurological recovery in motor skills. Conclusions: The tissue-engineered neural complex appears to have therapeutic effects on the functional recovery and anatomic reconstruction of the adult rats with spinal cord injury.

  19. Human Identification with Electrocardiogram Signals: a Neural Network Approach

    Science.gov (United States)

    Wan, Yongbo; Yao, Jianchu

    2009-05-01

    This paper presents a neural network developed to identify human subjects using electrocardiogram (ECG) signals collected from an "in-house" wearable electrocardiogram (ECG) sensor. In this project, noises were first removed from the raw signals with wavelet filters. ECG cycles were then extracted from the filtered signals and decomposed into wavelet coefficient structures. These coefficient structures were used as input vectors to a 3-layer feedforward neural network that generates the identification results. In the current study, 61 datasets collected from 23 subjects were utilized to train the neural network, which thereafter was tested with 15 new datasets from 15 different subjects. All the 15 subjects in the experiment were successfully identified. The testing results demonstrate that the neural network is effective.

  20. Neural correlates of the contents of visual awareness in humans.

    Science.gov (United States)

    Rees, Geraint

    2007-05-29

    The immediacy and directness of our subjective visual experience belies the complexity of the neural mechanisms involved, which remain incompletely understood. This review focuses on how the subjective contents of human visual awareness are encoded in neural activity. Empirical evidence to date suggests that no single brain area is both necessary and sufficient for consciousness. Instead, necessary and sufficient conditions appear to involve both activation of a distributed representation of the visual scene in primary visual cortex and ventral visual areas, plus parietal and frontal activity. The key empirical focus is now on characterizing qualitative differences in the type of neural activity in these areas underlying conscious and unconscious processing. To this end, recent progress in developing novel approaches to accurately decoding the contents of consciousness from brief samples of neural activity show great promise. PMID:17395576

  1. Senegenin promotes in vitro proliferation of human neural progenitor cells

    Institute of Scientific and Technical Information of China (English)

    Fang Shi; Zhigang Liang; Zixuan Guo; Ran Li; Fen Yu; Zhanjun Zhang; Xuan Wang; Xiaomin Wang

    2011-01-01

    Senegenin, an effective component of Polygala tenuifolia root extract, promotes proliferation and differentiation of neural progenitor cells in the hippocampus.However, the effects of senegenin on mesencephalon-derived neural progenitor cells remain poorly understood.Cells from a ventral mesencephalon neural progenitor cell line (ReNcell VM) were utilized as models for pharmaceutical screening.The effects of various senegenin concentrations on cell proliferation were analyzed,demonstrating that high senegenin concentrations (5, 10, 50, and 100 pmo/L), particularly 50 pmol/L, significantly promoted proliferation of ReNcell VM cells.In the mitogen-activated protein kinase signal transduction pathway, senegenin significantly increased phosphorylation levels of extracellular signal-regulated kinases.Moreover, cell proliferation was suppressed by extracellular signal-regulated kinase inhibitors.Results suggested that senegenin contributed to in vitro proliferation of human neural progenitor cells by upregulating phosphorylation of extracellular signal-regulated kinase.

  2. In Vivo Targeting of Adult Neural Stem Cells in the Dentate Gyrus by a Split-Cre Approach

    OpenAIRE

    Ruth Beckervordersandforth; Aditi Deshpande; Iris Schäffner; Hagen B. Huttner; Alexandra Lepier; Dieter Chichung Lie; Magdalena Götz

    2014-01-01

    Summary We describe the labeling of adult neural stem cells (aNSCs) in the mouse and human dentate gyrus (DG) by the combinatorial expression of glial fibrillary acidic protein (GFAP) and Prominin1, as revealed by immunohistochemistry. Split-Cre-based genetic fate mapping of these double-positive cells in the adult murine DG reveals their NSC identity, as they are self-renewing and contribute to neurogenesis over several months. Their progeny reacts to stimuli such as voluntary exercise with ...

  3. Estimating Neural Signal Dynamics in the Human Brain

    Directory of Open Access Journals (Sweden)

    Christopher W Tyler

    2011-06-01

    Full Text Available Although brain imaging methods are highly effective for localizing the effects of neural activation throughout the human brain in terms of the blood oxygenation level dependent (BOLD response, there is currently no way to estimate the underlying neural signal dynamics in generating the BOLD response in each local activation region (except for processes slower than the BOLD time course. Knowledge of the neural signal is critical information if spatial mapping is to progress to the analysis of dynamic information flow through the cortical networks as the brain performs its tasks. We introduce an analytic approach that provides a new level of conceptualization and specificity in the study of brain processing by noninvasive methods. This technique allows us to use brain imaging methods to determine the dynamics of local neural population responses to their native temporal resolution throughout the human brain, with relatively narrow confidence intervals on many response properties. The ability to characterize local neural dynamics in the human brain represents a significant enhancement of brain imaging capabilities, with potential application from general cognitive studies to assessment of neuropathologies.

  4. Xenotransplantation of human neural progenitor cells to the subretinal space of nonimmunosuppressed pigs

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Schwartz, Philip H; Kiilgaard, Jens Folke;

    2011-01-01

    vessels appeared normal without signs of exudation, bleeding, or subretinal elevation. Eyes were harvested at 10-28 days. H&E consistently showed mild retinal vasculitis, depigmentation of the RPE, and marked mononuclear cell infiltrate in the choroid adjacent to the site of transplantation. Human......To investigate the feasibility of transplanting human neural progenitor cells (hNPCs) to the retina of nonimmunosuppressed pigs, cultured hNPCs were injected into the subretinal space of 5 adult pigs after laser burns were applied to promote donor cell integration. Postoperatively, the retinal...

  5. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells.

    OpenAIRE

    Khalifa, Shaden,; de Medina, Philippe; Erlandsson, Anna; El-Seedi, Hesham; Silvente-Poirot, Sandrine; Poirot, Marc

    2014-01-01

    International audience Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. T...

  6. Neural progenitor cells from an adult patient with fragile X syndrome

    OpenAIRE

    Nethercott Hubert E; Greco Claudia M; Tassone Flora; Schwartz Philip H; Ziaeian Boback; Hagerman Randi J; Hagerman Paul J

    2005-01-01

    Abstract Background Currently, there is no adequate animal model to study the detailed molecular biochemistry of fragile X syndrome, the leading heritable form of mental impairment. In this study, we sought to establish the use of immature neural cells derived from adult tissues as a novel model of fragile X syndrome that could be used to more fully understand the pathology of this neurogenetic disease. Methods By modifying published methods for the harvest of neural progenitor cells from the...

  7. A Sox2 BAC transgenic approach for targeting adult neural stem cells.

    Directory of Open Access Journals (Sweden)

    Wenfei Kang

    Full Text Available The transcription factor gene Sox2 is expressed in embryonic neural stem/progenitor cells and previous evidence suggests that it is also expressed in adult neural stem cells. To target Sox2-expressing neural stem/progenitor cells in a temporal manner, we generated a bacterial artificial chromosome (BAC transgenic mouse line, in which an inducible form of Cre, CreER™, is expressed under Sox2 regulatory elements. Inducible Cre activity in these mice was characterized using floxed reporters. During development, the Sox2-CreER transgenic mice show inducible Cre activity specifically in CNS stem/progenitor cells, making them a useful tool to regulate the expression of floxed genes temporally in embryonic neural stem/progenitor cells. In the adult, we examined the cell-specific expression of Sox2 and performed long-term lineage tracing. Four months after the transient induction of Cre activity, recombined GFAP+ stem-like cells and DCX+ neuroblasts were still abundant in the neurogenic regions including the subventricular zone (SVZ, rostral migratory stream (RMS, and subgranular zone (SGZ of the dentate gyrus. These results provide definitive in vivo evidence that Sox2 is expressed in neural stem cells (NSC in both the SVZ and SGZ that are capable of self-renewal and long-term neurogenesis. Therefore, Sox2-CreER mice should be useful in targeting floxed genes in adult neural stem cells.

  8. Hand Gesture and Neural Network Based Human Computer Interface

    Directory of Open Access Journals (Sweden)

    Aekta Patel

    2014-06-01

    Full Text Available Computer is used by every people either at their work or at home. Our aim is to make computers that can understand human language and can develop a user friendly human computer interfaces (HCI. Human gestures are perceived by vision. The research is for determining human gestures to create an HCI. Coding of these gestures into machine language demands a complex programming algorithm. In this project, We have first detected, recognized and pre-processing the hand gestures by using General Method of recognition. Then We have found the recognized image’s properties and using this, mouse movement, click and VLC Media player controlling are done. After that we have done all these functions thing using neural network technique and compared with General recognition method. From this we can conclude that neural network technique is better than General Method of recognition. In this, I have shown the results based on neural network technique and comparison between neural network method & general method.

  9. Differential proliferation rhythm of neural progenitor and oligodendrocyte precursor cells in the young adult hippocampus.

    Directory of Open Access Journals (Sweden)

    Yoko Matsumoto

    Full Text Available Oligodendrocyte precursor cells (OPCs are a unique type of glial cells that function as oligodendrocyte progenitors while constantly proliferating in the normal condition from rodents to humans. However, the functional roles they play in the adult brain are largely unknown. In this study, we focus on the manner of OPC proliferation in the hippocampus of the young adult mice. Here we report that there are oscillatory dynamics in OPC proliferation that differ from neurogenesis in the subgranular zone (SGZ; the former showed S-phase and M-phase peaks in the resting and active periods, respectively, while the latter only exhibited M-phase peak in the active period. There is coincidence between different modes of proliferation and expression of cyclin proteins that are crucial for cell cycle; cyclin D1 is expressed in OPCs, while cyclin D2 is observed in neural stem cells. Similar to neurogenesis, the proliferation of hippocampal OPCs was enhanced by voluntary exercise that leads to an increase in neuronal activity in the hippocampus. These data suggest an intriguing control of OPC proliferation in the hippocampus.

  10. The neural underpinnings of reading skill in deaf adults.

    Science.gov (United States)

    Emmorey, Karen; McCullough, Stephen; Weisberg, Jill

    2016-09-01

    We investigated word-level reading circuits in skilled deaf readers (N=14; mean reading age=19.5years) and less skilled deaf readers (N=14; mean reading age=12years) who were all highly proficient users of American Sign Language. During fMRI scanning, participants performed a semantic decision (concrete concept?), a phonological decision (two syllables?), and a false-font control task (string underlined?). No significant group differences were observed with the full participant set. However, an analysis with the 10 most and 10 least skilled readers revealed that for the semantic task (vs. control task), proficient deaf readers exhibited greater activation in left inferior frontal and middle temporal gyri than less proficient readers. No group differences were observed for the phonological task. Whole-brain correlation analyses (all participants) revealed that for the semantic task, reading ability correlated positively with neural activity in the right inferior frontal gyrus and in a region associated with the orthography-semantics interface, located anterior to the visual word form area. Reading ability did not correlate with neural activity during the phonological task. Accuracy on the semantic task correlated positively with neural activity in left anterior temporal lobe (a region linked to conceptual processing), while accuracy on the phonological task correlated positively with neural activity in left posterior inferior frontal gyrus (a region linked to syllabification processes during speech production). Finally, reading comprehension scores correlated positively with vocabulary and print exposure measures, but not with phonological awareness scores. PMID:27448530

  11. Neural Mechanisms Underlying Action Observation in Adults with Down Syndrome

    Science.gov (United States)

    Virji-Babul, Naznin; Moiseev, Alexander; Cheung, Teresa; Weeks, Daniel J.; Cheyne, Douglas; Ribary, Urs

    2010-01-01

    Results of a magnetoencephalography (MEG) brain imaging study conducted to examine the cortical responses during action execution and action observation in 10 healthy adults and 8 age-matched adults with Down syndrome are reported. During execution, the motor responses were strongly lateralized on the ipsilateral rather than the contralateral side…

  12. Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

    Directory of Open Access Journals (Sweden)

    Montzka Katrin

    2009-03-01

    Full Text Available Abstract Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as

  13. GABA's Control of Stem and Cancer Cell Proliferation in Adult Neural and Peripheral Niches

    OpenAIRE

    Young, Stephanie Z.; Bordey, Angélique

    2009-01-01

    Aside from traditional neurotransmission and regulation of secretion, γ-amino butyric acid (GABA) through GABAA receptors negatively regulates proliferation of pluripotent and neural stem cells in embryonic and adult tissue. There has also been evidence that GABAergic signaling and its control over proliferation is not only limited to the nervous system, but is widespread through peripheral organs containing adult stem cells. GABA has emerged as a tumor signaling molecule in the periphery tha...

  14. Neural Mechanisms of Reading Facial Emotions in Young and Older Adults

    OpenAIRE

    Natalie C Ebner; Johnson, Marcia K.; Fischer, Håkan

    2012-01-01

    The ability to read and appropriately respond to emotions in others is central for successful social interaction. Young and older adults are better at identifying positive than negative facial expressions and also expressions of young than older faces. Little, however, is known about the neural processes associated with reading different emotions, particularly in faces of different ages, in samples of young and older adults. During fMRI, young and older participants identified expressions in ...

  15. Neural mechanisms of reading facial emotions in young and older adults

    OpenAIRE

    Natalie Christina Ebner; Johnson, Marcia K.; Håkan eFischer

    2012-01-01

    The ability to read and appropriately respond to emotions in others is central for successful social interaction. Young and older adults are better at identifying positive than negative facial expressions and expressions of young than older faces. Little, however, is known about the neural processes associated with reading different emotions, particularly in faces of different ages, in samples of young and older adults. During fMRI, young and older participants identified expressions in ha...

  16. Her4-Positive Population in the Tectum Opticum Is Proliferating Neural Precursors in the Adult Zebrafish Brain

    OpenAIRE

    Jung, Seung-Hyun; Kim, Hyung-Seok; Ryu, Jae-Ho; Gwak, Jung-Woo; Bae, Young-Ki; Kim, Cheol-Hee; Yeo, Sang-Yeob

    2012-01-01

    Previous studies have shown that Notch signaling not only regulates the number of early differentiating neurons, but also maintains proliferating neural precursors in the neural tube. Although it is well known that Notch signaling is closely related to the differentiation of adult neural stem cells, none of transgenic zebrafish provides a tool to figure out the relationship between Notch signaling and the differentiation of neural precursors. The goal of this study was to characterize Her4-po...

  17. Apoptotic gene expression in the neural tube during early human embryonic development

    Institute of Scientific and Technical Information of China (English)

    Guifang Chen; Tiandong Li; Peipei Ding; Ping Yang; Xiao Zhang

    2011-01-01

    Neural tube development comprises neural induction,neural epithelial cell proliferation,and apoptosis,as well as migration of nerve cells.Too much or too little apoptosis leads to abnormal nervous system development.The present study analyzed expression and distribution of apoptotic-related factors,including Fas,FasL,and caspase-3,during human embryonic neural tube development.Experimental results showed that increased caspase-3 expression promoted neural apoptosis via a mitochondriai-mediated intrinsic pathway at 4 weeks during early human embryonic neural tube development.Subsequently,Fas and FasL expression increased during embryonic development.The results suggest that neural cells influence neural apoptosis through synergistic effects of extrinsic pathways.Therefore,neural apoptosis during the early period of neural tube development in the human embryo might be regulated by the death receptor induced apoptotic extrinsic pathways.

  18. The Neural Basis of Sustained and Transient Attentional Control in Young Adults with ADHD

    Science.gov (United States)

    Banich, Marie T.; Burgess, Gregory C.; Depue, Brendan E.; Ruzic, Luka; Bidwell, L. Cinnamon; Hitt-Laustsen, Sena; Du, Yiping P.; Willcutt, Erik G.

    2009-01-01

    Differences in neural activation during performance on an attentionally demanding Stroop task were examined between 23 young adults with ADHD carefully selected to not be co-morbid for other psychiatric disorders and 23 matched controls. A hybrid blocked/single-trial design allowed for examination of more sustained vs. more transient aspects of…

  19. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells

    International Nuclear Information System (INIS)

    Highlights: • Dendrogenin A and B are new aminoalkyl oxysterols. • Dendrogenins stimulated neural stem cells proliferation. • Dendrogenins induce neuronal outgrowth from neurospheres. • Dendrogenins provide new therapeutic options for neurodegenerative disorders. - Abstract: Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain

  20. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Khalifa, Shaden A.M., E-mail: shaden.khalifa@ki.se [Department of Neuroscience, Karolinska Institute, Stockholm (Sweden); Medina, Philippe de [Affichem, Toulouse (France); INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); Erlandsson, Anna [Department of Public Health and Caring Sciences, Uppsala University, Uppsala (Sweden); El-Seedi, Hesham R. [Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Uppsala (Sweden); Silvente-Poirot, Sandrine [INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); University of Toulouse III, Toulouse (France); Institut Claudius Regaud, Toulouse (France); Poirot, Marc, E-mail: marc.poirot@inserm.fr [INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); University of Toulouse III, Toulouse (France); Institut Claudius Regaud, Toulouse (France)

    2014-04-11

    Highlights: • Dendrogenin A and B are new aminoalkyl oxysterols. • Dendrogenins stimulated neural stem cells proliferation. • Dendrogenins induce neuronal outgrowth from neurospheres. • Dendrogenins provide new therapeutic options for neurodegenerative disorders. - Abstract: Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain.

  1. Human pluripotent stem cell-derived neural constructs for predicting neural toxicity.

    Science.gov (United States)

    Schwartz, Michael P; Hou, Zhonggang; Propson, Nicholas E; Zhang, Jue; Engstrom, Collin J; Santos Costa, Vitor; Jiang, Peng; Nguyen, Bao Kim; Bolin, Jennifer M; Daly, William; Wang, Yu; Stewart, Ron; Page, C David; Murphy, William L; Thomson, James A

    2015-10-01

    Human pluripotent stem cell-based in vitro models that reflect human physiology have the potential to reduce the number of drug failures in clinical trials and offer a cost-effective approach for assessing chemical safety. Here, human embryonic stem (ES) cell-derived neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors were combined on chemically defined polyethylene glycol hydrogels and cultured in serum-free medium to model cellular interactions within the developing brain. The precursors self-assembled into 3D neural constructs with diverse neuronal and glial populations, interconnected vascular networks, and ramified microglia. Replicate constructs were reproducible by RNA sequencing (RNA-Seq) and expressed neurogenesis, vasculature development, and microglia genes. Linear support vector machines were used to construct a predictive model from RNA-Seq data for 240 neural constructs treated with 34 toxic and 26 nontoxic chemicals. The predictive model was evaluated using two standard hold-out testing methods: a nearly unbiased leave-one-out cross-validation for the 60 training compounds and an unbiased blinded trial using a single hold-out set of 10 additional chemicals. The linear support vector produced an estimate for future data of 0.91 in the cross-validation experiment and correctly classified 9 of 10 chemicals in the blinded trial. PMID:26392547

  2. Stroke increases neural stem cells and angiogenesis in the neurogenic niche of the adult mouse.

    Directory of Open Access Journals (Sweden)

    Rui Lan Zhang

    Full Text Available The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP positive neural stem cells that are in contact with the cerebrospinal fluid (CSF via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction.

  3. Biological properties of neural progenitor cells isolated from the hippocampus of adult cynomolgus monkeys

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells (NPCs) from this region remain to be extensively explored. The present work was to investigate on the expansion of NSCs/NPCs from the hippocampus of adult cynomolgus monkeys and the examination of their characteristics in vitro.Methods NPCs isolated from the hippocampus of adult cynomolgus monkeys were expanded in vitro in serum-free media containing growth factors, and were then allowed to differentiate by removing mitotic factors. The expansion capacity of NPCs and their differentiation potential were assayed by immunohistochemical and immunocytochemical analysis.Results During primary culture, NPCs underwent cell division, proliferation and aggregation to form neurospheres that were growing in suspension. Without mitotic stimulation, most neurospheres adhered to the culture dish and started to differentiate. Eventually, nearly 12% of the differentiated cells expressed neuron specific marker-βIII-tubulin (Tuj1) and 84% expressed astrocyte specific marker-fibrillary acidic protein (GFAP). In addition, the expression of a neural stem cell marker, nestin, was found both in NPCs and in the subgranular zone of adult monkey hippocampus, where NPCs were originally derived. Conclusions NPCs from the hippocampus of adult cynomolgus monkeys can be expanded to some extent in vitro and are capable of differentiating into neurons and astrocytes. Further experiments to promote the in vitro proliferation capacity of NPCs will be required before adult NPCs can be used as a useful cell model for studying adult neurogenesis and cell replacement therapy using adult stem cells.

  4. Xenotransplantation of human neural progenitor cells to the subretinal space of nonimmunosuppressed pigs

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Schwartz, Philip H; Kiilgaard, Jens Folke;

    2011-01-01

    To investigate the feasibility of transplanting human neural progenitor cells (hNPCs) to the retina of nonimmunosuppressed pigs, cultured hNPCs were injected into the subretinal space of 5 adult pigs after laser burns were applied to promote donor cell integration. Postoperatively, the retinal......-specific antibodies revealed donor cells in the subretinal space at 10-13 days and smaller numbers within the retina on days 12 and 13, with evidence suggesting a limited degree of morphological integration; however, no cells remained at 4 weeks. The strong mononuclear cell reaction and loss of donor cells indicate...

  5. Quantitative analysis of signaling mechanisms controlling adult neural progenitor cell proliferation.

    Science.gov (United States)

    Schaffer, David V; O'Neill, Analeah; Hochrein, Lisa; McGranahan, Tresa

    2004-01-01

    Tools of systems engineering and signal dynamics were employed to develop a quantitative model of the intracellular signaling systems involved in adult neural stem cell proliferation, based on pathways elucidated in our experimental systems. Neural progenitors isolated from the adult rat hippocampus are dependent on the basic fibroblast growth factor (FGF-2) and extracellular matrix (ECM) proteins. However, the intracellular effects of these stimuli were previously undetermined. We employed chemical inhibitors of known signal transduction molecules to identify important players in the FGF-2/ECM signal cascade, such as the cyclic AMP responsive element binding protein (CREB), protein kinase B/Akt, and several related molecules. Genetic mutants of these proteins were used to confirm their role in adult neural progenitor proliferation. Proliferation was assayed using the incorporation of a thymidine analog to determine cell doubling rate under various stimuli. Such assays have also uncovered novel synergistic signaling between FGF-2 and ECM components. This research is, to our knowledge, the first to elucidate intracellular signaling pathways for adult neural stem cell proliferation. Upon determination of the pertinent intracellular signaling pathways, quantitative immunoblots were employed to examine the dynamics of these systems. These data, as well as enzyme kinetics information from the literature, are being used to parameterize a dynamic mathematical model of progenitor proliferation events induced by FGF-2. This computational model will be used to predict the biochemical and mechanical signaling inputs necessary to achieve a desired proliferative output from the cells, based on specific extracellular stimuli. It is our hope that this essential quantitative understanding will facilitate the use of adult neural stem cells in medical applications. PMID:17271428

  6. Stem Cells from Human Exfoliated Deciduous Tooth Exhibit Stromal-Derived Inducing Activity and Lead to Generation of Neural Crest Cells from Human Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Khadijeh Karbalaie

    2015-04-01

    Full Text Available Objective: The neural crest is a transient structure of early vertebrate embryos that generates neural crest cells (NCCs. These cells can migrate throughout the body and produce a diverse array of mature tissue types. Due to the ethical and technical problems surrounding the isolation of these early human embryo cells, researchers have focused on in vitro studies to produce NCCs and increase their knowledge of neural crest development. Materials and Methods: In this experimental study, we cultured human embryonic stem cells (hESCs on stromal stem cells from human exfoliated deciduous teeth (SHED for a two-week period. We used different approaches to characterize these differentiated cells as neural precursor cells (NPCs and NCCs. Results: In the first co-culture week, hESCs appeared as crater-like structures with marginal rosettes. NPCs derived from these structures expressed the early neural crest marker p75 in addition to numerous other genes associated with neural crest induction such as SNAIL, SLUG, PTX3 and SOX9. Flow cytometry analysis showed 70% of the cells were AP2/P75 positive. Moreover, the cells were able to self-renew, sustain multipotent differentiation potential, and readily form neurospheres in suspension culture. Conclusion: SHED, as an adult stem cell with a neural crest origin, has stromal-derived inducing activity (SDIA and can be used as an NCC inducer from hESCs. These cells provide an invaluable resource to study neural crest differentiation in both normal and disordered human neural crest development.

  7. Neural correlate of human reciprocity in social interactions

    Directory of Open Access Journals (Sweden)

    ShiroSakaiya

    2013-12-01

    Full Text Available Reciprocity plays a key role maintaining cooperation in society. However, little is known about the neural process that underpins human reciprocity during social interactions. Our neuroimaging study manipulated partner identity (computer, human and strategy (random, tit-for-tat in repeated prisoner’s dilemma games and investigated the neural correlate of reciprocal interaction with humans. Reciprocal cooperation with humans but exploitation of computers by defection was associated with activation in the left amygdala. Amygdala activation was also positively and negatively correlated with a preference change for human partners following tit-for-tat and random strategies, respectively. The correlated activation represented the intensity of positive feeling toward reciprocal and negative feeling toward non-reciprocal partners, and so reflected reciprocity in social interaction. Reciprocity in social interaction, however, might plausibly be misinterpreted and so we also examined the neural coding of insight into the reciprocity of partners. Those with and without insight revealed differential brain activation across the reward-related circuitry (i.e., the right middle dorsolateral prefrontal cortex and dorsal caudate and theory of mind (ToM regions (i.e., ventromedial prefrontal cortex [VMPFC] and precuneus. Among differential activations, activation in the precuneus, which accompanied deactivation of the VMPFC, was specific to those without insight into human partners who were engaged in a tit-for-tat strategy. This asymmetric (deactivation might involve specific contributions of ToM regions to the human search for reciprocity. Consequently, the intensity of emotion attached to human reciprocity was represented in the amygdala, whereas insight into the reciprocity of others was reflected in activation across the reward-related and ToM regions. This suggests the critical role of mentalizing, which was not equated with reward expectation during

  8. Expectation modulates neural representations of valence throughout the human brain.

    Science.gov (United States)

    Ramayya, Ashwin G; Pedisich, Isaac; Kahana, Michael J

    2015-07-15

    The brain's sensitivity to unexpected gains or losses plays an important role in our ability to learn new behaviors (Rescorla and Wagner, 1972; Sutton and Barto, 1990). Recent work suggests that gains and losses are ubiquitously encoded throughout the human brain (Vickery et al., 2011), however, the extent to which reward expectation modulates these valence representations is not known. To address this question, we analyzed recordings from 4306 intracranially implanted electrodes in 39 neurosurgical patients as they performed a two-alternative probability learning task. Using high-frequency activity (HFA, 70-200 Hz) as an indicator of local firing rates, we found that expectation modulated reward-related neural activity in widespread brain regions, including regions that receive sparse inputs from midbrain dopaminergic neurons. The strength of unexpected gain signals predicted subjects' abilities to encode stimulus-reward associations. Thus, neural signals that are functionally related to learning are widely distributed throughout the human brain. PMID:25937489

  9. Experience-Dependent Neural Plasticity in the Adult Damaged Brain

    Science.gov (United States)

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper…

  10. Isolation of Human Neural Stem Cells from the Amniotic Fluid with Diagnosed Neural Tube Defects.

    Science.gov (United States)

    Chang, Yu-Jen; Su, Hong-Lin; Hsu, Lee-Feng; Huang, Po-Jui; Wang, Tzu-Hao; Cheng, Fu-Chou; Hsu, Li-Wen; Tsai, Ming-Song; Chen, Chih-Ping; Chang, Yao-Lung; Chao, An-Shine; Hwang, Shiaw-Min

    2015-08-01

    Human neural stem cells (NSCs) are particularly valuable for the study of neurogenesis process and have a therapeutic potential in treating neurodegenerative disorders. However, current progress in the use of human NSCs is limited due to the available NSC sources and the complicated isolation and culture techniques. In this study, we describe an efficient method to isolate and propagate human NSCs from the amniotic fluid with diagnosed neural tube defects (NTDs), specifically, anencephaly. These amniotic fluid-derived NSCs (AF-NSCs) formed neurospheres and underwent long-term expansion in vitro. In addition, these cells showed normal karyotypes and telomerase activity and expressed NSC-specific markers, including Nestin, Sox2, Musashi-1, and the ATP-binding cassette G2 (ABCG2). AF-NSCs displayed typical morphological patterns and expressed specific markers that were consistent with neurons, astrocytes, oligodendrocytes, and dopaminergic neurons after proper induction conditions. Furthermore, grafted AF-NSCs improved the physiological functions in a rat stroke model. The ability to isolate and bank human NSCs from this novel source provides a unique opportunity for translational studies of neurological disorders. PMID:25923707

  11. Human -Computer Interface using Gestures based on Neural Network

    Directory of Open Access Journals (Sweden)

    Aarti Malik

    2014-10-01

    Full Text Available - Gestures are powerful tools for non-verbal communication. Human computer interface (HCI is a growing field which reduces the complexity of interaction between human and machine in which gestures are used for conveying information or controlling the machine. In the present paper, static hand gestures are utilized for this purpose. The paper presents a novel technique of recognizing hand gestures i.e. A-Z alphabets, 0-9 numbers and 6 additional control signals (for keyboard and mouse control by extracting various features of hand ,creating a feature vector table and training a neural network. The proposed work has a recognition rate of 99%. .

  12. Substrate-mediated reprogramming of human fibroblasts into neural crest stem-like cells and their applications in neural repair.

    Science.gov (United States)

    Tseng, Ting-Chen; Hsieh, Fu-Yu; Dai, Niann-Tzyy; Hsu, Shan-Hui

    2016-09-01

    Cell- and gene-based therapies have emerged as promising strategies for treating neurological diseases. The sources of neural stem cells are limited while the induced pluripotent stem (iPS) cells have risk of tumor formation. Here, we proposed the generation of self-renewable, multipotent, and neural lineage-related neural crest stem-like cells by chitosan substrate-mediated gene transfer of a single factor forkhead box D3 (FOXD3) for the use in neural repair. A simple, non-toxic, substrate-mediated method was applied to deliver the naked FOXD3 plasmid into human fibroblasts. The transfection of FOXD3 increased cell proliferation and up-regulated the neural crest marker genes (FOXD3, SOX2, and CD271), stemness marker genes (OCT4, NANOG, and SOX2), and neural lineage-related genes (Nestin, β-tubulin and GFAP). The expression levels of stemness marker genes and neural crest maker genes in the FOXD3-transfected fibroblasts were maintained until the fifth passage. The FOXD3 reprogrammed fibroblasts based on the new method significantly rescued the neural function of the impaired zebrafish. The chitosan substrate-mediated delivery of naked plasmid showed feasibility in reprogramming somatic cells. Particularly, the FOXD3 reprogrammed fibroblasts hold promise as an easily accessible cellular source with neural crest stem-like behavior for treating neural diseases in the future. PMID:27341268

  13. Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors.

    Science.gov (United States)

    Figueres-Oñate, Maria; López-Mascaraque, Laura

    2016-01-01

    Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

  14. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    Science.gov (United States)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  15. Neural networks of tinnitus in humans: Elucidating severity and habituation.

    Science.gov (United States)

    Husain, Fatima T

    2016-04-01

    The article reviews current data about the neural correlates of an individual's reaction to tinnitus, primarily from studies that employ magnetic resonance imaging (MRI). Human studies employing brain imaging remain the most commonly used method to understand neural biomarkers of the reaction to tinnitus, a subjective hearing disorder. Evidence from anatomical and functional MRI studies is reviewed to better understand the large-scale neural networks implicated in tinnitus habituation and severity. These networks are concerned with attention, audition, and emotion, both during tasks and at 'rest' when no goal-directed activity is expected. I place the data in the context of published literature and current theories about tinnitus severity, while explaining the challenges and limitations of human MRI studies. A possible model of habituation to tinnitus is described, that of the attention system (via the frontal cortex) suppressing the response from the amygdala and the use of alternate nodes of the limbic system such as the insula and the parahippocampal gyrus when mediating emotion. PMID:26415997

  16. Stimulation of dendrogenesis and neural maturation in adult mammals.

    Science.gov (United States)

    Soto-Vázquez, Ramón; Labastida-López, Carlos; Romero-Castello, Samuel; Benítez-King, Gloria; Parra-Cervantes, Patricia

    2016-05-01

    This work is the result of a technical research patent on dendritogenesis and neuronal maturation, in which the existence was determined of patent documents involving the use of melatonin for the treatment of anxiety, obesity and related diseases of the peripheral and CNS. In this study, an analysis of the state of the art in order to collect technical and scientific elements for the drafting of a new patent on the use of the melatonin molecule in stimulating neuronal maturation in dendritogenesis and mammals was conducted in adults. This study is based on an invention related with this novel use of melatonin. PMID:27087552

  17. Period 2 regulates neural stem/progenitor cell proliferation in the adult hippocampus

    OpenAIRE

    Albrecht Urs; Maquet Pierre; Moonen Gustave; Nguyen Laurent; Vandenbosch Renaud; Beukelaers Pierre; Borgs Laurence; Belachew Shibeshih; Malgrange Brigitte

    2009-01-01

    Abstract Background Newborn granule neurons are generated from proliferating neural stem/progenitor cells and integrated into mature synaptic networks in the adult dentate gyrus of the hippocampus. Since light/dark variations of the mitotic index and DNA synthesis occur in many tissues, we wanted to unravel the role of the clock-controlled Period2 gene (mPer2) in timing cell cycle kinetics and neurogenesis in the adult DG. Results In contrast to the suprachiasmatic nucleus, we observed a non-...

  18. Curcumin Stimulates Proliferation of Embryonic Neural Progenitor Cells and Neurogenesis in the Adult Hippocampus*S⃞

    OpenAIRE

    Kim, So Jung; Son, Tae Gen; Park, Hee Ra; Park, Mikyung; Kim, Min-Sun; Kim, Hyung Sik; Chung, Hae Young; Mattson, Mark P.; Lee, Jaewon

    2008-01-01

    Curcumin is a natural phenolic component of yellow curry spice, which is used in some cultures for the treatment of diseases associated with oxidative stress and inflammation. Curcumin has been reported to be capable of preventing the death of neurons in animal models of neurodegenerative disorders, but its possible effects on developmental and adult neuroplasticity are unknown. In the present study, we investigated the effects of curcumin on mouse multi-potent neural progenitor cells (NPC) a...

  19. Brain micro-ecologies: neural stem cell niches in the adult mammalian brain

    OpenAIRE

    Riquelme, Patricio A; Drapeau, Elodie; Doetsch, Fiona

    2007-01-01

    Neurogenesis persists in two germinal regions in the adult mammalian brain, the subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal formation. Within these two neurogenic niches, specialized astrocytes are neural stem cells, capable of self-renewing and generating neurons and glia. Cues within the niche, from cell–cell interactions to diffusible factors, are spatially and temporally coordinated to regulate proliferation and neurogenesis, ultimately affect...

  20. Cell cycle restriction by histone H2AX limits proliferation of adult neural stem cells

    OpenAIRE

    Fernando, R. N.; Eleuteri, B.; Abdelhady, S.; Nussenzweig, A; Andang, M; Ernfors, P.

    2011-01-01

    Adult neural stem cell proliferation is dynamic and has the potential for massive self-renewal yet undergoes limited cell division in vivo. Here, we report an epigenetic mechanism regulating proliferation and self-renewal. The recruitment of the PI3K-related kinase signaling pathway and histone H2AX phosphorylation following GABAA receptor activation limits subventricular zone proliferation. As a result, NSC self-renewal and niche size is dynamic and can be directly modulated in both directio...

  1. Multipotent skin-derived precursors: adult neural crest-related precursors with therapeutic potential

    OpenAIRE

    Fernandes, Karl J.L; Toma, Jean G; Miller, Freda D.

    2007-01-01

    We previously made the surprising finding that cultures of multipotent precursors can be grown from the dermis of neonatal and adult mammalian skin. These skin-derived precursors (SKPs) display multi-lineage differentiation potential, producing both neural and mesodermal progeny in vitro, and are an apparently novel precursor cell type that is distinct from other known precursors within the skin. In this review, we begin by placing these findings within the context of the rapidly evolving ste...

  2. Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice

    OpenAIRE

    Mozafari, Sabah; Laterza, Cecilia; Roussel, Delphine; Bachelin, Corinne; Marteyn, Antoine; Deboux, Cyrille; Martino, Gianvito; Evercooren, Anne Baron-Van

    2015-01-01

    Induced pluripotent stem cell–derived (iPS-derived) neural precursor cells may represent the ideal autologous cell source for cell-based therapy to promote remyelination and neuroprotection in myelin diseases. So far, the therapeutic potential of reprogrammed cells has been evaluated in neonatal demyelinating models. However, the repair efficacy and safety of these cells has not been well addressed in the demyelinated adult CNS, which has decreased cell plasticity and scarring. Moreover, it i...

  3. Assigning Function to Adult-Born Neurons: A Theoretical Framework for Characterizing Neural Manipulation of Learning

    OpenAIRE

    Hersman, Sarah; Rodriguez Barrera, Vanessa; Fanselow, Michael

    2016-01-01

    Neuroscientists are concerned with neural processes or computations, but these may not be directly observable. In the field of learning, a behavioral procedure is observed to lead to performance outcomes, but differing inferences on underlying internal processes can lead to difficulties in interpreting conflicting results. An example of this challenge is how many functions have been attributed to adult-born granule cells in the dentate gyrus. Some of these functions were suggested by computat...

  4. In Vivo Targeted Magnetic Resonance Imaging of Endogenous Neural Stem Cells in the Adult Rodent Brain

    Directory of Open Access Journals (Sweden)

    Xiao-Mei Zhong

    2015-01-01

    Full Text Available Neural stem cells in the adult mammalian brain have a significant level of neurogenesis plasticity. In vivo monitoring of adult endogenous NSCs would be of great benefit to the understanding of the neurogenesis plasticity under normal and pathological conditions. Here we show the feasibility of in vivo targeted MR imaging of endogenous NSCs in adult mouse brain by intraventricular delivery of monoclonal anti-CD15 antibody conjugated superparamagnetic iron oxide nanoparticles. After intraventricular administration of these nanoparticles, the subpopulation of NSCs in the anterior subventricular zone and the beginning of the rostral migratory stream could be in situ labeled and were in vivo visualized with 7.0-T MR imaging during a period from 1 day to 7 days after the injection. Histology confirmed that the injected targeted nanoparticles were specifically bound to CD15 positive cells and their surrounding extracellular matrix. Our results suggest that in vivo targeted MR imaging of endogenous neural stem cells in adult rodent brain could be achieved by using anti-CD15-SPIONs as the molecular probe; and this targeting imaging strategy has the advantage of a rapid in vivo monitoring of the subpopulation of endogenous NSCs in adult brains.

  5. Neural Correlates of the Cortisol Awakening Response in Humans.

    Science.gov (United States)

    Boehringer, Andreas; Tost, Heike; Haddad, Leila; Lederbogen, Florian; Wüst, Stefan; Schwarz, Emanuel; Meyer-Lindenberg, Andreas

    2015-08-01

    The cortisol rise after awakening (cortisol awakening response, CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation related to psychosocial stress and stress-related psychiatric disorders. However, the neural regulation of the CAR has not been examined in humans. Here, we studied neural regulation related to the CAR in a sample of 25 healthy human participants using an established psychosocial stress paradigm together with multimodal functional and structural (voxel-based morphometry) magnetic resonance imaging. Across subjects, a smaller CAR was associated with reduced grey matter volume and increased stress-related brain activity in the perigenual ACC, a region which inhibits HPA axis activity during stress that is implicated in risk mechanisms and pathophysiology of stress-related mental diseases. Moreover, functional connectivity between the perigenual ACC and the hypothalamus, the primary controller of HPA axis activity, was associated with the CAR. Our findings provide support for a role of the perigenual ACC in regulating the CAR in humans and may aid future research on the pathophysiology of stress-related illnesses, such as depression, and environmental risk for illnesses such as schizophrenia. PMID:25781268

  6. Neural processing associated with cognitive and affective Theory of Mind in adolescents and adults.

    Science.gov (United States)

    Sebastian, Catherine L; Fontaine, Nathalie M G; Bird, Geoffrey; Blakemore, Sarah-Jayne; Brito, Stephane A De; McCrory, Eamon J P; Viding, Essi

    2012-01-01

    Theory of Mind (ToM) is the ability to attribute thoughts, intentions and beliefs to others. This involves component processes, including cognitive perspective taking (cognitive ToM) and understanding emotions (affective ToM). This study assessed the distinction and overlap of neural processes involved in these respective components, and also investigated their development between adolescence and adulthood. While data suggest that ToM develops between adolescence and adulthood, these populations have not been compared on cognitive and affective ToM domains. Using fMRI with 15 adolescent (aged 11-16 years) and 15 adult (aged 24-40 years) males, we assessed neural responses during cartoon vignettes requiring cognitive ToM, affective ToM or physical causality comprehension (control). An additional aim was to explore relationships between fMRI data and self-reported empathy. Both cognitive and affective ToM conditions were associated with neural responses in the classic ToM network across both groups, although only affective ToM recruited medial/ventromedial PFC (mPFC/vmPFC). Adolescents additionally activated vmPFC more than did adults during affective ToM. The specificity of the mPFC/vmPFC response during affective ToM supports evidence from lesion studies suggesting that vmPFC may integrate affective information during ToM. Furthermore, the differential neural response in vmPFC between adult and adolescent groups indicates developmental changes in affective ToM processing. PMID:21467048

  7. Frontal preparatory neural oscillations associated with cognitive control: A developmental study comparing young adults and adolescents.

    Science.gov (United States)

    Hwang, Kai; Ghuman, Avniel S; Manoach, Dara S; Jones, Stephanie R; Luna, Beatriz

    2016-08-01

    Functional magnetic resonance imaging (fMRI) studies suggest that age-related changes in the frontal cortex may underlie developmental improvements in cognitive control. In the present study we used magnetoencephalography (MEG) to identify frontal oscillatory neurodynamics that support age-related improvements in cognitive control during adolescence. We characterized the differences in neural oscillations in adolescents and adults during the preparation to suppress a prepotent saccade (antisaccade trials-AS) compared to preparing to generate a more automatic saccade (prosaccade trials-PS). We found that for adults, AS were associated with increased beta-band (16-38Hz) power in the dorsal lateral prefrontal cortex (DLPFC), enhanced alpha- to low beta-band (10-18Hz) power in the frontal eye field (FEF) that predicted performance, and increased cross-frequency alpha-beta (10-26Hz) amplitude coupling between the DLPFC and the FEF. Developmental comparisons between adults and adolescents revealed similar engagement of DLPFC beta-band power but weaker FEF alpha-band power, and lower cross-frequency coupling between the DLPFC and the FEF in adolescents. These results suggest that lateral prefrontal neural activity associated with cognitive control is adult-like by adolescence; the development of cognitive control from adolescence to adulthood is instead associated with increases in frontal connectivity and strengthening of inhibition signaling for suppressing task-incompatible processes. PMID:27173759

  8. Single-cell in vivo imaging of adult neural stem cells in the zebrafish telencephalon.

    Science.gov (United States)

    Barbosa, Joana S; Di Giaimo, Rossella; Götz, Magdalena; Ninkovic, Jovica

    2016-08-01

    Adult neural stem cells (aNSCs) in zebrafish produce mature neurons throughout their entire life span in both the intact and regenerating brain. An understanding of the behavior of aNSCs in their intact niche and during regeneration in vivo should facilitate the identification of the molecular mechanisms controlling regeneration-specific cellular events. A greater understanding of the process in regeneration-competent species may enable regeneration to be achieved in regeneration-incompetent species, including humans. Here we describe a protocol for labeling and repetitive imaging of aNSCs in vivo. We label single aNSCs, allowing nonambiguous re-identification of single cells in repetitive imaging sessions using electroporation of a red-reporter plasmid in Tg(gfap:GFP)mi2001 transgenic fish expressing GFP in aNSCs. We image using two-photon microscopy through the thinned skull of anesthetized and immobilized fish. Our protocol allows imaging every 2 d for a period of up to 1 month. This methodology allowed the visualization of aNSC behavior in vivo in their natural niche, in contrast to previously available technologies, which rely on the imaging of either dissociated cells or tissue slices. We used this protocol to follow the mode of aNSC division, fate changes and cell death in both the intact and injured zebrafish telencephalon. This experimental setup can be widely used, with minimal prior experience, to assess key factors for processes that modulate aNSC behavior. A typical experiment with data analysis takes up to 1.5 months. PMID:27362338

  9. Radiation sensitivity of adult human parenchymal hepatocytes

    International Nuclear Information System (INIS)

    The purpose of this study was to determine the radiosensitivity and repair kinetics of adult human parenchymal hepatocytes. Discarded viable human liver was obtained from the surgical pathology laboratory, and the cells were enzymatically isolated via a modification of the 2-step in situ collagenase perfusion technique used for the rat. The isolated hepatocytes were cultured with MEM media (10% FCS) in collagen coated 60 mm plates. Three hr after the cells were placed in culture, the media was changed to remove any dead unattached hepatocytes. After 24hr the viable hepatocytes were removed from the plates with collagenase and irradiated (40C, 21% O/sub 2/) with /sup 60/Co (1 Gy/min). The alkaline elution technique was used to quantify the single strand breaks (SSB). A linear dose response curve was obtained when the strand scission factor was plotted versus radiation dose and the slopes for the rat (4 cases) and human hepatocytes (6 cases) were 0.0302 and 0.0221 Gy/sup -1/, respectively. Thus, human hepatocytes are approximately 25% more radioresistant than those from the rat; this correlates with the GSH levels in the human hepatocytes (15 mM) being 20% greater than that in rat hepatocytes (12 mM). In contrast, the kinetics of repair of SSB in human hepatocytes was t/sub 1/2 fast/ = 20 min. t/sub 1/2 slow/ = 267 min) approximately 3 times slower than that in rat hepatocytes (t/sub 1/2 fast/ = 6 min, t/sub 1/2 slow/ = 98 min) and after 3 hr of repair the percent of the initial damage remaining was 20% and 15%, respectively. These date imply that in comparison to rat hepatocytes, human hepatocytes would be more radioresistant to large single doses, but equal if not more sensitive to fractionated radiation treatment

  10. Prediction of Clinical Deterioration in Hospitalized Adult Patients with Hematologic Malignancies Using a Neural Network Model

    Science.gov (United States)

    Hu, Scott B.; Wong, Deborah J. L.; Correa, Aditi; Li, Ning; Deng, Jane C.

    2016-01-01

    Introduction Clinical deterioration (ICU transfer and cardiac arrest) occurs during approximately 5–10% of hospital admissions. Existing prediction models have a high false positive rate, leading to multiple false alarms and alarm fatigue. We used routine vital signs and laboratory values obtained from the electronic medical record (EMR) along with a machine learning algorithm called a neural network to develop a prediction model that would increase the predictive accuracy and decrease false alarm rates. Design Retrospective cohort study. Setting The hematologic malignancy unit in an academic medical center in the United States. Patient Population Adult patients admitted to the hematologic malignancy unit from 2009 to 2010. Intervention None. Measurements and Main Results Vital signs and laboratory values were obtained from the electronic medical record system and then used as predictors (features). A neural network was used to build a model to predict clinical deterioration events (ICU transfer and cardiac arrest). The performance of the neural network model was compared to the VitalPac Early Warning Score (ViEWS). Five hundred sixty five consecutive total admissions were available with 43 admissions resulting in clinical deterioration. Using simulation, the neural network outperformed the ViEWS model with a positive predictive value of 82% compared to 24%, respectively. Conclusion We developed and tested a neural network-based prediction model for clinical deterioration in patients hospitalized in the hematologic malignancy unit. Our neural network model outperformed an existing model, substantially increasing the positive predictive value, allowing the clinician to be confident in the alarm raised. This system can be readily implemented in a real-time fashion in existing EMR systems. PMID:27532679

  11. Comparative study on influence of fetal bovine serum and serum of adult rat on cultivation of newborn rat neural cells

    Directory of Open Access Journals (Sweden)

    Sukach A. N.

    2014-09-01

    Full Text Available Aim. To study the influence of fetal bovine serum and serum of adult rats on behavior of newborn rat isolated neural cells during their cultivation in vitro. Methods. The isolation of neural cells from neonatal rat brain. The determination of the dynamics of cellular monolayer formation. Immunocytochemical staining of cells for β-tubulin III, nestin and vimentin. Results. It has been determined that the addition of serum of adult rats to the cultivation medium creates more favorable conditions for survival, attachment and spread of differentiated, and proliferation of the stem/progenitor neural cells of newborn rats during cultivation in vitro compared with the fetal bovine serum. Conclusions. Using the serum of adult rats is preferable for the cultivation of isolated neural cells of newborn rats compared with the fetal bovine serum.

  12. Neural mechanisms of sensitivity to peer information in young adult cannabis users.

    Science.gov (United States)

    Gilman, Jodi M; Schuster, Randi M; Curran, Max T; Calderon, Vanessa; van der Kouwe, Andre; Evins, A Eden

    2016-08-01

    Though social influence is a critical factor in the initiation and maintenance of marijuana use, the neural correlates of influence in those who use marijuana are unknown. In this study, marijuana-using young adults (MJ; n = 20) and controls (CON; n = 23) performed a decision-making task in which they made a perceptual choice after viewing the choices of unknown peers via photographs, while they underwent functional magnetic resonance imaging scans. The MJ and CON groups did not show differences in the overall number of choices that agreed with versus opposed group influence, but only the MJ group showed reaction time slowing when deciding against group choices. Longer reaction times were associated with greater activation of frontal regions. The MJ goup, compared to CON, showed significantly greater activation in the caudate when presented with peer information. Across groups, caudate activation was associated with self-reported susceptibility to influence. These findings indicate that young adults who use MJ may exhibit increased effort when confronted with opposing peer influence, as well as exhibit greater responsivity of the caudate to social information. These results not only better define the neural basis of social decisions, but also suggest that marijuana use is associated with exaggerated neural activity during decision making that involves social information. PMID:27068178

  13. Neural responses to perceiving suffering in humans and animals.

    Science.gov (United States)

    Franklin, Robert G; Nelson, Anthony J; Baker, Michelle; Beeney, Joseph E; Vescio, Theresa K; Lenz-Watson, Aurora; Adams, Reginald B

    2013-01-01

    The human ability to perceive and understand others' suffering is critical to reinforcing and maintaining our social bonds. What is not clear, however, is the extent to which this generalizes to nonhuman entities. Anecdotal evidence indicates that people may engage in empathy-like processes when observing suffering nonhuman entities, but psychological research suggests that we more readily empathize with those to whom we are closer and more similar. In this research, we examined neural responses in participants while they were presented with pictures of human versus dog suffering. We found that viewing human and animal suffering led to large overlapping regions of activation previously implicated in empathic responding to suffering, including the anterior cingulate gyrus and anterior insula. Direct comparisons of viewing human and animal suffering also revealed differences such that human suffering yielded significantly greater medial prefrontal activation, consistent with high-level theory of mind, whereas animal suffering yielded significantly greater parietal and inferior frontal activation, consistent with more semantic evaluation and perceptual simulation. PMID:23405957

  14. Characterization of neural stem cells and their progeny in the sensory circumventricular organs of adult mouse.

    Science.gov (United States)

    Furube, Eriko; Morita, Mitsuhiro; Miyata, Seiji

    2015-11-01

    Although evidence has accumulated that neurogenesis and gliogenesis occur in the subventricular zone (SVZ) and subgranular zone (SGZ) of adult mammalian brains, recent studies indicate the presence of neural stem cells (NSCs) in adult brains, particularly the circumventricular regions. In the present study, we aimed to determine characterization of NSCs and their progenitor cells in the sensory circumventricular organs (CVOs), including organum vasculosum of the lamina terminalis, subfornical organ, and area postrema of adult mouse. There were two types of NSCs: tanycyte-like ependymal cells and astrocyte-like cells. Astrocyte-like NSCs proliferated slowly and oligodendrocyte progenitor cells (OPCs) and neural progenitor cells (NPCs) actively divided. Molecular marker protein expression of NSCs and their progenitor cells were similar to those reported in the SVZ and SGZ, except that astrocyte-like NSCs expressed S100β. These circumventricular NSCs possessed the capacity to give rise to oligodendrocytes and sparse numbers of neurons and astrocytes in the sensory CVOs and adjacent brain regions. The inhibition of vascular endothelial growth factor (VEGF) signaling by using a VEGF receptor-associated tyrosine kinase inhibitor AZD2171 largely suppressed basal proliferation of OPCs. A single systemic administration of lipopolysaccharide attenuated proliferation of OPCs and induced remarkable proliferation of microglia. The present study indicates that sensory circumventricular NSCs provide new neurons and glial cells in the sensory CVOs and adjacent brain regions. PMID:25994374

  15. Residual neural processing of musical sound features in adult cochlear implant users

    Directory of Open Access Journals (Sweden)

    Lydia eTimm

    2014-04-01

    Full Text Available AbstractAuditory processing in general and music perception in particular are hampered in adult Cochlear Implant (CI users. To examine the residual music perception skills and their underlying neural correlates in CI users implanted in adolescence or adulthood, we conducted an electrophysiological and behavioural study comparing adult CI users with normal-hearing age-matched controls (NH controls. We used a newly developed musical multi-feature paradigm, which makes it possible to test automatic auditory discrimination of six different types of sound feature changes inserted within a musical enriched setting lasting only 20 minutes. The presentation of stimuli did not require the participants’ attention, allowing the study of the early automatic stage of feature processing in the auditory cortex. For the CI users, we obtained mismatch negativity (MMN brain responses to five feature changes but not to changes of rhythm, whereas we obtained MMNs for all the feature changes in the NH controls. Furthermore, the MMNs to Deviants of pitch of CI users were reduced in amplitude and later than those of NH controls for changes of pitch and guitar timbre. No other group differences in MMN parameters were found to changes in intensity and saxophone timbre. Furthermore, the MMNs in CI users reflected the behavioral scores from a respective discrimination task and were correlated with patients’ age and speech intelligibility. Our results suggest that even though CI users are not performing at the same level as NH controls in neural discrimination of pitch-based features, they do possess potential neural abilities for music processing. However, CI users showed a disrupted ability to automatically discriminate rhythmic changes compared with controls. The current behavioural and MMN findings highlight the residual neural skills for music processing even in CI users who have been implanted in adolescence or adulthood.

  16. Neural precursors derived from human embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    Peng Hongmei; Chen Gui'an

    2005-01-01

    Human embryonic stem (hES) cells provide a promising supply of specific cell types for transplantation therapy. We presented here the method to induce differentiation of purified neural precursors from hES cells, hES cells (Line PKU-1 and Line PKU-2) were cultured in suspension in bacteriological Petri dishes, which differentiated into cystic embryoid bodies (EBs).The EBs were then cultured in N2 medium containing bFGF in poly- L-lysine-coated tissue culture dishes for two weeks. The central, small cells with 2-3 short processes of the spreading outgrowth were isolated mechanically and replated. The resulting neurospheres were cultured in suspension for 10 days, then dissociated into single cell suspension with a Pasteur pipette and plated. Cells grew vigorously in an attached way and were passed every 4-5 days. Almost all the cells were proved nestin positive by immunostaining. Following withdrawal of bFGF, they differentiated into neurons expressing β-tubulin isotypeⅢ, GABA, serotonin and synaptophysin.Through induction of PDGF-AA, they differentiated into astrocytes expressing GFAP and oligodendrocytes expressing O4. The results showed that hES cells can differentiate into typical neural precursors expressing the specific marker nestin and capable of generating all three cell types of the central nervous system (CNS) in vitro.

  17. Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments

    Directory of Open Access Journals (Sweden)

    Sanna Maria

    2006-02-01

    Full Text Available Abstract Background It has recently been demonstrated that the fate of adult cells is not restricted to their tissues of origin. In particular, it has been shown that bone marrow stem cells can give rise to cells of different tissues, including neural cells, hepatocytes and myocytes, expanding their differentiation potential. Results In order to identify factors able to lead differentiation of stem cells towards cells of neural lineage, we isolated stromal cells from human adult bone marrow (BMSC. Cells were treated with: (1 TPA, forskolin, IBMX, FGF-1 or (2 retinoic acid and 2-mercaptoethanol (BME. Treatment (1 induced differentiation into neuron-like cells within 24 hours, while a longer treatment was required when using retinoic acid and BME. Morphological modifications were more dramatic after treatment (1 compared with treatment (2. In BMSC both treatments induced the expression of neural markers such as NF, GFAP, TUJ-1 and neuron-specific enolase. Moreover, the transcription factor Hes1 increased after both treatments. Conclusion Our study may contribute towards the identification of mechanisms involved in the differentiation of stem cells towards cells of neural lineage.

  18. Adult subependymal neural precursors, but not differentiated cells, undergo rapid cathodal migration in the presence of direct current electric fields.

    Directory of Open Access Journals (Sweden)

    Robart Babona-Pilipos

    Full Text Available BACKGROUND: The existence of neural stem and progenitor cells (together termed neural precursor cells in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke. METHODS AND FINDINGS: With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour. CONCLUSIONS: These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma.

  19. Cell pattern in adult human corneal endothelium.

    Directory of Open Access Journals (Sweden)

    Carlos H Wörner

    Full Text Available A review of the current data on the cell density of normal adult human endothelial cells was carried out in order to establish some common parameters appearing in the different considered populations. From the analysis of cell growth patterns, it is inferred that the cell aging rate is similar for each of the different considered populations. Also, the morphology, the cell distribution and the tendency to hexagonallity are studied. The results are consistent with the hypothesis that this phenomenon is analogous with cell behavior in other structures such as dry foams and grains in polycrystalline materials. Therefore, its driving force may be controlled by the surface tension and the mobility of the boundaries.

  20. Wnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow.

    Science.gov (United States)

    Glejzer, A; Laudet, E; Leprince, P; Hennuy, B; Poulet, C; Shakhova, O; Sommer, L; Rogister, B; Wislet-Gendebien, S

    2011-06-01

    Recent studies have shown that neural crest-derived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those "new" neural crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine. However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues. Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived cells, defining their identity and their differentiating abilities. PMID:20976520

  1. Chromatin-based epigenetics of adult subventricular zone neural stem cells

    Directory of Open Access Journals (Sweden)

    Gabriel eGonzales-Roybal

    2013-10-01

    Full Text Available In specific regions of the adult mammalian brain, neural stem cells (NSCs generate new neurons throughout life. Emerging evidence indicate that chromatin-based transcriptional regulation is a key epigenetic mechanism for the life-long function of adult NSCs. In the adult mouse brain, NSCs in the subventricular zone (SVZ retain the ability to produce both neurons and glia for the life of the animal. In this review, we discuss the origin and function of SVZ NSCs as they relate to key epigenetic concepts of development and potential underlying mechanism of chromatin-based transcriptional regulation. A central point of discussion is how SVZ NSCs – which possess many characteristics of mature, non-neurogenic astrocytes – maintain a youthful ability to produce both neuronal and glial lineages. In addition to reviewing data regarding the function of chromatin-modifying factors in SVZ neurogenesis, we incorporate our growing understanding that long noncoding RNAs (lncRNAs serve as an important element to chromatin-based transcriptional regulation, including that of SVZ NSCs. Discoveries regarding the epigenetic mechanisms of adult SVZ NSCs may provide key insights into fundamental principles of adult stem cell biology as well as the more complex and dynamic developmental environment of the embryonic brain.

  2. Distinct neural correlates of emotional and cognitive empathy in older adults.

    Science.gov (United States)

    Moore, Raeanne C; Dev, Sheena I; Jeste, Dilip V; Dziobek, Isabel; Eyler, Lisa T

    2015-04-30

    Empathy is thought to be a mechanism underlying prosocial behavior across the lifespan, yet little is known about how levels of empathy relate to individual differences in brain functioning among older adults. In this exploratory study, we examined the neural correlates of affective and cognitive empathy in older adults. Thirty older adults (M=79 years) underwent fMRI scanning and neuropsychological testing and completed a test of affective and cognitive empathy. Brain response during processing of cognitive and emotional stimuli was measured by fMRI in a priori and task-related regions and was correlated with levels of empathy. Older adults with higher levels of affective empathy showed more deactivation in the amygdala and insula during a working memory task, whereas those with higher cognitive empathy showed greater insula activation during a response inhibition task. Our preliminary findings suggest that brain systems linked to emotional and social processing respond differently among older adults with more or less affective and cognitive empathy. That these relationships can be seen both during affective and non-emotional tasks of "cold" cognitive abilities suggests that empathy may impact social behavior through both emotional and cognitive mechanisms. PMID:25770039

  3. Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Yuping Luo

    2010-04-01

    Full Text Available Fragile X syndrome (FXS, the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP. FMRP is an RNA-binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs. We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3beta. Dysregulation of GSK3beta led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis.

  4. Signs of noise-induced neural degeneration in humans

    DEFF Research Database (Denmark)

    Holtegaard, Pernille; Olsen, Steen Østergaard

    2015-01-01

    background noise, while leaving the processing of low-level stimuli unaffected. The purpose of this study was to investigate if signs of such primary neural damage from noise-exposure could also be found in noiseexposed human individuals. It was investigated: (1) if noise-exposed listeners with hearing...... thresholds within the “normal” range perform poorer, in terms of their speech recognition threshold in noise (SRTN), and (2) if auditory brainstem responses (ABR) reveal lower amplitude of wave I in the noise-exposed listeners. A test group of noise/music-exposed individuals and a control group were...... recruited. All subjects were between 18-32 years of age and had pure-tone thresholds ≤ 15 dB HL from 250-8000 Hz. Despite normal pure-tone thresholds, the noise-exposed listeners required a significantly better signal-to-noise ratio to obtain SRTN, compared to the control group. The ABR results showed...

  5. Finding the beat: a neural perspective across humans and non-human primates.

    Science.gov (United States)

    Merchant, Hugo; Grahn, Jessica; Trainor, Laurel; Rohrmeier, Martin; Fitch, W Tecumseh

    2015-03-19

    Humans possess an ability to perceive and synchronize movements to the beat in music ('beat perception and synchronization'), and recent neuroscientific data have offered new insights into this beat-finding capacity at multiple neural levels. Here, we review and compare behavioural and neural data on temporal and sequential processing during beat perception and entrainment tasks in macaques (including direct neural recording and local field potential (LFP)) and humans (including fMRI, EEG and MEG). These abilities rest upon a distributed set of circuits that include the motor cortico-basal-ganglia-thalamo-cortical (mCBGT) circuit, where the supplementary motor cortex (SMA) and the putamen are critical cortical and subcortical nodes, respectively. In addition, a cortical loop between motor and auditory areas, connected through delta and beta oscillatory activity, is deeply involved in these behaviours, with motor regions providing the predictive timing needed for the perception of, and entrainment to, musical rhythms. The neural discharge rate and the LFP oscillatory activity in the gamma- and beta-bands in the putamen and SMA of monkeys are tuned to the duration of intervals produced during a beat synchronization-continuation task (SCT). Hence, the tempo during beat synchronization is represented by different interval-tuned cells that are activated depending on the produced interval. In addition, cells in these areas are tuned to the serial-order elements of the SCT. Thus, the underpinnings of beat synchronization are intrinsically linked to the dynamics of cell populations tuned for duration and serial order throughout the mCBGT. We suggest that a cross-species comparison of behaviours and the neural circuits supporting them sets the stage for a new generation of neurally grounded computational models for beat perception and synchronization. PMID:25646516

  6. Secretome analysis of human oligodendrocytes derived from neural stem cells.

    Directory of Open Access Journals (Sweden)

    Woo Kyung Kim

    Full Text Available In this study, we investigated the secretome of human oligodendrocytes (F3.Olig2 cells generated from human neural stem cells by transduction with the gene encoding the Olig2 transcription factor. Using mRNA sequencing and protein cytokine arrays, we identified a number of biologically important secretory proteins whose expression has not been previously reported in oligodendrocytes. We found that F3.Olig2 cells secrete IL-6, PDGF-AA, GRO, GM-CSF, and M-CSF, and showed prominent expression of their corresponding receptors. Co-expression of ligands and receptors suggests that autocrine signaling loops may play important roles in both differentiation and maintenance of oligodendrocytes. We also found that F3.Olig2 cells secrete matrix metalloproteinases and matrix metalloproteinase-associated proteins associated with functional competence of oligodendrocytes. The results of our secretome analysis provide insights into the functional and molecular details of human oligodendrocytes. To the best of our knowledge, this is the first systematic analysis of the secretome of oligodendrocytes.

  7. Have you got any cholesterol? Adults' views of human nutrition

    Science.gov (United States)

    Schibeci, Renato; Wong, Khoon Yoong

    1994-12-01

    The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

  8. SIRT1 suppresses self-renewal of adult hippocampal neural stem cells.

    Science.gov (United States)

    Ma, Chen-Yan; Yao, Mao-jin; Zhai, Qi-wei; Jiao, Jian-wei; Yuan, Xiao-bing; Poo, Mu-ming

    2014-12-01

    The balance between self-renewal and differentiation of adult neural stem cells (aNSCs) is essential for the maintenance of the aNSC reservoir and the continuous supply of new neurons, but how this balance is fine-tuned in the adult brain is not fully understood. Here, we investigate the role of SIRT1, an important metabolic sensor and epigenetic repressor, in regulating adult hippocampal neurogenesis in mice. We found that there was an increase in SIRT1 expression during aNSC differentiation. In Sirt1 knockout (KO) mice, as well as in brain-specific and inducible stem cell-specific conditional KO mice, the proliferation and self-renewal rates of aNSCs in vivo were elevated. Proliferation and self-renewal rates of aNSCs and adult neural progenitor cells (aNPCs) were also elevated in neurospheres derived from Sirt1 KO mice and were suppressed by the SIRT1 agonist resveratrol in neurospheres from wild-type mice. In cultured neurospheres, 2-deoxy-D-glucose-induced metabolic stress suppressed aNSC/aNPC proliferation, and this effect was mediated in part by elevating SIRT1 activity. Microarray and biochemical analysis of neurospheres suggested an inhibitory effect of SIRT1 on Notch signaling in aNSCs/aNPCs. Inhibition of Notch signaling by a γ-secretase inhibitor also largely abolished the increased aNSC/aNPC proliferation caused by Sirt1 deletion. Together, these findings indicate that SIRT1 is an important regulator of aNSC/aNPC self-renewal and a potential mediator of the effect of metabolic changes. PMID:25468938

  9. Functional 3D Neural Mini-Tissues from Printed Gel-Based Bioink and Human Neural Stem Cells.

    Science.gov (United States)

    Gu, Qi; Tomaskovic-Crook, Eva; Lozano, Rodrigo; Chen, Yu; Kapsa, Robert M; Zhou, Qi; Wallace, Gordon G; Crook, Jeremy M

    2016-06-01

    Direct-write printing of stem cells within biomaterials presents an opportunity to engineer tissue for in vitro modeling and regenerative medicine. Here, a first example of constructing neural tissue by printing human neural stem cells that are differentiated in situ to functional neurons and supporting neuroglia is reported. The supporting biomaterial incorporates a novel clinically relevant polysaccharide-based bioink comprising alginate, carboxymethyl-chitosan, and agarose. The printed bioink rapidly gels by stable cross-linking to form a porous 3D scaffold encapsulating stem cells for in situ expansion and differentiation. Differentiated neurons form synaptic contacts, establish networks, are spontaneously active, show a bicuculline-induced increased calcium response, and are predominantly gamma-aminobutyric acid expressing. The 3D tissues will facilitate investigation of human neural development, function, and disease, and may be adaptable for engineering other 3D tissues from different stem cell types. PMID:27028356

  10. Human Adult Olfactory Bulb Neurogenesis? Novelty Is the Best Policy

    OpenAIRE

    Macklis, Jeffrey Daniel

    2012-01-01

    There is ongoing controversy as to whether the understanding of adult mammalian neurogenesis gained from rodent studies is applicable to humans. In this issue of Neuron, Bergmann et al. (2012) propose that adult human olfactory bulb neurogenesis with long-term neuronal survival is extremely limited.

  11. Adult Education & Human Resource Development: Overlapping and Disparate Fields

    Science.gov (United States)

    Watkins, Karen E.; Marsick, Victoria J.

    2014-01-01

    Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

  12. HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels

    OpenAIRE

    Jiang, Yindi; Hsieh, Jenny

    2014-01-01

    Cell cycle regulation is one of the most fundamental mechanisms to control various biological processes, including the proliferation of neural stem/progenitor cells (NSPCs) in adult mouse brain. This study shows that histone deacetylase 3 (HDAC3), a well-studied epigenetic factor, is required for the proliferation of neural stem cells. We also demonstrate that HDAC3 controls gap 2 and mitosis phase of cell cycle through stabilization of cell cycle protein cyclin-dependent kinase 1. These find...

  13. Gene expression analysis of neuronal precursors from adult mouse brain and differential screen for neural stem cell markers

    OpenAIRE

    Pennartz, Sandra

    2004-01-01

    In the adult mouse brain, neuronal precursor cells continuously emanate from neural stem cells (NSC) in the subventricular zone (SVZ) and migrate into the olfactory bulb (OB) where they differentiate to serve as replenishment for GABAergic interneurons. During the migration process, PSA-NCAM (Polysialic acid-Neural cell adhesion molecule) specifically marks the neuronal precursors (PSA+ cells). This phenomenon was exploited in the framework of this doctoral thesis to isolate a homogeneous cel...

  14. Hydrogel formulation determines cell fate of fetal and adult neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Emily R. Aurand

    2014-01-01

    Full Text Available Hydrogels provide a unique tool for neural tissue engineering. These materials can be customized for certain functions, i.e. to provide cell/drug delivery or act as a physical scaffold. Unfortunately, hydrogel complexities can negatively impact their biocompatibility, resulting in unintended consequences. These adverse effects may be combated with a better understanding of hydrogel chemical, physical, and mechanical properties, and how these properties affect encapsulated neural cells. We defined the polymerization and degradation rates and compressive moduli of 25 hydrogels formulated from different concentrations of hyaluronic acid (HA and poly(ethylene glycol (PEG. Changes in compressive modulus were driven primarily by the HA concentration. The in vitro biocompatibility of fetal-derived (fNPC and adult-derived (aNPC neural progenitor cells was dependent on hydrogel formulation. Acute survival of fNPC benefited from hydrogel encapsulation. NPC differentiation was divergent: fNPC differentiated into mostly glial cells, compared with neuronal differentiation of aNPC. Differentiation was influenced in part by the hydrogel mechanical properties. This study indicates that there can be a wide range of HA and PEG hydrogels compatible with NPC. Additionally, this is the first study comparing hydrogel encapsulation of NPC derived from different aged sources, with data suggesting that fNPC and aNPC respond dissimilarly within the same hydrogel formulation.

  15. Ultrastructure of human neural stem/progenitor cells and neurospheres

    Institute of Scientific and Technical Information of China (English)

    Yaodong Zhao; Tianyi Zhang; Qiang Huang; Aidong Wang; Jun Dong; Qing Lan; Zhenghong Qin

    2009-01-01

    BACKGROUND: Biological and morphological characteristics of neural stern/progenitor cells (NSPCs) have been widely investigated.OBJECTIVE: To explore the ultrastructure of human embryo-derived NSPCs and neurospheres cultivated in vitro using electron microscopy.DESIGN, TIME AND SETTING: A cell biology experiment was performed at the Brain Tumor Laboratory of Soochow University, and Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University between August 2007 and April 2008.MATERIALS: Human fetal brain tissue was obtained from an 8-week-old aborted fetus; serum-free Dulbecco's modified Eagle's medium/F12 culture medium was provided by Gibco, USA; scanning electron microscope was provided by Hitachi instruments, Japan; transmission electron microscope was provided by JEOL, Japan.METHODS: NSPCs were isolated from human fetal brain tissue and cultivated in serum-free Dulbecco's modified Eagle's medium/F12 culture medium. Cells were passaged every 5-7 days. After three passages, NSPCs were harvested and used for ultrastructural examination.MAIN OUTCOME MEASURES: Ultrastructural examination of human NSPCs and adjacent cells in neurospheres.RESULTS: Individual NSPCs were visible as spherical morphologies with rough surfaces under scanning electron microscope. Generally, they had large nuclei and little cytoplasm. Nuclei were frequently globular with large amounts of euchromatin and a small quantity of heterochromatin, and most NSPCs had only one nucleolus. The Golgi apparatus and endoplasmic reticulum were underdeveloped; however, autophagosomes were clearly visible. The neurospheres were made up of NSPCs and non-fixiform material inside. Between adjacent cells and at the cytoplasmic surface of apposed plasma membranes, there were vesicle-like structures. Some membrane boundaries with high permeabilities were observed between some contiguous NSPCs in neurospheres, possibly attributable to plasmalemmal fusion between adjacent cells.CONCLUSION: A large number

  16. The common and distinct neural bases of affect labeling and reappraisal in healthy adults

    Directory of Open Access Journals (Sweden)

    LisaJaneBurklund

    2014-03-01

    Full Text Available Emotion regulation is commonly characterized as involving conscious and intentional attempts to change felt emotions, such as, for example, through reappraisal whereby one intentionally decreases the intensity of one’s emotional response to a particular stimulus or situation by reinterpreting it in a less threatening way. However, there is growing evidence and appreciation that some types of emotion regulation are unintentional or incidental, meaning that affective modulation is a consequence but not an explicit goal. For example, affect labeling involves simply verbally labeling the emotional content of an external stimulus or one’s own affective responses without an intentional goal of altering emotional responses, yet has been associated with reduced affective responses at the neural and experiential levels. Although both intentional and incidental emotional regulation strategies have been associated with diminished limbic responses and self-reported distress, little previous research has directly compared their underlying neural mechanisms. In this study, we examined the extent to which incidental and intentional emotion regulation, namely, affect labeling and reappraisal, produced common and divergent neural and self-report responses to aversive images relative to an observe-only control condition in a sample of healthy older adults (N=39. Affect labeling and reappraisal produced common activations in several prefrontal regulatory regions, with affect labeling producing stronger responses in direct comparisons. Affect labeling and reappraisal were also associated with similar decreases in amygdala activity. Finally, affect labeling and reappraisal were associated with correlated reductions in self-reported distress. Together these results point to common neurocognitive mechanisms involved in affect labeling and reappraisal, supporting the idea that intentional and incidental emotion regulation may utilize overlapping neural processes.

  17. Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain

    Institute of Scientific and Technical Information of China (English)

    Congmin Wang; Qiangqiang Zhang; Yue Zhang; Rui Chen; Hongjun Song; Zhengang Yang; Fang Liu; Ying-Ying Liu; Cai-Hong Zhao; Yan You; Lei Wang; Jingxiao Zhang; Bin Wei; Tong Ma

    2011-01-01

    It is of great interest to identify new neurons in the adult human brain,but the persistence of neurogenesis in the subventricular zone (SVZ) and the existence of the rostral migratory stream (RMS)-like pathway in the adult human forebrain remain highly controversial.In the present study,we have described the general configuration of the RMS in adult monkey,fetal human and adult human brains.We provide evidence that neuroblasts exist continuously in the anterior ventral SVZ and RMS of the adult human brain.The neuroblasts appear singly or in pairs without forming chains; they exhibit migratory morphologies and co-express the immature neuronal markers doublecortin,polysialylated neural cell adhesion molecule and βI-tubulin.Few of these neuroblasts appear to be actively proliferating in the anterior ventral SVZ but none in the RMS,indicating that neuroblasts distributed along the RMS are most likely derived from the ventral SVZ.Interestingly,no neuroblasts are found in the adult human olfactory bulb.Taken together,our data suggest that the SVZ maintains the ability to produce neuroblasts in the adult human brain.

  18. Neural mechanisms of perceptual grouping in human visual cortex

    Institute of Scientific and Technical Information of China (English)

    MAO Lihua; HAN Shihui; GUO Chunyan; JIANG Yi

    2004-01-01

    The current work examined neural substrates of perceptual grouping in human visual cortex using event-related potential (ERP) recording. Stimulus arrays consisted of local elements that were either evenly spaced (uniform stimuli) or grouped into columns or rows by proximity or color similarity (grouping stimuli). High-density ERPs were recorded while subjects identified orientations of perceptual groups in stimulus arrays that were presented randomly in one of the four quadrants of the visual field. Both uniform and grouping stimulus arrays elicited an early ERP component (C1), which peaked at about 70 ms after stimulus onset and changed its polarity as a function of stimulated elevations. Dipole modeling based on realistic- head boundary-element models revealed generators of the C1 component in the calcarine cortex. The C1 was modulated by perceptual grouping of local elements based on proximity, and this grouping effect was stronger in the upper than in the lower visual field. The findings provide ERP evidence for the engagement of human primary visual cortex in the early stage of perceptual grouping.

  19. Functional integration of human neural precursor cells in mouse cortex.

    Directory of Open Access Journals (Sweden)

    Fu-Wen Zhou

    Full Text Available This study investigates the electrophysiological properties and functional integration of different phenotypes of transplanted human neural precursor cells (hNPCs in immunodeficient NSG mice. Postnatal day 2 mice received unilateral injections of 100,000 GFP+ hNPCs into the right parietal cortex. Eight weeks after transplantation, 1.21% of transplanted hNPCs survived. In these hNPCs, parvalbumin (PV-, calretinin (CR-, somatostatin (SS-positive inhibitory interneurons and excitatory pyramidal neurons were confirmed electrophysiologically and histologically. All GFP+ hNPCs were immunoreactive with anti-human specific nuclear protein. The proportions of PV-, CR-, and SS-positive cells among GFP+ cells were 35.5%, 15.7%, and 17.1%, respectively; around 15% of GFP+ cells were identified as pyramidal neurons. Those electrophysiologically and histological identified GFP+ hNPCs were shown to fire action potentials with the appropriate firing patterns for different classes of neurons and to display spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs. The amplitude, frequency and kinetic properties of sEPSCs and sIPSCs in different types of hNPCs were comparable to host cells of the same type. In conclusion, GFP+ hNPCs produce neurons that are competent to integrate functionally into host neocortical neuronal networks. This provides promising data on the potential for hNPCs to serve as therapeutic agents in neurological diseases with abnormal neuronal circuitry such as epilepsy.

  20. Increased Intraregional Synchronized Neural Activity in Adult Brain After Prolonged Adaptation to High-Altitude Hypoxia: A Resting-State fMRI Study.

    Science.gov (United States)

    Chen, Ji; Fan, Cunxiu; Li, Jinqiang; Han, Qiaoqing; Lin, Jianzhong; Yang, Tianhe; Zhang, Jiaxing

    2016-03-01

    Chen, Ji, Cunxiu Fan, Jinqiang Li, Qiaoqing Han, Jianzhong Lin, Tianhe Yang, and Jiaxing Zhang. Increased intraregional, synchronized neural activity in adult brain after prolonged adaptation to high-altitude hypoxia: a resting-state fMRI study. High Alt Med Biol. 17:16-24, 2016-The human brain is intrinsically plastic such that its functional architecture can be reorganized in response to environmental pressures and physiological changes. However, it remains unclear whether a compensatory modification of spontaneous neural activity occurs in adult brain during prolonged high-altitude (HA) adaptation. In this study, we obtained resting-state functional magnetic resonance (MR) images in 16 adults who have immigrated to Qinghai-Tibet Plateau (2300-4400 m) for 2 years and in 16 age-matched sea level (SL) controls. A validated regional homogeneity (Reho) method was employed to investigate the local synchronization of resting-state functional magnetic resonance imaging (fMRI) signals. Seed connectivity analysis was carried out subsequently. Cognitive and physiological assessments were made and correlated with the image metrics. Compared with SL controls, global mean Reho was significantly increased in HA immigrants as well as a regional increase in the right inferolateral sensorimotor cortex. Furthermore, mean z-Reho value extracted within the inferolateral sensorimotor area showed trend-level significant inverse correlation with memory search reaction time in HA immigrants. These observations, for the first time, provide evidence of adult brain resilience of spontaneous neural activity after long-term HA exposure without inherited and developmental effects. Resting-state fMRI could yield valuable information for central mechanisms underlying respiratory and cognitive compensations in adults during prolonged environmentally hypoxic adaptation, paving the way for future HA-adaptive training. PMID:26906285

  1. Neural and cardiovascular responses to emotional stress in humans

    OpenAIRE

    Carter, Jason R.; Durocher, John J.; Kern, Rosalie P.

    2008-01-01

    Sympathetic neural responses to mental stress are well documented but controversial, whereas sympathetic neural responses to emotional stress are unknown. The purpose of this study was to investigate neural and cardiovascular responses to emotional stress evoked by negative pictures and reexamine the relationship between muscle sympathetic nerve activity (MSNA) and perceived stress. Mean arterial pressure (MAP), heart rate (HR), MSNA, and perceived stress levels were recorded in 18 men during...

  2. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

    Energy Technology Data Exchange (ETDEWEB)

    Boku, Shuken, E-mail: shuboku@med.hokudai.ac.jp [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Nakagawa, Shin [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takamura, Naoki [Pharmaceutical Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Osaka (Japan); Kato, Akiko [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Takebayashi, Minoru [Department of Psychiatry, National Hospital Organization Kure Medical Center, Kure (Japan); Hisaoka-Nakashima, Kazue [Department of Pharmacology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima (Japan); Omiya, Yuki; Inoue, Takeshi; Kusumi, Ichiro [Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

    2013-05-17

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.

  3. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3

    International Nuclear Information System (INIS)

    Highlights: •GDNF has no effect on ADP proliferation and apoptosis. •GDNF increases ADP differentiation into astrocyte. •A specific inhibitor of STAT3 decreases the astrogliogenic effect of GDNF. •STAT3 knockdown by lentiviral shRNA vector also decreases the astrogliogenic effect of GDNF. •GDNF increases the phosphorylation of STAT3. -- Abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis

  4. Longitudinal evidence for functional specialization of the neural circuit supporting working memory in the human brain

    OpenAIRE

    Finn, Amy S.; Sheridan, Margaret A.; Hudson Kam, Carla L.; Hinshaw, Stephen; D’Esposito, Mark

    2010-01-01

    Although children perform more poorly than adults on many cognitive measures, they are better able to learn things such as language and music. These differences could result from the delayed specialization of neural circuits and asynchronies in the maturation of neural substrates required for learning. Working memory—the ability to hold information in mind that is no longer present in the environment—comprises a set of cognitive processes required for many, if not all, forms of learning. A cr...

  5. Human Embryonic Stem Cells: A Model for the Study of Neural Development and Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Piya Prajumwongs

    2016-01-01

    Full Text Available Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs recapitulated those in the early embryo development in vivo at certain degree. This underscores the usefulness of hESCs in understanding early human neural development and reinforces the need to integrate the principles of developmental biology and hESC biology for an efficient neural differentiation.

  6. Regional and Stage-Specific Effects of Prospectively Purified Vascular Cells on the Adult V-SVZ Neural Stem Cell Lineage

    OpenAIRE

    Crouch, Elizabeth E.; Liu, Chang; Silva-Vargas, Violeta; Doetsch, Fiona

    2015-01-01

    Adult neural stem cells reside in specialized niches. In the ventricular-subventricular zone (V-SVZ), quiescent neural stem cells (qNSCs) become activated (aNSCs), and generate transit amplifying cells (TACs), which give rise to neuroblasts that migrate to the olfactory bulb. The vasculature is an important component of the adult neural stem cell niche, but whether vascular cells in neurogenic areas are intrinsically different from those elsewhere in the brain is unknown. Moreover, the contri...

  7. Notch3 signaling gates cell cycle entry and limits neural stem cell amplification in the adult pallium

    OpenAIRE

    Alunni, A.; Krecsmarik, M.; A Bosco; Galant, S.; Pan, L.; Moens, C.B.; Bally-Cuif, L.

    2013-01-01

    Maintaining the homeostasis of germinal zones in adult organs is a fundamental but mechanistically poorly understood process. In particular, what controls stem cell activation remains unclear. We have previously shown that Notch signaling limits neural stem cell (NSC) proliferation in the adult zebrafish pallium. Combining pharmacological and genetic manipulations, we demonstrate here that long-term Notch invalidation primarily induces NSC amplification through their activation from quiescenc...

  8. Neural mechanisms of reading facial emotions in young and older adults

    Directory of Open Access Journals (Sweden)

    Natalie Christina Ebner

    2012-07-01

    Full Text Available The ability to read and appropriately respond to emotions in others is central for successful social interaction. Young and older adults are better at identifying positive than negative facial expressions and expressions of young than older faces. Little, however, is known about the neural processes associated with reading different emotions, particularly in faces of different ages, in samples of young and older adults. During fMRI, young and older participants identified expressions in happy, neutral, and angry young and older faces. The results suggest a functional dissociation of ventromedial prefrontal cortex (vmPFC and dorsomedial prefrontal cortex (dmPFC in reading facial emotions that is largely comparable in young and older adults: Both age groups showed greater vmPFC activity to happy compared to angry or neutral faces, which was positively correlated with expression identification for happy compared to angry faces. In contrast, both age groups showed greater activity in dmPFC to neutral or angry than happy faces which was negatively correlated with expression identification for neutral compared to happy faces. A similar region of dmPFC showed greater activity for older than young faces, but no brain-behavior correlations. Greater vmPFC activity in the present study may reflect greater affective processing, involved in reading happy compared to neutral or angry faces. Greater dmPFC activity may reflect more cognitive control involved in decoding and/or regulating negative emotions associated with neutral or angry than happy, and older than young, faces.

  9. Neural correlates of human somatosensory integration in tinnitus

    NARCIS (Netherlands)

    Lanting, C. P.; de Kleine, E.; Eppinga, R. N.; van Dijk, P.

    2010-01-01

    Possible neural correlates of somatosensory modulation of tinnitus were assessed. Functional magnetic resonance imaging (fMRI) was used to investigate differences in neural activity between subjects that can modulate their tinnitus by jaw protrusion and normal hearing controls. We measured responses

  10. Human neural stem cells over-expressing VEGF provide neuroprotection, angiogenesis and functional recovery in mouse stroke model.

    Directory of Open Access Journals (Sweden)

    Hong J Lee

    Full Text Available BACKGROUND: Intracerebral hemorrhage (ICH is a lethal stroke type. As mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs selectively migrate to the brain and induce behavioral recovery in rat ICH model, and that combined administration of NSCs and vascular endothelial growth factor (VEGF results in improved structural and functional outcome from cerebral ischemia. METHODS AND FINDINGS: We postulated that human NSCs overexpressing VEGF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs, increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by unilateral injection of bacterial collagenase into striatum. HB1.F3.VEGF human NSC line produced an amount of VEGF four times higher than parental F3 cell line in vitro, and induced behavioral improvement and 2-3 fold increase in cell survival at two weeks and eight weeks post-transplantation. CONCLUSIONS: Brain transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results suggest a possible application of the human neural stem cell line, which is genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke.

  11. Galectin-1 is expressed in early-type neural progenitor cells and down-regulates neurogenesis in the adult hippocampus

    Directory of Open Access Journals (Sweden)

    Imaizumi Yoichi

    2011-01-01

    Full Text Available Abstract Background In the adult mammalian brain, neural stem cells (NSCs proliferate in the dentate gyrus (DG of the hippocampus and generate new neurons throughout life. A multimodal protein, Galectin-1, is expressed in neural progenitor cells (NPCs and implicated in the proliferation of the NPCs in the DG. However, little is known about its detailed expression profile in the NPCs and functions in adult neurogenesis in the DG. Results Our immunohistochemical and morphological analysis showed that Galectin-1 was expressed in the type 1 and 2a cells, which are putative NSCs, in the subgranular zone (SGZ of the adult mouse DG. To study Galectin-1's function in adult hippocampal neurogenesis, we made galectin-1 knock-out mice on the C57BL6 background and characterized the effects on neurogenesis. In the SGZ of the galectin-1 knock-out mice, increased numbers of type 1 cells, DCX-positive immature progenitors, and NeuN-positive newborn neurons were observed. Using triple-labeling immunohistochemistry and morphological analyses, we found that the proliferation of the type-1 cells was increased in the SGZ of the galectin-1 knock-out mice, and we propose that this proliferation is the mechanism for the net increase in the adult neurogenesis in these knock-out mice DG. Conclusions Galectin-1 is expressed in the neural stem cells and down-regulates neurogenesis in the adult hippocampus.

  12. A computational model incorporating neural stem cell dynamics reproduces glioma incidence across the lifespan in the human population.

    Directory of Open Access Journals (Sweden)

    Roman Bauer

    Full Text Available Glioma is the most common form of primary brain tumor. Demographically, the risk of occurrence increases until old age. Here we present a novel computational model to reproduce the probability of glioma incidence across the lifespan. Previous mathematical models explaining glioma incidence are framed in a rather abstract way, and do not directly relate to empirical findings. To decrease this gap between theory and experimental observations, we incorporate recent data on cellular and molecular factors underlying gliomagenesis. Since evidence implicates the adult neural stem cell as the likely cell-of-origin of glioma, we have incorporated empirically-determined estimates of neural stem cell number, cell division rate, mutation rate and oncogenic potential into our model. We demonstrate that our model yields results which match actual demographic data in the human population. In particular, this model accounts for the observed peak incidence of glioma at approximately 80 years of age, without the need to assert differential susceptibility throughout the population. Overall, our model supports the hypothesis that glioma is caused by randomly-occurring oncogenic mutations within the neural stem cell population. Based on this model, we assess the influence of the (experimentally indicated decrease in the number of neural stem cells and increase of cell division rate during aging. Our model provides multiple testable predictions, and suggests that different temporal sequences of oncogenic mutations can lead to tumorigenesis. Finally, we conclude that four or five oncogenic mutations are sufficient for the formation of glioma.

  13. Differences between the neurogenic and proliferative abilities of Müller glia with stem cell characteristics and the ciliary epithelium from the adult human eye

    OpenAIRE

    Bhatia, Bhairavi; Jayaram, Hari; Singhal, Shweta; Jones, Megan F; Limb, G. Astrid

    2011-01-01

    Much controversy has arisen on the nature and sources of stem cells in the adult human retina. Whilst ciliary epithelium has been thought to constitute a source of neural stem cells, a population of Müller glia in the neural retina has also been shown to exhibit neurogenic characteristics. This study aimed to compare the neurogenic and proliferative abilities between these two major cell populations. It also examined whether differences exist between the pigmented and non-pigmented ciliary ep...

  14. Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence.

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    Martina Reske

    Full Text Available Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate, which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing.158 occasional stimulants users (OSU and 50 comparison subjects (CS performed a "risky gains" decision making task during which they could select safe options (cash in 20 cents or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, "risky decisions". The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42, or <50 lifetime marijuana uses (n = 32, were compared to CS with <50 lifetime uses (n = 46 to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed.There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options.Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions critical for performance monitoring

  15. PPARs Expression in Adult Mouse Neural Stem Cells: Modulation of PPARs during Astroglial Differentiaton of NSC

    Directory of Open Access Journals (Sweden)

    A. Cimini

    2007-01-01

    Full Text Available PPAR isotypes are involved in the regulation of cell proliferation, death, and differentiation, with different roles and mechanisms depending on the specific isotype and ligand and on the differentiated, undifferentiated, or transformed status of the cell. Differentiation stimuli are integrated by key transcription factors which regulate specific sets of specialized genes to allow proliferative cells to exit the cell cycle and acquire specialized functions. The main differentiation programs known to be controlled by PPARs both during development and in the adult are placental differentiation, adipogenesis, osteoblast differentiation, skin differentiation, and gut differentiation. PPARs may also be involved in the differentiation of macrophages, brain, and breast. However, their functions in this cell type and organs still awaits further elucidation. PPARs may be involved in cell proliferation and differentiation processes of neural stem cells (NSC. To this aim, in this work the expression of the three PPAR isotypes and RXRs in NSC has been investigated.

  16. Comprehensive interactome of Otx2 in the adult mouse neural retina.

    Science.gov (United States)

    Fant, Bruno; Samuel, Alexander; Audebert, Stéphane; Couzon, Agnès; El Nagar, Salsabiel; Billon, Nathalie; Lamonerie, Thomas

    2015-11-01

    The Otx2 homeodomain transcription factor exerts multiple functions in specific developmental contexts, probably through the regulation of different sets of genes. Protein partners of Otx2 have been shown to modulate its activity. Therefore, the Otx2 interactome may play a key role in selecting a precise target-gene repertoire, hence determining its function in a specific tissue. To address the nature of Otx2 interactome, we generated a new recombinant Otx2(CTAP-tag) mouse line, designed for protein complexes purification. We validated this mouse line by establishing the Otx2 interactome in the adult neural retina. In this tissue, Otx2 is thought to have overlapping function with its paralog Crx. Our analysis revealed that, in contrary to Crx, Otx2 did not develop interactions with proteins that are known to regulate phototransduction genes but showed specific partnership with factors associated with retinal development. The relationship between Otx2 and Crx in the neural retina should therefore be considered as complementarity rather than redundancy. Furthermore, study of the Otx2 interactome revealed strong associations with RNA processing and translation machineries, suggesting unexpected roles for Otx2 in the regulation of selected target genes all along the transcription/translation pathway. The Otx2(CTAP-tag) line, therefore, appears suitable for a systematic approach to Otx2 protein-protein interactions. genesis 53:685-694, 2015. © 2015 Wiley Periodicals, Inc. PMID:26426291

  17. Adult neural precursor cells form connexin-dependent networks that improve their survival.

    Science.gov (United States)

    Ravella, Ajaya; Ringstedt, Thomas; Brion, Jean-Pierre; Pandolfo, Massimo; Herlenius, Eric

    2015-10-21

    Establishment of cellular networks and calcium homeostasis are essential for embryonic stem cell proliferation and differentiation. We also hypothesized that adult neural progenitor cells form functional cellular networks relevant for their development. We isolated neuronal progenitor cells from the subventricular zone of 5-week-old mice to investigate the role of gap junctions, calcium homeostasis, and cellular networks in cell differentiation and survival. Western blotting and reverse transcription-PCR showed that the cells expressed the gap junction components connexin 26, 36, 43, and 45, and that expression of connexin 43 increased in early (8 days) differentiated cells. Transmission electron microscopy and immunocytochemistry also indicated that gap junctions were present. Scrape-loading experiments showed dye transfer between cells that could be prevented by gapjunction blockers; thus, functional intercellular gap junctions had been established. However, dye transfer was four times stronger in differentiated cultures, correlating with the increased connexin 43 expression. During time-lapse calcium imaging, both differentiated and undifferentiated cultures showed spontaneous calcium activity that was reduced by gap junction blockers. Cross-correlation analysis of the calcium recordings showed that the cells were interconnected through gap junctions and that the early-differentiated cells were organized in small-world networks. Gap junction blockers did not affect proliferation and differentiation, but resulted in twice as many apoptotic cells. mRNAi knockdown of connexin 43 also doubled the number of apoptotic cells. We conclude that adult neural progenitor cells form networks in vitro that are strengthened during early differentiation by increased expression of connexin 43. The networks are functional and improve cell survival. PMID:26351758

  18. Adult Literacy Education and Human Rights: A View from Afghanistan

    Science.gov (United States)

    Andersen, Susan M.; Kooij, Christina S.

    2007-01-01

    In this article, we argue that adult literacy as part of international development is an issue of both human rights and women's rights. We explore this by presenting a case study of the effects of one innovative adult literacy program in Afghanistan that places men and women, as well as various ethnicities, together in the same classroom as…

  19. Sensitive periods for the functional specialization of the neural system for human face processing

    OpenAIRE

    Röder, Brigitte; Ley, Pia; Shenoy, Bhamy H.; Kekunnaya, Ramesh; Bottari, Davide

    2013-01-01

    Sensitive periods in human functional brain development were tested in humans who had been blind from birth and whose sight was restored as long as 14 y later. In investigating this rare population, our data demonstrate a general principle of brain development: rather than being born with highly specialized neural systems (e.g., for specific object categories such as faces), the functional differentiation of neural circuits seems to depend on early (visual) experience involving a decrease in ...

  20. Encoding Redundancy for Task-dependent Optimal Control : A Neural Network Model of Human Reaching

    OpenAIRE

    Herbort, Oliver

    2008-01-01

    The human motor system is adaptive in two senses. It adapts to the properties of the body to enable effective control. It also adapts to different situational requirements and constraints. This thesis proposes a new neural network model of both kinds of adaptivity for the motor cortical control of human reaching movements, called SURE_REACH (sensorimotor unsupervised learning redundancy resolving control architecture). In this neural network approach, the kinematic and sensorimotor redundancy...

  1. Bacteriology of moderate (chronic) periodontitis in mature adult humans.

    OpenAIRE

    Moore, W E; Holdeman, L V; Cato, E P; Smibert, R M; Burmeister, J A; Ranney, R R

    1983-01-01

    A total of 171 taxa was represented among 1,900 bacterial isolates from 60 samples of sites affected with moderate periodontitis in 22 mature adult humans. The composition of the subgingival sulcus flora was statistically significantly different from that of the adjacent supragingival flora and the subgingival flora of 14 people with healthy gingiva, but was not significantly different from that of sulci affected with severe periodontitis in 21 young human adults. The sulcus floras of moderat...

  2. Editorial: Technology for higher education, adult learning and human performance

    OpenAIRE

    Minhong Wang; Chi-Cheng Chang; Feng Wu

    2013-01-01

    This special issue is dedicated to technology-enabled approaches for improving higher education, adult learning, and human performance. Improvement of learning and human development for sustainable development has been recognized as a key strategy for individuals, institutions, and organizations to strengthen their competitive advantages. It becomes crucial to help adult learners and knowledge workers to improve their self-directed and life-long learning capabilities. Meanwhile, advances in t...

  3. Neural correlates of training and transfer effects in working memory in older adults.

    Science.gov (United States)

    Heinzel, Stephan; Lorenz, Robert C; Pelz, Patricia; Heinz, Andreas; Walter, Henrik; Kathmann, Norbert; Rapp, Michael A; Stelzel, Christine

    2016-07-01

    As indicated by previous research, aging is associated with a decline in working memory (WM) functioning, related to alterations in fronto-parietal neural activations. At the same time, previous studies showed that WM training in older adults may improve the performance in the trained task (training effect), and more importantly, also in untrained WM tasks (transfer effects). However, neural correlates of these transfer effects that would improve understanding of its underlying mechanisms, have not been shown in older participants as yet. In this study, we investigated blood-oxygen-level-dependent (BOLD) signal changes during n-back performance and an untrained delayed recognition (Sternberg) task following 12sessions (45min each) of adaptive n-back training in older adults. The Sternberg task used in this study allowed to test for neural training effects independent of specific task affordances of the trained task and to separate maintenance from updating processes. Thirty-two healthy older participants (60-75years) were assigned either to an n-back training or a no-contact control group. Before (t1) and after (t2) training/waiting period, both the n-back task and the Sternberg task were conducted while BOLD signal was measured using functional Magnetic Resonance Imaging (fMRI) in all participants. In addition, neuropsychological tests were performed outside the scanner. WM performance improved with training and behavioral transfer to tests measuring executive functions, processing speed, and fluid intelligence was found. In the training group, BOLD signal in the right lateral middle frontal gyrus/caudal superior frontal sulcus (Brodmann area, BA 6/8) decreased in both the trained n-back and the updating condition of the untrained Sternberg task at t2, compared to the control group. fMRI findings indicate a training-related increase in processing efficiency of WM networks, potentially related to the process of WM updating. Performance gains in untrained tasks

  4. ZEB1 Promotes Invasion in Human Fetal Neural Stem Cells and Hypoxic Glioma Neurospheres.

    Science.gov (United States)

    Kahlert, Ulf D; Suwala, Abigail K; Raabe, Eric H; Siebzehnrubl, Florian A; Suarez, Maria J; Orr, Brent A; Bar, Eli E; Maciaczyk, Jaroslaw; Eberhart, Charles G

    2015-11-01

    Diffuse spread through brain parenchyma and the presence of hypoxic foci rimmed by neoplastic cells are two cardinal features of glioblastoma, and low oxygen is thought to drive movement of malignant gliomas in the core of the lesions. Transcription factors associated with epithelial-to-mesenchymal transition (EMT) have been linked to this invasion, and we found that hypoxia increased in vitro invasion up to fourfold in glioblastoma neurosphere lines and induced the expression of ZEB1. Immunohistochemical assessment of 295 surgical specimens consisting of various types of pediatric and adult brain cancers showed that ZEB1 expression was significantly higher in infiltrative lesions than less invasive tumors such as pilocytic astrocytoma and ependymoma. ZEB1 protein was also present in human fetal periventricular stem and progenitor cells and ZEB1 inhibition impaired migration of in vitro propagated human neural stem cells. The induction of ZEB1 protein in hypoxic glioblastoma neurospheres could be partially blocked by the HIF1alpha inhibitor digoxin. Targeting ZEB1 blocked hypoxia-augmented invasion of glioblastoma cells in addition to slowing them in normoxia. These data support the role for ZEB1 in invasive and high-grade brain tumors and suggest its key role in promoting invasion in the hypoxic tumor core as well as in the periphery. PMID:25521330

  5. Cell-extracellular matrix interactions regulate neural differentiation of human embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Rao Mahendra S

    2008-09-01

    Full Text Available Abstract Background Interactions of cells with the extracellular matrix (ECM are critical for the establishment and maintenance of stem cell self-renewal and differentiation. However, the ECM is a complex mixture of matrix molecules; little is known about the role of ECM components in human embryonic stem cell (hESC differentiation into neural progenitors and neurons. Results A reproducible protocol was used to generate highly homogenous neural progenitors or a mixed population of neural progenitors and neurons from hESCs. This defined adherent culture system allowed us to examine the effect of ECM molecules on neural differentiation of hESCs. hESC-derived differentiating embryoid bodies were plated on Poly-D-Lysine (PDL, PDL/fibronectin, PDL/laminin, type I collagen and Matrigel, and cultured in neural differentiation medium. We found that the five substrates instructed neural progenitors followed by neuronal differentiation to differing degrees. Glia did not appear until 4 weeks later. Neural progenitor and neuronal generation and neurite outgrowth were significantly greater on laminin and laminin-rich Matrigel substrates than on other 3 substrates. Laminin stimulated hESC-derived neural progenitor expansion and neurite outgrowth in a dose-dependent manner. The laminin-induced neural progenitor expansion was partially blocked by the antibody against integrin α6 or β1 subunit. Conclusion We defined laminin as a key ECM molecule to enhance neural progenitor generation, expansion and differentiation into neurons from hESCs. The cell-laminin interactions involve α6β1 integrin receptors implicating a possible role of laminin/α6β1 integrin signaling in directed neural differentiation of hESCs. Since laminin acts in concert with other ECM molecules in vivo, evaluating cellular responses to the composition of the ECM is essential to clarify further the role of cell-matrix interactions in neural derivation of hESCs.

  6. Adult neural stem cell behavior underlying constitutive and restorative neurogenesis in zebrafish.

    Science.gov (United States)

    Barbosa, Joana S; Ninkovic, Jovica

    2016-01-01

    Adult Neural Stem Cells (aNSCs) generate new neurons that integrate into the pre-existing networks in specific locations of the Vertebrate brain. Moreover, aNSCs contribute with new neurons to brain regeneration in some non-mammalian Vertebrates. The similarities and the differences in the cellular and molecular processes governing neurogenesis in the intact and regenerating brain are still to be assessed. Toward this end, we recently established a protocol for non-invasive imaging of aNSC behavior in their niche in vivo in the adult intact and regenerating zebrafish telencephalon. We observed different modes of aNSC division in the intact brain and a novel mode of neurogenesis by direct conversion, which contributes to stem cell depletion with age. After injury, the generation of neurons is increased both by the activation of additional aNSCs and a shift in the division mode of aNSCs, thereby contributing to the successful neuronal regeneration. The cellular behavior we observed opens new questions regarding long-term aNSC maintenance in homeostasis and in regeneration. In this commentary we discuss our data and new questions arising in the context of aNSC behavior, not only in zebrafish but also in other species, including mammals. PMID:27606336

  7. Tissue-specific and neural activity-regulated expression of human BDNF gene in BAC transgenic mice

    Directory of Open Access Journals (Sweden)

    Palm Kaia

    2009-06-01

    Full Text Available Abstract Background Brain-derived neurotrophic factor (BDNF is a small secreted protein that has important roles in the developing and adult nervous system. Altered expression or changes in the regulation of the BDNF gene have been implicated in a variety of human nervous system disorders. Although regulation of the rodent BDNF gene has been extensively investigated, in vivo studies regarding the human BDNF gene are largely limited to postmortem analysis. Bacterial artificial chromosome (BAC transgenic mice harboring the human BDNF gene and its regulatory flanking sequences constitute a useful tool for studying human BDNF gene regulation and for identification of therapeutic compounds modulating BDNF expression. Results In this study we have generated and analyzed BAC transgenic mice carrying 168 kb of the human BDNF locus modified such that BDNF coding sequence was replaced with the sequence of a fusion protein consisting of N-terminal BDNF and the enhanced green fluorescent protein (EGFP. The human BDNF-BAC construct containing all BDNF 5' exons preceded by different promoters recapitulated the expression of endogenous BDNF mRNA in the brain and several non-neural tissues of transgenic mice. All different 5' exon-specific BDNF-EGFP alternative transcripts were expressed from the transgenic human BDNF-BAC construct, resembling the expression of endogenous BDNF. Furthermore, BDNF-EGFP mRNA was induced upon treatment with kainic acid in a promotor-specific manner, similarly to that of the endogenous mouse BDNF mRNA. Conclusion Genomic region covering 67 kb of human BDNF gene, 84 kb of upstream and 17 kb of downstream sequences is sufficient to drive tissue-specific and kainic acid-induced expression of the reporter gene in transgenic mice. The pattern of expression of the transgene is highly similar to BDNF gene expression in mouse and human. This is the first study to show that human BDNF gene is regulated by neural activity.

  8. Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors

    Science.gov (United States)

    Zhang, Yue; Xu, Chi; Zheng, Hui; Loh, Horace H.; Law, Ping-Yee

    2016-01-01

    The regulation of adult neurogenesis by opiates has been implicated in modulating different addiction cycles. At which neurogenesis stage opiates exert their action remains unresolved. We attempt to define the temporal window of morphine’s inhibition effect on adult neurogenesis by using the POMC-EGFP mouse model, in which newborn granular cells (GCs) can be visualized between days 3–28 post-mitotic. The POMC-EGFP mice were trained under the 3-chambers conditioned place preference (CPP) paradigm with either saline or morphine. We observed after 4 days of CPP training with saline, the number of EGFP-labeled newborn GCs in sub-granular zone (SGZ) hippocampus significantly increased compared to mice injected with saline in their homecage. CPP training with morphine significantly decreased the number of EGFP-labeled GCs, whereas no significant difference in the number of EGFP-labeled GCs was observed with the homecage mice injected with the same dose of morphine. Using cell-type selective markers, we observed that morphine reduced the number of late stage progenitors and immature neurons such as Doublecortin (DCX) and βIII Tubulin (TuJ1) positive cells in the SGZ but did not reduce the number of early progenitors such as Nestin, SOX2, or neurogenic differentiation-1 (NeuroD1) positive cells. Analysis of co-localization between different cell markers shows that morphine reduced the number of adult-born GCs by interfering with differentiation of early progenitors, but not by inducing apoptosis. In addition, when NeuroD1 was over-expressed in DG by stereotaxic injection of lentivirus, it rescued the loss of immature neurons and prolonged the extinction of morphine-trained CPP. These results suggest that under the condition of CPP training paradigm, morphine affects the transition of neural progenitor/stem cells to immature neurons via a mechanism involving NeuroD1. PMID:27078155

  9. Neural stem cells and the regulation of neurogenesis in the adult hippocampus

    OpenAIRE

    Seri, Bettina; Alvarez-Buylla, Arturo

    2002-01-01

    Neurogenesis continues in the hippocampal dentate gyrus of adult rodents and primates including humans. Neurons are born in the underlying subgranular layer (SGL) and move into the granule cell layer (GCL) to become mature granule neurons. Recent work indicates that the primary precursors for these new neurons correspond to radial astrocytes whose cell body is in the SGL and their processes traverse the GCL. These astrocytes divide to give rise to intermediate precursors, D cells that likely ...

  10. In our own image? Emotional and neural processing differences when observing human-human vs human-robot interactions.

    Science.gov (United States)

    Wang, Yin; Quadflieg, Susanne

    2015-11-01

    Notwithstanding the significant role that human-robot interactions (HRI) will play in the near future, limited research has explored the neural correlates of feeling eerie in response to social robots. To address this empirical lacuna, the current investigation examined brain activity using functional magnetic resonance imaging while a group of participants (n = 26) viewed a series of human-human interactions (HHI) and HRI. Although brain sites constituting the mentalizing network were found to respond to both types of interactions, systematic neural variation across sites signaled diverging social-cognitive strategies during HHI and HRI processing. Specifically, HHI elicited increased activity in the left temporal-parietal junction indicative of situation-specific mental state attributions, whereas HRI recruited the precuneus and the ventromedial prefrontal cortex (VMPFC) suggestive of script-based social reasoning. Activity in the VMPFC also tracked feelings of eeriness towards HRI in a parametric manner, revealing a potential neural correlate for a phenomenon known as the uncanny valley. By demonstrating how understanding social interactions depends on the kind of agents involved, this study highlights pivotal sub-routes of impression formation and identifies prominent challenges in the use of humanoid robots. PMID:25911418

  11. Neural Progenitor Cells Derived from Human Embryonic Stem Cells as an Origin of Dopaminergic Neurons

    Directory of Open Access Journals (Sweden)

    Parinya Noisa

    2015-01-01

    Full Text Available Human embryonic stem cells (hESCs are able to proliferate in vitro indefinitely without losing their ability to differentiate into multiple cell types upon exposure to appropriate signals. Particularly, the ability of hESCs to differentiate into neuronal subtypes is fundamental to develop cell-based therapies for several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. In this study, we differentiated hESCs to dopaminergic neurons via an intermediate stage, neural progenitor cells (NPCs. hESCs were induced to neural progenitor cells by Dorsomorphin, a small molecule that inhibits BMP signalling. The resulting neural progenitor cells exhibited neural bipolarity with high expression of neural progenitor genes and possessed multipotential differentiation ability. CBF1 and bFGF responsiveness of these hES-NP cells suggested their similarity to embryonic neural progenitor cells. A substantial number of dopaminergic neurons were derived from hES-NP cells upon supplementation of FGF8 and SHH, key dopaminergic neuron inducers. Importantly, multiple markers of midbrain neurons were detected, including NURR1, PITX3, and EN1, suggesting that hESC-derived dopaminergic neurons attained the midbrain identity. Altogether, this work underscored the generation of neural progenitor cells that retain the properties of embryonic neural progenitor cells. These cells will serve as an unlimited source for the derivation of dopaminergic neurons, which might be applicable for treating patients with Parkinson’s disease.

  12. Neural Differentiation of Human Umbilical Cord Mesenchymal Stem Cells by Cerebrospinal Fluid

    Directory of Open Access Journals (Sweden)

    Shirin FARIVAR*

    2015-01-01

    cerebrospinal fluid promotes the expression of Nestin, MAP2, and GFAP mRNA in a dose-dependent manner, especially at a concentration of 200 μl/ml. In summary, CSF induces neurogenesis of WJ stem cells that encourages tissue engineering applications with these cells for treatments of neurodegenerative defects and traumatic brain injury.References Gage, F. H. Mammalian neural stem cells. Science 2000 Feb 25;287(5457:1433-8.Da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all postnatal organs and tissues. J Cell Sci 2006 Jun 1;119(Pt 11:2204- 13. Epub 2006 May 9.Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells Science 1999 Apr 2;284(5411:143-7.Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003 Feb 15;75(3:389- 97.Le Blanc K. Immuno-modulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy 2003;5(6:485-9.Stenderup K, Justesen J, Clausen C, Kassem M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 2003 Dec;33(6:919-26.Bongso A, Fong CY, Gauthaman K. Taking stem cells to the clinic: major challenges. J Cell Biochem 2008 Dec 15;105(6:1352-60. doi: 10.1002/jcb.21957.Fong CY, Chak LL, Biswas A. Human Wharton’s jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev 2011 Mar;7(1:1-16. doi: 10.1007/s12015-010-9166-x.Troyer DL, Weiss ML. Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells 2008 Mar; 26(3:591-9. Epub 2007 Dec 6.Yuan X, Desiderio DM. Proteomics analysis of human cerebrospinal fluid. J Chromatogr B Analyt Technol Biomed Life Sci 2005 Feb 5;815(1-2:179-89.Thompson, EJ. Cerebrospinal

  13. Involvement of Aminopeptidase N (CD13) in Infection of Human Neural Cells by Human Coronavirus 229E

    OpenAIRE

    Lachance, Claude; Arbour, Nathalie; Cashman, Neil R.; Talbot, Pierre J

    1998-01-01

    Attachment to a cell surface receptor can be a major determinant of virus tropism. Previous studies have shown that human respiratory coronavirus HCV-229E uses human aminopeptidase N (hAPN [CD13]) as its cellular receptor for infection of lung fibroblasts. Although human coronaviruses are recognized respiratory pathogens, occasional reports have suggested their possible neurotropism. We have previously shown that human neural cells, including glial cells in primary cultures, are susceptible t...

  14. Differential neural activity patterns for spatial relations in humans: a MEG study.

    Science.gov (United States)

    Scott, Nicole M; Leuthold, Arthur; Sera, Maria D; Georgopoulos, Apostolos P

    2016-02-01

    Children learn the words for above-below relations earlier than for left-right relations, despite treating these equally well in a simple visual categorization task. Even as adults--conflicts in congruency, such as when a stimulus is depicted in a spatially incongruent manner with respect to salient global cues--can be challenging. Here we investigated the neural correlates of encoding and maintaining in working memory above-below and left-right relational planes in 12 adults using magnetoencephalography in order to discover whether above-below relations are represented by the brain differently than left-right relations. Adults performed perfectly on the task behaviorally, so any differences in neural activity were attributed to the stimuli's cognitive attributes. In comparing above-below to left-right relations during stimulus encoding, we found the greatest differences in neural activity in areas associated with space and movement. In comparing congruent to incongruent trials, we found the greatest differential activity in premotor areas. For both contrasts, brain areas involved in the encoding phase were also involved in the maintenance phase, which provides evidence that those brain areas are particularly important in representing the relational planes or congruency types throughout the trial. When comparing neural activity associated with the relational planes during working memory, additional right posterior areas were implicated, whereas the congruent-incongruent contrast implicated additional bilateral frontal and temporal areas. These findings are consistent with the hypothesis left-right relations are represented differently than above-below relations. PMID:26514809

  15. Neural population tuning links visual cortical anatomy to human visual perception.

    OpenAIRE

    Song, C.; Schwarzkopf, D.S.; Kanai, R; Rees, G

    2015-01-01

    Summary The anatomy of cerebral cortex is characterized by two genetically independent variables, cortical thickness and cortical surface area, that jointly determine cortical volume. It remains unclear how cortical anatomy might influence neural response properties and whether such influences would have behavioral consequences. Here, we report that thickness and surface area of human early visual cortices exert opposite influences on neural population tuning with behavioral consequences for ...

  16. Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology

    Directory of Open Access Journals (Sweden)

    Callihan Phillip

    2008-12-01

    Full Text Available Abstract Background Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development. Results Our results demonstrate that Lysophosphatidic Acid (LPA and Sphingosine-1-phosphate (S1P receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown that transcript levels for S1P1 receptor increased significantly in the transition from embryonic stem cell to hES-NEP. hES-NEP cells express LPA and S1P receptors coupled to Gi/o G-proteins that inhibit adenylyl cyclase and to Gq-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via Gi/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR- and ERK-dependent pathway. In contrast, LPA and S1P stimulate transient cell rounding and aggregation that is independent of EGFR and ERK, but dependent on the Rho effector p160 ROCK. Conclusion Thus, lysophospholipids regulate neural progenitor growth and morphology through distinct mechanisms. These findings establish human ES cell-derived NEP cells as a model system for studying the role of lysophospholipids in neural progenitors.

  17. Neural Markers of Responsiveness to the Environment in Human Sleep

    DEFF Research Database (Denmark)

    Andrillon, Thomas; Poulsen, Andreas Trier; Hansen, Lars Kai;

    2016-01-01

    Sleep is characterized by a loss of behavioral responsiveness. However, recent research has shown that the sleeping brain is not completely disconnected from its environment. How neural activity constrains the ability to process sensory information while asleep is yet unclear. Here, we instructed...

  18. Expression of the cystic fibrosis gene in adult human lung.

    OpenAIRE

    Engelhardt, J F; Zepeda, M; Cohn, J.A.; Yankaskas, J R; Wilson, J. M.

    1994-01-01

    Critical to an understanding of the pulmonary disease in cystic fibrosis (CF) and the development of effective gene therapies is a definition of the distribution and regulation of CF gene expression in adult human lung. Previous studies have detected the product of the CF gene, the CF transmembrane conductance regulator (CFTR), in submucosal glands of human bronchi. In this report, we have characterized the distribution of CFTR RNA and protein in the distal airway and alveoli of human lungs. ...

  19. Hemodynamic correlates of spontaneous neural activity measured by human whole-head resting state EEG+fNIRS.

    Science.gov (United States)

    Keles, Hasan Onur; Barbour, Randall L; Omurtag, Ahmet

    2016-09-01

    The brains of awake, resting human subjects display spontaneously occurring neural activity patterns whose magnitude is typically many times greater than those triggered by cognitive or perceptual performance. Evoked and resting state activations affect local cerebral hemodynamic properties through processes collectively referred to as neurovascular coupling. Its investigation calls for an ability to track both the neural and vascular aspects of brain function. We used scalp electroencephalography (EEG), which provided a measure of the electrical potentials generated by cortical postsynaptic currents. Simultaneously we utilized functional near-infrared spectroscopy (NIRS) to continuously monitor hemoglobin concentration changes in superficial cortical layers. The multi-modal signal from 18 healthy adult subjects allowed us to investigate the association of neural activity in a range of frequencies over the whole-head to local changes in hemoglobin concentrations. Our results verified the delayed alpha (8-16Hz) modulation of hemodynamics in posterior areas known from the literature. They also indicated strong beta (16-32Hz) modulation of hemodynamics. Analysis revealed, however, that beta modulation was likely generated by the alpha-beta coupling in EEG. Signals from the inferior electrode sites were dominated by scalp muscle related activity. Our study aimed to characterize the phenomena related to neurovascular coupling observable by practical, cost-effective, and non-invasive multi-modal techniques. PMID:27236081

  20. A BOLD perspective on age-related flow-metabolism coupling and neural efficiency changes in human visual cortex

    OpenAIRE

    JoannaLynnHutchison; HanzhangLu

    2013-01-01

    Age-related performance declines in visual tasks have been attributed to reductions in processing efficiency. The neural basis of these declines has been explored by comparing the blood-oxygen-level-dependent (BOLD) index of neural activity in older and younger adults during visual task performance. However, neural activity is one of many factors that change with age and lead to BOLD signal differences. We investigated the origin of age-related BOLD changes by comparing blood-flow and oxygen-...

  1. Exogenous testosterone enhances responsiveness to social threat in the neural circuitry of social aggression in humans.

    NARCIS (Netherlands)

    Hermans, E.J.; Ramsey, N.F.; Honk, J van

    2008-01-01

    BACKGROUND: In a range of species, the androgen steroid testosterone is known to potentiate neural circuits involved in intraspecific aggression. Disorders of impulsive aggression in humans have likewise been associated with high testosterone levels, but human evidence for the link between testoster

  2. Human neural stem cell-induced endothelial morphogenesis requires autocrine/paracrine and juxtacrine signaling

    Science.gov (United States)

    Chou, Chung-Hsing; Modo, Michel

    2016-01-01

    Transplanted neural stem cells (NSC) interact with the host brain microenvironment. A neovascularization is commonly observed in the vicinity of the cell deposit, which is correlated with behavioral improvements. To elucidate the signaling mechanisms between human NSCs and endothelial cells (ECs), these were cocultured in an in vitro model in which NSC-induced endothelial morphogenesis produced a neurovascular environment. Soluble (autocrine/paracrine) and contact–mediated (juxtacrine) signaling molecules were evaluated for two conditionally immortalized fetal NSC lines derived from the cortical anlage (CTXOE03) and ganglionic eminence (STROC05), as well as an adult EC line (D3) derived from the cerebral microvasculature of a hippocampal biopsy. STROC05 were 4 times as efficient to induce endothelial morphogenesis compared to CTXOE03. The cascade of reciprocal interactions between NSCs and ECs in this process was determined by quantifying soluble factors, receptor mapping, and immunocytochemistry for extracellular matrix molecules. The mechanistic significance of these was further evaluated by pharmacological blockade. The sequential cell-specific regulation of autocrine/paracrine and juxtacrine signaling accounted for the differential efficiency of NSCs to induce endothelial morphogenesis. These in vitro studies shed new light on the reciprocal interactions between NSCs and ECs, which are pivotal for our mechanistic understanding of the efficacy of NSC transplantation. PMID:27374240

  3. Human Neural Stem Cell Aging Is Counteracted by α-Glycerylphosphorylethanolamine.

    Science.gov (United States)

    Daniele, Simona; Da Pozzo, Eleonora; Iofrida, Caterina; Martini, Claudia

    2016-07-20

    Neural stem cells (NSCs) represent a subpopulation of cells, located in specific regions of the adult mammalian brain, with the ability of self-renewing and generating neurons and glia. In aged NSCs, modifications in the amount and composition of membrane proteins/lipids, which lead to a reduction in membrane fluidity and cholinergic activities, have been reported. In this respect, molecules that are effective at normalizing the membrane composition and cholinergic signaling could counteract stem cell aging. α-Glycerylphosphorylethanolamine (GPE), a nootropic drug, plays a role in phospholipid biosynthesis and acetylcholine release. Herein, GPE was assayed on human NSC cultures and on hydroxyurea-aged cells. Using cell counting, colorimetric, and fluorimetric analyses, immunoenzymatic assays, and real time PCR experiments, NSC culture proliferation, senescence, reactive oxygen species, and ADP/ATP levels were assessed. Aged NSCs exhibited cellular senescence, decreased proliferation, and an impairment in mitochondrial metabolism. These changes included a substantial induction in the nuclear factor NF-κB, a key inflammatory mediator. GPE cell treatment significantly protected the redox state and functional integrity of mitochondria, and counteracted senescence and NF-κB activation. In conclusion, our data show the beneficial properties of GPE in this model of stem cell aging. PMID:27168476

  4. Review on Adult Neurogenesis in Humans and Other Mammals

    OpenAIRE

    Tesfamichael Berhe

    2015-01-01

    Research in the field of adult neurogenesis has recently indicated significant progress.The objective of this paper is to review the basic concepts, new findings and clinical implications of neurogenesis making emphasis on the significance, especially in humans. Although scientists still debate the extent and purpose of neurogenesis in the adult brain, research has identified certain areas of the brain where it is most evident. These areas include the hippocampus, caudate nucleus, and olfacto...

  5. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function.

    Science.gov (United States)

    Garza-Lombó, Carla; Gonsebatt, María E

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  6. Single-Trial Analysis of Neuroimaging Data: Inferring Neural Networks Underlying Perceptual Decision-Making in the Human Brain

    OpenAIRE

    Sajda, Paul; Philiastides, Marios G.; Parra, Lucas C.

    2009-01-01

    Advances in neural signal and image acquisition as well as in multivariate signal processing and machine learning are enabling a richer and more rigorous understanding of the neural basis of human decision-making. Decision-making is essentially characterized behaviorally by the variability of the decision across individual trials—e.g., error and response time distributions. To infer the neural processes that govern decision-making requires identifying neural correlates of such trial-to-trial ...

  7. Induction of Neural Progenitor-Like Cells from Human Fibroblasts via a Genetic Material-Free Approach.

    Directory of Open Access Journals (Sweden)

    Fahimeh Mirakhori

    Full Text Available A number of studies generated induced neural progenitor cells (iNPCs from human fibroblasts by viral delivering defined transcription factors. However, the potential risks associated with gene delivery systems have limited their clinical use. We propose it would be safer to induce neural progenitor-like cells from human adult fibroblasts via a direct non-genetic alternative approach.Here, we have reported that seven rounds of TAT-SOX2 protein transduction in a defined chemical cocktail under a 3D sphere culture gradually morphed fibroblasts into neuroepithelial-like colonies. We were able to expand these cells for up to 20 passages. These cells could give rise to cells that expressed neurons and glia cell markers both in vitro and in vivo.These results show that our approach is beneficial for the genetic material-free generation of iNPCs from human fibroblasts where small chemical molecules can provide a valuable, viable strategy to boost and improve induction in a 3D sphere culture.

  8. In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow.

    Directory of Open Access Journals (Sweden)

    Sabine Wislet-Gendebien

    Full Text Available Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC as mixed populations of cells including mesenchymal (MSC and neural crest stem cells (NCSC. Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application.

  9. In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow.

    Science.gov (United States)

    Wislet-Gendebien, Sabine; Poulet, Christophe; Neirinckx, Virginie; Hennuy, Benoit; Swingland, James T; Laudet, Emerence; Sommer, Lukas; Shakova, Olga; Bours, Vincent; Rogister, Bernard

    2012-01-01

    Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q) compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application. PMID:23071568

  10. PI3K mediated electrotaxis of embryonic and adult neural progenitor cells in the presence of growth factors

    OpenAIRE

    Meng, Xiaoting; Arocena, Miguel; Penninger, Josef; Gage, Fred H.; Zhao, Min; Song, Bing

    2010-01-01

    Correct guidance of the migration of neural progenitor cells (NPCs) is essential for the development and repair of the central nervous system (CNS). Electric field (EF)-guided migration, electrotaxis, has been observed in many cell types. We report here that, in applied EFs of physiological magnitude, embryonic and adult NPCs show marked electrotaxis, which is dependent on the PI3K/Akt pathway. The electrotaxis was also evidenced by ex vivo investigation that transplanted NPCs migrated direct...

  11. PPARβ/δ and PPARγ maintain undifferentiated phenotypes of mouse adult neural precursor cells from the subventricular zone.

    Science.gov (United States)

    Bernal, Carolina; Araya, Claudia; Palma, Verónica; Bronfman, Miguel

    2015-01-01

    The subventricular zone (SVZ) is one of the main niches of neural stem cells in the adult mammalian brain. Stem and precursor cells in this region are the source for neurogenesis and oligodendrogesis, mainly in the olfactory bulb and corpus callosum, respectively. The identification of the molecular components regulating the decision of these cells to differentiate or maintain an undifferentiated state is important in order to understand the modulation of neurogenic processes in physiological and pathological conditions. PPARs are a group of transcription factors, activated by lipid ligands, with important functions in cellular differentiation and proliferation in several tissues. In this work, we demonstrate that mouse adult neural precursor cells (NPCs), in situ and in vitro, express PPARβ/δ and PPARγ. Pharmacological activation of both PPARs isoforms induces proliferation and maintenance of the undifferentiated phenotype. Congruently, inhibition of PPARβ/δ and PPARγ results in a decrease of proliferation and loss of the undifferentiated phenotype. Interestingly, PPARγ regulates the level of EGFR in adult NPCs, concurrent with it is function described in embryonic NPCs. Furthermore, we describe for the first time that PPARβ/δ regulates SOX2 level in adult NPCs, probably through a direct transcriptional regulation, as we identified two putative PPAR response elements in the promoter region of Sox2. EGFR and SOX2 are key players in neural stem/precursor cells self-renewal. Finally, rosiglitazone, a PPARγ ligand, increases PPARβ/δ level, suggesting a possible cooperation between these two PPARs in the control of cell fate behavior. Our work contributes to the understanding of the molecular mechanisms associated to neural cell fate decision and places PPARβ/δ and PPARγ as interesting new targets of modulation of mammalian brain homeostasis. PMID:25852474

  12. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kyoung Ho [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Yeo, Sang Won, E-mail: swyeo@catholic.ac.kr [Department of Otolaryngology Head and Neck Surgery, College of Medicine, Catholic University, Seoul (Korea, Republic of); Troy, Frederic A., E-mail: fatroy@ucdavis.edu [Department of Biochemistry and Molecular Medicine, University of California, School of Medicine, Davis, CA 95616 (United States); Xiamen University, School of Medicine, Xiamen City (China)

    2014-10-17

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.

  13. In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow

    OpenAIRE

    Sabine Wislet-Gendebien; Christophe Poulet; Virginie Neirinckx; Benoit Hennuy; Swingland, James T.; Emerence Laudet; Lukas Sommer; Olga Shakova; Vincent Bours; Bernard Rogister

    2012-01-01

    Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the ...

  14. Mechanisms Underlying the Antiproliferative and Prodifferentiative Effects of Psoralen on Adult Neural Stem Cells via DNA Microarray

    OpenAIRE

    Zi-Yin Shen; Jing-Cheng Dong; Xin-Min Zhang; Yang Chen; Qin Bian; Shi-Jin Xia; Jian-Hua Huang; You Ning

    2013-01-01

    Adult neural stem cells (NSCs) persist throughout life to replace mature cells that are lost during turnover, disease, or injury. The investigation of NSC creates novel treatments for central nervous system (CNS) injuries and neurodegenerative disorders. The plasticity and reparative potential of NSC are regulated by different factors, which are critical for neurological regenerative medicine research. We investigated the effects of Psoralen, which is the mature fruit of Psoralea corylifolia ...

  15. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    International Nuclear Information System (INIS)

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC with epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders

  16. Adult human metapneumonovirus (hMPV) pneumonia mimicking Legionnaire's disease.

    Science.gov (United States)

    Cunha, Burke A; Irshad, Nadia; Connolly, James J

    2016-01-01

    In adults hospitalized with viral pneumonias the main differential diagnostic consideration is influenza pneumonia. The respiratory viruses causing viral influenza like illnesses (ILIs), e.g., RSV may closely resemble influenza. Rarely, extrapulmonary findings of some ILIs may resemble Legionnaire's disease (LD), e.g., adenovirus, human parainfluenza virus (HPIV-3). We present a most unusual case of human metapneumonovirus pneumonia (hMPV) with some characteristic extrapulmonary findings characteristic of LD, e.g., relative bradycardia, as well as mildly elevated serum transaminases and hyphosphatemia. We believe this is the first reported case of hMPV pneumonia in a hospitalized adult that had some features of LD. PMID:26988110

  17. In vitro characterization of a human neural progenitor cell coexpressing SSEA4 and CD133

    DEFF Research Database (Denmark)

    Barraud, Perrine; Stott, Simon; Møllgård, Kjeld;

    2007-01-01

    decreases as development proceeds. Flow cytometry analysis of forebrain-derived cells demonstrated that the SSEA4-expressing cells are enriched in the neural stem/progenitor cell fraction (CD133(+)), but are rarely codetected with the neural stem cell (NSC) marker CD15. Using a sphere-forming assay, we......The stage-specific embryonic antigen 4 (SSEA4) is commonly used as a cell surface marker to identify the pluripotent human embryonic stem (ES) cells. Immunohistochemistry on human embryonic central nervous system revealed that SSEA4 is detectable in the early neuroepithelium, and its expression....... Therefore, we propose that SSEA4 associated with CD133 can be used for both the positive selection and the enrichment of neural stem/progenitor cells from human embryonic forebrain....

  18. Proteomics Applied to Porcine and Human Neural Stem Cell Differentiation

    Czech Academy of Sciences Publication Activity Database

    Mairychová, Kateřina; Skalníková, Helena; Tylečková, Jiřina; Halada, Petr; Marsala, M.; Kovářová, Hana

    Liběchov : Institute of Animal Physiology and Genetics AS CR, v.v.i, 2010. s. 61-61. [Informal Proteomic Meeting 2010. 09.11.2010-10.11.2010, Liblice] R&D Projects: GA MŠk 1M0538; GA MŠk(CZ) ME10044 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : proteomics * cell differentiation * neural stem cell s Subject RIV: FH - Neurology

  19. Flexible neural mechanisms of cognitive control within human prefrontal cortex

    OpenAIRE

    Braver, Todd S.; Paxton, Jessica L.; Locke, Hannah S.; Barch, Deanna M

    2009-01-01

    A major challenge in research on executive control is to reveal its functional decomposition into underlying neural mechanisms. A typical assumption is that this decomposition occurs solely through anatomically based dissociations. Here we tested an alternative hypothesis that different cognitive control processes may be implemented within the same brain regions, with fractionation and dissociation occurring on the basis of temporal dynamics. Regions within lateral prefrontal cortex (PFC) wer...

  20. The weight of nations: an estimation of adult human biomass

    Directory of Open Access Journals (Sweden)

    Walpole Sarah

    2012-06-01

    Full Text Available Abstract Background The energy requirement of species at each trophic level in an ecological pyramid is a function of the number of organisms and their average mass. Regarding human populations, although considerable attention is given to estimating the number of people, much less is given to estimating average mass, despite evidence that average body mass is increasing. We estimate global human biomass, its distribution by region and the proportion of biomass due to overweight and obesity. Methods For each country we used data on body mass index (BMI and height distribution to estimate average adult body mass. We calculated total biomass as the product of population size and average body mass. We estimated the percentage of the population that is overweight (BMI > 25 and obese (BMI > 30 and the biomass due to overweight and obesity. Results In 2005, global adult human biomass was approximately 287 million tonnes, of which 15 million tonnes were due to overweight (BMI > 25, a mass equivalent to that of 242 million people of average body mass (5% of global human biomass. Biomass due to obesity was 3.5 million tonnes, the mass equivalent of 56 million people of average body mass (1.2% of human biomass. North America has 6% of the world population but 34% of biomass due to obesity. Asia has 61% of the world population but 13% of biomass due to obesity. One tonne of human biomass corresponds to approximately 12 adults in North America and 17 adults in Asia. If all countries had the BMI distribution of the USA, the increase in human biomass of 58 million tonnes would be equivalent in mass to an extra 935 million people of average body mass, and have energy requirements equivalent to that of 473 million adults. Conclusions Increasing population fatness could have the same implications for world food energy demands as an extra half a billion people living on the earth.

  1. PRELIMINARY MODELING OF AN INDUSTRIAL RECOMBINANT HUMAN ERYTHROPOIETIN PURIFICATION PROCESS BY ARTIFICIAL NEURAL NETWORKS

    Directory of Open Access Journals (Sweden)

    R. H. R. Garcel1

    2015-09-01

    Full Text Available AbstractIn the present study a preliminary neural network modelling to improve our understanding of Recombinant Human Erythropoietin purification process in a plant was explored. A three layer feed-forward back propagation neural network was constructed for predicting the efficiency of the purification section comprising four chromatographic steps as a function of eleven operational variables. The neural network model performed very well in the training and validation phases. Using the connection weight method the predictor variables were ranked based on their estimated explanatory importance in the neural network and five input variables were found to be predominant over the others. These results provided useful information showing that the first chromatographic step and the third chromatographic step are decisive to achieve high efficiencies in the purification section, thus enriching the control strategy of the plant.

  2. Fusing human knowledge with neural networks in machine condition monitoring systems

    Science.gov (United States)

    Melvin, David G.; Penman, J.

    1995-04-01

    There is currently much interest in the application of artificial neural network (ANN) technology to the field of on-line machine condition monitoring (CM) for complex electro- mechanical systems. In this paper the authors discuss, with the help of an industrial case study, a few of the difficulties inherent in the application of neural network based condition monitoring. A method of overcoming these difficulties by utilizing a combination of human knowledge, encoded using techniques borrowed from fuzzy logic, Kohonen neural networks, and statistical K-means clustering has been constructed. The methodology is discussed in the paper by means of a direct comparison between this new approach and a purely neural approach. An analysis of other situations where this approach would be applicable is also presented and the paper discusses other current research work in the area of hybrid AI technologies which should assist further with the alleviation of the problems under consideration.

  3. Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (PhosphoProteomic Profiling

    Directory of Open Access Journals (Sweden)

    Ilyas Singec

    2016-09-01

    Full Text Available Controlled differentiation of human embryonic stem cells (hESCs can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs. This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families, phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt.

  4. Prion replication occurs in endogenous adult neural stem cells and alters their neuronal fate: involvement of endogenous neural stem cells in prion diseases.

    Directory of Open Access Journals (Sweden)

    Aroa Relaño-Ginès

    Full Text Available Prion diseases are irreversible progressive neurodegenerative diseases, leading to severe incapacity and death. They are characterized in the brain by prion amyloid deposits, vacuolisation, astrocytosis, neuronal degeneration, and by cognitive, behavioural and physical impairments. There is no treatment for these disorders and stem cell therapy therefore represents an interesting new approach. Gains could not only result from the cell transplantation, but also from the stimulation of endogenous neural stem cells (NSC or by the combination of both approaches. However, the development of such strategies requires a detailed knowledge of the pathology, particularly concerning the status of the adult neurogenesis and endogenous NSC during the development of the disease. During the past decade, several studies have consistently shown that NSC reside in the adult mammalian central nervous system (CNS and that adult neurogenesis occurs throughout the adulthood in the subventricular zone of the lateral ventricle or the Dentate Gyrus of the hippocampus. Adult NSC are believed to constitute a reservoir for neuronal replacement during normal cell turnover or after brain injury. However, the activation of this system does not fully compensate the neuronal loss that occurs during neurodegenerative diseases and could even contribute to the disease progression. We investigated here the status of these cells during the development of prion disorders. We were able to show that NSC accumulate and replicate prions. Importantly, this resulted in the alteration of their neuronal fate which then represents a new pathologic event that might underlie the rapid progression of the disease.

  5. Classification of Human Emotions from EEG Signals using Statistical Features and Neural Network

    OpenAIRE

    Chai Tong Yuen; Woo San San; Tan Ching Seong; Mohamed Rizon

    2009-01-01

    A statistical based system for human emotions classification by using electroencephalogram (EEG) is proposed in this paper. The data used in this study is acquired using EEG and the emotions are elicited from six human subjects under the effect of emotion stimuli. This paper also proposed an emotion stimulation experiment using visual stimuli. From the EEG data, a total of six statistical features are computed and back-propagation neural network is applied for the classification of human emot...

  6. Two adult human voxel phantoms based on polygon mesh surfaces

    International Nuclear Information System (INIS)

    Among computational models used in radiation protection, voxel phantoms based on computer tomographic (CT), nuclear magnetic resonance (NMR) or colour photographic images, became very popular in recent years. Although being a true to nature representation of the scanned individual the scanning is usually made in supine position, which causes a shift of internal organs towards the ribcage, a compression of the lungs and a reduction of the sagittal diameter especially in the abdominal region compared to the anatomy of a person in upright standing position, which in turn can influence absorbed or equivalent dose estimates. This study proposes a method for human phantom design using tools recently developed in the areas of computer graphics and animated films and applies them to the creation and modeling of artificial 3D human organs and tissues. Two models, a male and a female adult human phantom have been developed based on anatomical atlases, observing at the same time the anatomical specifications published by the International Commission on Radiological Protection for the male and female reference adult. The phantoms are called FAXAA (Female Adult voXelAverage-Average) and MAXAA (Male Adult voXelAverage-Average) because they represent female and male adults with average weight and average height. (author)

  7. Naïve adult stem cells isolation from primary human fibroblast cultures.

    Science.gov (United States)

    Wenzel, Vera; Roedl, Daniela; Ring, Johannes; Djabali, Karima

    2013-01-01

    Over the last decade, several adult stem cell populations have been identified in human skin (1-4). The isolation of multipotent adult dermal precursors was first reported by Miller F. D laboratory (5, 6). These early studies described a multipotent precursor cell population from adult mammalian dermis (5). These cells--termed SKPs, for skin-derived precursors-- were isolated and expanded from rodent and human skin and differentiated into both neural and mesodermal progeny, including cell types never found in skin, such as neurons (5). Immunocytochemical studies on cultured SKPs revealed that cells expressed vimentin and nestin, an intermediate filament protein expressed in neural and skeletal muscle precursors, in addition to fibronectin and multipotent stem cell markers (6). Until now, the adult stem cells population SKPs have been isolated from freshly collected mammalian skin biopsies. Recently, we have established and reported that a population of skin derived precursor cells could remain present in primary fibroblast cultures established from skin biopsies (7). The assumption that a few somatic stem cells might reside in primary fibroblast cultures at early population doublings was based upon the following observations: (1) SKPs and primary fibroblast cultures are derived from the dermis, and therefore a small number of SKP cells could remain present in primary dermal fibroblast cultures and (2) primary fibroblast cultures grown from frozen aliquots that have been subjected to unfavorable temperature during storage or transfer contained a small number of cells that remained viable (7). These rare cells were able to expand and could be passaged several times. This observation suggested that a small number of cells with high proliferation potency and resistance to stress were present in human fibroblast cultures (7). We took advantage of these findings to establish a protocol for rapid isolation of adult stem cells from primary fibroblast cultures that are

  8. Subcellular distribution of N-methyl-D-aspartic acid receptor subunit 1 in neural stem cells within subventricular zone of adult rats

    Institute of Scientific and Technical Information of China (English)

    Zhining Li; Wenlong Lü; Hongyan Dong; Hongbin Fan; Ruiguo Dong; Tiejun Xu

    2011-01-01

    The subcellular localization of N-methyl-D-aspartic acid receptor subunit 1 in neural stem cells of the subventricular zone of adult rats was detected using electron microscopy, following immunohistochemistry and immunogold-silver double staining. Results confirmed the presence of neural stem cells in the subventricular zone, which is a key neurogenic region in the central nervous system of adult mammals. The expression of N-methyl-D-aspartic acid receptor subunit 1 was higher than that of nestin and mainly distributed in the cell membrane, cytoplasm, rough endoplasmic reticulum and Golgi complex of neural stem cells.

  9. Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor

    Directory of Open Access Journals (Sweden)

    Ebrahim Shahbazi

    2016-04-01

    Full Text Available Direct conversion of somatic cells into neural stem cells (NSCs by defined factors holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases. Here, we report that a single zinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent NSCs. In vitro, Zfp521-induced NSCs maintained their characteristics in the absence of exogenous factor expression and exhibited morphological, molecular, developmental, and functional properties that were similar to control NSCs. In addition, the single-seeded induced NSCs were able to form NSC colonies with efficiency comparable with control NSCs and expressed NSC markers. The converted cells were capable of surviving, migrating, and attaining neural phenotypes after transplantation into neonatal mouse and adult rat brains, without forming tumors. Moreover, the Zfp521-induced NSCs predominantly expressed rostral genes. Our results suggest a facilitated approach for establishing human NSCs through Zfp521-driven conversion of fibroblasts.

  10. An anatomically comprehensive atlas of the adult human brain transcriptome

    NARCIS (Netherlands)

    Hawrylycz, M.J.; Beckmann, C.F.; et al., et al.

    2012-01-01

    Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising

  11. The Reference Ability Neural Network Study: Life-time stability of reference-ability neural networks derived from task maps of young adults.

    Science.gov (United States)

    Habeck, C; Gazes, Y; Razlighi, Q; Steffener, J; Brickman, A; Barulli, D; Salthouse, T; Stern, Y

    2016-01-15

    Analyses of large test batteries administered to individuals ranging from young to old have consistently yielded a set of latent variables representing reference abilities (RAs) that capture the majority of the variance in age-related cognitive change: Episodic Memory, Fluid Reasoning, Perceptual Processing Speed, and Vocabulary. In a previous paper (Stern et al., 2014), we introduced the Reference Ability Neural Network Study, which administers 12 cognitive neuroimaging tasks (3 for each RA) to healthy adults age 20-80 in order to derive unique neural networks underlying these 4 RAs and investigate how these networks may be affected by aging. We used a multivariate approach, linear indicator regression, to derive a unique covariance pattern or Reference Ability Neural Network (RANN) for each of the 4 RAs. The RANNs were derived from the neural task data of 64 younger adults of age 30 and below. We then prospectively applied the RANNs to fMRI data from the remaining sample of 227 adults of age 31 and above in order to classify each subject-task map into one of the 4 possible reference domains. Overall classification accuracy across subjects in the sample age 31 and above was 0.80±0.18. Classification accuracy by RA domain was also good, but variable; memory: 0.72±0.32; reasoning: 0.75±0.35; speed: 0.79±0.31; vocabulary: 0.94±0.16. Classification accuracy was not associated with cross-sectional age, suggesting that these networks, and their specificity to the respective reference domain, might remain intact throughout the age range. Higher mean brain volume was correlated with increased overall classification accuracy; better overall performance on the tasks in the scanner was also associated with classification accuracy. For the RANN network scores, we observed for each RANN that a higher score was associated with a higher corresponding classification accuracy for that reference ability. Despite the absence of behavioral performance information in the

  12. Generation and properties of a new human ventral mesencephalic neural stem cell line

    DEFF Research Database (Denmark)

    Villa, Ana; Liste, Isabel; Courtois, Elise T;

    2009-01-01

    . Here we report the generation of a new stable cell line of human neural stem cells derived from ventral mesencephalon (hVM1) based on v-myc immortalization. The cells expressed neural stem cell and radial glia markers like nestin, vimentin and 3CB2 under proliferation conditions. After withdrawal of......Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to cell therapy in neurodegenerative diseases like Parkinson's disease. Several epigenetic and genetic strategies have been tested for long-term maintenance and expansion of these cells in vitro...... derivatives may constitute good candidates for the study of development and physiology of human dopaminergic neurons in vitro, and to develop tools for Parkinson's disease cell replacement preclinical research and drug testing....

  13. Pituitary Adenlylate Cyclase Activating Peptide Protects Adult Neural Stem Cells from a Hypoglycaemic milieu.

    Science.gov (United States)

    Mansouri, Shiva; Lietzau, Grazyna; Lundberg, Mathias; Nathanson, David; Nyström, Thomas; Patrone, Cesare

    2016-01-01

    Hypoglycaemia is a common side-effect of glucose-lowering therapies for type-2 diabetic patients, which may cause cognitive/neurological impairment. Although the effects of hypoglycaemia in the brain have been extensively studied in neurons, how hypoglycaemia impacts the viability of adult neural stem cells (NSCs) has been poorly investigated. In addition, the cellular and molecular mechanisms of how hypoglycaemia regulates NSCs survival have not been characterized. Recent work others and us have shown that the pituitary adenylate cyclase-activating polypeptide (PACAP) and the glucagon-like peptide-1 receptor (GLP-1R) agonist Exendin-4 stimulate NSCs survival against glucolipoapoptosis. The aim of this study was to establish an in vitro system where to study the effects of hypoglycaemia on NSC survival. Furthermore, we determine the potential role of PACAP and Exendin-4 in counteracting the effect of hypoglycaemia. A hypoglycaemic in vitro milieu was mimicked by exposing subventricular zone-derived NSC to low levels of glucose. Moreover, we studied the potential involvement of apoptosis and endoplasmic reticulum stress by quantifying protein levels of Bcl-2, cleaved caspase-3 and mRNA levels of CHOP. We show that PACAP via PAC-1 receptor and PKA activation counteracts impaired NSC viability induced by hypoglycaemia. The protective effect induced by PACAP correlated with endoplasmic reticulum stress, Exendin-4 was ineffective. The results show that hypoglycaemia decreases NSC viability and that this effect can be substantially counteracted by PACAP via PAC-1 receptor activation. The data supports a potential therapeutic role of PAC-1 receptor agonists for the treatment of neurological complications, based on neurogenesis impairment by hypoglycaemia. PMID:27305000

  14. In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation.

    Science.gov (United States)

    Barazzuol, Lara; Jeggo, Penny A

    2016-08-01

    The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5-14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C) ), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4(Y288C) embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4(Y288C) mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis. PMID:27125639

  15. Telocytes of the human adult trigeminal ganglion.

    Science.gov (United States)

    Rusu, Mugurel Constantin; Cretoiu, Dragos; Vrapciu, Alexandra Diana; Hostiuc, Sorin; Dermengiu, Dan; Manoiu, Vasile Sorin; Cretoiu, Sanda Maria; Mirancea, Nicolae

    2016-06-01

    Telocytes (TCs) are typically defined as cells with telopodes by their ultrastructural features. Their presence was reported in various organs, however little is known about their presence in human trigeminal ganglion. To address this issue, samples of trigeminal ganglia were tested by immunocytochemistry for CD34 and examined by transmission electron microscopy (TEM). We found that TCs are CD34 positive and form networks within the ganglion in close vicinity to microvessels and nerve fibers around the neuronal-glial units (NGUs). TEM examination confirmed the existence of spindle-shaped and bipolar TCs with one or two telopodes measuring between 15 to 53 μm. We propose that TCs are cells with stemness capacity which might contribute in regeneration and repair processes by: modulation of the stem cell activity or by acting as progenitors of other cells present in the normal tissue. In addition, further studies are needed to establish if they might influence the neuronal circuits. PMID:27147447

  16. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R., E-mail: mundy.william@epa.gov

    2011-11-15

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  17. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    International Nuclear Information System (INIS)

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  18. Predicting healthy older adult's brain age based on structural connectivity networks using artificial neural networks.

    Science.gov (United States)

    Lin, Lan; Jin, Cong; Fu, Zhenrong; Zhang, Baiwen; Bin, Guangyu; Wu, Shuicai

    2016-03-01

    Brain ageing is followed by changes of the connectivity of white matter (WM) and changes of the grey matter (GM) concentration. Neurodegenerative disease is more vulnerable to an accelerated brain ageing, which is associated with prospective cognitive decline and disease severity. Accurate detection of accelerated ageing based on brain network analysis has a great potential for early interventions designed to hinder atypical brain changes. To capture the brain ageing, we proposed a novel computational approach for modeling the 112 normal older subjects (aged 50-79 years) brain age by connectivity analyses of networks of the brain. Our proposed method applied principal component analysis (PCA) to reduce the redundancy in network topological parameters. Back propagation artificial neural network (BPANN) improved by hybrid genetic algorithm (GA) and Levenberg-Marquardt (LM) algorithm is established to model the relation among principal components (PCs) and brain age. The predicted brain age is strongly correlated with chronological age (r=0.8). The model has mean absolute error (MAE) of 4.29 years. Therefore, we believe the method can provide a possible way to quantitatively describe the typical and atypical network organization of human brain and serve as a biomarker for presymptomatic detection of neurodegenerative diseases in the future. PMID:26718834

  19. Neural mechanisms of the observation of human and non-human object touch in children: An event-related potential study.

    Science.gov (United States)

    Galilee, Alena; McCleery, Joseph P

    2016-03-01

    Previous behavioural research on the development of self-other tactile processing and perception suggests that this system may develop in a somewhat protracted manner relative to other aspects of social development. Neuroimaging research has shown that somatosensory mechanisms are activated when adults observe another person or object being touched. In this study, we measured event-related potentials from 4- to 5-year-old children to investigate the development of the neural correlates of the observation of human and object touch. Participants were presented with video clips of an arm or a cylindrical object being touched. Touch versus non-touch effects were observed in the amplitudes of the LSW component (600-700 ms) measured from electrodes over somatosensory region. Additionally, human versus non-human stimulus effects were reflected in the amplitudes of the parietal-central N100 component, as well as in the latencies of the N170 component recorded from parietal-occipital electrodes in children, as in adults in a previous study using this same paradigm. These findings provide evidence that relatively mature tactile mirroring mechanisms are activated during the observation of touch in children, and further suggest the possibility that these mechanisms are not particularly slow in their development relative to other aspects of social cognition. PMID:26659431

  20. The evidence for increased L1 activity in the site of human adult brain neurogenesis.

    Directory of Open Access Journals (Sweden)

    Alexey A Kurnosov

    Full Text Available Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus-the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.

  1. Differentiation of adult human bone marrow mesenchymal stem cells into Schwann-like cells in vitro

    Institute of Scientific and Technical Information of China (English)

    YANG Li-ye; ZHENG Jia-kun; WANG Chao-yang; LI Wen-yu

    2005-01-01

    Objective: To investigate the differentiative capability of adult human bone marrow mesenchymal stem cells (BMSCs) into Schwann-like cells. Methods: Bone marrows were aspirated from healthy donors and mononuclear cells were separated by Percoll lymphocytes separation liquid (1.073 g/ml) with centrifugation, cells were cultured in DMEM/F12 (1:1) medium containing 10% fetal bovine serum (FBS), 20 ng/ml epidermal growth factor (EGF) and 20 ng/ml basic fibroblast growth factor (bFGF). Cells of passage 1 were identified with immunocytochemistry. Conclusions: Bone marrow contains the stem cells with the ability of differentiating into Schwann-like cells, which may represent an alternative stem cell sources for neural transplantation.

  2. Stem Cell Bioprinting: Functional 3D Neural Mini-Tissues from Printed Gel-Based Bioink and Human Neural Stem Cells (Adv. Healthcare Mater. 12/2016).

    Science.gov (United States)

    Gu, Qi; Tomaskovic-Crook, Eva; Lozano, Rodrigo; Chen, Yu; Kapsa, Robert M; Zhou, Qi; Wallace, Gordon G; Crook, Jeremy M

    2016-06-01

    On page 1429 G. G. Wallace, J. M. Crook, and co-workers report the first example of fabricating neural tissue by 3D bioprinting human neural stem cells. A novel polysaccharide based bioink preserves stem cell viability and function within the printed construct, enabling self-renewal and differentiation to neurons and supporting neuroglia. Neurons are predominantly GABAergic, establish networks, are spontaneously active, and show a bicuculline induced increased calcium response. PMID:27333401

  3. Human Embryonic Stem Cells: A Model for the Study of Neural Development and Neurological Diseases

    OpenAIRE

    Piya Prajumwongs; Oratai Weeranantanapan; Thiranut Jaroonwitchawan; Parinya Noisa

    2016-01-01

    Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs) recapitulated those in the early embryo development in vivo at certain degree. This underscores the usefulness of hESCs in unders...

  4. Structured Prediction of 3D Human Pose with Deep Neural Networks

    OpenAIRE

    Tekin, Bugra; Katircioglu, Isinsu; Salzmann, Mathieu; Lepetit, Vincent; Fua, Pascal

    2016-01-01

    Most recent approaches to monocular 3D pose estimation rely on Deep Learning. They either train a Convolutional Neural Network to directly regress from image to 3D pose, which ignores the dependencies between human joints, or model these dependencies via a max-margin structured learning framework, which involves a high computational cost at inference time. In this paper, we introduce a Deep Learning regression architecture for structured prediction of 3D human pose from monocular images that ...

  5. Neural-Induced Human Mesenchymal Stem Cells Promote Cochlear Cell Regeneration in Deaf Guinea Pigs

    OpenAIRE

    Jang, Sujeong; Cho, Hyong-Ho; Kim, Song-Hee; Lee, Kyung-Hwa; Jun, Jae Yeoul; Park, Jong-Seong; Jeong, Han-Seong; Cho, Yong-Beom

    2015-01-01

    Objectives In mammals, cochlear hair cell loss is irreversible and may result in a permanent sensorineural hearing loss. Secondary to this hair cell loss, a progressive loss of spiral ganglion neurons (SGNs) is presented. In this study, we have investigated the effects of neural-induced human mesenchymal stem cells (NI-hMSCs) from human bone marrow on sensory neuronal regeneration from neomycin treated deafened guinea pig cochleae. Methods HMSCs were isolated from the bone marrow which was ob...

  6. Cytoarchitecture and Ultrastructure of Neural Stem Cell Niches and Neurogenic Complexes Maintaining Adult Neurogenesis in the Olfactory Midbrain of Spiny Lobsters, Panulirus argus

    OpenAIRE

    Schmidt, Manfred; Derby, Charles D.

    2011-01-01

    New interneurons are continuously generated in small proliferation zones within neuronal somata clusters in the olfactory deutocerebrum of adult decapod crustaceans. Each proliferation zone is connected to a clump of cells containing one neural stem cell (i.e., adult neuroblast), thus forming a “neurogenic complex.” Here we provide a detailed analysis of the cytoarchitecture of neurogenic complexes in adult spiny lobsters, Panulirus argus, based on transmission electron microscopy and labelin...

  7. Contour junctions underlie neural representations of scene categories in high-level human visual cortex.

    Science.gov (United States)

    Choo, Heeyoung; Walther, Dirk B

    2016-07-15

    Humans efficiently grasp complex visual environments, making highly consistent judgments of entry-level category despite their high variability in visual appearance. How does the human brain arrive at the invariant neural representations underlying categorization of real-world environments? We here show that the neural representation of visual environments in scene-selective human visual cortex relies on statistics of contour junctions, which provide cues for the three-dimensional arrangement of surfaces in a scene. We manipulated line drawings of real-world environments such that statistics of contour orientations or junctions were disrupted. Manipulated and intact line drawings were presented to participants in an fMRI experiment. Scene categories were decoded from neural activity patterns in the parahippocampal place area (PPA), the occipital place area (OPA) and other visual brain regions. Disruption of junctions but not orientations led to a drastic decrease in decoding accuracy in the PPA and OPA, indicating the reliance of these areas on intact junction statistics. Accuracy of decoding from early visual cortex, on the other hand, was unaffected by either image manipulation. We further show that the correlation of error patterns between decoding from the scene-selective brain areas and behavioral experiments is contingent on intact contour junctions. Finally, a searchlight analysis exposes the reliance of visually active brain regions on different sets of contour properties. Statistics of contour length and curvature dominate neural representations of scene categories in early visual areas and contour junctions in high-level scene-selective brain regions. PMID:27118087

  8. Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson's disease?

    Institute of Scientific and Technical Information of China (English)

    Hyung Ho Yoon; Joongkee Min; Nari Shin; Yong Hwan Kim; Jin-Mo Kim; Yu-Shik Hwang; Jun-Kyo Francis Suh; Onyou Hwang; Sang Ryong Jeon

    2013-01-01

    Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18 F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.

  9. Human -Computer Interface using Gestures based on Neural Network

    OpenAIRE

    Aarti Malik; Shalini Dhingra

    2014-01-01

    - Gestures are powerful tools for non-verbal communication. Human computer interface (HCI) is a growing field which reduces the complexity of interaction between human and machine in which gestures are used for conveying information or controlling the machine. In the present paper, static hand gestures are utilized for this purpose. The paper presents a novel technique of recognizing hand gestures i.e. A-Z alphabets, 0-9 numbers and 6 additional control signals (for keyboard and mouse contr...

  10. Gender Identification in Human Gait Using Neural Network

    OpenAIRE

    Richa Shukla; Reenu Shukla; Anupam Shukla; Sanjeev Sharma; Nirupama Tiwari

    2012-01-01

    Biometrics is an advanced way of person recognition as it establishes more direct and explicit link with humans than passwords, since biometrics use measurable physiological and behavioural features of a person. In this paper gender recognition from human gait in image sequence have been successfully investigated. Silhouette of 15 males and 15 females from the database collected from CASIR site have been extracted. The computer vision based gender classification is then carried out on the bas...

  11. Neurally augmented sexual function in human females: a preliminary investigation.

    Science.gov (United States)

    Meloy, T Stuart; Southern, Joan P

    2006-01-01

    Objective.  Neurally augmented sexual function (NASF) is the production of pleasurable genital stimulation and subsequent orgasm through the application of electrical energy to provide stimulation of the spinal cord or peripheral nerves. The purpose of this paper is to demonstrate the reproducibility of this phenomenon. Materials and Methods.  Eleven otherwise healthy women, ages 32-60 years, were selected for this study. Through standard techniques, quadripolar (octopolar in the final patient) leads were placed in the epidural space percutaneuously. The lead was maneuvered initially to an L1-L2 position and then repositioned based on feedback from the patient. The patients were allowed to utilize the device ad libitum for up to 9 days. Results.  Successful stimulation was achieved in 91% (10/11) of patients. These women described a greater frequency in sexual activity, increased lubrication, and overall satisfaction. A smaller subset had substantial improvement in sexual function as measured by orgasmic capacity. This subset consisted of women with secondary anorgasmia. A return of orgasmic capacity was found in 80% (4/5) of patients having secondary anorgasmia with an average intensity of ≥ 3/5 while using the device. Once the device was removed, the patients returned to their previous anorgasmic status. Conclusions.  Pleasurable genital stimulation of the spinal cord is a consistently reproducible phenomenon. In a subset of the population studied, improvement in orgasmic function was noted. This was noted in the group with secondary orgasmic dysfunction. PMID:22151591

  12. Editorial: Technology for higher education, adult learning and human performance

    Directory of Open Access Journals (Sweden)

    Minhong Wang

    2013-09-01

    Full Text Available This special issue is dedicated to technology-enabled approaches for improving higher education, adult learning, and human performance. Improvement of learning and human development for sustainable development has been recognized as a key strategy for individuals, institutions, and organizations to strengthen their competitive advantages. It becomes crucial to help adult learners and knowledge workers to improve their self-directed and life-long learning capabilities. Meanwhile, advances in technology have been increasingly enabling and facilitating learning and knowledge-related initiatives.. They have largely extended learning opportunities through the provision of resource-rich and learner-centered environment, computer-based learning support, and expanded social interactions and networks. Papers in this special issue are representative of ongoing research on integration of technology with learning for innovation and sustainable development in higher education institutions and organizational and community environments.

  13. Efficient and Rapid Derivation of Primitive Neural Stem Cells and Generation of Brain Subtype Neurons From Human Pluripotent Stem Cells

    OpenAIRE

    Yan, Yiping; Shin, Soojung; Jha, Balendu Shekhar; Liu, Qiuyue; Sheng, Jianting; Li, Fuhai; Zhan, Ming; Davis, Janine; Bharti, Kapil; Zeng, Xianmin; Rao, Mahendra; Malik, Nasir; Mohan C. Vemuri

    2013-01-01

    This study developed a highly efficient serum-free pluripotent stem cell (PSC) neural induction medium that can induce human PSCs into primitive neural stem cells (NSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. This method of primitive NSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

  14. Human Inspired Self-developmental Model of Neural Network (HIM): Introducing Content/Form Computing

    Science.gov (United States)

    Krajíček, Jiří

    This paper presents cross-disciplinary research between medical/psychological evidence on human abilities and informatics needs to update current models in computer science to support alternative methods for computation and communication. In [10] we have already proposed hypothesis introducing concept of human information model (HIM) as cooperative system. Here we continue on HIM design in detail. In our design, first we introduce Content/Form computing system which is new principle of present methods in evolutionary computing (genetic algorithms, genetic programming). Then we apply this system on HIM (type of artificial neural network) model as basic network self-developmental paradigm. Main inspiration of our natural/human design comes from well known concept of artificial neural networks, medical/psychological evidence and Sheldrake theory of "Nature as Alive" [22].

  15. Neuropeptide Y in the Adult and Fetal Human Pineal Gland

    OpenAIRE

    Morten Møller; Pansiri Phansuwan-Pujito; Corin Badiu

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passag...

  16. Long-term multilayer adherent network (MAN) expansion, maintenance, and characterization, chemical and genetic manipulation, and transplantation of human fetal forebrain neural stem cells.

    Science.gov (United States)

    Wakeman, Dustin R; Hofmann, Martin R; Redmond, D Eugene; Teng, Yang D; Snyder, Evan Y

    2009-05-01

    Human neural stem/precursor cells (hNSC/hNPC) have been targeted for application in a variety of research models and as prospective candidates for cell-based therapeutic modalities in central nervous system (CNS) disorders. To this end, the successful derivation, expansion, and sustained maintenance of undifferentiated hNSC/hNPC in vitro, as artificial expandable neurogenic micro-niches, promises a diversity of applications as well as future potential for a variety of experimental paradigms modeling early human neurogenesis, neuronal migration, and neurogenetic disorders, and could also serve as a platform for small-molecule drug screening in the CNS. Furthermore, hNPC transplants provide an alternative substrate for cellular regeneration and restoration of damaged tissue in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Human somatic neural stem/progenitor cells (NSC/NPC) have been derived from a variety of cadaveric sources and proven engraftable in a cytoarchitecturally appropriate manner into the developing and adult rodent and monkey brain while maintaining both functional and migratory capabilities in pathological models of disease. In the following unit, we describe a new procedure that we have successfully employed to maintain operationally defined human somatic NSC/NPC from developing fetal, pre-term post-natal, and adult cadaveric forebrain. Specifically, we outline the detailed methodology for in vitro expansion, long-term maintenance, manipulation, and transplantation of these multipotent precursors. PMID:19455542

  17. Transplantation of adult monkey neural stem cells into a contusion spinal cord injury model in rhesus macaque monkeys

    DEFF Research Database (Denmark)

    Nemati, Shiva Nemati; Jabbari, Reza; Hajinasrollah, Mostafa;

    2014-01-01

    confirmed by magnetic resonance imaging (MRI) and histological analysis. Animals were clinically observed for 6 months. RESULTS: Analysis confirmed homing of mNSCs into the injury site. Transplanted cells expressed neuronal markers (TubIII). Hind limb performance improved in trans- planted animals based on......, therefore, to explore the efficacy of adult monkey NSC (mNSC) in a primate SCI model. MATERIALS AND METHODS: In this experimental study, isolated mNSCs were analyzed by flow cytometry, immunocytochemistry, and RT-PCR. Next, BrdU-labeled cells were transplanted into a SCI model. The SCI animal model was......OBJECTIVE: Currently, cellular transplantation for spinal cord injuries (SCI) is the subject of numerous preclinical studies. Among the many cell types in the adult brain, there is a unique subpopulation of neural stem cells (NSC) that can self-renew and differentiate into neurons. The study aims...

  18. On the nature and evolution of the neural bases of human language

    Science.gov (United States)

    Lieberman, Philip

    2002-01-01

    The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on

  19. Prior Knowledge about Objects Determines Neural Color Representation in Human Visual Cortex.

    Science.gov (United States)

    Vandenbroucke, A R E; Fahrenfort, J J; Meuwese, J D I; Scholte, H S; Lamme, V A F

    2016-04-01

    To create subjective experience, our brain must translate physical stimulus input by incorporating prior knowledge and expectations. For example, we perceive color and not wavelength information, and this in part depends on our past experience with colored objects ( Hansen et al. 2006; Mitterer and de Ruiter 2008). Here, we investigated the influence of object knowledge on the neural substrates underlying subjective color vision. In a functional magnetic resonance imaging experiment, human subjects viewed a color that lay midway between red and green (ambiguous with respect to its distance from red and green) presented on either typical red (e.g., tomato), typical green (e.g., clover), or semantically meaningless (nonsense) objects. Using decoding techniques, we could predict whether subjects viewed the ambiguous color on typical red or typical green objects based on the neural response of veridical red and green. This shift of neural response for the ambiguous color did not occur for nonsense objects. The modulation of neural responses was observed in visual areas (V3, V4, VO1, lateral occipital complex) involved in color and object processing, as well as frontal areas. This demonstrates that object memory influences wavelength information relatively early in the human visual system to produce subjective color vision. PMID:25323417

  20. Neural Differentiation in the Third Dimension: Generating a Human Midbrain.

    Science.gov (United States)

    Marton, Rebecca M; Paşca, Sergiu P

    2016-08-01

    In recent years, technological improvements in three-dimensional (3D) culture systems have enabled the generation of organoids or spheroids representing a variety of tissues, including the brain. In this issue of Cell Stem Cell, Jo et al. (2016) describe a 3D culture model of the human midbrain containing dopaminergic neurons and neuromelanin. PMID:27494668

  1. Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Patrick eHecht

    2015-10-01

    Full Text Available Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer’s disease. Weighted gene co-expression network analysis (WGCNA was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7% to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders.

  2. Noncoding RNA in the transcriptional landscape of human neural progenitor cell differentiation.

    Science.gov (United States)

    Hecht, Patrick M; Ballesteros-Yanez, Inmaculada; Grepo, Nicole; Knowles, James A; Campbell, Daniel B

    2015-01-01

    Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8 and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer's disease. Weighted gene co-expression network analysis (WGCNA) was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7 to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders. PMID:26557050

  3. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  4. Increased Neural Responses to Reward in Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder and Their Unaffected Siblings

    Science.gov (United States)

    von Rhein, Daniel; Cools, Roshan; Zwiers, Marcel P.; van der Schaaf, Marieke; Franke, Barbara; Luman, Marjolein; Oosterlaan, Jaap; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Hartman, Catharina A.; Faraone, Stephen V.; van Rooij, Daan; van Dongen, Eelco V.; Lojowska, Maria; Mennes, Maarten; Buitelaar, Jan

    2015-01-01

    Objective Attention-deficit/hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder associated with abnormal reward processing. Limited and inconsistent data exist about the neural mechanisms underlying this abnormality. Furthermore, it is unknown whether reward processing is abnormal in unaffected siblings of participants with ADHD. Method We used event-related functional magnetic resonance imaging (fMRI) to investigate brain responses during reward anticipation and receipt with an adapted monetary incentive delay task in a large sample of adolescents and young adults with ADHD (n=150), their unaffected siblings (n=92), and control participants (n=108), all of the same age. Results Participants with ADHD showed, relative to control participants, increased responses in the anterior cingulate, anterior frontal cortex, and cerebellum during reward anticipation, and in the orbitofrontal, occipital cortex, and ventral striatum during reward receipt. Responses of unaffected siblings were increased in these regions as well, except for the cerebellum during anticipation and the orbitofrontal cortex during receipt. Conclusion ADHD in adolescents and young adults is associated with enhanced neural responses in frontostriatal circuitry to anticipation and receipt of reward. The findings support models emphasizing aberrant reward processing in ADHD and suggest that processing of reward is subject to familial influences. Future studies using standard monetary incentive delay task parameters have to replicate our findings. PMID:25901776

  5. Unlike adults, children and adolescents show predominantly increased neural activation to social exclusion by members of the opposite gender.

    Science.gov (United States)

    Bolling, Danielle Z; Pelphrey, Kevin A; Vander Wyk, Brent C

    2016-10-01

    The effects of group membership on brain responses to social exclusion have been investigated in adults, revealing greater anterior cingulate responses to exclusion by members of one's in-group (e.g., same-gender). However, social exclusion is a critical aspect of peer relations in youth and reaches heightened salience during adolescence, a time when social anxiety disorders are also emergent. While the behavioral and neural correlates of social exclusion in adolescence have been extensively explored, the effects of group membership on peer rejection are less clear. The current study used functional magnetic resonance imaging (fMRI) to investigate the differential neural correlates of being excluded by peers of one's same- versus opposite-gender during an online ball-toss game. Participants were a group of typically developing children and adolescents (7-17 years). As predicted, anterior cingulate cortex showed a main effect of social exclusion versus fair play. However, unlike a previous adult study, this region did not show increased activation to same-gender exclusion. Instead, several regions differentiating same- versus opposite-gender exclusion were exclusively more sensitive to exclusion by one's opposite gender. These results are discussed in the context of adolescent socio-emotional development. PMID:26592311

  6. Optimal Recognition Method of Human Activities Using Artificial Neural Networks

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    Oniga Stefan

    2015-12-01

    Full Text Available The aim of this research is an exhaustive analysis of the various factors that may influence the recognition rate of the human activity using wearable sensors data. We made a total of 1674 simulations on a publically released human activity database by a group of researcher from the University of California at Berkeley. In a previous research, we analyzed the influence of the number of sensors and their placement. In the present research we have examined the influence of the number of sensor nodes, the type of sensor node, preprocessing algorithms, type of classifier and its parameters. The final purpose is to find the optimal setup for best recognition rates with lowest hardware and software costs.

  7. Optimal Recognition Method of Human Activities Using Artificial Neural Networks

    Science.gov (United States)

    Oniga, Stefan; József, Sütő

    2015-12-01

    The aim of this research is an exhaustive analysis of the various factors that may influence the recognition rate of the human activity using wearable sensors data. We made a total of 1674 simulations on a publically released human activity database by a group of researcher from the University of California at Berkeley. In a previous research, we analyzed the influence of the number of sensors and their placement. In the present research we have examined the influence of the number of sensor nodes, the type of sensor node, preprocessing algorithms, type of classifier and its parameters. The final purpose is to find the optimal setup for best recognition rates with lowest hardware and software costs.

  8. Early androgen influences on human neural and behavioural development

    OpenAIRE

    Hines, Melissa

    2008-01-01

    Gonadal hormones, particularly androgens, influence sexual differentiation of the body, as well as the brain and behaviour. Ante-natal exposure to atypical hormone environments leads to alterations in human behaviours that show sex differences. These include childhood play, sexual orientation, gender identity, and personality characteristics, such as empathy and aggression. Individual variability among healthy children in antenatal hormone exposure show similar relationships to individual var...

  9. Deep Neural Networks as a Computational Model for Human Shape Sensitivity.

    Directory of Open Access Journals (Sweden)

    Jonas Kubilius

    2016-04-01

    Full Text Available Theories of object recognition agree that shape is of primordial importance, but there is no consensus about how shape might be represented, and so far attempts to implement a model of shape perception that would work with realistic stimuli have largely failed. Recent studies suggest that state-of-the-art convolutional 'deep' neural networks (DNNs capture important aspects of human object perception. We hypothesized that these successes might be partially related to a human-like representation of object shape. Here we demonstrate that sensitivity for shape features, characteristic to human and primate vision, emerges in DNNs when trained for generic object recognition from natural photographs. We show that these models explain human shape judgments for several benchmark behavioral and neural stimulus sets on which earlier models mostly failed. In particular, although never explicitly trained for such stimuli, DNNs develop acute sensitivity to minute variations in shape and to non-accidental properties that have long been implicated to form the basis for object recognition. Even more strikingly, when tested with a challenging stimulus set in which shape and category membership are dissociated, the most complex model architectures capture human shape sensitivity as well as some aspects of the category structure that emerges from human judgments. As a whole, these results indicate that convolutional neural networks not only learn physically correct representations of object categories but also develop perceptually accurate representational spaces of shapes. An even more complete model of human object representations might be in sight by training deep architectures for multiple tasks, which is so characteristic in human development.

  10. Deep Neural Networks as a Computational Model for Human Shape Sensitivity.

    Science.gov (United States)

    Kubilius, Jonas; Bracci, Stefania; Op de Beeck, Hans P

    2016-04-01

    Theories of object recognition agree that shape is of primordial importance, but there is no consensus about how shape might be represented, and so far attempts to implement a model of shape perception that would work with realistic stimuli have largely failed. Recent studies suggest that state-of-the-art convolutional 'deep' neural networks (DNNs) capture important aspects of human object perception. We hypothesized that these successes might be partially related to a human-like representation of object shape. Here we demonstrate that sensitivity for shape features, characteristic to human and primate vision, emerges in DNNs when trained for generic object recognition from natural photographs. We show that these models explain human shape judgments for several benchmark behavioral and neural stimulus sets on which earlier models mostly failed. In particular, although never explicitly trained for such stimuli, DNNs develop acute sensitivity to minute variations in shape and to non-accidental properties that have long been implicated to form the basis for object recognition. Even more strikingly, when tested with a challenging stimulus set in which shape and category membership are dissociated, the most complex model architectures capture human shape sensitivity as well as some aspects of the category structure that emerges from human judgments. As a whole, these results indicate that convolutional neural networks not only learn physically correct representations of object categories but also develop perceptually accurate representational spaces of shapes. An even more complete model of human object representations might be in sight by training deep architectures for multiple tasks, which is so characteristic in human development. PMID:27124699

  11. Deep Neural Networks as a Computational Model for Human Shape Sensitivity

    Science.gov (United States)

    Op de Beeck, Hans P.

    2016-01-01

    Theories of object recognition agree that shape is of primordial importance, but there is no consensus about how shape might be represented, and so far attempts to implement a model of shape perception that would work with realistic stimuli have largely failed. Recent studies suggest that state-of-the-art convolutional ‘deep’ neural networks (DNNs) capture important aspects of human object perception. We hypothesized that these successes might be partially related to a human-like representation of object shape. Here we demonstrate that sensitivity for shape features, characteristic to human and primate vision, emerges in DNNs when trained for generic object recognition from natural photographs. We show that these models explain human shape judgments for several benchmark behavioral and neural stimulus sets on which earlier models mostly failed. In particular, although never explicitly trained for such stimuli, DNNs develop acute sensitivity to minute variations in shape and to non-accidental properties that have long been implicated to form the basis for object recognition. Even more strikingly, when tested with a challenging stimulus set in which shape and category membership are dissociated, the most complex model architectures capture human shape sensitivity as well as some aspects of the category structure that emerges from human judgments. As a whole, these results indicate that convolutional neural networks not only learn physically correct representations of object categories but also develop perceptually accurate representational spaces of shapes. An even more complete model of human object representations might be in sight by training deep architectures for multiple tasks, which is so characteristic in human development. PMID:27124699

  12. Neural correlates of the age-related changes in motor sequence learning and motor adaptation in older adults

    Directory of Open Access Journals (Sweden)

    Bradley R King

    2013-04-01

    Full Text Available As the world’s population ages, a deeper understanding of the relationship between aging and motor learning will become increasingly relevant in basic research and applied settings. In this context, this review aims to address the effects of age on motor sequence learning (MSL and motor adaptation (MA with respect to behavioral, neurological and neuroimaging findings. Previous behavioral research investigating the influence of aging on motor learning has consistently reported the following results. First, the initial acquisition of motor sequences is not altered, except under conditions of increased task complexity. Second, older adults demonstrate deficits in motor sequence memory consolidation. And, third, although older adults demonstrate deficits during the exposure phase of MA paradigms, the aftereffects following removal of the sensorimotor perturbation are similar to young adults, suggesting that the adaptive ability of older adults is relatively intact. This paper will review the potential neural underpinnings of these behavioral results, with a particular emphasis on the influence of age-related dysfunctions in the cortico-striatal system on motor learning.

  13. Intertwining extracellular nucleotides and their receptors with Ca2+ in determining adult neural stem cell survival, proliferation and final fate.

    Science.gov (United States)

    Lecca, Davide; Fumagalli, Marta; Ceruti, Stefania; Abbracchio, Maria P

    2016-08-01

    In the central nervous system (CNS), during both brain and spinal cord development, purinergic and pyrimidinergic signalling molecules (ATP, UTP and adenosine) act synergistically with peptidic growth factors in regulating the synchronized proliferation and final specification of multipotent neural stem cells (NSCs) to neurons, astrocytes or oligodendrocytes, the myelin-forming cells. Some NSCs still persist throughout adulthood in both specific 'neurogenic' areas and in brain and spinal cord parenchyma, retaining the potentiality to generate all the three main types of adult CNS cells. Once CNS anatomical structures are defined, purinergic molecules participate in calcium-dependent neuron-to-glia communication and also control the behaviour of adult NSCs. After development, some purinergic mechanisms are silenced, but can be resumed after injury, suggesting a role for purinergic signalling in regeneration and self-repair also via the reactivation of adult NSCs. In this respect, at least three different types of adult NSCs participate in the response of the adult brain and spinal cord to insults: stem-like cells residing in classical neurogenic niches, in particular, in the ventricular-subventricular zone (V-SVZ), parenchymal oligodendrocyte precursor cells (OPCs, also known as NG2-glia) and parenchymal injury-activated astrocytes (reactive astrocytes). Here, we shall review and discuss the purinergic regulation of these three main adult NSCs, with particular focus on how and to what extent modulation of intracellular calcium levels by purinoceptors is mandatory to determine their survival, proliferation and final fate.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377726

  14. Expression of GD2 and GD3 gangliosides in human embryonic neural stem cells

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    Makoto Yanagisawa

    2011-04-01

    Full Text Available NSCs (neural stem cells are undifferentiated neural cells endowed with a high potential for proliferation and a capacity for self-renewal with retention of multipotency to differentiate into neurons and glial cells. It has been recently reported that GD3, a b-series ganglioside, is a marker molecule for identifying and isolating mouse NSCs. However, the expression of gangliosides in human NSCs is largely unknown. In the present study, we analysed the expression of gangliosides, GD2 and GD3, in human NSCs that were isolated from human brains at gestational week 17 in the form of neurospheres, which are floating clonal aggregates formed by NSCs in vitro. Employing immunocytochemistry, we found that human NSCs were strongly reactive to anti-GD2 antibody and relatively weakly reactive to anti-GD3 antibody. Treatment of these cells with an organic solvent such as 100% methanol, which selectively removes glycolipids from plasma membrane, abolished the immunoreactivity with those antibodies, indicating that the reactivity was due to GD2 and GD3, but not to GD2-/GD3-like glycoproteins or proteoglycans. The immunoreactivity of human NSCs to antibody against SSEA-1 (stage-specific embryonic antigen-1, a well-known carbohydrate antigen of NSCs, was not decreased by the treatment with 100% methanol, indicating that SSEA-1 is mainly carried by glycoproteins and/or proteoglycans in human NSCs. Our study suggests that GD2 and GD3 can be marker gangliosides for identifying human NSCs.

  15. Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson's disease?★

    OpenAIRE

    Yoon, Hyung Ho; Min, Joongkee; Shin, Nari; Kim, Yong Hwan; Kim, Jin-Mo; Hwang, Yu-Shik; Suh, Jun-Kyo Francis; Hwang, Onyou; Jeon, Sang Ryong

    2013-01-01

    Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-der...

  16. In vitro proliferation of adult human beta-cells.

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    Sabine Rutti

    Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

  17. Spontaneous neural activity during human slow wave sleep

    OpenAIRE

    Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Albouy, Geneviève; Boly, Mélanie; Darsaud, Annabelle; Gais, Steffen; Rauchs, Géraldine; Sterpenich, Virginie; Vandewalle, Gilles; Carrier, Julie; Moonen, Gustave; Balteau, Evelyne; Degueldre, Christian; Luxen, André

    2008-01-01

    Slow wave sleep (SWS) is associated with spontaneous brain oscillations that are thought to participate in sleep homeostasis and to support the processing of information related to the experiences of the previous awake period. At the cellular level, during SWS, a slow oscillation (140 μV) and delta waves (75–140 μV) during SWS in 14 non-sleep-deprived normal human volunteers. Significant increases in activity were associated with these waves in several cortical areas, including the inferior f...

  18. Molecular effect of ethanol during neural differentiation of human embryonic stem cells in vitro

    OpenAIRE

    Kim, Jeffrey J.; Lewei Duan; Tu, Thanh G.; Omid Elie; Yiyoung Kim; Nathan Mathiyakom; David Elashoff; Yong Kim

    2014-01-01

    Potential teratogenic effects of alcohol on fetal development have been documented. Especially studies have demonstrated deleterious effect of ethanol exposure on neuronal development in animal models and on the maintenance and differentiation of neuronal precursor cells derived from stem cells. To better understand the molecular effect of alcohol on the process of neural differentiation, we have performed gene expression microarray analysis on human embryonic stem cells being directed to neu...

  19. Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans.

    OpenAIRE

    Anderson, E A; Hoffman, R P; Balon, T W; Sinkey, C A; Mark, A L

    1991-01-01

    Hyperinsulinemia may contribute to hypertension by increasing sympathetic activity and vascular resistance. We sought to determine if insulin increases central sympathetic neural outflow and vascular resistance in humans. We recorded muscle sympathetic nerve activity (MSNA; microneurography, peroneal nerve), forearm blood flow (plethysmography), heart rate, and blood pressure in 14 normotensive males during 1-h infusions of low (38 mU/m2/min) and high (76 mU/m2/min) doses of insulin while hol...

  20. Ethanol reduces the phase locking of neural activity in human and rodent brain

    OpenAIRE

    Ehlers, Cindy L.; Wills, Derek N.; Havstad, James

    2012-01-01

    How the neuromolecular actions of ethanol translate to its observed intoxicating effects remains poorly understood. Synchrony of phase (phase locking) of event-related oscillations (EROs) within and between different brain areas has been suggested to reflect communication exchange between neural networks and as such may be a sensitive and translational measure of ethanol’s effects. Using a similar auditory event-related potential paradigm in both rats and humans we investigated the phase vari...

  1. In vivo bioluminescence imaging for viable human neural stem cells incorporated within in situ gelatin hydrogels

    OpenAIRE

    Hwang, Do Won; Park, Kyung Min; Shim, Hye-kyung; Jin, Yeona; Oh, Hyun Jeong; Oh, So Won; Lee, Song; Youn, Hyewon; Joung, Yoon Ki; Lee, Hong J.; Kim, Seung U.; Park, Ki Dong; Lee, Dong Soo

    2014-01-01

    Background Three-dimensional (3D) hydrogel-based stem cell therapies contribute to enhanced therapeutic efficacy in treating diseases, and determining the optimal mechanical strength of the hydrogel in vivo is important for therapeutic success. We evaluated the proliferation of human neural stem cells incorporated within in situ-forming hydrogels and compared the effect of hydrogels with different elastic properties in cell/hydrogel-xenografted mice. Methods The gelatin-polyethylene glycol-ty...

  2. Human Neural Stem Cell Replacement Therapy for Amyotrophic Lateral Sclerosis by Spinal Transplantation

    OpenAIRE

    Hefferan, Michael P.; Jan Galik; Osamu Kakinohana; Gabriela Sekerkova; Camila Santucci; Silvia Marsala; Roman Navarro; Marian Hruska-Plochan; Karl Johe; Eva Feldman; Cleveland, Don W.; Martin Marsala

    2012-01-01

    BACKGROUND: Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1) causes an inherited form of Amyotrophic Lateral Sclerosis (ALS). Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs) into the lumbar spinal cord of SOD1(G93A) rats leads to a moderate therapeutical effect as evidenced by local α-motoneuron sparing and extension ...

  3. Adolescent social defeat alters neural, endocrine and behavioral responses to amphetamine in adult male rats

    OpenAIRE

    Burke, Andrew R.; Renner, Kenneth J.; Forster, Gina L.; Watt, Michael J.

    2010-01-01

    The mesocorticolimbic dopamine system, which governs components of reward and goal-directed behaviors, undergoes final maturation during adolescence. Adolescent social stress contributes to adult behavioral dysfunction, and is linked to adult psychiatric and addiction disorders. Here, behavioral, corticosterone, and limbic dopamine responses to amphetamine were examined in adult male rats previously exposed to repeated social defeat stress during mid-adolescence. Amphetamine (2.5 mg/kg, ip) w...

  4. Differentiation of human embryonic stem cells to regional specific neural precursors in chemically defined medium conditions.

    Directory of Open Access Journals (Sweden)

    Slaven Erceg

    Full Text Available BACKGROUND: Human embryonic stem cells (hESC provide a unique model to study early events in human development. The hESC-derived cells can potentially be used to replace or restore different tissues including neuronal that have been damaged by disease or injury. METHODOLOGY AND PRINCIPAL FINDINGS: The cells of two different hESC lines were converted to neural rosettes using adherent and chemically defined conditions. The progenitor cells were exposed to retinoic acid (RA or to human recombinant basic fibroblast growth factor (bFGF in the late phase of the rosette formation. Exposing the progenitor cells to RA suppressed differentiation to rostral forebrain dopamine neural lineage and promoted that of spinal neural tissue including motor neurons. The functional characteristics of these differentiated neuronal precursors under both, rostral (bFGF and caudalizing (RA signals were confirmed by patch clamp analysis. CONCLUSIONS/SIGNIFICANCE: These findings suggest that our differentiation protocol has the capacity to generate region-specific and electrophysiologically active neurons under in vitro conditions without embryoid body formation, co-culture with stromal cells and without presence of cells of mesodermal or endodermal lineages.

  5. Differentiation of insulin-producing cells from human neural progenitor cells.

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    Yuichi Hori

    2005-04-01

    Full Text Available BACKGROUND: Success in islet-transplantation-based therapies for type 1 diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Islets and neurons share features, including common developmental programs, and in some species brain neurons are the principal source of systemic insulin. METHODS AND FINDINGS: Here we show that brain-derived human neural progenitor cells, exposed to a series of signals that regulate in vivo pancreatic islet development, form clusters of glucose-responsive insulin-producing cells (IPCs. During in vitro differentiation of neural progenitor cells with this novel method, genes encoding essential known in vivo regulators of pancreatic islet development were expressed. Following transplantation into immunocompromised mice, IPCs released insulin C-peptide upon glucose challenge, remained differentiated, and did not form detectable tumors. CONCLUSION: Production of IPCs solely through extracellular factor modulation in the absence of genetic manipulations may promote strategies to derive transplantable islet-replacement tissues from human neural progenitor cells and other types of multipotent human stem cells.

  6. Differences in neural connectivity between the substantia nigra and ventral tegmental area in the human brain

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    Sung Ho Jang

    2014-02-01

    Full Text Available Objectives: Many animal and a few human studies have reported on the neural connectivity of the substantia nigra (SN and the ventral tegmental area (VTA. However, it has not been clearly elucidated so far. We attempted to investigate any differences in neural connectivity of the SN/VTA in the human brain, using diffusion tensor imaging (DTI.Methods: Sixty-three healthy subjects were recruited for this study. DTIs were acquired using a sensitivity-encoding head coil at 1.5T. Connectivity was defined as the incidence of connection between the SN/VTA and each brain regions in the brain.Results: The connectivity of SN was higher than that of the VTA. This included in the primary motor cortex, primary somatosensory cortex, premotor cortex, prefrontal cortex, caudate nucleus, globus pallidus, putamen, nucleus accumbens, temporal lobe, amygdala, pontine basis, occipital lobe, anterior and posterior lobe of cerebellum, corpus callosum, and external capsule (p.05.Conclusions: We found the differences in neural connectivity of the SN/VTA in the human brain. The method and results of this study can provide useful information for clinicians and researchers in neuroscience, especially who work for Parkinson’s disease and patients with brain injury.

  7. Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury.

    Science.gov (United States)

    Gao, Junling; Prough, Donald S; McAdoo, David J; Grady, James J; Parsley, Margaret O; Ma, Long; Tarensenko, Yevgeniya I; Wu, Ping

    2006-10-01

    Traumatic brain injury (TBI) often produces cognitive impairments by primary or secondary neuronal loss. Stem cells are a potential tool to treat TBI. However, most previous studies using rodent stem or progenitor cells failed to correlate cell grafting and cognitive improvement. Furthermore, the efficacy of fetal human neural stem cells (hNSCs) for ameliorating TBI cognitive dysfunction is undetermined. This study therefore characterized phenotypic differentiation, neurotrophic factor expression and release and functional outcome of grafting hNSCs into TBI rat brains. Adult Sprague-Dawley rats underwent a moderate parasagittal fluid percussion TBI followed by ipsilateral hippocampal transplantation of hNSCs or vehicle 1 day post-injury. Prior to grafting, hNSCs were treated in vitro for 7 days with our previously developed priming procedure. Significant spatial learning and memory improvements were detected by the Morris water maze (MWM) test in rats 10 days after receiving hNSC grafts. Morphological analyses revealed that hNSCs survived and differentiated mainly into neurons in the injured hippocampus at 2 weeks after grafting. Furthermore, hNSCs expressed and released glial-cell-line-derived neurotrophic factor (GDNF) in vitro and when grafted in vivo, as detected by RT-PCR, immunostaining, microdialysis and ELISA. This is the first direct demonstration of the release of a neurotrophic factor in conjunction with stem cell grafting. In conclusion, human fetal neural stem cell grafts improved cognitive function of rats with acute TBI. Grafted cells survived and differentiated into neurons and expressed and released GNDF in vivo, which may help protect host cells from secondary damage and aid host regeneration. PMID:16904107

  8. Human neural progenitor cells decrease photoreceptor degeneration, normalize opsin distribution and support synapse structure in cultured porcine retina.

    Science.gov (United States)

    Mollick, Tanzina; Mohlin, Camilla; Johansson, Kjell

    2016-09-01

    Retinal neurodegenerative disorders like retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy and retinal detachment decrease retinal functionality leading to visual impairment. The pathological events are characterized by photoreceptor degeneration, synaptic disassembly, remodeling of postsynaptic neurons and activation of glial cells. Despite intense research, no effective treatment has been found for these disorders. The current study explores the potential of human neural progenitor cell (hNPC) derived factors to slow the degenerative processes in adult porcine retinal explants. Retinas were cultured for 3 days with or without hNPCs as a feeder layer and investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), immunohistochemical, western blot and quantitative real time-polymerase chain reaction (qRT-PCR) techniques. TUNEL showed that hNPCs had the capacity to limit photoreceptor cell death. Among cone photoreceptors, hNPC coculture resulted in better maintenance of cone outer segments and reduced opsin mislocalization. Additionally, maintained synaptic structural integrity and preservation of second order calbindin positive horizontal cells was also observed. However, Müller cell gliosis only seemed to be alleviated in terms of reduced Müller cell density. Our observations indicate that at 3 days of coculture, hNPC derived factors had the capacity to protect photoreceptors, maintain synaptic integrity and support horizontal cell survival. Human neural progenitor cell applied treatment modalities may be an effective strategy to help maintain retinal functionality in neurodegenerative pathologies. Whether hNPCs can independently hinder Müller cell gliosis by utilizing higher concentrations or by combination with other pharmacological agents still needs to be determined. PMID:27369448

  9. Human Neural Cells Transiently Express Reelin during Olfactory Placode Development

    Science.gov (United States)

    Antal, M. Cristina; Samama, Brigitte; Ghandour, M. Said; Boehm, Nelly

    2015-01-01

    Reelin, an extracellular glycoprotein is essential for migration and correct positioning of neurons during development. Since the olfactory system is known as a source of various migrating neuronal cells, we studied Reelin expression in the two chemosensory olfactory systems, main and accessory, during early developmental stages of human foetuses/embryos from Carnegie Stage (CS) 15 to gestational week (GW) 14. From CS 15 to CS 18, but not at later stages, a transient expression of Reelin was detected first in the presumptive olfactory and then in the presumptive vomeronasal epithelium. During the same period, Reelin-positive cells detach from the olfactory/vomeronasal epithelium and migrate through the mesenchyme beneath the telencephalon. Dab 1, an adaptor protein of the Reelin pathway, was simultaneously expressed in the migratory mass from CS16 to CS17 and, at later stages, in the presumptive olfactory ensheathing cells. Possible involvements of Reelin and Dab 1 in the peripheral migrating stream are discussed. PMID:26270645

  10. Counterfactual choice and learning in a neural network centered on human lateral frontopolar cortex.

    Directory of Open Access Journals (Sweden)

    Erie D Boorman

    2011-06-01

    Full Text Available Decision making and learning in a real-world context require organisms to track not only the choices they make and the outcomes that follow but also other untaken, or counterfactual, choices and their outcomes. Although the neural system responsible for tracking the value of choices actually taken is increasingly well understood, whether a neural system tracks counterfactual information is currently unclear. Using a three-alternative decision-making task, a Bayesian reinforcement-learning algorithm, and fMRI, we investigated the coding of counterfactual choices and prediction errors in the human brain. Rather than representing evidence favoring multiple counterfactual choices, lateral frontal polar cortex (lFPC, dorsomedial frontal cortex (DMFC, and posteromedial cortex (PMC encode the reward-based evidence favoring the best counterfactual option at future decisions. In addition to encoding counterfactual reward expectations, the network carries a signal for learning about counterfactual options when feedback is available-a counterfactual prediction error. Unlike other brain regions that have been associated with the processing of counterfactual outcomes, counterfactual prediction errors within the identified network cannot be related to regret theory. Furthermore, individual variation in counterfactual choice-related activity and prediction error-related activity, respectively, predicts variation in the propensity to switch to profitable choices in the future and the ability to learn from hypothetical feedback. Taken together, these data provide both neural and behavioral evidence to support the existence of a previously unidentified neural system responsible for tracking both counterfactual choice options and their outcomes.

  11. Environmental layout complexity affects neural activity during navigation in humans.

    Science.gov (United States)

    Slone, Edward; Burles, Ford; Iaria, Giuseppe

    2016-05-01

    Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation. PMID:26990572

  12. Neural signal processing: the underestimated contribution of peripheral human C-fibers.

    Science.gov (United States)

    Weidner, Christian; Schmelz, Martin; Schmidt, Roland; Hammarberg, Björn; Orstavik, Kristin; Hilliges, Marita; Torebjörk, H Erik; Handwerker, Hermann O

    2002-08-01

    The microneurography technique was used to analyze use-dependent frequency modulation of action potential (AP) trains in human nociceptive peripheral nerves. Fifty-one single C-afferent units (31 mechano-responsive, 20 mechano-insensitive) were recorded from cutaneous fascicles of the peroneal nerve in awake human subjects. Trains of two and four suprathreshold electrical stimuli at interstimulus intervals of 20 and 50 msec were applied to the receptive fields of single identified nociceptive units at varying repetition rates. The output frequency (interspike interval) recorded at knee level was compared with the input frequency (interstimulus interval) at different levels of accumulated neural accommodation. At low levels of use-dependent accommodation (measured as conduction velocity slowing of the first action potential in a train), intervals between spikes increased during conduction along the nerve. At increasing levels of neural accommodation, intervals decreased because of a relative supernormal period (SNP) and asymptotically approached the minimum "entrainment" interval of the nerve fiber (11 +/- 1.4 msec) corresponding to a maximum instantaneous discharge frequency (up to 190 Hz). For neural coding, this pattern of frequency decrease at low activity levels and frequency increase at high levels serves as a mechanism of peripheral contrast enhancement. The entrainment interval is a good minimum estimate for the duration of the refractory period of human C-fibers. At a given degree of neural accommodation, all afferent C-units exhibit a uniform pattern of aftereffects, independent of fiber class. The receptive class of a fiber only determines its susceptibility to accommodate. Thus, the time course of aftereffects and existence or absence of an SNP is fully explained by the amount of preexisting accommodation. PMID:12151549

  13. Noncoding RNA in the transcriptional landscape of human neural progenitor cell differentiation

    OpenAIRE

    Hecht, Patrick M.; Ballesteros-Yanez, Inmaculada; Grepo, Nicole; Knowles, James A; Campbell, Daniel B

    2015-01-01

    Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8 and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5–28.1% mapped to ...

  14. Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

    OpenAIRE

    Patrick eHecht; Inmaculada eBallesteros-Yanez; Nicole eGrepo; James eKnowles; Daniel eCampbell

    2015-01-01

    Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped ...

  15. Differences in neural activation for object-directed grasping in chimpanzees and humans.

    Science.gov (United States)

    Hecht, Erin E; Murphy, Lauren E; Gutman, David A; Votaw, John R; Schuster, David M; Preuss, Todd M; Orban, Guy A; Stout, Dietrich; Parr, Lisa A

    2013-08-28

    The human faculty for object-mediated action, including tool use and imitation, exceeds that of even our closest primate relatives and is a key foundation of human cognitive and cultural uniqueness. In humans and macaques, observing object-directed grasping actions activates a network of frontal, parietal, and occipitotemporal brain regions, but differences in human and macaque activation suggest that this system has been a focus of selection in the primate lineage. To study the evolution of this system, we performed functional neuroimaging in humans' closest living relatives, chimpanzees. We compare activations during performance of an object-directed manual grasping action, observation of the same action, and observation of a mimed version of the action that consisted of only movements without results. Performance and observation of the same action activated a distributed frontoparietal network similar to that reported in macaques and humans. Like humans and unlike macaques, these regions were also activated by observing movements without results. However, in a direct chimpanzee/human comparison, we also identified unique aspects of human neural responses to observed grasping. Chimpanzee activation showed a prefrontal bias, including significantly more activity in ventrolateral prefrontal cortex, whereas human activation was more evenly distributed across more posterior regions, including significantly more activation in ventral premotor cortex, inferior parietal cortex, and inferotemporal cortex. This indicates a more "bottom-up" representation of observed action in the human brain and suggests that the evolution of tool use, social learning, and cumulative culture may have involved modifications of frontoparietal interactions. PMID:23986247

  16. Neural Correlates of Decision Thresholds in the Human Subthalamic Nucleus.

    Science.gov (United States)

    Herz, Damian M; Zavala, Baltazar A; Bogacz, Rafal; Brown, Peter

    2016-04-01

    If humans are faced with difficult choices when making decisions, the ability to slow down responses becomes critical in order to avoid suboptimal choices. Current models of decision making assume that the subthalamic nucleus (STN) mediates this function by elevating decision thresholds, thereby requiring more evidence to be accumulated before responding [1-9]. However, direct electrophysiological evidence for the exact role of STN during adjustment of decision thresholds is lacking. Here, we show that trial-by-trial variations in STN low-frequency oscillatory activity predict adjustments of decision thresholds before subjects make a response. The relationship between STN activity and decision thresholds critically depends on the subjects' level of cautiousness. While increased oscillatory activity of the STN predicts elevated decision thresholds during high levels of cautiousness, it predicts decreased decision thresholds during low levels of cautiousness. This context-dependent relationship may be mediated by increased influence of the medial prefrontal cortex (mPFC)-STN pathway on decision thresholds during high cautiousness. Subjects who exhibit a stronger increase in phase alignment of low-frequency oscillatory activity in mPFC and STN before making a response have higher decision thresholds and commit fewer erroneous responses. Together, our results demonstrate that STN low-frequency oscillatory activity and corresponding mPFC-STN coupling are involved in determining how much evidence subjects accumulate before making a decision. This finding might explain why deep-brain stimulation of the STN can impair subjects' ability to slow down responses and can induce impulsive suboptimal decisions. PMID:26996501

  17. Neonatal Maternal Separation Alters the Capacity of Adult Neural Precursor Cells to Differentiate into Neurons Via Methylation of Retinoic Acid Receptor Gene Promoter

    OpenAIRE

    Boku, Shuken; Toda, Hiroyuki; Nakagawa, Shin; Kato, Akiko; Inoue, Takeshi; Koyama, Tsukasa; Hiroi, Noboru; Kusumi, Ichiro

    2015-01-01

    BACKGROUND: Early life stress is thought to contribute to psychiatric disorders, but the precise mechanisms underlying this link are poorly understood. As neonatal stress decreases adult hippocampal neurogenesis, which, in turn, functionally contributes to many behavioral phenotypes relevant to psychiatric disorders, we examined how in vivo neonatal maternal separation (NMS) impacts the capacity of adult hippocampal neural precursor cells via epigenetic alterations in vitro. METHODS: Rat pups...

  18. Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences.

    Science.gov (United States)

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Alix, Philippe; Leprince, Pierre; Glejzer, Aneta; Poulet, Christophe; Hennuy, Benoit; Sommer, Lukas; Shakhova, Olga; Rogister, Bernard

    2012-08-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crest stem cells (NCSC) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSC), including their similarities and differences. In this paper, using transcriptomic as well as proteomic technologies, we compared NCSC to MSC and stromal nestin-positive cells, all of them isolated from adult bone marrow. We demonstrated that the nestin-positive cell population, which was the first to be described as able to differentiate into functional neurons, was a mixed population of NCSC and MSC. More interestingly, we demonstrated that MSC shared with NCSC the same ability to truly differentiate into Tuj1-positive cells when co-cultivated with paraformaldehyde-fixed cerebellar granule neurons. Altogether, those results suggest that both NCSC and MSC can be considered as important tools for cellular therapies in order to replace neurons in various neurological diseases. PMID:22349262

  19. Ontogeny of morningness-eveningness across the adult human lifespan

    Science.gov (United States)

    Randler, Christoph

    2016-02-01

    Sleep timing of humans can be classified alongside a continuum from early to late sleepers, with some people (larks) having an early activity, early bed, and rise times and others (owls) with a more nocturnally orientated activity. Only a few studies reported that morningness-eveningness changes significantly during the adult lifespan based on community samples. Here, I applied a different methodological approach to seek for evidence for the age-related changes in morningness-eveningness preferences by using a meta-data from all available studies. The new aspect of this cross-sectional approach is that only a few studies themselves address the age-related changes of the adult lifespan development, but that many studies are available that provide exactly the data needed. The studies came from 27 countries and included 36,939 participants. Age was highly significantly correlated with scores on the Composite Scale of Morningness ( r = 0.70). This relationship seems linear, because a linear regression explained nearly the same amount of variance compared to other models such as logarithmic, quadratic, or cubic models. The standard deviation of age correlated with the standard deviation of CSM scores ( r = 0.55), suggesting when there is much variance in age in a study; in turn, there is much variance in morningness. This meta-analytical approach shows that morningness-eveningness changes across the adult lifespan and that older age is related to higher morningness.

  20. A wireless transmission neural interface system for unconstrained non-human primates

    Science.gov (United States)

    Fernandez-Leon, Jose A.; Parajuli, Arun; Franklin, Robert; Sorenson, Michael; Felleman, Daniel J.; Hansen, Bryan J.; Hu, Ming; Dragoi, Valentin

    2015-10-01

    Objective. Studying the brain in large animal models in a restrained laboratory rig severely limits our capacity to examine brain circuits in experimental and clinical applications. Approach. To overcome these limitations, we developed a high-fidelity 96-channel wireless system to record extracellular spikes and local field potentials from the neocortex. A removable, external case of the wireless device is attached to a titanium pedestal placed in the animal skull. Broadband neural signals are amplified, multiplexed, and continuously transmitted as TCP/IP data at a sustained rate of 24 Mbps. A Xilinx Spartan 6 FPGA assembles the digital signals into serial data frames for transmission at 20 kHz though an 802.11n wireless data link on a frequency-shift key-modulated signal at 5.7-5.8 GHz to a receiver up to 10 m away. The system is powered by two CR123A, 3 V batteries for 2 h of operation. Main results. We implanted a multi-electrode array in visual area V4 of one anesthetized monkey (Macaca fascicularis) and in the dorsolateral prefrontal cortex (dlPFC) of a freely moving monkey (Macaca mulatta). The implanted recording arrays were electrically stable and delivered broadband neural data over a year of testing. For the first time, we compared dlPFC neuronal responses to the same set of stimuli (food reward) in restrained and freely moving conditions. Although we did not find differences in neuronal responses as a function of reward type in the restrained and unrestrained conditions, there were significant differences in correlated activity. This demonstrates that measuring neural responses in freely moving animals can capture phenomena that are absent in the traditional head-fixed paradigm. Significance. We implemented a wireless neural interface for multi-electrode recordings in freely moving non-human primates, which can potentially move systems neuroscience to a new direction by allowing one to record neural signals while animals interact with their environment.

  1. ERK-dependent and -independent pathways trigger human neural progenitor cell migration

    International Nuclear Information System (INIS)

    Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2 phosphorylation and inhibited cell migration. We identified protein kinase C (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases governing ERK1/2 activation, thereby controlling NHNP cell migration. Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways

  2. Neural and Synaptic Defects in slytherin a Zebrafish Model for Human Congenital Disorders of Glycosylation

    Energy Technology Data Exchange (ETDEWEB)

    Y Song; J Willer; P Scherer; J Panzer; A Kugath; E Skordalakes; R Gregg; G Willer; R Balice-Gordon

    2011-12-31

    Congenital disorder of glycosylation type IIc (CDG IIc) is characterized by mental retardation, slowed growth and severe immunodeficiency, attributed to the lack of fucosylated glycoproteins. While impaired Notch signaling has been implicated in some aspects of CDG IIc pathogenesis, the molecular and cellular mechanisms remain poorly understood. We have identified a zebrafish mutant slytherin (srn), which harbors a missense point mutation in GDP-mannose 4,6 dehydratase (GMDS), the rate-limiting enzyme in protein fucosylation, including that of Notch. Here we report that some of the mechanisms underlying the neural phenotypes in srn and in CGD IIc are Notch-dependent, while others are Notch-independent. We show, for the first time in a vertebrate in vivo, that defects in protein fucosylation leads to defects in neuronal differentiation, maintenance, axon branching, and synapse formation. Srn is thus a useful and important vertebrate model for human CDG IIc that has provided new insights into the neural phenotypes that are hallmarks of the human disorder and has also highlighted the role of protein fucosylation in neural development.

  3. Neural and synaptic defects in slytherin, a zebrafish model for human congenital disorders of glycosylation.

    Directory of Open Access Journals (Sweden)

    Yuanquan Song

    Full Text Available Congenital disorder of glycosylation type IIc (CDG IIc is characterized by mental retardation, slowed growth and severe immunodeficiency, attributed to the lack of fucosylated glycoproteins. While impaired Notch signaling has been implicated in some aspects of CDG IIc pathogenesis, the molecular and cellular mechanisms remain poorly understood. We have identified a zebrafish mutant slytherin (srn, which harbors a missense point mutation in GDP-mannose 4,6 dehydratase (GMDS, the rate-limiting enzyme in protein fucosylation, including that of Notch. Here we report that some of the mechanisms underlying the neural phenotypes in srn and in CGD IIc are Notch-dependent, while others are Notch-independent. We show, for the first time in a vertebrate in vivo, that defects in protein fucosylation leads to defects in neuronal differentiation, maintenance, axon branching, and synapse formation. Srn is thus a useful and important vertebrate model for human CDG IIc that has provided new insights into the neural phenotypes that are hallmarks of the human disorder and has also highlighted the role of protein fucosylation in neural development.

  4. Generation and properties of a new human ventral mesencephalic neural stem cell line

    International Nuclear Information System (INIS)

    Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to cell therapy in neurodegenerative diseases like Parkinson's disease. Several epigenetic and genetic strategies have been tested for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new stable cell line of human neural stem cells derived from ventral mesencephalon (hVM1) based on v-myc immortalization. The cells expressed neural stem cell and radial glia markers like nestin, vimentin and 3CB2 under proliferation conditions. After withdrawal of growth factors, proliferation and expression of v-myc were dramatically reduced and the cells differentiated into astrocytes, oligodendrocytes and neurons. hVM1 cells yield a large number of dopaminergic neurons (about 12% of total cells are TH+) after differentiation, which also produce dopamine. In addition to proneural genes (NGN2, MASH1), differentiated cells show expression of several genuine mesencephalic dopaminergic markers such as: LMX1A, LMX1B, GIRK2, ADH2, NURR1, PITX3, VMAT2 and DAT, indicating that they retain their regional identity. Our data indicate that this cell line and its clonal derivatives may constitute good candidates for the study of development and physiology of human dopaminergic neurons in vitro, and to develop tools for Parkinson's disease cell replacement preclinical research and drug testing.

  5. Generation of retinal pigment epithelial cells from human embryonic stem cell-derived spherical neural masses.

    Science.gov (United States)

    Cho, Myung Soo; Kim, Sang Jin; Ku, Seung-Yup; Park, Jung Hyun; Lee, Haksup; Yoo, Dae Hoon; Park, Un Chul; Song, Seul Ae; Choi, Young Min; Yu, Hyeong Gon

    2012-09-01

    Dysfunction and loss of retinal pigment epithelium (RPE) are major pathologic changes observed in various retinal degenerative diseases such as aged-related macular degeneration. RPE generated from human pluripotent stem cells can be a good candidate for RPE replacement therapy. Here, we show the differentiation of human embryonic stem cells (hESCs) toward RPE with the generation of spherical neural masses (SNMs), which are pure masses of hESCs-derived neural precursors. During the early passaging of SNMs, cystic structures arising from opened neural tube-like structures showed pigmented epithelial morphology. These pigmented cells were differentiated into functional RPE by neuroectodermal induction and mechanical purification. Most of the differentiated cells showed typical RPE morphologies, such as a polygonal-shaped epithelial monolayer, and transmission electron microscopy revealed apical microvilli, pigment granules, and tight junctions. These cells also expressed molecular markers of RPE, including Mitf, ZO-1, RPE65, CRALBP, and bestrophin. The generated RPE also showed phagocytosis of isolated bovine photoreceptor outer segment and secreting pigment epithelium-derived factor and vascular endothelial growth factor. Functional RPE could be generated from SNM in our method. Because SNMs have several advantages, including the capability of expansion for long periods without loss of differentiation capability, easy storage and thawing, and no need for feeder cells, our method for RPE differentiation may be used as an efficient strategy for generating functional RPE cells for retinal regeneration therapy. PMID:22683799

  6. Generation and properties of a new human ventral mesencephalic neural stem cell line

    Energy Technology Data Exchange (ETDEWEB)

    Villa, Ana; Liste, Isabel; Courtois, Elise T.; Seiz, Emma G.; Ramos, Milagros [Center of Molecular Biology ' Severo Ochoa' , Autonomous University of Madrid-C.S.I.C., Campus Cantoblanco 28049-Madrid (Spain); Meyer, Morten [Department of Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark, Winslowparken 21,st, DK-500, Odense C (Denmark); Juliusson, Bengt; Kusk, Philip [NsGene A/S, Ballerup (Denmark); Martinez-Serrano, Alberto, E-mail: amserrano@cbm.uam.es [Center of Molecular Biology ' Severo Ochoa' , Autonomous University of Madrid-C.S.I.C., Campus Cantoblanco 28049-Madrid (Spain)

    2009-07-01

    Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to cell therapy in neurodegenerative diseases like Parkinson's disease. Several epigenetic and genetic strategies have been tested for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new stable cell line of human neural stem cells derived from ventral mesencephalon (hVM1) based on v-myc immortalization. The cells expressed neural stem cell and radial glia markers like nestin, vimentin and 3CB2 under proliferation conditions. After withdrawal of growth factors, proliferation and expression of v-myc were dramatically reduced and the cells differentiated into astrocytes, oligodendrocytes and neurons. hVM1 cells yield a large number of dopaminergic neurons (about 12% of total cells are TH{sup +}) after differentiation, which also produce dopamine. In addition to proneural genes (NGN2, MASH1), differentiated cells show expression of several genuine mesencephalic dopaminergic markers such as: LMX1A, LMX1B, GIRK2, ADH2, NURR1, PITX3, VMAT2 and DAT, indicating that they retain their regional identity. Our data indicate that this cell line and its clonal derivatives may constitute good candidates for the study of development and physiology of human dopaminergic neurons in vitro, and to develop tools for Parkinson's disease cell replacement preclinical research and drug testing.

  7. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Delaisse, Jean-Marie; Hinge, Maja;

    2016-01-01

    . Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone......The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter of...... debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts...

  8. Neural Plasticity following Abacus Training in Humans: A Review and Future Directions

    Directory of Open Access Journals (Sweden)

    Yongxin Li

    2016-01-01

    Full Text Available The human brain has an enormous capacity to adapt to a broad variety of environmental demands. Previous studies in the field of abacus training have shown that this training can induce specific changes in the brain. However, the neural mechanism underlying these changes remains elusive. Here, we reviewed the behavioral and imaging findings of comparisons between abacus experts and average control subjects and focused on changes in activation patterns and changes in brain structure. Finally, we noted the limitations and the future directions of this field. We concluded that although current studies have provided us with information about the mechanisms of abacus training, more research on abacus training is needed to understand its neural impact.

  9. Imaging of human differentiated 3D neural aggregates using light sheet fluorescence microscopy

    Directory of Open Access Journals (Sweden)

    Emilio J Gualda

    2014-08-01

    Full Text Available The development of three dimensional cell cultures represents a big step for the better understanding of cell behavior and disease in a more natural like environment, providing not only single but multiple cell type interactions in a complex three dimensional matrix, highly resembling physiological conditions. Light sheet fluorescence microscopy is becoming an excellent tool for fast imaging of such three-dimensional biological structures. We demonstrate the potential of this technique for the imaging of human differentiated 3D neural aggregates in fixed and live samples, namely calcium imaging and cell death processes, showing the power of imaging modality compared with traditional microscopy. The combination of light sheet microscopy and 3D neural cultures will open the door to more challenging experiments involving drug testing at large scale as well as a better understanding of relevant biological processes in a more realistic environment.

  10. Detection of some anaemia types in human blood smears using neural networks

    Science.gov (United States)

    Elsalamony, Hany A.

    2016-08-01

    The identification process based on measuring the level of haemoglobin and the classification of red blood cells using microscopic examination of blood smears is the principal way to diagnose anaemia. This paper presents a proposed algorithm for detecting some anaemia types like sickle and elliptocytosis and trying to count them with healthy ones in human red blood smears based on the circular Hough transform and some morphological tools. Some cells with unknown shapes (not platelets or white cells) also have been detected. The extracted data from the detection process has been analyzed by neural network. The experimental results have demonstrated high accuracy, and the proposed algorithm has achieved the highest detection of around 98.9% out of all the cells in 27 microscopic images. Effectiveness rates up to 100%, 98%, and 99.3% have been achieved by using neural networks for sickle, elliptocytosis and cells with unknown shapes, respectively.

  11. Stimulation of adult neural stem cells with a novel glycolipid biosurfactant

    OpenAIRE

    Stipcevic, Tamara; Knight, Christopher P.; Kippin, Tod E.

    2013-01-01

    Glycolipids are amphipatic molecules which are highly expressed on cell membranes in skin and brain where they mediate several key cellular processes. Neural stem cells are defined as undifferentiated, proliferative, multipotential cells with extensive self-renewal and are responsive to brain injury. Di-rhamnolipid: α-L-rhamnopyranosyl-(1-2)α-L-rhamnopyranosyl-3-hydroxydecanoyl-3-hydroxydecanoic acid, also referred to as di-rhamnolipid BAC-3, is a glycolipid isolated from bacteria Pseudomonas...

  12. Aberrant Neural Stem Cell Proliferation and Increased Adult Neurogenesis in Mice Lacking Chromatin Protein HMGB2

    OpenAIRE

    Abraham, Ariel B; Robert Bronstein; Avanish S Reddy; Mirjana Maletic-Savatic; Adan Aguirre; Tsirka, Stella E.

    2013-01-01

    Neural stem and progenitor cells (NSCs/NPCs) are distinct groups of cells found in the mammalian central nervous system (CNS). Previously we determined that members of the High Mobility Group (HMG) B family of chromatin structural proteins modulate NSC proliferation and self-renewal. Among them HMGB2 was found to be dynamically expressed in proliferating and differentiating NSCs, suggesting that it may regulate NSC maintenance. We report now that Hmgb2(-/-) mice exhibit SVZ hyperproliferation...

  13. Subjective and Neural Responses to Intravenous Alcohol in Young Adults with Light and Heavy Drinking Patterns

    OpenAIRE

    Gilman, Jodi M.; Ramchandani, Vijay A.; Crouss, Tess; Hommer, Daniel W.

    2011-01-01

    Heavy alcohol consumption during young adulthood is a risk factor for the development of serious alcohol use disorders. Research has shown that individual differences in subjective responses to alcohol may affect individuals' vulnerability to developing alcoholism. Studies comparing the subjective and objective response to alcohol between light and heavy drinkers (HDs), however, have yielded inconsistent results, and neural responses to alcohol in these groups have not been characterized. We ...

  14. The impact of abacus training on working memory and underlying neural correlates in young adults.

    Science.gov (United States)

    Dong, Shanshan; Wang, Chunjie; Xie, Ye; Hu, Yuzheng; Weng, Jian; Chen, Feiyan

    2016-09-22

    Abacus-based mental calculation (AMC) activates the frontoparietal areas largely overlapping with the working memory (WM) network. Given the critical role of WM in cognition, how to improve WM capability has attracted intensive attention in past years. However, it is still unclear whether WM could be enhanced by AMC training. The current research thus explored the impact of AMC training on verbal and visuospatial WM, as well as the underlying neural basis. Participants were randomly assigned to an abacus group and a control group. Their verbal WM was evaluated by digit/letter memory span (DMS/LMS) tests, and visuospatial WM was assessed by a visuospatial n-back task. Neural activity during the n-back task was examined using functional MRI. Our results showed reliable improvements of both verbal and visuospatial WM in the abacus group after 20-day AMC training but not in the control. In addition, the n-back task-induced activations in the right frontoparietal circuitry and left occipitotemporal junction (OTJ) declined as a result of training. Notably, the decreases in activity were positively correlated with performance gains across trained participants. These results suggest AMC training not only improves calculating skills but also have the potential to promote individuals' WM capabilities, which is associated with the functional plasticity of the common neural substrates. PMID:27393250

  15. Evaluating a genetically encoded optical sensor of neural activity using electrophysiology in intact adult fruit flies

    Directory of Open Access Journals (Sweden)

    Gilles Laurent

    2007-11-01

    Full Text Available Genetically encoded optical indicators hold the promise of enabling non-invasive monitoring of activity in identified neurons in behaving organisms. However, the interpretation of images of brain activity produced using such sensors is not straightforward. Several recent studies of sensory coding used G-CaMP 1.3-a calcium sensor-as an indicator of neural activity; some of these studies characterized the imaged neurons as having narrow tuning curves, a conclusion not always supported by parallel electrophysiological studies. To better understand the possible cause of these conflicting results, we performed simultaneous in vivo 2-photon imaging and electrophysiological recording of G-CaMP 1.3 expressing neurons in the antennal lobe (AL of intact fruitflies. We find that G-CaMP has a relatively high threshold, that its signal often fails to capture spiking response kinetics, and that it can miss even high instantaneous rates of activity if those are not sustained. While G-CaMP can be misleading, it is clearly useful for the identification of promising neural targets: when electrical activity is well above the sensor's detection threshold, its signal is fairly well correlated with mean firing rate and G-CaMP does not appear to alter significantly the responses of neurons that express it. The methods we present should enable any genetically encoded sensor, activator, or silencer to be evaluated in an intact neural circuit in vivo in Drosophila.

  16. Human Facial Expression Detection From Detected in Captured Image using Back Propagation Neural Network

    Directory of Open Access Journals (Sweden)

    Jagdish Lal Raheja

    2010-02-01

    Full Text Available In the field of image processing it is very interesting to recognize the human gesture for general lifeapplications. For example, observing the gesture of a driver when he/she is driving and alerting him/herwhen in sleepy mood will be quite useful. Human gestures can be identified by observing the differentmovements of eyes, mouth, nose and hands. In this paper we are focusing on the human face forrecognizing expression. Many techniques are available to recognize face. In this paper, face is detectedusing the Viola and Jones techniques. This paper introduces a simple architecture for human facialexpression recognition. The approach is based on add-boosted classifier for face detection and simpletoken finding and matching using back propagation neural network. This approach can be adapted toreal time system very easily. The paper briefly describes the schemes of capturing the image from webcam, detecting the face, processing the image to recognize the gestures as well as few results.

  17. The shared signal hypothesis and neural responses to expressions and gaze in infants and adults

    OpenAIRE

    Rigato, Silvia; Farroni, Teresa; Johnson, Mark H.

    2009-01-01

    Event-related potentials were recorded from adults and 4-month-old infants while they watched pictures of faces that varied in emotional expression (happy and fearful) and in gaze direction (direct or averted). Results indicate that emotional expression is temporally independent of gaze direction processing at early stages of processing, and only become integrated at later latencies. Facial expressions affected the face-sensitive ERP components in both adults (N170) and infants (N290 and P400...

  18. Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Liang [East Hospital, Tongji University School of Medicine, Shanghai (China); Dong, Chuanming [East Hospital, Tongji University School of Medicine, Shanghai (China); Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong (China); Sun, Chenxi; Ma, Rongjie; Yang, Danjing [East Hospital, Tongji University School of Medicine, Shanghai (China); Zhu, Hongwen, E-mail: hongwen_zhu@hotmail.com [Tianjin Hospital, Tianjin Academy of Integrative Medicine, Tianjin (China); Xu, Jun, E-mail: xunymc2000@yahoo.com [East Hospital, Tongji University School of Medicine, Shanghai (China)

    2015-08-21

    Aging of neural stem cell, which can affect brain homeostasis, may be caused by many cellular mechanisms. Autophagy dysfunction was found in aged and neurodegenerative brains. However, little is known about the relationship between autophagy and human neural stem cell (hNSC) aging. The present study used 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to treat neural precursor cells (NPCs) derived from human embryonic stem cell (hESC) line H9 and investigate related molecular mechanisms involved in this process. MPTP-treated NPCs were found to undergo premature senescence [determined by increased senescence-associated-β-galactosidase (SA-β-gal) activity, elevated intracellular reactive oxygen species level, and decreased proliferation] and were associated with impaired autophagy. Additionally, the cellular senescence phenotypes were manifested at the molecular level by a significant increase in p21 and p53 expression, a decrease in SOD2 expression, and a decrease in expression of some key autophagy-related genes such as Atg5, Atg7, Atg12, and Beclin 1. Furthermore, we found that the senescence-like phenotype of MPTP-treated hNPCs was rejuvenated through treatment with a well-known autophagy enhancer rapamycin, which was blocked by suppression of essential autophagy gene Beclin 1. Taken together, these findings reveal the critical role of autophagy in the process of hNSC aging, and this process can be reversed by activating autophagy. - Highlights: • We successfully establish hESC-derived neural precursor cells. • MPTP treatment induced senescence-like state in hESC-derived NPCs. • MPTP treatment induced impaired autophagy of hESC-derived NPCs. • MPTP-induced hESC-derived NPC senescence was rejuvenated by activating autophagy.

  19. Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy

    International Nuclear Information System (INIS)

    Aging of neural stem cell, which can affect brain homeostasis, may be caused by many cellular mechanisms. Autophagy dysfunction was found in aged and neurodegenerative brains. However, little is known about the relationship between autophagy and human neural stem cell (hNSC) aging. The present study used 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to treat neural precursor cells (NPCs) derived from human embryonic stem cell (hESC) line H9 and investigate related molecular mechanisms involved in this process. MPTP-treated NPCs were found to undergo premature senescence [determined by increased senescence-associated-β-galactosidase (SA-β-gal) activity, elevated intracellular reactive oxygen species level, and decreased proliferation] and were associated with impaired autophagy. Additionally, the cellular senescence phenotypes were manifested at the molecular level by a significant increase in p21 and p53 expression, a decrease in SOD2 expression, and a decrease in expression of some key autophagy-related genes such as Atg5, Atg7, Atg12, and Beclin 1. Furthermore, we found that the senescence-like phenotype of MPTP-treated hNPCs was rejuvenated through treatment with a well-known autophagy enhancer rapamycin, which was blocked by suppression of essential autophagy gene Beclin 1. Taken together, these findings reveal the critical role of autophagy in the process of hNSC aging, and this process can be reversed by activating autophagy. - Highlights: • We successfully establish hESC-derived neural precursor cells. • MPTP treatment induced senescence-like state in hESC-derived NPCs. • MPTP treatment induced impaired autophagy of hESC-derived NPCs. • MPTP-induced hESC-derived NPC senescence was rejuvenated by activating autophagy

  20. Human facial neural activities and gesture recognition for machine-interfacing applications

    Directory of Open Access Journals (Sweden)

    Hamedi M

    2011-12-01

    Full Text Available M Hamedi1, Sh-Hussain Salleh2, TS Tan2, K Ismail2, J Ali3, C Dee-Uam4, C Pavaganun4, PP Yupapin51Faculty of Biomedical and Health Science Engineering, Department of Biomedical Instrumentation and Signal Processing, University of Technology Malaysia, Skudai, 2Centre for Biomedical Engineering Transportation Research Alliance, 3Institute of Advanced Photonics Science, Nanotechnology Research Alliance, University of Technology Malaysia (UTM, Johor Bahru, Malaysia; 4College of Innovative Management, Valaya Alongkorn Rajabhat University, Pathum Thani, 5Nanoscale Science and Engineering Research Alliance (N'SERA, Advanced Research Center for Photonics, Faculty of Science, King Mongkut's Institute of Technology Ladkrabang, Bangkok, ThailandAbstract: The authors present a new method of recognizing different human facial gestures through their neural activities and muscle movements, which can be used in machine-interfacing applications. Human–machine interface (HMI technology utilizes human neural activities as input controllers for the machine. Recently, much work has been done on the specific application of facial electromyography (EMG-based HMI, which have used limited and fixed numbers of facial gestures. In this work, a multipurpose interface is suggested that can support 2–11 control commands that can be applied to various HMI systems. The significance of this work is finding the most accurate facial gestures for any application with a maximum of eleven control commands. Eleven facial gesture EMGs are recorded from ten volunteers. Detected EMGs are passed through a band-pass filter and root mean square features are extracted. Various combinations of gestures with a different number of gestures in each group are made from the existing facial gestures. Finally, all combinations are trained and classified by a Fuzzy c-means classifier. In conclusion, combinations with the highest recognition accuracy in each group are chosen. An average accuracy

  1. Differentiation of Human Breast-Milk Stem Cells to Neural Stem Cells and Neurons

    Directory of Open Access Journals (Sweden)

    Seyed Mojtaba Hosseini

    2014-01-01

    Full Text Available Objectives. Human breast milk contains a heterogeneous population of cells that have the potential to provide a noninvasive source of cells for cell therapy in many neurodegenerative diseases without any ethical concern. The objectives of this study were to differentiate the breast milk-derived stem cells (BMDSC toward neural stem cells and then into the neurons and neuroglia. Materials and Methods. To do this, the BMDSC were isolated from human breast milk and cultured in Dulbecco’s modified Eagle medium/F12 (DMEM/F12 containing fibroblast growth factor (bFGF. The cells were then characterized by evaluation of the embryonic and stem cell markers. Then, the cells were exposed to culture medium containing 1% B27 and 2% N2 for 7–10 days followed by medium supplemented with B27, N2, bFGF 10 µg/mL, and endothelial growth factor (EGF 20 µg/mL. Then, the sphere-forming assay was performed. The spheres were then differentiated into three neural lineages by withdrawing growth factor in the presence of 5% FBS (fetal bovine serum. The immunofluorescence was done for β-tubulin III, O4, and GFAP (glial fibrillary acidic protein. Results. The results indicated that the cells expressed both embryonic and mesenchymal stem cell (MSC markers. They also showed neurospheres formation that was nestin-positive. The cells were also differentiated into all three neural lineages. Conclusion. The BMDSC can behave in the same way with neural stem cells. They were differentiated into oligodendrocytes, and astrocytes as well as neurons.

  2. Human neural stem cells promote corticospinal axons regeneration and synapse reformation in injured spinal cord of rats

    Institute of Scientific and Technical Information of China (English)

    LIANG Peng; JIN Lian-hong; LIANG Tao; LIU En-zhong; ZHAO Shi-guang

    2006-01-01

    Background Axonal regeneration in lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. This paper studied the action of neural stem cell (NSC) in promoting corticospinal axons regeneration and synapse reformation in rats with injured spinal cord.Methods NSCs were isolated from the cortical tissue of spontaneous aborted human fetuses in accordance with the ethical request. The cells were discarded from the NSC culture to acquire NSC-conditioned medium. Sixty adult Wistar rats were randomly divided into four groups (n=15 in each): NSC graft, NSC medium, graft control and medium control groups. Microsurgical transection of the spinal cord was performed in all the rats at the T11. The NSC graft group received stereotaxic injections of NSCs suspension into both the spinal cord stumps immediately after transection; graft control group received DMEM injection. In NSC medium group,NSC-conditioned medium was administered into the spinal cord every week; NSC culture medium was administered to the medium control group. Hindlimb motor function was assessed using the BBB Locomotor Rating Scale. Regeneration of biotin dextran amine (BDA) labeled corticospinal tract was assessed. Differentiation of NSCs and the expression of synaptophysin at the distal end of the injured spinal cord were observed under a confocal microscope. Group comparisons of behavioral data were analyzed with ANOVA.Results NSCs transplantation resulted in extensive growth of corticospinal axons and locomotor recovery in adult rats after complete spinal cord transection, the mean BBB scores reached 12.5 in NSC graft group and 2.5 in graft control group (P< 0.05). There was also significant difference in BBB score between the NSC medium (11.7) and medium control groups (3.7, P< 0.05). BDA traces regenerated fibers sprouted across the lesion site and entered the caudal part of the spinal cord. Synaptophysin expression

  3. Inhibition of the histone demethylase Kdm5b promotes neurogenesis and derepresses Reln (reelin) in neural stem cells from the adult subventricular zone of mice.

    Science.gov (United States)

    Zhou, Qiong; Obana, Edwin A; Radomski, Kryslaine L; Sukumar, Gauthaman; Wynder, Christopher; Dalgard, Clifton L; Doughty, Martin L

    2016-02-15

    The role of epigenetic regulators in the control of adult neurogenesis is largely undefined. We show that the histone demethylase enzyme Kdm5b (Jarid1b) negatively regulates neurogenesis from adult subventricular zone (SVZ) neural stem cells (NSCs) in culture. shRNA-mediated depletion of Kdm5b in proliferating adult NSCs decreased proliferation rates and reduced neurosphere formation in culture. When transferred to differentiation culture conditions, Kdm5b-depleted adult NSCs migrated from neurospheres with increased velocity. Whole-genome expression screening revealed widespread transcriptional changes with Kdm5b depletion, notably the up-regulation of reelin (Reln), the inhibition of steroid biosynthetic pathway component genes and the activation of genes with intracellular transport functions in cultured adult NSCs. Kdm5b depletion increased extracellular reelin concentration in the culture medium and increased phosphorylation of the downstream reelin signaling target Disabled-1 (Dab1). Sequestration of extracellular reelin with CR-50 reelin-blocking antibodies suppressed the increase in migratory velocity of Kdm5b-depleted adult NSCs. Chromatin immunoprecipitation revealed that Kdm5b is present at the proximal promoter of Reln, and H3K4me3 methylation was increased at this locus with Kdm5b depletion in differentiating adult NSCs. Combined the data suggest Kdm5b negatively regulates neurogenesis and represses Reln in neural stem cells from the adult SVZ. PMID:26739753

  4. Impact of negative emotion on the neural correlates of long-term recognition in younger and older adults

    Directory of Open Access Journals (Sweden)

    Grégoria eKalpouzos

    2012-09-01

    Full Text Available Some studies have suggested that the memory advantage for negative emotional information over neutral information (negativity effect is reduced in aging. Besides the fact that most findings are based on immediate retrieval, the neural underpinnings of long-term emotional memory in aging have so far not been investigated. To address these issues, we assessed recognition of neutral and negative scenes after one- and 3-week retention intervals in younger and older adults using fMRI. We further used an event-related design in order to disentangle successful, false and true recognition. This study revealed 4 key findings: 1 Increased retention interval induced an increased rate of false recognitions for negative scenes, cancelling out the negativity effect (present for hit rates only on discrimination in both younger and older adults; 2 In younger, but not older, adults, reduced activity of the medial temporal lobe was observed over time for neutral scenes, but not for negative scenes, where stable or increased activity was seen; 3 Engagement of amygdala was observed in older adults after a 3-week delay during successful recognition of negative scenes (hits versus misses in comparison with neutral scenes, which may indicate engagement of automatic processes, but engagement of ventrolateral prefrontal cortex was unrelated to amygdala activity and performance; and 4 After 3 weeks, but not after one week, true recognition of negative scenes was characterized by more activity in left hippocampus and lateral occipito-temporal regions (hits versus false alarms. As these regions are known to be related to consolidation mechanisms, the observed pattern may indicate the presence of delayed consolidation of true memories. Nonetheless, older adults’ low performance in discrimination of negative scenes could reflect the fact that overall, after long delays of retention, they rely more on general information rather than on perceptual detail in making

  5. Integrated Model of DNA Sequence Numerical Representation and Artificial Neural Network for Human Donor and Acceptor Sites Prediction

    Directory of Open Access Journals (Sweden)

    Mohammed Abo-Zahhad

    2014-07-01

    Full Text Available Human Genome Project has led to a huge inflow of genomic data. After the completion of human genome sequencing, more and more effort is being put into identification of splicing sites of exons and introns (donor and acceptor sites. These invite bioinformatics to analysis the genome sequences and identify the location of exon and intron boundaries or in other words prediction of splicing sites. Prediction of splice sites in genic regions of DNA sequence is one of the most challenging aspects of gene structure recognition. Over the last two decades, artificial neural networks gradually became one of the essential tools in bioinformatics. In this paper artificial neural networks with different numerical mapping techniques have been employed for building integrated model for splice site prediction in genes. An artificial neural network is trained and then used to find splice sites in human genes. A comparison between different mapping methods using trained neural network in terms of their precision in prediction of donor and acceptor sites will be presented in this paper. Training and measuring performance of neural network are carried out using sequences of the human genome (GRch37/hg19- chr21. Simulation results indicate that using Electron-Ion Interaction Potential numerical mapping method with neural network yields to the best performance in prediction.

  6. Giant occipital meningohydroencephalocele in an adult: Another historical case in neural tube defects.

    Science.gov (United States)

    Coulibaly, O; Sogoba, Y; Kanikomo, D; Dama, M; Camara, M A; Diallo, O

    2016-08-01

    Meningohydroencephalocele is a herniation of meninges, cerebrospinal fluid, brain parenchyma and a part of the ventricular system through a bony defect in the skull. This bone defect may be congenital, spontaneous or traumatic in origin. The lesions are mostly congenital, discovered generally after birth or in very young infants. We report the first historical case of the entity in this location in a 29-year-old man and discuss the pathogenesis, surgical management and social considerations of this type of neural tube defect in our country. PMID:27389765

  7. 3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

    Science.gov (United States)

    Goodwin, Thomas J.

    2013-01-01

    Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

  8. Behavioral and genetic correlates of the neural response to infant crying among human fathers.

    Science.gov (United States)

    Mascaro, Jennifer S; Hackett, Patrick D; Gouzoules, Harold; Lori, Adriana; Rilling, James K

    2014-11-01

    Although evolution has shaped human infant crying and the corresponding response from caregivers, there is marked variation in paternal involvement and caretaking behavior, highlighting the importance of understanding the neurobiology supporting optimal paternal responses to cries. We explored the neural response to infant cries in fathers of children aged 1-2, and its relationship with hormone levels, variation in the androgen receptor (AR) gene, parental attitudes and parental behavior. Although number of AR CAG trinucleotide repeats was positively correlated with neural activity in brain regions important for empathy (anterior insula and inferior frontal gyrus), restrictive attitudes were inversely correlated with neural activity in these regions and with regions involved with emotion regulation (orbitofrontal cortex). Anterior insula activity had a non-linear relationship with paternal caregiving, such that fathers with intermediate activation were most involved. These results suggest that restrictive attitudes may be associated with decreased empathy and emotion regulation in response to a child in distress, and that moderate anterior insula activity reflects an optimal level of arousal that supports engaged fathering. PMID:24336349

  9. Long-term Cultured Human Neural Stem Cells Undergo Spontaneous Transformation to Tumor-Initiating Cells

    Directory of Open Access Journals (Sweden)

    Weihua Wu, Qihua He, Xiaoxia Li, Xiaoyan Zhang, Aili Lu, Ruimin Ge, HongYing Zhen, Alfred E. Chang, Qiao Li, Li Shen

    2011-01-01

    Full Text Available In this report, we describe the spontaneous malignant transformation of long-term cultured human fetal striatum neural stem cells (hsNSCs, passage 17. After subcutaneous transplantation of long-term cultured hsNSCs into immunodeficient nude mice, 2 out of 15 mice formed xenografts which expressed neuroendocrine tumor markers CgA and NSE. T1 cells, a cell line that we derived from one of the two subcutaneous xenografts, have undergone continuous expansion in vitro. These T1 cells showed stem cell-like features and expressed neural stem cell markers nestin and CD133. The T1 cells were involved in abnormal karyotype, genomic instability and fast proliferation. Importantly, after long-term in vitro culture, the T1 cells did not result in subcutaneous xenografts, but induced intracranial tumor formation, indicating that they adjusted themselves to the intracranial microenvironment. We further found that the T1 cells exhibited an overexpressed level of EGFR, and the CD133 positive T1 cells showed a truncation mutation in the exons 2-7 of the EGFR (EGFRvIII gene. These results suggest that continuous expansion of neural stem cells in culture may lead to malignant spontaneous transformation. This phenomenon may be functionally related to EGFR by EGFRvIII gene mutation.

  10. Neural dynamics of reward probability coding: a Magnetoencephalographic study in humans

    Directory of Open Access Journals (Sweden)

    Julie eThomas

    2013-11-01

    Full Text Available Prediction of future rewards and discrepancy between actual and expected outcomes (prediction error are crucial signals for adaptive behavior. In humans, a number of fMRI studies demonstrated that reward probability modulates these two signals in a large brain network. Yet, the spatio-temporal dynamics underlying the neural coding of reward probability remains unknown. Here, using magnetoencephalography, we investigated the neural dynamics of prediction and reward prediction error computations while subjects learned to associate cues of slot machines with monetary rewards with different probabilities. We showed that event-related magnetic fields (ERFs arising from the visual cortex coded the expected reward value 155 ms after the cue, demonstrating that reward value signals emerge early in the visual stream. Moreover, a prediction error was reflected in ERF peaking 300 ms after the rewarded outcome and showing decreasing amplitude with higher reward probability. This prediction error signal was generated in a network including the anterior and posterior cingulate cortex. These findings pinpoint the spatio-temporal characteristics underlying reward probability coding. Together, our results provide insights into the neural dynamics underlying the ability to learn probabilistic stimuli-reward contingencies.

  11. BrainCrafter: An investigation into human-based neural network engineering

    DEFF Research Database (Denmark)

    Piskur, J.; Greve, P.; Togelius, J.;

    2015-01-01

    This paper presents the online application Brain-Crafter, in which users can manually build artificial neural networks (ANNs) to control a robot in a maze environment. Users can either start to construct networks from scratch or elaborate on networks created by other users. In particular, Brain......) collaboration between users presented difficulties and (3) the human-developed ANNs that managed to solve the task had certain regularities, suggesting that humans can use some of their intuition and spatial understanding in the design of ANNs. Most importantly, the initial results in this paper can serve as a...... starting point for investigating how to best combine human and machine design capabilities to create more complex artificial brains....

  12. Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth.

    Science.gov (United States)

    Tang, Hengli; Hammack, Christy; Ogden, Sarah C; Wen, Zhexing; Qian, Xuyu; Li, Yujing; Yao, Bing; Shin, Jaehoon; Zhang, Feiran; Lee, Emily M; Christian, Kimberly M; Didier, Ruth A; Jin, Peng; Song, Hongjun; Ming, Guo-Li

    2016-05-01

    The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells. Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell-cycle-related pathways. Our results identify hNPCs as a direct ZIKV target. In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds. PMID:26952870

  13. Derivation of Neural Progenitors and Retinal Pigment Epithelium from Common Marmoset and Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Laughing Bear Torrez

    2012-01-01

    Full Text Available Embryonic and induced pluripotent stem cells (IPSCs derived from mammalian species are valuable tools for modeling human disease, including retinal degenerative eye diseases that result in visual loss. Restoration of vision has focused on transplantation of neural progenitor cells (NPCs and retinal pigmented epithelium (RPE to the retina. Here we used transgenic common marmoset (Callithrix jacchus and human pluripotent stem cells carrying the enhanced green fluorescent protein (eGFP reporter as a model system for retinal differentiation. Using suspension and subsequent adherent differentiation cultures, we observed spontaneous in vitro differentiation that included NPCs and cells with pigment granules characteristic of differentiated RPE. Retinal cells derived from human and common marmoset pluripotent stem cells provide potentially unlimited cell sources for testing safety and immune compatibility following autologous or allogeneic transplantation using nonhuman primates in early translational applications.

  14. Human activities recognition by head movement using partial recurrent neural network

    Science.gov (United States)

    Tan, Henry C. C.; Jia, Kui; De Silva, Liyanage C.

    2003-06-01

    Traditionally, human activities recognition has been achieved mainly by the statistical pattern recognition methods or the Hidden Markov Model (HMM). In this paper, we propose a novel use of the connectionist approach for the recognition of ten simple human activities: walking, sitting down, getting up, squatting down and standing up, in both lateral and frontal views, in an office environment. By means of tracking the head movement of the subjects over consecutive frames from a database of different color image sequences, and incorporating the Elman model of the partial recurrent neural network (RNN) that learns the sequential patterns of relative change of the head location in the images, the proposed system is able to robustly classify all the ten activities performed by unseen subjects from both sexes, of different race and physique, with a recognition rate as high as 92.5%. This demonstrates the potential of employing partial RNN to recognize complex activities in the increasingly popular human-activities-based applications.

  15. Neuropeptide Y in the Adult and Fetal Human Pineal Gland

    Directory of Open Access Journals (Sweden)

    Morten Møller

    2014-01-01

    Full Text Available Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  16. Direct Neural Conversion from Human Fibroblasts Using Self-Regulating and Nonintegrating Viral Vectors

    Directory of Open Access Journals (Sweden)

    Shong Lau

    2014-12-01

    Full Text Available Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These findings open up the possibility of generating subtype-specific neurons of human origin for therapeutic use from fetal cell, from patients themselves, or from matched donors. In this study, we present an improved system for direct neural conversion of human fibroblasts. The neural reprogramming genes are regulated by the neuron-specific microRNA, miR-124, such that each cell turns off expression of the reprogramming genes once the cell has reached a stable neuronal fate. The regulated system can be combined with integrase-deficient vectors, providing a nonintegrative and self-regulated conversion system that rids problems associated with the integration of viral transgenes into the host genome. These modifications make the system suitable for clinical use and therefore represent a major step forward in the development of induced neurons for cell therapy.

  17. Integrating verbal and nonverbal communication in a dynamic neural field architecture for human-robot interaction

    Directory of Open Access Journals (Sweden)

    Luis Louro

    2010-05-01

    Full Text Available How do humans coordinate their intentions, goals and motor behaviors when performing joint action tasks? Recent experimental evidence suggests that resonance processes in the observer's motor system are crucially involved in our ability to understand actions of others', to infer their goals and even to comprehend their action-related language. In this paper, we present a control architecture for human-robot collaboration that exploits this close perception-action linkage as a means to achieve more natural and efficient communication grounded in sensorimotor experiences. The architecture is formalized by a coupled system of dynamic neural fields representing a distributed network of neural populations that encode in their activation patterns goals, actions and shared task knowledge. We validate the verbal and non-verbal communication skills of the robot in a joint assembly task in which the human-robot team has to construct toy objects from their components. The experiments focus on the robot’s capacity to anticipate the user’s needs and to detect and communicate unexpected events that may occur during joint task execution.

  18. The experimental study of genetic engineering human neural stem cells mediated by lentivirus to express multigene

    Institute of Scientific and Technical Information of China (English)

    CAI Pei-qiang; TANG Xun; LIN Yue-qiu; Oudega Martin; SUN Guang-yun; XU Lin; YANG Yun-kang; ZHOU Tian-hua

    2006-01-01

    Objective:To explore the feasibility to construct genetic engineering human neural stem cells (hNSCs)mediated by lentivirus to express multigene in order to provide a graft source for further studies of spinal cord injury (SCI).Methods: Human neural stem cells from the brain cortex of human abortus were isolated and cultured, then gene was modified by lentivirus to express both green fluorescence protein (GFP) and rat neurotrophin-3(NT-3); the transgenic expression was detected by the methods of fluorescence microscope, dorsal root ganglion of fetal rats and slot blot.Results: Genetic engineering hNSCs were successfully constructed. All of the genetic engineering hNSCs which expressed bright green fluorescence were observed under the fluorescence microscope. The conditioned medium of transgenic hNSCs could induce neurite flourishing outgrowth from dorsal root ganglion (DRG). The genetic engineering hNSCs expressed high level NT-3 which could be detected by using slot blot.Conclusions: Genetic engineering hNSCs mediated by lentivirus can be constructed to express multigene successfully.

  19. Evolutionary Basis of Human Running and Its Impact on Neural Function.

    Science.gov (United States)

    Schulkin, Jay

    2016-01-01

    Running is not unique to humans, but it is seemingly a basic human capacity. This article addresses the evolutionary origins of humans running long distances, the basic physical capability of running, and the neurogenesis of aerobic fitness. This article more specifically speaks to the conditions that set the stage for the act of running, and then looks at brain expression, and longer-term consequences of running within a context of specific morphological features and diverse information molecules that participate in our capacity for running and sport. While causal factors are not known, we do know that physiological factors are involved in running and underlie neural function. Multiple themes about running are discussed in this article, including neurogenesis, neural plasticity, and memory enhancement. Aerobic exercise increases anterior hippocampus size. This expansion is linked to the improvement of memory, which reflects the improvement of learning as a function of running activity in animal studies. Higher fitness is associated with greater expansion, not only of the hippocampus, but of several other brain regions. PMID:27462208

  20. Cell-permeable p38 MAP kinase promotes migration of adult neural stem/progenitor cells

    Science.gov (United States)

    Hamanoue, Makoto; Morioka, Kazuhito; Ohsawa, Ikuroh; Ohsawa, Keiko; Kobayashi, Masaaki; Tsuburaya, Kayo; Akasaka, Yoshikiyo; Mikami, Tetsuo; Ogata, Toru; Takamatsu, Ken

    2016-01-01

    Endogenous neural stem/progenitor cells (NPCs) can migrate toward sites of injury, but the migration activity of NPCs is insufficient to regenerate damaged brain tissue. In this study, we showed that p38 MAP kinase (p38) is expressed in doublecortin-positive adult NPCs. Experiments using the p38 inhibitor SB203580 revealed that endogenous p38 participates in NPC migration. To enhance NPC migration, we generated a cell-permeable wild-type p38 protein (PTD-p38WT) in which the HIV protein transduction domain (PTD) was fused to the N-terminus of p38. Treatment with PTD-p38WT significantly promoted the random migration of adult NPCs without affecting cell survival or differentiation; this effect depended on the cell permeability and kinase activity of the fusion protein. These findings indicate that PTD-p38WT is a novel and useful tool for unraveling the roles of p38, and that this protein provides a reasonable approach for regenerating the injured brain by enhancing NPC migration. PMID:27067799

  1. Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks

    OpenAIRE

    Nebel, Rebecca A.; Dejian Zhao; Erika Pedrosa; Jill Kirschen; Lachman, Herbert M.; Deyou Zheng; Abrahams, Brett S

    2016-01-01

    Deletions encompassing the BP1-2 region at 15q11.2 increase schizophrenia and epilepsy risk, but only some carriers have either disorder. To investigate the role of CYFIP1, a gene within the region, we performed knockdown experiments in human neural progenitors derived from donors with 2 copies of each gene at the BP1-2 locus. RNA-seq and cellular assays determined that knockdown of CYFIP1 compromised cytoskeletal remodeling. FMRP targets and postsynaptic density genes, each implicated in sch...

  2. Long-term Cultured Human Neural Stem Cells Undergo Spontaneous Transformation to Tumor-Initiating Cells

    OpenAIRE

    Weihua Wu, Qihua He, Xiaoxia Li, Xiaoyan Zhang, Aili Lu, Ruimin Ge, HongYing Zhen, Alfred E. Chang, Qiao Li, Li Shen

    2011-01-01

    In this report, we describe the spontaneous malignant transformation of long-term cultured human fetal striatum neural stem cells (hsNSCs, passage 17). After subcutaneous transplantation of long-term cultured hsNSCs into immunodeficient nude mice, 2 out of 15 mice formed xenografts which expressed neuroendocrine tumor markers CgA and NSE. T1 cells, a cell line that we derived from one of the two subcutaneous xenografts, have undergone continuous expansion in vitro. These T1 cells showed stem ...

  3. Human conditionally immortalized neural stem cells improve locomotor function after spinal cord injury in the rat

    Czech Academy of Sciences Publication Activity Database

    Amemori, Takashi; Romanyuk, Nataliya; Jendelová, Pavla; Herynek, V.; Turnovcová, Karolína; Procházka, Pavel; Kapcalová, Miroslava; Cocks, G.; Price, J.; Syková, Eva

    2013-01-01

    Roč. 4, č. 3 (2013), s. 68. ISSN 1757-6512 R&D Projects: GA ČR(CZ) GAP304/12/1370; GA ČR GA13-00939S; GA MŠk LH12024; GA ČR(CZ) GBP304/12/G069 Grant ostatní: GA MZd(CZ) 00023001IKEM Institutional support: RVO:68378041 Keywords : human fetal neural stem cells * spinal cord injury * motor neuron differentiation Subject RIV: FH - Neurology Impact factor: 4.634, year: 2013

  4. Human behavioral momentum in a sample of older adults.

    Science.gov (United States)

    Plaud, J J; Plaud, D M; von Duvillard, S P

    1999-04-01

    Behavioral momentum, the persistence of behavior under altered environmental contingencies, is derived from Newtonian physics and operant psychology. It has relevance to behavior analysis in terms of shaping strong behaviors and ensuring effective relapse prevention strategies in behavior modification and therapy. The authors investigated whether changing the operant schedule contingencies affects the responses of older humans to different stimuli when reinforcement density is systematically manipulated. Fifteen older adults participated in a computer study in which each of 2 keys in a baseline condition was associated with the same schedule of reinforcement and multiple variable intervals; the only difference was that 1 reinforcer was 10 times larger than the other. After 6 sessions, the authors changed the contingency schedule to either an extinction condition, a variable-time schedule, or a different variable-interval schedule, to assess how participants' responses persisted when reinforcement contingencies were systematically changed. The results were consistent with the predictions of behavioral momentum. The participants not only biased their responses in favor of the more densely reinforcing key, but when contingencies changed, they showed significantly biased responses. Results supported the conclusion that healthy older adults allocate their behaviors in a manner very sensitive to training stimuli conditions; consistent with the basic principles of behavioral momentum, they show a degree of resistance to change in their behaviors when the behavioral contingencies are altered. PMID:10368942

  5. Neural processing of basic tastes in healthy young and older adults - an fMRI study.

    Science.gov (United States)

    Hoogeveen, Heleen R; Dalenberg, Jelle R; Renken, Remco J; ter Horst, Gert J; Lorist, Monicque M

    2015-10-01

    Ageing affects taste perception as shown in psychophysical studies, however, underlying structural and functional mechanisms of these changes are still largely unknown. To investigate the neurobiology of age-related differences associated with processing of basic tastes, we measured brain activation (i.e. fMRI-BOLD activity) during tasting of four increasing concentrations of sweet, sour, salty, and bitter tastes in young (average 23 years of age) and older (average 65 years of age) adults. The current study highlighted age-related differences in taste perception at the different higher order brain areas of the taste pathway. We found that the taste information delivered to the brain in young and older adults was not different, as illustrated by the absence of age effects in NTS and VPM activity. Our results indicate that multisensory integration changes with age; older adults showed less brain activation to integrate both taste and somatosensory information. Furthermore, older adults directed less attention to the taste stimulus; therefore attention had to be reallocated by the older individuals in order to perceive the tastes. In addition, we considered that the observed age-related differences in brain activation between taste concentrations in the amygdala reflect its involvement in processing both concentration and pleasantness of taste. Finally, we state the importance of homeostatic mechanisms in understanding the taste quality specificity in age related differences in taste perception. PMID:26072251

  6. Brain tumour stem cells: the undercurrents of human brain cancer and their relationship to neural stem cells

    OpenAIRE

    Dirks, Peter B.

    2007-01-01

    Conceptual and technical advances in neural stem cell biology are being applied to the study of human brain tumours. These studies suggest that human brain tumours are organized as a hierarchy and are maintained by a small number of tumour cells that have stem cell properties. Most of the bulk population of human brain tumours comprise cells that have lost the ability to initiate and maintain tumour growth. Although the cell of origin for human brain tumours is uncertain, recent evidence poin...

  7. Classification of human activity on water through micro-Dopplers using deep convolutional neural networks

    Science.gov (United States)

    Kim, Youngwook; Moon, Taesup

    2016-05-01

    Detecting humans and classifying their activities on the water has significant applications for surveillance, border patrols, and rescue operations. When humans are illuminated by radar signal, they produce micro-Doppler signatures due to moving limbs. There has been a number of research into recognizing humans on land by their unique micro-Doppler signatures, but there is scant research into detecting humans on water. In this study, we investigate the micro-Doppler signatures of humans on water, including a swimming person, a swimming person pulling a floating object, and a rowing person in a small boat. The measured swimming styles were free stroke, backstroke, and breaststroke. Each activity was observed to have a unique micro-Doppler signature. Human activities were classified based on their micro-Doppler signatures. For the classification, we propose to apply deep convolutional neural networks (DCNN), a powerful deep learning technique. Rather than using conventional supervised learning that relies on handcrafted features, we present an alternative deep learning approach. We apply the DCNN, one of the most successful deep learning algorithms for image recognition, directly to a raw micro-Doppler spectrogram of humans on the water. Without extracting any explicit features from the micro-Dopplers, the DCNN can learn the necessary features and build classification boundaries using the training data. We show that the DCNN can achieve accuracy of more than 87.8% for activity classification using 5- fold cross validation.

  8. TNF-α affects human cortical neural progenitor cell differentiation through the autocrine secretion of leukemia inhibitory factor.

    Directory of Open Access Journals (Sweden)

    Xiqian Lan

    Full Text Available Proinflammatory cytokine tumor necrosis factor-alpha (TNF-α is a crucial effector of immune responses in the brain that participates in the pathogenesis of several acute and chronic neurodegenerative disorders. Accumulating evidence has suggested that TNF-α negatively regulates embryonic and adult neurogenesis. However, the effect of TNF-α on cell fate decision in human neural progenitor cells (NPCs has rarely been studied. Our previous studies have shown that recombinant TNF-α enhances astrogliogenesis and inhibits neurogenesis of human NPCs through the STAT3 (signal transducer and activator of transcription 3 pathway. In the current study, we further elucidated the specific mechanism involved in TNF-α-induced astrogliogenesis. We found that TNF-α activated STAT3 at delayed time points (6 h and 24 h, whereas conditioned medium collected from TNF-α-treated NPCs induced an immediate STAT3 activation. These data suggest TNF-α plays an indirect role on STAT3 activation and the subsequent NPC differentiation. Further, we showed that TNF-α induced abundant amounts of the IL-6 family cytokines, including Leukemia inhibitory factor (LIF and Interleukin 6 (IL-6, in human NPCs. TNF-α-induced STAT3 phosphorylation and astrogliogenesis were abrogated by the addition of neutralizing antibody for LIF, but not for IL-6, revealing a critical role of autocrine secretion of LIF in TNF-α-induced STAT3 activation and astrogliogenesis. This study generates important data elucidating the role of TNF-α in neurogenesis and may provide insight into new therapeutic strategies for brain inflammation.

  9. Human herpesvirus 7 is a constitutive inhabitant of adult human saliva.

    OpenAIRE

    Wyatt, L S; Frenkel, N

    1992-01-01

    We report the frequent isolation of human herpesvirus 7 from the saliva of healthy adults. Virus isolates recovered from different individuals exhibited minimal restriction enzyme polymorphism, which was mostly confined to heterogeneous (het) sequences in the genome. DNAs of isolates recovered from the same individual over a period of several months showed the same characteristic het fragments, indicating the stability of the het sequences upon virus replication and shedding in vivo. In contr...

  10. Neural correlates of auditory-cognitive processing in older adult cochlear implant recipients.

    Science.gov (United States)

    Henkin, Yael; Yaar-Soffer, Yifat; Steinberg, Meidan; Muchnik, Chava

    2014-01-01

    With the growing number of older adults receiving cochlear implants (CI), there is general agreement that substantial benefits can be gained. Nonetheless, variability in speech perception performance is high, and the relative contribution and interactions among peripheral, central-auditory, and cognitive factors are not fully understood. The goal of the present study was to compare auditory-cognitive processing in older-adult CI recipients with that of older normal-hearing (NH) listeners by means of behavioral and electrophysiologic manifestations of a high-load cognitive task. Auditory event-related potentials (AERPs) were recorded from 9 older postlingually deafened adults with CI (age at CI >60) and 10 age-matched listeners with NH, while performing an auditory Stroop task. Participants were required to classify the speaker's gender (male/female) that produced the words 'mother' or 'father' while ignoring the irrelevant congruent or incongruent word meaning. Older CI and NH listeners exhibited comparable reaction time, performance accuracy, and initial sensory-perceptual processing (i.e. N1 potential). Nonetheless, older CI recipients showed substantially prolonged and less efficient perceptual processing (i.e. P3 potential). Congruency effects manifested in longer reaction time (i.e. Stroop effect), execution time, and P3 latency to incongruent versus congruent stimuli in both groups in a similar fashion; however, markedly prolonged P3 and shortened execution time were evident in older CI recipients. Collectively, older adults (CI and NH) employed a combined perceptual and postperceptual conflict processing strategy; nonetheless, the relative allotment of perceptual resources was substantially enhanced to maintain adequate performance in CI recipients. In sum, the recording of AERPs together with the simultaneously obtained behavioral measures during a Stroop task exposed a differential time course of auditory-cognitive processing in older CI recipients that

  11. Adult stem cells in neural repair: Current options,limitations and perspectives

    Institute of Scientific and Technical Information of China (English)

    Eric Domingos Mariano; Manoel Jacobsen Teixeira; Suely Kazue Nagahashi Marie; Guilherme Lepski

    2015-01-01

    Stem cells represent a promising step for the future ofregenerative medicine. As they are able to differentiateinto any cell type, tissue or organ, these cells are greatcandidates for treatments against the worst diseasesthat defy doctors and researchers around the world.Stem cells can be divided into three main groups (1)embryonic stem cells; (2) fetal stem cells; and (3) adultstem cells. In terms of their capacity for proliferation,stem cells are also classified as totipotent, pluripotentor multipotent. Adult stem cells, also known as somaticcells, are found in various regions of the adult organism,such as bone marrow, skin, eyes, viscera and brain.They can differentiate into unipotent cells of theresiding tissue, generally for the purpose of repair.These cells represent an excellent choice in regenerativemedicine, every patient can be a donor of adult stemcells to provide a more customized and efficient therapyagainst various diseases, in other words, they allow theopportunity of autologous transplantation. But in orderto start clinical trials and achieve great results, we needto understand how these cells interact with the hosttissue, how they can manipulate or be manipulated bythe microenvironment where they will be transplantedand for how long they can maintain their multipotentstate to provide a full regeneration.

  12. A biokinetic model for systemic technetium in adult humans

    International Nuclear Information System (INIS)

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection. Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood

  13. Unsupervised Decoding of Long-Term, Naturalistic Human Neural Recordings with Automated Video and Audio Annotations

    Science.gov (United States)

    Wang, Nancy X. R.; Olson, Jared D.; Ojemann, Jeffrey G.; Rao, Rajesh P. N.; Brunton, Bingni W.

    2016-01-01

    Fully automated decoding of human activities and intentions from direct neural recordings is a tantalizing challenge in brain-computer interfacing. Implementing Brain Computer Interfaces (BCIs) outside carefully controlled experiments in laboratory settings requires adaptive and scalable strategies with minimal supervision. Here we describe an unsupervised approach to decoding neural states from naturalistic human brain recordings. We analyzed continuous, long-term electrocorticography (ECoG) data recorded over many days from the brain of subjects in a hospital room, with simultaneous audio and video recordings. We discovered coherent clusters in high-dimensional ECoG recordings using hierarchical clustering and automatically annotated them using speech and movement labels extracted from audio and video. To our knowledge, this represents the first time techniques from computer vision and speech processing have been used for natural ECoG decoding. Interpretable behaviors were decoded from ECoG data, including moving, speaking and resting; the results were assessed by comparison with manual annotation. Discovered clusters were projected back onto the brain revealing features consistent with known functional areas, opening the door to automated functional brain mapping in natural settings. PMID:27148018

  14. Intermittent high oxygen influences the formation of neural retinal tissue from human embryonic stem cells.

    Science.gov (United States)

    Gao, Lixiong; Chen, Xi; Zeng, Yuxiao; Li, Qiyou; Zou, Ting; Chen, Siyu; Wu, Qian; Fu, Caiyun; Xu, Haiwei; Yin, Zheng Qin

    2016-01-01

    The vertebrate retina is a highly multilayered nervous tissue with a large diversity of cellular components. With the development of stem cell technologies, human retinas can be generated in three-dimensional (3-D) culture in vitro. However, understanding the factors modulating key productive processes and the way that they influence development are far from clear. Oxygen, as the most essential element participating in metabolism, is a critical factor regulating organic development. In this study, using 3-D culture of human stem cells, we examined the effect of intermittent high oxygen treatment (40% O2) on the formation and cellular behavior of neural retinas (NR) in the embryonic body (EB). The volume of EB and number of proliferating cells increased significantly under 40% O2 on day 38, 50, and 62. Additionally, the ratio of PAX6+ cells within NR was significantly increased. The neural rosettes could only develop with correct apical-basal polarity under 40% O2. In addition, the generation, migration and maturation of retinal ganglion cells were enhanced under 40% O2. All of these results illustrated that 40% O2 strengthened the formation of NR in EB with characteristics similar to the in vivo state, suggesting that the hyperoxic state facilitated the retinal development in vitro. PMID:27435522

  15. Unsupervised Decoding of Long-Term, Naturalistic Human Neural Recordings with Automated Video and Audio Annotations.

    Science.gov (United States)

    Wang, Nancy X R; Olson, Jared D; Ojemann, Jeffrey G; Rao, Rajesh P N; Brunton, Bingni W

    2016-01-01

    Fully automated decoding of human activities and intentions from direct neural recordings is a tantalizing challenge in brain-computer interfacing. Implementing Brain Computer Interfaces (BCIs) outside carefully controlled experiments in laboratory settings requires adaptive and scalable strategies with minimal supervision. Here we describe an unsupervised approach to decoding neural states from naturalistic human brain recordings. We analyzed continuous, long-term electrocorticography (ECoG) data recorded over many days from the brain of subjects in a hospital room, with simultaneous audio and video recordings. We discovered coherent clusters in high-dimensional ECoG recordings using hierarchical clustering and automatically annotated them using speech and movement labels extracted from audio and video. To our knowledge, this represents the first time techniques from computer vision and speech processing have been used for natural ECoG decoding. Interpretable behaviors were decoded from ECoG data, including moving, speaking and resting; the results were assessed by comparison with manual annotation. Discovered clusters were projected back onto the brain revealing features consistent with known functional areas, opening the door to automated functional brain mapping in natural settings. PMID:27148018

  16. Classification of Human Emotion from Deap EEG Signal Using Hybrid Improved Neural Networks with Cuckoo Search

    Directory of Open Access Journals (Sweden)

    M. Sreeshakthy

    2016-01-01

    Full Text Available Department of Computer Science and Engineering,Anna University Regional Centre, Coimbatore, Indiam.sribtechit@gmail.comJ. PreethiDepartment of Computer Science and EngineeringAnna University Regional Centre, Coimbatore, Indiapreethi17j@yahoo.comEmotions are very important in human decision handling, interaction and cognitive process. In this paper describes that recognize the human emotions from DEAP EEG dataset with different kind of methods. Audio – video based stimuli is used to extract the emotions. EEG signal is divided into different bands using discrete wavelet transformation with db8 wavelet function for further process. Statistical and energy based features are extracted from the bands, based on the features emotions are classified with feed forward neural network with weight optimized algorithm like PSO. Before that the particular band has to be selected based on the training performance of neural networks and then the emotions are classified. In this experimental result describes that the gamma and alpha bands are provides the accurate classification result with average classification rate of 90.3% of using NNRBF, 90.325% of using PNN, 96.3% of using PSO trained NN, 98.1 of using Cuckoo trained NN. At last the emotions are classified into two different groups like valence and arousal. Based on that identifies the person normal and abnormal behavioral using classified emotion.

  17. Neurofeedback of slow cortical potentials: neural mechanisms and feasibility of a placebo-controlled design in healthy adults

    Directory of Open Access Journals (Sweden)

    Holger eGevensleben

    2014-12-01

    Full Text Available To elucidate basic mechanisms underlying neurofeedback we investigated neural mechanisms of training of slow cortical potentials by considering EEG- and fMRI. Additionally, we analyzed the feasibility of a double-blind, placebo-controlled design in NF research based on regulation performance during treatment sessions and self-assessment of the participants. Twenty healthy adults participated in 16 sessions of SCP training: 9 participants received regular SCP training, 11 participants received sham feedback. At three time points (pre, intermediate, post fMRI and EEG/ERP-measurements were conducted during a continuous performance test (CPT. Performance-data during the sessions (regulation performance in the treatment group and the placebo group were analyzed. Analysis of EEG-activity revealed in the SCP group a strong enhancement of the CNV (electrode Cz at the intermediate assessment, followed by a decrease back to baseline at the post-treatment assessment. In contrast, in the placebo group a continuous but smaller increase of the CNV could be obtained from pre to post assessment. The increase of the CNV in the SCP group at intermediate testing was superior to the enhancement in the placebo group. The changes of the CNV were accompanied by a continuous improvement in the test performance of the CPT from pre to intermediate to post assessment comparable in both groups. The change of the CNV in the SCP group is interpreted as an indicator of neural plasticity and efficiency while an increase of the CNV in the placebo group might reflect learning and improved timing due to the frequent task repetition.In the fMRI analysis evidence was obtained for neuronal plasticity. After regular SCP neurofeedback activation in the posterior parietal cortex decreased from the pre- to the intermediate measurement and increased again in the post measurement, inversely following the U-shaped increase and decrease of the tCNV EEG amplitude in the SCP-trained group

  18. Congenital and prolonged adult-onset deafness cause distinct degradations in neural ITD coding with bilateral cochlear implants.

    Science.gov (United States)

    Hancock, Kenneth E; Chung, Yoojin; Delgutte, Bertrand

    2013-06-01

    Bilateral cochlear implant (CI) users perform poorly on tasks involving interaural time differences (ITD), which are critical for sound localization and speech reception in noise by normal-hearing listeners. ITD perception with bilateral CI is influenced by age at onset of deafness and duration of deafness. We previously showed that ITD coding in the auditory midbrain is degraded in congenitally deaf white cats (DWC) compared to acutely deafened cats (ADC) with normal auditory development (Hancock et al., J. Neurosci, 30:14068). To determine the relative importance of early onset of deafness and prolonged duration of deafness for abnormal ITD coding in DWC, we recorded from single units in the inferior colliculus of cats deafened as adults 6 months prior to experimentation (long-term deafened cats, LTDC) and compared neural ITD coding between the three deafness models. The incidence of ITD-sensitive neurons was similar in both groups with normal auditory development (LTDC and ADC), but significantly diminished in DWC. In contrast, both groups that experienced prolonged deafness (LTDC and DWC) had broad distributions of best ITDs around the midline, unlike the more focused distributions biased toward contralateral-leading ITDs present in both ADC and normal-hearing animals. The lack of contralateral bias in LTDC and DWC results in reduced sensitivity to changes in ITD within the natural range. The finding that early onset of deafness more severely degrades neural ITD coding than prolonged duration of deafness argues for the importance of fitting deaf children with sound processors that provide reliable ITD cues at an early age. PMID:23462803

  19. Behavioral outcome measures used for human neural stem cell transplantation in rat stroke models

    Directory of Open Access Journals (Sweden)

    Matthew B. Jensen

    2011-09-01

    Full Text Available Stroke is a leading cause of death and disability, leading to the development of various stroke models to test new treatments, most commonly in the rat. Human stroke trials focus on disability, related primarily to neurological deficits. To better model the clinical application of these treatments, many behavioral tests have been developed using the rat stroke model. We performed a systematic review of all the behavioral outcome measures used in published studies of human neural stem cell transplantation in rat stroke models. The reviewed tests include motor, sensory, cognitive, activity, and combination tests. For each test, we give a brief description, trace the origin of the test, and discuss test performance in the reviewed studies. We conclude that while many behavioral tests are available for this purpose, there does not appear to be consensus on an optimal testing strategy.

  20. Neuroscience of Human Social Interactions and Adult Attachment Style

    Directory of Open Access Journals (Sweden)

    Pascal Vrticka

    2012-07-01

    Full Text Available Since its first description four decades ago, attachment theory has become one of the principal developmental psychological frameworks for describing the role of individual differences in the establishment and maintenance of social bonds between people. Yet, still little is known about the neurobiological underpinnings of attachment orientations and their well-established impact on a range of social and affective behaviors. In the present review, we summarize data from recent studies using cognitive and imaging approaches to characterize attachment styles and their effect on emotion and social cognition. We propose a functional neuroanatomical framework to integrate the key brain mechanisms involved in the perception and regulation of social emotional information, and their modulation by individual differences in terms of secure versus insecure (more specifically avoidant, anxious, or resolved vs. unresolved attachment traits. This framework describes how each individual’s attachment style (built through interactions between personal relationship history and predispositions may influence the encoding of approach versus aversion tendencies (safety versus threat in social encounters, implicating the activation of a network of subcortical (amygdala, hippocampus, striatum and cortical (insula, cingulate limbic areas. These basic and automatic affective mentalization mechanisms are in turn modulated by more elaborate and voluntary cognitive mentalization processes, subserving theory of mind, cognitive control, and emotion regulation capacities, implicating a distinct network (in medial prefrontal cortex, superior temporal sulcus, and temporo-parietal junction, among others. Such research does not only help better understand the neural underpinnings of human social behavior, but also provides important insights on psychopathological conditions where attachment dysregulations is likely to play an important (causal role.

  1. Generation of human cortical neurons from a new immortal fetal neural stem cell line

    International Nuclear Information System (INIS)

    Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology

  2. Professional Fulfillment and Satisfaction of US and Canadian Adult Education and Human Resource Development Faculty

    Science.gov (United States)

    Peterson, Shari L.; Wiesenberg, Faye

    2004-01-01

    This comparative study explored the professional fulfillment and job satisfaction of US and Canadian college and university faculty in the fields of Adult Education and Human Resource Development. In Autumn 2001, we disseminated electronically "The Adult Education and Human Resource Development Faculty Survey" to a selected sample of Canadian and…

  3. Cardiovascular and coordination training differentially improve cognitive performance and neural processing in older adults

    Directory of Open Access Journals (Sweden)

    Claudia eVoelcker-Rehage

    2011-03-01

    Full Text Available Recent studies revealed a positive influence of physical activity on cognitive functioning in older adults. Studies that investigate the behavioral and neurophysiological effects of type and long term duration of physical training, however, are missing. We performed a 12-month longitudinal study to investigate the effects of cardiovascular and coordination training (control group: relaxation and stretching on cognitive functions (executive control and perceptual speed in older adults. We analyzed data of 44 participants aged 62 to 79 years. Participants were trained 3 times a week for 12 months. Their physical and cognitive performance was tested prior to training, and after 6 and 12 months. Changes in brain activation patterns were investigated using functional MRI. On the behavioral level, both experimental groups improved in executive functioning and perceptual speed but with differential effects on speed and accuracy. In line with the behavioral findings, neurophysiological results for executive control also revealed changes (increases and reductions in brain activity for both interventions in frontal, parietal, and sensorimotor cortical areas. In contrast to the behavioral findings, neurophysiological changes were linear without indication of a plateau. In both intervention groups, prefrontal areas showed decreased activation after 6 and 12 months when performing an executive control task, as compared to the control group, indicating more efficient information processing. Furthermore, cardiovascular training was associated with an increased activation of the sensorimotor network, whereas coordination training was associated with increased activation in the visual-spatial network. Our data suggest that besides cardiovascular training also other types of physical activity improve cognition of older adults. The mechanisms, however, that underlie the performance changes seem to differ depending on the intervention.

  4. Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective

    OpenAIRE

    Alexandra Zirra; Sarah Wiethoff; Rickie Patani

    2016-01-01

    Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs) became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover funda...

  5. STAT3 modulation to enhance motor neuron differentiation in human neural stem cells.

    Directory of Open Access Journals (Sweden)

    Rajalaxmi Natarajan

    Full Text Available Spinal cord injury or amyotrophic lateral sclerosis damages spinal motor neurons and forms a glial scar, which prevents neural regeneration. Signal transducer and activator of transcription 3 (STAT3 plays a critical role in astrogliogenesis and scar formation, and thus a fine modulation of STAT3 signaling may help to control the excessive gliogenic environment and enhance neural repair. The objective of this study was to determine the effect of STAT3 inhibition on human neural stem cells (hNSCs. In vitro hNSCs primed with fibroblast growth factor 2 (FGF2 exhibited a lower level of phosphorylated STAT3 than cells primed by epidermal growth factor (EGF, which correlated with a higher number of motor neurons differentiated from FGF2-primed hNSCs. Treatment with STAT3 inhibitors, Stattic and Niclosamide, enhanced motor neuron differentiation only in FGF2-primed hNSCs, as shown by increased homeobox gene Hb9 mRNA levels as well as HB9+ and microtubule-associated protein 2 (MAP2+ co-labeled cells. The increased motor neuron differentiation was accompanied by a decrease in the number of glial fibrillary acidic protein (GFAP-positive astrocytes. Interestingly, Stattic and Niclosamide did not affect the level of STAT3 phosphorylation; rather, they perturbed the nuclear translocation of phosphorylated STAT3. In summary, we demonstrate that FGF2 is required for motor neuron differentiation from hNSCs and that inhibition of STAT3 further increases motor neuron differentiation at the expense of astrogliogenesis. Our study thus suggests a potential benefit of targeting the STAT3 pathway for neurotrauma or neurodegenerative diseases.

  6. Early Life Manipulations of the Nonapeptide System Alter Pair Maintenance Behaviors and Neural Activity in Adult Male Zebra Finches.

    Science.gov (United States)

    Baran, Nicole M; Tomaszycki, Michelle L; Adkins-Regan, Elizabeth

    2016-01-01

    Adult zebra finches (T. guttata) form socially monogamous pair bonds characterized by proximity, vocal communication, and contact behaviors. In this experiment, we tested whether manipulations of the nonapeptide hormone arginine vasotocin (AVT, avian homolog of vasopressin) and the V1a receptor (V1aR) early in life altered species-typical pairing behavior in adult zebra finches of both sexes. Although there was no effect of treatment on the tendency to pair in either sex, males in different treatments exhibited profoundly different profiles of pair maintenance behavior. Following a brief separation, AVT-treated males were highly affiliative with their female partner but sang very little compared to Controls. In contrast, males treated with a V1aR antagonist sang significantly less than Controls, but did not differ in affiliation. These effects on behavior in males were also reflected in changes in the expression of V1aR and immediate early gene activity in three brain regions known to be involved in pairing behavior in birds: the medial amygdala, medial bed nucleus of the stria terminalis, and the lateral septum. AVT males had higher V1aR expression in the medial amygdala than both Control and antagonist-treated males and immediate early gene activity of V1aR neurons in the medial amygdala was positively correlated with affiliation. Antagonist treated males showed decreased activity in the medial amygdala. In addition, there was a negative correlation between the activity of V1aR cells in the medial bed nucleus of the stria terminalis and singing. Treatment also affected the expression of V1aR and activity in the lateral septum, but this was not correlated with any behaviors measured. These results provide evidence that AVT and V1aR play developmental roles in specific pair maintenance behaviors and the neural substrate underlying these behaviors in a bird. PMID:27065824

  7. Early Life Manipulations of the Nonapeptide System Alter Pair Maintenance Behaviors and Neural Activity in Adult Male Zebra Finches

    Directory of Open Access Journals (Sweden)

    Nicole M. Baran

    2016-03-01

    Full Text Available Adult zebra finches (T. guttata form socially monogamous pair bonds characterized by proximity, vocal communication, and contact behaviors. In this experiment, we tested whether manipulations of the nonapeptide hormone arginine vasotocin (AVT, avian homologue of vasopressin and the V1a receptor (V1aR early in life altered species-typical pairing behavior in adult zebra finches of both sexes. Although there was no effect of treatment on the tendency to pair in either sex, males in different treatments exhibited profoundly different profiles of pair maintenance behavior. Following a brief separation, AVT-treated males were highly affiliative with their female partner but sang very little compared to Controls. In contrast, males treated with a V1aR antagonist sang significantly less than Controls, but did not differ in affiliation. These effects on behavior in males were also reflected in changes in the expression of V1aR and immediate early gene activity in three brain regions known to be involved in pairing behavior in birds: the medial amygdala, medial bed nucleus of the stria terminalis, and the lateral septum. AVT males had higher V1aR expression in the medial amygdala than both Control and antagonist-treated males and immediate early gene activity of V1aR neurons in the medial amygdala was positively correlated with affiliation. Antagonist treated males showed decreased activity in the medial amygdala. In addition, there was a negative correlation between the activity of V1aR cells in the medial bed nucleus of the stria terminalis and singing. Treatment also affected the expression of V1aR and activity in the lateral septum, but this was not correlated with any behaviors measured. These results provide evidence that AVT and V1aR play developmental roles in specific pair maintenance behaviors and the neural substrate underlying these behaviors in a bird.

  8. Human teratomas express differentiated neural antigens. An immunohistochemical study with anti-neurofilament, anti-glial filament, and anti-myelin basic protein monoclonal antibodies.

    OpenAIRE

    Trojanowski, J Q.; Hickey, W. F.

    1984-01-01

    Monoclonal antibodies specific for neurofilament proteins, glial filament protein, or myelin basic protein were used with immunohistochemistry for evaluation of a series of 14 human benign and malignant teratomas for the presence of these neural specific antigens. The results indicate that human teratomas can express all of these neural antigens, reflecting the presence of differentiated neurons, astrocytes, and oligodendroglia, respectively. Although the tumors were selected because neural t...

  9. Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain

    Directory of Open Access Journals (Sweden)

    Anna-Lena Hallmann

    2016-05-01

    Full Text Available Reprogramming technology enables the production of neural progenitor cells (NPCs from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed transcriptome analyses on murine iNSCs in comparison to brain-derived neural stem cells (NSCs and pluripotent stem cell-derived NPCs, which revealed distinct global, neural, metabolic and cell cycle-associated marks in these populations. iNSCs carried a hindbrain/posterior cell identity, which could be shifted towards caudal, partially to rostral but not towards ventral fates in vitro. iNSCs survived after transplantation into the rodent brain and exhibited in vivo-characteristics, neural and metabolic programs similar to transplanted NSCs. However, iNSCs vastly retained caudal identities demonstrating cell-autonomy of regional programs in vivo. These data could have significant implications for a variety of in vitro- and in vivo-applications using iNSCs.

  10. Adult bone marrow mesenchymal and neural crest stem cells are chemoattractive and accelerate motor recovery in a mouse model of spinal cord injury

    OpenAIRE

    Neirinckx, Virginie; Agirman, Gulistan; Coste, Cécile; Marquet, Alice; Dion, Valérie; Rogister, Bernard; Franzen, Rachelle; Wislet, Sabine

    2015-01-01

    Introduction Stem cells from adult tissues were considered for a long time as promising tools for regenerative therapy of neurological diseases, including spinal cord injuries (SCI). Indeed, mesenchymal (MSCs) and neural crest stem cells (NCSCs) together constitute the bone marrow stromal stem cells (BMSCs) that were used as therapeutic options in various models of experimental SCI. However, as clinical approaches remained disappointing, we thought that reducing BMSC heterogeneity should be a...

  11. Human fetal cardiac progenitors: The role of stem cells and progenitors in the fetal and adult heart.

    Science.gov (United States)

    Bulatovic, Ivana; Månsson-Broberg, Agneta; Sylvén, Christer; Grinnemo, Karl-Henrik

    2016-02-01

    The human fetal heart is formed early during embryogenesis as a result of cell migrations, differentiation, and formative blood flow. It begins to beat around gestation day 22. Progenitor cells are derived from mesoderm (endocardium and myocardium), proepicardium (epicardium and coronary vessels), and neural crest (heart valves, outflow tract septation, and parasympathetic innervation). A variety of molecular disturbances in the factors regulating the specification and differentiation of these cells can cause congenital heart disease. This review explores the contribution of different cardiac progenitors to the embryonic heart development; the pathways and transcription factors guiding their expansion, migration, and functional differentiation; and the endogenous regenerative capacity of the adult heart including the plasticity of cardiomyocytes. Unfolding these mechanisms will become the basis for understanding the dynamics of specific congenital heart disease as well as a means to develop therapy for fetal as well as postnatal cardiac defects and heart failure. PMID:26421632

  12. Subliminal trauma reminders impact neural processing of cognitive control in adults with developmental earthquake trauma: a preliminary report.

    Science.gov (United States)

    Du, Xue; Li, Yu; Ran, Qian; Kim, Pilyoung; Ganzel, Barbara L; Liang, GuangSheng; Hao, Lei; Zhang, Qinglin; Meng, Huaqing; Qiu, Jiang

    2016-03-01

    Little is known about the effects of developmental trauma on the neural basis of cognitive control among adults who do not have posttraumatic stress disorder. To examine this question, we used functional magnetic resonance imaging to compare the effect of subliminal priming with earthquake-related images on attentional control during a Stroop task in survivors of the 2008 Wenchuan earthquake in China (survivor group, survivors were adolescents at the time of the earthquake) and in matched controls (control group). We found that the survivor group showed greater activation in the left ventral anterior cingulate cortex (vACC) and the bilateral parahippocampal gyrus during the congruent versus incongruent condition, as compared to the control group. Depressive symptoms were positively correlated with left vACC activation during the congruent condition. Moreover, psychophysiological interaction results showed that the survivor group had stronger functional connectivity between the left parahippocampal gyrus and the left vACC than the control group under the congruent-incongruent condition. These results suggested that trauma-related information was linked to abnormal activity in brain networks associated with cognitive control (e.g., vACC-parahippocampal gyrus). This may be a potential biomarker for depression following developmental trauma, and it may also provide a mechanism linking trauma reminders with depression. PMID:26670907

  13. Odor experiences during preimaginal stages cause behavioral and neural plasticity in adult honeybees

    Directory of Open Access Journals (Sweden)

    Gabriela eRamirez

    2016-06-01

    Full Text Available In eusocial insects, experiences acquired during the development have long-term consequences on mature behavior. In the honeybee that suffers profound changes associated with metamorphosis, the effect of odor experiences at larval instars on the subsequent physiological and behavioral response is still unclear. To address the impact of preimaginal experiences on the adult honeybee, colonies containing larvae were fed scented food. The effect of the preimaginal experiences with the food odor was assessed in learning performance, memory retention and generalization in 3-5- and 17-19-day-old bees, in the regulation of their expression of synaptic-related genes and in theperception and morphology of their antennae. Three-5 day old bees that experienced 1-hexanol (1-HEX as food scent responded more to the presentation of the odor during the 1-HEX conditioning than control bees (i.e. bees reared in colonies fed unscented food. Higher levels of PER to 1-HEX in this group also extent to HEXA, the most perceptually similar odor to the experienced one that we tested. These results were not observed for the group tested at older ages. In the brain of young adults, larval experiences triggered similar levels of neurexins and neuroligins expression, two proteins that have been involved in synaptic formation after associative learning. At the sensory periphery, the experience did not alter the number of the olfactory sensilla placoidea, but did reduce the electrical response of the antennae to the experienced and novel odor. Our study provides a new insight into the effects of preimaginal experiences in the honeybee and the mechanisms underlying olfactory plasticity at larval stage of holometabolous insects.

  14. Odor Experiences during Preimaginal Stages Cause Behavioral and Neural Plasticity in Adult Honeybees

    Science.gov (United States)

    Ramírez, Gabriela; Fagundez, Carol; Grosso, Juan P.; Argibay, Pablo; Arenas, Andrés; Farina, Walter M.

    2016-01-01

    In eusocial insects, experiences acquired during the development have long-term consequences on mature behavior. In the honeybee that suffers profound changes associated with metamorphosis, the effect of odor experiences at larval instars on the subsequent physiological and behavioral response is still unclear. To address the impact of preimaginal experiences on the adult honeybee, colonies containing larvae were fed scented food. The effect of the preimaginal experiences with the food odor was assessed in learning performance, memory retention and generalization in 3–5- and 17–19 day-old bees, in the regulation of their expression of synaptic-related genes and in the perception and morphology of their antennae. Three-five day old bees that experienced 1-hexanol (1-HEX) as food scent responded more to the presentation of the odor during the 1-HEX conditioning than control bees (i.e., bees reared in colonies fed unscented food). Higher levels of proboscis extension response (PER) to 1-HEX in this group also extended to HEXA, the most perceptually similar odor to the experienced one that we tested. These results were not observed for the group tested at older ages. In the brain of young adults, larval experiences triggered similar levels of neurexins (NRXs) and neuroligins (Nlgs) expression, two proteins that have been involved in synaptic formation after associative learning. At the sensory periphery, the experience did not alter the number of the olfactory sensilla placoidea, but did reduce the electrical response of the antennae to the experienced and novel odor. Our study provides a new insight into the effects of preimaginal experiences in the honeybee and the mechanisms underlying olfactory plasticity at larval stage of holometabolous insects. PMID:27375445

  15. A biokinetic model for systemic technetium in adult humans.

    Science.gov (United States)

    Leggett, R; Giussani, A

    2015-06-01

    This paper reviews biokinetic data for technetium and proposes a biokinetic model for systemic technetium in adult humans. The development of parameter values focuses on data for pertechnetate TcO(-)(4) the most commonly encountered form of technetium and the form expected to be present in body fluids. The model is intended as a default model for occupational or environmental intake of technetium, i.e. applicable in the absence of form- or site-specific information. Tissues depicted explicitly in the model include thyroid, salivary glands, stomach wall, right colon wall, liver, kidneys, and bone. Compared with the ICRP's current biokinetic model for occupational or environmental intake of technetium (ICRP 1993, 1994), the proposed model provides a more detailed and biologically realistic description of the systemic behaviour of technetium and is based on a broader set of experimental and medical data. For acute input of (99m)Tc (T(1/2) = 6.02 h) to blood, the ratios of cumulative (time-integrated) activity predicted by the current ICRP model to that predicted by the proposed model range from 0.4-7 for systemic regions addressed explicitly in both models. For acute input of (99)Tc (T(1/2) = 2.1 × 10(5) year) to blood, the corresponding ratios range from 0.2-30. PMID:25859762

  16. Biocompatibility of nanostructured boron doped diamond for the attachment and proliferation of human neural stem cells

    Science.gov (United States)

    Taylor, Alice C.; Vagaska, Barbora; Edgington, Robert; Hébert, Clément; Ferretti, Patrizia; Bergonzo, Philippe; Jackman, Richard B.

    2015-12-01

    Objective. We quantitatively investigate the biocompatibility of chemical vapour deposited (CVD) nanocrystalline diamond (NCD) after the inclusion of boron, with and without nanostructuring. The nanostructuring method involves a novel approach of growing NCD over carbon nanotubes (CNTs) that act as a 3D scaffold. This nanostructuring of BNCD leads to a material with increased capacitance, and this along with wide electrochemical window makes BNCD an ideal material for neural interface applications, and thus it is essential that their biocompatibility is investigated. Approach. Biocompatibility was assessed by observing the interaction of human neural stem cells (hNSCs) with a variety of NCD substrates including un-doped ones, and NCD doped with boron, which are both planar, and nanostructured. hNSCs were chosen due to their sensitivity, and various methods including cell population and confluency were used to quantify biocompatibility. Main results. Boron inclusion into NCD film was shown to have no observable effect on hNSC attachment, proliferation and viability. Furthermore, the biocompatibility of nanostructured boron-doped NCD is increased upon nanostructuring, potentially due to the increased surface area. Significance. Diamond is an attractive material for supporting the attachment and development of cells as it can show exceptional biocompatibility. When boron is used as a dopant within diamond it becomes a p-type semiconductor, and at high concentrations the diamond becomes quasi-metallic, offering the prospect of a direct electrical device-cell interfacing system.

  17. High-frequency oscillations in distributed neural networks reveal the dynamics of human decision making

    Directory of Open Access Journals (Sweden)

    Adrian G Guggisberg

    2008-03-01

    Full Text Available We examine the relative timing of numerous brain regions involved in human decisions that are based on external criteria, learned information, personal preferences, or unconstrained internal considerations. Using magnetoencephalography (MEG and advanced signal analysis techniques, we were able to non-invasively reconstruct oscillations of distributed neural networks in the high-gamma frequency band (60–150 Hz. The time course of the observed neural activity suggested that two-alternative forced choice tasks are processed in four overlapping stages: processing of sensory input, option evaluation, intention formation, and action execution. Visual areas are activated fi rst, and show recurring activations throughout the entire decision process. The temporo-occipital junction and the intraparietal sulcus are active during evaluation of external values of the options, 250–500 ms after stimulus presentation. Simultaneously, personal preference is mediated by cortical midline structures. Subsequently, the posterior parietal and superior occipital cortices appear to encode intention, with different subregions being responsible for different types of choice. The cerebellum and inferior parietal cortex are recruited for internal generation of decisions and actions, when all options have the same value. Action execution was accompanied by activation peaks in the contralateral motor cortex. These results suggest that high-gamma oscillations as recorded by MEG allow a reliable reconstruction of decision processes with excellent spatiotemporal resolution.

  18. Deep biomarkers of human aging: Application of deep neural networks to biomarker development

    Science.gov (United States)

    Putin, Evgeny; Mamoshina, Polina; Aliper, Alexander; Korzinkin, Mikhail; Moskalev, Alexey; Kolosov, Alexey; Ostrovskiy, Alexander; Cantor, Charles; Vijg, Jan; Zhavoronkov, Alex

    2016-01-01

    One of the major impediments in human aging research is the absence of a comprehensive and actionable set of biomarkers that may be targeted and measured to track the effectiveness of therapeutic interventions. In this study, we designed a modular ensemble of 21 deep neural networks (DNNs) of varying depth, structure and optimization to predict human chronological age using a basic blood test. To train the DNNs, we used over 60,000 samples from common blood biochemistry and cell count tests from routine health exams performed by a single laboratory and linked to chronological age and sex. The best performing DNN in the ensemble demonstrated 81.5 % epsilon-accuracy r = 0.90 with R2 = 0.80 and MAE = 6.07 years in predicting chronological age within a 10 year frame, while the entire ensemble achieved 83.5% epsilon-accuracy r = 0.91 with R2 = 0.82 and MAE = 5.55 years. The ensemble also identified the 5 most important markers for predicting human chronological age: albumin, glucose, alkaline phosphatase, urea and erythrocytes. To allow for public testing and evaluate real-life performance of the predictor, we developed an online system available at http://www.aging.ai. The ensemble approach may facilitate integration of multi-modal data linked to chronological age and sex that may lead to simple, minimally invasive, and affordable methods of tracking integrated biomarkers of aging in humans and performing cross-species feature importance analysis. PMID:27191382

  19. Deep biomarkers of human aging: Application of deep neural networks to biomarker development.

    Science.gov (United States)

    Putin, Evgeny; Mamoshina, Polina; Aliper, Alexander; Korzinkin, Mikhail; Moskalev, Alexey; Kolosov, Alexey; Ostrovskiy, Alexander; Cantor, Charles; Vijg, Jan; Zhavoronkov, Alex

    2016-05-01

    One of the major impediments in human aging research is the absence of a comprehensive and actionable set of biomarkers that may be targeted and measured to track the effectiveness of therapeutic interventions. In this study, we designed a modular ensemble of 21 deep neural networks (DNNs) of varying depth, structure and optimization to predict human chronological age using a basic blood test. To train the DNNs, we used over 60,000 samples from common blood biochemistry and cell count tests from routine health exams performed by a single laboratory and linked to chronological age and sex. The best performing DNN in the ensemble demonstrated 81.5 % epsilon-accuracy r = 0.90 with R(2) = 0.80 and MAE = 6.07 years in predicting chronological age within a 10 year frame, while the entire ensemble achieved 83.5% epsilon-accuracy r = 0.91 with R(2) = 0.82 and MAE = 5.55 years. The ensemble also identified the 5 most important markers for predicting human chronological age: albumin, glucose, alkaline phosphatase, urea and erythrocytes. To allow for public testing and evaluate real-life performance of the predictor, we developed an online system available at http://www.aging.ai. The ensemble approach may facilitate integration of multi-modal data linked to chronological age and sex that may lead to simple, minimally invasive, and affordable methods of tracking integrated biomarkers of aging in humans and performing cross-species feature importance analysis. PMID:27191382

  20. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults.

    Directory of Open Access Journals (Sweden)

    Nadja Larsen

    Full Text Available BACKGROUND: Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control. METHODS AND FINDINGS: The study included 36 male adults with a broad range of age and body-mass indices (BMIs, among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR and in a subgroup of subjects (N = 20 by tag-encoded amplicon pyrosequencing of the V4 region of the 16S rRNA gene. The proportions of phylum Firmicutes and class Clostridia were significantly reduced in the diabetic group compared to the control group (P = 0.03. Furthermore, the ratios of Bacteroidetes to Firmicutes as well as the ratios of Bacteroides-Prevotella group to C. coccoides-E. rectale group correlated positively and significantly with plasma glucose concentration (P = 0.04 but not with BMIs. Similarly, class Betaproteobacteria was highly enriched in diabetic compared to non-diabetic persons (P = 0.02 and positively correlated with plasma glucose (P = 0.04. CONCLUSIONS: The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies to control metabolic diseases by modifying the gut microbiota.

  1. PARTICIPANT’S ASSESSMENT TOWARDS HUMAN DEVELOPMENT ADULT EDUCATION PROGRAM IN MALAYSIA

    OpenAIRE

    Abdul Razaq Ahmad; Norhasni Zainal Abiddin; Wan Hasmah Wan Mamat

    2009-01-01

    Adult education has been sidelined by mainstream educational researchers in Malaysia. The purpose of this article was to survey the effect of Society Development Department (KEMAS) adult education from the participants’ perspectives. The focus was on the participants’ achievements in cognitive, affective, and skill in the KEMAS programs especially in Human Development. Human intellectual is an important resource to develop a country. Thus, this study was used to focus on human development t...

  2. Primary Adult Human Retinal Pigment Epithelial Cell Cultures on Human Amniotic Membranes

    Directory of Open Access Journals (Sweden)

    Singhal Shweta

    2005-01-01

    Full Text Available Purpose: Retinal pigment epithelial (RPE cells grow well on surfaces that provide an extracellular matrix. Our aim was to establish primary adult human RPE cell cultures that retain their epithelial morphology in vitro using human amniotic membrane (hAM as substrate. Materials and Methods: Human cadaver eyeballs (16 were obtained from the eye bank after corneal trephination. RPE cells were harvested by a mechanical dissection of the inner choroid surface (10, group 1 or by b enzymatic digestion using 0.25% Trypsin/0.02% EDTA (6, group 2. The cells were explanted onto de-epithelialized hAM, nourished using DMEM/HAMS F-12 media and monitored for growth under the phase contrast microscope. Cell cultures were characterised by whole mount studies and paraffin sections. Growth data in the two groups were compared using the students′ ′t′ test. Results: Eleven samples (68.75% showed positive cultures with small, hexagonal cells arising from around the explant which formed a confluent and progressively pigmented monolayer. Whole mounts showed closely placed polygonal cells with heavily pigmented cytoplasm and indistinct nuclei. The histologic sections showed monolayers of cuboidal epithelium with variable pigmentation within the cytoplasm. Growth was seen by day 6-23 (average 11.5 days in the mechanical group, significantly earlier ( P Conclusions: Primary adult human RPE cell cultures retain epithelial morphology in vitro when cultured on human amniotic membranes . Mechanical dissection of the inner choroid surface appears to be an effective method of isolating RPE cells and yields earlier growth in cultures as compared to isolation by enzymatic digestion

  3. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa;

    2008-01-01

    differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......-induced areas. The presence of dopamine in the conditioned culture medium was confirmed by HPLC analysis. Interestingly, not all striatal slice cultures induced TH-expression in underlying hNS1 cells. Common to TH-inductive cultures was, however, the presence of degenerating, necrotic areas, suggesting that...... factors released during striatal degeneration were responsible for the dopaminergic induction of the hNS1 cells. Ongoing experiments aim to identify such factors by comparing protein profiles of media conditioned by degenerating (necrotic) versus healthy striatal slice cultures....

  4. Neural Stem Cells and Glioblastoma

    OpenAIRE

    Rispoli, Rossella; Conti, Carlo; Celli, Paolo; Caroli, Emanuela; Carletti, Sandro

    2014-01-01

    Glioblastoma multiforme represents one of the most common brain cancers with a rather heterogeneous cellular composition, as indicated by the term “multiforme". Recent reports have described the isolation and identification of cancer neural stem cells from human adult glioblastoma multiforme, which possess the capacity to establish, sustain, and expand these tumours, even under the challenging settings posed by serial transplantation experiments. Our study focused on the distribution of neura...

  5. The Postischemic Environment Differentially Impacts Teratoma or Tumor Formation After Transplantation of Human Embryonic Stem Cell-Derived Neural Progenitors

    Czech Academy of Sciences Publication Activity Database

    Seminatore, CH.; Polentes, J.; Ellman, D.; Kozubenko, Nataliya; Itier, V.; Tine, S.; Tritschler, L.; Brenot, M.; Guidou, E.; Blondeau, J.; Lhuillier, M.; Bugi, A.; Aubry, L.; Jendelová, Pavla; Syková, Eva; Perrier, A. L.; Finsen, B.; Onteniente, B.

    2010-01-01

    Roč. 41, č. 1 (2010), s. 153-159. ISSN 0039-2499 Institutional research plan: CEZ:AV0Z50390703 Keywords : brain transplantation * human embryonic stem cells * neural differentiation Subject RIV: FH - Neurology Impact factor: 5.756, year: 2010

  6. MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells.

    Science.gov (United States)

    Zhang, Jie Ting; Weng, Zhi Hui; Tsang, Kam Sze; Tsang, Lai Ling; Chan, Hsiao Chang; Jiang, Xiao Hua

    2016-01-01

    The biologic studies of human neural crest stem cells (hNCSCs) are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs). For the first time, we show that suppression of MycN in hNCSCs inhibits cell growth and cell cycle progression. Knockdown of MycN in hNCSCs increases the expression of Cdkn1a, Cdkn2a and Cdkn2b, which encodes the cyclin-dependent kinases p21CIP1, p16 INK4a and p15INK4b. In addition, MycN is involved in the regulation of human sympathetic neurogenesis, as knockdown of MycN enhances the expression of key transcription factors involved in sympathetic neuron differentiation, including Phox2a, Phox2b, Mash1, Hand2 and Gata3. We propose that unlimited source of hNCSCs provides an invaluable platform for the studies of human neural crest development and diseases. PMID:26815535

  7. MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells.

    Directory of Open Access Journals (Sweden)

    Jie Ting Zhang

    Full Text Available The biologic studies of human neural crest stem cells (hNCSCs are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs. For the first time, we show that suppression of MycN in hNCSCs inhibits cell growth and cell cycle progression. Knockdown of MycN in hNCSCs increases the expression of Cdkn1a, Cdkn2a and Cdkn2b, which encodes the cyclin-dependent kinases p21CIP1, p16 INK4a and p15INK4b. In addition, MycN is involved in the regulation of human sympathetic neurogenesis, as knockdown of MycN enhances the expression of key transcription factors involved in sympathetic neuron differentiation, including Phox2a, Phox2b, Mash1, Hand2 and Gata3. We propose that unlimited source of hNCSCs provides an invaluable platform for the studies of human neural crest development and diseases.

  8. HISTOLOGICAL SEXUAL DIFFERENCES IN ADULT HUMAN PARATHYROID GLANDS

    Directory of Open Access Journals (Sweden)

    Fating Anita

    2014-07-01

    Full Text Available CONTEXT (BACKGROUND: Increasing problems of calcium deficiency with physiological conditions like pregnancy, lactation etc. it becomes the need of time to focus attention towards these glands as one of the essential entity. Hence we have undertaken this study to have an idea about normal variation in the gland as per sex. AIMS: To reveal sexual differences in adult human parathyroid glands. METHODS AND MATERIAL: Parathyroid glands from 25 autopsied cases of 20 to 59 years were studied after staining with Hematoxylin & Eosin, Masson’s Trichrome & Reticulin stains. STATISTICAL ANALYSIS: Data is analyzed on statistical software intercooled STATA version 8.0. Data was presented in mean± standard deviation & categorical variables were expressed in percentages. Comparison of oxyphil scores in male & female was done by unpaired‘t’ test. P < 0.05 was taken as statistical significance. RESULTS: Stroma composed of short often branching reticular fibres along with blood vessels and fat cells. By statistical examination the amount of fat was more in case of females than in males of same age groups. Oxyphil cells being less numerous than chief cells were distinguished by their dark eosinophilic, granular cytoplasm and were arranged mostly in closely packed groups without interstitial fat in between the cells. Oxyphil cells also found as placed singly among chief cells. It was also observed as continuous masses or anastomosing columns. As compared with males oxyphil cells are more in females. CONCLUSIONS: By statistical analysis 1 Percentage of stromal fat in case of females was slightly greater than in males of same age group. 2 The score of oxyphil cells in females was double to more than triple as compared to male score of same age group. 3 This study is clinically important as hormonal changes occurs early in females than in males and it is in favor of providing supplementary calcium with D3 along with minimal dose of estrogen as age advances in

  9. Nanosized fibers' effect on adult human articular chondrocytes behavior

    International Nuclear Information System (INIS)

    Tissue engineering with chondrogenic cell based therapies is an expanding field with the intention of treating cartilage defects. It has been suggested that scaffolds used in cartilage tissue engineering influence cellular behavior and thus the long-term clinical outcome. The objective of this study was to assess whether chondrocyte attachment, proliferation and post-expansion re-differentiation could be influenced by the size of the fibers presented to the cells in a scaffold. Polylactic acid (PLA) scaffolds with different fiber morphologies were produced, i.e. microfiber (MS) scaffolds as well as nanofiber-coated microfiber scaffold (NMS). Adult human articular chondrocytes were cultured in the scaffolds in vitro up to 28 days, and the resulting constructs were assessed histologically, immunohistochemically, and biochemically. Attachment of cells and serum proteins to the scaffolds was affected by the architecture. The results point toward nano-patterning onto the microfibers influencing proliferation of the chondrocytes, and the overall 3D environment having a greater influence on the re-differentiation. In the efforts of finding the optimal scaffold for cartilage tissue engineering, studies as the current contribute to the knowledge of how to affect and control chondrocytes behavior. - Highlights: ► Chondrocyte behavior in nanofiber-coated microfiber versus microfiber scaffolds ► High porosity (> 90%) and large pore sizes (a few hundred μm) of nanofibrous scaffolds ► Proliferation enhanced by presence of nanofibers ► Differentiation not significantly affected ► Cell attachment improved in presence of both nanofibers and serum

  10. Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury

    OpenAIRE

    Haus, DL; Lopez-Velazquez, L; Gold, EM; Cunningham, KM; Perez, H; Anderson, AJ; Cummings, BJ

    2016-01-01

    Traumatic brain injury (TBI) in humans can result in permanent tissue damage and has been linked to cognitive impairment that lasts years beyond the initial insult. Clinically effective treatment strategies have yet to be developed. Transplantation of human neural stem cells (hNSCs) has the potential to restore cognition lost due to injury, however, the vast majority of rodent TBI/hNSC studies to date have evaluated cognition only at early time points, typically

  11. Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory

    OpenAIRE

    Censor, Nitzan; Cohen, Leonardo G

    2010-01-01

    In the last two decades, there has been a rapid development in the research of the physiological brain mechanisms underlying human motor learning and memory. While conventional memory research performed on animal models uses intracellular recordings, microfusion of protein inhibitors to specific brain areas and direct induction of focal brain lesions, human research has so far utilized predominantly behavioural approaches and indirect measurements of neural activity. Repetitive transcranial m...

  12. Perfusion Stirred-Tank Bioreactors for 3D Differentiation of Human Neural Stem Cells.

    Science.gov (United States)

    Simão, Daniel; Arez, Francisca; Terasso, Ana P; Pinto, Catarina; Sousa, Marcos F Q; Brito, Catarina; Alves, Paula M

    2016-01-01

    Therapeutic breakthroughs in neurological disorders have been hampered by the lack of accurate central nervous system (CNS) models. The development of these models allows the study of the disease onset/progression mechanisms and the preclinical evaluation of new therapeutics. This has traditionally relied on genetically engineered animal models that often diverge considerably from the human phenotype (developmental, anatomic, and physiological) and 2D in vitro cell models, which fail to recapitulate the characteristics of the target tissue (cell-cell and cell-matrix interactions, cell polarity, etc.). Recapitulation of CNS phenotypic and functional features in vitro requires the implementation of advanced culture strategies, such as 3D culture systems, which enable to mimic the in vivo structural and molecular complexity. Models based on differentiation of human neural stem cells (hNSC) in 3D cultures have great potential as complementary tools in preclinical research, bridging the gap between human clinical studies and animal models. The development of robust and scalable processes for the 3D differentiation of hNSC can improve the accuracy of early stage development in preclinical research. In this context, the use of software-controlled stirred-tank bioreactors (STB) provides an efficient technological platform for hNSC aggregation and differentiation. This system enables to monitor and control important physicochemical parameters for hNSC culture, such as dissolved oxygen. Importantly, the adoption of a perfusion operation mode allows a stable flow of nutrients and differentiation/neurotrophic factors, while clearing the toxic by-products. This contributes to a setting closer to the physiological, by mimicking the in vivo microenvironment. In this chapter, we address the technical requirements and procedures for the implementation of 3D differentiation strategies of hNSC, by operating STB under perfusion mode for long-term cultures. This strategy is suitable

  13. A human neural stem cell line provides neuroprotection and improves neurological performance by early intervention of neuroinflammatory system.

    Science.gov (United States)

    Watanabe, Tatsuzo; Nagai, Atsushi; Sheikh, Abdullah Md; Mitaki, Shingo; Wakabayashi, Kiryo; Kim, Seung U; Kobayashi, Shotai; Yamaguchi, Shuhei

    2016-01-15

    A human neural stem cell line, HB1.F3, demonstrated neuroprotective properties in cerebral ischemia animal models. In this study, we have investigated about the mechanisms of such neuroprotection, mainly focusing on the neuroinflammatory system at an earlier time point of the pathology. Cerebral ischemia model was generated by middle cerebral artery occlusion (MCAO) in adult male Wister rats. HB1.F3 cells were transplanted through jugular vein 6h after MCAO. Forty eight hours after MCAO, transplanted rats showed better neurological performance and decreased TUNEL positive apoptotic cell number in the penumbra. However, haematoxylin and eosin staining and immunostaining showed that, HB1.F3 cells did not affect the necrotic cell death. Twenty four hours after MCAO (18h after HB1.F3 transplantation), infiltrated granulocytes and macrophage/microglia number in the core regions were decreased compared to PBS-treated controls. Immunohistochemical analysis further demonstrated that the transplantation decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expressing cell number in the core and penumbra, respectively. Double immunofluorescence results revealed that iNOS was mainly expressed in granulocytes and macrophage/microglia in the core region, and COX-2 mainly expressed in neurons, endothelial cells and granulocytes in penumbra. Further analysis showed that although the percentage of iNOS expressing granulocytes and macrophage/microglia was not decreased, COX-2 expressing neurons and vessel number was decreased by the transplantation. In vitro mRNA analysis showed that brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (βFGF) and bone morphogenic protein (BMP)-4 expression was high in cultured HB1.F3 cells. Thus, our results demonstrated that HB1.F3 cell transplantation provide neuroprotection possibly through the regulation of early inflammatory events in the cerebral ischemia condition. PMID:26620543

  14. Transplantation of Neural Differentiated Human Mesenchymal Stem Cells into the Cochlea of an Auditory-neuropathy Guinea Pig Model

    OpenAIRE

    Cho, Yong-Bum; Cho, Hyong-Ho; Jang, Sujeong; Jeong, Han-Seong; Park, Jong-Seong

    2011-01-01

    The aim of this study was to determine the effects of transplanted neural differentiated human mesenchymal stem cells (hMSCs) in a guinea pig model of auditory neuropathy. In this study, hMSCs were pretreated with a neural-induction protocol and transplanted into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. A control model was made by injection of Hanks balanced salt solution alone into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. We est...

  15. Brain stem auditory evoked responses in human infants and adults

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  16. Activity-dependent neural plasticity from bench to bedside.

    Science.gov (United States)

    Ganguly, Karunesh; Poo, Mu-Ming

    2013-10-30

    Much progress has been made in understanding how behavioral experience and neural activity can modify the structure and function of neural circuits during development and in the adult brain. Studies of physiological and molecular mechanisms underlying activity-dependent plasticity in animal models have suggested potential therapeutic approaches for a wide range of brain disorders in humans. Physiological and electrical stimulations as well as plasticity-modifying molecular agents may facilitate functional recovery by selectively enhancing existing neural circuits or promoting the formation of new functional circuits. Here, we review the advances in basic studies of neural plasticity mechanisms in developing and adult nervous systems and current clinical treatments that harness neural plasticity, and we offer perspectives on future development of plasticity-based therapy. PMID:24183023

  17. Analysis of neural activity in human motor cortex -- Towards brain machine interface system

    Science.gov (United States)

    Secundo, Lavi

    , the correlation of ECoG activity to kinematic parameters of arm movement is context-dependent, an important constraint to consider in future development of BMI systems. The third chapter delves into a fundamental organizational principle of the primate motor system---cortical control of contralateral limb movements. However, ipsilateral motor areas also appear to play a role in the control of ipsilateral limb movements. Several studies in monkeys have shown that individual neurons in ipsilateral primary motor cortex (M1) may represent, on average, the direction of movements of the ipsilateral arm. Given the increasing body of evidence demonstrating that neural ensembles can reliably represent information with a high temporal resolution, here we characterize the distributed neural representation of ipsilateral upper limb kinematics in both monkey and man. In two macaque monkeys trained to perform center-out reaching movements, we found that the ensemble spiking activity in M1 could continuously represent ipsilateral limb position. We also recorded cortical field potentials from three human subjects and also consistently found evidence of a neural representation for ipsilateral movement parameters. Together, our results demonstrate the presence of a high-fidelity neural representation for ipsilateral movement and illustrates that it can be successfully incorporated into a brain-machine interface.

  18. Reaching beyond the United States: Adventures in International Adult Education and Human Resource Development

    Science.gov (United States)

    Henschke, John A.

    2005-01-01

    In this article, the author shares his experience of how travel and adult education merged, for him, into a major emphasis in international adult education (AE) and human resource development (HRD). International ventures have been some of the most exciting and learning-filled aspects of the author's career in AE and HRD. His involvement in…

  19. Persistent oxidative stress in human neural stem cells exposed to low fluences of charged particles

    Directory of Open Access Journals (Sweden)

    Janet E. Baulch

    2015-08-01

    Full Text Available Exposure to the space radiation environment poses risks for a range of deleterious health effects due to the unique types of radiation encountered. Galactic cosmic rays are comprised of a spectrum of highly energetic nuclei that deposit densely ionizing tracks of damage along the particle trajectory. These tracks are distinct from those generated by the more sparsely ionizing terrestrial radiations, and define the geometric distribution of the complex cellular damage that results when charged particles traverse the tissues of the body. The exquisite radiosensitivity of multipotent neural stem and progenitor cells found within the neurogenic regions of the brain predispose the central nervous system to elevated risks for radiation induced sequelae. Here we show that human neural stem cells (hNSC exposed to different charged particles at space relevant fluences exhibit significant and persistent oxidative stress. Radiation induced oxidative stress was found to be most dependent on total dose rather than on the linear energy transfer of the incident particle. The use of redox sensitive fluorogenic dyes possessing relative specificity for hydroxyl radicals, peroxynitrite, nitric oxide (NO and mitochondrial superoxide confirmed that most irradiation paradigms elevated reactive oxygen and nitrogen species (ROS and RNS, respectively in hNSC over a 1 week interval following exposure. Nitric oxide synthase (NOS was not the major source of elevated nitric oxides, as the use of NOS inhibitors had little effect on NO dependent fluorescence. Our data provide extensive evidence for the capability of low doses of charged particles to elicit marked changes in the metabolic profile of irradiated hNSC. Radiation induced changes in redox state may render the brain more susceptible to the development of neurocognitive deficits that could affect an astronaut’s ability to perform complex tasks during extended missions in deep space.

  20. Interaction matters: A perceived social partner alters the neural processing of human speech.

    Science.gov (United States)

    Rice, Katherine; Redcay, Elizabeth

    2016-04-01

    Mounting evidence suggests that social interaction changes how communicative behaviors (e.g., spoken language, gaze) are processed, but the precise neural bases by which social-interactive context may alter communication remain unknown. Various perspectives suggest that live interactions are more rewarding, more attention-grabbing, or require increased mentalizing-thinking about the thoughts of others. Dissociating between these possibilities is difficult because most extant neuroimaging paradigms examining social interaction have not directly compared live paradigms to conventional "offline" (or recorded) paradigms. We developed a novel fMRI paradigm to assess whether and how an interactive context changes the processing of speech matched in content and vocal characteristics. Participants listened to short vignettes--which contained no reference to people or mental states--believing that some vignettes were prerecorded and that others were presented over a real-time audio-feed by a live social partner. In actuality, all speech was prerecorded. Simply believing that speech was live increased activation in each participant's own mentalizing regions, defined using a functional localizer. Contrasting live to recorded speech did not reveal significant differences in attention or reward regions. Further, higher levels of autistic-like traits were associated with altered neural specialization for live interaction. These results suggest that humans engage in ongoing mentalizing about social partners, even when such mentalizing is not explicitly required, illustrating how social context shapes social cognition. Understanding communication in social context has important implications for typical and atypical social processing, especially for disorders like autism where social difficulties are more acute in live interaction. PMID:26608245

  1. The Neural Correlates of Chronic Symptoms of Vertigo Proneness in Humans

    Science.gov (United States)

    Alsalman, Ola; Ost, Jan; Vanspauwen, Robby; Blaivie, Catherine; De Ridder, Dirk; Vanneste, Sven

    2016-01-01

    Vestibular signals are of significant importance for variable functions including gaze stabilization, spatial perception, navigation, cognition, and bodily self-consciousness. The vestibular network governs functions that might be impaired in patients affected with vestibular dysfunction. It is currently unclear how different brain regions/networks process vestibular information and integrate the information into a unified spatial percept related to somatosensory awareness and whether people with recurrent balance complaints have a neural signature as a trait affecting their development of chronic symptoms of vertigo. Pivotal evidence points to a vestibular-related brain network in humans that is widely distributed in nature. By using resting state source localized electroencephalography in non-vertiginous state, electrophysiological changes in activity and functional connectivity of 23 patients with balance complaints where chronic symptoms of vertigo and dizziness are among the most common reported complaints are analyzed and compared to healthy subjects. The analyses showed increased alpha2 activity within the posterior cingulate cortex and the precuneues/cuneus and reduced beta3 and gamma activity within the pregenual and subgenual anterior cingulate cortex for the subjects with balance complaints. These electrophysiological variations were correlated with reported chronic symptoms of vertigo intensity. A region of interest analysis found reduced functional connectivity for gamma activity within the vestibular cortex, precuneus, frontal eye field, intra-parietal sulcus, orbitofrontal cortex, and the dorsal anterior cingulate cortex. In addition, there was a positive correlation between chronic symptoms of vertigo intensity and increased alpha-gamma nesting in the left frontal eye field. When compared to healthy subjects, there is evidence of electrophysiological changes in the brain of patients with balance complaints even outside chronic symptoms of vertigo

  2. Controllability modulates the neural response to predictable but not unpredictable threat in humans.

    Science.gov (United States)

    Wood, Kimberly H; Wheelock, Muriah D; Shumen, Joshua R; Bowen, Kenton H; Ver Hoef, Lawrence W; Knight, David C

    2015-10-01

    Stress resilience is mediated, in part, by our ability to predict and control threats within our environment. Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threats may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders. To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI). Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable). Similar to animal model research that has employed yoked fear conditioning procedures, one group (controllable condition; CC), but not the other group (uncontrollable condition; UC) was able to terminate the UCS. The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS). In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable. These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress. PMID:26149610

  3. The Neural Correlates of Chronic Symptoms of Vertigo Proneness in Humans.

    Directory of Open Access Journals (Sweden)

    Ola Alsalman

    Full Text Available Vestibular signals are of significant importance for variable functions including gaze stabilization, spatial perception, navigation, cognition, and bodily self-consciousness. The vestibular network governs functions that might be impaired in patients affected with vestibular dysfunction. It is currently unclear how different brain regions/networks process vestibular information and integrate the information into a unified spatial percept related to somatosensory awareness and whether people with recurrent balance complaints have a neural signature as a trait affecting their development of chronic symptoms of vertigo. Pivotal evidence points to a vestibular-related brain network in humans that is widely distributed in nature. By using resting state source localized electroencephalography in non-vertiginous state, electrophysiological changes in activity and functional connectivity of 23 patients with balance complaints where chronic symptoms of vertigo and dizziness are among the most common reported complaints are analyzed and compared to healthy subjects. The analyses showed increased alpha2 activity within the posterior cingulate cortex and the precuneues/cuneus and reduced beta3 and gamma activity within the pregenual and subgenual anterior cingulate cortex for the subjects with balance complaints. These electrophysiological variations were correlated with reported chronic symptoms of vertigo intensity. A region of interest analysis found reduced functional connectivity for gamma activity within the vestibular cortex, precuneus, frontal eye field, intra-parietal sulcus, orbitofrontal cortex, and the dorsal anterior cingulate cortex. In addition, there was a positive correlation between chronic symptoms of vertigo intensity and increased alpha-gamma nesting in the left frontal eye field. When compared to healthy subjects, there is evidence of electrophysiological changes in the brain of patients with balance complaints even outside chronic

  4. In vivo tracking of human neural stem cells with 19F magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Philipp Boehm-Sturm

    Full Text Available BACKGROUND: Magnetic resonance imaging (MRI is a promising tool for monitoring stem cell-based therapy. Conventionally, cells loaded with ironoxide nanoparticles appear hypointense on MR images. However, the contrast generated by ironoxide labeled cells is neither specific due to ambiguous background nor quantitative. A strategy to overcome these drawbacks is (19F MRI of cells labeled with perfluorocarbons. We show here for the first time that human neural stem cells (NSCs, a promising candidate for clinical translation of stem cell-based therapy of the brain, can be labeled with (19F as well as detected and quantified in vitro and after brain implantation. METHODOLOGY/PRINCIPAL FINDINGS: Human NSCs were labeled with perfluoropolyether (PFPE. Labeling efficacy was assessed with (19F MR spectroscopy, influence of the label on cell phenotypes studied by immunocytochemistry. For in vitro MRI, NSCs were suspended in gelatin at varying densities. For in vivo experiments, labeled NSCs were implanted into the striatum of mice. A decrease of cell viability was observed directly after incubation with PFPE, which re-normalized after 7 days in culture of the replated cells. No label-related changes in the numbers of Ki67, nestin, GFAP, or βIII-tubulin+ cells were detected, both in vitro and on histological sections. We found that 1,000 NSCs were needed to accumulate in one image voxel to generate significant signal-to-noise ratio in vitro. A detection limit of ∼10,000 cells was found in vivo. The location and density of human cells (hunu+ on histological sections correlated well with observations in the (19F MR images. CONCLUSION/SIGNIFICANCE: Our results show that NSCs can be efficiently labeled with (19F with little effects on viability or proliferation and differentiation capacity. We show for the first time that (19F MRI can be utilized for tracking human NSCs in brain implantation studies, which ultimately aim for restoring loss of function after

  5. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yun; Wang, Jing [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Chen, Guian [Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Reproductive Medical Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Fan, Dongsheng, E-mail: dsfan@yahoo.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Deng, Min, E-mail: dengmin1706@yahoo.com.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China)

    2011-01-14

    Research highlights: {yields} Nicotinamide inhibit Sirt1. {yields} MASH1 and Ngn2 activation. {yields} Increase the expression of HB9. {yields} Motoneurons formation increases significantly. -- Abstract: Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increased motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and {beta}III-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 {mu}M) or inhibitor nicotinamide (100 {mu}M). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease.

  6. Propagation of Adult SSCs: From Mouse to Human

    OpenAIRE

    Martin, Laura A.; Marco Seandel

    2013-01-01

    Adult spermatogonial stem cells (SSCs) represent a distinctive source of stem cells in mammals for several reasons. First, by giving rise to spermatogenesis, SSCs are responsible for the propagation of a father’s genetic material. As such, autologous SSCs have been considered for treatment of infertility and other purposes, including correction of inherited disorders. Second, adult spermatogonia can spontaneously produce embryonic-like stem cells in vitro, which could be used a...

  7. Neural and non-neural control of skin blood flow during isometric handgrip exercise in the heat stressed human

    DEFF Research Database (Denmark)

    Shibasaki, M.; Rasmussen, P.; Secher, Niels H.;

    2009-01-01

    stressed individuals occurs via a neural mechanism. An axillary nerve blockade was performed to block efferent nerve traffic to the left forearm in seven healthy subjects. Two intradermal microdialysis probes were placed within forearm skin of the blocked area. Forearm skin blood flow was measured by laser......-Doppler flowmetry over the microdialysis probes as well as from skin of the contralateral (unblocked) forearm. Cutaneous vascular conductance (CVC) was calculated from the ratio of skin blood flow to mean arterial pressure. Effectiveness of nerve blockade was verified by the absence of tactile sensation, as well as...... an absence of sweating and cutaneous vasodilatation during a whole-body heat stress. Upon this confirmation, adenosine was perfused through one of the microdialysis probes to increase skin blood flow similar to that of the unblocked site. After internal temperature increased approximately 0.7 degrees...

  8. The neural dynamics of reward value and risk coding in the human orbitofrontal cortex.

    Science.gov (United States)

    Li, Yansong; Vanni-Mercier, Giovanna; Isnard, Jean; Mauguière, François; Dreher, Jean-Claude

    2016-04-01

    SEE KRINGELBACH AND RAPUANO DOI101093/BRAIN/AWW049 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The orbitofrontal cortex is known to carry information regarding expected reward, risk and experienced outcome. Yet, due to inherent limitations in lesion and neuroimaging methods, the neural dynamics of these computations has remained elusive in humans. Here, taking advantage of the high temporal definition of intracranial recordings, we characterize the neurophysiological signatures of the intact orbitofrontal cortex in processing information relevant for risky decisions. Local field potentials were recorded from the intact orbitofrontal cortex of patients suffering from drug-refractory partial epilepsy with implanted depth electrodes as they performed a probabilistic reward learning task that required them to associate visual cues with distinct reward probabilities. We observed three successive signals: (i) around 400 ms after cue presentation, the amplitudes of the local field potentials increased with reward probability; (ii) a risk signal emerged during the late phase of reward anticipation and during the outcome phase; and (iii) an experienced value signal appeared at the time of reward delivery. Both the medial and lateral orbitofrontal cortex encoded risk and reward probability while the lateral orbitofrontal cortex played a dominant role in coding experienced value. The present study provides the first evidence from intracranial recordings that the human orbitofrontal cortex codes reward risk both during late reward anticipation and during the outcome phase at a time scale of milliseconds. Our findings offer insights into the rapid mechanisms underlying the ability to learn structural relationships from the environment. PMID:26811252

  9. The neural mechanisms underlying the influence of pavlovian cues on human decision making.

    Science.gov (United States)

    Bray, Signe; Rangel, Antonio; Shimojo, Shinsuke; Balleine, Bernard; O'Doherty, John P

    2008-05-28

    In outcome-specific transfer, pavlovian cues that are predictive of specific outcomes bias action choice toward actions associated with those outcomes. This transfer occurs despite no explicit training of the instrumental actions in the presence of pavlovian cues. The neural substrates of this effect in humans are unknown. To address this, we scanned 23 human subjects with functional magnetic resonance imaging while they made choices between different liquid food rewards in the presence of pavlovian cues previously associated with one of these outcomes. We found behavioral evidence of outcome-specific transfer effects in our subjects, as well as differential blood oxygenation level-dependent activity in a region of ventrolateral putamen when subjects chose, respectively, actions consistent and inconsistent with the pavlovian-predicted outcome. Our results suggest that choosing an action incompatible with a pavlovian-predicted outcome might require the inhibition of feasible but nonselected action-outcome associations. The results of this study are relevant for understanding how marketing actions can affect consumer choice behavior as well as for how environmental cues can influence drug-seeking behavior in addiction. PMID:18509047

  10. Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury

    Directory of Open Access Journals (Sweden)

    Kyungha Shin

    2016-01-01

    Full Text Available Amygdala is involved in the fear memory that recognizes certain environmental cues predicting threatening events. Manipulation of neurotransmission within the amygdala affects the expression of conditioned and unconditioned emotional memories such as fear freezing behaviour. We previously demonstrated that F3.ChAT human neural stem cells (NSCs overexpressing choline acetyltransferase (ChAT improve cognitive function of Alzheimer’s disease model rats with hippocampal or cholinergic nerve injuries by increasing acetylcholine (ACh level. In the present study, we examined the effect of F3.ChAT cells on the deficit of unconditioned fear freezing. Rats given N-methyl-d-aspartate (NMDA in their amygdala 2 weeks prior to cat odor exposure displayed very short resting (freezing time compared to normal animals. NMDA induced neuronal degeneration in the amygdala, leading to a decreased ACh concentration in cerebrospinal fluid. However, intracerebroventricular transplantation of F3.ChAT cells attenuated amygdala lesions 4 weeks after transplantation. The transplanted cells were found in the NMDA-injury sites and produced ChAT protein. In addition, F3.ChAT-receiving rats recuperated freezing time staying remote from the cat odor source, according to the recovery of brain ACh concentration. The results indicate that human NSCs overexpressing ChAT may facilitate retrieval of unconditioned fear memory by increasing ACh level.

  11. Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury.

    Science.gov (United States)

    Shin, Kyungha; Cha, Yeseul; Kim, Kwang Sei; Choi, Ehn-Kyoung; Choi, Youngjin; Guo, Haiyu; Ban, Young-Hwan; Kim, Jong-Choon; Park, Dongsun; Kim, Yun-Bae

    2016-01-01

    Amygdala is involved in the fear memory that recognizes certain environmental cues predicting threatening events. Manipulation of neurotransmission within the amygdala affects the expression of conditioned and unconditioned emotional memories such as fear freezing behaviour. We previously demonstrated that F3.ChAT human neural stem cells (NSCs) overexpressing choline acetyltransferase (ChAT) improve cognitive function of Alzheimer's disease model rats with hippocampal or cholinergic nerve injuries by increasing acetylcholine (ACh) level. In the present study, we examined the effect of F3.ChAT cells on the deficit of unconditioned fear freezing. Rats given N-methyl-d-aspartate (NMDA) in their amygdala 2 weeks prior to cat odor exposure displayed very short resting (freezing) time compared to normal animals. NMDA induced neuronal degeneration in the amygdala, leading to a decreased ACh concentration in cerebrospinal fluid. However, intracerebroventricular transplantation of F3.ChAT cells attenuated amygdala lesions 4 weeks after transplantation. The transplanted cells were found in the NMDA-injury sites and produced ChAT protein. In addition, F3.ChAT-receiving rats recuperated freezing time staying remote from the cat odor source, according to the recovery of brain ACh concentration. The results indicate that human NSCs overexpressing ChAT may facilitate retrieval of unconditioned fear memory by increasing ACh level. PMID:27087745

  12. Abnormal Neural Responses to Emotional Stimuli but Not Go/NoGo and Stroop Tasks in Adults with a History of Childhood Nocturnal Enuresis.

    Directory of Open Access Journals (Sweden)

    Mengxing Wang

    Full Text Available Nocturnal enuresis (NE is a common disorder in school-aged children. Previous studies have reported that children with NE exhibit structural, functional and neurochemical abnormalities in the brain, suggesting that children with NE may have cognitive problems. Additionally, children with NE have been shown to process emotions differently from control children. In fact, most cases of NE resolve with age. However, adults who had experienced NE during childhood may still have potential cognitive or emotion problems, and this possibility has not been thoroughly investigated.In this work, we used functional magnetic resonance imaging (fMRI to evaluate brain functional changes in adults with a history of NE. Two groups, consisting of 21 adults with NE and 21 healthy controls, were scanned using fMRI. We did not observe a significant abnormality in activation during the Go/NoGo and Stroop tasks in adults with a history of NE compared with the control group. However, compared to healthy subjects, young adults with a history of NE mainly showed increased activation in the bilateral temporoparietal junctions, bilateral dorsolateral prefrontal cortex, and bilateral anterior cingulate cortex while looking at negative vs. neutral pictures.Our results demonstrate that adults with a history of childhood NE have no obvious deficit in response inhibition or cognitive control but showed abnormal neural responses to emotional stimuli.

  13. Abnormal Neural Responses to Emotional Stimuli but Not Go/NoGo and Stroop Tasks in Adults with a History of Childhood Nocturnal Enuresis

    Science.gov (United States)

    Wang, Mengxing; Zhang, Kaihua; Zhang, Jilei; Dong, Guangheng; Zhang, Hui; Du, Xiaoxia

    2015-01-01

    Background Nocturnal enuresis (NE) is a common disorder in school-aged children. Previous studies have reported that children with NE exhibit structural, functional and neurochemical abnormalities in the brain, suggesting that children with NE may have cognitive problems. Additionally, children with NE have been shown to process emotions differently from control children. In fact, most cases of NE resolve with age. However, adults who had experienced NE during childhood may still have potential cognitive or emotion problems, and this possibility has not been thoroughly investigated. Methodology/Principal Findings In this work, we used functional magnetic resonance imaging (fMRI) to evaluate brain functional changes in adults with a history of NE. Two groups, consisting of 21 adults with NE and 21 healthy controls, were scanned using fMRI. We did not observe a significant abnormality in activation during the Go/NoGo and Stroop tasks in adults with a history of NE compared with the control group. However, compared to healthy subjects, young adults with a history of NE mainly showed increased activation in the bilateral temporoparietal junctions, bilateral dorsolateral prefrontal cortex, and bilateral anterior cingulate cortex while looking at negative vs. neutral pictures. Conclusions/Significance Our results demonstrate that adults with a history of childhood NE have no obvious deficit in response inhibition or cognitive control but showed abnormal neural responses to emotional stimuli. PMID:26571500

  14. Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

    Directory of Open Access Journals (Sweden)

    Takayuki Kondo

    2014-08-01

    Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

  15. Discrimination of human bodies from bones and teeth remains by Laser Induced Breakdown Spectroscopy and Neural Networks

    Energy Technology Data Exchange (ETDEWEB)

    Moncayo, S.; Manzoor, S.; Ugidos, T.; Navarro-Villoslada, F.; Caceres, J.O., E-mail: jcaceres@ucm.es

    2014-11-01

    A fast and minimally destructive method based on Laser Induced Breakdown Spectroscopy (LIBS) and Neural Networks (NN) has been developed and applied to the classification and discrimination of human bones and teeth fragments. The methodology can be useful in Disaster Victim Identification (DVI) tasks. The elemental compositions of bone and teeth samples provided enough information to achieve a correct discrimination and reassembling of different human remains. Individuals were classified with spectral correlation higher than 95%, regardless of the type of bone or tooth sample analyzed. No false positive or false negative was observed, demonstrating the high robustness and accuracy of the proposed methodology. - Highlights: • Classification and discrimination of human remains have been studied. • Remains were analyzed by Laser Induced Breakdown Spectroscopy (LIBS). • Neural Networks models (NN) were used. • Individuals were classified with spectral correlation higher than 95 %. • LIBS-NN showed the potential for rapid and cost-effective analysis.

  16. Comparison of deep neural networks to spatio-temporal cortical dynamics of human visual object recognition reveals hierarchical correspondence.

    Science.gov (United States)

    Cichy, Radoslaw Martin; Khosla, Aditya; Pantazis, Dimitrios; Torralba, Antonio; Oliva, Aude

    2016-01-01

    The complex multi-stage architecture of cortical visual pathways provides the neural basis for efficient visual object recognition in humans. However, the stage-wise computations therein remain poorly understood. Here, we compared temporal (magnetoencephalography) and spatial (functional MRI) visual brain representations with representations in an artificial deep neural network (DNN) tuned to the statistics of real-world visual recognition. We showed that the DNN captured the stages of human visual processing in both time and space from early visual areas towards the dorsal and ventral streams. Further investigation of crucial DNN parameters revealed that while model architecture was important, training on real-world categorization was necessary to enforce spatio-temporal hierarchical relationships with the brain. Together our results provide an algorithmically informed view on the spatio-temporal dynamics of visual object recognition in the human visual brain. PMID:27282108

  17. Discrimination of human bodies from bones and teeth remains by Laser Induced Breakdown Spectroscopy and Neural Networks

    International Nuclear Information System (INIS)

    A fast and minimally destructive method based on Laser Induced Breakdown Spectroscopy (LIBS) and Neural Networks (NN) has been developed and applied to the classification and discrimination of human bones and teeth fragments. The methodology can be useful in Disaster Victim Identification (DVI) tasks. The elemental compositions of bone and teeth samples provided enough information to achieve a correct discrimination and reassembling of different human remains. Individuals were classified with spectral correlation higher than 95%, regardless of the type of bone or tooth sample analyzed. No false positive or false negative was observed, demonstrating the high robustness and accuracy of the proposed methodology. - Highlights: • Classification and discrimination of human remains have been studied. • Remains were analyzed by Laser Induced Breakdown Spectroscopy (LIBS). • Neural Networks models (NN) were used. • Individuals were classified with spectral correlation higher than 95 %. • LIBS-NN showed the potential for rapid and cost-effective analysis

  18. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

    International Nuclear Information System (INIS)

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  19. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

    Energy Technology Data Exchange (ETDEWEB)

    Colleoni, Silvia, E-mail: silviacolleoni@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Galli, Cesare [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy); Dipartimento Clinico Veterinario, Universita di Bologna, Via Tolara di Sopra 50, 40064 Ozzano Emilia (Italy); Giannelli, Serena G. [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Armentero, Marie-Therese; Blandini, Fabio [Laboratory of Functional Neurochemistry, Interdepartmental Research Center for Parkinson' s Disease, Neurological Institute C. Mondino, Via Mondino 2, 27100 Pavia (Italy); Broccoli, Vania, E-mail: broccoli.vania@hsr.it [Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan (Italy); Lazzari, Giovanna, E-mail: giovannalazzari@avantea.it [Laboratorio di Tecnologie della Riproduzione, Avantea, Via Porcellasco 7/f, 26100 Cremona (Italy)

    2010-04-15

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  20. Differentiation of Human Bone Marrow Stromal Cells into Neural-Like Cells Induced by Sodium Ferulate in vitro

    Institute of Scientific and Technical Information of China (English)

    Yang Wang; Zhifeng Deng; Xianliang Lai; Wei Tu

    2005-01-01

    Human marrow stromal cells (hMSCs) are multipotential stem cells, capable of differentiating into bone, cartilage,fat and muscle. Several recent reports demonstrated that hMSCs have been also differentiated into neural cells.However, only a few reported inducers are applicable for clinical use. This work is to explore the effects of sodium ferulate (SF) on differentiation of hMSCs into neural cells in vitro. We found that hMSCs could be induced to the cells with typical neural morphology when cultured with SF. The cells express neural proteins, such as nestin,neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP). About 30% of the hMSC-derived cells expressed nestin when cultured with SF for 3 h, but no expression was detected after 24 h. The percentages of positive cells for NSE or GFAP were about 67% and 39% separately at 6 h, and reached the plateau phage after treatment with SF for 3 days. The data suggest that SF can induce hMSCs to differentiate into neural-like cells in vitro.

  1. Isolation of alveolar epithelial type II progenitor cells from adult human lungs

    OpenAIRE

    Fujino, Naoya; Kubo, Hiroshi; Suzuki, Takaya; Ota, Chiharu; Hegab, Ahmed E.; He, Mei; Suzuki, Satoshi; Suzuki, Takashi; Yamada, Mitsuhiro; Kondo, Takashi; Kato, Hidemasa; Yamaya, Mutsuo

    2010-01-01

    Resident stem/progenitor cells in the lung are important for tissue homeostasis and repair. However, a progenitor population for alveolar type II (ATII) cells in adult human lungs has not been identified. The aim of this study is to isolate progenitor cells from adult human lungs with the ability to differentiate into ATII cells. We isolated colony-forming cells that had the capability for self-renewal and the potential to generate ATII cells in vitro. These undifferentiated progenitor cells ...

  2. MORPHOLOGICAL STUDY OF THE BASILAR ARTERY IN ADULT HUMAN CADAVERS

    Directory of Open Access Journals (Sweden)

    Harish A. Wankhede

    2014-09-01

    Full Text Available Background: The basilar artery is the large median and major artery of the posterior circulation of the brain. Many variations are seen in the basilar artery, majority of them in position, origin and shape of the artery. Many authors have documented various anomalies as well as differences of the anatomy in this area in the Indian population as compared to the Western literature. Context and purpose of study: Many studies are available on the anterior circulation of the brain i.e. on vessels of the circle of Willis but studies on the posterior circulation are very few. And such studies so far had been done mostly in the American and European races and are mostly based on imaging techniques. Studies in the Indian population have been few. Hence the present study is concentrated on the morphological study of the basilar artery of human adult brain, to show the frequency and type of variations in the morphology of the basilar artery. Results: The basilar artery most commonly takes origin from the vertebral artery where left vertebral artery is greater in size than the right vertebral artery (72.5%. Level of formation of the basilar artery is most commonly observed at the ponto-medullary junction (62.5%. Length of the basilar artery varied from minimum 2.4cm to maximum 3.6cm. More commonly artery lies in the range of 2.6-3.0cm (57.5%. Diameter of the basilar artery at origin ranges from 3.2-4.2mm, at mid level from 3-4mm and at termination 3.1-4mm. Level of termination of the basilar artery is more commonly at the mid brain-pons junction (50%. Most of the basilar arteries are of straight type (55% and next common is bent or curved type (37.5%. Fenestration of 4mm is seen in proximal part of the one basilar artery (2.5%. Conclusion: Variations of the basilar artery are common. Neurosurgical importance of this study lies during the exposure of the region for different purposes. Knowledge of the vascular variations will increase the success of the

  3. Carbon-ion beams effectively induce growth inhibition and apoptosis in human neural stem cells compared with glioblastoma A172 cells

    International Nuclear Information System (INIS)

    Carbon-ion radiotherapy (CIRT) holds promise in the treatment of glioblastoma, an aggressive X-ray–resistant brain tumor. However, since glioblastoma cells show a highly invasive nature, carbon-ion (C-ion) irradiation of normal tissues surrounding the tumor is inevitable. Recent studies have revealed the existence of neural stem cells in the adult brain. Therefore, the damaging effect of C-ion beams on the neural stem cells has to be carefully considered in the treatment planning of CIRT. Here, we investigated the growth and death mode of human neural stem cells (hNSCs) and glioblastoma A172 cells after X-ray or C-ion beam irradiation. The X-ray dose resulting in a 50% growth rate (D50) was 0.8 Gy in hNSCs and 3.0 Gy in A172 cells, while the D50 for C-ion beams was 0.4 Gy in hNSCs and 1.6 Gy in A172 cells; the relative biological effectiveness value of C-ion beams was 2.0 in hNSCs and 1.9 in A172 cells. Importantly, both X-rays and C-ion beams preferentially induced apoptosis, not necrosis, in hNSCs; however, radiation-induced apoptosis was less evident in A172 cells. The apoptosis-susceptible nature of the irradiated hNSCs was associated with prolonged upregulation of phosphorylated p53, whereas the apoptosis-resistant nature of A172 cells was associated with a high basal level of nuclear factor kappa B expression. Taken together, these data indicate that apoptosis is the major cell death pathway in hNSCs after irradiation. The high sensitivity of hNSCs to C-ion beams underscores the importance of careful target volume delineation in the treatment planning of CIRT for glioblastoma. (author)

  4. Neural Representations of Complex Temporal Modulations in the Human Auditory Cortex

    OpenAIRE

    Ding, Nai; Simon, Jonathan Z.

    2009-01-01

    Natural sounds such as speech contain multiple levels and multiple types of temporal modulations. Because of nonlinearities of the auditory system, however, the neural response to multiple, simultaneous temporal modulations cannot be predicted from the neural responses to single modulations. Here we show the cortical neural representation of an auditory stimulus simultaneously frequency modulated (FM) at a high rate, fFM ≈ 40 Hz, and amplitude modulation (AM) at a slow rate, fAM

  5. Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse.

    Science.gov (United States)

    Tanaka, Masayuki; Yoneyama, Masanori; Shiba, Tatsuo; Yamaguchi, Taro; Ogita, Kiyokazu

    2016-07-01

    Thrombin-activated protease-activated receptor (PAR)-1 regulates the proliferation of neural cells following brain injury. To elucidate the involvement of PAR-1 in the neurogenesis that occurs in the adult hippocampus, we examined whether PAR-1 regulated the proliferation of neural stem/progenitor cells (NPCs) derived from the murine hippocampal dentate gyrus. NPC cultures expressed PAR-1 protein and mRNA encoding all subtypes of PAR. Direct exposure of the cells to thrombin dramatically attenuated the cell proliferation without causing cell damage. This thrombin-induced attenuation was almost completely abolished by the PAR antagonist RWJ 56110, as well as by dabigatran and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), which are selective and non-selective thrombin inhibitors, respectively. Expectedly, the PAR-1 agonist peptide (AP) SFLLR-NH2 also attenuated the cell proliferation. The cell proliferation was not affected by the PAR-1 negative control peptide RLLFT-NH2, which is an inactive peptide for PAR-1. Independently, we determined the effect of in vivo treatment with AEBSF or AP on hippocampal neurogenesis in the adult mouse. The administration of AEBSF, but not that of AP, significantly increased the number of newly-generated cells in the hippocampal subgranular zone. These data suggest that PAR-1 negatively regulated adult neurogenesis in the hippocampus by inhibiting the proliferative activity of the NPCs. PMID:27426918

  6. The association of physical activity to neural adaptability during visuo-spatial processing in healthy elderly adults: A multiscale entropy analysis.

    Science.gov (United States)

    Wang, Chun-Hao; Tsai, Chia-Liang; Tseng, Philip; Yang, Albert C; Lo, Men-Tzung; Peng, Chung-Kang; Wang, Hsin-Yi; Muggleton, Neil G; Juan, Chi-Hung; Liang, Wei-Kuang

    2014-10-29

    Physical activity has been shown to benefit brain and cognition in late adulthood. However, this effect is still unexplored in terms of brain signal complexity, which reflects the level of neural adaptability and efficiency during cognitive processing that cannot be acquired via averaged neuroelectric signals. Here we employed multiscale entropy analysis (MSE) of electroencephalography (EEG), a new approach that conveys important information related to the temporal dynamics of brain signal complexity across multiple time scales, to reveal the association of physical activity with neural adaptability and efficiency in elderly adults. A between-subjects design that included 24 participants (aged 66.63±1.31years; female=12) with high physical activity and 24 age- and gender-matched low physical activity participants (aged 67.29±1.20years) was conducted to examine differences related to physical activity in performance and MSE of EEG signals during a visuo-spatial cognition task. We observed that physically active elderly adults had better accuracy on both visuo-spatial attention and working memory conditions relative to their sedentary counterparts. Additionally, these physically active elderly adults displayed greater MSE values at larger time scales at the Fz electrode in both attention and memory conditions. The results suggest that physical activity may be beneficial for adaptability of brain systems in tasks involving visuo-spatial information. MSE thus might be a promising approach to test the effects of the benefits of exercise on cognition. PMID:25463141

  7. Monocular Visual Deprivation Suppresses Excitability in Adult Human Visual Cortex

    DEFF Research Database (Denmark)

    Lou, Astrid Rosenstand; Madsen, Kristoffer Hougaard; Paulson, Olaf Bjarne;

    2011-01-01

    The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we...... employed TMS to trace plastic changes in adult visual cortex before, during, and after 48 h of monocular deprivation (MD) of the right dominant eye. In healthy adult volunteers, MD-induced changes in visual cortex excitability were probed with paired-pulse TMS applied to the left and right occipital cortex....... Stimulus–response curves were constructed by recording the intensity of the reported phosphenes evoked in the contralateral visual field at range of TMS intensities. Phosphene measurements revealed that MD produced a rapid and robust decrease in cortical excitability relative to a control condition without...

  8. In vivo transplantation of neurosphere-like bodies derived from the human postnatal and adult enteric nervous system: a pilot study.

    Directory of Open Access Journals (Sweden)

    Susan Hetz

    Full Text Available Recent advances in the in vitro characterization of human adult enteric neural progenitor cells have opened new possibilities for cell-based therapies in gastrointestinal motility disorders. However, whether these cells are able to integrate within an in vivo gut environment is still unclear. In this study, we transplanted neural progenitor-containing neurosphere-like bodies (NLBs in a mouse model of hypoganglionosis and analyzed cellular integration of NLB-derived cell types and functional improvement. NLBs were propagated from postnatal and adult human gut tissues. Cells were characterized by immunohistochemistry, quantitative PCR and subtelomere fluorescence in situ hybridization (FISH. For in vivo evaluation, the plexus of murine colon was damaged by the application of cationic surfactant benzalkonium chloride which was followed by the transplantation of NLBs in a fibrin matrix. After 4 weeks, grafted human cells were visualized by combined in situ hybridization (Alu and immunohistochemistry (PGP9.5, GFAP, SMA. In addition, we determined nitric oxide synthase (NOS-positive neurons and measured hypertrophic effects in the ENS and musculature. Contractility of treated guts was assessed in organ bath after electrical field stimulation. NLBs could be reproducibly generated without any signs of chromosomal alterations using subtelomere FISH. NLB-derived cells integrated within the host tissue and showed expected differentiated phenotypes i.e. enteric neurons, glia and smooth muscle-like cells following in vivo transplantation. Our data suggest biological effects of the transplanted NLB cells on tissue contractility, although robust statistical results could not be obtained due to the small sample size. Further, it is unclear, which of the NLB cell types including neural progenitors have direct restoring effects or, alternatively may act via 'bystander' mechanisms in vivo. Our findings provide further evidence that NLB transplantation can be

  9. Neural Basis of Interpersonal Traits in Neurodegenerative Diseases

    OpenAIRE

    Sollberger, Marc; Stanley, Christine M.; Wilson, Stephen M; Gyurak, Anett; Beckman, Victoria; Growdon, Matthew; Jang, Jung; Weiner, Michael W.; Miller, Bruce L.; Rankin, Katherine P.

    2009-01-01

    Several functional and structural imaging studies have investigated the neural basis of personality in healthy adults, but human lesions studies are scarce. Personality changes are a common symptom in patients with neurodegenerative diseases like frontotemporal dementia (FTD) and semantic dementia (SD), allowing a unique window into the neural basis of personality. In this study, we used the Interpersonal Adjective Scales to investigate the structural basis of eight interpersonal traits (domi...

  10. Degraded attentional modulation of cortical neural populations in strabismic amblyopia

    OpenAIRE

    Hou, Chuan; Kim, Yee-Joon; Lai, Xin Jie; Verghese, Preeti

    2016-01-01

    Behavioral studies have reported reduced spatial attention in amblyopia, a developmental disorder of spatial vision. However, the neural populations in the visual cortex linked with these behavioral spatial attention deficits have not been identified. Here, we use functional MRI–informed electroencephalography source imaging to measure the effect of attention on neural population activity in the visual cortex of human adult strabismic amblyopes who were stereoblind. We show that compared with...

  11. A BOLD Perspective on Age-Related Neurometabolic-Flow Coupling and Neural Efficiency Changes in Human Visual Cortex.

    Science.gov (United States)

    Hutchison, Joanna Lynn; Shokri-Kojori, Ehsan; Lu, Hanzhang; Rypma, Bart

    2013-01-01

    Age-related performance declines in visual tasks have been attributed to reductions in processing efficiency. The neural basis of these declines has been explored by comparing the blood-oxygen-level-dependent (BOLD) index of neural activity in older and younger adults during visual task performance. However, neural activity is one of many factors that change with age and lead to BOLD signal differences. We investigated the origin of age-related BOLD changes by comparing blood flow and oxygen metabolic constituents of BOLD signal. Subjects periodically viewed flickering annuli and pressed a button when detecting luminance changes in a central fixation cross. Using magnetic resonance dual-echo arterial spin labeling and CO2 ingestion, we observed age-equivalent (i.e., similar in older and younger groups) fractional cerebral blood flow (ΔCBF) in the presence of age-related increases in fractional cerebral metabolic rate of oxygen (ΔCMRO2). Reductions in ΔCBF responsiveness to increased ΔCMRO2 in elderly led to paradoxical age-related BOLD decreases. Age-related ΔCBF/ΔCMRO2 ratio decreases were associated with reaction times, suggesting that age-related slowing resulted from less efficient neural activity. We hypothesized that reduced vascular responsiveness to neural metabolic demand would lead to a reduction in ΔCBF/ΔCMRO2. A simulation of BOLD relative to ΔCMRO2 for lower and higher neurometabolic-flow coupling ratios (approximating those for old and young, respectively) indicated less BOLD signal change in old than young in relatively lower CMRO2 ranges, as well as greater BOLD signal change in young compared to old in relatively higher CMRO2 ranges. These results suggest that age-comparative studies relying on BOLD signal might be misinterpreted, as age-related BOLD changes do not merely reflect neural activity changes. Age-related declines in neurometabolic-flow coupling might lead to neural efficiency reductions that can adversely affect visual task

  12. A BOLD perspective on age-related flow-metabolism coupling and neural efficiency changes in human visual cortex

    Directory of Open Access Journals (Sweden)

    Joanna Lynn Hutchison

    2013-05-01

    Full Text Available Age-related performance declines in visual tasks have been attributed to reductions in processing efficiency. The neural basis of these declines has been explored by comparing the blood-oxygen-level-dependent (BOLD index of neural activity in older and younger adults during visual task performance. However, neural activity is one of many factors that change with age and lead to BOLD signal differences. We investigated the origin of age-related BOLD changes by comparing blood-flow and oxygen-metabolic constituents of BOLD signal. Subjects periodically viewed flickering annuli and pressed a button when detecting luminance changes in a central fixation cross. Using magnetic resonance dual-echo arterial spin labeling and CO2 ingestion, we observed age-equivalent (i.e., similar in older and younger groups fractional cerebral blood flow (∆CBF in the presence of age-related increases in fractional cerebral metabolic rate of oxygen (∆CMRO2. Reductions in ∆CBF responsiveness to increased ∆CMRO2 in elderly led to paradoxical age-related BOLD decreases. Age-related ∆CBF/∆CMRO2 ratio decreases were associated with reaction times, suggesting that age-related slowing resulted from less efficient neural activity. We hypothesized that reduced vascular responsiveness to neural metabolic demand would lead to a reduction in ∆CBF/∆CMRO2. A simulation of BOLD relative to ∆CMRO2 for lower and higher neurometabolic-flow coupling ratios (approximating those for old and young, respectively indicated less BOLD signal change in old than young in relatively lower CMRO2 ranges, as well as greater BOLD signal change in young compared to old in relatively higher CMRO2 ranges. These results suggest that age-comparative studies relying on BOLD signal might be misinterpreted, as age-related BOLD changes do not merely reflect neural activity changes. Age-related declines in neurometabolic-flow coupling might lead to neural efficiency reductions that can

  13. The Human Function Compunction: Teleological Explanation in Adults

    Science.gov (United States)

    Kelemen, Deborah; Rosset, Evelyn

    2009-01-01

    Research has found that children possess a broad bias in favor of teleological--or purpose-based--explanations of natural phenomena. The current two experiments explored whether adults implicitly possess a similar bias. In Study 1, undergraduates judged a series of statements as "good" (i.e., correct) or "bad" (i.e., incorrect) explanations for…

  14. Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Lu Chen

    2014-06-01

    Full Text Available Using a viral model of the demyelinating disease multiple sclerosis (MS, we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.

  15. Metabonomic profiling of human placentas reveals different metabolic patterns among subtypes of neural tube defects.

    Science.gov (United States)

    Chi, Yi; Pei, Lijun; Chen, Gong; Song, Xinming; Zhao, Aihua; Chen, Tianlu; Su, Mingming; Zhang, Yinan; Liu, Jianmeng; Ren, Aiguo; Zheng, Xiaoying; Xie, Guoxiang; Jia, Wei

    2014-02-01

    Neural tube defects (NTDs) are one of the most common types of birth defects with a complex etiology. We have previously profiled serum metabolites of pregnant women in Lvliang prefecture, Shanxi Province of China, which revealed distinct metabolic changes in pregnant women with NTDs outcome. Here we present a metabonomics study of human placentas of 144 pregnant women with normal pregnancy outcome and 115 pregnant women affected with NTDs recruited from four rural counties (Pingding, Xiyang, Taigu, and Zezhou) of Shanxi Province, the area with the highest prevalence worldwide. A panel of 19 metabolites related to one-carbon metabolism was also quantitatively determined. We observed obvious differences in global metabolic profiles and one-carbon metabolism among three subtypes of NTDs, anencephaly (Ane), spina bifida (SB), and Ane complicated with SB (Ane & SB) via mass-spectrometry-based metabonomics approach. Disturbed carbohydrate, amino acid, lipid, and nucleic acid metabolism were identified. Placental transport of amino acids might be depressed in Ane and Ane & SB group. Deficiency of choline contributes to Ane and Ane & SB pathogenesis via different metabolic pathways. The formation of NTDs seemed to be weakly related to folates. The metabonomic analysis reveals that the physiological and biochemical processes of the three subtypes of NTDs might be different and the subtype condition should be considered for the future investigation of NTDs. PMID:24397701

  16. Human neural precursor cells promote neurologic recovery in a viral model of multiple sclerosis.

    Science.gov (United States)

    Chen, Lu; Coleman, Ronald; Leang, Ronika; Tran, Ha; Kopf, Alexandra; Walsh, Craig M; Sears-Kraxberger, Ilse; Steward, Oswald; Macklin, Wendy B; Loring, Jeanne F; Lane, Thomas E

    2014-06-01

    Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments. PMID:24936469

  17. Comprehensive quantitative comparison of the membrane proteome and PTM-ome of human embryonic stem cells and neural stem cells

    DEFF Research Database (Denmark)

    Braga, Marcella Nunes de Melo; Schulz, Melanie; Jakobsen, Lene;

    Introduction: Human embryonic stem cells (hESCs) can differentiate into all three germ layers and self-renew. Due to its ability to differentiate in vitro into human neural stem cells (hNSCs), which can further be differentiated into motor neurons and dopaminergic neurons, these cells are potential...... source for treatment of neurological diseases such as Parkinson´s disease. Membrane proteins are very important in cellular signaling and they are regulated by post-translational modifications such as phosphorylation and glycosylation. In order to obtain more information about important membrane proteins...... identified phosphorylated and SA glycosylated proteins, respectively. This study allowed us to identify several significantly regulated proteins during the differentiation process, including proteins involved in the early embryonic development as well as in the neural development. In the latter group of...

  18. Adults with high social anhedonia have altered neural connectivity with ventral lateral prefrontal cortex when processing positive social signals

    OpenAIRE

    Hong Yin

    2015-01-01

    Social anhedonia (SA) is a debilitating characteristic of schizophrenia and a vulnerability for developing schizophrenia among people at risk. Prior work (Hooker et al, 2014) has revealed neural deficits in ventral lateral prefrontal cortex (VLPFC) during processing of positive emotion in a community sample of people with high social anhedonia. Deficits in VLPFC neural activity are related to worse self-reported schizophrenia-spectrum symptoms and worse mood and behavior after social stress...

  19. A study on the possible involvement of the PAX3 gene in human neural tube defects

    Energy Technology Data Exchange (ETDEWEB)

    Hol, F.A.; Hamel, B.C.J.; Geurds, M.P.A. [University Hospital Nijmegen (Netherlands)] [and others

    1994-09-01

    Neural tube defects (NTD) are congenital malformations of the central nervous system which are generally attributed to a combination of environmental and genetic factors. Recently, the molecular defect responsible for the phenotype of the Splotch mouse, a monogenic model system for NTD, was determined. A mutation disrupts the homeodomain of the gene for Pax3. In humans, mutations in the cognate gene for PAX3 can cause Waardenburg syndrome (WS), which is associated with NTD. Based on these findings, PAX3 can be regarded as a candidate gene for human NTD. To test this hypothesis we have screened the DNA of 39 familial and 70 sporadic NTD patients for mutations in the coding exons and flanking intron sequences of the PAX3 gene. SSC analysis revealed abnormal bands in exon 2, exon 5, exon 6 and exon 7 in different patients. A missense mutation was identified in exon 6 downstream from the homeodomain in several patients resulting in an amino acid substitution (Thr315Lys) in the protein. However, the same substitution was detected in unaffected controls suggesting no biological significance. Above shifts most likely represent polymorphisms that are irrelevant for NTD. A conspicuous SSC-band shift was observed in exon 5 of one familial patient with spina bifida. Sequencing revealed that the patient was heterozygous for a 5 bp deletion upstream of the homeodomain. The deletion causes a frameshift, which leads to premature termination of translation. Mild characteristics of WS were detected in several members of the family including the index patient. DNA analysis showed co-segregation of the mutation with these symptoms. Although PAX3 mutations can increase the penetrance of NTD in families with WS, our results show that their presence is not sufficient to cause NTD.

  20. PPARγ Is Activated during Congenital Cytomegalovirus Infection and Inhibits Neuronogenesis from Human Neural Stem Cells

    Science.gov (United States)

    Rolland, Maude; Li, Xiaojun; Perez-Berezo, Teresa; Rauwel, Benjamin; Benchoua, Alexandra; Bessières, Bettina; Aziza, Jacqueline; Cenac, Nicolas; Luo, Minhua; Casper, Charlotte; Peschanski, Marc; Gonzalez-Dunia, Daniel; Leruez-Ville, Marianne; Davrinche, Christian; Chavanas, Stéphane

    2016-01-01

    Congenital infection by human cytomegalovirus (HCMV) is a leading cause of permanent sequelae of the central nervous system, including sensorineural deafness, cerebral palsies or devastating neurodevelopmental abnormalities (0.1% of all births). To gain insight on the impact of HCMV on neuronal development, we used both neural stem cells from human embryonic stem cells (NSC) and brain sections from infected fetuses and investigated the outcomes of infection on Peroxisome Proliferator-Activated Receptor gamma (PPARγ), a transcription factor critical in the developing brain. We observed that HCMV infection dramatically impaired the rate of neuronogenesis and strongly increased PPARγ levels and activity. Consistent with these findings, levels of 9-hydroxyoctadecadienoic acid (9-HODE), a known PPARγ agonist, were significantly increased in infected NSCs. Likewise, exposure of uninfected NSCs to 9-HODE recapitulated the effect of infection on PPARγ activity. It also increased the rate of cells expressing the IE antigen in HCMV-infected NSCs. Further, we demonstrated that (1) pharmacological activation of ectopically expressed PPARγ was sufficient to induce impaired neuronogenesis of uninfected NSCs, (2) treatment of uninfected NSCs with 9-HODE impaired NSC differentiation and (3) treatment of HCMV-infected NSCs with the PPARγ inhibitor T0070907 restored a normal rate of differentiation. The role of PPARγ in the disease phenotype was strongly supported by the immunodetection of nuclear PPARγ in brain germinative zones of congenitally infected fetuses (N = 20), but not in control samples. Altogether, our findings reveal a key role for PPARγ in neurogenesis and in the pathophysiology of HCMV congenital infection. They also pave the way to the identification of PPARγ gene targets in the infected brain. PMID:27078877

  1. Self-organizing neural integration of pose-motion features for human action recognition.

    Science.gov (United States)

    Parisi, German I; Weber, Cornelius; Wermter, Stefan

    2015-01-01

    The visual recognition of complex, articulated human movements is fundamental for a wide range of artificial systems oriented toward human-robot communication, action classification, and action-driven perception. These challenging tasks may generally involve the processing of a huge amount of visual information and learning-based mechanisms for generalizing a set of training actions and classifying new samples. To operate in natural environments, a crucial property is the efficient and robust recognition of actions, also under noisy conditions caused by, for instance, systematic sensor errors and temporarily occluded persons. Studies of the mammalian visual system and its outperforming ability to process biological motion information suggest separate neural pathways for the distinct processing of pose and motion features at multiple levels and the subsequent integration of these visual cues for action perception. We present a neurobiologically-motivated approach to achieve noise-tolerant action recognition in real time. Our model consists of self-organizing Growing When Required (GWR) networks that obtain progressively generalized representations of sensory inputs and learn inherent spatio-temporal dependencies. During the training, the GWR networks dynamically change their topological structure to better match the input space. We first extract pose and motion features from video sequences and then cluster actions in terms of prototypical pose-motion trajectories. Multi-cue trajectories from matching action frames are subsequently combined to provide action dynamics in the joint feature space. Reported experiments show that our approach outperforms previous results on a dataset of full-body actions captured with a depth sensor, and ranks among the best results for a public benchmark of domestic daily actions. PMID:26106323

  2. Self-Organizing Neural Integration of Pose-Motion Features for Human Action Recognition

    Directory of Open Access Journals (Sweden)

    German Ignacio Parisi

    2015-06-01

    Full Text Available The visual recognition of complex, articulated human movements is fundamental for a wide range of artificial systems oriented towards human-robot communication, action classification, and action-driven perception. These challenging tasks may generally involve the processing of a huge amount of visual information and learning-based mechanisms for generalizing a set of training actions and classifying new samples. To operate in natural environments, a crucial property is the efficient and robust recognition of actions, also under noisy conditions caused by, for instance, systematic sensor errors and temporarily occluded persons. Studies of the mammalian visual system and its outperforming ability to process biological motion information suggest separate neural pathways for the distinct processing of pose and motion features at multiple levels and the subsequent integration of these visual cues for action perception. We present a neurobiologically-motivated approach to achieve noise-tolerant action recognition in real time. Our model consists of self-organizing Growing When Required (GWR networks that obtain progressively generalized representations of sensory inputs and learn inherent spatiotemporal dependencies. During the training, the GWR networks dynamically change their topological structure to better match the input space. We first extract pose and motion features from video sequences and then cluster actions in terms of prototypical pose-motion trajectories. Multi-cue trajectories from matching action frames are subsequently combined to provide action dynamics in the joint feature space. Reported experiments show that our approach outperforms previous results on a dataset of full-body actions captured with a depth sensor, and ranks among the best 21 results for a public benchmark of domestic daily actions.

  3. TNF-α respecifies human mesenchymal stem cells to a neural fate and promotes migration toward experimental glioma

    OpenAIRE

    Ries, Christian; von Baumgarten, Louisa; Schichor, Christian; Berninger, Benedikt; Popp, Tanja; Neth, Peter; Goldbrunner, Roland; Kienast, Yvonne; Winkler, Frank; Jochum, Marianne; Egea, Virginia

    2010-01-01

    Abstract Bone marrow-derived human mesenchymal stem cells (hMSCs) have become valuable candidates for cell-based therapeutical applications including neuroregenerative and anti-tumor strategies. Yet, the molecular mechanisms that control hMSC transdifferentiation to neural cells and hMSC tropism toward glioma remain unclear. Here, we demonstrate that hMSCs incubated with 50 ng/ml TNF-? acquired astroglial cell morphology without affecting proliferation which was increased at 5 ng/m...

  4. Neonatal Neural Progenitor Cells and Their Neuronal and Glial Cell Derivatives Are Fully Permissive for Human Cytomegalovirus Infection▿

    OpenAIRE

    Luo, Min Hua; Philip H. Schwartz; Fortunato, Elizabeth A.

    2008-01-01

    Congenital human cytomegalovirus (HCMV) infection causes central nervous system structural abnormalities and functional disorders, affecting both astroglia and neurons with a pathogenesis that is only marginally understood. To better understand HCMV's interactions with such clinically important cell types, we utilized neural progenitor cells (NPCs) derived from neonatal autopsy tissue, which can be differentiated down either glial or neuronal pathways. Studies were performed using two viral i...

  5. Induction of apoptotic death and retardation of neuronal differentiation of human neural stem cells by sodium arsenite treatment

    OpenAIRE

    Ivanov, Vladimir N.; Hei, Tom K.

    2012-01-01

    Chronic arsenic toxicity is a global health problem that affects more than 100 million people worldwide. Long-term health effects of inorganic sodium arsenite in drinking water may result in skin, lung and liver cancer and severe neurological abnormalities. We investigated in the present study whether sodium arsenite affects signaling pathways that control cell survival, proliferation and neuronal differentiation of human neural stem cells (NSC). We demonstrated that the critical signaling pa...

  6. Evaluation of Developmental Toxicants and Signaling Pathways in a Functional Test Based on the Migration of Human Neural Crest Cells

    OpenAIRE

    Zimmer, Bastian; Lee, Gabsang; Balmer, Nina V.; Meganathan, Kesavan; Sachinidis, Agapios; Studer, Lorenz; Leist, Marcel

    2012-01-01

    Background: Information on the potential developmental toxicity (DT) of the majority of chemicals is scarce, and test capacities for further animal-based testing are limited. Therefore, new approaches with higher throughput are required. A screening strategy based on the use of relevant human cell types has been proposed by the U.S. Environmental Protection Agency and others. Because impaired neural crest (NC) function is one of the known causes for teratologic effects, testing of toxicant ef...

  7. Comprehensive Quantitative Comparison of the Membrane Proteome, Phosphoproteome, and Sialiome of Human Embryonic and Neural Stem Cells*

    OpenAIRE

    Melo-Braga, Marcella Nunes; Schulz, Melanie; Liu, Qiuyue; Swistowski, Andrzej; Palmisano, Giuseppe; Engholm-Keller, Kasper; Jakobsen, Lene; Zeng, Xianmin; Larsen, Martin Røssel

    2013-01-01

    Human embryonic stem cells (hESCs) can differentiate into neural stem cells (NSCs), which can further be differentiated into neurons and glia cells. Therefore, these cells have huge potential as source for treatment of neurological diseases. Membrane-associated proteins are very important in cellular signaling and recognition, and their function and activity are frequently regulated by post-translational modifications such as phosphorylation and glycosylation. To obtain information about memb...

  8. An externally head-mounted wireless neural recording device for laboratory animal research and possible human clinical use.

    Science.gov (United States)

    Yin, Ming; Li, Hao; Bull, Christopher; Borton, David A; Aceros, Juan; Larson, Lawrence; Nurmikko, Arto V

    2013-01-01

    In this paper we present a new type of head-mounted wireless neural recording device in a highly compact package, dedicated for untethered laboratory animal research and designed for future mobile human clinical use. The device, which takes its input from an array of intracortical microelectrode arrays (MEA) has ninety-seven broadband parallel neural recording channels and was integrated on to two custom designed printed circuit boards. These house several low power, custom integrated circuits, including a preamplifier ASIC, a controller ASIC, plus two SAR ADCs, a 3-axis accelerometer, a 48MHz clock source, and a Manchester encoder. Another ultralow power RF chip supports an OOK transmitter with the center frequency tunable from 3GHz to 4GHz, mounted on a separate low loss dielectric board together with a 3V LDO, with output fed to a UWB chip antenna. The IC boards were interconnected and packaged in a polyether ether ketone (PEEK) enclosure which is compatible with both animal and human use (e.g. sterilizable). The entire system consumes 17mA from a 1.2Ahr 3.6V Li-SOCl2 1/2AA battery, which operates the device for more than 2 days. The overall system includes a custom RF receiver electronics which are designed to directly interface with any number of commercial (or custom) neural signal processors for multi-channel broadband neural recording. Bench-top measurements and in vivo testing of the device in rhesus macaques are presented to demonstrate the performance of the wireless neural interface. PMID:24110386

  9. Neural coding and perception of pitch in the normal and impaired human auditory system

    DEFF Research Database (Denmark)

    Santurette, Sébastien

    2011-01-01

    Pitch is an important attribute of hearing that allows us to perceive the musical quality of sounds. Besides music perception, pitch contributes to speech communication, auditory grouping, and perceptual segregation of sound sources. In this work, several aspects of pitch perception in humans were...... for a variety of basic auditory tasks, indicating that it may be a crucial measure to consider for hearing-loss characterization. In contrast to hearing-impaired listeners, adults with dyslexia showed no deficits in binaural pitch perception, suggesting intact low-level auditory mechanisms. The second part...... that the use of spectral cues remained plausible. Simulations of auditory-nerve representations of the complex tones further suggested that a spectrotemporal mechanism combining precise timing information across auditory channels might best account for the behavioral data. Overall, this work provides insights...

  10. The hematopoietic factor GM-CSF (Granulocyte-macrophage colony-stimulating factor promotes neuronal differentiation of adult neural stem cells in vitro

    Directory of Open Access Journals (Sweden)

    Schäbitz Wolf-Rüdiger

    2007-10-01

    Full Text Available Abstract Background Granulocyte-macrophage colony stimulating factor (GM-CSF is a hematopoietic growth factor involved in the generation of granulocytes, macrophages, and dendritic cells from hematopoietic progenitor cells. We have recently demonstrated that GM-CSF has anti-apoptotic functions on neurons, and is neuroprotective in animal stroke models. Results The GM-CSF receptor α is expressed on adult neural stem cells in the rodent brain, and in culture. Addition of GM-CSF to NSCs in vitro increased neuronal differentiation in a dose-dependent manner as determined by quantitative PCR, reporter gene assays, and FACS analysis. Conclusion Similar to the hematopoietic factor Granulocyte-colony stimulating factor (G-CSF, GM-CSF stimulates neuronal differentiation of adult NSCs. These data highlight the astonishingly similar functions of major hematopoietic factors in the brain, and raise the clinical attractiveness of GM-CSF as a novel drug for neurological disorders.

  11. Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS.

    Directory of Open Access Journals (Sweden)

    Marco Schlepütz

    Full Text Available The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS respond to electric field stimulation (EFS and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM caused bronchoconstriction in human (4 from 7 and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC. However, this effect was notably smaller in human responder (30 ± 7.1% than in guinea pig (79 ± 5.1% PCLS. The transient receptor potential (TRP channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.

  12. Neural Networks

    International Nuclear Information System (INIS)

    Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing

  13. RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro.

    Science.gov (United States)

    Soldati, Chiara; Caramanica, Pasquale; Burney, Matthew J; Toselli, Camilla; Bithell, Angela; Augusti-Tocco, Gabriella; Stanton, Lawrence W; Biagioni, Stefano; Buckley, Noel J; Cacci, Emanuele

    2015-08-01

    Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST-mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome- and transcriptome-wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST-regulated manner together with other signals can contribute to regulation of NSC maintenance and fate. PMID:25691247

  14. Effects of neonatal neural progenitor cell implantation on adult neuroanatomy and cognition in the Ts65Dn model of Down syndrome.

    Directory of Open Access Journals (Sweden)

    Angela L Rachubinski

    Full Text Available As much of the aberrant neural development in Down syndrome (DS occurs postnatally, an early opportunity exists to intervene and influence life-long cognitive development. Recent success using neural progenitor cells (NPC in models of adult neurodegeneration indicate such therapy may be a viable option in diseases such as DS. Murine NPC (mNPC, C17.2 cell line or saline were implanted bilaterally into the dorsal hippocampus of postnatal day 2 (PND 2 Ts65Dn pups to explore the feasibility of early postnatal treatment in this mouse model of DS. Disomic littermates provided karyotype controls for trisomic pups. Pups were monitored for developmental milestone achievement, and then underwent adult behavior testing at 14 weeks of age. We found that implanted mNPC survived into adulthood and migrated beyond the implant site in both karyotypes. The implantation of mNPC resulted in a significant increase in the density of dentate granule cells. However, mNPC implantation did not elicit cognitive changes in trisomic mice either neonatally or in adulthood. To the best of our knowledge, these results constitute the first assessment of mNPC as an early intervention on cognitive ability in a DS model.

  15. Assessing the Neural Correlates of Task-unrelated Thoughts during Episodic Encoding and Their Association with Subsequent Memory in Young and Older Adults.

    Science.gov (United States)

    Maillet, David; Rajah, M Natasha

    2016-06-01

    Recent evidence indicates that young adults frequently exhibit task-unrelated thoughts (TUTs) such as mind-wandering during episodic encoding tasks and that TUTs negatively impact subsequent memory. In the current study, we assessed age-related differences in the frequency and neural correlates of TUTs during a source memory encoding task, as well as age-related differences in the relationship between the neural correlates of TUTs and subsequent source forgetting effects (i.e., source misses). We found no age-related differences in frequency of TUTs during fMRI scanning. Moreover, TUT frequency at encoding was positively correlated with source misses at retrieval across age groups. In both age groups, brain regions including bilateral middle/superior frontal gyri and precuneus were activated to a greater extent during encoding for subsequent source misses versus source hits and during TUTs versus on-task episodes. Overall, our results reveal that, during a source memory encoding task in an fMRI environment, young and older adults exhibit a similar frequency of TUTs and that experiencing TUTs at encoding is associated with decreased retrieval performance. In addition, in both age groups, experiencing TUTs at encoding is associated with increased activation in some of the same regions that exhibit subsequent source forgetting effects. PMID:26845110

  16. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases.

    Science.gov (United States)

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors. PMID:27375363

  17. HUMAN FACE RECOGNITION BY PSEUDO ZERNIKE MOMENT AND PROBABILISTIC NEURAL NETWORK

    OpenAIRE

    ESMAEEL FATEMI BEHBAHANI; AZADEH BASTANI

    2011-01-01

    In this paper a new face recognition method has been introduced. By this method face features have been extracted by pseudo-Zernike moments (PZM).Then a probabilistic neural network has applied to classify thesemoments as feature vectors. Moment features are invariant under scaling, translation, rotation and reflection. Probabilistic Neural Networks have fast computational time. Results show that PZM of order of 14 with PNN have the best performance among all the moments

  18. Tracking cortical entrainment in neural activity: Auditory processes in human temporal cortex

    OpenAIRE

    Thwaites, Andrew; Nimmo-Smith, Ian; Fonteneau, Elisabeth; Patterson, Roy D.; Buttery, Paula; Marslen-Wilson, William D.

    2015-01-01

    A primary objective for cognitive neuroscience is to identify how features of the sensory environment are encoded in neural activity. Current auditory models of loudness perception can be used to make detailed predictions about the neural activity of the cortex as an individual listens to speech. We used two such models (loudness-sones and loudness-phons), varying in their psychophysiological realism, to predict the instantaneous loudness contours produced by 480 isolated words. These two set...

  19. Neural Coding of Sound Intensity and Loudness in the Human Auditory System

    OpenAIRE

    Röhl, Markus; Uppenkamp, Stefan

    2012-01-01

    Inter-individual differences in loudness sensation of 45 young normal-hearing participants were employed to investigate how and at what stage of the auditory pathway perceived loudness, the perceptual correlate of sound intensity, is transformed into neural activation. Loudness sensation was assessed by categorical loudness scaling, a psychoacoustical scaling procedure, whereas neural activation in the auditory cortex, inferior colliculi, and medial geniculate bodies was investigated with fun...

  20. Role of ERK1/2, Akt, and PLCy pathways in proliferation and neuronal differentiation in the adult rat spinal cord neural stem/progenitor cell culture

    Directory of Open Access Journals (Sweden)

    Wai Si eChan

    2013-08-01

    Full Text Available Proliferation of endogenous neural stem/progenitor cells (NSPCs has been identified in both normal and injured adult mammalian spinal cord. Yet the signaling mechanisms underlying the regulation of adult spinal cord NSPCs proliferation and commitment toward a neuronal lineage remain undefined. In this study, the role of three growth factor-mediated signaling pathways in proliferation and neuronal differentiation was examined. Adult spinal cord NSPCs were enriched in the presence of fibroblast growth factor 2 (FGF2. We observed an increase in the number of cells expressing the microtubule-associated protein 2 (MAP2 over time, indicating neuronal differentiation in the culture. Inhibition of the mitogen-activated protein kinase or extracellular signal-regulated kinase (ERK kinase 1 and 2/ERK 1 and 2 (MEK/ERK1/2 or the phosphoinositide 3-kinase (PI3K/Akt pathways suppressed active proliferation in adult spinal cord NSPC cultures; whereas neuronal differentiation was negatively affected only when the ERK1/2 pathway was inhibited. Inhibition of the phospholipase C gamma (PLCy pathway did not affect proliferation or neuronal differentiation. Finally, we demonstrated that the blockade of either the ERK1/2 or PLCy signaling pathways reduced neurite branching of MAP2+ cells derived from the NSPC cultures. Many of the MAP2+ cells expressed synaptophysin and had a glutamatergic phenotype, indicating that over time adult spinal cord NSPCs had differentiated into mostly glutamatergic neurons. Our work provides new information regarding the contribution of these pathways to the proliferation and neuronal differentiation of NSPCs derived from adult spinal cord cultures, and emphasizes that the contribution of these pathways is dependent on the origin of the NSPCs.

  1. Artificial neural network analysis for predicting human percutaneous absorption taking account of vehicle properties.

    Science.gov (United States)

    Atobe, Tomomi; Mori, Masaaki; Yamashita, Fumiyoshi; Hashida, Mitsuru; Kouzuki, Hirokazu

    2015-04-01

    An in silico method for predicting percutaneous absorption of cosmetic ingredients was developed by using artificial neural network (ANN) analysis to predict the human skin permeability coefficient (log Kp), taking account of the physicochemical properties of the vehicle, and the apparent diffusion coefficient (log D). Molecular weight and octanol-water partition coefficient (log P) of chemicals, and log P of the vehicles, were used as molecular descriptors for predicting log Kp and log D of 359 samples, for which literature values of either or both of log Kp and log D were available. Adaptivity of the ANN model was evaluated in comparison with a multiple linear regression model (MLR) by calculating the root-mean-square (RMS) errors. Accuracy and robustness were confirmed by 10-fold cross-validation. The predictive RMS errors of the ANN model were smaller than those of the MLR model (log Kp; 0.675 vs 0.887, log D; 0.553 vs 0.658), indicating superior performance. The predictive RMS errors for log Kp and log D with the ANN model after 10-fold cross-validation analysis were 0.723 and 0.606, respectively. Moreover, we estimated the cumulative amounts of chemicals permeated into the skin during 24 hr (Q24hr) from the values of log Kp and log D by applying Fick's law of diffusion. Our results suggest that this newly established ANN analysis method, taking account of the property of the vehicle, could contribute to non-animal risk assessment of cosmetic ingredients by providing a tool for calculating Q24hr, which is required for evaluating the margin of safety. PMID:25786531

  2. Human neural progenitors differentiate into astrocytes and protect motor neurons in aging rats.

    Science.gov (United States)

    Das, Melanie M; Avalos, Pablo; Suezaki, Patrick; Godoy, Marlesa; Garcia, Leslie; Chang, Christine D; Vit, Jean-Philippe; Shelley, Brandon; Gowing, Genevieve; Svendsen, Clive N

    2016-06-01

    Age-associated health decline presents a significant challenge to healthcare, although there are few animal models that can be used to test potential treatments. Here, we show that there is a significant reduction in both spinal cord motor neurons and motor function over time in the aging rat. One explanation for this motor neuron loss could be reduced support from surrounding aging astrocytes. Indeed, we have previously shown using in vitro models that aging rat astrocytes are less supportive to rat motor neuron function and survival over time. Here, we test whether rejuvenating the astrocyte niche can improve the survival of motor neurons in an aging spinal cord. We transplanted fetal-derived human neural progenitor cells (hNPCs) into the aging rat spinal cord and found that the cells survive and differentiate into astrocytes with a much higher efficiency than when transplanted into younger animals, suggesting that the aging environment stimulates astrocyte maturation. Importantly, the engrafted astrocytes were able to protect against motor neuron loss associated with aging, although this did not result in an increase in motor function based on behavioral assays. We also transplanted hNPCs genetically modified to secrete glial cell line-derived neurotrophic factor (GDNF) into the aging rat spinal cord, as this combination of cell and protein delivery can protect motor neurons in animal models of ALS. During aging, GDNF-expressing hNPCs protected motor neurons, though to the same extent as hNPCs alone, and again had no effect on motor function. We conclude that hNPCs can survive well in the aging spinal cord, protect motor neurons and mature faster into astrocytes when compared to transplantation into the young spinal cord. While there was no functional improvement, there were no functional deficits either, further supporting a good safety profile of hNPC transplantation even into the older patient population. PMID:27032721

  3. Neural Stem Cell or Human Induced Pluripotent Stem Cell-Derived GABA-ergic Progenitor Cell Grafting in an Animal Model of Chronic Temporal Lobe Epilepsy.

    Science.gov (United States)

    Upadhya, Dinesh; Hattiangady, Bharathi; Shetty, Geetha A; Zanirati, Gabriele; Kodali, Maheedhar; Shetty, Ashok K

    2016-01-01

    Grafting of neural stem cells (NSCs) or GABA-ergic progenitor cells (GPCs) into the hippocampus could offer an alternative therapy to hippocampal resection in patients with drug-resistant chronic epilepsy, which afflicts >30% of temporal lobe epilepsy (TLE) cases. Multipotent, self-renewing NSCs could be expanded from multiple regions of the developing and adult brain, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). On the other hand, GPCs could be generated from the medial and lateral ganglionic eminences of the embryonic brain and from hESCs and hiPSCs. To provide comprehensive methodologies involved in testing the efficacy of transplantation of NSCs and GPCs in a rat model of chronic TLE, NSCs derived from the rat medial ganglionic eminence (MGE) and MGE-like GPCs derived from hiPSCs are taken as examples in this unit. The topics comprise description of the required materials, reagents and equipment, methods for obtaining rat MGE-NSCs and hiPSC-derived MGE-like GPCs in culture, generation of chronically epileptic rats, intrahippocampal grafting procedure, post-grafting evaluation of the effects of grafts on spontaneous recurrent seizures and cognitive and mood impairments, analyses of the yield and the fate of graft-derived cells, and the effects of grafts on the host hippocampus. © 2016 by John Wiley & Sons, Inc. PMID:27532817

  4. Clinical characteristics analysis of adult human adenovirus type 7 infection

    Institute of Scientific and Technical Information of China (English)

    张乃春

    2014-01-01

    Objective To investigate the clinical characteristics of patients infected with human adenovirus type 7 and to provide guidance for early diagnosis and timely control of the outbreak.Methods A total of 301 patients infected with the human adenoviruses who were quarantined in hospital from December 2012 to February 2013 were observed.Epidemiological questionnaires were used to collect data of clinical features of the disease including

  5. The weight of nations: an estimation of adult human biomass

    OpenAIRE

    Walpole Sarah; Prieto-Merino David; Edwards Phil; Cleland John; Stevens Gretchen; Roberts Ian

    2012-01-01

    Abstract Background The energy requirement of species at each trophic level in an ecological pyramid is a function of the number of organisms and their average mass. Regarding human populations, although considerable attention is given to estimating the number of people, much less is given to estimating average mass, despite evidence that average body mass is increasing. We estimate global human biomass, its distribution by region and the proportion of biomass due to overweight and obesity. M...

  6. A century of trends in adult human height

    Science.gov (United States)

    2016-01-01

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. DOI: http://dx.doi.org/10.7554/eLife.13410.001 PMID:27458798

  7. Development and application of the Chinese adult female computational phantom Rad-HUMAN

    International Nuclear Information System (INIS)

    Rad-HUMAN is a whole-body numerical phantom of a Chinese adult woman which contains 46 organs and tissues and was created by MCAM6 software using the color photographs of the Chinese Visible Human dataset. This dataset was obtained from a 22-year old Chinese female cadaver judged to represent normal human anatomy as much as possible. The density and elemental composition recommended in the ICRP Publication 89 and in the ICRU report 44 were assigned to the organ and tissue in Rad-HUMAN for radiation protection purpose. The last step was to implement the anatomical data into a Monte Carlo code. Rad-HUMAN contains more than 28.8 billion tiny volume units, which produces an accurately whole-body numerical phantom of a Chinese adult female

  8. Analysis of G-banding in tumor cell lines derived from human neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Junhua Zou; Yanhui Li

    2006-01-01

    BACKGROUND: The application of neural stem cell (NSC) is restricted because of its tumorigenesis, and the possible pathogenesis needs investigation.OBJECTIVE: To compare the differences of chromosomal G-banding between human NSCs (hNSCs) derived tumor cell line and hNSCs derived normal cell lines.DESIGN: A randomized controlled observation.SETTING: Building of Anatomy, Peking University Health Science Center.MATERIALS: The hNSC lines and hNSC-derived tumor cell lines were provided by the Research Center of Stem Cells, Peking University; DMEM/F12 (1:1) medium, N2 additive, B27 additive epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were produced by GIBCO BRL Company (USA); fetal bovine serum by HYCLONE Company (USA).METHODS: The experiments were carried out in the Department of Genetics, Peking University Health Science Center from February 2003 to July 2004. Human fetal striatal NSCs were inoculated hypodermically on the right scapular of nude mice; Normal human fetal striatal NSCs were cultured to 5-8 passages as controls. Karyotyping was performed on the 5th passage of hNSC-derived tumor cells at 6 weeks after hN-SC transplantation into nude mice (T1) and tumor cells at 15 weeks after transplantation (T2). Metaphase chromosomes were examined with microscope, G-banding cytogenetic analysis and karyotyping were performed according to the Cytoscan Karyotyping FISH and CGH software system (United biotechnology USA Corporation).MAIN OUTCOME MEASURES: G-banded analytical results of human fetal striatal nerve stem cells derived tumor cell lines (T1 and T2) of metaphase chromosomes were observed.RESULTS: ① Chromosome analysis of hNSC-derived tumor cell lines 1 (T1): Twenty-five well-spread metaphases were randomly selected for analysis. The karyotypes were 64, XX (8, 32%); 65, XX (1, 4%); 67,XX (5, 20%); 68, XX (11, 44%). The modal number of chromosomes in this cell lines was 68, which were all hypotriploid. The analysis of 8 G

  9. Comparative Neuronal Differentiation of Self-Renewing Neural Progenitor Cell Lines Obtained from Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Chiara Verpelli

    2013-10-01

    Full Text Available Most human neuronal disorders are associated with genetic alterations that cause defects in neuronal development and induce precocious neurodegeneration. In order to fully characterize the molecular mechanisms underlying the onset of these devastating diseases, it is important to establish in vitro models able to recapitulate the human pathology as closely as possible. Here we compared three different differentiation protocols for obtaining functional neurons from human induced pluripotent stem cells (hiPSCs: human neural progenitors (hNPs obtained from hiPSCs were differentiated by co-culturing them with rat primary neurons, glial cells or simply by culturing them on matrigel in neuronal differentiation medium, and the differentiation level was compared using immunofluorescence, biochemical and electrophysiological methods.We show that the differentiated neurons displayed distinct maturation properties depending on the protocol used and the faster morphological and functional maturation was obtained when hNPs were co-cultured with rat primary neurons.

  10. Happiness, depression and human benevolence beliefs in institutionalized and non institutionalized major adults

    Directory of Open Access Journals (Sweden)

    Walter L. Arias

    2013-12-01

    Full Text Available In this study we analyze the relations between happiness, depression and human benevolence beliefs in a group of major people who live in asylums (24 and others who live with their families (38. We use Lima’s happiness scale, Yesavage’s Geriatric depression scale and Belief in human scale. We found that there were no significant differences between two groups of major adults in depression levels, but in happiness, positive sense of life and satisfaction with life, non institutionalized older adults had higher punctuations than major people who lived in asylums.

  11. Neural correlates of a standardized version of the trail making test in young and elderly adults: a functional near-infrared spectroscopy study.

    Science.gov (United States)

    Müller, Laura D; Guhn, Anne; Zeller, Julia B M; Biehl, Stefanie C; Dresler, Thomas; Hahn, Tim; Fallgatter, Andreas J; Polak, Thomas; Deckert, Jürgen; Herrmann, Martin J

    2014-04-01

    The trail making test (TMT) is a widely applied diagnostic tool measuring executive functioning in order to discriminate between healthy and pathological aging processes. However, due to its paper-and-pencil nature it is difficult to adapt for functional brain imaging. Related neural underpinnings even in healthy aging are mostly unknown since no consistent administration for imaging is available. In this study a standardized implementation of the TMT for functional near-infrared spectroscopy (fNIRS) is proposed to investigate associated frontal cortex activation in healthy young (mean age 25.7 ± 3.02 years) and elderly adults (mean age 70.95 ± 3.55 years). The TMT consisted of a number condition (TMT-A), an alternating number and letter condition (TMT-B) as well as a control task. Behavioral results demonstrated that elderly participants performed slower but committed a similar number of errors compared to younger adults. The fNIRS results showed that particularly the TMT-B provoked bilateral activation in the ventro- and dorsolateral prefrontal cortex (vlPFC and dlPFC) as well as in premotor regions. Elderly participants displayed more significantly activated channels and a different activation pattern compared to younger participants especially manifesting in more bilateral dlPFC activation. In line with the hemispheric asymmetry reduction in elderly adults (HAROLD) model, the results were interpreted as an additional need for cognitive control resources in elderly participants. This study succeeded in implementing an appropriate version of the TMT for fNIRS and helps elucidating neural aging effects associated with this task. PMID:24524911

  12. You and your kin: Neural signatures of family-based group perception in the subgenual cortex

    OpenAIRE

    Rüsch, Nicolas; Bado, Patricia; Zahn, Roland; Bramati, Ivanei E.; de Oliveira-Souza, Ricardo; Moll, Jorge

    2014-01-01

    Attachment to one's kin as an in-group emerges from a fundamental human motivation and is vital for human survival. Despite important recent advances in the field of social neuroscience, the neural mechanisms underlying family-related in-group perception remain obscure. To examine the neural basis of perceiving family-related in-group boundaries in response to written kinship scenarios, we used functional magnetic resonance imaging in 27 healthy adults and obtained self-report ratings of fami...

  13. Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts

    Directory of Open Access Journals (Sweden)

    James C K Lai

    2008-12-01

    Full Text Available James C K Lai1, Maria B Lai1, Sirisha Jandhyam1, Vikas V Dukhande1, Alok Bhushan1, Christopher K Daniels1, Solomon W Leung21Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, and Biomedical Research Institute; 2Department of Civil and Environmental Engineering, College of Engineering and Biomedical Research Institute, Idaho State University, Pocatello, ID, USAAbstract: The use of titanium dioxide (TiO2 in various industrial applications (eg, production of paper, plastics, cosmetics, and paints has been expanding thereby increasing the occupational and other environmental exposure of these nanoparticles to humans and other species. However, the health effects of exposure to TiO2 nanoparticles have not been systematically assessed even though recent studies suggest that such exposure induces inflammatory responses in lung tissue and cells. Because the effects of such nanoparticles on human neural cells are unknown, we have determined the putative cytotoxic effects of these nanoparticles on human astrocytes-like astrocytoma U87 cells and compared their effects on normal human fibroblasts. We found that TiO2 micro- and nanoparticles induced cell death on both human cell types in a concentration-related manner. We further noted that zinc oxide (ZnO nanoparticles were the most effective, TiO2 nanoparticles the second most effective, and magnesium oxide (MgO nanoparticles the least effective in inducing cell death in U87 cells. The cell death mechanisms underlying the effects of TiO2 micro- and nanoparticles on U87 cells include apoptosis, necrosis, and possibly apoptosis-like and necrosis-like cell death types. Thus, our findings may have toxicological and other pathophysiological implications on exposure of humans and other mammalian species to metallic oxide nanoparticles.Keywords: cytotoxicity of titanium dioxide micro- and nanoparticles, cytotoxicity of zinc oxide and magnesium oxide nanoparticles, human neural cells

  14. The human traffickers and exploitation of children and young adults.

    Directory of Open Access Journals (Sweden)

    Sara Scala

    2012-06-01

    Full Text Available The article focuses on the traffic of children, who are kidnapped, cheated and purchased by their families to be exploited in many ways. These victims have severe mental and physical traumas. Many of them, slaves of their exploiters, remain invisible and live their lifes without fundamental rights and without any kind of support or help. The traffic in human beings is a new kind of slavery, which acts in the dark, is criminal and involves different subjects of different ages, different nationalities and generations. The traffic in human beings is managed by transnational criminal organizations and is a disturbing and growing phenomena around the world.

  15. Adults with high social anhedonia have altered neural connectivity with ventral lateral prefrontal cortex when processing positive social signals

    Directory of Open Access Journals (Sweden)

    Hong Yin

    2015-08-01

    Full Text Available Social anhedonia (SA is a debilitating characteristic of schizophrenia and a vulnerability for developing schizophrenia among people at risk. Prior work (Hooker et al, 2014 has revealed neural deficits in ventral lateral prefrontal cortex (VLPFC during processing of positive emotion in a community sample of people with high social anhedonia. Deficits in VLPFC neural activity are related to worse self-reported schizophrenia-spectrum symptoms and worse mood and behavior after social stress. In the current study, psychophysiological interaction (PPI analysis was applied to investigate the neural mechanisms mediated by VLPFC during emotion processing. PPI analysis revealed that, compared to low SA controls, participants with high SA displayed reduced VLPFC integration, specifically reduced connectivity between VLPFC and premotor cortex, inferior parietal and posterior temporal regions when viewing positive relative to neutral emotion. Across all participants, connectivity between VLPFC and inferior parietal region when viewing positive (versus neutral emotion was significantly correlated with measures of emotion management and attentional control. Additionally connectivity between VLPFC and superior temporal sulcus was related to reward and pleasure anticipation, and connectivity between VLPFC and inferior temporal sulcus correlated with attentional control measure. Our results suggest that impairments to VLPFC mediated neural circuitry underlie the cognitive and emotional deficits.

  16. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults

    DEFF Research Database (Denmark)

    Larsen, Nadja; Vogensen, Finn Kvist; van der Berg, Franciscus Winfried J;

    2010-01-01

    Background Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control...... control metabolic diseases by modifying the gut microbiota....... = 0.04). Conclusions The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies to...

  17. Neurogenesis in the embryonic and adult brain: same regulators, different roles.

    Directory of Open Access Journals (Sweden)

    Noelia eUrban

    2014-11-01

    Full Text Available Neurogenesis persists in adult mammals in specific brain areas, known as neurogenic niches. Adult neurogenesis is highly dynamic and is modulated by multiple physiological stimuli and pathological states. There is a strong interest in understanding how this process is regulated, particularly since active neuronal production has been demonstrated in both the hippocampus and the subventricular zone of adult humans.The molecular mechanisms that control neurogenesis have been extensively studied during embryonic development. Therefore, we have a broad knowledge of the intrinsic factors and extracellular signalling pathways driving proliferation and differentiation of embryonic neural precursors. Many of these factors also play important roles during adult neurogenesis, but essential differences exist in the biological responses of neural precursors in the embryonic and adult contexts. Because adult neural stem cells are normally found in a quiescent state, regulatory pathways can affect adult neurogenesis in ways that have no clear counterpart during embryogenesis. BMP signalling, for instance, regulates neural stem cell behaviour both during embryonic and adult neurogenesis. However, this pathway maintains stem cell proliferation in the embryo, while it promotes quiescence to prevent stem cell exhaustion in the adult brain. In this review, we will compare and contrast the functions of transcription factors and other regulatory molecules in the embryonic brain and in adult neurogenic regions of the adult brain in the mouse, with a special focus on the hippocampal niche and on the regulation of the balance between quiescence and activation of adult neural stem cells in this region.

  18. Two animated adult human voxel phantoms based on polygon mesh surfaces

    International Nuclear Information System (INIS)

    Among computational models used in radiation protection, voxel phantoms based on computer tomographic (CT), nuclear magnetic resonance (NMR) or colour photographic images, became very popular in recent years. Although being a true to nature representation of the scanned individual the scanning is usually made in supine position, which causes a shift of internal organs towards the ribcage, a compression of the lungs and a reduction of the sagittal diameter especially in the abdominal region compared to the anatomy of a person in upright standing position, which in turn can influence absorbed or equivalent dose estimates. This study proposes a method for human phantom design using tools recently developed in the areas of computer graphics and animated films and applies them to the creation and modelling of artificial 3 D human organs and tissues. Two animated models, a male and a female adult human phantom have been developed based on anatomical atlases, observing at the same time the anatomical specifications published by the International Commission on Radiological Protection for the male and female reference adult. The phantoms are called FAXAA (Female Adult voXelAverage-Average) and MAXAA (Male Adult voXelAverage-Average) because they represent female and male adults with average weight and average height. (author)

  19. Canonical Genetic Signatures of the Adult Human Brain

    OpenAIRE

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Anil G. Jegga; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L; Menche, Jörge; Szafer, Aaron; Collman, Forrest

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological ann...

  20. Testosterone affects language areas of the adult human brain.

    Science.gov (United States)

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  1. Shifts in human skin and nares microbiota of healthy children and adults

    OpenAIRE

    Oh, Julia; Conlan, Sean; Polley, Eric C.; Segre, Julia A.; Kong, Heidi H.

    2012-01-01

    Background Characterization of the topographical and temporal diversity of the microbial collective (microbiome) hosted by healthy human skin established a reference for studying disease-causing microbiomes. Physiologic changes occur in the skin as humans mature from infancy to adulthood. Thus, characterizations of adult microbiomes might have limitations when considering pediatric disorders such as atopic dermatitis (AD) or issues such as sites of microbial carriage. The objective of this st...

  2. Happiness, depression and human benevolence beliefs in institutionalized and non institutionalized major adults

    OpenAIRE

    Walter L. Arias; Luis Yepez; Ana L. Núñez; Adriana Oblitas; Susana Pinedo; María A. Masías; Joice Hurtado

    2013-01-01

    In this study we analyze the relations between happiness, depression and human benevolence beliefs in a group of major people who live in asylums (24) and others who live with their families (38). We use Lima’s happiness scale, Yesavage’s Geriatric depression scale and Belief in human scale. We found that there were no significant differences between two groups of major adults in depression levels, but in happiness, positive sense of life and satisfaction with life, non institutionalized olde...

  3. Human neural stem cell replacement therapy for amyotrophic lateral sclerosis by spinal transplantation.

    Directory of Open Access Journals (Sweden)

    Michael P Hefferan

    Full Text Available BACKGROUND: Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1 causes an inherited form of Amyotrophic Lateral Sclerosis (ALS. Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs into the lumbar spinal cord of SOD1(G93A rats leads to a moderate therapeutical effect as evidenced by local α-motoneuron sparing and extension of lifespan. The aim of the present study was to analyze the degree of therapeutical effect of hNSCs once grafted into the lumbar spinal ventral horn in presymptomatic immunosuppressed SOD1(G93A rats and to assess the presence and functional integrity of the descending motor system in symptomatic SOD1(G93A animals. METHODS/PRINCIPAL FINDINGS: Presymptomatic SOD1(G93A rats (60-65 days old received spinal lumbar injections of hNSCs. After cell grafting, disease onset, disease progression and lifespan were analyzed. In separate symptomatic SOD1(G93A rats, the presence and functional conductivity of descending motor tracts (corticospinal and rubrospinal was analyzed by spinal surface recording electrodes after electrical stimulation of the motor cortex. Silver impregnation of lumbar spinal cord sections and descending motor axon counting in plastic spinal cord sections were used to validate morphologically the integrity of descending motor tracts. Grafting of hNSCs into the lumbar spinal cord of SOD1(G93A rats protected α-motoneurons in the vicinity of grafted cells, provided transient functional improvement, but offered no protection to α-motoneuron pools distant from grafted lumbar segments. Analysis of motor-evoked potentials recorded from the thoracic spinal cord of symptomatic SOD1(G93A rats showed a near complete loss of descending motor tract conduction, corresponding to a significant (50-65% loss of large caliber descending motor axons. CONCLUSIONS

  4. Emotional expectations influence neural sensitivity to fearful faces in humans:An event-related potential study

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The present study tested whether neural sensitivity to salient emotional facial expressions was influenced by emotional expectations induced by a cue that validly predicted the expression of a subsequently presented target face. Event-related potentials (ERPs) elicited by fearful and neutral faces were recorded while participants performed a gender discrimination task under cued (‘expected’) and uncued (‘unexpected’) conditions. The behavioral results revealed that accuracy was lower for fearful compared with neutral faces in the unexpected condition, while accuracy was similar for fearful and neutral faces in the expected condition. ERP data revealed increased amplitudes in the P2 component and 200–250 ms interval for unexpected fearful versus neutral faces. By contrast, ERP responses were similar for fearful and neutral faces in the expected condition. These findings indicate that human neural sensitivity to fearful faces is modulated by emotional expectations. Although the neural system is sensitive to unpredictable emotionally salient stimuli, sensitivity to salient stimuli is reduced when these stimuli are predictable.

  5. Self-Organizing 3D Human Neural Tissue Derived from Induced Pluripotent Stem Cells Recapitulate Alzheimer's Disease Phenotypes.

    Science.gov (United States)

    Raja, Waseem K; Mungenast, Alison E; Lin, Yuan-Ta; Ko, Tak; Abdurrob, Fatema; Seo, Jinsoo; Tsai, Li-Huei

    2016-01-01

    The dismal success rate of clinical trials for Alzheimer's disease (AD) motivates us to develop model systems of AD pathology that have higher predictive validity. The advent of induced pluripotent stem cells (iPSCs) allows us to model pathology and study disease mechanisms directly in human neural cells from healthy individual as well as AD patients. However, two-dimensional culture systems do not recapitulate the complexity of neural tissue, and phenotypes such as extracellular protein aggregation are difficult to observe. We report brain organoids that use pluripotent stem cells derived from AD patients and recapitulate AD-like pathologies such as amyloid aggregation, hyperphosphorylated tau protein, and endosome abnormalities. These pathologies are observed in an age-dependent manner in organoids derived from multiple familial AD (fAD) patients harboring amyloid precursor protein (APP) duplication or presenilin1 (PSEN1) mutation, compared to controls. The incidence of AD pathology was consistent amongst several fAD lines, which carried different mutations. Although these are complex assemblies of neural tissue, they are also highly amenable to experimental manipulation. We find that treatment of patient-derived organoids with β- and γ-secretase inhibitors significantly reduces amyloid and tau pathology. Moreover, these results show the potential of this model system to greatly increase the translatability of pre-clinical drug discovery in AD. PMID:27622770

  6. Human insulin-like growth factor 1-transfected umbilical cord blood neural stem cell transplantation improves hypoxic-ischemic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dengna Zhu; Yanjie Jia; Jun Wang; Boai Zhang; Guohui Niu; Yazhen Fan

    2011-01-01

    Human insulin-like growth factor 1-transfected umbilical cord blood neural stem cells were transplanted into a hypoxic-ischemic neonatal rat model via the tail vein.BrdU-positive cells at day 7post-transplantation,as well as nestin-and neuron specific enolase-positive cells at day 14 wereincreased compared with those of the single neural stem cell transplantation group.In addition,theproportion of neuronal differentiation was enhanced.The genetically modified cell-transplanted ratsexhibited enhanced performance in correctly crossing a Y-maze and climbing an angled slope compared with those of the single neural stem cell transplantation group.These results showed that human insulin-like growth factor 1-transfected neural stem cell transplantation promotes therecovery of the learning,memory and motor functions in hypoxic-ischemic rats.

  7. The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors

    DEFF Research Database (Denmark)

    Seminatore, Christine; Polentes, Jerome; Ellman, Ditte;

    2010-01-01

    Risk of tumorigenesis is a major obstacle to human embryonic and induced pluripotent stem cell therapy. Likely linked to the stage of differentiation of the cells at the time of implantation, formation of teratoma/tumors can also be influenced by factors released by the host tissue. We have analy...... analyzed the relative effects of the stage of differentiation and the postischemic environment on the formation of adverse structures by transplanted human embryonic stem cell-derived neural progenitors.......Risk of tumorigenesis is a major obstacle to human embryonic and induced pluripotent stem cell therapy. Likely linked to the stage of differentiation of the cells at the time of implantation, formation of teratoma/tumors can also be influenced by factors released by the host tissue. We have...

  8. An Assessemnt of Graduate Adult Education and Human Resource Development Programs: A U.S. Perspective

    Science.gov (United States)

    Akdere, Mesut; Conceicao, Simone C. O.

    2009-01-01

    Due to recent changes in the workplace, the workforce and higher education have driven academic programs of adult education (AE) and human resource development (HRD) in the U.S. to become more integrated as part of the mission of institutions of higher education. In this exploratory study, existing graduate programs in AE and HRD in the U.S. were…

  9. An Instrument Development Model for Online Surveys in Human Resource Development and Adult Education

    Science.gov (United States)

    Strachota, Elaine M.; Conceicao, Simone C. O.; Schmidt, Steven W.

    2006-01-01

    This article describes the use of a schematic model for developing and distributing online surveys. Two empirical studies that developed and implemented online surveys to collect data to measure satisfaction in various aspects of human resource development and adult education exemplify the use of the model to conduct online survey research. The…

  10. Equality and Human Capital: Conflicting Concepts within State-Funded Adult Education in Ireland

    Science.gov (United States)

    Hurley, Kevin

    2015-01-01

    This article offers a critique of the concept of equality as it informs the White Paper on Adult Education: Learning for Life (2000). It also outlines the extent to which human capital theory can be seen to have effectively colonised lifelong learning from the outset of its adoption by the European Union with highly constraining implications for…

  11. Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming

    DEFF Research Database (Denmark)

    Swales, Nathalie; Martens, Geert A; Bonné, Stefan;

    2012-01-01

    Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3). In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it....

  12. Bridging the Gap between Human Resource Development and Adult Education: Part One, Assumptions, Definitions, and Critiques

    Science.gov (United States)

    Hatcher, Tim; Bowles, Tuere

    2013-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995).…

  13. Concept Maps: Practice Applications in Adult Education and Human Resource Development

    Science.gov (United States)

    Daley, Barbara J.

    2010-01-01

    Concept maps can be used as both a cognitive and constructivist learning strategy in teaching and learning in adult education and human resource development. The maps can be used to understand course readings, analyze case studies, develop reflective thinking and enhance research skills. The creation of concept maps can also be supported by the…

  14. Perspectives on Adult Education, Human Resource Development, and the Emergence of Workforce Development

    Science.gov (United States)

    Jacobs, Ronald L.

    2014-01-01

    This article presents a perspective on the relationship between adult education and human resource development of the past two decades and the subsequent emergence of workforce development. The lesson taken from the article should be more than simply a recounting of events related to these fields of study. Instead, the more general lesson may be…

  15. Bridging the Gap between Human Resource Development and Adult Education: Part Two, the Critical Turn

    Science.gov (United States)

    Hatcher, Tim; Bowles, Tuere

    2014-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995). The…

  16. Profile of the Adult Education and Human Resource Development Professoriate: Characteristics and Professional Fulfillment.

    Science.gov (United States)

    Peterson, Shari L.; Provo, Joanne

    1998-01-01

    A survey of 113 members of the Commission of Professors of Adult Education and 50 of the Academy of Human Resource Development found few differences except in age, rank, and salary. The two faculties are compatible and could be integrated. Overall job satisfaction is high. Professors tended to come from other fields and to remain. (SK)

  17. Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Katja M. Piltti

    2015-09-01

    Full Text Available The effect of transplantation dose on the spatiotemporal dynamics of human neural stem cell (hNSC engraftment has not been quantitatively evaluated in the central nervous system. We investigated changes over time in engraftment/survival, proliferation, and migration of multipotent human central nervous system-derived neural stem cells (hCNS-SCns transplanted at doses ranging from 10,000 to 500,000 cells in spinal cord injured immunodeficient mice. Transplant dose was inversely correlated with measures of donor cell proliferation at 2 weeks post-transplant (WPT and dose-normalized engraftment at 16 WPT. Critically, mice receiving the highest cell dose exhibited an engraftment plateau, in which the total number of engrafted human cells never exceeded the initial dose. These data suggest that donor cell expansion was inversely regulated by target niche parameters and/or transplantation density. Investigation of the response of donor cells to the host microenvironment should be a key variable in defining target cell dose in pre-clinical models of CNS disease and injury.

  18. An Efficient Feature Extraction Method with Pseudo-Zernike Moment in RBF Neural Network-Based Human Face Recognition System

    Directory of Open Access Journals (Sweden)

    Ahmadi Majid

    2003-01-01

    Full Text Available This paper introduces a novel method for the recognition of human faces in digital images using a new feature extraction method that combines the global and local information in frontal view of facial images. Radial basis function (RBF neural network with a hybrid learning algorithm (HLA has been used as a classifier. The proposed feature extraction method includes human face localization derived from the shape information. An efficient distance measure as facial candidate threshold (FCT is defined to distinguish between face and nonface images. Pseudo-Zernike moment invariant (PZMI with an efficient method for selecting moment order has been used. A newly defined parameter named axis correction ratio (ACR of images for disregarding irrelevant information of face images is introduced. In this paper, the effect of these parameters in disregarding irrelevant information in recognition rate improvement is studied. Also we evaluate the effect of orders of PZMI in recognition rate of the proposed technique as well as RBF neural network learning speed. Simulation results on the face database of Olivetti Research Laboratory (ORL indicate that the proposed method for human face recognition yielded a recognition rate of 99.3%.

  19. Adult human adipose tissue contains several types of multipotent cells.

    Science.gov (United States)

    Tallone, Tiziano; Realini, Claudio; Böhmler, Andreas; Kornfeld, Christopher; Vassalli, Giuseppe; Moccetti, Tiziano; Bardelli, Silvana; Soldati, Gianni

    2011-04-01

    Multipotent mesenchymal stromal cells (MSCs) are a type of adult stem cells that can be easily isolated from various tissues and expanded in vitro. Many reports on their pluripotency and possible clinical applications have raised hopes and interest in MSCs. In an attempt to unify the terminology and the criteria to label a cell as MSC, in 2006 the International Society for Cellular Therapy (ISCT) proposed a standard set of rules to define the identity of these cells. However, MSCs are still extracted from different tissues, by diverse isolation protocols, are cultured and expanded in different media and conditions. All these variables may have profound effects on the selection of cell types and the composition of heterogeneous subpopulations, on the selective expansion of specific cell populations with totally different potentials and ergo, on the long-term fate of the cells upon in vitro culture. Therefore, specific molecular and cellular markers that identify MSCs subsets as well as standardization of expansion protocols for these cells are urgently needed. Here, we briefly discuss new useful markers and recent data supporting the rapidly emerging concept that many different types of progenitor cells are found in close association with blood vessels. This knowledge may promote the necessary technical improvements required to reduce variability and promote higher efficacy and safety when isolating and expanding these cells for therapeutic use. In the light of the discussed data, particularly the identification of new markers, and advances in the understanding of fundamental MSC biology, we also suggest a revision of the 2006 ISCT criteria. PMID:21327755

  20. Genomic Analysis Reveals Disruption of Striatal Neuronal Development and Therapeutic Targets in Human Huntington’s Disease Neural Stem Cells

    OpenAIRE

    Karen L. Ring; Mahru C. An; Ningzhe Zhang; Robert N. O’Brien; Eliana Marisa Ramos; Fuying Gao; Robert Atwood; Barbara J. Bailus; Simon Melov; Sean D. Mooney; Giovanni Coppola; Lisa M. Ellerby

    2015-01-01

    We utilized induced pluripotent stem cells (iPSCs) derived from Huntington’s disease (HD) patients as a human model of HD and determined that the disease phenotypes only manifest in the differentiated neural stem cell (NSC) stage, not in iPSCs. To understand the molecular basis for the CAG repeat expansion-dependent disease phenotypes in NSCs, we performed transcriptomic analysis of HD iPSCs and HD NSCs compared to isogenic controls. Differential gene expression and pathway analysis pointed t...