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Sample records for adult subventricular zone

  1. Long-term hydrocephalus alters the cytoarchitecture of the adult subventricular zone

    Science.gov (United States)

    Campos-Ordoñez, Tania; Herranz-Pérez, Vicente; Chaichana, Kaisorn L.; Rincon-Torroella, Jordina; Rigamonti, Daniele; García-Verdugo, Jose M.; Quiñones-Hinojosa, Alfredo; Gonzalez-Perez, Oscar

    2014-01-01

    Hydrocephalus can develop secondarily to a disturbance in production, flow and/or absorption of cerebrospinal fluid. Experimental models of hydrocephalus, especially subacute and chronic hydrocephalus, are few and limited, and the effects of hydrocephalus on the subventricular zone are unclear. The aim of this study was to analyze the effects of long-term obstructive hydrocephalus on the subventricular zone, which is the neurogenic niche lining the lateral ventricles. We developed a new method to induce hydrocephalus by obstructing the aqueduct of Sylvius in the mouse brain, thus simulating aqueductal stenosis in humans. In 120-day-old rodents (n = 18 per group), the degree of ventricular dilatation and cellular composition of the subventricular zone were studied by immunofluorescence and transmission electron microscopy. In adult patients (age > 18 years), the sizes of the subventricular zone, corpus callosum, and internal capsule were analyzed by magnetic resonance images obtained from patients with and without aqueductal stenosis (n=25 per group). Mice with 60-day hydrocephalus had a reduced number of Ki67+ and doublecortin+ cells on immunofluorescence, as well as decreased number of neural progenitors and neuroblasts in the subventricular zone on electron microscopy analysis as compared to non-hydrocephalic mice. Remarkably, a number of extracellular matrix structures (fractones) contacting the ventricular lumen and blood vessels were also observed around the subventricular zone in mice with hydrocephalus. In humans, the widths of the subventricular zone, corpus callosum, and internal capsule in patients with aqueductal stenosis were significantly smaller than age and gender-matched patients without aqueductal stenosis. In summary, supratentorial hydrocephalus reduces the proliferation rate of neural progenitors and modifies the cytoarchitecture and extracellular matrix compounds of the subventricular zone. In humans, this similar process reduces the

  2. A Model of Ischemia-Induced Neuroblast Activation in the Adult Subventricular Zone

    OpenAIRE

    Vergni, Davide; Castiglione, Filippo; Briani, Maya; Middei, Silvia; Alberdi, Elena; Reymann, Klaus G.; Natalini, Roberto; Volont?, Cinzia; Matute, Carlos; Cavaliere, Fabio

    2009-01-01

    12 p. We have developed a rat brain organotypic culture model, in which tissue slices contain cortex-subventricular zone-striatum regions, to model neuroblast activity in response to in vitro ischemia. Neuroblast activation has been described in terms of two main parameters, proliferation and migration from the subventricular zone into the injured cortex. We observed distinct phases of neuroblast activation as is known to occur after in vivo ischemia. Thus, immediately after oxygen/glucose...

  3. Cellular and Behavioral Effects of Cranial Irradiation of the Subventricular Zone in Adult Mice

    OpenAIRE

    Lazarini, Fran?oise; Mouthon, Marc-Andr?; Gheusi, Gilles; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Lamarque, St?phanie; Abrous, Djoher Nora; Boussin, Fran?ois D.; Lledo, Pierre-Marie

    2009-01-01

    International audience; BACKGROUND: In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we irradiated adult mice to impair c...

  4. A model of ischemia-induced neuroblast activation in the adult subventricular zone.

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    Davide Vergni

    Full Text Available We have developed a rat brain organotypic culture model, in which tissue slices contain cortex-subventricular zone-striatum regions, to model neuroblast activity in response to in vitro ischemia. Neuroblast activation has been described in terms of two main parameters, proliferation and migration from the subventricular zone into the injured cortex. We observed distinct phases of neuroblast activation as is known to occur after in vivo ischemia. Thus, immediately after oxygen/glucose deprivation (6-24 hours, neuroblasts reduce their proliferative and migratory activity, whereas, at longer time points after the insult (2 to 5 days, they start to proliferate and migrate into the damaged cortex. Antagonism of ionotropic receptors for extracellular ATP during and after the insult unmasks an early activation of neuroblasts in the subventricular zone, which responded with a rapid and intense migration of neuroblasts into the damaged cortex (within 24 hours. The process is further enhanced by elevating the production of the chemoattractant SDf-1alpha and may also be boosted by blocking the activation of microglia. This organotypic model which we have developed is an excellent in vitro system to study neurogenesis after ischemia and other neurodegenerative diseases. Its application has revealed a SOS response to oxygen/glucose deprivation, which is inhibited by unfavorable conditions due to the ischemic environment. Finally, experimental quantifications have allowed us to elaborate a mathematical model to describe neuroblast activation and to develop a computer simulation which should have promising applications for the screening of drug candidates for novel therapies of ischemia-related pathologies.

  5. RAE-1 is expressed in the adult subventricular zone and controls cell proliferation of neurospheres

    DEFF Research Database (Denmark)

    Popa, Natalia; Cédile, Oriane; Pollet-Villard, Xavier

    2011-01-01

    playing either immune or nonimmune function. Among the latter, MHC functions in the central nervous system has started to receive recent interest. Here, our first goal was to investigate the potential relationship between MHC class I molecules and neurogenesis. For the first time, we report the expression......, and we demonstrate they persist in one of the main area of adult neurogenesis, the subventricular zone (SVZ). So far, RAE-1 is only known for its immune functions as a ligand of the activating receptor NKG2D expressed by natural killer (NK) cells, natural killer T, Tγδ, and some T CD8 lymphocytes. Here...

  6. Location of subventricular zone recurrence and its radiation dose predicts survival in patients with glioblastoma.

    Science.gov (United States)

    Weinberg, Brent D; Boreta, Lauren; Braunstein, Steve; Cha, Soonmee

    2018-07-01

    Glioblastomas are aggressive brain tumors that frequently recur in the subventricular zone (SVZ) despite maximal treatment. The purpose of this study was to evaluate imaging patterns of subventricular progression and impact of recurrent subventricular tumor involvement and radiation dose to patient outcome. Retrospective review of 50 patients diagnosed with glioblastoma and treated with surgery, radiation, and concurrent temozolomide from January 2012 to June 2013 was performed. Tumors were classified based on location, size, and cortical and subventricular zone involvement. Survival was compared based on recurrence type, distance from the initial enhancing tumor (local ≤ 2 cm, distant > 2 cm), and the radiation dose at the recurrence site. Progression of enhancing subventricular tumor was common at both local (58%) and distant (42%) sites. Median survival was better after local SVZ recurrence than distant SVZ recurrence (8.7 vs. 4.3 months, p = 0.04). Radiation doses at local SVZ recurrence sites recurrence averaged 57.0 ± 4.0 Gy compared to 44.7 ± 6.7 Gy at distant SVZ recurrence sites (p = 0.008). Distant subventricular progression at a site receiving ≤ 45 Gy predicted worse subsequent survival (p = 0.05). Glioblastomas frequently recurred in the subventricular zone, and patient survival was worse when enhancing tumor occurred at sites that received lower radiation doses. This recurrent disease may represent disease undertreated at the time of diagnosis, and further study is needed to determine if improved treatment strategies, such as including the subventricular zone in radiation fields, could improve clinical outcomes.

  7. Regulation by commensal bacteria of neurogenesis in the subventricular zone of adult mouse brain.

    Science.gov (United States)

    Sawada, Naoki; Kotani, Takenori; Konno, Tasuku; Setiawan, Jajar; Nishigaito, Yuka; Saito, Yasuyuki; Murata, Yoji; Nibu, Ken-Ichi; Matozaki, Takashi

    2018-04-15

    In the mouse olfactory bulb (OB), interneurons such as granule cells and periglomerular cells are continuously replaced by adult-born neurons, which are generated in the subventricular zone (SVZ) of the brain. We have now investigated the role of commensal bacteria in regulation of such neuronal cell turnover in the adult mouse brain. Administration of mixture of antibiotics to specific pathogen-free (SPF) mice markedly attenuated the incorporation of bromodeoxyuridine (BrdU) into the SVZ cells. The treatment with antibiotics also reduced newly generated BrdU-positive neurons in the mouse OB. In addition, the incorporation of BrdU into the SVZ cells of germ-free (GF) mice was markedly reduced compared to that apparent for SPF mice. In contrast, the reduced incorporation of BrdU into the SVZ cells of GF mice was recovered by their co-housing with SPF mice, suggesting that commensal bacteria promote the incorporation of BrdU into the SVZ cells. Finally, we found that administration of ampicillin markedly attenuated the incorporation of BrdU into the SVZ cells of SPF mice. Our results thus suggest that ampicillin-sensitive commensal bacteria regulate the neurogenesis in the SVZ of adult mouse brain. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. The aged brain: genesis and fate of residual progenitor cells in the subventricular zone

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    Vivian eCapilla-Gonzalez

    2015-09-01

    Full Text Available Neural stem cells persist in the adult mammalian brain through life. The subventricular zone is the largest source of stem cells in the nervous system, and continuously generates new neuronal and glial cells involved in brain regeneration. During aging, the germinal potential of the subventricular zone suffers a widespread decline, but the causes of this turn down are not fully understood. This review provides a compilation of the current knowledge about the age-related changes in the neural stem cell population, as well as the fate of the newly generated cells in the aged brain. It is known that the neurogenic capacity is clearly disrupted during aging, while the production of oligodendroglial cells is not compromised. Interestingly, the human brain seems to primarily preserve the ability to produce new oligodendrocytes instead of neurons, which could be related to the development of neurological disorders. Further studies in this matter are required to improve our understanding and the current strategies for fighting neurological diseases associated with senescence.

  9. Cellular and Behavioral Effects of Cranial Irradiation of the Subventricular Zone in Adult Mice

    Science.gov (United States)

    Lazarini, Françoise; Mouthon, Marc-André; Gheusi, Gilles; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Lamarque, Stéphanie; Abrous, Djoher Nora; Boussin, François D.; Lledo, Pierre-Marie

    2009-01-01

    Background In mammals, new neurons are added to the olfactory bulb (OB) throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ) lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear. Methodology/Principal Findings In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation. Conclusion/Significance These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces. PMID:19753118

  10. Cellular and behavioral effects of cranial irradiation of the subventricular zone in adult mice.

    Directory of Open Access Journals (Sweden)

    Françoise Lazarini

    2009-09-01

    Full Text Available In mammals, new neurons are added to the olfactory bulb (OB throughout life. Most of these new neurons, granule and periglomerular cells originate from the subventricular zone (SVZ lining the lateral ventricles and migrate via the rostral migratory stream toward the OB. Thousands of new neurons appear each day, but the function of this ongoing neurogenesis remains unclear.In this study, we irradiated adult mice to impair constitutive OB neurogenesis, and explored the functional impacts of this irradiation on the sense of smell. We found that focal irradiation of the SVZ greatly decreased the rate of production of new OB neurons, leaving other brain areas intact. This effect persisted for up to seven months after exposure to 15 Gray. Despite this robust impairment, the thresholds for detecting pure odorant molecules and short-term olfactory memory were not affected by irradiation. Similarly, the ability to distinguish between odorant molecules and the odorant-guided social behavior of irradiated mice were not affected by the decrease in the number of new neurons. Only long-term olfactory memory was found to be sensitive to SVZ irradiation.These findings suggest that the continuous production of adult-generated neurons is involved in consolidating or restituting long-lasting olfactory traces.

  11. Neural stem cell heterogeneity through time and space in the ventricular-subventricular zone.

    Science.gov (United States)

    Rushing, Gabrielle; Ihrie, Rebecca A

    2016-08-01

    The origin and classification of neural stem cells (NSCs) has been a subject of intense investigation for the past two decades. Efforts to categorize NSCs based on their location, function and expression have established that these cells are a heterogeneous pool in both the embryonic and adult brain. The discovery and additional characterization of adult NSCs has introduced the possibility of using these cells as a source for neuronal and glial replacement following injury or disease. To understand how one could manipulate NSC developmental programs for therapeutic use, additional work is needed to elucidate how NSCs are programmed and how signals during development are interpreted to determine cell fate. This review describes the identification, classification and characterization of NSCs within the large neurogenic niche of the ventricular-subventricular zone (V-SVZ). A literature search was conducted using Pubmed including the keywords "ventricular-subventricular zone," "neural stem cell," "heterogeneity," "identity" and/or "single cell" to find relevant manuscripts to include within the review. A special focus was placed on more recent findings using single-cell level analyses on neural stem cells within their niche(s). This review discusses over 20 research articles detailing findings on V-SVZ NSC heterogeneity, over 25 articles describing fate determinants of NSCs, and focuses on 8 recent publications using distinct single-cell analyses of neural stem cells including flow cytometry and RNA-seq. Additionally, over 60 manuscripts highlighting the markers expressed on cells within the NSC lineage are included in a chart divided by cell type. Investigation of NSC heterogeneity and fate decisions is ongoing. Thus far, much research has been conducted in mice however, findings in human and other mammalian species are also discussed here. Implications of NSC heterogeneity established in the embryo for the properties of NSCs in the adult brain are explored, including

  12. BTG1 is required to maintain the pool of stem and progenitor cells of dentate gyrus and subventricular zone

    OpenAIRE

    Stefano eFarioli-Vecchioli; Laura eMicheli; Daniele eSaraulli; Manuela eCeccarelli; Sara eCannas; Raffaella eScardigli; Luca eLeonardi; Irene eCinà; Marco eCostanzi; Maria Teresa eCiotti; Pedro eMoreira; Jean-Pierre eRouault; Vincenzo eCestari; Felice eTirone

    2012-01-01

    Btg1 belongs to a family of cell cycle inhibitory genes. We observed that Btg1 is highly expressed in adult neurogenic niches, i.e., the dentate gyrus and subventricular zone (SVZ). Thus, we generated Btg1 knockout mice to analyze the role of Btg1 in the process of generation of adult new neurons.Ablation of Btg1 causes a transient increase of the proliferating dentate gyrus stem and progenitor cells at post-natal day 7; however, at two months of age the number of these proliferating cells, a...

  13. Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone

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    Anna Engler

    2018-01-01

    Full Text Available Neurogenesis continues in the ventricular-subventricular zone (V-SVZ of the adult forebrain from quiescent neural stem cells (NSCs. V-SVZ NSCs are a reservoir for new olfactory bulb (OB neurons that migrate through the rostral migratory stream (RMS. To generate neurons, V-SVZ NSCs need to activate and enter the cell cycle. The mechanisms underlying NSC transition from quiescence to activity are poorly understood. We show that Notch2, but not Notch1, signaling conveys quiescence to V-SVZ NSCs by repressing cell-cycle-related genes and neurogenesis. Loss of Notch2 activates quiescent NSCs, which proliferate and generate new neurons of the OB lineage. Notch2 deficiency results in accelerated V-SVZ NSC exhaustion and an aging-like phenotype. Simultaneous loss of Notch1 and Notch2 resembled the total loss of Rbpj-mediated canonical Notch signaling; thus, Notch2 functions are not compensated in NSCs, and Notch2 is indispensable for the maintenance of NSC quiescence in the adult V-SVZ.

  14. RAE-1 is expressed in the adult subventricular zone and controls cell proliferation of neurospheres.

    Science.gov (United States)

    Popa, Natalia; Cedile, Oriane; Pollet-Villard, Xavier; Bagnis, Claude; Durbec, Pascale; Boucraut, José

    2011-01-01

    Improving and controlling the capacity of endogenous or grafted adult neural stem cells to repair the nervous system relies on a better knowledge of interactions between immune cells and neural stem cells. Class I major histocompatibility complex (MHC) family members comprise numerous proteins playing either immune or nonimmune function. Among the latter, MHC functions in the central nervous system has started to receive recent interest. Here, our first goal was to investigate the potential relationship between MHC class I molecules and neurogenesis. For the first time, we report the expression of two MHC class I-related members by neural stem/progenitor cells: retinoic acid early induced transcript (RAE)-1 and CD1d. The expression of RAE-1 but not CD1d disappears when differentiation of neurosphere cells is induced. Interestingly, RAE-1 transcripts are expressed in the brain during development, and we demonstrate they persist in one of the main area of adult neurogenesis, the subventricular zone (SVZ). So far, RAE-1 is only known for its immune functions as a ligand of the activating receptor NKG2D expressed by natural killer (NK) cells, natural killer T, Tγδ, and some T CD8 lymphocytes. Here, we do not detect any NKG2D expression in the SVZ either in physiological or in pathological conditions. Interestingly, inhibition of RAE-1 expression in neurosphere cells reduces cell proliferation without alteration of cell viability, which argues for a nonimmune role for RAE-1. These results reveal an unexpected role of RAE-1 in regulating adult SVZ neurogenesis by supporting stem/progenitor cells proliferation. © 2010 Wiley-Liss, Inc.

  15. The proliferative capacity of the subventricular zone is maintained in the parkinsonian brain

    NARCIS (Netherlands)

    van den Berge, S.A.; van Strien, M.E.; Korecka, J.A.; Dijkstra, A.A.; Sluijs, J.A; Kooijman, L.; Eggers, R.; De Filippis, L.; Vescovi, A.L.; Verhaagen, J.; van de Berg, W.D.J.; Hol, E.M.

    2011-01-01

    There are many indications that neurogenesis is impaired in Parkinson's disease, which might be due to a lack of dopamine in the subventricular zone. An impairment in neurogenesis may have negative consequences for the development of new therapeutic approaches in Parkinson's disease, as neural stem

  16. Btg1 is Required to Maintain the Pool of Stem and Progenitor Cells of the Dentate Gyrus and Subventricular Zone

    OpenAIRE

    Farioli-Vecchioli, Stefano; Micheli, Laura; Saraulli, Daniele; Ceccarelli, Manuela; Cannas, Sara; Scardigli, Raffaella; Leonardi, Luca; Cinà, Irene; Costanzi, Marco; Ciotti, Maria Teresa; Moreira, Pedro; Rouault, Jean-Pierre; Cestari, Vincenzo; Tirone, Felice

    2012-01-01

    Btg1 belongs to a family of cell cycle inhibitory genes. We observed that Btg1 is highly expressed in adult neurogenic niches, i.e., the dentate gyrus and subventricular zone (SVZ). Thus, we generated Btg1 knockout mice to analyze the role of Btg1 in the process of generation of adult new neurons. Ablation of Btg1 causes a transient increase of the proliferating dentate gyrus stem and progenitor cells at post-natal day 7; however, at 2 months of age the number of these proliferating cells, as...

  17. Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone.

    Science.gov (United States)

    Domenichini, Florence; Terrié, Elodie; Arnault, Patricia; Harnois, Thomas; Magaud, Christophe; Bois, Patrick; Constantin, Bruno; Coronas, Valérie

    2018-05-01

    The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment. By Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and immunocytochemistry experiments, we demonstrate that SVZ cells express molecular actors known to build up SOC, namely transient receptor potential canonical 1 (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1 (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ stem cell division from symmetric proliferative to asymmetric, thereby reducing the stem cell population. Brain section immunostainings show that TRPC1, Orai1, and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365 in brain lateral ventricle diminishes SVZ cell proliferation and reduces the ability of SVZ cells to form neurospheres in vitro. The present study combining in vitro and in vivo approaches uncovers a major role for SOC in the control of SVZ NSC population and opens new fields of investigation for stem cell biology in health and disease. Stem Cells 2018;36:761-774. © AlphaMed Press 2018.

  18. Longterm quiescent cells in the aged human subventricular neurogenic system specifically express GFAP-delta

    NARCIS (Netherlands)

    van den Berge, S.A.; Middeldorp, J.; Zhang, C.E.; Curtis, M.A.; Leonard, B.W.; Mastroeni, D.; Voorn, P.; van de Berg, W.D.J.; Huitinga, I.; Hol, E.M.

    2010-01-01

    A main neurogenic niche in the adult human brain is the subventricular zone (SVZ). Recent data suggest that the progenitors that are born in the human SVZ migrate via the rostral migratory stream (RMS) towards the olfactory bulb (OB), similar to what has been observed in other mammals. A

  19. A comparative study of the structural organization of spheres derived from the adult human subventricular zone and glioblastoma biopsies

    International Nuclear Information System (INIS)

    Vik-Mo, Einar Osland; Sandberg, Cecilie; Joel, Mrinal; Stangeland, Biljana; Watanabe, Yasuhiro; Mackay-Sim, Alan; Moe, Morten Carstens; Murrell, Wayne; Langmoen, Iver Arne

    2011-01-01

    Sphere forming assays have been useful to enrich for stem like cells in a range of tumors. The robustness of this system contrasts the difficulties in defining a stem cell population based on cell surface markers. We have undertaken a study to describe the cellular and organizational composition of tumorspheres, directly comparing these to neurospheres derived from the adult human subventricular zone (SVZ). Primary cell cultures from brain tumors were found to contain variable fractions of cells positive for tumor stem cell markers (CD133 (2-93%)/SSEA1 (3-15%)/CXCR4 (1-72%)). All cultures produced tumors upon xenografting. Tumorspheres contained a heterogeneous population of cells, but were structurally organized with stem cell markers present at the core of spheres, with markers of more mature glial progenitors and astrocytes at more peripheral location. Ultrastructural studies showed that tumorspheres contained a higher fraction of electron dense cells in the core than the periphery (36% and 19%, respectively). Neurospheres also contained a heterogeneous cell population, but did not have an organization similar to tumorspheres. Although tumorspheres clearly display irregular and neoplastic cells, they establish an organized structure with an outward gradient of differentiation. We suggest that this organization is central in maintaining the tumor stem cell pool.

  20. Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone.

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    Gould, Elizabeth A; Busquet, Nicolas; Shepherd, Douglas; Dietz, Robert M; Herson, Paco S; Simoes de Souza, Fabio M; Li, Anan; George, Nicholas M; Restrepo, Diego; Macklin, Wendy B

    2018-02-13

    Myelin, the insulating sheath around axons, supports axon function. An important question is the impact of mild myelin disruption. In the absence of the myelin protein proteolipid protein (PLP1), myelin is generated but with age, axonal function/maintenance is disrupted. Axon disruption occurs in Plp1 -null mice as early as 2 months in cortical projection neurons. High-volume cellular quantification techniques revealed a region-specific increase in oligodendrocyte density in the olfactory bulb and rostral corpus callosum that increased during adulthood. A distinct proliferative response of progenitor cells was observed in the subventricular zone (SVZ), while the number and proliferation of parenchymal oligodendrocyte progenitor cells was unchanged. This SVZ proliferative response occurred prior to evidence of axonal disruption. Thus, a novel SVZ response contributes to the region-specific increase in oligodendrocytes in Plp1 -null mice. Young adult Plp1- null mice exhibited subtle but substantial behavioral alterations, indicative of an early impact of mild myelin disruption. © 2018, Gould et al.

  1. Modulation of subventricular zone oligodendrogenesis: a role for hemopressin?

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    Sara eXapelli

    2014-02-01

    Full Text Available Neural stem cells (NSCs from the subventricular zone (SVZ have been indicated as a source of new oligodendrocytes to use in regenerative medicine for myelin pathologies. Indeed, NSCs are multipotent cells that can self-renew and differentiate into all neural cell types of the central nervous system (CNS. In normal conditions, SVZ cells are poorly oligodendrogenic, nevertheless their oligodendrogenic potential is boosted following demyelination. Importantly, progressive restriction into the oligodendrocyte fate is specified by extrinsic and intrinsic factors, endocannabinoids being one of these factors. Although a role for endocannabinoids in oligodendrogenesis has already been foreseen, selective agonists and antagonists of cannabinoids receptors produce severe adverse side effects. Herein, we show that hemopressin, a modulator of CB1 receptors, increased oligodendroglial differentiation in SVZ neural stem/progenitor cell cultures derived from neonatal mice. The original results presented in this work suggest that hemopressin and derivatives may be of potential interest for the development of future strategies to treat demyelinating diseases.

  2. Midbrain dopamine neurons associated with reward processing innervate the neurogenic subventricular zone.

    Science.gov (United States)

    Lennington, Jessica B; Pope, Sara; Goodheart, Anna E; Drozdowicz, Linda; Daniels, Stephen B; Salamone, John D; Conover, Joanne C

    2011-09-14

    Coordinated regulation of the adult neurogenic subventricular zone (SVZ) is accomplished by a myriad of intrinsic and extrinsic factors. The neurotransmitter dopamine is one regulatory molecule implicated in SVZ function. Nigrostriatal and ventral tegmental area (VTA) midbrain dopamine neurons innervate regions adjacent to the SVZ, and dopamine synapses are found on SVZ cells. Cell division within the SVZ is decreased in humans with Parkinson's disease and in animal models of Parkinson's disease following exposure to toxins that selectively remove nigrostriatal neurons, suggesting that dopamine is critical for SVZ function and nigrostriatal neurons are the main suppliers of SVZ dopamine. However, when we examined the aphakia mouse, which is deficient in nigrostriatal neurons, we found no detrimental effect to SVZ proliferation or organization. Instead, dopamine innervation of the SVZ tracked to neurons at the ventrolateral boundary of the VTA. This same dopaminergic neuron population also innervated the SVZ of control mice. Characterization of these neurons revealed expression of proteins indicative of VTA neurons. Furthermore, exposure to the neurotoxin MPTP depleted neurons in the ventrolateral VTA and resulted in decreased SVZ proliferation. Together, these results reveal that dopamine signaling in the SVZ originates from a population of midbrain neurons more typically associated with motivational and reward processing.

  3. Aging results in copper accumulations in glial fibrillary acidic protein-positive cells in the subventricular zone.

    Science.gov (United States)

    Pushkar, Yulia; Robison, Gregory; Sullivan, Brendan; Fu, Sherleen X; Kohne, Meghan; Jiang, Wendy; Rohr, Sven; Lai, Barry; Marcus, Matthew A; Zakharova, Taisiya; Zheng, Wei

    2013-10-01

    Analysis of rodent brains with X-ray fluorescence (XRF) microscopy combined with immunohistochemistry allowed us to demonstrate that local Cu concentrations are thousands of times higher in the glia of the subventricular zone (SVZ) than in other cells. Using XRF microscopy with subcellular resolution and intracellular X-ray absorption spectroscopy we determined the copper (I) oxidation state and the sulfur ligand environment. Cu K-edge X-ray absorption near edge spectroscopy is consistent with Cu being bound as a multimetallic Cu-S cluster similar to one present in Cu-metallothionein. Analysis of age-related changes show that Cu content in astrocytes of the SVZ increases fourfold from 3 weeks to 9 months, while Cu concentration in other brain areas remain essentially constant. This increase in Cu correlates with a decrease in adult neurogenesis assessed using the Ki67 marker (both, however, can be age-related effects). We demonstrate that the Cu distribution and age-related concentration changes in the brain are highly cell specific. © 2013 The Anatomical Society and John Wiley & Sons Ltd.

  4. 3-dimensional examination of the adult mouse subventricular zone reveals lineage-specific microdomains.

    Science.gov (United States)

    Azim, Kasum; Fiorelli, Roberto; Zweifel, Stefan; Hurtado-Chong, Anahi; Yoshikawa, Kazuaki; Slomianka, Lutz; Raineteau, Olivier

    2012-01-01

    Recent studies suggest that the subventricular zone (SVZ) of the lateral ventricle is populated by heterogeneous populations of stem and progenitor cells that, depending on their exact location, are biased to acquire specific neuronal fates. This newly described heterogeneity of SVZ stem and progenitor cells underlines the necessity to develop methods for the accurate quantification of SVZ stem and progenitor subpopulations. In this study, we provide 3-dimensional topographical maps of slow cycling "stem" cells and progenitors based on their unique cell cycle properties. These maps revealed that both cell populations are present throughout the lateral ventricle wall as well as in discrete regions of the dorsal wall. Immunodetection of transcription factors expressed in defined progenitor populations further reveals that divergent lineages have clear regional enrichments in the rostro-caudal as well as in the dorso-ventral span of the lateral ventricle. Thus, progenitors expressing Tbr2 and Dlx2 were confined to dorsal and dorso-lateral regions of the lateral ventricle, respectively, while Mash1+ progenitors were more homogeneously distributed. All cell populations were enriched in the rostral-most region of the lateral ventricle. This diversity and uneven distribution greatly impede the accurate quantification of SVZ progenitor populations. This is illustrated by measuring the coefficient of error of estimates obtained by using increasing section sampling interval. Based on our empirical data, we provide such estimates for all progenitor populations investigated in this study. These can be used in future studies as guidelines to judge if the precision obtained with a sampling scheme is sufficient to detect statistically significant differences between experimental groups if a biological effect is present. Altogether, our study underlines the need to consider the SVZ of the lateral ventricle as a complex 3D structure and define methods to accurately assess neural

  5. GABA(A) Increases Calcium in Subventricular Zone Astrocyte-Like Cells Through L- and T-Type Voltage-Gated Calcium Channels

    DEFF Research Database (Denmark)

    Young, Stephanie Z; Platel, Jean-Claude; Nielsen, Jakob V

    2010-01-01

    In the adult neurogenic subventricular zone (SVZ), the behavior of astrocyte-like cells and some of their functions depend on changes in intracellular Ca(2+) levels and tonic GABA(A) receptor activation. However, it is unknown whether, and if so how, GABA(A) receptor activity regulates...... intracellular Ca(2+) dynamics in SVZ astrocytes. To monitor Ca(2+) activity selectively in astrocyte-like cells, we used two lines of transgenic mice expressing either GFP fused to a Gq-coupled receptor or DsRed under the human glial fibrillary acidic protein (hGFAP) promoter. GABA(A) receptor activation...... induced Ca(2+) increases in 40-50% of SVZ astrocytes. GABA(A)-induced Ca(2+) increases were prevented with nifedipine and mibefradil, blockers of L- and T-type voltage-gated calcium channels (VGCC). The L-type Ca(2+) channel activator BayK 8644 increased the percentage of GABA(A)-responding astrocyte...

  6. Optimizing culture medium composition to improve oligodendrocyte progenitor cell yields in vitro from subventricular zone-derived neural progenitor cell neurospheres.

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    Paula G Franco

    Full Text Available Neural Stem and Progenitor Cells (NSC/NPC are gathering tangible recognition for their uses in cell therapy and cell replacement therapies for human disease, as well as a model system to continue research on overall neural developmental processes in vitro. The Subventricular Zone is one of the largest NSC/NPC niches in the developing mammalian Central Nervous System, and persists through to adulthood. Oligodendrocyte progenitor cell (OPC enriched cultures are usefull tools for in vitro studies as well as for cell replacement therapies for treating demyelination diseases. We used Subventricular Zone-derived NSC/NPC primary cultures from newborn mice and compared the effects of different growth factor combinations on cell proliferation and OPC yield. The Platelet Derived Growth Factor-AA and BB homodimers had a positive and significant impact on OPC generation. Furthermore, heparin addition to the culture media contributed to further increase overall culture yields. The OPC generated by this protocol were able to mature into Myelin Basic Protein-expressing cells and to interact with neurons in an in vitro co-culture system. As a whole, we describe an optimized in vitro method for increasing OPC.

  7. 3-dimensional examination of the adult mouse subventricular zone reveals lineage-specific microdomains.

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    Kasum Azim

    Full Text Available Recent studies suggest that the subventricular zone (SVZ of the lateral ventricle is populated by heterogeneous populations of stem and progenitor cells that, depending on their exact location, are biased to acquire specific neuronal fates. This newly described heterogeneity of SVZ stem and progenitor cells underlines the necessity to develop methods for the accurate quantification of SVZ stem and progenitor subpopulations. In this study, we provide 3-dimensional topographical maps of slow cycling "stem" cells and progenitors based on their unique cell cycle properties. These maps revealed that both cell populations are present throughout the lateral ventricle wall as well as in discrete regions of the dorsal wall. Immunodetection of transcription factors expressed in defined progenitor populations further reveals that divergent lineages have clear regional enrichments in the rostro-caudal as well as in the dorso-ventral span of the lateral ventricle. Thus, progenitors expressing Tbr2 and Dlx2 were confined to dorsal and dorso-lateral regions of the lateral ventricle, respectively, while Mash1+ progenitors were more homogeneously distributed. All cell populations were enriched in the rostral-most region of the lateral ventricle. This diversity and uneven distribution greatly impede the accurate quantification of SVZ progenitor populations. This is illustrated by measuring the coefficient of error of estimates obtained by using increasing section sampling interval. Based on our empirical data, we provide such estimates for all progenitor populations investigated in this study. These can be used in future studies as guidelines to judge if the precision obtained with a sampling scheme is sufficient to detect statistically significant differences between experimental groups if a biological effect is present. Altogether, our study underlines the need to consider the SVZ of the lateral ventricle as a complex 3D structure and define methods to

  8. NMDA modulates oligodendrocyte differentiation of subventricular zone cells through PKC activation

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    Fabio eCavaliere

    2013-12-01

    Full Text Available Multipotent cells from the juvenile subventricular zone (SVZ possess the ability to differentiate into new neural cells. Depending on local signals, SVZ can generate new neurons, astrocytes or oligodendrocytes. We previously demonstrated that activation of NMDA receptors in SVZ progenitors increases the rate of oligodendrocyte differentiation. Here we investigated the mechanisms involved in NMDA receptor-dependent differentiation. Using functional studies performed with the reporter gene luciferase we found that activation of NMDA receptor stimulates PKC. In turn, stimulation of PKC precedes the activation of NADPH oxidase (NOX as demonstrated by translocation of the p67phox subunit to the cellular membrane. We propose that NOX2 is involved in the transduction of the signal from NMDA receptors through PKC activation as the inhibitor gp91 reduced their pro-differentiation effect. In addition, our data and that from other groups suggest that signaling through the NMDA receptor/PKC/NOX2 cascade generates ROS that activate the PI3/mTOR pathway and finally leads to the generation of new oligodendrocytes.

  9. Imaging and recording subventricular zone progenitor cells in live tissue of postnatal mice

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    Benjamin Lacar

    2010-07-01

    Full Text Available The subventricular zone (SVZ is one of two regions where neurogenesis persists in the postnatal brain. The SVZ, located along the lateral ventricle, is the largest neurogenic zone in the brain that contains multiple cell populations including astrocyte-like cells and neuroblasts. Neuroblasts migrate in chains to the olfactory bulb where they differentiate into interneurons. Here, we discuss the experimental approaches to record the electrophysiology of these cells and image their migration and calcium activity in acute slices. Although these techniques were in place for studying glial cells and neurons in mature networks, the SVZ raises new challenges due to the unique properties of SVZ cells, the cellular diversity, and the architecture of the region. We emphasize different methods, such as the use of transgenic mice and in vivo electroporation that permit identification of the different SVZ cell populations for patch clamp recording or imaging. Electroporation also permits genetic labeling of cells using fluorescent reporter mice and modification of the system using either RNA interference technology or floxed mice. In this review, we aim to provide conceptual and technical details of the approaches to perform electrophysiological and imaging studies of SVZ cells.

  10. Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development.

    Science.gov (United States)

    Guerrero-Cazares, Hugo; Lavell, Emily; Chen, Linda; Schiapparelli, Paula; Lara-Velazquez, Montserrat; Capilla-Gonzalez, Vivian; Clements, Anna Christina; Drummond, Gabrielle; Noiman, Liron; Thaler, Katrina; Burke, Anne; Quiñones-Hinojosa, Alfredo

    2017-07-01

    Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860-1865. © 2017 AlphaMed Press.

  11. Neurogenic radial glia in the outer subventricular zone of human neocortex.

    Science.gov (United States)

    Hansen, David V; Lui, Jan H; Parker, Philip R L; Kriegstein, Arnold R

    2010-03-25

    Neurons in the developing rodent cortex are generated from radial glial cells that function as neural stem cells. These epithelial cells line the cerebral ventricles and generate intermediate progenitor cells that migrate into the subventricular zone (SVZ) and proliferate to increase neuronal number. The developing human SVZ has a massively expanded outer region (OSVZ) thought to contribute to cortical size and complexity. However, OSVZ progenitor cell types and their contribution to neurogenesis are not well understood. Here we show that large numbers of radial glia-like cells and intermediate progenitor cells populate the human OSVZ. We find that OSVZ radial glia-like cells have a long basal process but, surprisingly, are non-epithelial as they lack contact with the ventricular surface. Using real-time imaging and clonal analysis, we demonstrate that these cells can undergo proliferative divisions and self-renewing asymmetric divisions to generate neuronal progenitor cells that can proliferate further. We also show that inhibition of Notch signalling in OSVZ progenitor cells induces their neuronal differentiation. The establishment of non-ventricular radial glia-like cells may have been a critical evolutionary advance underlying increased cortical size and complexity in the human brain.

  12. Pharmacogenomic identification of small molecules for lineage specific manipulation of subventricular zone germinal activity.

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    Kasum Azim

    2017-03-01

    Full Text Available Strategies for promoting neural regeneration are hindered by the difficulty of manipulating desired neural fates in the brain without complex genetic methods. The subventricular zone (SVZ is the largest germinal zone of the forebrain and is responsible for the lifelong generation of interneuron subtypes and oligodendrocytes. Here, we have performed a bioinformatics analysis of the transcriptome of dorsal and lateral SVZ in early postnatal mice, including neural stem cells (NSCs and their immediate progenies, which generate distinct neural lineages. We identified multiple signaling pathways that trigger distinct downstream transcriptional networks to regulate the diversity of neural cells originating from the SVZ. Next, we used a novel in silico genomic analysis, searchable platform-independent expression database/connectivity map (SPIED/CMAP, to generate a catalogue of small molecules that can be used to manipulate SVZ microdomain-specific lineages. Finally, we demonstrate that compounds identified in this analysis promote the generation of specific cell lineages from NSCs in vivo, during postnatal life and adulthood, as well as in regenerative contexts. This study unravels new strategies for using small bioactive molecules to direct germinal activity in the SVZ, which has therapeutic potential in neurodegenerative diseases.

  13. P2X7 receptor inhibition increases CNTF in the subventricular zone, but not neurogenesis or neuroprotection after stroke in adult mice.

    Science.gov (United States)

    Kang, Seong Su; Keasey, Matthew Phillip; Hagg, Theo

    2013-10-01

    Increasing endogenous ciliary neurotrophic factor (CNTF) expression with a pharmacological agent might be beneficial after stroke as CNTF both promotes neurogenesis and, separately, is neuroprotective. P2X7 purinergic receptor inhibition is neuroprotective in rats and increases CNTF release in rat CMT1A Schwann cells. We, first, investigated the role of P2X7 in regulating CNTF and neurogenesis in adult mouse subventricular zone (SVZ). CNTF expression was increased by daily intravenous injections of the P2X7 antagonist Brilliant Blue G (BBG) in naïve C57BL/6 or Balb/c mice over 3 days. Despite the ∼40-60 % increase or decrease in CNTF with BBG or the agonist BzATP, respectively, the number of proliferated BrdU+SVZ nuclei did not change. BBG failed to increase FGF2, which is involved in CNTF-regulated neurogenesis, but induced IL-6, LIF, and EGF, which are known to reduce SVZ proliferation. Injections of IL-6 next to the SVZ induced CNTF and FGF2, but not proliferation, suggesting that IL-6 counteracts their neurogenesis-inducing effects. Following ischemic injury of the striatum by middle cerebral artery occlusion (MCAO), a 3-day BBG treatment increased CNTF in the medial penumbra containing the SVZ. BBG also induced CNTF and LIF, which are known to be protective following stroke, in the whole striatum after MCAO, but not GDNF or BDNF. However, BBG treatment did not reduce the lesion area or apoptosis in the penumbra. Even so, this study shows that P2X7 can be targeted with systemic drug treatments to differentially regulate neurotrophic factors in the brain following stroke.

  14. Btg1 is Required to Maintain the Pool of Stem and Progenitor Cells of the Dentate Gyrus and Subventricular Zone

    Science.gov (United States)

    Farioli-Vecchioli, Stefano; Micheli, Laura; Saraulli, Daniele; Ceccarelli, Manuela; Cannas, Sara; Scardigli, Raffaella; Leonardi, Luca; Cinà, Irene; Costanzi, Marco; Ciotti, Maria Teresa; Moreira, Pedro; Rouault, Jean-Pierre; Cestari, Vincenzo; Tirone, Felice

    2012-01-01

    Btg1 belongs to a family of cell cycle inhibitory genes. We observed that Btg1 is highly expressed in adult neurogenic niches, i.e., the dentate gyrus and subventricular zone (SVZ). Thus, we generated Btg1 knockout mice to analyze the role of Btg1 in the process of generation of adult new neurons. Ablation of Btg1 causes a transient increase of the proliferating dentate gyrus stem and progenitor cells at post-natal day 7; however, at 2 months of age the number of these proliferating cells, as well as of mature neurons, greatly decreases compared to wild-type controls. Remarkably, adult dentate gyrus stem and progenitor cells of Btg1-null mice exit the cell cycle after completing the S phase, express p53 and p21 at high levels and undergo apoptosis within 5 days. In the SVZ of adult (two-month-old) Btg1-null mice we observed an equivalent decrease, associated to apoptosis, of stem cells, neuroblasts, and neurons; furthermore, neurospheres derived from SVZ stem cells showed an age-dependent decrease of the self-renewal and expansion capacity. We conclude that ablation of Btg1 reduces the pool of dividing adult stem and progenitor cells in the dentate gyrus and SVZ by decreasing their proliferative capacity and inducing apoptosis, probably reflecting impairment of the control of the cell cycle transition from G1 to S phase. As a result, the ability of Btg1-null mice to discriminate among overlapping contextual memories was affected. Btg1 appears, therefore, to be required for maintaining adult stem and progenitor cells quiescence and self-renewal. PMID:22969701

  15. Olfactory memory is enhanced in mice exposed to extremely low-frequency electromagnetic fields via Wnt/β-catenin dependent modulation of subventricular zone neurogenesis.

    Science.gov (United States)

    Mastrodonato, Alessia; Barbati, Saviana Antonella; Leone, Lucia; Colussi, Claudia; Gironi, Katia; Rinaudo, Marco; Piacentini, Roberto; Denny, Christine A; Grassi, Claudio

    2018-01-10

    Exposure to extremely low-frequency electromagnetic fields (ELFEF) influences the expression of key target genes controlling adult neurogenesis and modulates hippocampus-dependent memory. Here, we assayed whether ELFEF stimulation affects olfactory memory by modulating neurogenesis in the subventricular zone (SVZ) of the lateral ventricle, and investigated the underlying molecular mechanisms. We found that 30 days after the completion of an ELFEF stimulation protocol (1 mT; 50 Hz; 3.5 h/day for 12 days), mice showed enhanced olfactory memory and increased SVZ neurogenesis. These effects were associated with upregulated expression of mRNAs encoding for key regulators of adult neurogenesis and were mainly dependent on the activation of the Wnt pathway. Indeed, ELFEF stimulation increased Wnt3 mRNA expression and nuclear localization of its downstream target β-catenin. Conversely, inhibition of Wnt3 by Dkk-1 prevented ELFEF-induced upregulation of neurogenic genes and abolished ELFEF's effects on olfactory memory. Collectively, our findings suggest that ELFEF stimulation increases olfactory memory via enhanced Wnt/β-catenin signaling in the SVZ and point to ELFEF as a promising tool for enhancing SVZ neurogenesis and olfactory function.

  16. Radio-Protective Effects of Melatonin on Subventricular Zone in Irradiated Rat: Decrease in Apoptosis and Upregulation of Nestin.

    Science.gov (United States)

    Naseri, Shafigheh; Moghahi, Seyed Mohammad Hossein Noori; Mokhtari, Tahmineh; Roghani, Mehrdad; Shirazi, Ali Reza; Malek, Fatemeh; Rastegar, Tayebeh

    2017-10-01

    Neural stem cells are self-renewing, multipotent cells that can be found in subventricular (SVZ) and subgranular (SGZ) zones of the brain. These zones are susceptible to irradiation-induced apoptosis and oxidative stress. Melatonin (MLT) is a natural protector of neural cells against toxicity. The aim of this study was to evaluate the effects of MLT as a radio-protective material effective in reducing tissue lesions in the SVZ of the brain and changing local apoptotic potential in rats. Twenty-five Gray irradiation was applied on adult rat brain for this study. One hour before irradiation, 100 mg/kg/IP MLT was injected, and 6 h later, the animals were sacrificed. The antioxidant enzymes and MDA activity levels were measured post-sacrifice. Also, the expression level of Nestin and caspase 3 were studied by immunohistochemistry. Spectrophotometric analysis showed significant increases in the amount of malondialdehyde (MDA) levels in the irradiation-exposed (RAD) group compared to that of the control (Co) group (P < 0.05). Pre-treatment with MLT (100 mg/kg) ameliorates the harmful effects of the aforementioned 25 Gy irradiation by increasing antioxidant enzyme activity and decreasing MDA levels. A significant reduction in apoptotic cells was observed in rats treated with MLT 1 h before exposure (P < 0.001). Nestin-positive cells were also reduced in the RAD group (P < 0.001). Our results confirm the anti-apoptotic and antioxidant role of MLT. The MLT concentration used may serve as a threshold for significant protection against 25 Gy gamma irradiations on neural stem cells in SVZ.

  17. Stroke Repair via Biomimicry of the Subventricular Zone

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    Rita Matta

    2018-03-01

    Full Text Available Stroke is among the leading causes of death and disability worldwide, 85% of which are ischemic. Current stroke therapies are limited by a narrow effective therapeutic time and fail to effectively complete the recovery of the damaged area. Magnetic resonance imaging of the subventricular zone (SVZ following infarct/stroke has allowed visualization of new axonal connections and projections being formed, while new immature neurons migrate from the SVZ to the peri-infarct area. Such studies suggest that the SVZ is a primary source of regenerative cells for the repair and regeneration of stroke-damaged neurons and tissue. Therefore, the development of tissue engineered scaffolds that serve as a bioreplicative SVZ niche would support the survival of multiple cell types that reside in the SVZ. Essential to replication of the human SVZ microenvironment is the establishment of microvasculature that regulates both the healthy and stroke-injured blood–brain barrier, which is dysregulated poststroke. In order to reproduce this niche, understanding how cells interact in this environment is critical, in particular neural stem cells, endothelial cells, pericytes, ependymal cells, and microglia. Remodeling and repair of the matrix-rich SVZ niche by endogenous reparative mechanisms may then support functional recovery when enhanced by an artificial niche that supports the survival and proliferation of migrating vascular and neuronal cells. Critical considerations to mimic this area include an understanding of resident cell types, delivery method, and the use of biocompatible materials. Controlling stem cell survival, differentiation, and migration are key factors to consider when transplanting stem cells. Here, we discuss the role of the SVZ architecture and resident cells in the promotion and enhancement of endogenous repair mechanisms. We elucidate the interplay between the extracellular matrix composition and cell interactions prior to and following stroke

  18. Stroke Repair via Biomimicry of the Subventricular Zone

    Science.gov (United States)

    Matta, Rita; Gonzalez, Anjelica L.

    2018-03-01

    Stroke is among the leading causes of death and disability worldwide, 85% of which are ischemic. Current stroke therapies are limited by a narrow effective therapeutic time and fail to effectively complete the recovery of the damaged area. Magnetic resonance imaging of the subventricular zone (SVZ) following infarct/stroke has allowed visualization of new axonal connections and projections being formed, while new immature neurons migrate from the SVZ to the peri-infarct area. Such studies suggest that the SVZ is a primary source of regenerative cells for the repair and regeneration of stroke-damaged neurons and tissue. Therefore, the development of tissue engineered scaffolds that serve as a bioreplicative SVZ niche would support the survival of multiple cell types that reside in the SVZ. Essential to replication of the human SVZ microenvironment is the establishment of microvasculature that regulates both the healthy and stroke-injured blood brain barrier, which is dysregulated post-stroke. In order to reproduce this niche, understanding how cells interact in this environment is critical, in particular neural stem cells, endothelial cells, pericytes, ependymal cells, and microglia. Remodeling and repair of the matrix-rich SVZ niche by endogenous reparative mechanisms may then support functional recovery when enhanced by an artificial niche that supports the survival and proliferation of migrating vascular and neuronal cells. Critical considerations to mimic this area include an understanding of resident cell types, delivery method, and the use of biocompatible materials. Controlling stem cell survival, differentiation, and migration are key factors to consider when transplanting stem cells. Here, we discuss the role of the SVZ architecture and resident cells in the promotion and enhancement of endogenous repair mechanisms. We elucidate the interplay between the extracellular matrix composition and cell interactions prior to and following stroke. Lastly, we review

  19. New neurons in the adult brain : The role of sleep and consequences of sleep loss

    NARCIS (Netherlands)

    Meerlo, Peter; Mistiberger, Ralph E.; Jacobs, Barry L.; Heller, H. Craig; McGinty, Dennis; Mistlberger, Ralph E.

    2009-01-01

    Research over the last few decades has firmly established that new neurons are generated in selected areas of the adult mammalian brain, particularly the dentate gyrus of the hippocampal formation and the subventricular zone of the lateral ventricles. The function of adult-born neurons is still a

  20. Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis.

    Science.gov (United States)

    Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

    2013-01-01

    Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch ligand Delta-like 1 (Dll1) is required to maintain quiescent NSCs in the adult mouse subventricular zone. Dll1 protein is induced in activated NSCs and segregates to one daughter cell during mitosis. Dll1-expressing cells reside in close proximity to quiescent NSCs, suggesting a feedback signal for NSC maintenance by their sister cells and progeny. Our data suggest a model in which NSCs produce their own niche cells for their maintenance through asymmetric Dll1 inheritance at mitosis.

  1. Glioblastoma Recurrence Patterns After Radiation Therapy With Regard to the Subventricular Zone

    Energy Technology Data Exchange (ETDEWEB)

    Adeberg, Sebastian, E-mail: Sebastian.adeberg@med.uni-heidelberg [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); König, Laila; Bostel, Tilman; Harrabi, Semi; Welzel, Thomas [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Debus, Jürgen [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Heidelberg Ion Therapy Center, Heidelberg (Germany); DKFZ Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center Heidelberg (Germany); Combs, Stephanie E. [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Heidelberg Ion Therapy Center, Heidelberg (Germany)

    2014-11-15

    Purpose: We evaluated the influence of tumor location and tumor spread in primary glioblastoma (GBM), with respect to the subventricular zone (SVZ), on recurrence behavior, progression-free survival (PFS), and overall survival (OS). Methods and Materials: 607 patients (376 male and 231 female) with a median age of 61.3 years (range, 3.0-87.9 years) and primary GBM treated with radiation therapy (RT) from 2004 to 2012 at a single institution were included in this retrospective study. Preoperative images and follow-up examination results were assessed to evaluate tumor location. Tumors were classified according to the tumor location in relation to the SVZ. Results: The median PFS of the study population was 5.2 months (range, 1-91 months), and the median OS was 13.8 months (range, 1-102 months). Kaplan-Meier analysis showed that tumor location in close proximity to the SVZ was associated with a significant decline in PFS and OS (4.8 and 12.3 months, respectively; each P<.001). Furthermore, in cases where tumors were involved with the SVZ, distant cerebral progression (43.8%; P=.005) and multifocal progression (39.8%; P=.008) were more common. Interestingly, opening of the ventricle during the previous surgery showed no impact on PFS and OS. Conclusion: GBM in close proximity to the SVZ was associated with decreased survival and had a higher risk of multifocal or distant progression. Ventricle opening during surgery had no effect on survival rates.

  2. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    Science.gov (United States)

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  3. Cultured subventricular zone progenitor cells transduced with neurogenin-2 become mature glutamatergic neurons and integrate into the dentate gyrus.

    Directory of Open Access Journals (Sweden)

    Xia Chen

    Full Text Available We have previously shown that transplantation of immature DCX+/NeuN+/Prox1+ neurons (found in the neonatal DG, but not undifferentiated neuronal progenitor cells (NPCs from ventral subventricular zone (SVZ, results in neuronal maturation in vivo within the dentate niche. Here we investigated whether we could enhance the integration of SVZ NPCs by forced expression of the proneural gene Neurogenin 2 (NEUROG2. NPCs cultured from neonatal GFP-transgenic rat SVZ for 7 days in a non-differentiating medium were transduced with a retrovirus encoding NEUROG2 and DsRed or the DsRed reporter gene alone (control. By 3 days post-transduction, the NEUROG2-transduced cells maintained in culture contained mostly immature neurons (91% DCX+; 76% NeuN+, whereas the control virus-transduced cells remained largely undifferentiated (30% DCX+; <1% NeuN+. At 6 weeks following transplantation into the DG of adult male rats, there were no neurons among the transplanted cells treated with the control virus but the majority of the NEUROG2-transduced DsRed+ SVZ cells became mature neurons (92% NeuN+; DCX-negative. Although the NEUROG2-transduced SVZ cells did not express the dentate granule neuron marker Prox1, most of the NEUROG2-transduced SVZ cells (78% expressed the glutamatergic marker Tbr1, suggesting the acquisition of a glutamatergic phenotype. Moreover, some neurons extended dendrites into the molecular layer, grew axons containing Ankyrin G+ axonal initial segments, and projected into the CA3 region, thus resembling mature DG granule neurons. A proportion of NEUROG2 transduced cells also expressed c-Fos and P-CREB, two markers of neuronal activation. We conclude that NEUROG2-transduction is sufficient to promote neuronal maturation and integration of transplanted NPCs from SVZ into the DG.

  4. Hard-Diet Feeding Recovers Neurogenesis in the Subventricular Zone and Olfactory Functions of Mice Impaired by Soft-Diet Feeding

    Science.gov (United States)

    Utsugi, Chizuru; Miyazono, Sadaharu; Osada, Kazumi; Sasajima, Hitoshi; Noguchi, Tomohiro; Matsuda, Mitsuyoshi; Kashiwayanagi, Makoto

    2014-01-01

    The subventricular zone (SVZ) generates an immense number of neurons even during adulthood. These neurons migrate to the olfactory bulb (OB) and differentiate into granule cells and periglomerular cells. The information broadcast by general odorants is received by the olfactory sensory neurons and transmitted to the OB. Recent studies have shown that a reduction of mastication impairs both neurogenesis in the hippocampus and brain functions. To examine these effects, we first measured the difference in Fos-immunoreactivity (Fos-ir) at the principal sensory trigeminal nucleus (Pr5), which receives intraoral touch information via the trigeminal nerve, when female adult mice ingested a hard or soft diet to explore whether soft-diet feeding could mimic impaired mastication. Ingestion of a hard diet induced greater expression of Fos-ir cells at the Pr5 than did a soft diet or no diet. Bromodeoxyuridine-immunoreactive (BrdU-ir) structures in sagittal sections of the SVZ and in the OB of mice fed a soft or hard diet were studied to explore the effects of changes in mastication on newly generated neurons. After 1 month, the density of BrdU-ir cells in the SVZ and OB was lower in the soft-diet-fed mice than in the hard-diet-fed mice. The odor preferences of individual female mice to butyric acid were tested in a Y-maze apparatus. Avoidance of butyric acid was reduced by the soft-diet feeding. We then explored the effects of the hard-diet feeding on olfactory functions and neurogenesis in the SVZ of mice impaired by soft-diet feeding. At 3 months of hard-diet feeding, avoidance of butyric acid was reversed and responses to odors and neurogenesis were recovered in the SVZ. The present results suggest that feeding with a hard diet improves neurogenesis in the SVZ, which in turn enhances olfactory function at the OB. PMID:24817277

  5. Effect of leukemia inhibitory factor on long-term propagation of precursor cells derived from rat forebrain subventricular zone and ventral mesencephalon

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Zimmer, Jens; Wahlberg, Lars U

    2008-01-01

    Tissue blocks containing neural precursor cells were isolated from the rat forebrain subventricular zone (SVZ) and ventral mesencephalon (VM) and propagated as neural tissue-spheres (NTS). In the presence of fibroblast growth factor-2 (FGF2) and epidermal growth factor (EGF), SVZ-derived NTS were...... propagated and maintained for more than 6 months with a cell population doubling time of 21.5 days. The replacement of EGF by leukemia inhibitory factor (LIF) resulted in a cell population doubling time of 19.8 days, corresponding to a 10-fold increase in estimated cell numbers over a period of 70 days......, at which point these NTS ceased to grow. In the presence of FGF2 and LIF, VM-derived NTS displayed a cell population doubling time of 24.6 days, which was maintained over a period of more than 200 days. However, when LIF was replaced by EGF, the cell numbers only increased 1.2 fold over 50 days. Using...

  6. Novel in vivo imaging techniques for trafficking the behavior of subventricular zone neural stem cells (SVZSC) and SVZSC induced functional repair

    Energy Technology Data Exchange (ETDEWEB)

    Anna-Liisa Brownell

    2003-11-28

    Adult progenitor cells hold promise for therapeutic treatment where there has been a disabling loss of function due to death of cells from trauma, disease or aging. However, it will be essential in clinical application to be able to follow the fate of the transplanted cells over time using in vivo tracking methods. We have developed protocol for labeling of progenitor cells to monitor cell trafficking by high resolution magnetic resonance imaging (MRI) and super high resolution positron emission tomography (PET). We have transfected rat subventricular zone stem cells (SVZ, progenitor cell line) and another control cell line (PC12, pheochromocytoma cells) utilizing super paramagnetic iron oxide and poly-L-lysine complex for MR imaging or radiolabeling with 18F-fluor deoxy-D- glucose for PET imaging. The labeled cells were transplanted into the rostral migratory stream (RMS) or striatum of normal or 6-hydroxydopamine lesioned Spraque-Dawley rats. Longitudinal MRI studies (up to 40 days) showed that transplantation site has significant impact to the fate of the cells; when SVZ cells were transplanted into the RMS, cells migrated several centimeter into the olfactory bulb; after transplantation into the striatum, the migration was minimal, only 2 mm. PC 12 cells grew a massive tumor after the striatal implantation and significantly smaller tumor after the RMS implantation. PET studies conducted immediately after transplantation verified the transplantation site. MRI studies were able to show the whole path of migration in one image, since part of the cells die during migration and will get detected because of iron content. Endpoint histological studies verified the cell survival and immunohistochemical studies revealed the differentiation of the transplanted cells into astrocytes and neurons.

  7. Novel in vivo imaging techniques for trafficking the behavior of subventricular zone neural stem cells (SVZSC) and SVZSC induced functional repair

    International Nuclear Information System (INIS)

    Anna-Liisa Brownell

    2003-01-01

    Adult progenitor cells hold promise for therapeutic treatment where there has been a disabling loss of function due to death of cells from trauma, disease or aging. However, it will be essential in clinical application to be able to follow the fate of the transplanted cells over time using in vivo tracking methods. We have developed protocol for labeling of progenitor cells to monitor cell trafficking by high resolution magnetic resonance imaging (MRI) and super high resolution positron emission tomography (PET). We have transfected rat subventricular zone stem cells (SVZ, progenitor cell line) and another control cell line (PC12, pheochromocytoma cells) utilizing super paramagnetic iron oxide and poly-L-lysine complex for MR imaging or radiolabeling with 18F-fluor deoxy-D- glucose for PET imaging. The labeled cells were transplanted into the rostral migratory stream (RMS) or striatum of normal or 6-hydroxydopamine lesioned Spraque-Dawley rats. Longitudinal MRI studies (up to 40 days) showed that transplantation site has significant impact to the fate of the cells; when SVZ cells were transplanted into the RMS, cells migrated several centimeter into the olfactory bulb; after transplantation into the striatum, the migration was minimal, only 2 mm. PC 12 cells grew a massive tumor after the striatal implantation and significantly smaller tumor after the RMS implantation. PET studies conducted immediately after transplantation verified the transplantation site. MRI studies were able to show the whole path of migration in one image, since part of the cells die during migration and will get detected because of iron content. Endpoint histological studies verified the cell survival and immunohistochemical studies revealed the differentiation of the transplanted cells into astrocytes and neurons

  8. Subventricular zone predicts high velocity of tumor expansion and poor clinical outcome in patients with low grade astrocytoma.

    Science.gov (United States)

    Wen, Bing; Fu, Feixian; Hu, Liangbo; Cai, Qiuyi; Xie, Junshi

    2018-05-01

    The aim of this study is to clarify the association between subventricular zone (SVZ) involvement and velocity of diametric expansion(VDE) in patients with low-grade astrocytoma and also assessed the clinical outcome of those patients. A total of 168 adult patients with newly diagnosed supratentorial low-grade astrocytoma were studied retrospectively. There were 73 patients had SVZ involvement. Patients with SVZ involvement(7.16 ± 6.53 mm/y) had a higher VDE than patients without SVZ involvement(4.38 ± 5.35 mm/y). VDE was modeled as a categorical variable(<4, ≥4 and, <8, ≥8 and, <12, ≥12 mm/y). Logistic regression showed that SVZ involvement was associated with high VDE after adjusting by confounding variables. On the univariate analysis, the results showed that tumor involved with SVZ, VDE ≥ 4 mm/y, VDE ≥ 8 mm/y, and VDE ≥ 8 mm/y were significant predictors of a shorter OS, progression-free survival (PFS) and malignant progression-free survival (MFS)(all p <0.05). The categorical variables of VDE (<4 mm/y, ≥4 mm/y and, <8 mm/y, ≥8 mm/y and, <12 mm/y, ≥12 mm/y) were adjusted by confounding variables in multivariate analysis, respectively. The results indicated that VDE ≥ 8 mm/y, VDE ≥ 12 mm/y were worse prognostic factors for OS, while VDE ≥ 4 mm/y, VDE ≥ 8 mm/y and VDE ≥ 12 mm/y were related to shorter PFS and MFS. In addition, SVZ involvement was prognostic factors in predicting OS and PFS except MFS. Our results demonstrated that SVZ involvement predicted high VDE and worse clinical outcome, and high VDE was associated with poor prognosis in patients with low-grade astrocytoma. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis

    OpenAIRE

    Kawaguchi, Daichi; Furutachi, Shohei; Kawai, Hiroki; Hozumi, Katsuto; Gotoh, Yukiko

    2013-01-01

    Stem cells often divide asymmetrically to produce one stem cell and one differentiating cell, thus maintaining the stem cell pool. Although neural stem cells (NSCs) in the adult mouse subventricular zone have been suggested to divide asymmetrically, intrinsic cell fate determinants for asymmetric NSC division are largely unknown. Stem cell niches are important for stem cell maintenance, but the niche for the maintenance of adult quiescent NSCs has remained obscure. Here we show that the Notch...

  10. Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage

    NARCIS (Netherlands)

    McAllister, James P.; Guerra, Maria Montserrat; Ruiz, Leandro Castaneyra; Jimenez, Antonio J.; Dominguez-Pinos, Dolores; Sival, Deborah; den Dunnen, Wilfred; Morales, Diego M.; Schmidt, Robert E.; Rodriguez, Esteban M.; Limbrick, David D.

    2017-01-01

    To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls

  11. Graphene Functionalized Scaffolds Reduce the Inflammatory Response and Supports Endogenous Neuroblast Migration when Implanted in the Adult Brain.

    Directory of Open Access Journals (Sweden)

    Kun Zhou

    Full Text Available Electroactive materials have been investigated as next-generation neuronal tissue engineering scaffolds to enhance neuronal regeneration and functional recovery after brain injury. Graphene, an emerging neuronal scaffold material with charge transfer properties, has shown promising results for neuronal cell survival and differentiation in vitro. In this in vivo work, electrospun microfiber scaffolds coated with self-assembled colloidal graphene, were implanted into the striatum or into the subventricular zone of adult rats. Microglia and astrocyte activation levels were suppressed with graphene functionalization. In addition, self-assembled graphene implants prevented glial scarring in the brain 7 weeks following implantation. Astrocyte guidance within the scaffold and redirection of neuroblasts from the subventricular zone along the implants was also demonstrated. These findings provide new functional evidence for the potential use of graphene scaffolds as a therapeutic platform to support central nervous system regeneration.

  12. Dose-escalated intensity-modulated radiotherapy and irradiation of subventricular zones in relation to tumor control outcomes of patients with glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Kusumawidjaja G

    2016-03-01

    Full Text Available Grace Kusumawidjaja,1 Patricia Zhun Hong Gan,1 Whee Sze Ong,2 Achiraya Teyateeti,3 Pittaya Dankulchai,3 Daniel Yat Harn Tan,1 Eu Tiong Chua,1 Kevin Lee Min Chua,1 Chee Kian Tham,4 Fuh Yong Wong,1 Melvin Lee Kiang Chua1,5 1Division of Radiation Oncology, National Cancer Centre, Singapore; 2Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, Singapore; 3Department of Radiology, Division of Radiation Oncology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand; 4Division of Medical Oncology, National Cancer Centre, Singapore; 5Duke-NUS Graduate Medical School, Singapore Background: Glioblastoma multiforme (GBM is the most aggressive primary brain tumor with high relapse rate. In this study, we aimed to determine if dose-escalated (DE radiotherapy improved tumor control and survival in GBM patients. Methods: We conducted a retrospective analysis of 49 and 23 newly-diagnosed histology-proven GBM patients, treated with DE radiotherapy delivered in 70 Gy (2.33 Gy per fraction and conventional doses (60 Gy, respectively, between 2007 and 2013. Clinical target volumes for 70 and 60 Gy were defined by 0.5 and 2.0 cm expansion of magnetic resonance imaging T1-gadolinium-enhanced tumor/surgical cavity, respectively. Bilateral subventricular zones (SVZ were contoured on a co-registered pre-treatment magnetic resonance imaging and planning computed tomography dataset as a 5 mm wide structure along the lateral margins of the lateral ventricles. Survival outcomes of both cohorts were compared using log-rank test. Radiation dose to SVZ in the DE cohort was evaluated. Results: Median follow-up was 13.6 and 15.1 months for the DE- and conventionally-treated cohorts, respectively. Median overall survival (OS of patients who received DE radiotherapy was 15.2 months (95% confidence interval [CI] =11.0–18.6, while median OS of the latter cohort was 18.4 months (95% CI =12.5–31.4, P=0.253. Univariate analyses of

  13. Neurotransmitter regulation of adult neurogenesis: putative therapeutic targets.

    Science.gov (United States)

    Vaidya, V A; Vadodaria, K C; Jha, S

    2007-10-01

    The evidence that new neuron addition takes place in the mammalian brain throughout adult life has dramatically altered our perspective of the potential for plasticity in the adult CNS. Although several recent reports suggest a latent neurogenic capacity in multiple brain regions, the two major neurogenic niches that retain the ability to generate substantial numbers of new neurons in adult life are the subventricular zone (SVZ) lining the lateral ventricles and the subgranular zone (SGZ) in the hippocampal formation. The discovery of adult neurogenesis has also unveiled a novel therapeutic target for the repair of damaged neuronal circuits. In this regard, understanding the endogenous mechanisms that regulate adult neurogenesis holds promise both for a deeper understanding of this form of structural plasticity, as well as the identification of pathways that can serve as therapeutic targets to manipulate adult neurogenesis. The purpose of the present review is to discuss the regulation of adult neurogenesis by neurotransmitters and to highlight the relevance of these endogenous regulators as targets to modulate adult neurogenesis in a clinical context.

  14. Metallic gold treatment reduces proliferation of inflammatory cells, increases expression of VEGF and FGF, and stimulates cell proliferation in the subventricular zone following experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Pedersen, Mie Østergaard; Larsen, Agnete; Pedersen, Dan Sonne

    2009-01-01

    Traumatic brain injury represents a leading cause of morbidity in young individuals and there is an imperative need for neuroprotective treatments limiting the neurologic impairment following such injury. It has recently been demonstrated that bio-liberated gold ions liberated from small metallic...... gold implants reduce inflammation and neuronal apoptosis, while generating an increased neuronal stem cell response following focal brain damage. In this study mice were subjected to a unilateral traumatic cryo-lesion with concomitant injection of 25-45 microm gold particles near the lesion. Placebo...... increase in cell proliferation in both the ipsilateral and the contralateral subventricular zone was found in response to gold-treatment. In conclusion: we confirmed the previously demonstrated anti-inflammatory effect of bio-liberated gold ions, and further show that metallic gold increases growth factor...

  15. The Role of Astrocytes in the Generation, Migration, and Integration of New Neurons in the Adult Olfactory Bulb

    Science.gov (United States)

    Gengatharan, Archana; Bammann, Rodrigo R.; Saghatelyan, Armen

    2016-01-01

    In mammals, new neurons in the adult olfactory bulb originate from a pool of neural stem cells in the subventricular zone of the lateral ventricles. Adult-born cells play an important role in odor information processing by adjusting the neuronal network to changing environmental conditions. Olfactory bulb neurogenesis is supported by several non-neuronal cells. In this review, we focus on the role of astroglial cells in the generation, migration, integration, and survival of new neurons in the adult forebrain. In the subventricular zone, neural stem cells with astrocytic properties display regional and temporal specificity when generating different neuronal subtypes. Non-neurogenic astrocytes contribute to the establishment and maintenance of the neurogenic niche. Neuroblast chains migrate through the rostral migratory stream ensheathed by astrocytic processes. Astrocytes play an important regulatory role in neuroblast migration and also assist in the development of a vasculature scaffold in the migratory stream that is essential for neuroblast migration in the postnatal brain. In the olfactory bulb, astrocytes help to modulate the network through a complex release of cytokines, regulate blood flow, and provide metabolic support, which may promote the integration and survival of new neurons. Astrocytes thus play a pivotal role in various processes of adult olfactory bulb neurogenesis, and it is likely that many other functions of these glial cells will emerge in the near future. PMID:27092050

  16. S phase entry of neural progenitor cells correlates with increased blood flow in the young subventricular zone.

    Directory of Open Access Journals (Sweden)

    Benjamin Lacar

    Full Text Available The postnatal subventricular zone (SVZ contains proliferating neural progenitor cells in close proximity to blood vessels. Insults and drug treatments acutely stimulate cell proliferation in the SVZ, which was assessed by labeling cells entering S phase. Although G1-to-S progression is metabolically demanding on a minute-to-hour time scale, it remains unknown whether increased SVZ cell proliferation is accompanied by a local hemodynamic response. This neurovascular coupling provides energy substrates to active neuronal assemblies. Transcardial dye perfusion revealed the presence of capillaries throughout the SVZ that constrict upon applications of the thromboxane A(2 receptor agonist U-46119 in acute brain slice preparations. We then monitored in vivo blood flow using laser Doppler flowmetry via a microprobe located either in the SVZ or a mature network. U-46119 injections into the lateral ventricle decreased blood flow in the SVZ and the striatum, which are near the ventricle. A 1-hour ventricular injection of epidermal and basic fibroblast growth factor (EGF and bFGF significantly increased the percentage of Sox2 transcription factor-positive cells in S phase 1.5 hours post-injection. This increase was accompanied by a sustained rise in blood flow in the SVZ but not in the striatum. Direct growth factor injections into the cortex did not alter local blood flow, ruling out direct effects on capillaries. These findings suggest that an acute increase in the number of G1-to-S cycling SVZ cells is accompanied by neurometabolic-vascular coupling, which may provide energy and nutrient for cell cycle progression.

  17. Neural stem cells in the immature, but not the mature, subventricular zone respond robustly to traumatic brain injury.

    Science.gov (United States)

    Goodus, Matthew T; Guzman, Alanna M; Calderon, Frances; Jiang, Yuhui; Levison, Steven W

    2015-01-01

    Pediatric traumatic brain injury is a significant problem that affects many children each year. Progress is being made in developing neuroprotective strategies to combat these injuries. However, investigators are a long way from therapies to fully preserve injured neurons and glia. To restore neurological function, regenerative strategies will be required. Given the importance of stem cells in repairing damaged tissues and the known persistence of neural precursors in the subventricular zone (SVZ), we evaluated regenerative responses of the SVZ to a focal brain lesion. As tissues repair more slowly with aging, injury responses of male Sprague Dawley rats at 6, 11, 17, and 60 days of age and C57Bl/6 mice at 14 days of age were compared. In the injured immature animals, cell proliferation in the dorsolateral SVZ more than doubled by 48 h. By contrast, the proliferative response was almost undetectable in the adult brain. Three approaches were used to assess the relative numbers of bona fide neural stem cells, as follows: the neurosphere assay (on rats injured at postnatal day 11, P11), flow cytometry using a novel 4-marker panel (on mice injured at P14) and staining for stem/progenitor cell markers in the niche (on rats injured at P17). Precursors from the injured immature SVZ formed almost twice as many spheres as precursors from uninjured age-matched brains. Furthermore, spheres formed from the injured brain were larger, indicating that the neural precursors that formed these spheres divided more rapidly. Flow cytometry revealed a 2-fold increase in the percentage of stem cells, a 4-fold increase in multipotential progenitor-3 cells and a 2.5-fold increase in glial-restricted progenitor-2/multipotential-3 cells. Analogously, there was a 2-fold increase in the mitotic index of nestin+/Mash1- immunoreactive cells within the immediately subependymal region. As the early postnatal SVZ is predominantly generating glial cells, an expansion of precursors might not

  18. MRI visualization of endogenous neural progenitor cell migration along the RMS in the adult mouse brain

    DEFF Research Database (Denmark)

    Vreys, Ruth; Vande Velde, Greetje; Krylychkina, Olga

    2010-01-01

    The adult rodent brain contains neural progenitor cells (NPCs), generated in the subventricular zone (SVZ), which migrate along the rostral migratory stream (RMS) towards the olfactory bulb (OB) where they differentiate into neurons. The aim of this study was to visualize endogenous NPC migration...... by a longitudinal MRI study and validated with histology. Here, we visualized endogenous NPC migration in the mouse brain by in vivo MRI and demonstrated accumulation of MPIO-labeled NPCs in the OB over time with ex vivo MRI. Furthermore, we investigated the influence of in situ injection of MPIOs on adult...

  19. Hypoxic-preconditioning enhances the regenerative capacity of neural stem/progenitors in subventricular zone of newborn piglet brain.

    Science.gov (United States)

    Ara, Jahan; De Montpellier, Sybille

    2013-09-01

    Perinatal hypoxia-ischemia (HI) results in brain injury, whereas mild hypoxic episodes result in preconditioning, which can significantly reduce the vulnerability of the brain to subsequent severe hypoxia-ischemia. Hypoxic-preconditioning (PC) has been shown to enhance cell survival and differentiation of progenitor cells in the central nervous system (CNS). The purpose of this study was to determine whether pretreatment with PC prior to HI stimulates subventricular zone (SVZ) proliferation and neurogenesis in newborn piglets. One-day-old piglets were subjected to PC (8% O2/92% N2) for 3h and 24h later were exposed to HI produced by combination of hypoxia (5% FiO2) for a pre-defined period of 30min and ischemia induced by a period of 10min of hypotension. Here we demonstrate that SVZ derived neural stem/progenitor cells (NSPs) from PC, HI and PC+HI piglets proliferated as neurospheres, expressed neural progenitor and neurodevelopmental markers, and that greater proportion of the spheres generated are multipotential. Neurosphere assay revealed that preconditioning pretreatment increased the number of NSP-derived neurospheres in SVZ following HI compared to normoxic and HI controls. NSPs from preconditioned SVZ generated twice as many neurons and astrocytes in vitro. Injections with 5-Bromo-2-deoxyuridine (BrdU) after PC revealed a robust proliferative response within the SVZ that continued for one week. PC also increased neurogenesis in vivo, doublecortin positive cells with migratory profiles were observed streaming from the SVZ to striatum and neocortex. These findings show that the induction of proliferation and neurogenesis by PC might be a positive adaptation for an efficient repair and plasticity in the event of a hypoxic-ischemic insult. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions

    Science.gov (United States)

    Ming, Guo-li; Song, Hongjun

    2011-01-01

    Summary Adult neurogenesis, a process of generating functional neurons from adult neural precursors, occurs throughout life in restricted brain regions in mammals. The past decade has witnessed tremendous progress in addressing questions related to almost every aspect of adult neurogenesis in the mammalian brain. Here we review major advances in our understanding of adult mammalian neurogenesis in the dentate gyrus of the hippocampus and from the subventricular zone of the lateral ventricle, the rostral migratory stream to the olfactory bulb. We highlight emerging principles that have significant implications for stem cell biology, developmental neurobiology, neural plasticity, and disease mechanisms. We also discuss remaining questions related to adult neural stem cells and their niches, underlying regulatory mechanisms and potential functions of newborn neurons in the adult brain. Building upon the recent progress and aided by new technologies, the adult neurogenesis field is poised to leap forward in the next decade. PMID:21609825

  1. Detrimental role of prolonged sleep deprivation on adult neurogenesis

    Directory of Open Access Journals (Sweden)

    Carina eFernandes

    2015-04-01

    Full Text Available Adult mammalian brains continuously generate new neurons, a phenomenon called neurogenesis. Both environmental stimuli and endogenous factors are important regulators of neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and neurogenesis in brain function, such as learning, memory and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on neurogenesis.

  2. Abundant Occurrence of Basal Radial Glia in the Subventricular Zone of Embryonic Neocortex of a Lissencephalic Primate, the Common Marmoset Callithrix jacchus

    Science.gov (United States)

    Kelava, Iva; Reillo, Isabel; Murayama, Ayako Y.; Kalinka, Alex T.; Stenzel, Denise; Tomancak, Pavel; Matsuzaki, Fumio; Lebrand, Cécile; Sasaki, Erika; Schwamborn, Jens C.; Okano, Hideyuki; Borrell, Víctor

    2012-01-01

    Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at high relative abundance in the SVZ of gyrencephalic primates (human) and nonprimates (ferret) but not lissencephalic rodents (mouse). Here, we analyzed the occurrence of bRG cells in the embryonic neocortex of the common marmoset Callithrix jacchus, a near-lissencephalic primate. bRG cells, expressing Pax6, Sox2 (but not Tbr2), glutamate aspartate transporter, and glial fibrillary acidic protein and retaining a basal process at mitosis, occur at similar relative abundance in the marmoset SVZ as in human and ferret. The proportion of progenitors in M-phase was lower in embryonic marmoset than developing ferret neocortex, raising the possibility of a longer cell cycle. Fitting the gyrification indices of 26 anthropoid species to an evolutionary model suggested that the marmoset evolved from a gyrencephalic ancestor. Our results suggest that a high relative abundance of bRG cells may be necessary, but is not sufficient, for gyrencephaly and that the marmoset's lissencephaly evolved secondarily by changing progenitor parameters other than progenitor type. PMID:22114084

  3. Conditional reduction of adult born doublecortin-positive neurons reversibly impairs selective behaviours

    Directory of Open Access Journals (Sweden)

    Lillian eGarrett

    2015-11-01

    Full Text Available Adult neurogenesis occurs in the adult mammalian subventricular zone (SVZ along the walls of the lateral ventricles and the subgranular zone (SGZ of the hippocampal dentate gyrus. While a burgeoning body of research implicates adult neurogenesis in olfactory bulb (OB - and hippocampal-related behaviors, the precise function continues to elude. To further assess the behavioral importance of adult neurogenesis, we herein generated a novel inducible transgenic mouse model of adult neurogenesis reduction where mice with CreERT2 under doublecortin (DCX promoter control were crossed with mice where diphtheria toxin A (DTA was driven by the Rosa26 promoter. Activation of DTA, through the administration of tamoxifen (TAM, results in a specific reduction of DCX+ immature neurons in both the hippocampal dentate gyrus and OB. We show that the decrease of DCX+ cells causes impaired social discrimination ability in both young adult (from 3 months and middle (from 10 months aged mice. Furthermore, these animals showed an age-independent altered coping behavior in the Forced Swim Test without clear changes in anxiety-related behavior. Notably, these behavior changes were reversible on repopulating the neurogenic zones with DCX+ cells on cessation of the tamoxifen treatment, demonstrating the specificity of this effect. Overall, these results support the notion that adult neurogenesis plays a role in social memory and in stress coping but not necessarily in anxiety-related behavior.

  4. Recent Advances on the Role of Neurogenesis in the Adult Brain: Therapeutic Potential in Parkinson's and Alzheimer's Diseases.

    Science.gov (United States)

    Radad, Khaled; Moldzio, Rudolf; Al-Shraim, Mubarak; Kranner, Barbara; Krewenka, Christopher; Rausch, Wolf-Dieter

    2017-01-01

    Generation of nascent functional neurons from neural stem cells in the adult brain has recently become largely accepted by the neuroscience community. In adult mammals including humans, the process of neurogenesis has been well documented in two brain regions; the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus. Some evidence has indicated neurogenesis in other regions of the adult mammalian brain such as the neocortex, cerebellum, striatum, amygdala and hypothalamus. These discoveries question a long standing dogma on nervous system regeneration and provide medical science with potential new strategies to harness the process of neurogenesis for treating neurological disabilities and neurodegenerative diseases. In this current review, we address the most recent advances on the role of neurogenesis in the adult brain and therapeutic potential in the two most common neurodegenerative disorders, Parkinson's and Alzheimer's diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

    Directory of Open Access Journals (Sweden)

    Fabio Cavaliere

    2016-01-01

    Full Text Available Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.

  6. Adult-Brain-Derived Neural Stem Cells Grafting into a Vein Bridge Increases Postlesional Recovery and Regeneration in a Peripheral Nerve of Adult Pig

    Directory of Open Access Journals (Sweden)

    Olivier Liard

    2012-01-01

    Full Text Available We attempted transplantation of adult neural stem cells (ANSCs inside an autologous venous graft following surgical transsection of nervis cruralis with 30 mm long gap in adult pig. The transplanted cell suspension was a primary culture of neurospheres from adult pig subventricular zone (SVZ which had been labeled in vitro with BrdU or lentivirally transferred fluorescent protein. Lesion-induced loss of leg extension on the thigh became definitive in controls but was reversed by 45–90 days after neurosphere-filled vein grafting. Electromyography showed stimulodetection recovery in neurosphere-transplanted pigs but not in controls. Postmortem immunohistochemistry revealed neurosphere-derived cells that survived inside the venous graft from 10 to 240 post-lesion days and all displayed a neuronal phenotype. Newly formed neurons were distributed inside the venous graft along the severed nerve longitudinal axis. Moreover, ANSC transplantation increased CNPase expression, indicating activation of intrinsic Schwann cells. Thus ANSC transplantation inside an autologous venous graft provides an efficient repair strategy.

  7. Axonal Control of the Adult Neural Stem Cell Niche

    Science.gov (United States)

    Tong, Cheuk Ka; Chen, Jiadong; Cebrián-Silla, Arantxa; Mirzadeh, Zaman; Obernier, Kirsten; Guinto, Cristina D.; Tecott, Laurence H.; García-Verdugo, Jose Manuel; Kriegstein, Arnold; Alvarez-Buylla, Arturo

    2014-01-01

    SUMMARY The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSC) in the walls of the lateral ventricles of the adult brain. How the adult brain’s neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C. PMID:24561083

  8. Targeting p38 Mitogen-Activated Protein Kinase Signaling Restores Subventricular Zone Neural Stem Cells and Corrects Neuromotor Deficits in Atm Knockout Mouse

    Science.gov (United States)

    Kim, Jeesun

    2012-01-01

    Ataxia-telangiectasia (A-T) is a progressive degenerative disorder that results in major neurological disability. In A-T patients, necropsy has revealed atrophy of cerebellar cortical layers along with Purkinje and granular cell loss. We have previously identified an oxidative stress-mediated increase in phospho-p38 mitogen-activated protein kinase (MAPK) and the resultant downregulation of Bmi-1 and upregulation of p21 as key components of the mechanism causing defective proliferation of neural stem cells (NSCs) isolated from the subventricular zone (SVZ) of Atm−/− mice. However, the in vivo aspect of alteration in SVZ tissue and the functional significance of p38MAPK activation in NSCs for neuropathogenesis of ATM deficiency remain unknown. Here we show that the NSC population was abnormally decreased in the SVZ of 3-month-old Atm−/− mice; this decrease was accompanied by p38MAPK activation. However, after a 2-month treatment with the p38MAPK inhibitor SB203580, starting at 1 month old, Atm−/− mice showed restoration of normal levels of Bmi-1 and p21 with the rescue of NSC population in the SVZ. In addition, treated Atm−/− mice exhibited more Purkinje cells in the cerebellum. Most importantly, motor coordination of Atm−/− mice was significantly improved in the treatment group. Our results show for the first time in vivo evidence of depleted NSCs in the SVZ of Atm−/− mice and also demonstrate that pharmacologic inhibition of p38MAPK signaling has the potential to treat neurological defects of A-T. This study provides a promising approach targeting the oxidative stress-dependent p38 signaling pathway not only for A-T but also for other neurodegenerative disorders. PMID:23197859

  9. [Brain repair after ischemic stroke: role of neurotransmitters in post-ischemic neurogenesis].

    Science.gov (United States)

    Sánchez-Mendoza, Eduardo; Bellver-Landete, Víctor; González, María Pilar; Merino, José Joaquín; Martínez-Murillo, Ricardo; Oset-Gasque, María Jesús

    2012-11-01

    Brain ischemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells towards the peri-infarct region occurs. The success of new neurorestorative treatments for damaged brain implies the need to know, with greater accuracy, the mechanisms in charge of regulating adult neurogenesis, both under physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone, thus being part of the complex signalling network that influences the production of new neurons. Neurotransmitters provide a link between brain activity and subventricular zone neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may provide a valuable tool to be used as a neurorestorative therapy in this pathology.

  10. The number of stem cells in the subependymal zone of the adult rodent brain is correlated with the number of ependymal cells and not with the volume of the niche.

    Science.gov (United States)

    Kazanis, Ilias; Ffrench-Constant, Charles

    2012-05-01

    The mammalian subependymal zone (SEZ; often called subventricular) situated at the lateral walls of the lateral ventricles of the brain contains a pool of relatively quiescent adult neural stem cells whose neurogenic activity persists throughout life. These stem cells are positioned in close proximity both to the ependymal cells that provide the cerebrospinal fluid interface and to the blood vessel endothelial cells, but the relative contribution of these 2 cell types to stem cell regulation remains undetermined. Here, we address this question by analyzing a naturally occurring example of volumetric scaling of the SEZ in a comparison of the mouse SEZ with the larger rat SEZ. Our analysis reveals that the number of stem cells in the SEZ niche is correlated with the number of ependymal cells rather than with the volume, thereby indicating the importance of ependymal-derived factors in the formation and function of the SEZ. The elucidation of the factors generated by ependymal cells that regulate stem cell numbers within the SEZ is, therefore, of importance for stem cell biology and regenerative neuroscience.

  11. What is CAR doing in the middle of the adult neurogenic road?

    Science.gov (United States)

    Junyent, Felix; Coré, Nathalie; Cremer, Harold

    2017-01-01

    ABSTRACT The molecular and cellular basis of adult neurogenesis has attracted considerable attention for fundamental and clinical applications because neural stem cells and newborn neurons may, one day, be harnessed to replace neurons and allow cognitive improvement in the diseased brain. In rodents, neural progenitors are located in the dentate gyrus and the sub/periventricular zone. In the dentate gyrus the generation of newborn neurons is associated with plasticity, including regulation of memory. The role of subventricular zone neural precursors that migrate to the olfactory bulb is less characterized. Identifying factors that impact neural stem cell proliferation, migration and differentiation is therefore sine qua non before we can harness their potential. Here, we expand upon our recent results showing that CAR, the coxsackievirus and adenovirus receptor, is among the developing list of key players when it comes to the complex process of integrating newborn neurons into existing circuits in the mature brain. PMID:28516108

  12. The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro.

    Science.gov (United States)

    Morales-García, Jose A; de la Fuente Revenga, Mario; Alonso-Gil, Sandra; Rodríguez-Franco, María Isabel; Feilding, Amanda; Perez-Castillo, Ana; Riba, Jordi

    2017-07-13

    Banisteriopsis caapi is the basic ingredient of ayahuasca, a psychotropic plant tea used in the Amazon for ritual and medicinal purposes, and by interested individuals worldwide. Animal studies and recent clinical research suggests that B. caapi preparations show antidepressant activity, a therapeutic effect that has been linked to hippocampal neurogenesis. Here we report that harmine, tetrahydroharmine and harmaline, the three main alkaloids present in B. caapi, and the harmine metabolite harmol, stimulate adult neurogenesis in vitro. In neurospheres prepared from progenitor cells obtained from the subventricular and the subgranular zones of adult mice brains, all compounds stimulated neural stem cell proliferation, migration, and differentiation into adult neurons. These findings suggest that modulation of brain plasticity could be a major contribution to the antidepressant effects of ayahuasca. They also expand the potential application of B. caapi alkaloids to other brain disorders that may benefit from stimulation of endogenous neural precursor niches.

  13. Adult Hippocampal Neurogenesis in Parkinson’s Disease: Impact on Neuronal Survival and Plasticity

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    Martin Regensburger

    2014-01-01

    Full Text Available In Parkinson’s disease (PD and other synucleinopathies, chronic neurodegeneration occurs within different areas of the central nervous system leading to progressive motor and nonmotor symptoms. The symptomatic treatment options that are currently available do not slow or halt disease progression. This highlights the need of a better understanding of disease mechanisms and disease models. The generation of newborn neurons in the adult hippocampus and in the subventricular zone/olfactory bulb system is affected by many different regulators and possibly involved in memory processing, depression, and olfaction, symptoms which commonly occur in PD. The pathology of the adult neurogenic niches in human PD patients is still mostly elusive, but different preclinical models have shown profound alterations of adult neurogenesis. Alterations in stem cell proliferation, differentiation, and survival as well as neurite outgrowth and spine formation have been related to different aspects in PD pathogenesis. Therefore, neurogenesis in the adult brain provides an ideal model to study disease mechanisms and compounds. In addition, adult newborn neurons have been proposed as a source of endogenous repair. Herein, we review current knowledge about the adult neurogenic niches in PD and highlight areas of future research.

  14. The effects of chronic alcoholism on cell proliferation in the human brain.

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    Sutherland, G T; Sheahan, P J; Matthews, J; Dennis, C V P; Sheedy, D S; McCrossin, T; Curtis, M A; Kril, J J

    2013-09-01

    Neurogenesis continues in the human subventricular zone and to a lesser extent in the hippocampal subgranular zone throughout life. Subventricular zone-derived neuroblasts migrate to the olfactory bulb where survivors become integrated as interneurons and are postulated to contribute to odor discrimination. Adult neurogenesis is dysregulated in many neurological, neurovascular and neurodegenerative diseases. Alcohol abuse can result in a neurodegenerative condition called alcohol-related brain damage. Alcohol-related brain damage manifests clinically as cognitive dysfunction and the loss of smell sensation (hyposmia) and pathologically as generalized white matter atrophy and focal neuronal loss. The exact mechanism linking chronic alcohol intoxication with alcohol-related brain damage remains largely unknown but rodent models suggest that decreased neurogenesis is an important component. We investigated this idea by comparing proliferative events in the subventricular zone and olfactory bulb of a well-characterized cohort of 15 chronic alcoholics and 16 age-matched controls. In contrast to the findings in animal models there was no difference in the number of proliferative cell nuclear antigen-positive cells in the subventricular zone of alcoholics (mean±SD=28.7±20.0) and controls (27.6±18.9, p=1.0). There were also no differences in either the total (p=0.89) or proliferative cells (p=0.98) in the granular cell layer of the olfactory bulb. Our findings show that chronic alcohol consumption does not affect cell proliferation in the human SVZ or olfactory bulb. In fact only microglial proliferation could be demonstrated in the latter. Therefore neurogenic deficits are unlikely to contribute to hyposmia in chronic alcoholics. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. The satiating hormone amylin enhances neurogenesis in the area postrema of adult rats

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    Claudia G. Liberini

    2016-10-01

    Full Text Available Objective: Adult neurogenesis in the subgranular zone and subventricular zone is generally accepted, but its existence in other brain areas is still controversial. Circumventricular organs, such as the area postrema (AP have recently been described as potential neurogenic niches in the adult brain. The AP is the major site of action of the satiating hormone amylin. Amylin has been shown to promote the formation of neuronal projections originating from the AP in neonatal rodents but the role of amylin in adult neurogenesis remains unknown. Methods: To test this, we first performed an RNA-sequencing of the AP of adult rats acutely injected with either amylin (20 μg/kg, amylin plus the amylin receptor antagonist AC187 (500 μg/kg or vehicle. Second, animals were subcutaneously equipped with minipumps releasing either amylin (50 μg/kg/day or vehicle for 3 weeks to assess cell proliferation and differentiation with the 5′-bromo-2-deoxyuridine (BrdU technique. Results: Acute amylin injections affected genes involved in pathways and processes that control adult neurogenesis. Amylin consistently upregulated NeuroD1 transcript and protein in the adult AP, and this effect was blocked by the co-administration of AC187. Further, chronic amylin treatment increased the number of newly proliferated AP-cells and significantly promoted their differentiation into neurons rather than astrocytes. Conclusion: Our findings revealed a novel role of the satiating hormone amylin in promoting neurogenesis in the AP of adult rats. Keywords: Amylin, Adult neurogenesis, Area postrema, BrdU, Circumventricular organs

  16. Perlecan is required for FGF-2 signaling in the neural stem cell niche

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    Aurelien Kerever

    2014-03-01

    Full Text Available In the adult subventricular zone (neurogenic niche, neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.

  17. Astrocitary niches in human adult medulla oblongata.

    Science.gov (United States)

    Rusu, Mugurel Constantin; Dermengiu, Dan; Loreto, Carla; Motoc, Andrei Gheorghe Marius; Pop, Elena

    2013-04-01

    Astrocytes are considered as neuromodulators of the CNS. Whereas experimental studies on astrocitary functions are gaining importance, the anatomy of the astrocitary niches in the human CNS has been overlooked. The study was performed on the brainstem of 10 adult cadavers. We aimed to determine astrocitary niches in the human medulla oblongata using immunohistochemical labeling with vimentin and also CD34 immunostaining to accurately diagnose associated microvessels. Niches rich in astrocytes were identified as follows: (a) the superficial layer of astrocytes, ventral and ventrolateral, in the rostral medulla oblongata; (b) the median raphe; (c) medullary nuclei: arcuate nucleus, area postrema, nucleus of the solitary tract; (d) the subependymal zone (SEZ, caudal medulla) and subventricular zone (SVZ, rostral medulla). Astrocytes were scarce in the ventrolateral medulla, and mostly present within the pyramidal tract and the olivary nucleus. Apart from the SEZ and SVZ, the brainstem niches of astrocytes mostly overlap those regions known to perform roles as central respiratory chemoreceptors. The astrocytes of the SEZ and SVZ, which are known as stem cell niches, are related to an increased microvascular density. Copyright © 2012 Elsevier GmbH. All rights reserved.

  18. Is forebrain neurogenesis a potential repair mechanism after stroke?

    OpenAIRE

    Inta, Dragos; Gass, Peter

    2015-01-01

    The use of adult subventricular zone (SVZ) neurogenesis as brain repair strategy after stroke represents a hot topic in neurologic research. Recent radiocarbon-14 dating has revealed a lack of poststroke neurogenesis in the adult human neocortex; however, adult neurogenesis has been shown to occur, even under physiologic conditions, in the human striatum. Here, these results are contrasted with experimental poststroke neurogenesis in the murine brain. Both in humans and in rodents, the SVZ ge...

  19. Retinoic acid-pretreated Wharton's jelly mesenchymal stem cells in combination with triiodothyronine improve expression of neurotrophic factors in the subventricular zone of the rat ischemic brain injury.

    Science.gov (United States)

    Sabbaghziarani, Fatemeh; Mortezaee, Keywan; Akbari, Mohammad; Kashani, Iraj Ragerdi; Soleimani, Mansooreh; Moini, Ashraf; Ataeinejad, Nahid; Zendedel, Adib; Hassanzadeh, Gholamreza

    2017-02-01

    Stroke is the consequence of limited blood flow to the brain with no established treatment to reduce the neurological deficits. Focusing on therapeutic protocols in targeting subventricular zone (SVZ) neurogenesis has been investigated recently. This study was designed to evaluate the effects of retinoic acid (RA)-pretreated Wharton's jelly mesenchymal stem cells (WJ-MSCs) in combination with triiodothyronine (T3) in the ischemia stroke model. Male Wistar rats were used to induce focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were seven groups of six animals: Sham, Ischemic, WJ-MSCs, RA-pretreated WJ-MSCs, T3, WJ-MSCs +T3, and RA-pretreated WJ-MSCs + T3. The treatment was performed at 24 h after ischemia, and animals were sacrificed one week later for assessments of retinoid X receptor β (RXRβ), brain-derived neurotrophic factor (BDNF), Sox2 and nestin in the SVZ. Pro-inflammatory cytokines in sera were measured at days four and seven after ischemia. RXRβ, BDNF, Sox2 and nestin had the significant expressions in gene and protein levels in the treatment groups, compared with the ischemic group, which were more vivid in the RA-pretreated WJ-MSCs + T3 (p ≤ 0.05). The same trend was also resulted for the levels of TNF-α and IL-6 at four days after ischemia (p ≤ 0.05). In conclusion, application of RA-pretreated WJ-MSCs + T3 could be beneficial in exerting better neurotrophic function probably via modulation of pro-inflammatory cytokines.

  20. Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain

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    Michalina Respondek

    2015-12-01

    Full Text Available Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC, which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

  1. The Role of Adult-Born Neurons in the Constantly Changing Olfactory Bulb Network

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    Sarah Malvaut

    2016-01-01

    Full Text Available The adult mammalian brain is remarkably plastic and constantly undergoes structurofunctional modifications in response to environmental stimuli. In many regions plasticity is manifested by modifications in the efficacy of existing synaptic connections or synapse formation and elimination. In a few regions, however, plasticity is brought by the addition of new neurons that integrate into established neuronal networks. This type of neuronal plasticity is particularly prominent in the olfactory bulb (OB where thousands of neuronal progenitors are produced on a daily basis in the subventricular zone (SVZ and migrate along the rostral migratory stream (RMS towards the OB. In the OB, these neuronal precursors differentiate into local interneurons, mature, and functionally integrate into the bulbar network by establishing output synapses with principal neurons. Despite continuous progress, it is still not well understood how normal functioning of the OB is preserved in the constantly remodelling bulbar network and what role adult-born neurons play in odor behaviour. In this review we will discuss different levels of morphofunctional plasticity effected by adult-born neurons and their functional role in the adult OB and also highlight the possibility that different subpopulations of adult-born cells may fulfill distinct functions in the OB neuronal network and odor behaviour.

  2. The Role of Adult-Born Neurons in the Constantly Changing Olfactory Bulb Network

    Science.gov (United States)

    Malvaut, Sarah; Saghatelyan, Armen

    2016-01-01

    The adult mammalian brain is remarkably plastic and constantly undergoes structurofunctional modifications in response to environmental stimuli. In many regions plasticity is manifested by modifications in the efficacy of existing synaptic connections or synapse formation and elimination. In a few regions, however, plasticity is brought by the addition of new neurons that integrate into established neuronal networks. This type of neuronal plasticity is particularly prominent in the olfactory bulb (OB) where thousands of neuronal progenitors are produced on a daily basis in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) towards the OB. In the OB, these neuronal precursors differentiate into local interneurons, mature, and functionally integrate into the bulbar network by establishing output synapses with principal neurons. Despite continuous progress, it is still not well understood how normal functioning of the OB is preserved in the constantly remodelling bulbar network and what role adult-born neurons play in odor behaviour. In this review we will discuss different levels of morphofunctional plasticity effected by adult-born neurons and their functional role in the adult OB and also highlight the possibility that different subpopulations of adult-born cells may fulfill distinct functions in the OB neuronal network and odor behaviour. PMID:26839709

  3. Brain Barriers and a Subpopulation of Astroglial Progenitors of Developing Human Forebrain Are Immunostained for the Glycoprotein YKL-40

    DEFF Research Database (Denmark)

    Bjørnbak, Camilla; Brøchner, Christian B; Larsen, Lars A

    2014-01-01

    and subventricular zones showed specific YKL-40 reactivity confined to pericytes. Furthermore, a population of YKL-40-positive, small, rounded cells was identified in the ventricular and subventricular zones. Real-time quantitative RT-PCR analysis showed strong YKL-40 mRNA expression in the leptomeninges...

  4. Fledgling survival increases with development time and adult survival across north and south temperate zones

    Science.gov (United States)

    Lloyd, Penn; Martin, Thomas E.

    2016-01-01

    Slow life histories are characterized by high adult survival and few offspring, which are thought to allow increased investment per offspring to increase juvenile survival. Consistent with this pattern, south temperate zone birds are commonly longer-lived and have fewer young than north temperate zone species. However, comparative analyses of juvenile survival, including during the first few weeks of the post-fledging period when most juvenile mortality occurs, are largely lacking. We combined our measurements of fledgling survival for eight passerines in South Africa with estimates from published studies of 57 north and south temperate zone songbird species to test three predictions: (1) fledgling survival increases with length of development time in the nest; (2) fledgling survival increases with adult survival and reduced brood size controlled for development time; and (3) south temperate zone species, with their higher adult survival and smaller brood sizes, exhibit higher fledgling survival than north temperate zone species controlled for development time. We found that fledgling survival was higher among south temperate zone species and generally increased with development time and adult survival within and between latitudinal regions. Clutch size did not explain additional variation, but was confounded with adult survival. Given the importance of age-specific mortality to life history evolution, understanding the causes of these geographical patterns of mortality is important.

  5. Upregulated expression of Nogo-A and NgR in an experimental model of focal microgyria regulates the migration, proliferation and self-renewal of subventricular zone neural progenitors

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Sixun; Shu, Haifeng; Yang, Tao; Huang, Haidong [Department of Neurosurgery, General Hospital of the People' s Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083 (China); Li, Song [Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Zhao, Ziyi [Central Laboratory, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, 610075 (China); Kuang, Yongqin, E-mail: kuangyongqin@163.com [Department of Neurosurgery, General Hospital of the People' s Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083 (China)

    2016-04-29

    Nogo-A and its receptor (NgR) were first described as myelin-associated inhibitors of neuronal regeneration in response to injury. In recent years, knowledge about the important role of the Nogo-A protein in several neuronal pathologies has grown considerably. Here, we employed a neonatal cortex freeze-lesion (NFL) model in neonatal rats and measured the expression of Nogo-A and NgR in the resulting cerebrocortical microdysgenesis 5–75 days after freezing injury. We observed marked upregulation of Nogo-A and NgR in protein levels. Furthermore, the migration of neural precursor cells (NPCs) derived from the subventricular zone (SVZ) toward the sits of injury was perturbed by treatment of NgR antagonist peptide NEP1-40. In vitro analysis showed that the knockdown of NgR by lentivirus-delivered siRNA promoted in axonal regeneration and SVZ-derived neural stem cell/progenitor cell (SVZ-NPCs) adhesion and migration, findings which were similar to the effects of NEP1-40. Taken together, our results indicate an important role for NgR in regulating the physiological processes of SVZ-NPCs. The observation of upregulated Nogo-A/NgR in lesion sites in the NFL model suggest that the effects of the perturbed Nogo-A are a key feature during the development and/or the progression of cortical malformation. - Highlights: • NFL model is an accurate experimental reproduction of focal microgyria of FCD. • The increase of the Nogo-A Levels occurs in response to freeze-induced focal lesioning. • Nogo-A/NgR may play a critical role for in the pathologic progression of FCD. • Nogo-A is associated with the migration, proliferation and self-renewal of SVZ-NPCs.

  6. Low levels of endogenous or X-ray-induced DNA double-strand breaks activate apoptosis in adult neural stem cells.

    Science.gov (United States)

    Barazzuol, Lara; Rickett, Nicole; Ju, Limei; Jeggo, Penny A

    2015-10-01

    The embryonic neural stem cell compartment is characterised by rapid proliferation from embryonic day (E)11 to E16.5, high endogenous DNA double-strand break (DSB) formation and sensitive activation of apoptosis. Here, we ask whether DSBs arise in the adult neural stem cell compartments, the sub-ventricular zone (SVZ) of the lateral ventricles and the sub-granular zone (SGZ) of the hippocampal dentate gyrus, and whether they activate apoptosis. We used mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C)), ataxia telangiectasia mutated (Atm(-/-)) and double mutant Atm(-/-)/Lig4(Y288C) mice. We demonstrate that, although DSBs do not arise at a high frequency in adult neural stem cells, the low numbers of DSBs that persist endogenously in Lig4(Y288C) mice or that are induced by low radiation doses can activate apoptosis. A temporal analysis shows that DSB levels in Lig4(Y288C) mice diminish gradually from the embryo to a steady state level in adult mice. The neonatal SVZ compartment of Lig4(Y288C) mice harbours diminished DSBs compared to its differentiated counterpart, suggesting a process selecting against unfit stem cells. Finally, we reveal high endogenous apoptosis in the developing SVZ of wild-type newborn mice. © 2015. Published by The Company of Biologists Ltd.

  7. A Distinct Population of Microglia Supports Adult Neurogenesis in the Subventricular Zone

    DEFF Research Database (Denmark)

    Ribeiro Xavier, Anna L.; Kress, Benjamin T.; Goldman, Steven A.

    2015-01-01

    found that microglia residing in the SVZ and adjacent rostral migratory stream (RMS) comprise a morphologically and antigenically distinct phenotype of immune effectors. Whereas exhibiting characteristics of alternatively activated microglia, the SVZ/RMS microglia were clearly distinguished by their low...... STATEMENT: Microglial cells are a specialized population of macrophages in the CNS, playing key roles as immune mediators. As integral components in the CNS, the microglia stand out for using the same mechanisms, phagocytosis and cytochemokine release, to promote homeostasis, synaptic pruning, and neural...... toward olfactory bulb layers. In addition to other unique populations residing in the SVZ niche, microglia display distinct morphofunctional properties that boost neuronal progenitor survival and migration in the mammalian brain....

  8. 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.

  9. Inducible Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis in the Olfactory Bulb and Improves Olfactory Function

    Science.gov (United States)

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M.; Xu, Lihong; Storm, Daniel R.

    2015-01-01

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. PMID:25995470

  10. Exosomes as novel regulators of adult neurogenic niches

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    Luis Federico Batiz

    2016-01-01

    Full Text Available Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ of the dentate gyrus (DG in the hippocampus, and the sub-ventricular zone (SVZ of the lateral ventricles. SGZ newborn neurons are destined to the granular cell layer of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb. The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs, which reside in a unique and specialized microenvironment known as neurogenic niche. Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs. EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs, proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their roles in adult

  11. Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

    Science.gov (United States)

    Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

    2010-10-01

    In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

  12. Effects of neuroinflammation on the regenerative capacity of brain stem cells

    OpenAIRE

    Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

    2011-01-01

    In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system ...

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

    International Nuclear Information System (INIS)

    Barazzuol, Lara; Jeggo, Penny A.

    2016-01-01

    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

  14. Activities and Ecological Role of Adult Aquatic Insects in the Riparian Zone of Streams

    Science.gov (United States)

    John K. Jackson; Vincent H. Resh

    1989-01-01

    Most adult aquatic insects that emerge from streams live briefly in the nearby riparian zone. Adult activities, such as mating, dispersal, and feeding, influence their distribution in the terrestrial habitat. A study at Big Sulphur Creek, California, has shown that both numbers and biomass of adult aquatic insects are greatest in the near-stream vegetation; however,...

  15. Adult Neurogenesis in Sheep: Characterization and Contribution to Reproduction and Behavior

    Science.gov (United States)

    Lévy, Frederic; Batailler, Martine; Meurisse, Maryse; Migaud, Martine

    2017-01-01

    Sheep have many advantages to study neurogenesis in comparison to the well-known rodent models. Their development and life expectancy are relatively long and they possess a gyrencephalic brain. Sheep are also seasonal breeders, a characteristic that allows studying the involvement of hypothalamic neurogenesis in the control of seasonal reproduction. Sheep are also able to individually recognize their conspecifics and develop selective and lasting bonds. Adult olfactory neurogenesis could be adapted to social behavior by supporting recognition of conspecifics. The present review reveals the distinctive features of the hippocampal, olfactory, and hypothalamic neurogenesis in sheep. In particular, the organization of the subventricular zone and the dynamic of neuronal maturation differs from that of rodents. In addition, we show that various physiological conditions, such as seasonal reproduction, gestation, and lactation differently modulate these three neurogenic niches. Last, we discuss recent evidence indicating that hypothalamic neurogenesis acts as an important regulator of the seasonal control of reproduction and that olfactory neurogenesis could be involved in odor processing in the context of maternal behavior. PMID:29109674

  16. Posttraining ablation of adult-generated olfactory granule cells degrades odor-reward memories.

    Science.gov (United States)

    Arruda-Carvalho, Maithe; Akers, Katherine G; Guskjolen, Axel; Sakaguchi, Masanori; Josselyn, Sheena A; Frankland, Paul W

    2014-11-19

    Proliferation of neural progenitor cells in the subventricular zone leads to the continuous generation of new olfactory granule cells (OGCs) throughout life. These cells synaptically integrate into olfactory bulb circuits after ∼2 weeks and transiently exhibit heightened plasticity and responses to novel odors. Although these observations suggest that adult-generated OGCs play important roles in olfactory-related memories, global suppression of olfactory neurogenesis does not typically prevent the formation of odor-reward memories, perhaps because residual OGCs can compensate. Here, we used a transgenic strategy to selectively ablate large numbers of adult-generated OGCs either before or after learning in mice. Consistent with previous studies, pretraining ablation of adult-generated OGCs did not prevent the formation of an odor-reward memory, presumably because existing OGCs can support memory formation in their absence. However, ablation of a similar cohort of adult-generated OGCs after training impaired subsequent memory expression, indicating that if these cells are available at the time of training, they play an essential role in subsequent expression of odor-reward memories. Memory impairment was associated with the loss of adult-generated OGCs that were >10 d in age and did not depend on the developmental stage in which they were generated, suggesting that, once sufficiently mature, OGCs generated during juvenility and adulthood play similar roles in the expression of odor-reward memories. Finally, ablation of adult-generated OGCs 1 month after training did not produce amnesia, indicating that adult-generated OGCs play a time-limited role in the expression of odor-reward memories. Copyright © 2014 the authors 0270-6474/14/3415793-11$15.00/0.

  17. Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.

    Science.gov (United States)

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M; Xu, Lihong; Storm, Daniel R; Xia, Zhengui

    2015-05-20

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. Copyright © 2015 the authors 0270-6474/15/357833-17$15.00/0.

  18. Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal Differentiation of Adult SVZ Progenitors

    Directory of Open Access Journals (Sweden)

    Jasmine Kolb

    2018-04-01

    Full Text Available Summary: Adult neurogenesis is regulated by stem cell niche-derived extrinsic factors and cell-intrinsic regulators, yet the mechanisms by which niche signals impinge on the activity of intrinsic neurogenic transcription factors remain poorly defined. Here, we report that MEIS2, an essential regulator of adult SVZ neurogenesis, is subject to posttranslational regulation in the SVZ olfactory bulb neurogenic system. Nuclear accumulation of MEIS2 in adult SVZ-derived progenitor cells follows downregulation of EGFR signaling and is modulated by methylation of MEIS2 on a conserved arginine, which lies in close proximity to nested binding sites for the nuclear export receptor CRM1 and the MEIS dimerization partner PBX1. Methylation impairs interaction with CRM1 without affecting PBX1 dimerization and thereby allows MEIS2 nuclear accumulation, a prerequisite for neuronal differentiation. Our results describe a form of posttranscriptional modulation of adult SVZ neurogenesis whereby an extrinsic signal fine-tunes neurogenesis through posttranslational modification of a transcriptional regulator of cell fate. : A hallmark of adult neurogenesis is its strong dependence on physiological stimuli and environmental signals. Schulte and colleagues show that the nuclear localization and activity of a transcriptional regulator of adult neurogenesis is controlled by posttranslational modification. Their results link intrinsic control over neuron production to external signals and help to explain how adult neurogenesis can occur “on demand.” Keywords: subventricular zone, stem cell niche, posttranslational modification, controlled nuclear import, TALE-homdomain protein, MEIS2, PBX1, CRM1, neurogenesis, stem cell niche

  19. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Increased 5-hydroxymethylation levels in the sub ventricular zone of the Alzheimer's brain

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    Diego Mastroeni

    2016-06-01

    Full Text Available The subventricular zone (SVZ is a site of neurogenesis in the aging brain, and epigenetic mechanisms have been implicated in regulating the “normal” distribution of new nerve cells into the existing cellular milieu. In a case-control study of human primary SVZ cultures and fixed tissue from the same individuals, we have found significant increases in DNA hydroxymethylation levels in the SVZ of Alzheimer's disease patients compared with nondiseased control subjects. We show that this increase in hydroxymethylation directly correlates to an increase in cellular proliferation in Alzheimer's disease precursor cells, which implicates the hydroxymethylation tag to a higher degree of cellular proliferation.

  1. 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. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  2. Hyperexpressed netrin-1promoted neural stem cells migration in mice after focal cerebral ischemia

    OpenAIRE

    Haiyan Lu; Xiaoyan Song; Feng Wang; Guodong Wang; Yuncheng Wu; Qiaoshu Wang; Yongting Wang; Guoyuan Yang; Zhijun Zhang

    2016-01-01

    Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explored whether NT-1 can be steadily overexpressed by adeno-associated virus (AAV) and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with AAV carrying NT-1 gene (AAV-NT-1). Mice underwent ...

  3. Chronic fluoxetine treatment in middle-aged rats induces changes in the expression of plasticity-related molecules and in neurogenesis

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    Guirado Ramon

    2012-01-01

    Full Text Available Abstract Background Antidepressants promote neuronal structural plasticity in young-adult rodents, but little is known of their effects on older animals. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM may mediate these structural changes through its anti-adhesive properties. PSA-NCAM is expressed in immature neurons and in a subpopulation of mature interneurons and its expression is modulated by antidepressants in the telencephalon of young-adult rodents. Results We have analyzed the effects of 14 days of fluoxetine treatment on the density of puncta expressing PSA-NCAM and different presynaptic markers in the medial prefrontal cortex, hippocampus and amygdala of middle-aged (8 months old rats. The density of puncta expressing PSA-NCAM increased in the dorsal cingulate cortex, as well as in different hippocampal and amygdaloid regions. In these later regions there were also increases in the density of puncta expressing glutamic acid decarboxylase 65/67 (GAD6, synaptophysin (SYN, PSA-NCAM/SYN and PSA-NCAM/GAD6, but a decrease of those expressing vesicular glutamate transporter 1 (VGluT1. Since there is controversy on the effects of antidepressants on neurogenesis during aging, we analyzed the number of proliferating cells expressing Ki67 and that of immature neurons expressing doublecortin or PSA-NCAM. No significant changes were found in the subgranular zone, but the number of proliferating cells decreased in the subventricular zone. Conclusions These results indicate that the effects of fluoxetine in middle-aged rats are different to those previously described in young-adult animals, being more restricted in the mPFC and even following an opposite direction in the amygdala or the subventricular zone.

  4. 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.

  5. Adult and Child Development in the Zone of Proximal Development: Socratic Dialogue in a Playworld

    Science.gov (United States)

    Ferholt, Beth; Lecusay, Robert

    2010-01-01

    This article analyses adult and child development in the zone of proximal development in an educational practice based in Vygotsky's theories of play: the playworld educational practice. The playworld educational practice is a central component of a Scandinavian play pedagogy that promotes shared responsibility amongst adults and children for…

  6. SSEA-4 and YKL-40 positive progenitor subtypes in the subventricular zone of developing human neocortex

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Møllgård, Kjeld

    2016-01-01

    The glycosphingolipid SSEA-4 and the glycoprotein YKL-40 have both been associated with human embryonic and neural stem cell differentiation. We investigated the distribution of SSEA-4 and YKL-40 positive cells in proliferative zones of human fetal forebrain using immunohistochemistry and double-...

  7. In vivo transcriptional profile analysis reveals RNA splicing and chromatin remodeling as prominent processes for adult neurogenesis.

    Science.gov (United States)

    Lim, Daniel A; Suárez-Fariñas, Mayte; Naef, Felix; Hacker, Coleen R; Menn, Benedicte; Takebayashi, Hirohide; Magnasco, Marcelo; Patil, Nila; Alvarez-Buylla, Arturo

    2006-01-01

    Neural stem cells and neurogenesis persist in the adult mammalian brain subventricular zone (SVZ). Cells born in the rodent SVZ migrate to the olfactory bulb (Ob) where they differentiate into interneurons. To determine the gene expression and functional profile of SVZ neurogenesis, we performed three complementary sets of transcriptional analysis experiments using Affymetrix GeneChips: (1) comparison of adult mouse SVZ and Ob gene expression profiles with those of the striatum, cerebral cortex, and hippocampus; (2) profiling of SVZ stem cells and ependyma isolated by fluorescent-activated cell sorting (FACS); and (3) analysis of gene expression changes during in vivo SVZ regeneration after anti-mitotic treatment. Gene Ontology (GO) analysis of data from these three separate approaches showed that in adult SVZ neurogenesis, RNA splicing and chromatin remodeling are biological processes as statistically significant as cell proliferation, transcription, and neurogenesis. In non-neurogenic brain regions, RNA splicing and chromatin remodeling were not prominent processes. Fourteen mRNA splicing factors including Sf3b1, Sfrs2, Lsm4, and Khdrbs1/Sam68 were detected along with 9 chromatin remodeling genes including Mll, Bmi1, Smarcad1, Baf53a, and Hat1. We validated the transcriptional profile data with Northern blot analysis and in situ hybridization. The data greatly expand the catalogue of cell cycle components, transcription factors, and migration genes for adult SVZ neurogenesis and reveal RNA splicing and chromatin remodeling as prominent biological processes for these germinal cells.

  8. The adult spinal cord harbors a population of GFAP-positive progenitors with limited self-renewal potential.

    Science.gov (United States)

    Fiorelli, Roberto; Cebrian-Silla, Arantxa; Garcia-Verdugo, Jose-Manuel; Raineteau, Olivier

    2013-12-01

    Adult neural stem cells (aNSCs) of the forebrain are GFAP-expressing cells that are intercalated within ependymal cells of the subventricular zone (SVZ). Cells showing NSCs characteristics in vitro can also be isolated from the periaqueductal region in the adult spinal cord (SC), but contradicting results exist concerning their glial versus ependymal identity. We used an inducible transgenic mouse line (hGFAP-CreERT2) to conditionally label GFAP-expressing cells in the adult SVZ and SC periaqueduct, and directly and systematically compared their self-renewal and multipotential properties in vitro. We demonstrate that a population of GFAP(+) cells that share the morphology and the antigenic properties of SVZ-NSCs mostly reside in the dorsal aspect of the central canal (CC) throughout the spinal cord. These cells are non-proliferative in the intact spinal cord, but incorporate the S-phase marker EdU following spinal cord injury. Multipotent, clonal YFP-expressing neurospheres (i.e., deriving from recombined GFAP-expressing cells) were successfully obtained from both the intact and injured spinal cord. These spheres however showed limited self-renewal properties when compared with SVZ-neurospheres, even after spinal cord injury. Altogether, these results demonstrate that significant differences exist in NSCs lineages between neurogenic and non-neurogenic regions of the adult CNS. Thus, although we confirm that a population of multipotent GFAP(+) cells co-exists alongside with multipotent ependymal cells within the adult SC, we identify these cells as multipotent progenitors showing limited self-renewal properties. Copyright © 2013 Wiley Periodicals, Inc.

  9. Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

    Science.gov (United States)

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

    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 analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.

  10. Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb

    Directory of Open Access Journals (Sweden)

    LaRocca Greg

    2007-11-01

    Full Text Available Abstract Background New neurons are generated in the adult brain from stem cells found in the subventricular zone (SVZ. These cells proliferate in the SVZ, generating neuroblasts which then migrate to the main olfactory bulb (MOB, ending their migration in the glomerular layer (GLL and the granule cell layer (GCL of the MOB. Neuronal populations in these layers undergo turnover throughout life, but whether all neuronal subtypes found in these areas are replaced and when neurons begin to express subtype-specific markers is not known. Results Here we use BrdU injections and immunohistochemistry against (calretinin, calbindin, N-copein, tyrosine hydroxylase and GABA and show that adult-generated neurons express markers of all major subtypes of neurons in the GLL and GCL. Moreover, the fractions of new neurons that express subtype-specific markers at 40 and 75 days post BrdU injection are very similar to the fractions of all neurons expressing these markers. We also show that many neurons in the glomerular layer do not express NeuN, but are readily and specifically labeled by the fluorescent nissl stain Neurotrace. Conclusion The expression of neuronal subtype-specific markers by new neurons in the GLL and GCL changes rapidly during the period from 14–40 days after BrdU injection before reaching adult levels. This period may represent a critical window for cell fate specification similar to that observed for neuronal survival.

  11. Transcriptional profiling of adult neural stem-like cells from the human brain.

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    Cecilie Jonsgar Sandberg

    Full Text Available There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60. Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate. We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6, foetal human neural stem cells (n = 1 and human brain tissues (n = 12. The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular

  12. Effects of curcumin on short-term spatial and recognition memory, adult neurogenesis and neuroinflammation in a streptozotocin-induced rat model of dementia of Alzheimer's type.

    Science.gov (United States)

    Bassani, Taysa B; Turnes, Joelle M; Moura, Eric L R; Bonato, Jéssica M; Cóppola-Segovia, Valentín; Zanata, Silvio M; Oliveira, Rúbia M M W; Vital, Maria A B F

    2017-09-29

    Curcumin is a natural polyphenol with evidence of antioxidant, anti-inflammatory and neuroprotective properties. Recent evidence also suggests that curcumin increases cognitive performance in animal models of dementia, and this effect would be related to its capacity to enhance adult neurogenesis. The aim of this study was to test the hypothesis that curcumin treatment would be able to preserve cognition by increasing neurogenesis and decreasing neuroinflammation in the model of dementia of Alzheimer's type induced by an intracerebroventricular injection of streptozotocin (ICV-STZ) in Wistar rats. The animals were injected with ICV-STZ or vehicle and curcumin treatments (25, 50 and 100mg/kg, gavage) were performed for 30days. Four weeks after surgery, STZ-lesioned animals exhibited impairments in short-term spatial memory (Object Location Test (OLT) and Y maze) and short-term recognition memory (Object Recognition Test - ORT), decreased cell proliferation and immature neurons (Ki-67- and doublecortin-positive cells, respectively) in the subventricular zone (SVZ) and dentate gyrus (DG) of hippocampus, and increased immunoreactivity for the glial markers GFAP and Iba-1 (neuroinflammation). Curcumin treatment in the doses of 50 and 100mg/kg prevented the deficits in recognition memory in the ORT, but not in spatial memory in the OLT and Y maze. Curcumin treatment exerted only slight improvements in neuroinflammation, resulting in no improvements in hippocampal and subventricular neurogenesis. These results suggest a positive effect of curcumin in object recognition memory which was not related to hippocampal neurogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. IGF-I: A key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain

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    Vanesa eNieto-Estévez

    2016-02-01

    Full Text Available The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs. This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP and the subventricular zone-olfactory bulb (SVZ-OB. By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also, by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis and neuron integration in synaptic circuits.

  14. IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

    Science.gov (United States)

    Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

    2016-01-01

    The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

  15. Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

    Science.gov (United States)

    López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

    2016-01-01

    Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice

  16. Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

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    Shengxiu Li

    Full Text Available 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 analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.

  17. Neural Stem Cells: Implications for the Conventional Radiotherapy of Central Nervous System Malignancies

    International Nuclear Information System (INIS)

    Barani, Igor J.; Benedict, Stanley H.; Lin, Peck-Sun

    2007-01-01

    Advances in basic neuroscience related to neural stem cells and their malignant counterparts are challenging traditional models of central nervous system tumorigenesis and intrinsic brain repair. Neurogenesis persists into adulthood predominantly in two neurogenic centers: subventricular zone and subgranular zone. Subventricular zone is situated adjacent to lateral ventricles and subgranular zone is confined to the dentate gyrus of the hippocampus. Neural stem cells not only self-renew and differentiate along multiple lineages in these regions, but also contribute to intrinsic brain plasticity and repair. Ionizing radiation can depopulate these exquisitely sensitive regions directly or impair in situ neurogenesis by indirect, dose-dependent and inflammation-mediated mechanisms, even at doses <2 Gy. This review discusses the fundamental neural stem cell concepts within the framework of cumulative clinical experience with the treatment of central nervous system malignancies using conventional radiotherapy

  18. Molecular Targets of Chromatin Repressive Mark H3K9me3 in Primate Progenitor Cells within Adult Neurogenic Niches

    Directory of Open Access Journals (Sweden)

    Michael R Foret

    2014-07-01

    Full Text Available Histone 3 Lysine 9 (H3K9 methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3 is enriched in an adult neural stem cell niche- the subventricular zone (SVZ on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche.

  19. Transplanted Adult Neural Stem Cells Express Sonic Hedgehog In Vivo and Suppress White Matter Neuroinflammation after Experimental Traumatic Brain Injury

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    Genevieve M. Sullivan

    2017-01-01

    Full Text Available Neural stem cells (NSCs delivered intraventricularly may be therapeutic for diffuse white matter pathology after traumatic brain injury (TBI. To test this concept, NSCs isolated from adult mouse subventricular zone (SVZ were transplanted into the lateral ventricle of adult mice at two weeks post-TBI followed by analysis at four weeks post-TBI. We examined sonic hedgehog (Shh signaling as a candidate mechanism by which transplanted NSCs may regulate neuroregeneration and/or neuroinflammation responses of endogenous cells. Mouse fluorescent reporter lines were generated to enable in vivo genetic labeling of cells actively transcribing Shh or Gli1 after transplantation and/or TBI. Gli1 transcription is an effective readout for canonical Shh signaling. In ShhCreERT2;R26tdTomato mice, Shh was primarily expressed in neurons and was not upregulated in reactive astrocytes or microglia after TBI. Corroborating results in Gli1CreERT2;R26tdTomato mice demonstrated that Shh signaling was not upregulated in the corpus callosum, even after TBI or NSC transplantation. Transplanted NSCs expressed Shh in vivo but did not increase Gli1 labeling of host SVZ cells. Importantly, NSC transplantation significantly reduced reactive astrogliosis and microglial/macrophage activation in the corpus callosum after TBI. Therefore, intraventricular NSC transplantation after TBI significantly attenuated neuroinflammation, but did not activate host Shh signaling via Gli1 transcription.

  20. Functional organization of the transcriptome in human brain

    Science.gov (United States)

    Oldham, Michael C; Konopka, Genevieve; Iwamoto, Kazuya; Langfelder, Peter; Kato, Tadafumi; Horvath, Steve; Geschwind, Daniel H

    2009-01-01

    The enormous complexity of the human brain ultimately derives from a finite set of molecular instructions encoded in the human genome. These instructions can be directly studied by exploring the organization of the brain’s transcriptome through systematic analysis of gene coexpression relationships. We analyzed gene coexpression relationships in microarray data generated from specific human brain regions and identified modules of coexpressed genes that correspond to neurons, oligodendrocytes, astrocytes and microglia. These modules provide an initial description of the transcriptional programs that distinguish the major cell classes of the human brain and indicate that cell type–specific information can be obtained from whole brain tissue without isolating homogeneous populations of cells. Other modules corresponded to additional cell types, organelles, synaptic function, gender differences and the subventricular neurogenic niche. We found that subventricular zone astrocytes, which are thought to function as neural stem cells in adults, have a distinct gene expression pattern relative to protoplasmic astrocytes. Our findings provide a new foundation for neurogenetic inquiries by revealing a robust and previously unrecognized organization to the human brain transcriptome. PMID:18849986

  1. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

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    Kuan Zhang

    Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

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

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    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.

  3. Adult and embryonic GAD transcripts are spatiotemporally regulated during postnatal development in the rat brain.

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    Anke Popp

    Full Text Available BACKGROUND: GABA (gamma-aminobutyric acid, the main inhibitory neurotransmitter in the brain, is synthesized by glutamic acid decarboxylase (GAD. GAD exists in two adult isoforms, GAD65 and GAD67. During embryonic brain development at least two additional transcripts exist, I-80 and I-86, which are distinguished by insertions of 80 or 86 bp into GAD67 mRNA, respectively. Though it was described that embryonic GAD67 transcripts are not detectable during adulthood there are evidences suggesting re-expression under certain pathological conditions in the adult brain. In the present study we systematically analyzed for the first time the spatiotemporal distribution of different GADs with emphasis on embryonic GAD67 mRNAs in the postnatal brain using highly sensitive methods. METHODOLOGY/PRINCIPAL FINDINGS: QPCR was used to precisely investigate the postnatal expression level of GAD related mRNAs in cortex, hippocampus, cerebellum, and olfactory bulb of rats from P1 throughout adulthood. Within the first three postnatal weeks the expression of both GAD65 and GAD67 mRNAs reached adult levels in hippocampus, cortex, and cerebellum. The olfactory bulb showed by far the highest expression of GAD65 as well as GAD67 transcripts. Embryonic GAD67 splice variants were still detectable at birth. They continuously declined to barely detectable levels during postnatal development in all investigated regions with exception of a comparatively high expression in the olfactory bulb. Radioactive in situ hybridizations confirmed the occurrence of embryonic GAD67 transcripts in the olfactory bulb and furthermore detected their localization mainly in the subventricular zone and the rostral migratory stream. CONCLUSIONS/SIGNIFICANCE: Embryonic GAD67 transcripts can hardly be detected in the adult brain, except for specific regions associated with neurogenesis and high synaptic plasticity. Therefore a functional role in processes like proliferation, migration or

  4. Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia

    Science.gov (United States)

    Ferland, Russell J.; Batiz, Luis Federico; Neal, Jason; Lian, Gewei; Bundock, Elizabeth; Lu, Jie; Hsiao, Yi-Chun; Diamond, Rachel; Mei, Davide; Banham, Alison H.; Brown, Philip J.; Vanderburg, Charles R.; Joseph, Jeffrey; Hecht, Jonathan L.; Folkerth, Rebecca; Guerrini, Renzo; Walsh, Christopher A.; Rodriguez, Esteban M.; Sheen, Volney L.

    2009-01-01

    Periventricular heterotopia (PH) is a disorder characterized by neuronal nodules, ectopically positioned along the lateral ventricles of the cerebral cortex. Mutations in either of two human genes, Filamin A (FLNA) or ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2), cause PH (Fox et al. in ‘Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia'. Neuron, 21, 1315–1325, 1998; Sheen et al. in ‘Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex'. Nat. Genet., 36, 69–76, 2004). Recent studies have shown that mutations in mitogen-activated protein kinase kinase kinase-4 (Mekk4), an indirect interactor with FlnA, also lead to periventricular nodule formation in mice (Sarkisian et al. in ‘MEKK4 signaling regulates filamin expression and neuronal migration'. Neuron, 52, 789–801, 2006). Here we show that neurons in post-mortem human PH brains migrated appropriately into the cortex, that periventricular nodules were primarily composed of later-born neurons, and that the neuroependyma was disrupted in all PH cases. As studied in the mouse, loss of FlnA or Big2 function in neural precursors impaired neuronal migration from the germinal zone, disrupted cell adhesion and compromised neuroepithelial integrity. Finally, the hydrocephalus with hop gait (hyh) mouse, which harbors a mutation in Napa [encoding N-ethylmaleimide-sensitive factor attachment protein alpha (α-SNAP)], also develops a progressive denudation of the neuroepithelium, leading to periventicular nodule formation. Previous studies have shown that Arfgef2 and Napa direct vesicle trafficking and fusion, whereas FlnA associates dynamically with the Golgi membranes during budding and trafficking of transport vesicles. Our current findings suggest that PH formation arises from a final common pathway involving disruption of vesicle trafficking, leading to impaired cell

  5. Leptin-dependent neurotoxicity via induction of apoptosis in adult rat neural stem cells

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    Stéphanie eSEGURA

    2015-09-01

    Full Text Available Adipocyte-derived hormone leptin has been recently implicated in the control of neuronal plasticity. To explore whether modulation of adult neurogenesis may contribute to leptin control of neuronal plasticity, we used the neurosphere assay of neural stem cells derived from the adult rat subventricular zone (SVZ. Endogenous expression of specific leptin receptor (ObRb transcripts, as revealed by RT-PCR, is associated with activation of both ERK and STAT-3 pathways via phosphorylation of the critical ERK/STAT-3 amino acid residues upon addition of leptin to neurospheres. Furthermore, leptin triggered withdrawal of neural stem cells from the cell cycle as monitored by Ki67 labelling. This effect was blocked by pharmacological inhibition of ERK activation thus demonstrating that ERK mediates leptin effects on neural stem cell expansion. Leptin-dependent withdrawal of neural stem cells from the cell cycle was associated with increased apoptosis, as detected by TUNEL, which was preceded by cyclin D1 induction. Cyclin D1 was indeed extensively colocalized with TUNEL-positive apoptotic cells. Cyclin-D1 silencing by specific shRNA prevented leptin-induced decrease of the cell number per neurosphere thus pointing to the causal relationship between leptin actions on apoptosis and cyclin D1 induction. Leptin target cells in SVZ neurospheres were identified by double TUNEL/phenotypic marker immunocytofluorescence as differentiating neurons mostly. The inhibition of neural stem cell expansion via ERK/cyclin D1-triggered apoptosis defines novel biological action of leptin which may be involved in adiposity-dependent neurotoxicity.

  6. Hippocampal Neurogenesis, Depressive Disorders, and Antidepressant Therapy

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    Eleni Paizanis

    2007-01-01

    Full Text Available There is a growing body of evidence that neural stem cells reside in the adult central nervous system where neurogenesis occurs throughout lifespan. Neurogenesis concerns mainly two areas in the brain: the subgranular zone of the dentate gyrus in the hippocampus and the subventricular zone, where it is controlled by several trophic factors and neuroactive molecules. Neurogenesis is involved in processes such as learning and memory and accumulating evidence implicates hippocampal neurogenesis in the physiopathology of depression. We herein review experimental and clinical data demonstrating that stress and antidepressant treatments affect neurogenesis in opposite direction in rodents. In particular, the stimulation of hippocampal neurogenesis by all types of antidepressant drugs supports the view that neuroplastic phenomena are involved in the physiopathology of depression and underlie—at least partly—antidepressant therapy.

  7. Functional studies of microRNAs in neural stem cells: problems and perspectives.

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    Malin eÅkerblom

    2012-02-01

    Full Text Available In adult mammals, neural stem cells (NSCs are found in two niches of the brain; the subventricular zone at the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Neurogenesis is a complex process that is tightly controlled on a molecular level. Recently, microRNAs (miRNAs have been implicated to play a central role in the regulation of NCSs. miRNAs are small, endogenously expressed RNAs that regulate gene expression at the post-transcriptional level. However, functional studies of miRNAs are complicated due to current technical limitations. In this review we describe recent findings about miRNAs in NSCs looking closely at miR-124, miR-9 and let-7. We also highlight technical strategies used to investigate miRNA function, accentuating limitations and potentials.

  8. Conical expansion of the outer subventricular zone and the role of neocortical folding in evolution and development

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    Eric eLewitus

    2013-08-01

    Full Text Available There is a basic rule to mammalian neocortical expansion: as it expands, so does it fold. The degree to which it folds, however, cannot strictly be attributed to its expansion. Across species, cortical volume does not keep pace with cortical surface area, but rather folds appear more rapidly than expected. As a result, larger brains quickly become disproportionately more convoluted than smaller brains. Both the absence (lissencephaly and presence (gyrencephaly of cortical folds is observed in all mammalian orders and, while there is likely some phylogenetic signature to the evolutionary appearance of gyri and sulci, there are undoubtedly universal trends to the acquisition of folds in an expanding neocortex. Whether these trends are governed by conical expansion of neocortical germinal zones, the distribution of cortical connectivity, or a combination of growth- and connectivity-driven forces remains an open question. But the importance of cortical folding for evolution of the uniquely mammalian neocortex, as well as for the incidence of neuropathologies in humans, is undisputed. In this hypothesis and theory article, we will summarize the development of cortical folds in the neocortex, consider the relative influence of growth- versus connectivity-driven forces for the acquisition of cortical folds between and within species, assess the genetic, cell-biological, and mechanistic implications for neocortical expansion, and discuss the significance of these implications for human evolution, development, and disease. We will argue that evolutionary increases in the density of neuron production, achieved via maintenance of a basal proliferative niche in the neocortical germinal zones, drive the conical migration of neurons towards the cortical surface and ultimately lead to the establishment of cortical folds in large-brained mammal species.

  9. Irradiation in adulthood as a new model of schizophrenia.

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    Yasuhide Iwata

    Full Text Available BACKGROUND: Epidemiological studies suggest that radiation exposure may be a potential risk factor for schizophrenia in adult humans. Here, we investigated whether adult irradiation in rats caused behavioral abnormalities relevant to schizophrenia. METHODOLOGY/PRINCIPAL FINDINGS: A total dose of 15-Gy irradiation in six fractionations during 3 weeks was exposed to the forebrain including the subventricular zone (SVZ and subgranular zone (SGZ with male rats in the prone position. Behavioral, immunohistochemical, and neurochemical studies were performed three months after fractionated ionizing irradiation. Three months after fractionated ionizing irradiation, the total numbers of BrdU-positive cells in both the SVZ and SGZ zones of irradiated rats were significantly lower than those of control (sham-irradiated rats. Hyperactivity after administration of the dopaminergic agonist methamphetamine, but not the N-methyl-D-aspartate (NMDA receptor antagonist dizocilpine, was significantly enhanced in the irradiated rats although spontaneous locomotion in the irradiated rats was significantly lower than that of controls. Behavioral abnormalities including auditory sensory gating deficits, social interaction deficits, and working memory deficits were observed in the irradiated rats. CONCLUSION/SIGNIFICANCE: The present study suggests that irradiation in adulthood caused behavioral abnormalities relevant to schizophrenia, and that reduction of adult neurogenesis by irradiation may be associated with schizophrenia-like behaviors in rats.

  10. Effects of Maternal Behavior Induction and Pup Exposure on Neurogenesis in Adult, Virgin Female Rats

    Science.gov (United States)

    Furuta, Miyako; Bridges, Robert S.

    2009-01-01

    The states of pregnancy and lactation bring about a range of physiological and behavioral changes in the adult mammal that prepare the mother to care for her young. Cell proliferation increases in the subventricular zone (SVZ) of the female rodent brain during both pregnancy and lactation when compared to that in cycling, diestrous females. In the present study, the effects of maternal behavior induction and pup exposure on neurogenesis in nulliparous rats were examined in order to determine whether maternal behavior itself, independent of pregnancy and lactation, might affect neurogenesis. Adult, nulliparous, Sprague-Dawley, female rats were exposed daily to foster young in order to induce maternal behavior. Following the induction of maternal behavior each maternal subject plus females that were exposed to pups for a comparable number of test days, but did not display maternal behavior, and subjects that had received no pup exposure were injected with bromodeoxyuridine (BrdU, 90 mg/kg, i.v.). Brain sections were double-labeled for BrdU and the neural marker, NeuN, to examine the proliferating cell population. Increases in the number of double-labeled cells were found in the maternal virgin brain when compared with the number of double-labeled cells present in non-maternal, pup-exposed nulliparous rats and in females not exposed to young. No changes were evident in the dentate gyrus of the hippocampus as a function of maternal behavior. These data indicate that in nulliparous female rats maternal behavior itself is associated with the stimulation of neurogenesis in the SVZ. PMID:19712726

  11. Lineage analysis of quiescent regenerative stem cells in the adult brain by genetic labelling reveals spatially restricted neurogenic niches in the olfactory bulb.

    Science.gov (United States)

    Giachino, Claudio; Taylor, Verdon

    2009-07-01

    The subventricular zone (SVZ) of the lateral ventricles is the major neurogenic region in the adult mammalian brain, harbouring neural stem cells within defined niches. The identity of these stem cells and the factors regulating their fate are poorly understood. We have genetically mapped a population of Nestin-expressing cells during postnatal development to study their potential and fate in vivo. Taking advantage of the recombination characteristics of a nestin::CreER(T2) allele, we followed a subpopulation of neural stem cells and traced their fate in a largely unrecombined neurogenic niche. Perinatal nestin::CreER(T2)-expressing cells give rise to multiple glial cell types and neurons, as well as to stem cells of the adult SVZ. In the adult SVZ nestin::CreER(T2)-expressing neural stem cells give rise to several neuronal subtypes in the olfactory bulb (OB). We addressed whether the same population of neural stem cells play a role in SVZ regeneration. Following anti-mitotic treatment to eliminate rapidly dividing progenitors, relatively quiescent nestin::CreER(T2)-targeted cells are spared and contribute to SVZ regeneration, generating new proliferating precursors and neuroblasts. Finally, we have identified neurogenic progenitors clustered in ependymal-like niches within the rostral migratory stream (RMS) of the OB. These OB-RMS progenitors generate neuroblasts that, upon transplantation, graft, migrate and differentiate into granule and glomerular neurons. In summary, using conditional lineage tracing we have identified neonatal cells that are the source of neurogenic and regenerative neural stem cells in the adult SVZ and occupy a novel neurogenic niche in the OB.

  12. Dannelse af nye nerveceller i den voksne hjerne

    DEFF Research Database (Denmark)

    Poulsen, Frantz Rom; Meyer, Morten; Rasmussen, Jens Zimmer

    2003-01-01

    neurogenesis in the adult human brain. In particular two brain regions show continuous division of neural stem and progenitor cells generating neurons and glial cells, namely the subgranular zone of the dentate gyrus and the subventricular zones of the lateral ventricles. From the latter region newly generated......Generation of new nerve cells (neurogenesis) is normally considered to be limited to the fetal and early postnatal period. Thus, damaged nerve cells are not expected to be replaced by generation of new cells. The brain is, however, more plastic than previously assumed. This also includes...... neuroblasts (immature nerve cells) migrate toward the olfactory bulb where they differentiate into neurons. In the dentate gyrus the newly generated neurons become functionally integrated in the granule cell layer, where they are believed to be of importance to learning and memory. It is at present not known...

  13. Thyroid hormone participates in the regulation of neural stem cells and oligodendrocyte precursor cells in the central nervous system of adult rat.

    Science.gov (United States)

    Fernandez, M; Pirondi, S; Manservigi, M; Giardino, L; Calzà, L

    2004-10-01

    Oligodendrocyte development and myelination are under thyroid hormone control. In this study we analysed the effects of chronic manipulation of thyroid status on the expression of a wide spectrum of oligodendrocyte precursor cells (OPCs) markers and myelin basic protein (MBP) in the subventricular zone (SVZ), olfactory bulb and optic nerve, and on neural stem cell (NSC) lineage in adult rats. Hypo- and hyperthyroidism were induced in male rats, by propyl-thio-uracil (PTU) and L-thyroxin (T4) treatment, respectively. Hypothyroidism increased and hyperthyroidism downregulated proliferation in the SVZ and olfactory bulb (Ki67 immunohistochemistry and Western blotting, bromodeoxyuridine uptake). Platelet-derived growth factor receptor alpha (PDGFalpha-R) and MBP mRNA levels decreased in the optic nerve of hypothyroid rats; the same also occurred at the level of MBP protein. Hyperthyroidism slightly upregulates selected markers such as NG2 in the olfactory bulb. The lineage of cells derived from primary cultures of NSC prepared from the forebrain of adult hypo- and hyperthyroid also differs from those derived from control animals. Although no difference of in vitro proliferation of NSCs was observed in the presence of epidermal growth factor, maturation of oligodendrocytes (defined by process number and length) was enhanced in hyperthyroidism, suggesting a more mature state than in control animals. This difference was even greater when compared with the hypothyroid group, the morphology of which suggested a delay in differentiation. These results indicate that thyroid hormone affects NSC and OPC proliferation and maturation also in adulthood.

  14. Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling.

    Science.gov (United States)

    Dong, Huimin; Lin, Xi; Li, Yuntao; Hu, Ronghua; Xu, Yang; Guo, Xiaojie; La, Qiong; Wang, Shun; Fang, Congcong; Guo, Junli; Li, Qi; Mao, Shanping; Liu, Baohui

    2017-10-31

    Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics through the Rho kinase-dependent signaling pathway. We previously demonstrated that mice with genetic deletion of Rnd3 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice developed an enlarged subventricular zone, and we identify a novel role for Rnd3 as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in vivo and in vitro , resulted in increased levels of Notch intracellular domain protein. This led to enhanced Notch signaling and promotion of aberrant neural stem cell growth, thereby resulting in a larger subventricular zone and a markedly larger brain. Inhibition of Notch activity abrogated this aberrant neural stem cell growth.

  15. Bilateral Transplantation of Allogenic Adult Human Bone Marrow-Derived Mesenchymal Stem Cells into the Subventricular Zone of Parkinson’s Disease: A Pilot Clinical Study

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    N. K. Venkataramana

    2012-01-01

    Full Text Available The progress of PD and its related disorders cannot be prevented with the medications available. In this study, we recruited 8 PD and 4 PD plus patients between 5 to 15 years after diagnosis. All patients received BM-MSCs bilaterally into the SVZ and were followed up for 12 months. PD patients after therapy reported a mean improvement of 17.92% during “on” and 31.21% during “off” period on the UPDRS scoring system. None of the patients increased their medication during the follow-up period. Subjectively, the patients reported clarity in speech, reduction in tremors, rigidity, and freezing attacks. The results correlated with the duration of the disease. Those patients transplanted in the early stages of the disease (less than 5 years showed more improvement and no further disease progression than the later stages (11–15 years. However, the PD plus patients did not show any change in their clinical status after stem cell transplantation. This study demonstrates the safety of adult allogenic human BM-MSCs transplanted into the SVZ of the brain and its efficacy in early-stage PD patients.

  16. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    International Nuclear Information System (INIS)

    Evers, Patrick; Lee, Percy P; DeMarco, John; Agazaryan, Nzhde; Sayre, James W; Selch, Michael; Pajonk, Frank

    2010-01-01

    Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs

  17. Of Mice and Men: Neurogenesis, Cognition and Alzheimer’s disease

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    Orly eLazarov

    2013-08-01

    Full Text Available Neural stem cells are maintained in the subgranular layer of the dentate gyrus and in the subventricular zone in the adult mammalian brain throughout life. Neurogenesis is continuous, but its extent is tightly regulated by environmental factors, behavior, hormonal state, age and brain health. Increasing evidence supports a role for new neurons in cognitive function in rodents. Recent evidence delineates potential significant differences between adult neurogenesis in rodents and humans. Being context-dependent, neurogenesis in the human brain might be manifested differently than in the rodent brain. Decline in neurogenesis may play a role in cognitive deterioration, leading to the development of progressive learning and memory disorders, such as Alzheimer’s disease. This review discusses the different observations concerning neurogenesis in the rodent and human brain, and their functional implications for the healthy and diseased brain.

  18. The NKG2D ligands RAE-1δ and RAE-1ε differ with respect to their receptor affinity, expression profiles and transcriptional regulation

    DEFF Research Database (Denmark)

    Cédile, Oriane; Popa, Natalia; Pollet-Villard, Frédéric

    2010-01-01

    RAE-1 is a ligand of the activating receptor NKG2D expressed by NK cells, NKT, γδT and some CD8(+)T lymphocytes. RAE-1 is overexpressed in tumor cell lines and its expression is induced after viral infection and genotoxic stress. We have recently demonstrated that RAE-1 is expressed in the adult...... subventricular zone (SVZ) from C57BL/6 mice. RAE-1 is also expressed in vitro by neural stem/progenitor cells (NSPCs) and plays a non-immune role in cell proliferation. The C57BL/6 mouse genome contains two rae-1 genes, rae-1δ and rae-1ε encoding two different proteins. The goals of this study are first...

  19. Telocytes in meninges and choroid plexus.

    Science.gov (United States)

    Popescu, B O; Gherghiceanu, M; Kostin, S; Ceafalan, L; Popescu, L M

    2012-05-16

    Telocytes (TCs) are a recently identified type of interstitial cells present in a wide variety of organs in humans and mammals (www.telocytes.com). They are characterized by a small cell body, but extremely long cell processes - telopodes (Tp), and a specific phenotype. TCs establish close contacts with blood capillaries, nerve fibers and stem cells. We report here identification of TCs by electron microscopy and immunofluorescence in rat meninges and choroid plexus/subventricular zone, in the vicinity of putative stem cells. The presence of TCs in brain areas involved in adult neurogenesis might indicate that they have a role in modulation of neural stem cell fate. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Developmental Patterns of Doublecortin Expression and White Matter Neuron Density in the Postnatal Primate Prefrontal Cortex and Schizophrenia

    Science.gov (United States)

    Fung, Samantha J.; Joshi, Dipesh; Allen, Katherine M.; Sivagnanasundaram, Sinthuja; Rothmond, Debora A.; Saunders, Richard; Noble, Pamela L.; Webster, Maree J.; Shannon Weickert, Cynthia

    2011-01-01

    Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC). Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX), a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque) and density of white matter neurons (humans) during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37) and matched controls (n = 37) and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in schizophrenia. PMID

  1. Developmental patterns of doublecortin expression and white matter neuron density in the postnatal primate prefrontal cortex and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Samantha J Fung

    Full Text Available Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC. Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX, a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque and density of white matter neurons (humans during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37 and matched controls (n = 37 and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in

  2. Nestin Reporter Transgene Labels Multiple Central Nervous System Precursor Cells

    Directory of Open Access Journals (Sweden)

    Avery S. Walker

    2010-01-01

    Full Text Available Embryonic neuroepithelia and adult subventricular zone (SVZ stem and progenitor cells express nestin. We characterized a transgenic line that expresses enhanced green fluorescent protein (eGFP specified to neural tissue by the second intronic enhancer of the nestin promoter that had several novel features. During embryogenesis, the dorsal telencephalon contained many and the ventral telencephalon few eGFP+ cells. eGFP+ cells were found in postnatal and adult neurogenic regions. eGFP+ cells in the SVZ expressed multiple phenotype markers, glial fibrillary acidic protein, Dlx, and neuroblast-specific molecules suggesting the transgene is expressed through the lineage. eGFP+ cell numbers increased in the SVZ after cortical injury, suggesting this line will be useful in probing postinjury neurogenesis. In non-neurogenic regions, eGFP was strongly expressed in oligodendrocyte progenitors, but not in astrocytes, even when they were reactive. This eGFP+ mouse will facilitate studies of proliferative neuroepithelia and adult neurogenesis, as well as of parenchymal oligodendrocytes.

  3. Putative Adult Neurogenesis in Old World Parrots: The Congo African Grey Parrot (Psittacus erithacus and Timneh Grey Parrot (Psittacus timneh

    Directory of Open Access Journals (Sweden)

    Pedzisai Mazengenya

    2018-02-01

    Full Text Available In the current study, we examined for the first time, the potential for adult neurogenesis throughout the brain of the Congo African grey parrot (Psittacus erithacus and Timneh grey parrot (Psittacus timneh using immunohistochemistry for the endogenous markers proliferating cell nuclear antigen (PCNA, which labels proliferating cells, and doublecortin (DCX, which stains immature and migrating neurons. A similar distribution of PCNA and DCX immunoreactivity was found throughout the brain of the Congo African grey and Timneh grey parrots, but minor differences were also observed. In both species of parrots, PCNA and DCX immunoreactivity was observed in the olfactory bulbs, subventricular zone of the lateral wall of the lateral ventricle, telencephalic subdivisions of the pallium and subpallium, diencephalon, mesencephalon and the rhombencephalon. The olfactory bulb and telencephalic subdivisions exhibited a higher density of both PCNA and DCX immunoreactive cells than any other brain region. DCX immunoreactive staining was stronger in the telencephalon than in the subtelencephalic structures. There was evidence of proliferative hot spots in the dorsal and ventral poles of the lateral ventricle in the Congo African grey parrots at rostral levels, whereas only the dorsal accumulation of proliferating cells was observed in the Timneh grey parrot. In most pallial regions the density of PCNA and DCX stained cells increased from rostral to caudal levels with the densest staining in the nidopallium caudolaterale (NCL. The widespread distribution of PCNA and DCX in the brains of both parrot species suggest the importance of adult neurogenesis and neuronal plasticity during learning and adaptation to external environmental variations.

  4. Putative Adult Neurogenesis in Old World Parrots: The Congo African Grey Parrot (Psittacus erithacus) and Timneh Grey Parrot (Psittacus timneh).

    Science.gov (United States)

    Mazengenya, Pedzisai; Bhagwandin, Adhil; Manger, Paul R; Ihunwo, Amadi O

    2018-01-01

    In the current study, we examined for the first time, the potential for adult neurogenesis throughout the brain of the Congo African grey parrot ( Psittacus erithacus ) and Timneh grey parrot ( Psittacus timneh ) using immunohistochemistry for the endogenous markers proliferating cell nuclear antigen (PCNA), which labels proliferating cells, and doublecortin (DCX), which stains immature and migrating neurons. A similar distribution of PCNA and DCX immunoreactivity was found throughout the brain of the Congo African grey and Timneh grey parrots, but minor differences were also observed. In both species of parrots, PCNA and DCX immunoreactivity was observed in the olfactory bulbs, subventricular zone of the lateral wall of the lateral ventricle, telencephalic subdivisions of the pallium and subpallium, diencephalon, mesencephalon and the rhombencephalon. The olfactory bulb and telencephalic subdivisions exhibited a higher density of both PCNA and DCX immunoreactive cells than any other brain region. DCX immunoreactive staining was stronger in the telencephalon than in the subtelencephalic structures. There was evidence of proliferative hot spots in the dorsal and ventral poles of the lateral ventricle in the Congo African grey parrots at rostral levels, whereas only the dorsal accumulation of proliferating cells was observed in the Timneh grey parrot. In most pallial regions the density of PCNA and DCX stained cells increased from rostral to caudal levels with the densest staining in the nidopallium caudolaterale (NCL). The widespread distribution of PCNA and DCX in the brains of both parrot species suggest the importance of adult neurogenesis and neuronal plasticity during learning and adaptation to external environmental variations.

  5. Neurogenesis in the aging brain.

    Science.gov (United States)

    Apple, Deana M; Solano-Fonseca, Rene; Kokovay, Erzsebet

    2017-10-01

    Adult neurogenesis is the process of producing new neurons from neural stem cells (NSCs) for integration into the brain circuitry. Neurogenesis occurs throughout life in the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. However, during aging, NSCs and their progenitors exhibit reduced proliferation and neuron production, which is thought to contribute to age-related cognitive impairment and reduced plasticity that is necessary for some types of brain repair. In this review, we describe NSCs and their niches during tissue homeostasis and how they undergo age-associated remodeling and dysfunction. We also discuss some of the functional ramifications in the brain from NSC aging. Finally, we discuss some recent insights from interventions in NSC aging that could eventually translate into therapies for healthy brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Running rescues defective adult neurogenesis by shortening the length of the cell cycle of neural stem and progenitor cells.

    Science.gov (United States)

    Farioli-Vecchioli, Stefano; Mattera, Andrea; Micheli, Laura; Ceccarelli, Manuela; Leonardi, Luca; Saraulli, Daniele; Costanzi, Marco; Cestari, Vincenzo; Rouault, Jean-Pierre; Tirone, Felice

    2014-07-01

    Physical exercise increases the generation of new neurons in adult neurogenesis. However, only few studies have investigated the beneficial effects of physical exercise in paradigms of impaired neurogenesis. Here, we demonstrate that running fully reverses the deficient adult neurogenesis within the hippocampus and subventricular zone of the lateral ventricle, observed in mice lacking the antiproliferative gene Btg1. We also evaluated for the first time how running influences the cell cycle kinetics of stem and precursor subpopulations of wild-type and Btg1-null mice, using a new method to determine the cell cycle length. Our data show that in wild-type mice running leads to a cell cycle shortening only of NeuroD1-positive progenitor cells. In contrast, in Btg1-null mice, physical exercise fully reactivates the defective hippocampal neurogenesis, by shortening the S-phase length and the overall cell cycle duration of both neural stem (glial fibrillary acidic protein(+) and Sox2(+)) and progenitor (NeuroD1(+)) cells. These events are sufficient and necessary to reactivate the hyperproliferation observed in Btg1-null early-postnatal mice and to expand the pool of adult neural stem and progenitor cells. Such a sustained increase of cell proliferation in Btg1-null mice after running provides a long-lasting increment of proliferation, differentiation, and production of newborn neurons, which rescues the impaired pattern separation previously identified in Btg1-null mice. This study shows that running positively affects the cell cycle kinetics of specific subpopulations of newly generated neurons and suggests that the plasticity of neural stem cells without cell cycle inhibitory control is reactivated by running, with implications for the long-term modulation of neurogenesis. © 2014 AlphaMed Press.

  7. Expression and cellular localization of hepcidin mRNA and protein in normal rat brain

    Czech Academy of Sciences Publication Activity Database

    Raha-Chowdhury, R.; Raha, A.A.; Forostyak, Serhiy; Zhao, J.W.; Stott, S.R.W.; Bomford, A.

    2015-01-01

    Roč. 16, APR 21 (2015), s. 24 ISSN 1471-2202 Institutional support: RVO:68378041 Keywords : hepcidin * ferroportin * defensin * inflammatory cytokines * brain iron homeostasis * blood brain barrier * pericytes * sub-ventricular zone * neurogenesis Subject RIV: FH - Neurology Impact factor: 2.304, year: 2015

  8. Communities on the Move: Pedestrian-Oriented Zoning as a Facilitator of Adult Active Travel to Work in the United States.

    Science.gov (United States)

    Chriqui, Jamie F; Leider, Julien; Thrun, Emily; Nicholson, Lisa M; Slater, Sandy

    2016-01-01

    Communities across the United States have been reforming their zoning codes to create pedestrian-friendly neighborhoods with increased street connectivity, mixed use and higher density, open space, transportation infrastructure, and a traditional neighborhood structure. Zoning code reforms include new urbanist zoning such as the SmartCode, form-based codes, transects, transportation and pedestrian-oriented developments, and traditional neighborhood developments. To examine the relationship of zoning code reforms and more active living--oriented zoning provisions with adult active travel to work via walking, biking, or by using public transit. Zoning codes effective as of 2010 were compiled for 3,914 municipal-level jurisdictions located in 471 counties and 2 consolidated cities in 48 states and the District of Columbia, and that collectively covered 72.9% of the U.S. population. Zoning codes were evaluated for the presence of code reform zoning and nine pedestrian-oriented zoning provisions (1 = yes): sidewalks, crosswalks, bike-pedestrian connectivity, street connectivity, bike lanes, bike parking, bike-pedestrian trails/paths, mixed-use development, and other walkability/pedestrian orientation. A zoning scale reflected the number of provisions addressed (out of 10). Five continuous outcome measures were constructed using 2010-2014 American Community Survey municipal-level 5-year estimates to assess the percentage of workers: walking, biking, walking or biking, or taking public transit to work OR engaged in any active travel to work. Regression models controlled for municipal-level socioeconomic characteristics and a GIS-constructed walkability scale and were clustered on county with robust standard errors. Adjusted models indicated that several pedestrian-oriented zoning provisions were statistically associated (p biking, or engaging in any active travel (walking, biking, or any active travel) to work: code reform zoning, bike parking (street furniture

  9. Plasmodium berghei ANKA: erythropoietin activates neural stem cells in an experimental cerebral malaria model

    DEFF Research Database (Denmark)

    Core, Andrew; Hempel, Casper; Kurtzhals, Jørgen A L

    2011-01-01

    investigated if EPO's neuroprotective effects include activation of endogenous neural stem cells (NSC). By using immunohistochemical markers of different NSC maturation stages, we show that EPO increased the number of nestin(+) cells in the dentate gyrus and in the sub-ventricular zone of the lateral...

  10. Impaired TGF-beta induced growth inhibition contributes to the increased proliferation rate of neural stem cells harboring mutant p53

    DEFF Research Database (Denmark)

    Kumar, Praveen; Naumann, Ulrike; Aigner, Ludwig

    2015-01-01

    Gliomas have been classified according to their histological properties. However, their respective cells of origin are still unknown. Neural progenitor cells (NPC) from the subventricular zone (SVZ) can initiate tumors in murine models of glioma and are likely cells of origin in the human disease...

  11. Early Postnatal but Not Late Adult Neurogenesis Is Impaired in the Pitx3-Mutant Animal Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Moritz D. Brandt

    2017-08-01

    Full Text Available The generation of new neurons in the adult dentate gyrus has functional implications for hippocampal formation. Reduced hippocampal neurogenesis has been described in various animal models of hippocampal dysfunction such as dementia and depression, which are both common non-motor-symptoms of Parkinson's disease (PD. As dopamine plays an important role in regulating precursor cell proliferation, the loss of dopaminergic neurons in the substantia nigra (SN in PD may be related to the reduced neurogenesis observed in the neurogenic regions of the adult brain: subventricular zone (SVZ and dentate gyrus (DG. Here we examined adult hippocampal neurogenesis in the Pitx3-mutant mouse model of PD (aphakia mice, which phenotypically shows a selective embryonic degeneration of dopamine neurons within the SN and to a smaller extent in the ventral tegmental area (VTA. Proliferating cells were labeled with BrdU in aphakia mice and healthy controls from 3 to 42 weeks of age. Three weeks old mutant mice showed an 18% reduction of proliferating cells in the DG and of 26% in the SVZ. Not only proliferation but also the number of new neurons was impaired in young aphakia mice resulting in 33% less newborn cells 4 weeks after BrdU-labeling. Remarkably, however, the decline in the number of proliferating cells in the neurogenic regions vanished in older animals (8–42 weeks indicating that aging masks the effect of dopamine depletion on adult neurogenesis. Region specific reduction in precursor cells proliferation correlated with the extent of dopaminergic degeneration in mesencephalic subregions (VTA and SN, which supports the theory of age- and region-dependent regulatory effects of dopaminergic projections. Physiological stimulation of adult neurogenesis by physical activity (wheel running almost doubled the number of proliferating cells in the dentate gyrus of 8 weeks old aphakia mice to a number comparable to that of wild-type mice, abolishing the slight

  12. A brain slice culture model for studies of endogenous and exogenous precursor cell migration in the rostral migratory stream

    DEFF Research Database (Denmark)

    Tanvig, Mette; Blaabjerg, Morten; Andersen, Rikke K

    2009-01-01

    The rostral migratory stream (RMS) is the main pathway by which newly born subventricular zone (SVZ) cells reach the olfactory bulb (OB) in rodents. This migration has been well studied in vivo, but an organotypic in vitro model would facilitate more experimental investigations. Here we introduce...

  13. A cell junction pathology of neural stem cells leads to abnormal neurogenesis and hydrocephalus

    NARCIS (Netherlands)

    Rodríguez, Esteban M; Guerra, María M; Vío, Karin; González, César; Ortloff, Alexander; Bátiz, Luis F; Rodríguez, Sara; Jara, María C; Muñoz, Rosa I; Ortega, Eduardo; Jaque, Jaime; Guerra, Francisco; Sival, Deborah A; den Dunnen, Wilfred F A; Jiménez, Antonio J; Domínguez-Pinos, María D; Pérez-Fígares, José M; McAllister, James P; Johanson, Conrad

    2012-01-01

    Most cells of the developing mammalian brain derive from the ventricular (VZ) and the subventricular (SVZ) zones. The VZ is formed by the multipotent radial glia/neural stem cells (NSCs) while the SVZ harbors the rapidly proliferative neural precursor cells (NPCs). Evidence from human and animal

  14. EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex.

    Science.gov (United States)

    Kanemitsu, Michiko; Tsupykov, Oleg; Potter, Gaël; Boitard, Michael; Salmon, Patrick; Zgraggen, Eloisa; Gascon, Eduardo; Skibo, Galina; Dayer, Alexandre G; Kiss, Jozsef Z

    2017-11-01

    Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system. We found that EMMPRIN-transduced progenitors exhibited enhanced MMP-2 activity in vitro and showed improved motility in 3D collagen gel as well as in cortical slices. Using a rat model of neonatal ischemia, we showed that EMMPRIN overexpressing SVZ cells invade the injured cortical tissue more efficiently than controls. Our results suggest that EMMPRIN overexpression could be suitable approach to improve capacities of endogenous or transplanted progenitors to invade the injured cortex. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Communities on the move: Pedestrian-oriented zoning as a facilitator of adult active travel to work in the United States

    Directory of Open Access Journals (Sweden)

    Jamie Friedman Chriqui

    2016-04-01

    Full Text Available Background: Communities across the United States have been reforming their zoning codes to create pedestrian-friendly neighborhoods with increased street connectivity, mixed-use and higher density, open space, transportation infrastructure, and a traditional neighborhood structure. Zoning code reforms include new urbanist zoning such as the SmartCode, form-based codes, transects, transportation and pedestrian-oriented developments, and traditional neighborhood developments.Purpose: To examine the relationship of zoning code reforms and more active living-oriented zoning provisions with adult active travel to work via walking, biking, or by using public transit.Methods: Zoning codes effective as of 2010 were compiled for 3,914 municipal-level jurisdictions located in 471 counties and 2 consolidated cities in 48 states and the District of Columbia, and that collectively covered 72.9% of the U.S. population. Zoning codes were evaluated for the presence of code reform zoning and nine pedestrian-oriented zoning provisions (1=yes: sidewalks, crosswalks, bike-pedestrian connectivity, street connectivity, bike lanes, bike parking, bike-pedestrian trails/paths, mixed use development, and other walkability/pedestrian-orientation. A zoning scale reflected the number of provisions addressed (out of 10. Five continuous outcome measures were constructed using 2010-2014 American Community Survey municipal-level 5-year estimates to assess the percentage of workers: walking, biking, walking or biking, or taking public transit to work OR engaged in any active travel to work. Regression models controlled for municipal-level socioeconomic characteristics and a GIS-constructed walkability scale and were clustered on county with robust standard errors. Results: Adjusted models indicated that several pedestrian-oriented zoning provisions were statistically associated (p<.05 or lower with increased rates of walking, biking, or engaging in any active travel (walking

  16. Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury.

    Science.gov (United States)

    Llorens-Bobadilla, Enric; Zhao, Sheng; Baser, Avni; Saiz-Castro, Gonzalo; Zwadlo, Klara; Martin-Villalba, Ana

    2015-09-03

    Heterogeneous pools of adult neural stem cells (NSCs) contribute to brain maintenance and regeneration after injury. The balance of NSC activation and quiescence, as well as the induction of lineage-specific transcription factors, may contribute to diversity of neuronal and glial fates. To identify molecular hallmarks governing these characteristics, we performed single-cell sequencing of an unbiased pool of adult subventricular zone NSCs. This analysis identified a discrete, dormant NSC subpopulation that already expresses distinct combinations of lineage-specific transcription factors during homeostasis. Dormant NSCs enter a primed-quiescent state before activation, which is accompanied by downregulation of glycolytic metabolism, Notch, and BMP signaling and a concomitant upregulation of lineage-specific transcription factors and protein synthesis. In response to brain ischemia, interferon gamma signaling induces dormant NSC subpopulations to enter the primed-quiescent state. This study unveils general principles underlying NSC activation and lineage priming and opens potential avenues for regenerative medicine in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The male sex pheromone darcin stimulates hippocampal neurogenesis and cell proliferation in the subventricular zone in female mice

    Directory of Open Access Journals (Sweden)

    Emma eHoffman

    2015-04-01

    Full Text Available The integration of newly generated neurons persists throughout life in the mammalian olfactory bulb and hippocampus, regions involved in olfactory and spatial learning. Social cues can be potent stimuli for increasing adult neurogenesis; for example, odors from dominant but not subordinate male mice increase neurogenesis in both brain regions of adult females. However, little is known about the role of neurogenesis in social recognition or the assessment of potential mates. Dominant male mice scent-mark territories using urine that contains a number of pheromones including darcin (MUP20, a male-specific major urinary protein that stimulates rapid learned attraction to the spatial location and individual odor signature of the scent owner. Here we investigate whether exposure to darcin stimulates neurogenesis in the female brain. Hippocampal neurons and cellular proliferation in the lateral ventricles that supply neurons to the olfactory bulbs increased in females exposed for seven days to male urine containing at least 0.5µg/µl darcin. Darcin was effective whether presented alone or in the context of male urine, but other information in male urine appeared to modulate the proliferative response. When exposed to urine from wild male mice, hippocampal proliferation increased only if urine was from the same individual over seven days, suggesting that consistency of individual scent signatures is important. While seven days exposure to male scent initiated the first stages of increased neurogenesis, this caused no immediate increase in female attraction to the scent or in the strength or robustness of spatial learning in short-term conditioned place preference tests. The reliable and consistent stimulation of neurogenesis by a pheromone important in rapid social learning suggests that this may provide an excellent model to explore the relationship between the integration of new neurons and plasticity in spatial and olfactory learning in a socially

  18. Axons take a dive

    Science.gov (United States)

    Tong, Cheuk Ka; Cebrián-Silla, Arantxa; Paredes, Mercedes F; Huang, Eric J; García-Verdugo, Jose Manuel; Alvarez-Buylla, Arturo

    2015-01-01

    In the walls of the lateral ventricles of the adult mammalian brain, neural stem cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular–subventricular zone (V–SVZ). In a recent article, we show that supraependymal serotonergic (5HT) axons originating from the raphe nuclei in mice form an extensive plexus on the walls of the lateral ventricles where they contact E1 cells and NSCs. Here we further characterize the contacts between 5HT supraependymal axons and E1 cells in mice, and show that suprependymal axons tightly associated to E1 cells are also present in the walls of the human lateral ventricles. These observations raise interesting questions about the function of supraependymal axons in the regulation of E1 cells. PMID:26413556

  19. Environmental enrichment, age and PPARα interact to regulate proliferation in neurogenic niches

    Directory of Open Access Journals (Sweden)

    Margarita ePerez-Martin

    2016-03-01

    Full Text Available Peroxisome proliferator-activated receptor alpha (PPARα ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC in the adult brain. The study was performed in aged Pparα-/- mice exposed to nutritional (treats and environmental (games enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2’-deoxyuridine (BrdU+ and the immature neuronal marker doublecortin (Dcx+ in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ, subventricular zone of lateral ventricles (SVZ and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, 18 months. Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα-/- mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα-/--induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα-/- mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments.

  20. Altered morphologies and functions of the olfactory bulb and hippocampus induced by miR-30c

    Directory of Open Access Journals (Sweden)

    Tingting eSun

    2016-05-01

    Full Text Available Adult neurogenesis is considered to contribute to a certain degree of plasticity for the brain. However, the effects of adult-born neurons on the brain are still largely unknown. Here, we specifically altered the expression of miR-30c in the subventricular zone (SVZ and dentate gyrus (DG by stereotaxic injection with their respective up-and down-regulated lentiviruses. Results showed an increased level of miR-30c enhanced adult neurogenesis by prompting cell-cycles of stem cells, whereas down-regulated miR-30c led to the opposite results. When these effects of miR-30c lasted for three months, we detected significant morphological changes in the olfactory bulb (OB and lineage alteration in the hippocampus. Tests of olfactory sensitivity and associative and spatial memory showed that a certain amount of adult-born neurons are essential for the normal functions of the OB and hippocampus, but there also exist redundant newborn neurons that do not further improve the functioning of these areas. Our study revealed the interactions between miRNA, adult neurogenesis, brain morphology and function, and this provides a novel insight into understanding the role of newborn neurons in the adult brain.

  1. Identifying endogenous neural stem cells in the adult brain in vitro and in vivo: novel approaches.

    Science.gov (United States)

    Rueger, Maria Adele; Androutsellis-Theotokis, Andreas

    2013-01-01

    In the 1960s, Joseph Altman reported that the adult mammalian brain is capable of generating new neurons. Today it is understood that some of these neurons are derived from uncommitted cells in the subventricular zone lining the lateral ventricles, and the dentate gyrus of the hippocampus. The first area generates new neuroblasts which migrate to the olfactory bulb, whereas hippocampal neurogenesis seems to play roles in particular types of learning and memory. A part of these uncommitted (immature) cells is able to divide and their progeny can generate all three major cell types of the nervous system: neurons, astrocytes, and oligodendrocytes; these properties define such cells as neural stem cells. Although the roles of these cells are not yet clear, it is accepted that they affect functions including olfaction and learning/memory. Experiments with insults to the central nervous system also show that neural stem cells are quickly mobilized due to injury and in various disorders by proliferating, and migrating to injury sites. This suggests a role of endogenous neural stem cells in disease. New pools of stem cells are being discovered, suggesting an even more important role for these cells. To understand these cells and to coax them to contribute to tissue repair it would be very useful to be able to image them in the living organism. Here we discuss advances in imaging approaches as well as new concepts that emerge from stem cell biology with emphasis on the interface between imaging and stem cells.

  2. Clinical chemistry reference intervals of healthy adult populations in Gojjam Zones of Amhara National Regional State, Northwest Ethiopia.

    Science.gov (United States)

    Mekonnen, Zewdie; Amuamuta, Asmare; Mulu, Wondemagegn; Yimer, Mulat; Zenebe, Yohannes; Adem, Yesuf; Abera, Bayeh; Gebeyehu, Wondemu; Gebregziabher, Yakob

    2017-01-01

    Reference interval is crucial for disease screening, diagnosis, monitoring, progression and treatment efficacy. Due to lack of locally derived reference values for the parameters, clinicians use reference intervals derived from western population. But, studies conducted in different African countries have indicated differences between locally and western derived reference values. Different studies also indicated considerable variation in clinical chemistry reference intervals by several variables such as age, sex, geographical location, environment, lifestyle and genetic variation. This study aimed to determine the reference intervals of common clinical chemistry parameters of the community of Gojjam Zones, Northwest Ethiopia. Population based cross-sectional study was conducted from November 2015 to December 2016 in healthy adult populations of Gojjam zone. Data such as, medical history, physical examination and socio-demographic data were collected. In addition, laboratory investigations were undertaken to screen the population. Clinical chemistry parameters were measured using Mindray BS 200 clinical chemistry autoanalyzer as per the manufacturer's instructions. Descriptive statistics was used to calculate mean, median and 95th percentiles. Independent sample T-test and one way ANOVA were used to see association between variables. After careful screening of a total of 799 apparently healthy adults who were consented for this study, complete data from 446 (224 females and 222 males) were included for the analysis. The mean age of both the study participants was 28.8 years. Males had high (Preference intervals of amylase, LDH, total protein and total bilirubin were not significantly different between the two sex groups (P>0.05). Mean, median, 95% percentile values of AST, ALP, amylase, LDH, creatinine, total protein, total bilirubin, and direct bilirubin across all age groups of participants were similar (P>0.05). But, there was a significant difference in the

  3. Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer's disease

    International Nuclear Information System (INIS)

    Tang, Jun; Song, Min; Wang, Yanyan; Fan, Xiaotang; Xu, Haiwei; Bai, Yun

    2009-01-01

    In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP swe /PS1 ΔE9 mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP swe /PS1 ΔE9 transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

  4. Histone deacetylase inhibitors SAHA and sodium butyrate block G1-to-S cell cycle progression in neurosphere formation by adult subventricular cells

    Directory of Open Access Journals (Sweden)

    Doughty Martin L

    2011-05-01

    Full Text Available Abstract Background Histone deacetylases (HDACs are enzymes that modulate gene expression and cellular processes by deacetylating histones and non-histone proteins. While small molecule inhibitors of HDAC activity (HDACi are used clinically in the treatment of cancer, pre-clinical treatment models suggest they also exert neuroprotective effects and stimulate neurogenesis in neuropathological conditions. However, the direct effects of HDACi on cell cycle progression and proliferation, two properties required for continued neurogenesis, have not been fully characterized in adult neural stem cells (NSCs. In this study, we examined the effects of two broad class I and class II HDACi on adult mouse NSCs, the hydroxamate-based HDACi suberoylanilide hydroxamic acid (vorinostat, SAHA and the short chain fatty acid HDACi sodium butyrate. Results We show that both HDACi suppress the formation of neurospheres by adult mouse NSCs grown in proliferation culture conditions in vitro. DNA synthesis is significantly inhibited in adult mouse NSCs exposed to either SAHA or sodium butyrate and inhibition is associated with an arrest in the G1 phase of the cell cycle. HDACi exposure also resulted in transcriptional changes in adult mouse NSCs. Cdk inhibitor genes p21 and p27 transcript levels are increased and associated with elevated H3K9 acetylation levels at proximal promoter regions of p21 and p27. mRNA levels for notch effector Hes genes and Spry-box stem cell transcription factors are downregulated, whereas pro-neural transcription factors Neurog1 and Neurod1 are upregulated. Lastly, we show HDAC inhibition under proliferation culture conditions leads to long-term changes in cell fate in adult mouse NSCs induced to differentiate in vitro. Conclusion SAHA and sodium butyrate directly regulate cdk inhibitor transcription to control cell cycle progression in adult mouse NSCs. HDAC inhibition results in G1 arrest in adult mouse NSCs and transcriptional changes

  5. Postnatal development of cerebellar zones revealed by neurofilament heavy chain protein expression

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    Joshua J White

    2013-05-01

    Full Text Available The cerebellum is organized into parasagittal zones that control sensory-motor behavior. Although the architecture of adult zones is well understood, very little is known about how zones emerge during development. Understanding the process of zone formation is an essential step towards unraveling how circuits are constructed to support specific behaviors. Therefore, we focused this study on postnatal development to determine the spatial and temporal changes that establish zonal patterns during circuit formation. We used a combination of wholemount and tissue section immunohistochemistry in mice to show that the cytoskeletal protein neurofilament heavy chain (NFH is a robust marker for postnatal cerebellar zonal patterning. The patterned expression of NFH is initiated shortly after birth, and compared to the domains of several known zonal markers such as zebrin II, HSP25, neurogranin, and phospholipase Cβ4 (PLCβ4, NFH does not exhibit transient expression patterns that are typically remodeled between stages, and the adult zones do not emerge after a period of uniform expression in all lobules. Instead, we found that throughout postnatal development NFH gradually reveals distinct zones in each cerebellar lobule. The boundaries of individual NFH zones sharpen over time, as zones are refined during the second and third weeks after birth. Double labeling with neurogranin and PLCβ4 further revealed that although the postnatal expression of NFH is spatially and temporally unique, its pattern of zones respects a fundamental and well-known molecular topography in the cerebellum. The dynamics of NFH expression support the hypothesis that adult circuits are derived from an embryonic map that is refined into zones during the first three-weeks of life.

  6. Effects of Electroacupuncture Combined with Repetitive Transcranial Magnetic Stimulation on the Expression of Nestin in Neural Stem Cell after Focal Cerebral Ischemia in Adult Rats

    Institute of Scientific and Technical Information of China (English)

    HUANG Guofu; HUANG Xiaolin; CHEN Hong; HAY Xiaohua

    2009-01-01

    Objective: To investigate the influence of electroacupuncture (EA) combined with repetitive transeranial magnetic stimulation(rTMS) on the temporal profile of nestin expression after induction of focal cerebral isehemia in adult rats and to explore the mechanism of EA combined with rTMS in treating ischemic brain injury. Method: The model of transient focal ischemia was produced by occlusion of middle cerebral artery. Seventy-five Wistar rats were randomly divided into normal group, model group, EA group, rTMS group and EA +rTMS group. The neurologic impairment rating and ability of learning and memory were observed at the 7th、14th and 28th d after infarction respectively. Meanwhile, Western blotting was used to observe the number of nestin expression positive cells. Result: Nestin-positive cells were found in cortex, subgranular zone (SGZ), subventricular zone (SVZ) of the ipsilateral side at different time points after cerebral isehemia. The number of nestin-positive cells peaked at the 7th d, began to decrease at the 14th d and was significantly higher in EA+rTMS group than that in model group (P<0.05), then almost reached normal at the 28th d. The improvement of neural motor function deficits as well as the indexes of learning and memory were more obvious in EA+rTMS group compared with model group (P<0.01, P<0.05). These effects were most obvious in EA+rTMS group compared with the EA and rTMS group (P<0.05). Conclusion: EA and rTMS possess the potency of building up and can increase the number of nestin-positive cells in some brain regions after focal cerebral ischemia, which might be one of the important mechanisms of EA combined with rTMS in treating ischemia brain injury.

  7. Neural tissue-spheres

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Johansen, Mathias; Blaabjerg, Morten

    2007-01-01

    By combining new and established protocols we have developed a procedure for isolation and propagation of neural precursor cells from the forebrain subventricular zone (SVZ) of newborn rats. Small tissue blocks of the SVZ were dissected and propagated en bloc as free-floating neural tissue...... content, thus allowing experimental studies of neural precursor cells and their niche...

  8. Development and aging of a brain neural stem cell niche.

    Science.gov (United States)

    Conover, Joanne C; Todd, Krysti L

    2017-08-01

    In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the ventricular-subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new neurons to the olfactory bulb throughout adulthood; however, with increasing age stem cell numbers are reduced and neurogenic capacity is significantly diminished, but new olfactory bulb neurons continue to be produced even in old age. Humans, in contrast, show little to no new neurogenesis after two years of age and whether V-SVZ neural stem cells persist in the adult human brain remains unclear. Here, we review functional and organizational differences in the V-SVZ stem cell niche of mice and humans, and examine how aging affects the V-SVZ niche and its associated functions. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Creating a safe place for pediatric care: A no hit zone.

    Science.gov (United States)

    Frazier, Erin R; Liu, Gilbert C; Dauk, Kelly L

    2014-07-01

    Our goal was to create and implement a program, Kosair Children's Hospital's No Hit Zone, which trains health care workers in de-escalation techniques to address parental disruptive behaviors and physical discipline of children commonly encountered in the hospital environment. The Child Abuse Task Force, a multidisciplinary group, along with key hospital administrators developed specific content for the policy, as well as marketing and educational materials. The No Hit Zone policy designates Kosair Children's Hospital as "an environment in which no adult shall hit a child, no adult shall hit another adult, no child shall hit an adult, and no child shall hit another child. When hitting is observed, it is everyone's responsibility to interrupt the behavior as well as communicate system policy to those present." Via a multidisciplinary, collaborative approach, the No Hit Zone was successfully implemented at Kosair Children's Hospital in 2012. Cost was nominal, and the support of key hospital administrators was critical to the program's success. Education of health professionals on de-escalation techniques and intervention with families at the early signs of parental stress occurred via live sessions and online training via case-based scenarios. The No Hit Zone is an important program used to provide a safe and caring environment for all families and staff of Kosair Children's Hospital. Demand for the program continues, demonstrated by the establishment of No Hit Zones at other local hospitals and multiple outpatient clinics. This article offers information for other organizations planning to conduct similar initiatives. Copyright © 2014 by the American Academy of Pediatrics.

  10. Newborn Interneurons in the Accessory Olfactory Bulb Promote Mate Recognition in Female Mice

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    Livio eOboti

    2011-09-01

    Full Text Available In the olfactory bulb of adult rodents, local interneurons are constantly replaced by immature precursors derived from the subventricular zone. Whether any olfactory sensory process specifically relies on this cell renewal remains largely unclear. By using the well-known model of mating-induced imprinting, we demonstrate that this olfactory memory formation critically depends on the presence of newborn granule neurons in the accessory olfactory bulb. Accordingly, we show that, in adult female mice, exposure to male pheromones increases the number of new granule cells surviving in the accessory olfactory bulb. This neuronal addition depends on the detection of sensory cues by the vomeronasal organ and requires centrifugal feedback activity from the amygdala. The stimuli affecting neuronal survival are contained in the low molecular weight fraction of urine and are implied in pheromonal recognition during mating. By chemical depletion of newly generated bulbar interneurons, we show a direct role of renewed granule cells in the accessory olfactory bulb in preventing pregnancy block by mating male odours. Taken together, our results indicate that adult neurogenesis is essential for specific brain functions such as persistent odour learning and mate recognition.

  11. Pathology of nodal marginal zone lymphomas.

    Science.gov (United States)

    Pileri, Stefano; Ponzoni, Maurilio

    Nodal marginal zone B cell lymphomas (NMZLs) are a rare group of lymphoid disorders part of the spectrum of marginal zone B-cell lymphomas, which encompass splenic marginal one B-cell lymphoma (SMZL) and extra nodal marginal zone of B-cell lymphoma (EMZL), often of MALT-type. Two clinicopathological forms of NMZL are recognized: adult-type and pediatric-type, respectively. NMZLs show overlapping features with other types of MZ, but distinctive features as well. In this review, we will focus on the salient distinguishing features of NMZL mostly under morphological/immunophenotypical/molecular perspectives in views of the recent acquisitions and forthcoming updated 2016 WHO classification of lymphoid malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Effects of neuroinflammation on the regenerative capacity of brain stem cells.

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    Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

    2011-03-01

    In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system associated with neuroinflammation, inflammatory mediators such as cytokines and chemokines can affect the capacity of brain stem cells and alter neurogenesis. In this review, we summarize the state of the art on the effects of neuroinflammation on adult neurogenesis and discuss the use of the lipopolysaccharide-model to study the effects of inflammation and reactive-microglia on brain stem cells and neurogenesis. Furthermore, we discuss the possible causes underlying reduced neurogenesis with normal aging and potential anti-inflammatory, pro-neurogenic interventions aimed at improving memory deficits in normal and pathological aging and in neurodegenerative diseases. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  13. The functional significance of newly born neurons integrated into olfactory bulb circuits.

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    Sakamoto, Masayuki; Kageyama, Ryoichiro; Imayoshi, Itaru

    2014-01-01

    The olfactory bulb (OB) is the first central processing center for olfactory information connecting with higher areas in the brain, and this neuronal circuitry mediates a variety of odor-evoked behavioral responses. In the adult mammalian brain, continuous neurogenesis occurs in two restricted regions, the subventricular zone (SVZ) of the lateral ventricle and the hippocampal dentate gyrus. New neurons born in the SVZ migrate through the rostral migratory stream and are integrated into the neuronal circuits of the OB throughout life. The significance of this continuous supply of new neurons in the OB has been implicated in plasticity and memory regulation. Two decades of huge investigation in adult neurogenesis revealed the biological importance of integration of new neurons into the olfactory circuits. In this review, we highlight the recent findings about the physiological functions of newly generated neurons in rodent OB circuits and then discuss the contribution of neurogenesis in the brain function. Finally, we introduce cutting edge technologies to monitor and manipulate the activity of new neurons.

  14. The functional significance of newly born neurons integrated into olfactory bulb circuits

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    Masayuki eSakamoto

    2014-05-01

    Full Text Available The olfactory bulb (OB is the first central processing center for olfactory information connecting with higher areas in the brain, and this neuronal circuitry mediates a variety of odor-evoked behavioral responses. In the adult mammalian brain, continuous neurogenesis occurs in two restricted regions, the subventricular zone (SVZ of the lateral ventricle and the hippocampal dentate gyrus. New neurons born in the SVZ migrate through the rostral migratory stream and are integrated into the neuronal circuits of the OB throughout life. The significance of this continuous supply of new neurons in the OB has been implicated in plasticity and memory regulation. Two decades of huge investigation in adult neurogenesis revealed the biological importance of integration of new neurons into the olfactory circuits. In this review, we highlight the recent findings about the physiological functions of newly generated neurons in rodent OB circuits and then discuss the contribution of neurogenesis in the brain function. Finally, we introduce cutting edge technologies to monitor and manipulate the activity of new neurons.

  15. Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APP{sub swe}/PS1{sub {Delta}E9} transgenic mouse model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jun [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China); Department of Physiology, Third Military Medical University, Chongqing 400038 (China); Song, Min; Wang, Yanyan [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China); Fan, Xiaotang [Department of Histology and Embryology, Third Military Medical University, Chongqing 400038 (China); Xu, Haiwei, E-mail: haiweixu2001@yahoo.com.cn [Department of Physiology, Third Military Medical University, Chongqing 400038 (China); Bai, Yun, E-mail: baiyungene@gmail.com [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China)

    2009-07-31

    In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP{sub swe}/PS1{sub {Delta}E9} mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP{sub swe}/PS1{sub {Delta}E9} transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

  16. The receptor for Granulocyte-colony stimulating factor (G-CSF is expressed in radial glia during development of the nervous system

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    Krüger Carola

    2008-03-01

    Full Text Available Abstract Background Granulocyte colony-stimulating (G-CSF factor is a well-known hematopoietic growth factor stimulating the proliferation and differentiation of myeloid progenitors. Recently, we uncovered that G-CSF acts also as a neuronal growth factor in the brain, which promotes adult neural precursor differentiation and enhances regeneration of the brain after insults. In adults, the receptor for G-CSF is predominantly expressed in neurons in many brain areas. We also described expression in neurogenic regions of the adult brain, such as the subventricular zone and the subgranular layer of the dentate gyrus. In addition, we found close co-localization of the G-CSF receptor and its ligand G-CSF. Here we have conducted a systematic expression analysis of G-CSF receptor and its ligand in the developing embryo. Results Outside the central nervous system (CNS we found G-CSF receptor expression in blood vessels, muscles and their respective precursors and neurons. The expression of the G-CSF receptor in the developing CNS was most prominent in radial glia cells. Conclusion Our data imply that in addition to the function of G-CSF and its receptor in adult neurogenesis, this system also has a role in embryonic neurogenesis and nervous system development.

  17. The oncoprotein BCL11A binds to orphan nuclear receptor TLX and potentiates its transrepressive function.

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    Sara B Estruch

    Full Text Available Nuclear orphan receptor TLX (NR2E1 functions primarily as a transcriptional repressor and its pivotal role in brain development, glioblastoma, mental retardation and retinopathologies make it an attractive drug target. TLX is expressed in the neural stem cells (NSCs of the subventricular zone and the hippocampus subgranular zone, regions with persistent neurogenesis in the adult brain, and functions as an essential regulator of NSCs maintenance and self-renewal. Little is known about the TLX social network of interactors and only few TLX coregulators are described. To identify and characterize novel TLX-binders and possible coregulators, we performed yeast-two-hybrid (Y2H screens of a human adult brain cDNA library using different TLX constructs as baits. Our screens identified multiple clones of Atrophin-1 (ATN1, a previously described TLX interactor. In addition, we identified an interaction with the oncoprotein and zinc finger transcription factor BCL11A (CTIP1/Evi9, a key player in the hematopoietic system and in major blood-related malignancies. This interaction was validated by expression and coimmunoprecipitation in human cells. BCL11A potentiated the transrepressive function of TLX in an in vitro reporter gene assay. Our work suggests that BCL11A is a novel TLX coregulator that might be involved in TLX-dependent gene regulation in the brain.

  18. The oncoprotein BCL11A binds to orphan nuclear receptor TLX and potentiates its transrepressive function.

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    Estruch, Sara B; Buzón, Víctor; Carbó, Laia R; Schorova, Lenka; Lüders, Jens; Estébanez-Perpiñá, Eva

    2012-01-01

    Nuclear orphan receptor TLX (NR2E1) functions primarily as a transcriptional repressor and its pivotal role in brain development, glioblastoma, mental retardation and retinopathologies make it an attractive drug target. TLX is expressed in the neural stem cells (NSCs) of the subventricular zone and the hippocampus subgranular zone, regions with persistent neurogenesis in the adult brain, and functions as an essential regulator of NSCs maintenance and self-renewal. Little is known about the TLX social network of interactors and only few TLX coregulators are described. To identify and characterize novel TLX-binders and possible coregulators, we performed yeast-two-hybrid (Y2H) screens of a human adult brain cDNA library using different TLX constructs as baits. Our screens identified multiple clones of Atrophin-1 (ATN1), a previously described TLX interactor. In addition, we identified an interaction with the oncoprotein and zinc finger transcription factor BCL11A (CTIP1/Evi9), a key player in the hematopoietic system and in major blood-related malignancies. This interaction was validated by expression and coimmunoprecipitation in human cells. BCL11A potentiated the transrepressive function of TLX in an in vitro reporter gene assay. Our work suggests that BCL11A is a novel TLX coregulator that might be involved in TLX-dependent gene regulation in the brain.

  19. Circadian Clock Genes Are Essential for Normal Adult Neurogenesis, Differentiation, and Fate Determination.

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    Astha Malik

    Full Text Available Adult neurogenesis creates new neurons and glia from stem cells in the human brain throughout life. It is best understood in the dentate gyrus (DG of the hippocampus and the subventricular zone (SVZ. Circadian rhythms have been identified in the hippocampus, but the role of any endogenous circadian oscillator cells in hippocampal neurogenesis and their importance in learning or memory remains unclear. Any study of stem cell regulation by intrinsic circadian timing within the DG is complicated by modulation from circadian clocks elsewhere in the brain. To examine circadian oscillators in greater isolation, neurosphere cultures were prepared from the DG of two knockout mouse lines that lack a functional circadian clock and from mPer1::luc mice to identify circadian oscillations in gene expression. Circadian mPer1 gene activity rhythms were recorded in neurospheres maintained in a culture medium that induces neurogenesis but not in one that maintains the stem cell state. Although the differentiating neural stem progenitor cells of spheres were rhythmic, evidence of any mature neurons was extremely sparse. The circadian timing signal originated in undifferentiated cells within the neurosphere. This conclusion was supported by immunocytochemistry for mPER1 protein that was localized to the inner, more stem cell-like neurosphere core. To test for effects of the circadian clock on neurogenesis, media conditions were altered to induce neurospheres from BMAL1 knockout mice to differentiate. These cultures displayed unusually high differentiation into glia rather than neurons according to GFAP and NeuN expression, respectively, and very few BetaIII tubulin-positive, immature neurons were observed. The knockout neurospheres also displayed areas visibly devoid of cells and had overall higher cell death. Neurospheres from arrhythmic mice lacking two other core clock genes, Cry1 and Cry2, showed significantly reduced growth and increased astrocyte

  20. The neural elements in the lining of the ventricular-subventricular zone: making an old story new by high-resolution scanning electron microscopy

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    Carlos Alexandre Dos Santos Haemmerle

    2015-10-01

    Full Text Available The classical description of the neural elements that compose the lining of brain ventricles introduces us to the single layer of ependymal cells. However, new findings, especially in the lateral ventricle - the major niche for the generation of new neurons in the adult brain - have provided information about additional cell elements that influence the organization of this part of the ventricular system and produce important contributions to neurogenesis. To complement the cell neurochemistry findings, we present a three-dimensional in situ description that demonstrates the anatomical details of the different types of ciliated cells and the innervation of these elements. After processing adult rat brains for ultrastructural analysis by high-resolution scanning electron microscopy and transmission electron microscopy, we observed a heterogeneous pattern of cilia distribution at the different poles of the lateral ventricle surface. Furthermore, we describe the particular three-dimensional aspects of the ciliated cells of the lateral ventricle, in addition the fiber bundles and varicose axons surrounding these cells. Therefore, we provide a unique ultrastructural description of the three-dimensional in situ organization of the lateral ventricle surface, highlighting its innervation, to corroborate the available neurochemical and functional findings regarding the factors that regulate this neurogenic niche.

  1. Vascular pattern of the dentate gyrus is regulated by neural progenitors.

    Science.gov (United States)

    Pombero, Ana; Garcia-Lopez, Raquel; Estirado, Alicia; Martinez, Salvador

    2018-05-01

    Neurogenesis is a vital process that begins during early embryonic development and continues until adulthood, though in the latter case, it is restricted to the subventricular zone and the subgranular zone of the dentate gyrus (DG). In particular, the DG's neurogenic properties are structurally and functionally unique, which may be related to its singular vascular pattern. Neurogenesis and angiogenesis share molecular signals and act synergistically, supporting the concept of a neurogenic niche as a functional unit between neural precursors cells and their environment, in which the blood vessels play an important role. Whereas it is well known that vascular development controls neural proliferation in the embryonary and in the adult brain, by releasing neurotrophic factors; the potential influence of neural cells on vascular components during angiogenesis is largely unknown. We have demonstrated that the reduction of neural progenitors leads to a significant impairment of vascular development. Since VEGF is a potential regulator in the neurogenesis-angiogenesis crosstalk, we were interested in assessing the possible role of this molecule in the hippocampal neurovascular development. Our results showed that VEGF is the molecule involved in the regulation of vascular development by neural progenitor cells in the DG.

  2. Predictors of Treatment Failure among Adult Antiretroviral Treatment (ART) Clients in Bale Zone Hospitals, South Eastern Ethiopia.

    Science.gov (United States)

    Haile, Demewoz; Takele, Abulie; Gashaw, Ketema; Demelash, Habtamu; Nigatu, Dabere

    2016-01-01

    Treatment failure defined as progression of disease after initiation of ART or when the anti-HIV medications can't control the infection. One of the major concerns over the rapid scaling up of ART is the emergence and transmission of HIV drug resistant strains at the population level due to treatment failure. This could lead to the failure of basic ART programs. Thus this study aimed to investigate the predictors of treatment failure among adult ART clients in Bale Zone Hospitals, South east Ethiopia. Retrospective cohort study was employed in four hospitals of Bale zone named Goba, Robe, Ginir and Delomena. A total of 4,809 adult ART clients were included in the analysis from these four hospitals. Adherence was measured by pill count method. The Kaplan Meier (KM) curve was used to describe the survival time of ART patients without treatment failure. Bivariate and multivariable Cox proportional hazards regression models were used for identifying associated factors of treatment failure. The incidence rate of treatment failure was found 9.38 (95% CI 7.79-11.30) per 1000 person years. Male ART clients were more likely to experience treatment failure as compared to females [AHR = 4.49; 95% CI: (2.61-7.73)].Similarly, lower CD4 count (ART was found significantly associated with higher odds of treatment failure [AHR = 3.79; 95% CI: (2.46-5.84).Bedridden [AHR = 5.02; 95% CI: (1.98-12.73)] and ambulatory [AHR = 2.12; 95% CI: (1.08-4.07)] patients were more likely to experience treatment failure as compared to patients with working functional status. TB co-infected clients had also higher odds to experience treatment failure [AHR = 3.06; 95% CI: (1.72-5.44)]. Those patients who had developed TB after ART initiation had higher odds to experience treatment failure as compared to their counter parts [AHR = 4.35; 95% CI: (1.99-9.54]. Having other opportunistic infection during ART initiation was also associated with higher odds of experiencing treatment failure [AHR = 7.0, 95

  3. Neurogenic and non neurogenic functions of endogenous neural stem cells.

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    Erica eButti

    2014-04-01

    Full Text Available Adult neurogenesis is a lifelong process that occurs in two main neurogenic niches of the brain, namely in the subventricular zone (SVZ of the lateral ventricles and in the subgranular zone (SGZ of the dentate gyrus (DG in the hippocampus. In the 1960s, studies on adult neurogenesis have been hampered by the lack of established phenotypic markers. The precise tracing of neural stem/progenitor cells (NPCs was therefore, not properly feasible. After the (partial identification of those markers, it was the lack of specific tools that hindered a proper experimental elimination and tracing of those cells to demonstrate their terminal fate and commitment. Nowadays, irradia-tion, cytotoxic drugs as well as genetic tracing/ablation procedures have moved the field forward and increased our understanding of neurogenesis processes in both physiological and pathological conditions. Newly formed NPC progeny from the SVZ can replace granule cells in the olfactory bulbs of rodents, thus contributing to orchestrate sophisticated odour behaviour. SGZ-derived new granule cells, instead, integrate within the DG where they play an essential role in memory functions. Furthermore, converging evidence claim that endogenous NPCs not only exert neurogenic functions, but might also have non-neurogenic homeostatic functions by the release of different types of neuroprotective molecules. Remarkably, these non-neurogenic homeostatic functions seem to be necessary, both in healthy and diseased conditions, for example for preventing or limiting tissue damage. In this review, we will discuss the neurogenic and the non-neurogenic functions of adult NPCs both in physiological and pathological conditions.

  4. Photoperiod mediated changes in olfactory bulb neurogenesis and olfactory behavior in male white-footed mice (Peromyscus leucopus.

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    James C Walton

    Full Text Available Brain plasticity, in relation to new adult mammalian neurons generated in the subgranular zone of the hippocampus, has been well described. However, the functional outcome of new adult olfactory neurons born in the subventricular zone of the lateral ventricles is not clearly defined, as manipulating neurogenesis through various methods has given inconsistent and conflicting results in lab mice. Several small rodent species, including Peromyscus leucopus, display seasonal (photoperiodic brain plasticity in brain volume, hippocampal function, and hippocampus-dependent behaviors; plasticity in the olfactory system of photoperiodic rodents remains largely uninvestigated. We exposed adult male P. leucopus to long day lengths (LD and short day lengths (SD for 10 to 15 weeks and then examined olfactory bulb cell proliferation and survival using the thymidine analog BrdU, olfactory bulb granule cell morphology using Golgi-Cox staining, and behavioral investigation of same-sex conspecific urine. SD mice did not differ from LD counterparts in granular cell morphology of the dendrites or in dendritic spine density. Although there were no differences due to photoperiod in habituation to water odor, SD mice rapidly habituated to male urine, whereas LD mice did not. In addition, short day induced changes in olfactory behavior were associated with increased neurogenesis in the caudal plexiform and granule cell layers of the olfactory bulb, an area known to preferentially respond to water-soluble odorants. Taken together, these data demonstrate that photoperiod, without altering olfactory bulb neuronal morphology, alters olfactory bulb neurogenesis and olfactory behavior in Peromyscus leucopus.

  5. Neural stem cell isolation and culture from C57BL/6 mice

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    S Koirala

    2015-07-01

    Full Text Available INTRODUCTION A widely used in vitro culture, the neurosphere assay (NSA has provided a means to retrospectively identify neural progenitor cells as well as to determine both their selfrenewal capacity. Objective of study was to isolate and compare growth of the embryonic neuronal stem cell and adult neuronal stem cells in presence of Epidermal Growth Factor (EGF and Fibroblastic Growth Factor (FGF2. MATERIALS AND METHODS Embryonic neuronal stem cell were collected from cortical plate of dorsal telencephalon of fifteen C57BL/6 transgenic mice using stereoscopic microscope on 11th gestational day (GD. Adult mammalian neuronal stem cells taken from subventricular zone (SVZ of the lateral ventricles and subgranular layer of the dentate gyrus of the hippocampus were cultured. The growth for the neurosphere was then observed in interval of 24 and 72 hours. RESULT The adult stem cell culture showed few intact cells with high amount of debris and 9% heterogeneous sphere after 24 hours while only 20 % was observed at the end of 72 hours. Higher proliferation rate was observed in embryonic neurospheres than the adult stem cell culture. CONCLUSION Presence of EGF and basic FGF2 is essential for culture of neurospheres.DOI: http://dx.doi.org/10.3126/jcmsn.v10i2.12946 Journal of College of Medical Sciences-Nepal, 2014, Vol.10(2; 1-3

  6. Current Opinion on the Role of Neurogenesis in the Therapeutic Strategies for Alzheimer Disease, Parkinson Disease, and Ischemic Stroke; Considering Neuronal Voiding Function

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    Myung-Hoon Han

    2016-12-01

    Full Text Available Neurological diseases such as Alzheimer, Parkinson, and ischemic stroke have increased in occurrence and become important health issues throughout the world. There is currently no effective therapeutic strategy for addressing neurological deficits after the development of these major neurological disorders. In recent years, it has become accepted that adult neural stem cells located in the subventricular and subgranular zones have the ability to proliferate and differentiate in order to replace lost or damaged neural cells. There have been many limitations in the clinical application of both endogenous and exogenous neurogenesis for neurological disorders. However, many studies have investigated novel mechanisms in neurogenesis and have shown that these limitations can potentially be overcome with appropriate stimulation and various approaches. We will review concepts related to possible therapeutic strategies focused on the perspective of neurogenesis for the treatment of patients diagnosed with Alzheimer disease, Parkinson disease, and ischemic stroke based on current reports.

  7. Unique Organization of the Nuclear Envelope in the Post-natal Quiescent Neural Stem Cells

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    Arantxa Cebrián-Silla

    2017-07-01

    Full Text Available Neural stem cells (B1 astrocytes; NSCs in the adult ventricular-subventricular-zone (V-SVZ originate in the embryo. Surprisingly, recent work has shown that B1 cells remain largely quiescent. They are reactivated postnatally to function as primary progenitors for neurons destined for the olfactory bulb and some corpus callosum oligodendrocytes. The cellular and molecular properties of quiescent B1 cells remain unknown. Here we found that a subpopulation of B1 cells has a unique nuclear envelope invagination specialization similar to envelope-limited chromatin sheets (ELCS, reported in certain lymphocytes and some cancer cells. Using molecular markers, [3H]thymidine birth-dating, and Ara-C, we found that B1 cells with ELCS correspond to quiescent NSCs. ELCS begin forming in embryonic radial glia cells and represent a specific nuclear compartment containing particular epigenetic modifications and telomeres. These results reveal a unique nuclear compartment in quiescent NSCs, which is useful for identifying these primary progenitors and study their gene regulation.

  8. Testosterone-induced adult neurosphere growth is mediated by sexually-dimorphic aromatase expression

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    Mark Ian Ransome

    2015-07-01

    Full Text Available We derived adult neural stem/progenitor cells (NSPCs from the sub-ventricular zone of male and female mice to examine direct responses to principal sex hormones. In the presence of epidermal growth factor (EGF and fibroblast growth factor-2 (FGF2 NSPCs of both sexes expressed nestin and sox2 and could be maintained as neurospheres without addition of any sex hormones. The reverse was not observed; neither testosterone (T, 17β-oestradiol (E2 nor progesterone (P4 was able to support neurosphere growth in the absence of EGF and FGF2. 10nM T, E2 or P4 induced nestin(+ cell proliferation within 20 minutes and enhanced neurosphere growth over 7 days irrespective of sex, which was abolished by Erk inhibition with 20M U0126. Maintaining neurospheres with each sex hormone did not affect subsequent neuronal differentiation. However, 10nM T, E2 or P4 added during differentiation increased III tubulin(+ neuron production with E2 being more potent compared to T and P4 in both sexes. Androgen receptor (AR inhibition with 20M flutamide but not aromatase inhibition with 10M letrozole reduced basal and T-induced neurosphere growth in females, while only concurrent inhibition of AR and aromatase produced the same effect in males. This sex-specific effect was supported by higher aromatase expression in male neurospheres compared to females measured by Western blot and green fluorescent protein reporter. 10M menadione induced oxidative stress, impaired neurosphere growth and up-regulated aromatase expression in both sexes. However, under oxidative stress letrozole significantly exacerbated impaired neurosphere growth in males only. While both E2 and T could prevent oxidative stress-induced growth reduction in both sexes, the effects of T were dependent on innate aromatase activity. We show for the first time that intrinsic androgen and estrogen signalling may impact the capacity of NSPCs to produce neural progenitors under pathological conditions of

  9. Predictors of Treatment Failure among Adult Antiretroviral Treatment (ART Clients in Bale Zone Hospitals, South Eastern Ethiopia.

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    Demewoz Haile

    Full Text Available Treatment failure defined as progression of disease after initiation of ART or when the anti-HIV medications can't control the infection. One of the major concerns over the rapid scaling up of ART is the emergence and transmission of HIV drug resistant strains at the population level due to treatment failure. This could lead to the failure of basic ART programs. Thus this study aimed to investigate the predictors of treatment failure among adult ART clients in Bale Zone Hospitals, South east Ethiopia.Retrospective cohort study was employed in four hospitals of Bale zone named Goba, Robe, Ginir and Delomena. A total of 4,809 adult ART clients were included in the analysis from these four hospitals. Adherence was measured by pill count method. The Kaplan Meier (KM curve was used to describe the survival time of ART patients without treatment failure. Bivariate and multivariable Cox proportional hazards regression models were used for identifying associated factors of treatment failure.The incidence rate of treatment failure was found 9.38 (95% CI 7.79-11.30 per 1000 person years. Male ART clients were more likely to experience treatment failure as compared to females [AHR = 4.49; 95% CI: (2.61-7.73].Similarly, lower CD4 count (<100 m3/dl at initiation of ART was found significantly associated with higher odds of treatment failure [AHR = 3.79; 95% CI: (2.46-5.84.Bedridden [AHR = 5.02; 95% CI: (1.98-12.73] and ambulatory [AHR = 2.12; 95% CI: (1.08-4.07] patients were more likely to experience treatment failure as compared to patients with working functional status. TB co-infected clients had also higher odds to experience treatment failure [AHR = 3.06; 95% CI: (1.72-5.44]. Those patients who had developed TB after ART initiation had higher odds to experience treatment failure as compared to their counter parts [AHR = 4.35; 95% CI: (1.99-9.54]. Having other opportunistic infection during ART initiation was also associated with higher odds of

  10. Orphan nuclear receptor TLX activates Wnt/β-catenin signalling to stimulate neural stem cell proliferation and self-renewal

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    Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T.; Gage, Fred H.; Evans, Ronald M.; Shi, Yanhong

    2010-01-01

    The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/β-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/β-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active β-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a β-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active β-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active β-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active β-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/β-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode. PMID:20010817

  11. Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal.

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    Qu, Qiuhao; Sun, Guoqiang; Li, Wenwu; Yang, Su; Ye, Peng; Zhao, Chunnian; Yu, Ruth T; Gage, Fred H; Evans, Ronald M; Shi, Yanhong

    2010-01-01

    The nuclear receptor TLX (also known as NR2E1) is essential for adult neural stem cell self-renewal; however, the molecular mechanisms involved remain elusive. Here we show that TLX activates the canonical Wnt/beta-catenin pathway in adult mouse neural stem cells. Furthermore, we demonstrate that Wnt/beta-catenin signalling is important in the proliferation and self-renewal of adult neural stem cells in the presence of epidermal growth factor and fibroblast growth factor. Wnt7a and active beta-catenin promote neural stem cell self-renewal, whereas the deletion of Wnt7a or the lentiviral transduction of axin, a beta-catenin inhibitor, led to decreased cell proliferation in adult neurogenic areas. Lentiviral transduction of active beta-catenin led to increased numbers of type B neural stem cells in the subventricular zone of adult brains, whereas deletion of Wnt7a or TLX resulted in decreased numbers of neural stem cells retaining bromodeoxyuridine label in the adult brain. Both Wnt7a and active beta-catenin significantly rescued a TLX (also known as Nr2e1) short interfering RNA-induced deficiency in neural stem cell proliferation. Lentiviral transduction of an active beta-catenin increased cell proliferation in neurogenic areas of TLX-null adult brains markedly. These results strongly support the hypothesis that TLX acts through the Wnt/beta-catenin pathway to regulate neural stem cell proliferation and self-renewal. Moreover, this study suggests that neural stem cells can promote their own self-renewal by secreting signalling molecules that act in an autocrine/paracrine mode.

  12. Presynaptic active zones of mammalian neuromuscular junctions: Nanoarchitecture and selective impairments in aging.

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    Badawi, Yomna; Nishimune, Hiroshi

    2018-02-01

    Neurotransmitter release occurs at active zones, which are specialized regions of the presynaptic membrane. A dense collection of proteins at the active zone provides a platform for molecular interactions that promote recruitment, docking, and priming of synaptic vesicles. At mammalian neuromuscular junctions (NMJs), muscle-derived laminin β2 interacts with presynaptic voltage-gated calcium channels to organize active zones. The molecular architecture of presynaptic active zones has been revealed using super-resolution microscopy techniques that combine nanoscale resolution and multiple molecular identification. Interestingly, the active zones of adult NMJs are not stable structures and thus become impaired during aging due to the selective degeneration of specific active zone proteins. This review will discuss recent progress in the understanding of active zone nanoarchitecture and the mechanisms underlying active zone organization in mammalian NMJs. Furthermore, we will summarize the age-related degeneration of active zones at NMJs, and the role of exercise in maintaining active zones. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  13. Population morbidity in the Zaporizhzhia Nuclear Power Plant observation zone as an integral part of public health.

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    Khomenko, I M; Zakladna, N V; Orlova, N M

    2017-12-01

    To evaluate the health status of adult population living in the Ukrainian nuclear power industry obser vation zone on the example of Zaporizhzhia Nuclear Power Plant. System review, analytic, sociological survey and statistical methods. There was established an increase in the incidence of digestive diseases among adult population in Nikopol of Dnipropetrovsk region, which is included in the Zaporizhzhia NPP observation zone. The highest increase was observed in the incidence of peptic ulcer, gastritis and duodenitis, cholecystitis and cholangitis by 340 %, 305 % and 83 %, respectively. In connection with the residence in industrially developed region and NPP life extension in Ukraine, the possible influence of harmful factors on health status of the population of observation zones, an increase in the incidence of digestive diseases among adult population, there is required continuous monitoring and detailed study of public health. I. M. Khomenko, N. V. Zakladna, N. M. Orlova.

  14. Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

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    Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

    2014-01-01

    Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2′-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned

  15. Web-Browsing Competencies of Pre-Service Adult Facilitators: Implications for Curriculum Transformation and Distance Learning

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    Theresa, Ofoegbu; Ugwu, Agboeze Matthias; Ihebuzoaju, Anyanwu Joy; Uche, Asogwa

    2013-01-01

    The study investigated the Web-browsing competencies of pre-service adult facilitators in the southeast geopolitical zone of Nigeria. Survey design was adopted for the study. The population consists of all pre-service adult facilitators in all the federal universities in the southeast geopolitical zone of Nigeria. Accidental sampling technique was…

  16. Does developmental hypothyroidism produce lasting effects on adult neurogenesis?

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    The subgranular zone of the dentate gyrus (DO) of the adult hippocampus generates new neurons throughout life. Thyroid hormones (TH) are essential for brain development, but impaired neurogenesis with adult hypothyroidism has also been reported. We investigated the role of milder...

  17. Resilience in Elders of the Sardinian Blue Zone: An Explorative Study.

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    Fastame, Maria Chiara; Hitchcott, Paul Kenneth; Mulas, Ilaria; Ruiu, Marilena; Penna, Maria Pietronilla

    2018-02-26

    Background : older adults from the Sardinian Blue Zone self-report low depressive symptoms and high psychological well-being. However, the role of dispositional resilience as a determinant of these characteristics is unknown. Objectives : the current study had three aims. First, to investigate associations among several putative predictors, including dispositional resilience and three established markers of positive and negative mental health. Second, to determine if gender differences in dispositional resilience, independent of age and cognitive impairment, are present in this population. Third, to examine the relative importance of the predictors of self-reported mental health and well-being. Methods : 160 elders were recruited in the Sardinian Blue Zone. The participants completed self-report measures of dispositional resilience, satisfaction with social ties, physical health, depressive symptoms, and psychological well-being. Results : trait resilience was significantly associated with predictors and markers of mental health. Males had significantly greater trait resilience. In regression analyses, dispositional resilience and satisfaction with social ties were significant predictors of all markers of mental health. Other factors were significantly associated only with certain markers. Conclusions : trait resilience and strong social ties appear to be key determinants of the high mental health of Sardinian Blue Zone older adults.

  18. Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen

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    Anna Benedykcinska

    2016-02-01

    Full Text Available Targeted cell- or region-specific gene recombination is widely used in the functional analysis of genes implicated in development and disease. In the brain, targeted gene recombination has become a mainstream approach to study neurodegeneration or tumorigenesis. The use of the Cre-loxP system to study tumorigenesis in the adult central nervous system (CNS can be limited, when the promoter (such as GFAP is also transiently expressed during development, which can result in the recombination of progenies of different lineages. Engineering of transgenic mice expressing Cre recombinase fused to a mutant of the human oestrogen receptor (ER allows the circumvention of transient developmental Cre expression by inducing recombination in the adult organism. The recombination of loxP sequences occurs only in the presence of tamoxifen. Systemic administration of tamoxifen can, however, exhibit toxicity and might also recombine unwanted cell populations if the promoter driving Cre expression is active at the time of tamoxifen administration. Here, we report that a single site-specific injection of an active derivative of tamoxifen successfully activates Cre recombinase and selectively recombines tumour suppressor genes in neural progenitor cells of the subventricular zone in mice, and we demonstrate its application in a model for the generation of intrinsic brain tumours.

  19. Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen.

    Science.gov (United States)

    Benedykcinska, Anna; Ferreira, Andreia; Lau, Joanne; Broni, Jessica; Richard-Loendt, Angela; Henriquez, Nico V; Brandner, Sebastian

    2016-02-01

    Targeted cell- or region-specific gene recombination is widely used in the functional analysis of genes implicated in development and disease. In the brain, targeted gene recombination has become a mainstream approach to study neurodegeneration or tumorigenesis. The use of the Cre-loxP system to study tumorigenesis in the adult central nervous system (CNS) can be limited, when the promoter (such as GFAP) is also transiently expressed during development, which can result in the recombination of progenies of different lineages. Engineering of transgenic mice expressing Cre recombinase fused to a mutant of the human oestrogen receptor (ER) allows the circumvention of transient developmental Cre expression by inducing recombination in the adult organism. The recombination of loxP sequences occurs only in the presence of tamoxifen. Systemic administration of tamoxifen can, however, exhibit toxicity and might also recombine unwanted cell populations if the promoter driving Cre expression is active at the time of tamoxifen administration. Here, we report that a single site-specific injection of an active derivative of tamoxifen successfully activates Cre recombinase and selectively recombines tumour suppressor genes in neural progenitor cells of the subventricular zone in mice, and we demonstrate its application in a model for the generation of intrinsic brain tumours. © 2016. Published by The Company of Biologists Ltd.

  20. Molecular Characteristics in MRI-classified Group 1 Glioblastoma Multiforme

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    William E Haskins

    2013-07-01

    Full Text Available Glioblastoma multiforme (GBM is a clinically and pathologically heterogeneous brain tumor. Previous study of MRI-classified GBM has revealed a spatial relationship between Group 1 GBM (GBM1 and the subventricular zone (SVZ. The SVZ is an adult neural stem cell niche and is also suspected to be the origin of a subtype of brain tumor. The intimate contact between GBM1 and the SVZ raises the possibility that tumor cells in GBM1 may be most related to SVZ cells. In support of this notion, we found that neural stem cell and neuroblast markers are highly expressed in GBM1. Additionally, we identified molecular characteristics in this type of GBM that include up-regulation of metabolic enzymes, ribosomal proteins, heat shock proteins, and c-Myc oncoprotein. As GBM1 often recurs at great distances from the initial lesion, the rewiring of metabolism and ribosomal biogenesis may facilitate cancer cells’ growth and survival during tumor migration. Taken together, combined our findings and MRI-based classification of GBM1 would offer better prediction and treatment for this multifocal GBM.

  1. Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin

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    Yiwen Jiang

    2017-01-01

    Full Text Available The identity of the glioblastoma (GBM cell of origin and its contributions to disease progression and treatment response remain largely unknown. We have analyzed how the phenotypic state of the initially transformed cell affects mouse GBM development and essential GBM cell (GC properties. We find that GBM induced in neural stem-cell-like glial fibrillary acidic protein (GFAP-expressing cells in the subventricular zone of adult mice shows accelerated tumor development and produces more malignant GCs (mGC1GFAP that are less resistant to cancer drugs, compared with those originating from more differentiated nestin- (mGC2NES or 2,′3′-cyclic nucleotide 3′-phosphodiesterase (mGC3CNP-expressing cells. Transcriptome analysis of mouse GCs identified a 196 mouse cell origin (MCO gene signature that was used to partition 61 patient-derived GC lines. Human GC lines that clustered with the mGC1GFAP cells were also significantly more self-renewing, tumorigenic, and sensitive to cancer drugs compared with those that clustered with mouse GCs of more differentiated origin.

  2. Lineage Reprogramming of Astroglial Cells from Different Origins into Distinct Neuronal Subtypes

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    Malek Chouchane

    2017-07-01

    Full Text Available Astroglial cells isolated from the rodent postnatal cerebral cortex are particularly susceptible to lineage reprogramming into neurons. However, it remains unknown whether other astroglial populations retain the same potential. Likewise, little is known about the fate of induced neurons (iNs in vivo. In this study we addressed these questions using two different astroglial populations isolated from the postnatal brain reprogrammed either with Neurogenin-2 (Neurog2 or Achaete scute homolog-1 (Ascl1. We show that cerebellum (CerebAstro and cerebral cortex astroglia (CtxAstro generates iNs with distinctive neurochemical and morphological properties. Both astroglial populations contribute iNs to the olfactory bulb following transplantation in the postnatal and adult mouse subventricular zone. However, only CtxAstro transfected with Neurog2 differentiate into pyramidal-like iNs after transplantation in the postnatal cerebral cortex. Altogether, our data indicate that the origin of the astroglial population and transcription factors used for reprogramming, as well as the region of integration, affect the fate of iNs.

  3. In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis.

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    Africa, Jonathan A; Behling, Cynthia A; Brunt, Elizabeth M; Zhang, Nan; Luo, Yunjun; Wells, Alan; Hou, Jiayi; Belt, Patricia H; Kohil, Rohit; Lavine, Joel E; Molleston, Jean P; Newton, Kimberly P; Whitington, Peter F; Schwimmer, Jeffrey B

    2018-03-01

    Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. We performed a cross-sectional study of baseline data from 813 children (age Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P 51%; P zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice.

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    Wei, Zheng Zachory; Zhang, James Ya; Taylor, Tammi M; Gu, Xiaohuan; Zhao, Yingying; Wei, Ling

    2018-03-01

    Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 µg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls. Wnt-3a intranasal treatment of seven days upregulated the expression of brain-derived growth factor (BDNF), increased the proliferation and migration of neuroblasts from the subventricular zone (SVZ), resulting in increased numbers of newly formed neurons and endothelial cells in the peri-infarct zone. Both the molecular and cellular effects of Wnt-3a were blocked by the Wnt specific inhibitors XAV-939 or Dkk-1. In functional assays, Wnt-3a treatment enhanced the local cerebral blood flow (LCBF) in the peri-infarct, as well as improved sensorimotor functions in a battery of behavioral tests. Together, our data demonstrates that the Wnt-3a signaling can act as a dual neuroprotective and regenerative factor for the treatment of ischemic stroke.

  5. Zone separator for multiple zone vessels

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    Jones, John B.

    1983-02-01

    A solids-gas contact vessel, having two vertically disposed distinct reaction zones, includes a dynamic seal passing solids from an upper to a lower zone and maintaining a gas seal against the transfer of the separate treating gases from one zone to the other, and including a stream of sealing fluid at the seal.

  6. Parapapillary atrophy: histological gamma zone and delta zone.

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    Jost B Jonas

    Full Text Available BACKGROUND: To examine histomorphometrically the parapapillary region in human eyes. METHODOLOGY/PRINCIPAL FINDINGS: The histomorphometric study included 65 human globes (axial length:21-37 mm. On anterior-posterior histological sections, we measured the distance Bruch's membrane end (BME-optic nerve margin ("Gamma zone", BME-retinal pigment epithelium (RPE ("Beta zone", BME-beginning of non-occluded choriocapillaris, and BME-beginning of photoreceptor layer. "Delta zone" was defined as part of gamma zone in which blood vessels of at least 50 µm diameter were not present over a length of >300 µm. Beta zone (mean length:0.35±0.52 mm was significantly (P = 0.01 larger in the glaucoma group than in the non-glaucomatous group. It was not significantly (P = 0.28 associated with axial length. Beta zone was significantly (P = 0.004 larger than the region with occluded choriocapillaris. Gamma zone (mean length:0.63±1.25 mm was associated with axial length (P50 µm diameter within gamma zone was present only in highly axially elongated globes and was not related with glaucoma. Beta zone (Bruch's membrane without RPE was correlated with glaucoma but not with globe elongation. Since the region with occluded choriocapillaris was smaller than beta zone, complete loss of RPE may have occurred before complete choriocapillaris closure.

  7. The development of primary and secondary lymphoid tissues in the nurse shark Ginglymostoma cirratum: B-cell zones precede dendritic cell immigration and T-cell zone formation during ontogeny of the spleen.

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    Rumfelt, L L; McKinney, E C; Taylor, E; Flajnik, M F

    2002-08-01

    Secondary lymphoid tissue and immunoglobulin (Ig) production in mammals is not fully developed at birth, requiring time postnatally to attain all features required for adaptive immune responses. The immune system of newborn sharks - the oldest vertebrate group having adaptive immunity - also displays immature characteristics such as low serum IgM concentration and high levels of IgM1gj, an innate-like Ig. Primary and secondary lymphoid tissues in sharks and other cartilaginous fish were identified previously, but their cellular organization was not examined in detail. In this study of nurse shark lymphoid tissue, we demonstrate that the adult spleen contains well-defined, highly vascularized white pulp (WP) areas, composed of a central T-cell zone containing a major histocompatibility complex (MHC) class II+ dendritic cell (DC) network and a small number of Ig+ secretory cells, surrounded by smaller zones of surface Ig+ (sIg+) B cells. In neonates, splenic WPs are exclusively B-cell zones containing sIgM+-MHC class IIlow B cells; thus compartmentalized areas with T cells and DCs, as well as surface Ig novel antigen receptor (sIgNAR)-expressing B cells are absent at birth. Not until the pups are 5 months old do these WP areas become adult-like; concomitantly, sIgNAR+ B cells are readily detectable, indicating that this Ig class requires a 'mature immune-responsive environment'. The epigonal organ is the major site of neonatal B lymphopoiesis, based on the presence of developing B cells and recombination-activating gene 1 (RAG1)/terminal deoxynucleotidyl transferase (TdT) expression, indicative of antigen receptor rearrangement; such expression persists into adult life, whereas the spleen has negligible lymphopoietic activity. In adults but not neonates, many secretory B cells reside in the epigonal organ, suggesting, like in mammals, that B cells home to this primary lymphoid tissue after activation in other areas of the body.

  8. Transcriptome signature of the adult mouse choroid plexus

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    Marques Fernanda

    2011-01-01

    Full Text Available Abstract Background Although the gene expression profile of several tissues in humans and in rodent animal models has been explored, analysis of the complete choroid plexus (CP transcriptome is still lacking. A better characterization of the CP transcriptome can provide key insights into its functions as one of the barriers that separate the brain from the periphery and in the production of cerebrospinal fluid. Methods This work extends further what is known about the mouse CP transcriptome through a microarray analysis of CP tissue from normal mice under physiological conditions. Results We found that the genes most highly expressed are those implicated in energy metabolism (oxidative phosphorylation, glycolysis/gluconeogenesis and in ribosomal function, which is in agreement with the secretory nature of the CP. On the other hand, genes encoding for immune mediators are among those with lower expression in basal conditions. In addition, we found genes known to be relevant during brain development, and not previously identified to be expressed in the CP, including those encoding for various axonal guidance and angiogenesis molecules and for growth factors. Some of these are known to influence the neural stem cell niche in the subventricular zone, highlighting the involvement of the CP as a likely modulator of neurogenesis. Interestingly, our observations confirm that the CP transcriptome is unique, displaying low homology with that of other tissues. Of note, we describe here that the closest similarity is with the transcriptome of the endothelial cells of the blood-brain barrier. Conclusions Based on the data presented here, it will now be possible to further explore the function of particular proteins of the CP secretome in health and in disease.

  9. The temporal expression pattern of alpha-synuclein modulates olfactory neurogenesis in transgenic mice.

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    Sebastian R Schreglmann

    Full Text Available Adult neurogenesis mirrors the brain´s endogenous capacity to generate new neurons throughout life. In the subventricular zone/ olfactory bulb system adult neurogenesis is linked to physiological olfactory function and has been shown to be impaired in murine models of neuronal alpha-Synuclein overexpression. We analyzed the degree and temporo-spatial dynamics of adult olfactory bulb neurogenesis in transgenic mice expressing human wild-type alpha-Synuclein (WTS under the murine Thy1 (mThy1 promoter, a model known to have a particularly high tg expression associated with impaired olfaction.Survival of newly generated neurons (NeuN-positive in the olfactory bulb was unchanged in mThy1 transgenic animals. Due to decreased dopaminergic differentiation a reduction in new dopaminergic neurons within the olfactory bulb glomerular layer was present. This is in contrast to our previously published data on transgenic animals that express WTS under the control of the human platelet-derived growth factor β (PDGF promoter, that display a widespread decrease in survival of newly generated neurons in regions of adult neurogenesis, resulting in a much more pronounced neurogenesis deficit. Temporal and quantitative expression analysis using immunofluorescence co-localization analysis and Western blots revealed that in comparison to PDGF transgenic animals, in mThy1 transgenic animals WTS is expressed from later stages of neuronal maturation only but at significantly higher levels both in the olfactory bulb and cortex.The dissociation between higher absolute expression levels of alpha-Synuclein but less severe impact on adult olfactory neurogenesis in mThy1 transgenic mice highlights the importance of temporal expression characteristics of alpha-Synuclein on the maturation of newborn neurons.

  10. Morphometric Traits of Muscovy Ducks from Two Agro Ecological Zones of Nigeria

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    Yakubu, A.

    2011-01-01

    Full Text Available Morphological variation between Muscovy ducks from the guinea savannah and rainforest zones of Nigeria was examined using multivariate discriminant analysis. Data comprised eight morphometric traits measured in a total of 435 adult ducks randomly selected in the two agro-ecological zones. Common descriptive statistics showed that ducks from the rainforest zone had higher (P< 0.05 body weight, foot length and thigh circumference, while their guinea savannah counterparts were longer (P< 0.05 in the neck. Stepwise discriminant analysis indicated that foot length, neck length, thigh circumference and body length were more effective in discriminating between the duck populations. The low Mahalanobis distance of 3.39, as revealed by the canonical discriminant analysis, is an indication of high gene flow between ducks from the two agro-ecological zones. The cluster analysis also revealed the homogeneity of the genetic identity of the duck populations. The present information will be the basis for further characterization, conservation and sustainable genetic improvement strategies for indigenous ducks.

  11. A prospective evaluation of hippocampal radiation dose volume effects and memory deficits following cranial irradiation.

    Science.gov (United States)

    Ma, Ting Martin; Grimm, Jimm; McIntyre, Riley; Anderson-Keightly, Heather; Kleinberg, Lawrence R; Hales, Russell K; Moore, Joseph; Vannorsdall, Tracy; Redmond, Kristin J

    2017-11-01

    To prospectively evaluate hippocampal radiation dose volume effects and memory decline following cranial irradiation. Effects of hippocampal radiation over a wide range of doses were investigated by combining data from three prospective studies. In one, adults with small cell lung cancer received hippocampal-avoidance prophylactic cranial irradiation. In the other two, adults with glioblastoma multiforme received neural progenitor cell sparing radiation or no sparing with extra dose delivered to subventricular zone. Memory was measured by the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 6 months after radiation. Dose-volume histograms were generated and dose-response data were fitted to a nonlinear model. Of 60 patients enrolled, 30 were analyzable based on HVLT-R DR testing completion status, baseline HVLT-R DR and intracranial metastasis/recurrence or prior hippocampal resection status. We observed a dose-response of radiation to the hippocampus with regard to decline in HVLT-R DR. D50% of the bilateral hippocampi of 22.1 Gy is associated with 20% risk of decline. This prospective study demonstrates an association between hippocampal dose volume effects and memory decline measured by HVLT-R DR over a wide dose range. These data support a potential benefit of hippocampal sparing and encourage continued trial enrollment. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Radial glial cells in the adult dentate gyrus: what are they and where do they come from?

    Science.gov (United States)

    Berg, Daniel A; Bond, Allison M; Ming, Guo-Li; Song, Hongjun

    2018-01-01

    Adult neurogenesis occurs in the dentate gyrus in the mammalian hippocampus. These new neurons arise from neural precursor cells named radial glia-like cells, which are situated in the subgranular zone of the dentate gyrus. Here, we review the emerging topic of precursor heterogeneity in the adult subgranular zone. We also discuss how this heterogeneity may be established during development and focus on the embryonic origin of the dentate gyrus and radial glia-like stem cells. Finally, we discuss recently developed single-cell techniques, which we believe will be critical to comprehensively investigate adult neural stem cell origin and heterogeneity.

  13. Radiation protection zoning

    International Nuclear Information System (INIS)

    2015-01-01

    Radiation being not visible, the zoning of an area containing radioactive sources is important in terms of safety. Concerning radiation protection, 2 work zones are defined by regulations: the monitored zone and the controlled zone. The ministerial order of 15 may 2006 settles the frontier between the 2 zones in terms of radiation dose rates, the rules for access and the safety standards in both zones. Radioprotection rules and the name of the person responsible for radiation protection must be displayed. The frontier between the 2 zones must be materialized and marked with adequate equipment (specific danger signs and tapes). Both zones are submitted to selective entrance, the access for the controlled zone is limited because of the radiation risk and of the necessity of confining radioactive contamination while the limitation of the access to the monitored zone is due to radiation risk only. (A.C.)

  14. Polysaccharides from Wolfberry Prevents Corticosterone-Induced Inhibition of Sexual Behavior and Increases Neurogenesis

    Science.gov (United States)

    Lau, Benson Wui-Man; Lee, Jada Chia-Di; Li, Yue; Fung, Sophia Man-Yuk; Sang, Yan-Hua; Shen, Jiangang; Chang, Raymond Chuen-Chung; So, Kwok-Fai

    2012-01-01

    Lycium barbarum, commonly known as wolfberry, has been used as a traditional Chinese medicine for the treatment of infertility and sexual dysfunction. However, there is still a scarcity of experimental evidence to support the pro-sexual effect of wolfberry. The aim of this study is to determine the effect of Lycium barbarum polysaccharides (LBP) on male sexual behavior of rats. Here we report that oral feeding of LBP for 21 days significantly improved the male copulatory performance including increase of copulatory efficiency, increase of ejaculation frequency and shortening of ejaculation latency. Furthermore, sexual inhibition caused by chronic corticosterone was prevented by LBP. Simultaneously, corticosterone suppressed neurogenesis in subventricular zone and hippocampus in adult rats, which could be reversed by LBP. The neurogenic effect of LBP was also shown in vitro. Significant correlation was found between neurogenesis and sexual performance, suggesting that the newborn neurons are associated with reproductive successfulness. Blocking neurogenesis in male rats abolished the pro-sexual effect of LBP. Taken together, these results demonstrate the pro-sexual effect of LBP on normal and sexually-inhibited rats, and LBP may modulate sexual behavior by regulating neurogenesis. PMID:22523540

  15. The generation of oligodendroglial cells is preserved in the rostral migratory stream during aging

    Directory of Open Access Journals (Sweden)

    Vivian eCapilla-Gonzalez

    2013-09-01

    Full Text Available The subventricular zone (SVZ is the largest source of newly generated cells in the adult mammalian brain. SVZ-derived neuroblasts migrate via the rostral migratory stream (RMS to the olfactory bulb (OB, where they differentiate into mature neurons. Additionally, a small proportion of SVZ-derived cells contribute to the generation of myelinating oligodendrocytes. The production of new cells in the SVZ decreases during aging, affecting the incorporation of new neurons into the OB. However, the age-related changes that occur across the RMS are not fully understood. In this study we evaluate how aging affects the cellular organization of migrating neuroblast chains, the proliferation, and the fate of the newly generated cells in the SVZ-OB system. By using electron microscopy and immunostaining, we found that the RMS path becomes discontinuous and its cytoarchitecture is disorganized in aged mice (24-month-old mice. Subsequently, OB neurogenesis was impaired in the aged brain while the production of oligodendrocytes was not compromised. These findings provide new insight into oligodendrocyte preservation throughout life. Further exploration of this matter could help the development of new strategies to prevent neurological disorders associated with senescence.

  16. Evidence for a stem cell hierarchy in the adult human breast

    DEFF Research Database (Denmark)

    Villadsen, René; Fridriksdottir, Agla J; Rønnov-Jessen, Lone

    2007-01-01

    Cellular pathways that contribute to adult human mammary gland architecture and lineages have not been previously described. In this study, we identify a candidate stem cell niche in ducts and zones containing progenitor cells in lobules. Putative stem cells residing in ducts were essentially...... in laminin-rich extracellular matrix gels. Staining for the lineage markers keratins K14 and K19 further revealed multipotent cells in the stem cell zone and three lineage-restricted cell types outside this zone. Multiparameter cell sorting and functional characterization with reference to anatomical sites...

  17. Fuel conditioning facility zone-to-zone transfer administrative controls

    International Nuclear Information System (INIS)

    Pope, C. L.

    2000-01-01

    The administrative controls associated with transferring containers from one criticality hazard control zone to another in the Argonne National Laboratory (ANL) Fuel Conditioning Facility (FCF) are described. FCF, located at the ANL-West site near Idaho Falls, Idaho, is used to remotely process spent sodium bonded metallic fuel for disposition. The process involves nearly forty widely varying material forms and types, over fifty specific use container types, and over thirty distinct zones where work activities occur. During 1999, over five thousand transfers from one zone to another were conducted. Limits are placed on mass, material form and type, and container types for each zone. Ml material and containers are tracked using the Mass Tracking System (MTG). The MTG uses an Oracle database and numerous applications to manage the database. The database stores information specific to the process, including material composition and mass, container identification number and mass, transfer history, and the operators involved in each transfer. The process is controlled using written procedures which specify the zone, containers, and material involved in a task. Transferring a container from one zone to another is called a zone-to-zone transfer (ZZT). ZZTs consist of four distinct phases, select, request, identify, and completion

  18. Molecular differences in transition zone and peripheral zone prostate tumors

    Science.gov (United States)

    Sinnott, Jennifer A.; Rider, Jennifer R.; Carlsson, Jessica; Gerke, Travis; Tyekucheva, Svitlana; Penney, Kathryn L.; Sesso, Howard D.; Loda, Massimo; Fall, Katja; Stampfer, Meir J.; Mucci, Lorelei A.; Pawitan, Yudi; Andersson, Sven-Olof; Andrén, Ove

    2015-01-01

    Prostate tumors arise primarily in the peripheral zone (PZ) of the prostate, but 20–30% arise in the transition zone (TZ). Zone of origin may have prognostic value or reflect distinct molecular subtypes; however, it can be difficult to determine in practice. Using whole-genome gene expression, we built a signature of zone using normal tissue from five individuals and found that it successfully classified nine tumors of known zone. Hypothesizing that this signature captures tumor zone of origin, we assessed its relationship with clinical factors among 369 tumors of unknown zone from radical prostatectomies (RPs) and found that tumors that molecularly resembled TZ tumors showed lower mortality (P = 0.09) that was explained by lower Gleason scores (P = 0.009). We further applied the signature to an earlier study of 88 RP and 333 transurethral resection of the prostate (TURP) tumor samples, also of unknown zone, with gene expression on ~6000 genes. We had observed previously substantial expression differences between RP and TURP specimens, and hypothesized that this might be because RPs capture primarily PZ tumors, whereas TURPs capture more TZ tumors. Our signature distinguished these two groups, with an area under the receiver operating characteristic curve of 87% (P zones. Zone of origin may be important to consider in prostate tumor biomarker research. PMID:25870172

  19. The Tlx gene regulates the timing of neurogenesis in the cortex.

    Science.gov (United States)

    Roy, Kristine; Kuznicki, Kathleen; Wu, Qiang; Sun, Zhuoxin; Bock, Dagmar; Schutz, Gunther; Vranich, Nancy; Monaghan, A Paula

    2004-09-22

    The tailless (tlx) gene is a forebrain-restricted transcription factor. Tlx mutant animals exhibit a reduction in the size of the cerebral hemispheres and associated structures (Monaghan et al., 1997). Superficial cortical layers are specifically reduced, whereas deep layers are relatively unaltered (Land and Monaghan, 2003). To determine whether the adult laminar phenotype has a developmental etiology and whether it is associated with a change in proliferation/differentiation decisions, we examined the cell cycle and neurogenesis in the embryonic cortex. We found that there is a temporal and regional requirement for the Tlx protein in progenitor cells (PCs). Neurons prematurely differentiate at all rostrocaudal levels up to mid-neurogenesis in mutant animals. Heterozygote animals have an intermediate phenotype indicating there is a threshold requirement for Tlx in early cortical neurogenesis. Our studies indicate that PCs in the ventricular zone are sensitive to loss of Tlx in caudal regions only; however, PCs in the subventricular zone are altered at all rostrocaudal levels in tlx-deficient animals. Furthermore, we found that the cell cycle is shorter from embryonic day 9.5 in tlx-/- embryos. At mid-neurogenesis, the PC population becomes depleted, and late PCs have a longer cell cycle in tlx-deficient animals. Consequently, later generated structures, such as upper cortical layers, the dentate gyrus, and the olfactory bulbs, are severely reduced. These studies indicate that tlx is an essential intrinsic regulator in the decision to proliferate or differentiate in the developing forebrain.

  20. Expression pattern of the thrombopoietin receptor (Mpl) in the murine central nervous system.

    Science.gov (United States)

    Ivanova, Anna; Wuerfel, Jens; Zhang, Juan; Hoffmann, Olaf; Ballmaier, Matthias; Dame, Christof

    2010-07-28

    Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons. Mpl expression has been analysed in brain tissue on transcript level and in cultured primary rat neurons and astrocytes on protein level. Herein, we analysed Mpl expression in the developing and adult murine CNS by immunohistochemistry and investigated the brain of mice with homozygous Mpl deficiency (Mpl-/-) by MRI. Mpl was not detectable at developmental stages E12 to E15 in any resident cells of the CNS. From E18 onwards, robust Mpl expression was found in various brain areas, including cerebral cortex, olfactory bulb, thalamus, hypothalamus, medulla, pons, and the grey matter of spinal cord. However, major developmental changes became obvious: In the subventricular zone of the cerebral cortex Mpl expression occurred only during late gestation, while in the hippocampus Mpl expression was detectable for first time at stage P4. In the white matter of the cerebellum Mpl expression was restricted to the perinatal period. In the adult cerebellum, Mpl expression switched to Purkinje cell. The majority of other Mpl-positive cells were NeuN-positive neurons. None of the cells could be double-labelled with astrocyte marker GFAP. Mpl-/- mice showed no gross abnormalities of the brain. Our data locate Mpl expression to neurons at different subdivisions of the spinal cord, rhombencephalon, midbrain and prosencephalon. Besides neuronal cells Mpl protein is also expressed in Purkinje cells of the adult cerebellum.

  1. Ectoparasites of sheep in three agro-ecological zones in central Oromia, Ethiopia

    Directory of Open Access Journals (Sweden)

    Bersissa Kumsa

    2012-10-01

    Full Text Available A cross-sectional study was conducted to determine the prevalence and risk factors for ectoparasites infestation in sheep in three agro-ecological zones in central Oromia, Ethiopia, from October 2009 to April 2010. The study revealed that 637 (48.1% of the 1325 sheep examined were infested with one or more ectoparasites. The ectoparasites identified were Bovicola ovis (27.2%, Melophagus ovinus (16.4%, Ctenocephalides sp. (2.3%, Linognathus africanus (1.2%, Linognathus ovillus (0.3%, Sarcoptes sp. (1.2%, Amblyomma variegatum (4.4%, Rhipicephalus evertsi evertsi (1.9%, Rhipicephalus pravus (1.9%, Rhipicephalus (Boophilus decoloratus (1.1%, Rhipicephalus sanguineus (0.9%, Rhipicephalus praetextatus (1.1% and Hyalomma truncatum (1.6%. Statistically significant difference was observed in prevalence of B. ovis amongst study agroecological zones: highland 36.6%, midland 20.9% and lowland 14.0%. Significantly higher prevalence was recorded in highland agroecological zone. A significantly (OR = 0.041, p  0.05 was never recorded in the prevalence of all the identified species of ectoparasites between male and female sheep hosts. However, a significantly (p = 0.006 higher prevalence of B. ovis was recorded between young and adult sheep. The risk of B. ovis infestation was 1.45 times higher in young than the adult sheep. Furthermore, a significantly (p < 0.001 higher prevalence of M. ovinus, B. ovis and Sarcoptes sp. was found between sheep with poor and a good body condition. The ever increasing threat of ectoparasites on overall sheep productivity and tanning industry in Ethiopia warrants urgent control intervention. Further studies on the role of ectoparasites in transmission of diseases to sheep, zoonotic importance, comparative prevalence and load, and the importance of sheep as alternative hosts in different agroecological zones, breeds and management systems in Ethiopia are recommended so as to design applicable control programme in the country.

  2. Astrocyte morphology, heterogeneity and density in the developing African Giant Rat (Cricetomys gambianus

    Directory of Open Access Journals (Sweden)

    James Olukayode Olopade

    2015-05-01

    Full Text Available Astrocyte morphologies and heterogeneity were described in male African giant rats (AGR (Cricetomys gambianus, Waterhouse across three age groups (5 neonates, 5 juveniles and 5 adults using Silver impregnation method and immunohistochemistry against glia fibrillary acidic protein (GFAP. Immunopositive cell signaling, cell size and population were least in neonates, followed by adults and juveniles respectively. In neonates, astrocyte processes were mostly detected within the glia limitans of the mid and hind brain; their cell bodies measuring 32±4.8 µm in diameter against 91±5.4µm and 75± 1.9µm in juveniles and adults respectively. Astrocyte heterogeneity in juvenile and adult groups revealed eight subtypes to include fibrous astrocytes chiefly in the corpus callosum and brain stem, protoplasmic astrocytes in the cortex and dentate gyrus (DG; radial glia were found along the olfactory bulb (OB and subventricular zone (SVZ; velate astrocytes were mainly found in the cerebellum and hippocampus; marginal astrocytes close to the pia mater; Bergmann glia in the molecular layer of the cerebellum; perivascular and periventricular astrocytes in the cortex and third ventricle respectively. Cell counts from twelve anatomical regions of the brain were significantly higher in juveniles than in adults (p≤0.01 using unpaired student t-test in the cerebral cortex, pia, corpus callosum, rostral migratory stream (RMS, DG and cerebellum. Highest astrocyte count was found in the DG, while the least count was in the brain stem and sub cortex. Astrocytes along the periventricular layer of the OB are believed to be part of the radial glia system that transport newly formed cells towards the hippocampus and play roles in neurogenesis migration and homeostasis in the AGR. Therefore, astrocyte heterogeneity was examined across age groups in the AGR to determine whether age influences astrocytes population in different regions of the AGR brain and discuss

  3. Distribution and function of splash, an achaete-scute homolog in the adult olfactory organ of the Caribbean spiny lobster Panulirus argus

    Science.gov (United States)

    Tadesse, Tizeta; Schmidt, Manfred; Walthall, William W.; Tai, Phang C.; Derby, Charles D.

    2011-01-01

    achaete-scute complex (ASC) genes, which encode basic helix-loop-helix transcription factors, regulate embryonic and adult neurogenesis in many animals. In adult arthropods, including crustaceans, ASC homologs have been identified but rarely functionally characterized. We took advantage of the recently identified crustacean homolog, splash (spiny lobster achaete scute homolog), in the olfactory organ of the Caribbean spiny lobster Panulirus argus to examine its role in adult neurogenesis. We tested the hypothesis that splash is associated with but not restricted to sensory neuron formation in the olfactory organ, the antennular lateral flagellum (LF), of adult spiny lobsters. We demonstrated splash labeling in epithelial cells across LF developmental zones (i.e., proliferation and mature zones), in auxiliary cells surrounding dendrites of olfactory receptor neurons (ORNs), and in immature and mature ORNs, but not in granulocytes or chromatophores. Since ORN proliferation varies with molt stage, we examined splash expression across molt stages and found that molt stage affected splash expression in the ORN mature zone but not in the proliferation zone. In vivo incorporation of bromodeoxyuridine (BrdU) showed no correlation in the cellular pattern of splash expression and BrdU labeling. The intensity of splash labeling was dramatically enhanced in the proliferation zones following LF damage, suggesting enhanced splash expression during repair and/or regeneration. We conclude that splash is not closely associated with the formation of sensory neurons under normal physiological conditions, and we propose that splash is involved in repair and regeneration. We also propose that splash has additional roles other than neurogenesis in adult crustaceans. PMID:21394934

  4. WorkZoneQ user guide for two-lane freeway work zones.

    Science.gov (United States)

    2013-06-01

    WorkZoneQ was developed in Visual Basic for Applications (VBA) to implement the results of the previous study, : Queue and Users Costs in Highway Work Zones. This report contains the WorkZoneQ user guide. WorkZoneQ : consists of eight Excel ...

  5. The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage.

    Science.gov (United States)

    Wrage, Philip C; Tran, Thi; To, Khai; Keefer, Edward W; Ruhn, Kelly A; Hong, John; Hattangadi, Supriya; Treviño, Isaac; Tansey, Malú G

    2008-01-16

    We investigated whether adipose-derived adult stromal (ADAS) are of neural crest origin and the extent to which Notch 1 regulates their growth and differentiation. Mouse ADAS cells cultured in media formulated for neural stem cells (NSC) displayed limited capacity for self-renewal, clonogenicity, and neurosphere formation compared to NSC from the subventricular zone in the hippocampus. Although ADAS cells expressed Nestin, GFAP, NSE and Tuj1 in vitro, exposure to NSC differentiation supplements did not induce mature neuronal marker expression. In contrast, in mesenchymal stem cell (MSC) media, ADAS cells retained their ability to proliferate and differentiate beyond 20 passages and expressed high levels of Nestin. In neuritizing cocktails, ADAS cells extended processes, downregulated Nestin expression, and displayed depolarization-induced Ca(2+) transients but no spontaneous or evoked neural network activity on Multi-Electrode Arrays. Deletion of Notch 1 in ADAS cell cultures grown in NSC proliferation medium did not significantly alter their proliferative potential in vitro or the differentiation-induced downregulation of Nestin. Co-culture of ADAS cells with fibroblasts that stably expressed the Notch ligand Jagged 1 or overexpression of the Notch intracellular domain (NICD) did not alter ADAS cell growth, morphology, or cellular marker expression. ADAS cells did not display robust expression of neural crest transcription factors or genes (Sox, CRABP2, and TH); and lineage tracing analyses using Wnt1-Cre;Rosa26R-lacZ or -EYFP reporter mice confirmed that fewer than 2% of the ADAS cell population derived from a Wnt1-positive population during development. In summary, although media formulations optimized for MSCs or NSCs enable expansion of mouse ADAS cells in vitro, we find no evidence that these cells are of neural crest origin, that they can undergo robust terminal differentiation into functionally mature neurons, and that Notch 1 is likely to be a key

  6. ZoneLib

    DEFF Research Database (Denmark)

    Jessen, Jan Jacob; Schiøler, Henrik

    2006-01-01

    We present a dynamic model for climate in a livestock building divided into a number of zones, and a corresponding modular Simulink library (ZoneLib). While most literature in this area consider air flow as a control parameter we show how to model climate dynamics using actual control signals...... development of ZoneLib....

  7. Communities on the move: Pedestrian-oriented zoning as a facilitator of adult active travel to work in the United States

    OpenAIRE

    Jamie Friedman Chriqui; Jamie Friedman Chriqui; Julien eLeider; Emily eThrun; Lisa eNicholson; Sandy eSlater; Sandy eSlater

    2016-01-01

    Background: Communities across the United States have been reforming their zoning codes to create pedestrian-friendly neighborhoods with increased street connectivity, mixed-use and higher density, open space, transportation infrastructure, and a traditional neighborhood structure. Zoning code reforms include new urbanist zoning such as the SmartCode, form-based codes, transects, transportation and pedestrian-oriented developments, and traditional neighborhood developments.Purpose: To examine...

  8. Concomitant occurrence of sinus histiocytosis with massive lymphadenopathy and nodal marginal zone lymphoma.

    Science.gov (United States)

    Pang, Changlee S; Grier, David D; Beaty, Michael W

    2011-03-01

    Sinus histiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease, is a rare self-limiting disorder of histiocytes with unknown etiology. Sinus histiocytosis with massive lymphadenopathy is most common in children and young adults and is characterized by painless lymphadenopathy. Histologically there is a proliferation of sinus histiocytes with lymphophagocytosis or emperipolesis. On rare occasions, SHML has been associated with lymphoma, usually involving different anatomic sites and developing at different times. We report a case of concomitant SHML and nodal marginal zone lymphoma involving the same lymph node without involvement of other nodal or extranodal sites. The presence of concomitant SHML within the lymph node involved by nodal marginal zone lymphoma may represent the responsiveness of SHML histiocytes to B-cell-derived cytokines in lymphoproliferative disorders. To our knowledge, this is the first description of concomitant occurrence of SHML and nodal marginal zone lymphoma.

  9. Empowerment Zones and Enterprise Districts - MDC_EnterpriseZone

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Polygon feature class of Miami Dade County Enterprise Zones. Enterprise Zones are special areas in the county where certain incentives from the State are available...

  10. Slip Zone versus Damage Zone Micromechanics, Arima-Takasuki Tectonic Line, Japan

    Science.gov (United States)

    White, J. C.; Lin, A.

    2017-12-01

    The Arima-Takasuki Tectonic Line (ATTL) of southern Honshu, Japan is defined by historically active faults and multiple splays producing M7 earthquakes. The damage zone of the ATTL comprises a broad zone of crushed, comminuted and pulverized granite/rhyolite1,2containing cm-scale slip zones and highly comminuted injection veins. In this presentation, prior work on the ATTL fault rocks is extending to include microstructural characterization by transmission electron microscopy (TEM) from recent trenching of the primary slip zone, as well as secondary slip zones. This is necessary to adequately characterize the extremely fine-grained material (typically less than 1mm) in both damage and core zones. Damage zone material exhibits generally random textures3 whereas slip zones are macroscopically foliated, and compositionally layered, notwithstanding a fairly homogeneous protolith. The latter reflects fluid-rock interaction during both coseismic and interseismic periods. The slip zones are microstructurally heterogeneous at all scales, comprising not only cataclasites and phyllosilicate (clay)-rich gouge zones, but Fe/Mn pellets or clasts that are contained within gouge. These structures appear to have rolled and would suggest rapid recrystallization and/or growth. A central question related to earthquake recurrence along existing faults is the nature of the gouge. In both near-surface exposures and ongoing drilling at depth, "plastic" or "viscous" gouge zones comprise ultra-fine-grained clay-siliciclastic particles that would not necessarily respond in a simple frictional manner. Depending on whether the plastic nature of these slip zones develops during or after slip, subsequent focusing of slip within them could be complicated. 1 Mitchell, T.A., Ben-Zion, Y., Shimamoto, T., 2011. Ear. Planet. Sci. Lett. 308, 284-297. 2 Lin, A., Yamashita, K, Tanaka, M. J., 2013. Struc. Geol. 48, 3-13. 3 White, J.C., Lin, A. 2016. Proc. AGU Fall Mtg., T42-02 San Francisco.

  11. Evaluation of Ohio work zone speed zones process.

    Science.gov (United States)

    2014-06-01

    This report describes the methodology and results of analyses performed to determine the effectiveness of Ohio Department of Transportation processes for establishing work zone speed zones. Researchers observed motorists speed choice upstream of a...

  12. Spatial distribution of juvenile and adult stages of limnetic Cladocera in relation to selected environmental factors

    Directory of Open Access Journals (Sweden)

    Małgorzata Adamczuk

    2012-01-01

    Full Text Available Environmental factors have a varied impact on the development of juvenile and adult Cladocera, depending on their different physiological conditions and body size. The values of these factors alter spatially and temporarily, thus implying that they play a role in the spatial distribution of the pre-reproductive and potentially reproductive stages of cladocerans. The aim of the study was to determine seasonal and spatial variations in the distribution of juvenile and adult individuals of limnetic Cladocera in relation to selected physicochemical factors (temperature, conductivity, pH, concentration of dissolved oxygen, total organic carbon, total suspended solids and fish predation pressure (measured by Chesson’s coefficient λ in deep Lake Piaseczno (eastern Poland. Adult Cladocera displayed spatial distribution related to fish predation pressure. The species selectively eaten, B. coregoni and D. longispina, and non-selectively eaten, D. cucullata, selected the pelagic zone to exist, whereas those avoided by fish, D. brachyurum and B. longirostris, were evenly distributed in the littoral and pelagic zone. Juvenile cladocerans were strongly impacted by physico-chemical factors. Juvenile Daphnia, Diaphanosoma and B. longirostris showed preferences to biotic zones similar to the adults but differed in their habitat choices. Juvenile and adult stages of B. coregoni differed in their distribution, indicating that adult individuals impacted by high predation pressure alternatively modified their habitat selection. Principal component analysis (PCA ordination showed a seasonal tendency for the spatial segregation of the cladocerans, suggesting that possible competitive interactions between the studied cladocerans may also influence their distribution patterns.

  13. Histone Methylation and microRNA-dependent Regulation of Epigenetic Activities in Neural Progenitor Self-Renewal and Differentiation.

    Science.gov (United States)

    Cacci, Emanuele; Negri, Rodolfo; Biagioni, Stefano; Lupo, Giuseppe

    2017-01-01

    Neural stem/progenitor cell (NSPC) self-renewal and differentiation in the developing and the adult brain are controlled by extra-cellular signals and by the inherent competence of NSPCs to produce appropriate responses. Stage-dependent responsiveness of NSPCs to extrinsic cues is orchestrated at the epigenetic level. Epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulation control crucial aspects of NSPC development and function, and are also implicated in pathological conditions. While their roles in the regulation of stem cell fate have been largely explored in pluripotent stem cell models, the epigenetic signature of NSPCs is also key to determine their multipotency as well as their progressive bias towards specific differentiation outcomes. Here we review recent developments in this field, focusing on the roles of histone methylation marks and the protein complexes controlling their deposition in NSPCs of the developing cerebral cortex and the adult subventricular zone. In this context, we describe how bivalent promoters, carrying antagonistic epigenetic modifications, feature during multiple steps of neural development, from neural lineage specification to neuronal differentiation. Furthermore, we discuss the emerging cross-talk between epigenetic regulators and microRNAs, and how the interplay between these different layers of regulation can finely tune the expression of genes controlling NSPC maintenance and differentiation. In particular, we highlight recent advances in the identification of astrocyte-enriched microRNAs and their function in cell fate choices of NSPCs differentiating towards glial lineages.

  14. Identification of the rostral migratory stream in the canine and feline brain.

    Directory of Open Access Journals (Sweden)

    Saafan Z Malik

    Full Text Available In the adult rodent brain, neural progenitor cells migrate from the subventricular zone of the lateral ventricle towards the olfactory bulb in a track known as the rostral migratory stream (RMS. To facilitate the study of neural progenitor cells and stem cell therapy in large animal models of CNS disease, we now report the location and characteristics of the normal canine and feline RMS. The RMS was found in Nissl-stained sagittal sections of adult canine and feline brains as a prominent, dense, continuous cellular track beginning at the base of the anterior horn of the lateral ventricle, curving around the head of the caudate nucleus and continuing laterally and ventrally to the olfactory peduncle before entering the olfactory tract and bulb. To determine if cells in the RMS were proliferating, the thymidine analog 5-bromo-2-deoxyuridine (BrdU was administered and detected by immunostaining. BrdU-immunoreactive cells were present throughout this track. The RMS was also immunoreactive for markers of proliferating cells, progenitor cells and immature neurons (Ki-67 and doublecortin, but not for NeuN, a marker of mature neurons. Luxol fast blue and CNPase staining indicated that myelin is closely apposed to the RMS along much of its length and may provide guidance cues for the migrating cells. Identification and characterization of the RMS in canine and feline brain will facilitate studies of neural progenitor cell biology and migration in large animal models of neurologic disease.

  15. On the nature of the Cu-rich aggregates in brain astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, Brendan; Robison, Gregory; Osborn, Jenna; Kay, Martin; Thompson, Peter; Davis, Katherine; Zakharova, Taisiya; Antipova, Olga; Pushkar, Yulia

    2017-04-01

    Fulfilling a bevy of biological roles, copper is an essential metal for healthy brain function. Cu dyshomeostasis has been demonstrated to be involved in some neurological conditions including Menkes and Alzheimer’s diseases. We have previously reported localized Cu-rich aggregates in astrocytes of the subventricular zone (SVZ) in rodent brains with Cu concentrations in the hundreds of millimolar. Metallothionein, a cysteine-rich protein critical to metal homeostasis and known to participate in a variety of neuroprotective and neuroregenerative processes, was proposed as a binding protein. Here, we present an analysis of metallothionein(1,2) knockout (MTKO) mice and age-matched controls using X-ray fluorescence microscopy. In large structures such as the corpus callosum, cortex, and striatum, there is no significant difference in Cu, Fe, or Zn concentrations in MTKO mice compared to age-matched controls. In the astrocyte-rich subventricular zone where Cu-rich aggregates reside, approximately 1/3 as many Cu-rich aggregates persist in MTKO mice resulting in a decrease in periventricular Cu concentration. Aggregates in both wild-type and MTKO mice show XANES spectra characteristic of CuxSy multimetallic clusters and have similar [S]/[Cu] ratios. Consistent with assignment as a CuxSy multimetallic cluster, the astrocyte-rich SVZ of both MTKO and wild-type mice exhibit autofluorescent bodies, though MTKO mice exhibit fewer. Furthermore, XRF imaging of Au-labeled lysosomes and ubiquitin demonstrates a lack of co-localization with Cu-rich aggregates suggesting they are not involved in a degradation pathway. Overall, these data suggest that Cu in aggregates is bound by either metallothionein-3 or a yet unknown protein similar to metallothionein.

  16. Estimated clinical benefit of protecting neurogenesis in the developing brain during radiation therapy for pediatric medulloblastoma

    DEFF Research Database (Denmark)

    Blomstrand, M.; Berthelsen, Anne Kiil; Munck af Rosenschöld, Per Martin

    2012-01-01

    to the whole-brain irradiation that is part of standard management. Neurogenesis is very sensitive to radiation, and limiting the radiation dose to the hippocampus and the subventricular zone (SVZ) may preserve neurocognitive function. Radiotherapy plans were created using 4 techniques: standard opposing...... fields, intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (IMAT), and intensity-modulated proton therapy (IMPT). Mean dose to the hippocampus and SVZ (mean for both sites) could be limited to 88.3% (range, 83.6%-91.0%), 77.1% (range, 71.5%-81.3%), and 42.3% (range, 26......-modulated proton therapy, thus making this an attractive option to be tested in a prospective clinical trial....

  17. Radial glial cells in the adult dentate gyrus: what are they and where do they come from? [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Daniel A. Berg

    2018-03-01

    Full Text Available Adult neurogenesis occurs in the dentate gyrus in the mammalian hippocampus. These new neurons arise from neural precursor cells named radial glia-like cells, which are situated in the subgranular zone of the dentate gyrus. Here, we review the emerging topic of precursor heterogeneity in the adult subgranular zone. We also discuss how this heterogeneity may be established during development and focus on the embryonic origin of the dentate gyrus and radial glia-like stem cells. Finally, we discuss recently developed single-cell techniques, which we believe will be critical to comprehensively investigate adult neural stem cell origin and heterogeneity.

  18. Fault zone hydrogeology

    Science.gov (United States)

    Bense, V. F.; Gleeson, T.; Loveless, S. E.; Bour, O.; Scibek, J.

    2013-12-01

    Deformation along faults in the shallow crust (research effort of structural geologists and hydrogeologists. However, we find that these disciplines often use different methods with little interaction between them. In this review, we document the current multi-disciplinary understanding of fault zone hydrogeology. We discuss surface- and subsurface observations from diverse rock types from unlithified and lithified clastic sediments through to carbonate, crystalline, and volcanic rocks. For each rock type, we evaluate geological deformation mechanisms, hydrogeologic observations and conceptual models of fault zone hydrogeology. Outcrop observations indicate that fault zones commonly have a permeability structure suggesting they should act as complex conduit-barrier systems in which along-fault flow is encouraged and across-fault flow is impeded. Hydrogeological observations of fault zones reported in the literature show a broad qualitative agreement with outcrop-based conceptual models of fault zone hydrogeology. Nevertheless, the specific impact of a particular fault permeability structure on fault zone hydrogeology can only be assessed when the hydrogeological context of the fault zone is considered and not from outcrop observations alone. To gain a more integrated, comprehensive understanding of fault zone hydrogeology, we foresee numerous synergistic opportunities and challenges for the discipline of structural geology and hydrogeology to co-evolve and address remaining challenges by co-locating study areas, sharing approaches and fusing data, developing conceptual models from hydrogeologic data, numerical modeling, and training interdisciplinary scientists.

  19. Tau protein and adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Almudena eFuster-Matanzo

    2012-07-01

    Full Text Available Tau protein is a microtubule associated protein found in the axonal compartment that stabilizes neuronal microtubules under normal physiological conditions. Tau metabolism has attracted much attention because of its role in neurodegenerative disorders called tauopathies, mainly Alzheimer disease. Here, we review recent findings suggesting that axonal outgrowth in subgranular zone during adult hippocampal neurogenesis requires a dynamic microtubule network and tau protein facilitates to maintain that dynamic cytoskeleton. Those functions are carried out in part by tau isoform with only three microtubule-binding domains (without exon 10 and by presence of hypherphosphorylated tau forms. Thus, tau is a good marker and a valuable tool to study new axons in adult neurogenesis.

  20. Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline.

    Science.gov (United States)

    Lupo, Giuseppe; Nisi, Paola S; Esteve, Pilar; Paul, Yu-Lee; Novo, Clara Lopes; Sidders, Ben; Khan, Muhammad A; Biagioni, Stefano; Liu, Hai-Kun; Bovolenta, Paola; Cacci, Emanuele; Rugg-Gunn, Peter J

    2018-06-01

    Adult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age-associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale. In this study, we compare the transcriptional, histone methylation and DNA methylation signatures of NSPCs derived from the subventricular zone (SVZ) of young adult (3 months old) and aged (18 months old) mice. Surprisingly, the transcriptional and epigenomic profiles of SVZ-derived NSPCs are largely unchanged in aged cells. Despite the global similarities, we detect robust age-dependent changes at several hundred genes and regulatory elements, thereby identifying putative regulators of neurogenic decline. Within this list, the homeobox gene Dbx2 is upregulated in vitro and in vivo, and its promoter region has altered histone and DNA methylation levels, in aged NSPCs. Using functional in vitro assays, we show that elevated Dbx2 expression in young adult NSPCs promotes age-related phenotypes, including the reduced proliferation of NSPC cultures and the altered transcript levels of age-associated regulators of NSPC proliferation and differentiation. Depleting Dbx2 in aged NSPCs caused the reverse gene expression changes. Taken together, these results provide new insights into the molecular programmes that are affected during mouse NSPC aging, and uncover a new functional role for Dbx2 in promoting age-related neurogenic decline. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  1. 33 CFR 165.169 - Safety and Security Zones: New York Marine Inspection Zone and Captain of the Port Zone.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety and Security Zones: New... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY... Areas First Coast Guard District § 165.169 Safety and Security Zones: New York Marine Inspection Zone...

  2. 33 CFR 165.814 - Security Zones; Captain of the Port Houston-Galveston Zone.

    Science.gov (United States)

    2010-07-01

    ... Port Houston-Galveston Zone. 165.814 Section 165.814 Navigation and Navigable Waters COAST GUARD... § 165.814 Security Zones; Captain of the Port Houston-Galveston Zone. (a) Location. The following areas are designated as security zones: (1) Houston, Texas. The Houston Ship Channel and all associated...

  3. Proliferation zones in the axolotl brain and regeneration of the telencephalon

    Directory of Open Access Journals (Sweden)

    Maden Malcolm

    2013-01-01

    Full Text Available Abstract Background Although the brains of lower vertebrates are known to exhibit somewhat limited regeneration after incisional or stab wounds, the Urodele brain exhibits extensive regeneration after massive tissue removal. Discovering whether and how neural progenitor cells that reside in the ventricular zones of Urodeles proliferate to mediate tissue repair in response to injury may produce novel leads for regenerative strategies. Here we show that endogenous neural progenitor cells resident to the ventricular zone of Urodeles spontaneously proliferate, producing progeny that migrate throughout the telencephalon before terminally differentiating into neurons. These progenitor cells appear to be responsible for telencephalon regeneration after tissue removal and their activity may be up-regulated by injury through an olfactory cue. Results There is extensive proliferation of endogenous neural progenitor cells throughout the ventricular zone of the adult axolotl brain. The highest levels are observed in the telencephalon, especially the dorsolateral aspect, and cerebellum. Lower levels are observed in the mesencephalon and rhombencephalon. New cells produced in the ventricular zone migrate laterally, dorsally and ventrally into the surrounding neuronal layer. After migrating from the ventricular zone, the new cells primarily express markers of neuronal differentiative fates. Large-scale telencephalic tissue removal stimulates progenitor cell proliferation in the ventricular zone of the damaged region, followed by proliferation in the tissue that surrounds the healing edges of the wound until the telencephalon has completed regeneration. The proliferative stimulus appears to reside in the olfactory system, because telencephalic regeneration does not occur in the brains of olfactory bulbectomized animals in which the damaged neural tissue simply heals over. Conclusion There is a continual generation of neuronal cells from neural progenitor cells

  4. Ectoparasites of sheep in three agro-ecological zones in central Oromia, Ethiopia

    Directory of Open Access Journals (Sweden)

    Bersissa Kumsa

    2012-02-01

    Full Text Available A cross-sectional study was conducted to determine the prevalence and risk factors for ectoparasites infestation in sheep in three agro-ecological zones in central Oromia, Ethiopia, from October 2009 to April 2010. The study revealed that 637 (48.1% of the 1325 sheep examined were infested with one or more ectoparasites. The ectoparasites identified were Bovicola ovis (27.2%, Melophagus ovinus (16.4%, Ctenocephalides sp. (2.3%, Linognathus africanus (1.2%, Linognathus ovillus (0.3%, Sarcoptes sp. (1.2%, Amblyomma variegatum (4.4%, Rhipicephalus evertsi evertsi (1.9%, Rhipicephalus pravus (1.9%, Rhipicephalus (Boophilus decoloratus (1.1%, Rhipicephalus sanguineus (0.9%, Rhipicephalus praetextatus (1.1% and Hyalomma truncatum (1.6%. Statistically significant difference was observed in prevalence of B. ovis amongst study agroecological zones: highland 36.6%, midland 20.9% and lowland 14.0%. Significantly higher prevalence was recorded in highland agroecological zone. A significantly (OR = 0.041, p < 0.001 higher prevalence of M. ovinus in the highland (31.7% than in both the lowland (0% and midland (1.9% was observed. The risk of tick infestation in the lowland and midland was 9.883 times and 13.988 times higher than the risk in the highland, respectively. A significantly higher prevalence of Ctenocephalides species was encountered in both the lowland (OR = 4.738, p = 0.011 and midland (OR = 8.078, p = 0.000 than in the highland agro-ecological zone. However, a significant difference (p = 0.191 amongst agro-ecological zones was not found for the prevalence of Linognathus and Sarcoptes species. Statistically significant variation (p > 0.05 was never recorded in the prevalence of all the identified species of ectoparasites between male and female sheep hosts. However, a significantly (p = 0.006 higher prevalence of B. ovis was recorded between young and adult sheep. The risk of B. ovis infestation was 1.45 times higher in young than the adult sheep

  5. Ectoparasites of sheep in three agro-ecological zones in central Oromia, Ethiopia.

    Science.gov (United States)

    Kumsa, Bersissa; Beyecha, Kebede; Geloye, Mesula

    2012-10-23

    A cross-sectional study was conducted to determine the prevalence and risk factors for ectoparasites infestation in sheep in three agro-ecological zones in central Oromia, Ethiopia, from October 2009 to April 2010. The study revealed that 637 (48.1%) of the 1325 sheep examined were infested with one or more ectoparasites. The ectoparasites identified were Bovicola ovis (27.2%), Melophagus ovinus (16.4%), Ctenocephalides sp. (2.3%), Linognathus africanus (1.2%), Linognathus ovillus (0.3%), Sarcoptes sp. (1.2%), Amblyomma variegatum (4.4%), Rhipicephalus evertsi evertsi (1.9%), Rhipicephalus pravus (1.9%), Rhipicephalus (Boophilus) decoloratus (1.1%), Rhipicephalus sanguineus (0.9%), Rhipicephalus praetextatus (1.1%) and Hyalomma truncatum (1.6%). Statistically significant difference was observed in prevalence of B. ovis amongst study agroecological zones: highland 36.6%, midland 20.9% and lowland 14.0%. Significantly higher prevalence was recorded in highland agroecological zone. A significantly (OR = 0.041, p < 0.001) higher prevalence of M. ovinus in the highland (31.7%) than in both the lowland (0%) and midland (1.9%) was observed. The risk of tick infestation in the lowland and midland was 9.883 times and 13.988 times higher than the risk in the highland, respectively. A significantly higher prevalence of Ctenocephalides species was encountered in both the lowland (OR = 4.738, p = 0.011) and midland (OR = 8.078, p = 0.000) than in the highland agro-ecological zone. However, a significant difference (p = 0.191) amongst agro-ecological zones was not found for the prevalence of Linognathus and Sarcoptes species. Statistically significant variation (p > 0.05) was never recorded in the prevalence of all the identified species of ectoparasites between male and female sheep hosts. However, a significantly (p = 0.006) higher prevalence of B. ovis was recorded between young and adult sheep. The risk of B. ovis infestation was 1.45 times higher in young than the adult

  6. Intravenous grafts of amniotic fluid-derived stem cells induce endogenous cell proliferation and attenuate behavioral deficits in ischemic stroke rats.

    Directory of Open Access Journals (Sweden)

    Naoki Tajiri

    Full Text Available We recently reported isolation of viable rat amniotic fluid-derived stem (AFS cells [1]. Here, we tested the therapeutic benefits of AFS cells in a rodent model of ischemic stroke. Adult male Sprague-Dawley rats received a 60-minute middle cerebral artery occlusion (MCAo. Thirty-five days later, animals exhibiting significant motor deficits received intravenous transplants of rat AFS cells or vehicle. At days 60-63 post-MCAo, significant recovery of motor and cognitive function was seen in stroke animals transplanted with AFS cells compared to vehicle-infused stroke animals. Infarct volume, as revealed by hematoxylin and eosin (H&E staining, was significantly reduced, coupled with significant increments in the cell proliferation marker, Ki67, and the neuronal marker, MAP2, in the dentate gyrus (DG [2] and the subventricular zone (SVZ of AFS cell-transplanted stroke animals compared to vehicle-infused stroke animals. A significantly higher number of double-labeled Ki67/MAP2-positive cells and a similar trend towards increased Ki67/MAP2 double-labeling were observed in the DG and SVZ of AFS cell-transplanted stroke animals, respectively, compared to vehicle-infused stroke animals. This study reports the therapeutic potential of AFS cell transplantation in stroke animals, possibly via enhancement of endogenous repair mechanisms.

  7. The Sorong Fault Zone, Indonesia: Mapping a Fault Zone Offshore

    Science.gov (United States)

    Melia, S.; Hall, R.

    2017-12-01

    The Sorong Fault Zone is a left-lateral strike-slip fault zone in eastern Indonesia, extending westwards from the Bird's Head peninsula of West Papua towards Sulawesi. It is the result of interactions between the Pacific, Caroline, Philippine Sea, and Australian Plates and much of it is offshore. Previous research on the fault zone has been limited by the low resolution of available data offshore, leading to debates over the extent, location, and timing of movements, and the tectonic evolution of eastern Indonesia. Different studies have shown it north of the Sula Islands, truncated south of Halmahera, continuing to Sulawesi, or splaying into a horsetail fan of smaller faults. Recently acquired high resolution multibeam bathymetry of the seafloor (with a resolution of 15-25 meters), and 2D seismic lines, provide the opportunity to trace the fault offshore. The position of different strands can be identified. On land, SRTM topography shows that in the northern Bird's Head the fault zone is characterised by closely spaced E-W trending faults. NW of the Bird's Head offshore there is a fold and thrust belt which terminates some strands. To the west of the Bird's Head offshore the fault zone diverges into multiple strands trending ENE-WSW. Regions of Riedel shearing are evident west of the Bird's Head, indicating sinistral strike-slip motion. Further west, the ENE-WSW trending faults turn to an E-W trend and there are at least three fault zones situated immediately south of Halmahera, north of the Sula Islands, and between the islands of Sanana and Mangole where the fault system terminates in horsetail strands. South of the Sula islands some former normal faults at the continent-ocean boundary with the North Banda Sea are being reactivated as strike-slip faults. The fault zone does not currently reach Sulawesi. The new fault map differs from previous interpretations concerning the location, age and significance of different parts of the Sorong Fault Zone. Kinematic

  8. A two-dimensional time domain near zone to far zone transformation

    Science.gov (United States)

    Luebbers, Raymond J.; Ryan, Deirdre; Beggs, John H.; Kunz, Karl S.

    1991-01-01

    In a previous paper, a time domain transformation useful for extrapolating 3-D near zone finite difference time domain (FDTD) results to the far zone was presented. In this paper, the corresponding 2-D transform is outlined. While the 3-D transformation produced a physically observable far zone time domain field, this is not convenient to do directly in 2-D, since a convolution would be required. However, a representative 2-D far zone time domain result can be obtained directly. This result can then be transformed to the frequency domain using a Fast Fourier Transform, corrected with a simple multiplicative factor, and used, for example, to calculate the complex wideband scattering width of a target. If an actual time domain far zone result is required it can be obtained by inverse Fourier transform of the final frequency domain result.

  9. Assessing Movements of Brushtail Possums (Trichosurus vulpecula) in Relation to Depopulated Buffer Zones for the Management of Wildlife Tuberculosis in New Zealand.

    Science.gov (United States)

    Byrom, Andrea E; Anderson, Dean P; Coleman, Morgan; Thomson, Caroline; Cross, Martin L; Pech, Roger P

    2015-01-01

    In New Zealand, managing the threat of bovine tuberculosis (TB) to livestock includes population reduction of potentially infectious wildlife, primarily the brushtail possum (Trichosurus vulpecula). Population control is often targeted on forested buffer zones adjacent to farmland, in order to limit movements of possums across the buffer and reduce the risk of disease transmission to livestock. To assess the effectiveness of buffers in protecting livestock we analysed GPS telemetry data from possums located in untreated forest adjacent to buffers, and used these data to characterise patterns of movement that could lead to possums reaching farmland during the season when most dispersal occurs. Analyses of movement data showed that the direction of dispersal by sub-adult and adult possums and the extent of long exploratory movements were not biased toward forest buffers, even though these provided vacant habitat as suitable for possums as untreated forest. Instead, dispersal and exploratory movements were uncommon even for sub-adult possums and such events typically lasted buffer to reach farmland. Our results indicate short-term reduction in the risk of TB transmission from possums to livestock in New Zealand by the use of depopulated buffer zones, while acknowledging that the threat of disease spread from untreated forest is likely to increase over time as possum population density and, potentially, TB prevalence among those possums, increase in the buffer zone.

  10. Root zone effects on tracer migration in arid zones

    International Nuclear Information System (INIS)

    Tyler, S.W.; Walker, G.R.

    1994-01-01

    The study of groundwater recharge and soil water movement in arid regions has received increased attention in the search for safe disposal sites for hazardous wastes. In passing through the upper 1 to 2 m of most soil profiles, tracers indicative of recharge such as Cl, 2 H, 18 O, Br, 3 H, and 56 Cl are subjected to a wide range of processes not encountered deeper in the profile. This transition zone, where water enters as precipitation and leaves as recharge, is often ignored when environmental tracers are used to estimate deep soil water flux and recharge, yet its effect may be profound. In this work, we reexamine the processes of root extraction and its effect on the velocity and distribution of tracers. Examples are presented for idealized conditions, which show clearly the relation between the root zone processes and the deep drainage or recharge. The results indicate that, when recharge is small and root zone processes are not accounted for, tracer techniques can significantly overestimate recharge until the tracer has moved well below the root zone. By incorporating simple models of root zone processes, a clearer understanding of tracer distributions and a more accurate estimate of recharge can then be made. 11 refs., 9 figs

  11. Malaria vector populations across ecological zones in Guinea Conakry and Mali, West Africa.

    Science.gov (United States)

    Coulibaly, Boubacar; Kone, Raymond; Barry, Mamadou S; Emerson, Becky; Coulibaly, Mamadou B; Niare, Oumou; Beavogui, Abdoul H; Traore, Sekou F; Vernick, Kenneth D; Riehle, Michelle M

    2016-04-08

    Malaria remains a pervasive public health problem in sub-Saharan West Africa. Here mosquito vector populations were explored across four sites in Mali and the Republic of Guinea (Guinea Conakry). The study samples the major ecological zones of malaria-endemic regions in West Africa within a relatively small distance. Mosquito vectors were sampled from larval pools, adult indoor resting sites, and indoor and outdoor human-host seeking adults. Mosquitoes were collected at sites spanning 350 km that represented arid savannah, humid savannah, semi-forest and deep forest ecological zones, in areas where little was previously known about malaria vector populations. 1425 mosquito samples were analysed by molecular assays to determine species, genetic attributes, blood meal sources and Plasmodium infection status. Anopheles gambiae and Anopheles coluzzii were the major anophelines represented in all collections across the ecological zones, with A. coluzzii predominant in the arid savannah and A. gambiae in the more humid sites. The use of multiple collection methodologies across the sampling sites allows assessment of potential collection bias of the different methods. The L1014F kdr insecticide resistance mutation (kdr-w) is found at high frequency across all study sites. This mutation appears to have swept almost to fixation, from low frequencies 6 years earlier, despite the absence of widespread insecticide use for vector control. Rates of human feeding are very high across ecological zones, with only small fractions of animal derived blood meals in the arid and humid savannah. About 30 % of freshly blood-fed mosquitoes were positive for Plasmodium falciparum presence, while the rate of mosquitoes with established infections was an order of magnitude lower. The study represents detailed vector characterization from an understudied area in West Africa with endemic malaria transmission. The deep forest study site includes the epicenter of the 2014 Ebola virus epidemic

  12. Frequency of a typical radiological pattern of pulmonary tuberculosis in adults and elderly (dissertation based article)

    International Nuclear Information System (INIS)

    Jamal, A.N.; Pasha, M.B.

    2011-01-01

    Tuberculosis is one of the oldest diseases and one third of the world's population is affected. Typical pattern (infiltration and or nodules with or without cavitations involving upper zone lung field) of pulmonary tuberculosis is the most common mode of radiological presentation in adults. There is a trend towards a relative increase in the unusual radiological presentations. This study was conducted to determine the frequency of atypical radiological trend of pulmonary tuberculosis in adults and elderly. Subjects and Methods: The objective of the study was to determine frequency of a typical radiological pattern of pulmonary tuberculosis in adults and elderly. It was a descriptive (case series) study and was conducted in the Department of Pulmonology, Nishtar Hospital Multan. The study duration was six months from 24 May 2006 to 23 November 2006. 300 patients presenting with pulmonary tuberculosis were selected. History and clinical examination was done. Relevant investigations and x-ray chest were carried out. Lesions like infiltration with or without cavitation were localized in upper, middle and lower zones. Groups of patients with their x-ray findings in different zones were made and analyzed accordingly, data collected were entered in specific proforma. Results: 205 (97.6%) adults and 85 (94.4%) elderly presented with cough while 205 (97.6%) adults and 75 (83.3%) elderly presented with fever. Out of 300 cases infiltration was found in 141 (46.19% vs 48.88%) young adult and elderly cases. There were 99 cases with nodule (35.71% vs 26.66%) and 60 cases had cavitation (18.09% vs 24.44%). Conclusion: There is a trend towards a relative increase in the frequency of unusual radiological presentations which is more common in elderly. (author)

  13. 75 FR 50700 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, and Drawbridge...

    Science.gov (United States)

    2010-08-17

    ...] Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, and Drawbridge Operation... notice lists temporary safety zones, security zones, special local regulations, and drawbridge operation... responsive to the safety and security needs within their jurisdiction; therefore, District Commanders and...

  14. Radiant zone heated particulate filter

    Science.gov (United States)

    Gonze, Eugene V [Pinckney, MI

    2011-12-27

    A system includes a particulate matter (PM) filter including an upstream end for receiving exhaust gas and a downstream end. A radiant zoned heater includes N zones, where N is an integer greater than one, wherein each of the N zones includes M sub-zones, where M is an integer greater than or equal to one. A control module selectively activates at least a selected one of the N zones to initiate regeneration in downstream portions of the PM filter from the one of the N zones, restricts exhaust gas flow in a portion of the PM filter that corresponds to the selected one of the N zones, and deactivates non-selected ones of the N zones.

  15. The Disruption of Subsistence Agricultural Systems in Rural Yucatan, Mexico may have Contributed to the Coexistence of Stunting in Children with Adult Overweight and Obesity.

    Science.gov (United States)

    Gurri, Francisco D

    2015-12-01

    This paper attempts to link last century's disruption of local agricultural systems to today's presence of childhood under nutrition and adult overweight and obesity in the Yucatan Peninsula. It first compares Height for Age (H/A), Weight for Age (W/A) and Body Mass Index (BMI) of children from three rural populations in Yucatan and Campeche, Mexico whose subsistence strategy had been altered to different degrees since 1970. It then compares BMI in adults, in the same regions, born before and after the alteration of their environment in the 1970's. Children in the least disrupted zone were taller and had lower BMI than children in the other two, but were not heavier than children from the richest disrupted zone. Children in the poorest disrupted zone were shorter and lighter than the rest. BMI in adult men was higher in the two most disrupted zones only in those cohorts that grew up after the traditional agricultural regime was altered. It is concluded that disruptions of staple-based subsistence agriculture promoted a stockier phenotype in children and a tendency to accumulate body fat. Persistence of these conditions in the twenty first century has favored the coexistence of stunting during childhood with adults who easily become overweight.

  16. Towards stacked zone plates

    International Nuclear Information System (INIS)

    Werner, S; Rehbein, S; Guttman, P; Heim, S; Schneider, G

    2009-01-01

    Fresnel zone plates are the key optical elements for soft and hard x-ray microscopy. For short exposure times and minimum radiation load of the specimen the diffraction efficiency of the zone plate objectives has to be maximized. As the efficiency strongly depends on the height of the diffracting zone structures the achievable aspect ratio of the nanostructures determines these limits. To reach aspect ratios ≥ 20:1 for high efficient optics we propose to superimpose zone plates on top of each other. With this multiplication approach the final aspect ratio is only limited by the number of stacked zone plate layers. For the stack process several nanostructuring process steps have to be developed and/or improved. Our results show for the first time two layers of zone plates stacked on top of each other.

  17. 76 FR 70342 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

    Science.gov (United States)

    2011-11-14

    ...] Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation... published in the Federal Register. This notice lists temporary safety zones, security zones, special local... Commanders and Captains of the Port (COTP) must be immediately responsive to the safety and security needs...

  18. 76 FR 48751 - Security Zones; Captain of the Port Lake Michigan Zone

    Science.gov (United States)

    2011-08-09

    ... Jardine Water Filtration Plant security zone would encompass all U.S. navigable waters of Lake Michigan... areas near shore to Chicago's water filtration plants; the security zones have been designed to allow.... 165.910 Security Zones; Captain of the Port Lake Michigan. (a) * * * (1) Jardine Water Filtration...

  19. Cues for Cure; From within

    Directory of Open Access Journals (Sweden)

    Editorial

    2016-05-01

    Full Text Available Nature's innate ability to effect the process of healing after any type of injury, is a phenomena known to be existing across phylogeny. However, the processes, mechanisms and the outcome differ between organisms, organs, tissues and other relevant biological and environmental factors. The maintenance and repair of adult tissues are dependent on tissue-resident stem cells [1]. Studies now reveal that the regeneration of damaged or dysfunctional or lost tissues and cells which occur after transplantation of exogenous stem cells and adult cells are mainly due to paracrine effects of these transplanted cells stimulating the tissue resident stem cells [2]. Thus, based on the available evidence, it is the body's natural endogenous regenerative mechanisms which gain more significance in regenerative biology. This could be enhanced by the exogenously applied cells for the best outcome. Two studies presented in this issue have reiterated this faith. Takeuchi et al [1] have tested the hypothesis that electro-resection of bladder tissue induces resident stem cells to participate in tissue repair. They have studied the levels of stem cell markers such as Oct4, CD90, and CD73 after bladder electro-resection. They have concluded that CD90 and CD73, which are markers of mesenchymal stromal cells (MSCs, are upregulated and thus, these MSCs participate in the tissue repair process [3]. The other study by Jones and Connor has authenticated the transient recruitment of migratory neuroblasts and oligodendrocyte precursor cells (OPC from the subventricular zone (SVZ during endogenous repair in a rodent model and the interaction that occurs between signals released from the environment of the lesion and gene expression in the recruited cells following excitotoxic brain Injury [4]. The common theme to both the studies is the recruitment of tissue resident stem cells or precursors for contribution to regeneration after tissue injury. Clinical applications using

  20. Cytoarchitecture and ultrastructure of neural stem cell niches and neurogenic complexes maintaining adult neurogenesis in the olfactory midbrain of spiny lobsters, Panulirus argus.

    Science.gov (United States)

    Schmidt, Manfred; Derby, Charles D

    2011-08-15

    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 labeling with cell-type-selective markers. The clump of cells is composed of unique bipolar clump-forming cells that collectively completely envelop the adult neuroblast and are themselves ensheathed by a layer of processes of multipolar cell body glia. An arteriole is attached to the clump of cells, but dye perfusion experiments show that hemolymph has no access to the interior of the clump of cells. Thus, the clump of cells fulfills morphological criteria of a protective stem cell niche, with clump-forming cells constituting the adult neuroblast's microenvironment together with the cell body glia processes separating it from other tissue components. Bromodeoxyuridine pulse-chase experiments with short survival times suggest that adult neuroblasts are not quiescent but rather cycle actively during daytime. We propose a cell lineage model in which an asymmetrically dividing adult neuroblast repopulates the pool of neuronal progenitor cells in the associated proliferation zone. In conclusion, as in mammalian brains, adult neurogenesis in crustacean brains is fueled by neural stem cells that are maintained by stem cell niches that preserve elements of the embryonic microenvironment and contain glial and vascular elements. Copyright © 2011 Wiley-Liss, Inc.

  1. SVCT2 vitamin C transporter expression in progenitor cells of the postnatal neurogenic niche

    Science.gov (United States)

    Pastor, Patricia; Cisternas, Pedro; Salazar, Katterine; Silva-Alvarez, Carmen; Oyarce, Karina; Jara, Nery; Espinoza, Francisca; Martínez, Agustín D.; Nualart, Francisco

    2013-01-01

    Known as a critical antioxidant, recent studies suggest that vitamin C plays an important role in stem cell generation, proliferation and differentiation. Vitamin C also enhances neural differentiation during cerebral development, a function that has not been studied in brain precursor cells. We observed that the rat neurogenic niche is structurally organized at day 15 of postnatal development, and proliferation and neural differentiation increase at day 21. In the human brain, a similar subventricular niche was observed at 1-month of postnatal development. Using immunohistochemistry, sodium-vitamin C cotransporter 2 (SVCT2) expression was detected in the subventricular zone (SVZ) and rostral migratory stream (RMS). Low co-distribution of SVCT2 and βIII-tubulin in neuroblasts or type-A cells was detected, and minimal co-localization of SVCT2 and GFAP in type-B or precursor cells was observed. Similar results were obtained in the human neurogenic niche. However, BrdU-positive cells also expressed SVCT2, suggesting a role of vitamin C in neural progenitor proliferation. Primary neurospheres prepared from rat brain and the P19 teratocarcinoma cell line, which forms neurospheres in vitro, were used to analyze the effect of vitamin C in neural stem cells. Both cell types expressed functional SVCT2 in vitro, and ascorbic acid (AA) induced their neural differentiation, increased βIII-tubulin and SVCT2 expression, and amplified vitamin C uptake. PMID:23964197

  2. Cell Therapy in Parkinson's Disease: Host Brain Repair Machinery Gets a Boost From Stem Cell Grafts.

    Science.gov (United States)

    Napoli, Eleonora; Borlongan, Cesar V

    2017-06-01

    This commentary highlights the major findings and future research directions arising from the recent publication by Zuo and colleagues in Stem Cells 2017 (in press). Here, we discuss the novel observations that transplanted human neural stem cells can induce endogenous brain repair by specifically stimulating a host of regenerative processes in the neurogenic niche (i.e., subventricular zone [SVZ]) in an animal model of Parkinson's disease. That the identified therapeutic proteomes, neurotrophic factors, and anti-inflammatory cytokines in the SVZ may facilitate brain regeneration and behavioral recovery open a new venue of research for our understanding of the pathology and treatment of Parkinson's disease. Stem Cells 2017;35:1443-1445. © 2017 AlphaMed Press.

  3. 76 FR 44803 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

    Science.gov (United States)

    2011-07-27

    ... USCG-2009-1081 New Orleans, LA Safety Zone (Part 165)..... 12/23/2009 USCG-2009-1084 Rio Vista, CA...-1096 Port Portland Zone......... Safety Zone (Part 165)..... 7/3/2010 USCG-2009-0040 La Push, WA Safety...-0950 Madisonville, LA Safety Zone (Part 165)..... 12/31/2009 USCG-2009-0951 Lower Mississippi River...

  4. RADIATION ACCESS ZONE AND VENTILATION CONFINEMENT ZONE CRITERIA FOR THE MGR SURFACE FACILITIES

    International Nuclear Information System (INIS)

    D. A. Padula

    2000-01-01

    The objectives of this technical report are to: (1) Establish the criteria for Radiation Access Zone (RAZ) designation. (2) Establish the criteria for the Ventilation Confinement Zone (VCZ) designation. The scope will be to formulate the RAZ and VCZ zoning designation for the Monitored Geologic Repository (MGR) surface facilities and to apply the zoning designations to the current Waste Handling Building (WHB), Waste Treatment Building (WTB), and Carrier Preparation Building (CPB) configurations

  5. Cortical neurogenesis in the absence of centrioles.

    Science.gov (United States)

    Insolera, Ryan; Bazzi, Hisham; Shao, Wei; Anderson, Kathryn V; Shi, Song-Hai

    2014-11-01

    Neuronal production in the mammalian cortex depends on extensive mitoses of radial glial progenitors (RGPs) residing in the ventricular zone (VZ). We examined the function of centrioles in RGPs during cortical neurogenesis in mice by conditional removal of SAS-4, a protein that is required for centriole biogenesis. SAS-4 deletion led to a progressive loss of centrioles, accompanied by RGP detachment from the VZ. Delocalized RGPs did not become outer subventricular zone RGPs (oRGs). Although they remained proliferative, ectopic RGPs, as well as those in the VZ, with a centrosomal deficit exhibited prolonged mitosis, p53 upregulation and apoptosis, resulting in neuronal loss and microcephaly. Simultaneous removal of p53 fully rescued RGP death and microcephaly, but not RGP delocalization and randomized mitotic spindle orientation. Our findings define the functions of centrioles in anchoring RGPs in the VZ and ensuring their efficient mitoses, and reveal the robust adaptability of RGPs in the developing cortex.

  6. Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease

    Institute of Scientific and Technical Information of China (English)

    Rui Li; Le Sun; Ai Fang; Peng Li; Qian Wu; Xiaoqun Wang

    2017-01-01

    The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex.Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases.Several previous efforts have shown to grow neural organoid in culture dishes successfully,however we demonstrate a new paradigm that recapitulates neocortical development process with VZ,OSVZ formation and the lamination organization of cortical layer structure.In addition,using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient,we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids,suggesting a new strategy to study human developmental diseases in central nerve system.

  7. Atmospheric deposition of trace elements around point sources and human health risk assessment. I: Impact zones around a lead source

    DEFF Research Database (Denmark)

    Moseholm, L.; Larsen, Erik Huusfeldt; Andersen, B.

    1992-01-01

    The deposition of lead was monitored over 8 years in the area around a car battery factory north of Copenhagen, Denmark. The area also has heavy traffic. Deposition was measured by in-situ grown vegetables, transplant grass culture biomonitors, bulk deposition and soil samples. Three impact zones...... were identified by a multivariate statistical analysis. Within each zone, the total dietary intake of lead was estimated for adults and children as a percentage of the provisional tolerably weekly intake (PTWI), and as a result recommendation on restrictions in use of locally grown fruit and vegetables...

  8. Abundance of adult ticks (Acari: Ixodidae) in the Chernobyl nuclear power plant exclusion zone.

    Science.gov (United States)

    Movila, A; Deriabina, T; Morozov, A; Sitnicova, N; Toderas, I; Uspenskaia, I; Alekhnovici, A

    2012-08-01

    The Chernobyl nuclear disaster resulted in contamination of vast areas in Europe. To date, there is little knowledge about the effects of radioactive contamination on tick species. We sampled ticks from vegetation and large-sized wild mammals belonging to orders Carnivora and Artiodactyla at sites with 0.76, 1.91, and 4.50 mSv/hr ionizing radiation background values in the Polesky State Radio-Ecological Reserve of the Chernobyl nuclear disaster zone in spring 2010. Altogether, 122 questing ticks were collected from vegetation. Among collected ticks, Dermacentor reticulatus (Fabricius) was, by far, the most abundant species (99.2%), followed by Ixodes ricnus (L.) (0.8%), which was collected only at the 0.76 mSv/hr site. The average sex ratio female∶male was 2.9∶1.0. In parallel with the present study, we examined 3 Sus scrofa (L.), 2 Nyctereutes procyonoides (Gray), and 1 Alces alces (L.) at the 4.50 mSv/hr site; 96 D. reticulatus ticks were found on 2 N. procyonoides specimens. The mean density and the intensity of infestation were 16 ticks per animal and 48 ticks per infested animal, respectively. Future investigations are warranted to further characterize the role of various tick vectors, vertebrate reservoirs, and diversity of tick-borne pathogens in the Chernobyl exclusion zone.

  9. 33 CFR 165.1315 - Safety Zones: Fireworks displays in the Captain of the Port Portland Zone.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety Zones: Fireworks displays... Coast Guard District § 165.1315 Safety Zones: Fireworks displays in the Captain of the Port Portland Zone. (a) Safety zones. The following areas are designated safety zones: (1) Cinco de Mayo Fireworks...

  10. 77 FR 30245 - Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone

    Science.gov (United States)

    2012-05-22

    ...'' N, 082-51'-18.70'' W (NAD 83). This proposed zone would be enforced one evening during the last week...-AA00 Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone AGENCY: Coast Guard... by adding three permanent safety zones within the Captain of the Port Detroit Zone. This action is...

  11. The mandibular angles of dry adult human mandibles from north ...

    African Journals Online (AJOL)

    The mandibular angles of dry adult human mandibles from north-eastern arid zone of Nigeria. EF Mbajiorgu, AU Ekanem. Abstract. (Central African Journal of Medicine: 2002 48 (1-2): 9-13). http://dx.doi.org/10.4314/cajm.v48i1.8417 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

  12. 33 CFR 165.503 - Security Zone; Captain of the Port Hampton Roads Zone.

    Science.gov (United States)

    2010-07-01

    ... Port Hampton Roads Zone. 165.503 Section 165.503 Navigation and Navigable Waters COAST GUARD... § 165.503 Security Zone; Captain of the Port Hampton Roads Zone. (a) Definitions. As used in this... been authorized by the Captain of the Port (COTP), Hampton Roads, Virginia to act on his or her behalf...

  13. Formulating a coastal zone health metric for landuse impact management in urban coastal zones.

    Science.gov (United States)

    Anilkumar, P P; Varghese, Koshy; Ganesh, L S

    2010-11-01

    The need for ICZM arises often due to inadequate or inappropriate landuse planning practices and policies, especially in urban coastal zones which are more complex due to the larger number of components, their critical dimensions, attributes and interactions. A survey of literature shows that there is no holistic metric for assessing the impacts of landuse planning on the health of a coastal zone. Thus there is a need to define such a metric. The proposed metric, CHI (Coastal zone Health Indicator), developed on the basis of coastal system sustainability, attempts to gauge the health status of any coastal zone. It is formulated and modeled through an expert survey and pertains to the characteristic components of coastal zones, their critical dimensions, and relevant attributes. The proposed metric is applied to two urban coastal zones and validated. It can be used for more coast friendly and sustainable landuse planning/masterplan preparation and thereby for the better management of landuse impacts on coastal zones. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. 77 FR 6007 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

    Science.gov (United States)

    2012-02-07

    ...] Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation... they could be published in the Federal Register. This notice lists temporary safety zones, security... the safety and security needs within their jurisdiction; therefore, District Commanders and COTPs have...

  15. 78 FR 26508 - Safety Zone; Fireworks Event in Captain of the Port New York Zone

    Science.gov (United States)

    2013-05-07

    ... Harbor located in approximate Safety Zone, 33 CFR 165.160(3.8). position 40[deg]51'58'' N, 073[deg]39'34... Zone; Fireworks Event in Captain of the Port New York Zone AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast Guard will enforce safety zones in the Captain of the Port New...

  16. The distinguishing characteristics of interlayer oxidation zone and burial ancient ground oxidation zone

    International Nuclear Information System (INIS)

    Zhang Zhanshi; Zhou Wenbin

    1998-01-01

    The author discusses the main characteristics of interlayer oxidation zones and the burial ancient ground oxidation zones of Uranium deposit No. 512 in Xinjiang Uigur municipality. The epigenetic genesis, depending on some aquifer, the tongue-like in section, having the zonation along dip direction and having certain mineral assemblage are the typical features for interlayer oxidation zones

  17. Phosphorylation of Histone H2AX in the Mouse Brain from Development to Senescence

    Directory of Open Access Journals (Sweden)

    Serena Barral

    2014-01-01

    Full Text Available Phosphorylation of the histone H2AX (γH2AX form is an early response to DNA damage and a marker of aging and disease in several cells and tissues outside the nervous system. Little is known about in vivo phosphorylation of H2AX in neurons, although it was suggested that γH2AX is an early marker of neuronal endangerment thus opening the possibility to target it as a neuroprotective strategy. After experimental labeling of DNA-synthesizing cells with 5-bromo-2-deoxyuridine (BrdU, we studied the brain occurrence of γH2AX in developing, postnatal, adult and senescent (2 years mice by light and electron microscopic immunocytochemistry and Western blotting. Focal and/or diffuse γH2AX immunostaining appears in interkinetic nuclei, mitotic chromosomes, and apoptotic nuclei. Immunoreactivity is mainly associated with neurogenetic areas, i.e., the subventricular zone (SVZ of telencephalon, the cerebellar cortex, and, albeit to a much lesser extent, the subgranular zone of the hippocampal dentate gyrus. In addition, γH2AX is highly expressed in the adult and senescent cerebral cortex, particularly the piriform cortex. Double labeling experiments demonstrate that γH2AX in neurogenetic brain areas is temporally and functionally related to proliferation and apoptosis of neuronal precursors, i.e., the type C transit amplifying cells (SVZ and the granule cell precursors (cerebellum. Conversely, γH2AX-immunoreactive cortical neurons incorporating the S phase-label BrdU do not express the proliferation marker phosphorylated histone H3, indicating that these postmitotic cells undergo a significant DNA damage response. Our study paves the way for a better comprehension of the role of H2AX phosphorylation in the normal brain, and offers additional data to design novel strategies for the protection of neuronal precursors and mature neurons in central nervous system (CNS degenerative diseases.

  18. Zoning Districts - Volusia County HUB Zones

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Historically Underutilized Business (HUB) Zones in Volusia County. Go to http://www.sba.gov/hubzone or contact the Department of Economic Development (386) 248-8048...

  19. VT Data - Zoning 20120709, Huntington

    Data.gov (United States)

    Vermont Center for Geographic Information — Zoning district data for the Town of Huntington, Vermont. For details regarding each zoning district refer to the current zoning regulations on town of Huntington's...

  20. Epidemiology of hematological diseases of adult population living in a zone of Semipalatinsk nuclear test site, 1994-2003

    International Nuclear Information System (INIS)

    Akilzhanova, A.; Urazalina, Z.; Urazalin, M.

    2005-01-01

    Analyses of the dynamics of frequency of hematological diseases were conducted in the area of former Semipalatinsk nuclear test site and in different zones of radiation risk during the period of 1994-2003. Hematological diseases were diagnosed in 1,667 persons who were directly exposed to radiation, including their second and third generations. General morbidity of hematological diseases in this period gradually increased from 19.8 to 23.8 per 100,000 population. To observe dynamics of structure of hematological morbidity for the 10-year period we compared the proportion of each disease in 1994, 1999, 2003, i.e., at the beginning, the middle and the end of the observation period. In the analyses, the specific weight of chronic lymphoid leukemia for this period was reduced, the specific weight of acute leukemia increased in 1999 and then decreased in 2003, while chronic myeloid leukemia had no positive dynamics. The increasing tendency of specific weight of autoimmune diseases and pernicious anaemias was marked. There was still a high frequency of blood diseases in the zones of extreme and maximal radiation risk. The changes in structure of hematological diseases in a zone of the former Semipalatinsk nuclear test site are probably related to a hereditable predisposition of radiation induced immune imbalances. (author)

  1. Bottom-up effects of a no-take zone on endangered penguin demographics.

    Science.gov (United States)

    Sherley, Richard B; Winker, Henning; Altwegg, Res; van der Lingen, Carl D; Votier, Stephen C; Crawford, Robert J M

    2015-07-01

    Marine no-take zones can have positive impacts for target species and are increasingly important management tools. However, whether they indirectly benefit higher order predators remains unclear. The endangered African penguin (Spheniscus demersus) depends on commercially exploited forage fish. We examined how chick survival responded to an experimental 3-year fishery closure around Robben Island, South Africa, controlling for variation in prey biomass and fishery catches. Chick survival increased by 18% when the closure was initiated, which alone led to a predicted 27% higher population compared with continued fishing. However, the modelled population continued to decline, probably because of high adult mortality linked to poor prey availability over larger spatial scales. Our results illustrate that small no-take zones can have bottom-up benefits for highly mobile marine predators, but are only one component of holistic, ecosystem-based management regimes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  2. [Radioecological studies of freshwater mollusks in the Chernobyl accident exclusion zone].

    Science.gov (United States)

    Gudkov, D I; Nazarov, A B; Dziubenko, E V; Kaglian, A E; Klenus, V G

    2009-01-01

    Species-specificity and dynamics of 90Sr, 137Cs and some transuranic elements accumulation in bivalve and gastropod freshwater molluscs of the Chernobyl exclusion zone during 1997-2008 was analyzed. The results of radiation dose and chromosome aberration rate estimation and the analysis of hemolymph composition of freshwater snail (Lymnaea stagnalis L.) was produced. The absorbed dose rate was registered in the range of 0.3-85.0 microGy/h. In closed water bodies the heightened chromosome aberration rate (up to 27%) in embryo tissues, and also the change of haematological indexes for the adult individuals of snails was registered.

  3. Simvastatin Attenuates Neurogenetic Damage and Improves Neurocongnitive Deficits Induced by Isoflurane in Neonatal Rats

    Directory of Open Access Journals (Sweden)

    Ning Wang

    2018-03-01

    Full Text Available Background/Aims: Isoflurane inhibited neurogenesis and induced subsequent neurocognitive deficits in developing brain. Simvastatin exerts neuroprotection in a wide range of brain injury models. In the present study, we investigated whether simvastatin could attenuate neurogenetic inhibition and cognitive deficits induced by isoflurane exposure in neonatal rats. Methods: Sprague-Dawley rats at postnatal day (PND 7 and neural stem cells (NSCs were treated with either gas mixture, isoflurane, or simvastatin 60 min prior to isoflurane exposure, respectively. The rats were decapitated at PND 8 and PND 10 for detection of neurogenesis in the subventricular zone (SVZ and subgranular zone (SGZ of the hippocampus by immunostaining. NSC proliferation, viability and apoptosis were assessed by immunohistochemistry, CCK-8 and TUNEL, respectively. The protein expressions of caspase-3, p-Akt and p-GSK-3β both in vivo and vitro were assessed by western blotting. Cognitive functions were assessed by Morris Water Maze test and context fear conditioning test at the adult. Results: Isoflurane exposure inhibited neurogenesis in the SVZ and SGZ, decreased NSC proliferation and viability, promoted NSC apoptosis and led to late cognitive deficits. Furthermore, isoflurane increased caspase-3 expression and decreased protein expressions of p-Akt and p-GSK-3β both in vivo and in vitro. Pretreatment with simvastatin attenuated isoflurane-elicited changes in NSCs and cognitive function. Co-treatment with LY294002 reversed the effect of simvastatin on NSCs in vitro. Conclusion: We for the first time showed that simvastatin, by upregulating Akt/GSK-3β signaling pathway, alleviated isoflurane-induced neurogenetic damage and neurocognitive deficits in developing rat brain.

  4. 33 CFR 147.847 - Safety Zone; BW PIONEER Floating Production, Storage, and Offloading System Safety Zone.

    Science.gov (United States)

    2010-07-01

    ... Production, Storage, and Offloading System Safety Zone. 147.847 Section 147.847 Navigation and Navigable... ZONES § 147.847 Safety Zone; BW PIONEER Floating Production, Storage, and Offloading System Safety Zone. (a) Description. The BW PIONEER, a Floating Production, Storage and Offloading (FPSO) system, is in...

  5. 78 FR 5717 - Safety Zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal...

    Science.gov (United States)

    2013-01-28

    ...-AA00 Safety Zone; Military Ocean Terminal Concord Safety Zone, Suisun Bay, Military Ocean Terminal... Guard is establishing a safety zone in the navigable waters of Suisun Bay near Military Ocean Terminal Concord, CA in support of military onload and offload operations. This safety zone is established to...

  6. Noninvasive Evaluation of Cellular Proliferative Activity in Brain Neurogenic Regions in Rats under Depression and Treatment by Enhanced [18F]FLT-PET Imaging.

    Science.gov (United States)

    Tamura, Yasuhisa; Takahashi, Kayo; Takata, Kumi; Eguchi, Asami; Yamato, Masanori; Kume, Satoshi; Nakano, Masayuki; Watanabe, Yasuyoshi; Kataoka, Yosky

    2016-08-03

    Neural stem cells in two neurogenic regions, the subventricular zone and the subgranular zone (SGZ) of the hippocampal dentate gyrus, can divide and produce new neurons throughout life. Hippocampal neurogenesis is related to emotions, including depression/anxiety, and the therapeutic effects of antidepressants, as well as learning and memory. The establishment of in vivo imaging for proliferative activity of neural stem cells in the SGZ might be used to diagnose depression and to monitor the therapeutic efficacy of antidepressants. Positron emission tomography (PET) imaging with 3'-deoxy-3'-[(18)F]fluoro-l-thymidine ([(18)F]FLT) has been studied to allow visualization of proliferative activity in two neurogenic regions of adult mammals; however, the PET imaging has not been widely used because of lower accumulation of [(18)F]FLT, which does not allow quantitative assessment of the decline in cellular proliferative activity in the SGZ under the condition of depression. We report the establishment of an enhanced PET imaging method with [(18)F]FLT combined with probenecid, an inhibitor of drug transporters at the blood-brain barrier, which can allow the quantitative visualization of neurogenic activity in rats. Enhanced PET imaging allowed us to evaluate reduced cell proliferation in the SGZ of rats with corticosterone-induced depression, and further the recovery of proliferative activity in rats under treatment with antidepressants. This enhanced [(18)F]FLT-PET imaging technique with probenecid can be used to assess the dynamic alteration of neurogenic activity in the adult mammalian brain and may also provide a means for objective diagnosis of depression and monitoring of the therapeutic effect of antidepressant treatment. Adult hippocampal neurogenesis may play a role in major depression and antidepressant therapy. Establishment of in vivo imaging for hippocampal neurogenic activity may be useful to diagnose depression and monitor the therapeutic efficacy of

  7. 78 FR 24679 - Safety Zones; Fireworks Displays in Captain of the Port Long Island Sound Zone

    Science.gov (United States)

    2013-04-26

    ...-AA00 Safety Zones; Fireworks Displays in Captain of the Port Long Island Sound Zone AGENCY: Coast Guard... zones for fireworks displays within the Captain of the Port (COTP) Long Island Sound (LIS) Zone. This... Sector Long Island Sound. DATES: This rule is effective from April 27, 2013, until June 22, 2013. This...

  8. 76 FR 34867 - Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone

    Science.gov (United States)

    2011-06-15

    ....941(a)(51) Target Fireworks, Detroit, MI The first safety zone will be enforced from 7 a.m. on June 24... Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast Guard will enforce various safety zones for...

  9. Notch receptor expression in neurogenic regions of the adult zebrafish brain.

    Directory of Open Access Journals (Sweden)

    Vanessa de Oliveira-Carlos

    Full Text Available The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 [Formula: see text] of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA [Formula: see text] cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA [Formula: see text] cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches.

  10. Theoretical analysis of recirculation zone and buffer zone in the ADS windowless spallation target

    International Nuclear Information System (INIS)

    Liu, Jie; Pan, Chang-zhao; Tong, Jian-fei; Lu, Wen-qiang

    2015-01-01

    Highlights: • Height of recirculation zone is very important in windowless target design. • A theoretical formula for the height is derived based on the Bernoulli equation. • Numerical simulation for the LBE is performed and the height of recirculation zone is also obtained. • The theoretically-derived simulation-predicted recirculation zone heights agree with each other very well and the theoretical derivation is proved to be correct. - Abstract: The thermo-hydraulic analysis including reduction of the height of recirculation zone and stability of the free surface is very important in the design and optimization of ADS windowless spallation targets. In the present study, the Bernoulli equation is used to analyze the entire flow process in the target. Formulae for the height of the recirculation zone and the buffer zone are both obtained explicitly. Furthermore, numerical simulation for the heavy metal lead–bismuth eutectic liquid and vapor with cavitation phase change is also performed, and a novel method to calculate the height of the recirculation zone is put forward. By comparison of the theoretical formulae and numerical results, it is clearly shown that they agree with each other very well, and the heights predicted by the two methods are both determined by their own upstream flow parameters

  11. 76 FR 42048 - Safety Zones; Swimming Events in Captain of the Port Boston Zone

    Science.gov (United States)

    2011-07-18

    ...-AA00 Safety Zones; Swimming Events in Captain of the Port Boston Zone AGENCY: Coast Guard, DHS. ACTION... events within the Captain of the Port (COTP) Boston Zone for swimming events. This action is necessary to... property on navigable waters from the hazardous nature of swimming events such as large numbers of swimmers...

  12. Habitable Zones in the Universe

    OpenAIRE

    Gonzalez, G.

    2005-01-01

    Habitability varies dramatically with location and time in the universe. This was recognized centuries ago, but it was only in the last few decades that astronomers began to systematize the study of habitability. The introduction of the concept of the habitable zone was key to progress in this area. The habitable zone concept was first applied to the space around a star, now called the Circumstellar Habitable Zone. Recently, other, vastly broader, habitable zones have been proposed. We review...

  13. Oligodendrogenesis and neurogenesis in remyelination in the cuprizone model of multiple sclerosis: correlation with the degree of lesion

    Science.gov (United States)

    Pishchelko, A.; Khodanovich, M.; Pan, E.; Glazacheva, V.; Akulov, A.; Yarnykh, V.

    2017-08-01

    In this research, a cuprizone model of multiple sclerosis (MS) was used to study oligodendrogenesis and neurogenesis in remyelination. It has been shown that, with the administration of cuprizone, the amount of myelin in a number of structures of white and gray matter and the level of neurogenesis decrease, while the level of oligodendrogenesis increases. The withdrawal of cuprizone leads to the restoration of myelin content, the reduction of the excessive production of oligodendrocytes and to the restoration of the number of neurons to control values. The negative correlation between the number of oligodendrocyte precursors (OPCs) and the degree of demyelination of the corpus callosum indicates migration of OLG precursors from the subventricular zone (SVZ) to the structure during demyelination.

  14. Ichthyoplankton in a southern african surf zone: Nursery area for the postlarvae of estuarine associated fish species?

    Science.gov (United States)

    Whitfield, A. K.

    1989-12-01

    The surf zone ichthyoplankton of Swartvlei Bay was studied between February 1986 and June 1987, with particular emphasis on its potential role as a nursery area for estuarine associated marine fish species. Larvae and/or postlarvae of 16 families were identified from the surf zone, with the Gobiidae, Soleidae, Sparidae and Mugilidae comprising 85·7% of all teleosts sampled. The postlarvae of several taxa (including the six most common species), which utilize the Swartvlei estuary as a juvenile nursery area, were abundant in the surf zone. Conversely, species which are common in nearshore marine waters as juveniles and adults, but seldom enter estuaries, totalled less than 8% of the surf zone ichthyoplankton assemblage. Larval and postlarval densities peaked during summer when water temperatures exceeded 19°C and the estuary mouth was open. Concentrations of ichthyoplankton were highest at those sampling stations closest to the estuary mouth during the summer period. Diel changes in total catches revealed no significant difference between day and night densities; but of the four major taxa, the Mugilidae and Sparidae tended to be more abundant during the day, the Gobiidae at night and the Soleidae showed no distinct pattern. Results from a 24 h sampling session indicated that tidal phase may also be important in governing ichthyoplankton abundance in the surf zone.

  15. Elimination of the geomagnetic field stimulates the proliferation of mouse neural progenitor and stem cells

    Directory of Open Access Journals (Sweden)

    Jing-Peng Fu

    2016-08-01

    Full Text Available Abstract Living organisms are exposed to the geomagnetic field (GMF throughout their lifespan. Elimination of the GMF, resulting in a hypogeomagnetic field (HMF, leads to central nervous system dysfunction and abnormal development in animals. However, the cellular mechanisms underlying these effects have not been identified so far. Here, we show that exposure to an HMF (<200 nT, produced by a magnetic field shielding chamber, promotes the proliferation of neural progenitor/stem cells (NPCs/NSCs from C57BL/6 mice. Following seven-day HMF-exposure, the primary neurospheres (NSs were significantly larger in size, and twice more NPCs/NSCs were harvested from neonatal NSs, when compared to the GMF controls. The self-renewal capacity and multipotency of the NSs were maintained, as HMF-exposed NSs were positive for NSC markers (Nestin and Sox2, and could differentiate into neurons and astrocyte/glial cells and be passaged continuously. In addition, adult mice exposed to the HMF for one month were observed to have a greater number of proliferative cells in the subventricular zone. These findings indicate that continuous HMF-exposure increases the proliferation of NPCs/NSCs, in vitro and in vivo. HMF-disturbed NPCs/NSCs production probably affects brain development and function, which provides a novel clue for elucidating the cellular mechanisms of the bio-HMF response.

  16. Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.

    Directory of Open Access Journals (Sweden)

    Yiping Fan

    Full Text Available Neural stem/progenitor cells (NSC have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6% over other sources (range of 0%-27.5%, p<0.004. Whole genome expression analysis showed differential gene expression between these regionally-derived NSC, which involved the Notch, epidermal growth factor as well as interleukin pathways. We have shown the presence of phenotypically-distinct regionally-derived NSC from the mid-trimester CNS, which may reflect the ontological differences occurring within the CNS. Aside from informing on the role of such cells during fetal growth, they may be useful for different cellular therapy applications.

  17. Mechanical properties of fracture zones

    International Nuclear Information System (INIS)

    Leijon, B.

    1993-05-01

    Available data on mechanical characteristics of fracture zones are compiled and discussed. The aim is to improve the basis for adequate representation of fracture zones in geomechanical models. The sources of data researched are primarily borehole investigations and case studies in rock engineering, involving observations of fracture zones subjected to artificial load change. Boreholes only yield local information about the components of fracture zones, i.e. intact rock, fractures and various low-strength materials. Difficulties are therefore encountered in evaluating morphological and mechanical properties of fracture zones from borehole data. Although often thought of as macroscopically planar features, available field data consistently show that fracture zones are characterized by geometrical irregularities such as thickness variations, surface undulation and jogs. These irregularities prevail on all scales. As a result, fracture zones are on all scales characterized by large, in-plane variation of strength- and deformational properties. This has important mechanical consequences in terms of non-uniform stress transfer and complex mechanisms of shear deformation. Field evidence for these findings, in particular results from the underground research laboratory in Canada and from studies of induced fault slip in deep mines, is summarized and discussed. 79 refs

  18. Track treeing mechanism and plastic zone in solid Part 1: Initial development of plastic zone

    International Nuclear Information System (INIS)

    Li Boyang

    2008-01-01

    After neutron exposure and chemical etching in advance, latent tracks of recoil nucleon develop into pits on CR39 surface. During electrochemical etching, plastic zone is formed at top of pits. Some pits develop into tree cracks in the initial stage of plastic zone development. Physical and mathematical model of crack and plastic zone is proposed; parameter of development free path of plastic zone is presented. Based on integration of elementary theories the stress analysis is build up; based on analyses of measured parameters, a set of common relations between parameters is obtained. Integrate parameter analysis and stress analysis, depth of plastic zone development, law and phenomenon in experimental data can be interpreted completely

  19. 77 FR 42176 - Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone

    Science.gov (United States)

    2012-07-18

    ... fireworks launch site located at position 41-34'-18.10'' N, 082-51'-18.70'' W (NAD 83). This zone will be... at position 41-34'-18.10'' N, 082- 51'-18.70'' W (NAD 83). (ii) Expected date. This safety zone will...-AA00 Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone AGENCY: Coast Guard...

  20. Sound Zones

    DEFF Research Database (Denmark)

    Møller, Martin Bo; Olsen, Martin

    2017-01-01

    Sound zones, i.e. spatially confined regions of individual audio content, can be created by appropriate filtering of the desired audio signals reproduced by an array of loudspeakers. The challenge of designing filters for sound zones is twofold: First, the filtered responses should generate...... an acoustic separation between the control regions. Secondly, the pre- and post-ringing as well as spectral deterioration introduced by the filters should be minimized. The tradeoff between acoustic separation and filter ringing is the focus of this paper. A weighted L2-norm penalty is introduced in the sound...

  1. 33 CFR 165.154 - Safety and Security Zones: Long Island Sound Marine Inspection Zone and Captain of the Port Zone.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety and Security Zones: Long... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY... Areas First Coast Guard District § 165.154 Safety and Security Zones: Long Island Sound Marine...

  2. Clinical, immunophenotypic, and genetic analysis of adult lymphomas with morphologic features of Burkitt lymphoma

    NARCIS (Netherlands)

    Haralambieva, E; Boerma, EJ; van Imhoff, GW; Rosati, S; Schuuring, E; Muller-Hermelink, HK; Kluin, PM; Ott, G

    A prompt distinction of Burkitt lymphoma (BL) versus diffuse large B cell lymphomas (DLBCL) has important clinical implications; however, this distinction can be difficult. We analyzed 74 adult gray zone and 10 reference pediatric BL using immunohistochemistry (Ki-67, CD10, bcl2, bcl6) and

  3. Radial glia in the proliferative ventricular zone of the embryonic and adult turtle, Trachemys scripta elegans.

    Science.gov (United States)

    Clinton, Brian K; Cunningham, Christopher L; Kriegstein, Arnold R; Noctor, Stephen C; Martínez-Cerdeño, Verónica

    2014-01-01

    To better understand the role of radial glial (RG) cells in the evolution of the mammalian cerebral cortex, we investigated the role of RG cells in the dorsal cortex and dorsal ventricular ridge of the turtle, Trachemys scripta elegans. Unlike mammals, the glial architecture of adult reptile consists mainly of ependymoradial glia, which share features with mammalian RG cells, and which may contribute to neurogenesis that continues throughout the lifespan of the turtle. To evaluate the morphology and proliferative capacity of ependymoradial glia (here referred to as RG cells) in the dorsal cortex of embryonic and adult turtle, we adapted the cortical electroporation technique, commonly used in rodents, to the turtle telencephalon. Here, we demonstrate the morphological and functional characteristics of RG cells in the developing turtle dorsal cortex. We show that cell division occurs both at the ventricle and away from the ventricle, that RG cells undergo division at the ventricle during neurogenic stages of development, and that mitotic Tbr2+ precursor cells, a hallmark of the mammalian SVZ, are present in the turtle cortex. In the adult turtle, we show that RG cells encompass a morphologically heterogeneous population, particularly in the subpallium where proliferation is most prevalent. One RG subtype is similar to RG cells in the developing mammalian cortex, while 2 other RG subtypes appear to be distinct from those seen in mammal. We propose that the different subtypes of RG cells in the adult turtle perform distinct functions.

  4. 33 CFR 165.20 - Safety zones.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety zones. 165.20 Section 165... WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND LIMITED ACCESS AREAS Safety Zones § 165.20 Safety zones. A Safety Zone is a water area, shore area, or water and shore area to which, for safety or environmental...

  5. Zone distillation: a new purification method

    International Nuclear Information System (INIS)

    Kravchenko, A.I.

    2011-01-01

    The features of zone distillation (with zone melting of refined material and with pulling of condensate) as a new purification method are shown. The method is based on similarity of equations of distillation and crystallization refining. The analogy between some distillation and condensation methods (particularly between zone distillation and zone recrystallization) is should up

  6. Structure and properties of melt-spun high acrylonitrile copolymer fibers via continuous zone-drawing and zone-annealing processes

    International Nuclear Information System (INIS)

    Wu Zongquan; Zhang Anqiu; Percec, Simona; Jin Shi; Jing, Alexander J.; Ge, Jason J.; Cheng, Stephen Z.D.

    2003-01-01

    Continuous zone-drawing and zone-annealing processes have been utilized to probe improvements in mechanical performance of melt-spun high acrylonitrile copolymer fibers (AMLON TM ). The as-spun fibers were zone-drawn at different ratios in a narrow temperature range of 100-105 deg. C and then zone-annealed. As a result of these processes, the fibers show substantial increases in tensile strength and tensile modulus (about three times) and significant improvements in elongation-at-break (about two times) after zone annealing. The thermal transition behavior, dimensional stability and dynamic relaxation properties of the as-spun, zone-drawn and zone-annealed fibers have been studied using differential scanning calorimetry, thermal mechanical and dynamic mechanical experiments. Their mechanical and thermal property changes after the zone-drawing and zone-annealing processes can be associated with the microscopic structural evolution including crystallinity, crystal orientation and apparent crystallite size detected by wide angle X-ray diffraction experiments

  7. 46 CFR 76.23-5 - Zoning.

    Science.gov (United States)

    2010-10-01

    ... deck, large common areas may be zoned in accordance with table 76.23-5(b). All such zones within one common area shall be of approximately the same size. Zones of this type shall overlap in such a manner that the end sprinkler heads of both adjoining zones will cover the identical area. Table 76.23-5(b...

  8. Cell-type-specific expression of NFIX in the developing and adult cerebellum.

    Science.gov (United States)

    Fraser, James; Essebier, Alexandra; Gronostajski, Richard M; Boden, Mikael; Wainwright, Brandon J; Harvey, Tracey J; Piper, Michael

    2017-07-01

    Transcription factors from the nuclear factor one (NFI) family have been shown to play a central role in regulating neural progenitor cell differentiation within the embryonic and post-natal brain. NFIA and NFIB, for instance, promote the differentiation and functional maturation of granule neurons within the cerebellum. Mice lacking Nfix exhibit delays in the development of neuronal and glial lineages within the cerebellum, but the cell-type-specific expression of this transcription factor remains undefined. Here, we examined the expression of NFIX, together with various cell-type-specific markers, within the developing and adult cerebellum using both chromogenic immunohistochemistry and co-immunofluorescence labelling and confocal microscopy. In embryos, NFIX was expressed by progenitor cells within the rhombic lip and ventricular zone. After birth, progenitor cells within the external granule layer, as well as migrating and mature granule neurons, expressed NFIX. Within the adult cerebellum, NFIX displayed a broad expression profile, and was evident within granule cells, Bergmann glia, and interneurons, but not within Purkinje neurons. Furthermore, transcriptomic profiling of cerebellar granule neuron progenitor cells showed that multiple splice variants of Nfix are expressed within this germinal zone of the post-natal brain. Collectively, these data suggest that NFIX plays a role in regulating progenitor cell biology within the embryonic and post-natal cerebellum, as well as an ongoing role within multiple neuronal and glial populations within the adult cerebellum.

  9. 33 CFR 3.25-10 - Sector Hampton Roads Marine Inspection Zone and Captain of the Port Zone.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Sector Hampton Roads Marine... ZONES, AND CAPTAIN OF THE PORT ZONES Fifth Coast Guard District § 3.25-10 Sector Hampton Roads Marine Inspection Zone and Captain of the Port Zone. Sector Hampton Roads' office is located in Portsmouth, VA. The...

  10. Irradiation damage 'displacement zone'; Dommages sous irradiation zone de deplacements

    Energy Technology Data Exchange (ETDEWEB)

    Genthon, J P [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1969-07-01

    It is well known that a charged particle (ion, primary atom, etc...) moving in a solid slows down and can cause a cascade of displacements of the atoms in the solid. A study is made here of the extent to which the cascade is made up, or not, of independent collisions, as a function of the energy of the initial charged particle. When the distance between the collisions is small, these latter are no longer independent; the cascade, which then has to be considered as a whole, perturbs and locates, in the irradiated solid , a zone which has been named a 'displacement zone'. It is shown that the proportion of displacement zones increases with increasing atom size (high atomic number Z), with decreasing atomic distance D in the substance considered and with decreasing energy of the ion undergoing the slowing down process (although always remaining above a few hundred eV). The proportions obtained are higher than those corresponding to the calculations of J. A. Brinkman [3]. An interatomic potential required for this work has also been determined. (author) [French] On sait qu'une particule chargee (ions, atomes primaires, etc...) en mouvement dans un solide se ralentit, avec eventuellement deplacement en cascade d'atomes du solide. On etudie ici dans quelle proportion, en fonction de l'energie de la particule chargee initiale, la cascade est constituee, ou non, de 'chocs independants'. Lorsque la distance entre chocs est petite, ceux-ci ne sont plus independants; la cascade, qui doit alors etre consideree dans son ensemble, perturbe et definit dans le solide irradie, une zone qu'on a appele zone de deplacements. On montre que la proportion de zones de deplacements est d'autant plus grande que les atomes sont gros (nombre atomique Z grand), que la distance interatomique D est petite dans le corps considere, et que l'energie de l'ion en ralentissement est petite (tout en restant superieure a quelques centaines d'eV). Les proportions obtenues sont superieures a celles qui

  11. Oxygenated gasoline release in the unsaturated zone - Part 1: Source zone behavior.

    Science.gov (United States)

    Freitas, Juliana G; Barker, James F

    2011-11-01

    Oxygenates present in gasoline, such as ethanol and MTBE, are a concern in subsurface contamination related to accidental spills. While gasoline hydrocarbon compounds have low solubility, MTBE and ethanol are more soluble, ethanol being completely miscible with water. Consequently, their fate in the subsurface is likely to differ from that of gasoline. To evaluate the fate of gasoline containing oxygenates following a release in the unsaturated zone shielded from rainfall/recharge, a controlled field test was performed at Canadian Forces Base Borden, in Ontario. 200L of a mixture composed of gasoline with 10% ethanol and 4.5% MTBE was released in the unsaturated zone, into a trench 20cm deep, about 32cm above the water table. Based on soil cores, most of the ethanol was retained in the source, above the capillary fringe, and remained there for more than 100 days. Ethanol partitioned from the gasoline to the unsaturated pore-water and was retained, despite the thin unsaturated zone at the site (~35cm from the top of the capillary fringe to ground surface). Due to its lower solubility, most of the MTBE remained within the NAPL as it infiltrated deeper into the unsaturated zone and accumulated with the gasoline on top of the depressed capillary fringe. Only minor changes in the distribution of ethanol were noted following oscillations in the water table. Two methods to estimate the capacity of the unsaturated zone to retain ethanol are explored. It is clear that conceptual models for sites impacted by ethanol-fuels must consider the unsaturated zone. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Knowing Their Place: Feminist Understandings and Perceptions of Women Adult Educators in Museums

    Science.gov (United States)

    Clover, Darlene E.; Sanford, K.

    2016-01-01

    Arguing gender inequity remains one of the biggest challenges of our time, and framed within the concept of "pedagogic contact zones", our article shares findings from a five-year feminist, cross-national study of women adult educators and community practitioners in public museums and art galleries in Canada and the United Kingdom.…

  13. Work zone safety analysis.

    Science.gov (United States)

    2013-11-01

    This report presents research performed analyzing crashes in work zones in the state of New Jersey so as to : identify critical areas in work zones susceptible to crashes and key factors that contribute to these crashes. A field : data collection on ...

  14. EGF-induced expansion of migratory cells in the rostral migratory stream.

    Directory of Open Access Journals (Sweden)

    Olle R Lindberg

    Full Text Available The presence of neural stem cells in the adult brain is currently widely accepted and efforts are made to harness the regenerative potential of these cells. The dentate gyrus of the hippocampal formation, and the subventricular zone (SVZ of the anterior lateral ventricles, are considered the main loci of adult neurogenesis. The rostral migratory stream (RMS is the structure funneling SVZ progenitor cells through the forebrain to their final destination in the olfactory bulb. Moreover, extensive proliferation occurs in the RMS. Some evidence suggest the presence of stem cells in the RMS, but these cells are few and possibly of limited differentiation potential. We have recently demonstrated the specific expression of the cytoskeleton linker protein radixin in neuroblasts in the RMS and in oligodendrocyte progenitors throughout the brain. These cell populations are greatly altered after intracerebroventricular infusion of epidermal growth factor (EGF. In the current study we investigate the effect of EGF infusion on the rat RMS. We describe a specific increase of radixin(+/Olig2(+ cells in the RMS. Negative for NG2 and CNPase, these radixin(+/Olig2(+ cells are distinct from typical oligodendrocyte progenitors. The expanded Olig2(+ population responds rapidly to EGF and proliferates after only 24 hours along the entire RMS, suggesting local activation by EGF throughout the RMS rather than migration from the SVZ. In addition, the radixin(+/Olig2(+ progenitors assemble in chains in vivo and migrate in chains in explant cultures, suggesting that they possess migratory properties within the RMS. In summary, these results provide insight into the adaptive capacity of the RMS and point to an additional stem cell source for future brain repair strategies.

  15. Mechano growth factor, a splice variant of IGF-1, promotes neurogenesis in the aging mouse brain.

    Science.gov (United States)

    Tang, Jason J; Podratz, Jewel L; Lange, Miranda; Scrable, Heidi J; Jang, Mi-Hyeon; Windebank, Anthony J

    2017-07-07

    Mechano growth factor (MGF) is a splice variant of IGF-1 first described in skeletal muscle. MGF induces muscle cell proliferation in response to muscle stress and injury. In control mice we found endogenous expression of MGF in neurogenic areas of the brain and these levels declined with age. To better understand the role of MGF in the brain, we used transgenic mice that constitutively overexpressed MGF from birth. MGF overexpression significantly increased the number of BrdU+ proliferative cells in the dentate gyrus (DG) of the hippocampus and subventricular zone (SVG). Although MGF overexpression increased the overall rate of adult hippocampal neurogenesis at the proliferation stage it did not alter the distribution of neurons at post-mitotic maturation stages. We then used the lac-operon system to conditionally overexpress MGF in the mouse brain beginning at 1, 3 and 12 months with histological and behavioral observation at 24 months of age. With conditional overexpression there was an increase of BrdU+ proliferating cells and BrdU+ differentiated mature neurons in the olfactory bulbs at 24 months when overexpression was induced from 1 and 3 months of age but not when started at 12 months. This was associated with preserved olfactory function. In vitro, MGF increased the size and number of neurospheres harvested from SVZ-derived neural stem cells (NSCs). These findings indicate that MGF overexpression increases the number of neural progenitor cells and promotes neurogenesis but does not alter the distribution of adult newborn neurons at post-mitotic stages. Maintaining youthful levels of MGF may be important in reversing age-related neuronal loss and brain dysfunction.

  16. Dengue fever and dengue haemorrhagic fever in adolescents and adults.

    Science.gov (United States)

    Tantawichien, Terapong

    2012-05-01

    Dengue fever (DF) is endemic in tropical and subtropical zones and the prevalence is increasing across South-east Asia, Africa, the Western Pacific and the Americas. In recent years, the spread of unplanned urbanisation, with associated substandard housing, overcrowding and deterioration in water, sewage and waste management systems, has created ideal conditions for increased transmission of the dengue virus in tropical urban centres. While dengue infection has traditionally been considered a paediatric disease, the age distribution of dengue has been rising and more cases have been observed in adolescents and adults. Furthermore, the development of tourism in the tropics has led to an increase in the number of tourists who become infected, most of whom are adults. Symptoms and risk factors for dengue haemorrhagic fever (DHF) and severe dengue differ between children and adults, with co-morbidities and incidence in more elderly patients associated with greater risk of mortality. Treatment options for DF and DHF in adults, as for children, centre round fluid replacement (either orally or intravenously, depending on severity) and antipyretics. Further data are needed on the optimal treatment of adult patients.

  17. "No zone" approach in penetrating neck trauma reduces unnecessary computed tomography angiography and negative explorations.

    Science.gov (United States)

    Ibraheem, Kareem; Khan, Muhammad; Rhee, Peter; Azim, Asad; O'Keeffe, Terence; Tang, Andrew; Kulvatunyou, Narong; Joseph, Bellal

    2018-01-01

    The most recent management guidelines advocate computed tomography angiography (CTA) for any suspected vascular or aero-digestive injuries in all zones and give zone II injuries special consideration. We hypothesized that physical examination can safely guide CTA use in a "no zone" approach. An 8-year retrospective analysis of all adult trauma patients with penetrating neck trauma (PNT) was performed. We included all patients in whom the platysma was violated. Patients were classified into three groups as follows: hard signs, soft signs, and asymptomatic. CTA use, positive CTA (contrast extravasation, dissection, or intimal flap) and operative details were reported. Primary outcomes were positive CTA and therapeutic neck exploration (TNE) (defined by repair of major vascular or aero-digestive injuries). A total of 337 patients with PNT met the inclusion criteria. Eighty-two patients had hard signs and all of them went to the operating room, of which 59 (72%) had TNE. One hundred fifty-six patients had soft signs, of which CTA was performed in 121 (78%), with positive findings in 12 (10%) patients. The remaining 35 (22%) underwent initial neck exploration, of which 14 (40%) were therapeutic yielding a high rate of negative exploration. Ninty-nine patients were asymptomatic, of which CTA was performed in 79 (80%), with positive findings in 3 (4%), however, none of these patients required TNE. On sub analysis based on symptoms, there was no difference in the rate of TNE between the neck zones in patients with hard signs (P = 0.23) or soft signs (P = 0.51). Regardless of the zone of injury, asymptomatic patients did not require a TNE. Physical examination regardless of the zone of injury should be the primary guide to CTA or TNE in patients with PNT. Following traditional zone-based guidelines can result in unnecessary negative explorations in patients with soft signs and may need rethinking. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Unsaturated Zone and Saturated Zone Transport Properties (U0100)

    Energy Technology Data Exchange (ETDEWEB)

    J. Conca

    2000-12-20

    This Analysis/Model Report (AMR) summarizes transport properties for the lower unsaturated zone hydrogeologic units and the saturated zone at Yucca Mountain and provides a summary of data from the Busted Butte Unsaturated Zone Transport Test (UZTT). The purpose of this report is to summarize the sorption and transport knowledge relevant to flow and transport in the units below Yucca Mountain and to provide backup documentation for the sorption parameters decided upon for each rock type. Because of the complexity of processes such as sorption, and because of the lack of direct data for many conditions that may be relevant for Yucca Mountain, data from systems outside of Yucca Mountain are also included. The data reported in this AMR will be used in Total System Performance Assessment (TSPA) calculations and as general scientific support for various Process Model Reports (PMRs) requiring knowledge of the transport properties of different materials. This report provides, but is not limited to, sorption coefficients and other relevant thermodynamic and transport properties for the radioisotopes of concern, especially neptunium (Np), plutonium (Pu), Uranium (U), technetium (Tc), iodine (I), and selenium (Se). The unsaturated-zone (UZ) transport properties in the vitric Calico Hills (CHv) are discussed, as are colloidal transport data based on the Busted Butte UZTT, the saturated tuff, and alluvium. These values were determined through expert elicitation, direct measurements, and data analysis. The transport parameters include information on interactions of the fractures and matrix. In addition, core matrix permeability data from the Busted Butte UZTT are summarized by both percent alteration and dispersion.

  19. Unsaturated Zone and Saturated Zone Transport Properties (U0100)

    International Nuclear Information System (INIS)

    Conca, J.

    2000-01-01

    This Analysis/Model Report (AMR) summarizes transport properties for the lower unsaturated zone hydrogeologic units and the saturated zone at Yucca Mountain and provides a summary of data from the Busted Butte Unsaturated Zone Transport Test (UZTT). The purpose of this report is to summarize the sorption and transport knowledge relevant to flow and transport in the units below Yucca Mountain and to provide backup documentation for the sorption parameters decided upon for each rock type. Because of the complexity of processes such as sorption, and because of the lack of direct data for many conditions that may be relevant for Yucca Mountain, data from systems outside of Yucca Mountain are also included. The data reported in this AMR will be used in Total System Performance Assessment (TSPA) calculations and as general scientific support for various Process Model Reports (PMRs) requiring knowledge of the transport properties of different materials. This report provides, but is not limited to, sorption coefficients and other relevant thermodynamic and transport properties for the radioisotopes of concern, especially neptunium (Np), plutonium (Pu), Uranium (U), technetium (Tc), iodine (I), and selenium (Se). The unsaturated-zone (UZ) transport properties in the vitric Calico Hills (CHv) are discussed, as are colloidal transport data based on the Busted Butte UZTT, the saturated tuff, and alluvium. These values were determined through expert elicitation, direct measurements, and data analysis. The transport parameters include information on interactions of the fractures and matrix. In addition, core matrix permeability data from the Busted Butte UZTT are summarized by both percent alteration and dispersion

  20. Correlation Between Intercritical Heat-Affected Zone and Type IV Creep Damage Zone in Grade 91 Steel

    Science.gov (United States)

    Wang, Yiyu; Kannan, Rangasayee; Li, Leijun

    2018-04-01

    A soft zone in Cr-Mo steel weldments has been reported to accompany the infamous Type IV cracking, the highly localized creep damage in the heat-affected zone of creep-resistant steels. However, the microstructural features and formation mechanism of this soft zone are not well understood. In this study, using microhardness profiling and microstructural verification, the initial soft zone in the as-welded condition was identified to be located in the intercritical heat-affected zone of P91 steel weldments. It has a mixed structure, consisting of Cr-rich re-austenitized prior austenite grains and fine Cr-depleted, tempered martensite grains retained from the base metal. The presence of these further-tempered retained grains, originating from the base metal, is directly responsible for the hardness reduction of the identified soft zone in the as-welded condition. The identified soft zone exhibits a high location consistency at three thermal stages. Local chemistry analysis and thermodynamic calculation show that the lower chromium concentrations inside these retained grains thermodynamically decrease their potentials for austenitic transformation during welding. Heterogeneous grain growth is observed in the soft zone during postweld heat treatment. The mismatch of strengths between the weak Cr-depleted grains and strong Cr-rich grains enhances the creep damage. Local deformation of the weaker Cr-depleted grains accelerates the formation of creep cavities.

  1. Women in Chernobyl Exclusion Zone

    International Nuclear Information System (INIS)

    Balashevska, Y.; Kireev, S.; Navalikhin, V.

    2015-01-01

    Today, 29 years after the Chernobyl accident, the Exclusion Zone still remains an areal unsealed radiation source of around 2600 km"2. It is not just a gigantic radioactive waste storage facility (the amount of radioactive waste accumulated within the Zone, except for the Shelter, is estimated at about 2.8 million m"3), but also a unique research and engineering platform for biologists, radiologists, chemists and physicists. Taking into account the amount of the radionuclides released during the accident, it becomes quite understood that the radiological environment in the Exclusion Zone is far from favorable. However, among the Exclusion Zone personnel who numbers 5000, there are female workers. The poster represents the results of the research performed among the female employees of the largest enterprise of the Exclusion Zone, “Chornobyl Spetskombinat”. The survey was performed with the view to knowing what makes women work in the most radioactively contaminated area in Europe, and what their role is, to revealing their fears and hopes, and to estimating the chances of the brave women of Chernobyl Exclusion Zone to succeed in their careers. (author)

  2. Problems of Chernobyl Exclusion Zone

    International Nuclear Information System (INIS)

    Kholosha, V.Yi.

    2014-01-01

    The collection comprises the results of researches and design activity in the ChNPP exclusion zone, aimed at the development of technologies, equipment and devices for radioactive waste management and ChNPP accident clean-up, at studying the composition and structure of the Exclusion zone soil activity solid bearers, form transformation of the fission products of fuel fallout radionuclide composition in the ChNPP near zone, the spatial distribution of radionuclides and other radioecological issues.. Much attention is paid to medical and biological aspects of the accident influence on the flora, fauna and people's health, labour conditions and incidence of the workers of the Exclusion zone

  3. 75 FR 19304 - Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone

    Science.gov (United States)

    2010-04-14

    ... previously published in Coast Guard regulations. These safety zones are necessary to protect spectators...-AA00 Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The Coast Guard proposes establishment of safety...

  4. A viscoplastic shear-zone model for episodic slow slip events in oceanic subduction zones

    Science.gov (United States)

    Yin, A.; Meng, L.

    2016-12-01

    Episodic slow slip events occur widely along oceanic subduction zones at the brittle-ductile transition depths ( 20-50 km). Although efforts have been devoted to unravel their mechanical origins, it remains unclear about the physical controls on the wide range of their recurrence intervals and slip durations. In this study we present a simple mechanical model that attempts to account for the observed temporal evolution of slow slip events. In our model we assume that slow slip events occur in a viscoplastic shear zone (i.e., Bingham material), which has an upper static and a lower dynamic plastic yield strength. We further assume that the hanging wall deformation is approximated as an elastic spring. We envision the shear zone to be initially locked during forward/landward motion but is subsequently unlocked when the elastic and gravity-induced stress exceeds the static yield strength of the shear zone. This leads to backward/trenchward motion damped by viscous shear-zone deformation. As the elastic spring progressively loosens, the hanging wall velocity evolves with time and the viscous shear stress eventually reaches the dynamic yield strength. This is followed by the termination of the trenchward motion when the elastic stress is balanced by the dynamic yield strength of the shear zone and the gravity. In order to account for the zig-saw slip-history pattern of typical repeated slow slip events, we assume that the shear zone progressively strengthens after each slow slip cycle, possibly caused by dilatancy as commonly assumed or by progressive fault healing through solution-transport mechanisms. We quantify our conceptual model by obtaining simple analytical solutions. Our model results suggest that the duration of the landward motion increases with the down-dip length and the static yield strength of the shear zone, but decreases with the ambient loading velocity and the elastic modulus of the hanging wall. The duration of the backward/trenchward motion depends

  5. Coastal zone

    International Nuclear Information System (INIS)

    2002-01-01

    The report entitled Climate Change Impacts and Adaptation : A Canadian Perspective, presents a summary of research regarding the impacts of climate change on key sectors over the past five years as it relates to Canada. This chapter on the coastal zone focuses on the impact of climate change on Canada's marine and Great Lakes coasts with tips on how to deal with the impacts associated with climate change in sensitive environments. This report is aimed at the sectors that will be most affected by adaptation decisions in the coastal zone, including fisheries, tourism, transportation and water resources. The impact of climate change in the coastal zone may include changes in water levels, wave patterns, storm surges, and thickness of seasonal ice cover. The Intergovernmental Panel on Climate Change projects global average sea level will rise between 9 and 88 centimetres between 1990 to 2100, but not all areas of Canada will experience the same rate of future sea level change. The main physical impact would be shoreline change that could result in a range of biophysical and socio-economic impacts, some beneficial, some negative. The report focuses on issues related to infrastructure and communities in coastal regions. It is noted that appropriate human adaptation will play a vital role in reducing the extent of potential impacts by decreasing the vulnerability of average zone to climate change. The 3 main trends in coastal adaptation include: (1) increase in soft protection, retreat and accommodation, (2) reliance on technology such as geographic information systems to manage information, and (3) awareness of the need for coastal adaptation that is appropriate for local conditions. 61 refs., 7 figs

  6. Louisiana Speaks Regional Plan Vision Special Economic Zones, UTM Zone 15N NAD83, Louisiana Recovery Authority (2007), [louisiana_speaks_vision_special_economic_zones

    Data.gov (United States)

    Louisiana Geographic Information Center — This GIS shapefile data illustrates special economic zones included in the Louisiana Speaks Regional Plan Vision. Special economic zones include existing national,...

  7. Life cycle strategies of copepods in coastal upwelling zones

    Science.gov (United States)

    Peterson, W.

    1998-06-01

    Life cycles of copepods of coastal upwelling zones are of the multigenerational type—as many as 10 or more generations may be produced each year, depending upon water temperature, food concentration and length of the upwelling season. Abundant food resources and moderate temperature convey advantages to those copepods living in coastal upwelling zones, however, there is a clear disadvantage in that coastal upwelling zones are highly advective environments. Typically, water circulation patterns are such that surface waters are carried offshore, deeper waters carried onshore and most of the water column over the continental shelf is moving equatorward. The challenge to copepod species that inhabit upwelling systems is life cycle closure—how do eggs, nauplii, juveniles and adults avoid being swept out of these ecosystems in the face of persistent transport out of the system? In this review, I first list the species which dominate coastal upwelling ecosystems then discuss three variations on the multigenerational life cycle scheme that are observed in upwelling systems. The latter part of the review is devoted to discussion of how individuals are retained in the productive continental shelf waters within coastal upwelling ecosystems. The suggestion is made that the only copepod species that successfully achieve life cycle closure in such systems are those that are preadapted to upwelling circulation patterns. Our quantitative understanding of the relative importance of physical factors (such as advection) and biological factors (birth, growth, and mortality) on life cycle strategies and population dynamics is quite rudimentary. It would help our understanding if there were more field studies and more computer modeling studies that focused on seasonal cycles of abundance, development times and vertical distribution of life cycle stages, and measurements of water circulation patterns.

  8. Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall

    Directory of Open Access Journals (Sweden)

    Li Shengwen

    2012-09-01

    Full Text Available Abstract Background The cancer stem cell (CSC hypothesis posits that deregulated neural stem cells (NSCs form the basis of brain tumors such as glioblastoma multiforme (GBM. GBM, however, usually forms in the cerebral white matter while normal NSCs reside in subventricular and hippocampal regions. We attempted to characterize CSCs from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall. Methods We described isolating CSCs from a GBM involving the lateral ventricles and characterized these cells with in vitro molecular biomarker profiling, cellular behavior, ex vivo and in vivo techniques. Results The patient’s MRI revealed a heterogeneous mass with associated edema, involving the left subventricular zone. Histological examination of the tumor established it as being a high-grade glial neoplasm, characterized by polygonal and fusiform cells with marked nuclear atypia, amphophilic cytoplasm, prominent nucleoli, frequent mitotic figures, irregular zones of necrosis and vascular hyperplasia. Recurrence of the tumor occurred shortly after the surgical resection. CD133-positive cells, isolated from the tumor, expressed stem cell markers including nestin, CD133, Ki67, Sox2, EFNB1, EFNB2, EFNB3, Cav-1, Musashi, Nucleostemin, Notch 2, Notch 4, and Pax6. Biomarkers expressed in differentiated cells included Cathepsin L, Cathepsin B, Mucin18, Mucin24, c-Myc, NSE, and TIMP1. Expression of unique cancer-related transcripts in these CD133-positive cells, such as caveolin-1 and −2, do not appear to have been previously reported in the literature. Ex vivo organotypic brain slice co-culture showed that the CD133+ cells behaved like tumor cells. The CD133-positive cells also induced tumor formation when they were stereotactically transplanted into the brains of the immune-deficient NOD/SCID mice. Conclusions This brain tumor involving the neurogenic lateral ventricular wall was comprised of tumor-forming, CD133-positive cancer

  9. 77 FR 9528 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound

    Science.gov (United States)

    2012-02-17

    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2012-0087] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound AGENCY: Coast Guard, DHS... Waterway Security Zone in Commencement Bay, Tacoma, Washington from 6 a.m. on February 17, 2012, through 11...

  10. 78 FR 40396 - Safety Zone; America's Cup Safety Zone and No Loitering Area, San Francisco, CA

    Science.gov (United States)

    2013-07-05

    ...-AA00 Safety Zone; America's Cup Safety Zone and No Loitering Area, San Francisco, CA AGENCY: Coast... America's Cup races. This safety zone and no loitering area are established to enhance the safety of spectators and mariners near the north east corner of the America's Cup regulated area. All persons or...

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

    Directory of Open Access Journals (Sweden)

    Andreas Androutsellis-Theotokis

    2010-02-01

    Full Text Available 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.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.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.

  12. 78 FR 54588 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound

    Science.gov (United States)

    2013-09-05

    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2012-0087] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound AGENCY: Coast Guard, DHS... Security Zone in Commencement Bay, Tacoma, Washington from 6:00 a.m. on September 2, 2013 through 11:59 p.m...

  13. 78 FR 57485 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound

    Science.gov (United States)

    2013-09-19

    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2012-0087] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound AGENCY: Coast Guard, DHS... Security Zone in Commencement Bay, Tacoma, Washington from 6 a.m. on September 12, 2013 through 11:59 p.m...

  14. Quantitative analysis of benign prostate hyperplasia with MRS in Chinese adult

    International Nuclear Information System (INIS)

    Li Feiyu; Wang Xiaoying; Huang Rong; Jiang Xuexiang; Ding Jianping; Zhou Liangping

    2005-01-01

    Objective: To evaluate the metabolic level of different types of benign prostate hyperplasia (BPH) with MRS in Chinese adult. Methods: Ten BPH patients verified by biopsy were divided into two types: glandular BPH and stromal BPH. 3DMRS were performed on the central zone to measure the ratio of (Cho + Cre) /Cit. Results: The mean ratio of (Cho + Cre)/Cit in central zone of glandular BPH was 0.55 ± 0.32, whereas that of stromal BPH was 0.87 ± 0.34. Statistically significant difference was detected between the two types of BPH (t=8.18, P<0.05). Conclusion: The metabolic levels of prostate with BPH could be measured with MRS quantitatively, and metabolic difference could be detected between glandular BPH and stromal BPH. (authors)

  15. Global correlations between maximum magnitudes of subduction zone interface thrust earthquakes and physical parameters of subduction zones

    NARCIS (Netherlands)

    Schellart, W. P.; Rawlinson, N.

    2013-01-01

    The maximum earthquake magnitude recorded for subduction zone plate boundaries varies considerably on Earth, with some subduction zone segments producing giant subduction zone thrust earthquakes (e.g. Chile, Alaska, Sumatra-Andaman, Japan) and others producing relatively small earthquakes (e.g.

  16. A broader classification of damage zones

    Science.gov (United States)

    Peacock, D. C. P.; Dimmen, V.; Rotevatn, A.; Sanderson, D. J.

    2017-09-01

    Damage zones have previously been classified in terms of their positions at fault tips, walls or areas of linkage, with the latter being described in terms of sub-parallel and synchronously active faults. We broaden the idea of linkage to include structures around the intersections of non-parallel and/or non-synchronous faults. These interaction damage zones can be divided into approaching damage zones, where the faults kinematically interact but are not physically connected, and intersection damage zones, where the faults either abut or cross-cut. The damage zone concept is applied to other settings in which strain or displacement variations are taken up by a range of structures, such as at fault bends. It is recommended that a prefix can be added to a wide range of damage zones, to describe the locations in which they formed, e.g., approaching, intersection and fault bend damage zone. Such interpretations are commonly based on limited knowledge of the 3D geometries of the structures, such as from exposure surfaces, and there may be spatial variations. For example, approaching faults and related damage seen in outcrop may be intersecting elsewhere on the fault planes. Dilation in intersection damage zones can represent narrow and localised channels for fluid flow, and such dilation can be influenced by post-faulting stress patterns.

  17. Assessing Movements of Brushtail Possums (Trichosurus vulpecula in Relation to Depopulated Buffer Zones for the Management of Wildlife Tuberculosis in New Zealand.

    Directory of Open Access Journals (Sweden)

    Andrea E Byrom

    Full Text Available In New Zealand, managing the threat of bovine tuberculosis (TB to livestock includes population reduction of potentially infectious wildlife, primarily the brushtail possum (Trichosurus vulpecula. Population control is often targeted on forested buffer zones adjacent to farmland, in order to limit movements of possums across the buffer and reduce the risk of disease transmission to livestock. To assess the effectiveness of buffers in protecting livestock we analysed GPS telemetry data from possums located in untreated forest adjacent to buffers, and used these data to characterise patterns of movement that could lead to possums reaching farmland during the season when most dispersal occurs. Analyses of movement data showed that the direction of dispersal by sub-adult and adult possums and the extent of long exploratory movements were not biased toward forest buffers, even though these provided vacant habitat as suitable for possums as untreated forest. Instead, dispersal and exploratory movements were uncommon even for sub-adult possums and such events typically lasted <10 days. Dispersing possums settled predominantly in river valleys. A simulation model was developed for the 3-6-month dispersal season; it demonstrated a probability of <0.001 that an infected possum, originating from a low-density population with low disease prevalence in untreated forest, would move across 3 km of recently controlled forest buffer to reach farmland. Our results indicate short-term reduction in the risk of TB transmission from possums to livestock in New Zealand by the use of depopulated buffer zones, while acknowledging that the threat of disease spread from untreated forest is likely to increase over time as possum population density and, potentially, TB prevalence among those possums, increase in the buffer zone.

  18. 33 CFR 2.30 - Exclusive Economic Zone.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Exclusive Economic Zone. 2.30... JURISDICTION Jurisdictional Terms § 2.30 Exclusive Economic Zone. (a) With respect to the United States... States exercises sovereignty, exclusive economic zone means the zone seaward of and adjacent to the...

  19. Realization of the Zone Length Measurement during Zone Refining Process via Implementation of an Infrared Camera

    Directory of Open Access Journals (Sweden)

    Danilo C. Curtolo

    2018-05-01

    Full Text Available Zone refining, as the currently most common industrial process to attain ultrapure metals, is influenced by a variety of factors. One of these parameters, the so-called “zone length”, affects not only the ultimate concentration distribution of impurities, but also the rate at which this distribution is approached. This important parameter has however neither been investigated experimentally, nor ever varied for the purpose of optimization. This lack of detections may be due to the difficult temperature measurement of a moving molten area in a vacuum system, of which the zone refining methodology is comprised. Up to now, numerical simulation as a combination of complex mathematical calculations, as well as many assumptions has been the only way to reveal it. This paper aims to propose an experimental method to accurately measure the molten zone length and to extract helpful information on the thermal gradient, temperature profile and real growth rate in the zone refining of an exemplary metal, in this case aluminum. This thermographic method is based on the measurement of the molten surface temperature via an infrared camera, as well as further data analysis through the mathematical software MATLAB. The obtained results show great correlation with the visual observations of zone length and provide helpful information to determine the thermal gradient and real growth rate during the whole process. The investigations in this paper approved the application of an infrared camera for this purpose as a promising technique to automatically control the zone length during a zone refining process.

  20. VT Data - Zoning 20070306, Marlboro

    Data.gov (United States)

    Vermont Center for Geographic Information — Zoning districts, Marlboro, Vermont. Surface water buffer overlay is in a separate shapefile. Data were originally created by WRC in 2005. Marlboro's zoning bylaw...

  1. Reductive dechlorination of trichloroethene DNAPL source zones: source zone architecture versus electron donor availability

    Science.gov (United States)

    Krol, M.; Kokkinaki, A.; Sleep, B.

    2014-12-01

    The persistence of dense-non-aqueous-phase liquids (DNAPLs) in the subsurface has led practitioners and regulatory agencies to turn towards low-maintenance, low-cost remediation methods. Biological degradation has been suggested as a possible solution, based on the well-proven ability of certain microbial species to break down dissolved chlorinated ethenes under favorable conditions. However, the biodegradation of pure phase chlorinated ethenes is subject to additional constraints: the continuous release of electron acceptor at a rate governed by mass transfer kinetics, and the temporal and spatial heterogeneity of DNAPL source zones which leads to spatially and temporally variable availability of the reactants for reductive dechlorination. In this work, we investigate the relationship between various DNAPL source zone characteristics and reaction kinetics using COMPSIM, a multiphase groundwater model that considers non-equilibrium mass transfer and Monod-type kinetics for reductive dechlorination. Numerical simulations are performed for simple, homogeneous trichloroethene DNAPL source zones to demonstrate the effect of single source zone characteristics, as well as for larger, more realistic heterogeneous source zones. It is shown that source zone size, and mass transfer kinetics may have a decisive effect on the predicted bio-enhancement. Finally, we evaluate the performance of DNAPL bioremediation for realistic, thermodynamically constrained, concentrations of electron donor. Our results indicate that the latter may be the most important limitation for the success of DNAPL bioremediation, leading to reduced bio-enhancement and, in many cases, comparable performance with water flooding.

  2. Multichannel imager for littoral zone characterization

    Science.gov (United States)

    Podobna, Yuliya; Schoonmaker, Jon; Dirbas, Joe; Sofianos, James; Boucher, Cynthia; Gilbert, Gary

    2010-04-01

    This paper describes an approach to utilize a multi-channel, multi-spectral electro-optic (EO) system for littoral zone characterization. Advanced Coherent Technologies, LLC (ACT) presents their EO sensor systems for the surf zone environmental assessment and potential surf zone target detection. Specifically, an approach is presented to determine a Surf Zone Index (SZI) from the multi-spectral EO sensor system. SZI provides a single quantitative value of the surf zone conditions delivering an immediate understanding of the area and an assessment as to how well an airborne optical system might perform in a mine countermeasures (MCM) operation. Utilizing consecutive frames of SZI images, ACT is able to measure variability over time. A surf zone nomograph, which incorporates targets, sensor, and environmental data, including the SZI to determine the environmental impact on system performance, is reviewed in this work. ACT's electro-optical multi-channel, multi-spectral imaging system and test results are presented and discussed.

  3. The fracture zone project - final report

    International Nuclear Information System (INIS)

    Andersson, Peter

    1993-09-01

    This report summarizes the work and the experiences gained during the fracture zone project at the Finnsjoen study site. The project is probably the biggest effort, so far, to characterize a major fracture zone in crystalline bedrock. The project was running between 1984-1990 involving a large number of geological, geohydrological, geochemical, and geomechanical investigation. The methods used for identification and characterization are reviewed and discussed in terms of applicability and possible improvements for future investigations. The discussion is exemplified with results from the investigation within the project. Flow and transport properties of the zone determined from hydraulic tests and tracer tests are discussed. A large number of numerical modelling efforts performed within the fracture zone project, the INTRAVAL project, and the SKB91-study are summarized and reviewed. Finally, occurrence of similar zones and the relevance of major low angle fracture zones in connection to the siting of an underground repository is addressed

  4. Do "Some" Enterprise Zones Create Jobs?

    Science.gov (United States)

    Kolko, Jed; Neumark, David

    2010-01-01

    We study how the employment effects of enterprise zones vary with their location, implementation, and administration, based on evidence from California. We use new establishment-level data and geographic mapping methods, coupled with a survey of enterprise zone administrators. Overall, the evidence indicates that enterprise zones do not increase…

  5. SEMIAUTOMATIC DETECTION OF TUMORAL ZONE

    Directory of Open Access Journals (Sweden)

    Ezzeddine Zagrouba

    2011-05-01

    Full Text Available This paper describes a robust method based on the cooperation of fuzzy classification and regions segmentation algorithms, in order to detect the tumoral zone in the brain Magnetic Resonance Imaging (MRI. On one hand, the classification in fuzzy sets is done by the Fuzzy C-Means algorithm (FCM, where a study of its different parameters and its complexity has been previously realised, which led us to improve it. On the other hand, the segmentation in regions is obtained by an hierarchical method through adaptive thresholding. Then, an operator expert selects a germ in the tumoral zone, and the class containing the sick zone is localised in return for the FCM algorithm. Finally, the superposition of the two partitions of the image will determine the sick zone. The originality of our approach is the parallel exploitation of different types of information in the image by the cooperation of two complementary approaches. This allows us to carry out a pertinent approach for the detection of sick zone in MRI images.

  6. Splenic marginal zone lymphoma.

    Science.gov (United States)

    Piris, Miguel A; Onaindía, Arantza; Mollejo, Manuela

    Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed. Mutational spectrum of SMZL identifies specific findings, such as 7q loss and NOTCH2 and KLF2 mutations, both genes related with marginal zone differentiation. There is a striking clinical variability in SMZL cases, dependent of the tumoral load and performance status. Specific molecular markers such as 7q loss, p53 loss/mutation, NOTCH2 and KLF2 mutations have been found to be associated with the clinical variability. Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Cornell Mixing Zone Expert System

    Science.gov (United States)

    This page provides an overview Cornell Mixing Zone Expert System water quality modeling and decision support system designed for environmental impact assessment of mixing zones resulting from wastewater discharge from point sources

  8. Drug-Free School Zones: Taking Charge.

    Science.gov (United States)

    Thomas, Carol F.

    Information for planning and implementing drug-free school zones within a broader school-community prevention and intervention program is provided in this guidebook. The first section provides background information on drug-free school zone legislation and common elements of drug-free school zones. The risk and protective factors for alcohol and…

  9. State Enterprise Zone Programs: Have They Worked?

    Science.gov (United States)

    Peters, Alan H.; Fisher, Peter S.

    The effectiveness of state enterprise zone programs was examined by using a hypothetical-firm model called the Tax and Incentives Model-Enterprise Zones (TAIM-ez) model to analyze the value of enterprise zone incentives to businesses across the United States and especially in the 13 states that had substantial enterprise zone programs by 1990. The…

  10. Dead zone characteristics of a gas counter

    International Nuclear Information System (INIS)

    Nohtomi, Akihiro; Sakae, Takeji; Matoba, Masaru; Koori, Norihiko.

    1990-01-01

    The dead zone was recently defined as the product of dead length and dead time in order to describe the characteristics of the self-quenching streamer (SQS) mode of a gas counter. Investigation of the dead zone characteristics has been extended for the proportional and GM modes, and the measured dead zone has been compared with that of the SQS mode. Accurate values for the dead zone could be determined by means of a newly developed method with a pulse interval time to amplitude converter. Each operation mode indicates distinct dead zone characteristics. Properties of gas counters for high counting rates may be improved on the basis of measurements of the dead zone. (author)

  11. Street Prostitution Zones and Crime

    OpenAIRE

    Bisschop, Paul; Kastoryano, Stephen; van der Klaauw, Bas

    2015-01-01

    This paper studies the effects of introducing legal street prostitution zones on both registered and perceived crime. We exploit a unique setting in the Netherlands where legal street prostitution zones were opened in nine cities under different regulation systems. We provide evidence that the opening of these zones was not in response to changes in crime. Our difference-in-difference analysis using data on the largest 25 Dutch cities between 1994 and 2011 shows that opening a legal street pr...

  12. Elevational Distribution of Adult Trees and Seedlings in a Tropical Montane Transect, Southwest China

    Directory of Open Access Journals (Sweden)

    Xiaoyang Song

    2016-08-01

    Full Text Available Montane habitats are characterized by high variation of environmental factors within small geographic ranges, which offers opportunities to explore how forest assemblages respond to changes in environmental conditions. Understanding the distributional transition of adult trees and seedlings will provide insight into the fate of forest biodiversity in response to future climate change. We investigated the elevational distribution of 156 species of adult trees and 152 species of seedlings in a tropical montane forest in Xishuangbanna, southwest China. Adult trees and seedlings were surveyed within 5 replicate plots established at each of 4 elevational bands (800, 1000, 1200, and 1400 m above sea level. We found that species richness of both adult trees and seedlings changed with elevation, showing a notable decline in diversity values from 1000 to 1200 m. Tree species composition also demonstrated distinct differences between 1000 and 1200 m, marking the division between tropical seasonal rain forest (800 and 1000 m and tropical montane evergreen broad-leaved forest (1200 and 1400 m. The results suggested that soil moisture and temperature regimes were associated with elevational distribution of tree species in this region. We also observed that seedlings from certain species found at high elevations were also distributed in low-elevation zones, but no seedlings of species from low elevations were distributed in high-elevation zones. The increase in temperature and droughts predicted for this region may result in the contraction of tropical seasonal rain forest at lower elevations and a downhill shift of higher tropical montane tree species.

  13. 76 FR 3014 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA

    Science.gov (United States)

    2011-01-19

    ... Coast Guard will enforce the Blair Waterway security zone in Commencement Bay, WA for protection of... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2011-0015] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA AGENCY: Coast Guard, DHS...

  14. Radiation danger of exclusion zone objects

    International Nuclear Information System (INIS)

    Kholosha, V.I.; Proskura, N.I.; Ivanov, Yu.A.; Kazakov, S.V.; Arkhipov, A.N.

    2001-01-01

    The analysis of radiation danger of the Exclusion Zone objects was made. Here, the Zone is defined as the territory from which the population has been evacuated in 1986 owing to the Chernobyl accident and possible outflow of the contaminated substances out of the borders is potentially dangerous to the Ukraine. In the present work were analyzed such problems as sources of radiation danger in the Zone, ways of radionuclide migration out of the borders of the Zone in normal and emergency situations, the non-radiation (ecological) danger factors of the Zone objects, doses (individual and collective) from various sources and on separate ways of their formation, and the characteristics of radiation danger of the Zone objects. The conclusions are: (1) Radionuclide flows both from technologic and natural sources exceed those from Shelter objects, (2) Under emergency conditions, radionuclide flows and doze loading remain comparable with those from emergency sources, (3) To solve some management tasks in radiation situation, the basic works on the Shelter objects should be oriented to decrease probability of emergency occurrence and to reduce radiation influence (prevention wash-outs during high waters, fire-prevention measures in forests and strengthening of the control behind non-authorized use of objects in the Zone). (S. Ohno)

  15. 76 FR 9646 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

    Science.gov (United States)

    2011-02-22

    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Parts 100, 117, 147, and 165 [USCG-2010-0399] Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation Regulations and Regulated Navigation Areas AGENCY: Coast Guard, DHS. ACTION: Notice of expired temporary rules...

  16. Tracing the influence of the Trans-European Suture Zone into the mantle transition zone

    Czech Academy of Sciences Publication Activity Database

    Knapmeyer-Endrun, B.; Krüger, F.; Legendre, C. P.; Geissler, W.H.; Plomerová, Jaroslava; Babuška, Vladislav; Gaždová, Renata; Jedlička, Petr; Kolínský, Petr; Málek, Jiří; Novotný, Oldřich; Růžek, Bohuslav

    2013-01-01

    Roč. 363, FEB 1 (2013), s. 73-87 ISSN 0012-821X Institutional support: RVO:67985530 ; RVO:67985891 Keywords : mantle transition zone * Trans-European Suture Zone * East European Craton Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 4.724, year: 2013

  17. VT Data - Zoning Stream Buffers 20081014, Hartford

    Data.gov (United States)

    Vermont Center for Geographic Information — OVERLAY DISTRICT. Models a municipality’s zoning zones and related information. Final boundary determinations must be obtained from the town Zoning Administrator....

  18. GAMMA RAYS FROM THE TYCHO SUPERNOVA REMNANT: MULTI-ZONE VERSUS SINGLE-ZONE MODELING

    Energy Technology Data Exchange (ETDEWEB)

    Atoyan, Armen [Department of Mathematics, Concordia University, 1455 de Maisonneuve Blvd. West, Montreal, Quebec H3G 1M8 (Canada); Dermer, Charles D., E-mail: atoyan@mathstat.concordia.ca, E-mail: charles.dermer@nrl.navy.mil [Code 7653, Naval Research Laboratory, Washington, DC 20375-5352 (United States)

    2012-04-20

    Recent Fermi and VERITAS observations of the prototypical Type Ia supernova remnant (SNR) Tycho have discovered {gamma}-rays with energies E in the range 0.4 GeV {approx}< E {approx}< 10 TeV. Crucial for the theory of Galactic cosmic-ray origin is whether the {gamma}-rays from SNRs are produced by accelerated hadrons (protons and ions) or by relativistic electrons. Here we show that strong constraints on the leptonic model imposed in the framework of the commonly used single-zone model are essentially removed if the analysis of the broadband radiation spectrum of Tycho is done in the two-zone (or, in general, multi-zone) approach, which is likely to apply to every SNR. Importantly, we show that the single-zone approach may underpredict the {gamma}-ray fluxes by an order of magnitude. A hadronic model can, however, also fit the detected {gamma}-ray spectrum. The difference between {gamma}-ray fluxes of hadronic and leptonic origins becomes significant only at {approx}<300 MeV, which could be revealed by spectral measurements of Tycho and other SNRs at these energies.

  19. Chaotic Zones around Rotating Small Bodies

    Energy Technology Data Exchange (ETDEWEB)

    Lages, José; Shevchenko, Ivan I. [Institut UTINAM, Observatoire des Sciences de l’Univers THETA, CNRS, Université de Franche-Comté, Besançon F-25030 (France); Shepelyansky, Dima L., E-mail: jose.lages@utinam.cnrs.fr [Laboratoire de Physique Théorique du CNRS, IRSAMC, Université de Toulouse, UPS, Toulouse F-31062 (France)

    2017-06-01

    Small bodies of the solar system, like asteroids, trans-Neptunian objects, cometary nuclei, and planetary satellites, with diameters smaller than 1000 km usually have irregular shapes, often resembling dumb-bells or contact binaries. The spinning of such a gravitating dumb-bell creates around it a zone of chaotic orbits. We determine its extent analytically and numerically. We find that the chaotic zone swells significantly if the rotation rate is decreased; in particular, the zone swells more than twice if the rotation rate is decreased 10 times with respect to the “centrifugal breakup” threshold. We illustrate the properties of the chaotic orbital zones in examples of the global orbital dynamics about asteroid 243 Ida (which has a moon, Dactyl, orbiting near the edge of the chaotic zone) and asteroid 25143 Itokawa.

  20. 76 FR 55566 - Safety Zones; Fireworks Displays and Surfing Events in Captain of the Port Long Island Sound Zone

    Science.gov (United States)

    2011-09-08

    ...-AA00 Safety Zones; Fireworks Displays and Surfing Events in Captain of the Port Long Island Sound Zone... zones for marine events within the Captain of the Port (COTP) Long Island Sound Zone for a surfing event... unless authorized by the COTP Sector Long Island Sound. DATES: This rule is effective in the CFR on...

  1. Light-zone(s: as Concept and Tool

    Directory of Open Access Journals (Sweden)

    Merete Madsen

    2012-11-01

    Full Text Available Daylight is essential to the experience of an architectural space. Nevertheless, amongst the handful of predominantly scientific methods available to assess daylight in architecture, there are only a few considering the spatial and form-giving characteristics of daylight. This paper investigates light-zone(s as concept and tool, which can be taken as a point of departure for a new method to perceive, consider and analyse daylight in architecture. As concept, light-zone(s are areas, fields or zones of light. It is a way of considering a space’s daylight as (forms of bubbles or spheres of light, which as light-zones can be compressed, expanded, combined, exploded, etc., all according to the character of 'the meeting' between the light-zone(s and the space itself (inclusive of the space’scontent. Thus, the daylight in a space can be regarded asa composition of light-zones.As tool, light-zone(s are (spatial groupings of the lightingvariables (intensity, direction, distribution and colour, whichare significant to the space and form-giving characteristicsof light. That is to say, the light-zone(s tool is the point ofdeparture for a method of creating a spatial ‘grasp’ on daylighting variables in a given space. The relation between the light-zone(s concept and tool respectively can be described as follows: On the one level light-zone(s can be explored as an architectural idea or notion, thus belonging more to the field of architectural theory. On another more practice-driven level, light-zone(s can be articulated and specified in relation to lighting technology.

  2. Quantifying the Variation in Shear Zone Character with Depth: a Case Study from the Simplon Shear Zone, Central Alps

    Science.gov (United States)

    Cawood, T. K.; Platt, J. P.

    2017-12-01

    A widely-accepted model for the rheology of crustal-scale shear zones states that they comprise distributed strain at depth, in wide, high-temperature shear zones, which narrow to more localized, high-strain zones at lower temperature and shallower crustal levels. We test and quantify this model by investigating how the width, stress, temperature and deformation mechanisms change with depth in the Simplon Shear Zone (SSZ). The SSZ marks a major tectonic boundary in the central Alps, where normal-sense motion and rapid exhumation of the footwall have preserved evidence of older, deeper deformation in rocks progressively further into the currently-exposed footwall. As such, microstructures further from the brittle fault (which represents the most localized, most recently-active part of the SSZ) represent earlier, higher- temperature deformation from deeper crustal levels, while rocks closer to the fault have been overprinted by successively later, cooler deformation at shallower depths. This study uses field mapping and microstructural studies to identify zones representing deformation at various crustal levels, and characterize each in terms of zone width (representing width of the shear zone at that time and depth) and dominant deformation mechanism. In addition, quartz- (by Electron Backscatter Diffraction, EBSD) and feldspar grain size (measured optically) piezometry are used to calculate the flow stress for each zone, while the Ti-in-quartz thermometer (TitaniQ) is used to calculate the corresponding temperature of deformation. We document the presence of a broad zone in which quartz is recrystallized by the Grain Boundary Migration (GBM) mechanism and feldspar by Subgrain Rotation (SGR), which represents the broad, deep zone of deformation occurring at relatively high temperatures and low stresses. In map view, this transitions to successively narrower zones, respectively characterized by quartz SGR and feldspar Bulge Nucleation (BLG); quartz BLG and brittle

  3. Replantation of fingertip amputation by using the pocket principle in adults.

    Science.gov (United States)

    Lee, P K; Ahn, S T; Lim, P

    1999-04-01

    There are several treatment modalities for zone 1 or zone 2 fingertip amputations that cannot be replanted by using microsurgical techniques, such as delayed secondary healing, stump revision, skin graft, local flaps, distant flaps, and composite graft. Among these, composite graft of the amputated digit tip is the only possible means of achieving a full-length digit with a normal nail complex. The pocket principle can provide an extra blood supply for survival of the composite graft of the amputated finger by enlarging the area of vascular contact. The surgery was performed in two stages. The amputated digit was debrided, deepithelialized, and reattached to the proximal stump. The reattached finger was inserted into the abdominal pocket. About 3 weeks later, the finger was removed from the pocket and covered with a skin graft. We have consecutively replanted 29 fingers in 25 adult patients with fingertip amputations by using the pocket principle. All were complete amputations with crushing or avulsion injuries. Average age was 33.64 years, and men were predominant. The right hand, the dominant one, was more frequently injured, with the middle finger being the most commonly injured. Of the 29 fingers, 16 (55.2 percent) survived completely and 10 (34.5 percent) had partial necrosis less than one-quarter of the length of the amputated part. The results of the above 26 fingers were satisfactory from both functional and cosmetic aspects. Twenty of the 29 fingers, which had been followed up for more than 6 months (an average of 16 months), were included in a sensory evaluation. Fifteen of these 20 fingers (75 percent) were classified as "good" (static two-point discrimination of less than 8 mm and normal use). From the overall results and our experience, we suggest that the pocket principle is a safe and valuable method in replantation of zone 1 or zone 2 fingertip amputation, an alternative to microvascular replantation, even in adults.

  4. Empowerment Zones and Enterprise Districts - Volusia County Enterprise Zones

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Florida's Enterprise Zone Program encourages economic growth and investment in distressed areas by offering tax advantages and incentives to businesses that are...

  5. 78 FR 7265 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA

    Science.gov (United States)

    2013-02-01

    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2012-0087] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA AGENCY: Coast Guard, DHS... Security Zone in Commencement Bay, Tacoma, Washington from 6 a.m. on February 1, 2013, through 11:59 p.m...

  6. 78 FR 11981 - Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA

    Science.gov (United States)

    2013-02-21

    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2012-0087] Security Zone; Protection of Military Cargo, Captain of the Port Zone Puget Sound, WA AGENCY: Coast Guard, DHS... Security Zone in Commencement Bay, Tacoma, Washington from 6 a.m. on February 23, 2013, through 11:59 p.m...

  7. Automatic detection and classification of damage zone(s) for incorporating in digital image correlation technique

    Science.gov (United States)

    Bhattacharjee, Sudipta; Deb, Debasis

    2016-07-01

    Digital image correlation (DIC) is a technique developed for monitoring surface deformation/displacement of an object under loading conditions. This method is further refined to make it capable of handling discontinuities on the surface of the sample. A damage zone is referred to a surface area fractured and opened in due course of loading. In this study, an algorithm is presented to automatically detect multiple damage zones in deformed image. The algorithm identifies the pixels located inside these zones and eliminate them from FEM-DIC processes. The proposed algorithm is successfully implemented on several damaged samples to estimate displacement fields of an object under loading conditions. This study shows that displacement fields represent the damage conditions reasonably well as compared to regular FEM-DIC technique without considering the damage zones.

  8. An early geikiid dicynodont from the Tropidostoma Assemblage Zone (late Permian of South Africa

    Directory of Open Access Journals (Sweden)

    Christian F. Kammerer

    2017-01-01

    Full Text Available Based on specimens previously identified as Tropidostoma, a new taxon of dicynodont (Bulbasaurus phylloxyron gen. et sp. nov. from the Karoo Basin of South Africa is described. Bulbasaurus is a medium-sized dicynodont (maximum dorsal skull length 16.0 cm restricted to the Tropidostoma Assemblage Zone (early Lopingian of the Beaufort Group. Bulbasaurus can be distinguished from Tropidostoma by an array of characters including the presence of a tall, sharp premaxillary ridge, large, rugose, nearly-confluent nasal bosses, a nasofrontal ridge, massive tusks, robust pterygoids, prominently twisted subtemporal bar, and absence of a distinct postfrontal. Inclusion of Bulbasaurus in a phylogenetic analysis of anomodont therapsids recovers it as a member of Geikiidae, a clade of otherwise later Permian dicynodonts such as Aulacephalodon and Pelanomodon. Bulbasaurus exhibits many of the characters typical of adult Aulacephalodon, but at substantially smaller skull size (these characters are absent in comparably-sized Aulacephalodon juveniles, suggesting that the evolution of typical geikiid morphology preceded gigantism in the clade. Bulbasaurus is the earliest known geikiid and the only member of the group known from the Tropidostoma Assemblage Zone; discovery of this taxon shortens a perplexing ghost lineage and indicates that abundant clades from the later Permian of South Africa (e.g., Geikiidae, Dicynodontoidea may have originated as rare components of earlier Karoo assemblage zones.

  9. New geometrical compactness measures for zones design

    Directory of Open Access Journals (Sweden)

    Eric Alfredo Rincón-García

    2012-07-01

    Full Text Available The design of compact zones has been studied because of its influence in the creation of zones with regular forms, which are easier to analyze, to investigate or to administer. This paper propose a new method to measure compactness,by means of the transformation of the original geographical spaces, into figures formed with square cells, which are used to measure the similarity between the original zone and an ideal zone with straight forms. The proposed method was applied to design electoral zones, which must satisfy constraints of compactness, contiguity and population balance, in a topographical configuration that favors the creation of twisted and diffuse shapes. The results show that the new method favors the creation of zones with straight forms, without an important effect to the population balance, which are considered zones of high quality. Keywords: Redistricting, compactness, simulated annealing, GIS. Mathematics Subject Classification: 90C59, 90C29, 68T20.

  10. Trading Zones in Early Modern Europe.

    Science.gov (United States)

    Long, Pamela O

    2015-12-01

    This essay adopts the concept of trading zones first developed for the history of science by Peter Galison and redefines it for the early modern period. The term "trading zones" is used to mean arenas in which substantive and reciprocal communication occurred between individuals who were artisanally trained and learned (university-trained) individuals. Such trading zones proliferated in the sixteenth century. They tended to arise in certain kinds of places and not in others, but their existence must be determined empirically. The author's work on trading zones differs from the ideas of Edgar Zilsel, who emphasized the influence of artisans on the scientific revolution. In contrast, in this essay, the mutual influence of artisans and the learned on each other is stressed, and translation is used as a modality that was important to communication within trading zones.

  11. Main principles of the Chernobyl' NPP zone development

    International Nuclear Information System (INIS)

    Ignatenko, E.I.; Komarov, V.I.; Zverkov, V.V.; Proskuryakov, A.G.

    1989-01-01

    It is suggested to divide the Chernobyl' NPP zone into two parts, which are the alienation and evacuation (buffer) zones. The alienation zone includes the areas with greatest contamination around the Chernobyl' NPP. The population residence in this zone is forbidden. The watching method of working with short-time personnel residence is suggested to be used in this zone. The buffer zone is the territory out of the alienation zone boundaries including all settlements, from which the population is evacuated. Constant residence is permitted in the buffer zone for persons 50 and more years old with introduction of restrictions for diet and residence organization. The production activity in this zone includes operation of three units of the Chernobyl' NPP, works with the Ukrytie object and researches. Operations connected with radioactive waste processing and redisposal from places of storage is not recommended to be done. It is suggested to develop methods for local radioactive waste processing

  12. Planktonic Subsidies to Surf-Zone and Intertidal Communities

    Science.gov (United States)

    Morgan, Steven G.; Shanks, Alan L.; MacMahan, Jamie H.; Reniers, Ad J. H. M.; Feddersen, Falk

    2018-01-01

    Plankton are transported onshore, providing subsidies of food and new recruits to surf-zone and intertidal communities. The transport of plankton to the surf zone is influenced by wind, wave, and tidal forcing, and whether they enter the surf zone depends on alongshore variation in surf-zone hydrodynamics caused by the interaction of breaking waves with coastal morphology. Areas with gently sloping shores and wide surf zones typically have orders-of-magnitude-higher concentrations of plankton in the surf zone and dense larval settlement in intertidal communities because of the presence of bathymetric rip currents, which are absent in areas with steep shores and narrow surf zones. These striking differences in subsidies have profound consequences; areas with greater subsidies support more productive surf-zone communities and possibly more productive rocky intertidal communities. Recognition of the importance of spatial subsidies for rocky community dynamics has recently advanced ecological theory, and incorporating surf-zone hydrodynamics would be an especially fruitful line of investigation.

  13. Problems of Chernobyl exclusion zone

    International Nuclear Information System (INIS)

    1996-01-01

    The collection comprises the results of researches and design activity in the ChNPP exclusion zone with the aim to develop technology, equipment and instruments for RAW management and accident clean-up, studying of the composition and structure of the activity solid bearers in the soil of the exclusion zone and transformation of the radionuclides in the nearest zone of ChNPP. Much attention is paid to medical and biological problems of the accident influence on the flora, fauna and people's health labour conditions and incidence of the people involved

  14. Problems of Chornobyl Exclusion Zone

    International Nuclear Information System (INIS)

    Kashparov, V.A.

    2009-01-01

    The collection comprises the results of researches and design activity in the ChNPP exclusion zone with the aim to develop technology, equipment and instruments for RAW management and accident clean-up, studying of the composition and structure of the activity solid bearers in the soil of the exclusion zone and transformation of the radionuclides in the nearest zone of ChNPP. Much attention is paid to medical and biological problems of the accident influence on the flora, fauna and people's health, labour conditions and incidence of the people involved.

  15. Numerical calculation procedure for criticality parameters of the two-zone reflected reactor with flat central zone

    International Nuclear Information System (INIS)

    Bosevski, T.; Strugar, P.

    1966-10-01

    In determining the criticality parameters of a two-zone reactor with flat central zone one encounters a numerical problem requiring the solution of a system of two non-linear equations. To solve them the Newton method, which proved convenient, was used n this work. By comparing our results with those reported one obtains about 5% smaller values of both the radius of the flat zone and of the radial buckling of the outer zone. This discrepancy probably results from some approximations used in solving the same system of equations used in solving the same system of equations where the procedure form was applied, whereas the calculation time is by one order of magnitude smaller

  16. Nuclear weapons free zones

    International Nuclear Information System (INIS)

    Stahl, K.

    1990-01-01

    The article analyses the concept and problems of the two nuclear weapons free zones in Latin America and in the South Pacific established by the Treaty of Tlatelolco and the Treaty of Rarotonga. So far the nuclear weapons states except China have refused to sign the additional protocols of the Treaties or have signed them only with considerable provisos. Therefore they don't fully recognize the nuclear weapons free status of those zones, or they don't recognize it at all. Both Treaties contain no provisions to regulate the transit of nuclear weapons through the zones. This allows de facto the stationing of nuclear weapons in the military bases of the US which are located within the nuclear weapons free zone of Latin America. The Treaty of Tlatelolco contains also the right of the states, party to the Treaty, to explode nuclear devices for peaceful purposes. Since peaceful and military nuclear explosions cannot be distinguished technically, this right could also undermine the nuclear weapons free status of the region. Important nuclear threshold countries like Argentina and Brazil have furthermore refrained from putting the Treaty into force. (orig.) [de

  17. Instrumentation for coastal zone management

    Digital Repository Service at National Institute of Oceanography (India)

    Joseph, A.

    stream_size 11 stream_content_type text/plain stream_name Trg_Course_Coast_Zone_Manage_1993_91.pdf.txt stream_source_info Trg_Course_Coast_Zone_Manage_1993_91.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset...

  18. Management of coastal zone vegetation

    Digital Repository Service at National Institute of Oceanography (India)

    Untawale, A.G.

    stream_size 14 stream_content_type text/plain stream_name Trg_Course_Coast_Zone_Manage_1993_22.pdf.txt stream_source_info Trg_Course_Coast_Zone_Manage_1993_22.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset...

  19. Structure and function of nematode communities across the Indian western continental margin and its oxygen minimum zone

    Science.gov (United States)

    Singh, R.; Ingole, B. S.

    2016-01-01

    We studied patterns of nematode distribution along the western Indian continental margin to determine the influence of habitat heterogeneity and low oxygen levels on the community's taxonomic and functional structure. A single transect, perpendicular to the coast at 14° N latitude was sampled from 34 to 2546 m depth for biological and environmental variables during August 2007. The oxygen minimum zone extended from 102 to 1001 m. Nematodes (described and undescribed) were identified to species and classified according to biological and functional traits. A total of 110 nematode species belonging to 24 families were found along the transect. Three depth zones were identified: the shelf (depth range: 34-102 m; highest nematode mean density: 176.6 ± 37 ind 10 cm-2), the slope (525-1524 m; 124.3 ± 16 ind 10 cm-2), and the basin (2001-2546 m; 62.9 ± 2 ind 10 cm-2). Across the entire study area, the dominant species were Terschellingia longicaudata, Desmodora sp. 1, Sphaerolaimus gracilis, and Theristus ensifer; their maximum density was at shelf stations. Nematode communities in different zones differed in species composition. Chromadorita sp. 2 (2.78 %) and Sphaerolaimus gracilis (2.21 %) were dominant on the shelf, whereas Terschellingia longicaudata (4.73 %) and Desmodora sp. 1 (4.42 %) were dominant on the slope, but in the basin, Halalaimus sp. 1(1.11 %) and Acantholaimus elegans (1.11 %) were dominant. The information in a particular functional group was not a simple reflection of the information in species abundance. Ecological information captured by adult length, adult shape, and life-history strategy was less site-specific and thus differed notably from information contained in other taxonomic groups. The functional composition of nematodes was strongly linked to the organic-carbon and dissolved-oxygen concentration. Seven species were found exclusively in the oxygen minimum zone: Pselionema sp. 1, Choanolaimus sp. 2, Halichoanolaimus sp. 1, Cobbia dentata

  20. White Light Photorefractive Phase Zone Plates

    International Nuclear Information System (INIS)

    Yuan-Mei, Gao; Si-Min, Liu

    2008-01-01

    Incoherent white light from an incandescent source is employed to fabricate volume phase zone plates in LiNbO 3 : Fe, for the first time to our knowledge, which can guide and modulate the input white light or laser light. The diffractive efficiency of the white light volume phase zone plates fabricated can reach as high as 12%. In addition, we test the volume phase zone plates by a probe beam and find that the volume phase zone plate is present in the direction perpendicular to the c-axis and absent in the direction parallel to the c-axis. This directly proves the existence of photovoltaic photorefractive anisotropy of white light

  1. Radiopaque zones in the dentin beneath amalgam restorations

    International Nuclear Information System (INIS)

    You, Young Jun; Ahn, Hyung Kyu

    1978-01-01

    The purpose of the present investigation is determine how frequently radiopaque zones are seen on standard intraoral film and to research some other things about radiopaque bones. This study obtained the following results: 1. According to the standard intraoral films of the charts that were kept at the Dept. of Oral Diagnosis in Seoul National University Hospital, radiopaque zones were found in the rate of 4.1% among 1150 cases of amalgam-restored teeth that were treated at least two years ago. 2. Out of teeth that possessed radiopaque zones, 38.3% had radiolucent area between amalgam restoration and radiopaque zone. 3. Out of teeth that possessed radiopaque zones, 36.2% had cement base between amalgam restoration and radiopaque zone. 4. Out of teeth that possessed radiopaque zones, no tooth had periapical radiolucency. 5. Radiopaque zones were found more frequently in the mandibular teeth than the maxillary teeth. 6. According to the result of direct x-ray taking of 50 teeth that were treated at least 2 years ago, 6% had radiopaque zone.

  2. Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice.

    Directory of Open Access Journals (Sweden)

    Li-Li Wang

    Full Text Available Stroke is a major neurovascular disorder threatening human life and health. Very limited clinical treatments are currently available for stroke patients. Stem cell transplantation has shown promising potential as a regenerative treatment after ischemic stroke. The present investigation explores a new concept of mobilizing endogenous stem cells/progenitor cells from the bone marrow using a parathyroid hormone (PTH therapy after ischemic stroke in adult mice. PTH 1-34 (80 µg/kg, i.p. was administered 1 hour after focal ischemia and then daily for 6 consecutive days. After 6 days of PTH treatment, there was a significant increase in bone marrow derived CD-34/Fetal liver kinase-1 (Flk-1 positive endothelial progenitor cells (EPCs in the peripheral blood. PTH treatment significantly increased the expression of trophic/regenerative factors including VEGF, SDF-1, BDNF and Tie-1 in the brain peri-infarct region. Angiogenesis, assessed by co-labeled Glut-1 and BrdU vessels, was significantly increased in PTH-treated ischemic brain compared to vehicle controls. PTH treatment also promoted neuroblast migration from the subventricular zone (SVZ and increased the number of newly formed neurons in the peri-infarct cortex. PTH-treated mice showed significantly better sensorimotor functional recovery compared to stroke controls. Our data suggests that PTH therapy improves endogenous repair mechanisms after ischemic stroke with functional benefits. Mobilizing endogenous bone marrow-derived stem cells/progenitor cells using PTH and other mobilizers appears an effective and feasible regenerative treatment after ischemic stroke.

  3. mRNA transfection of mouse and human neural stem cell cultures.

    Directory of Open Access Journals (Sweden)

    Samuel McLenachan

    Full Text Available The use of synthetic mRNA as an alternative gene delivery vector to traditional DNA-based constructs provides an effective method for inducing transient gene expression in cell cultures without genetic modification. Delivery of mRNA has been proposed as a safer alternative to viral vectors in the induction of pluripotent cells for regenerative therapies. Although mRNA transfection of fibroblasts, dendritic and embryonic stem cells has been described, mRNA delivery to neurosphere cultures has not been previously reported. Here we sought to establish an efficient method for delivering mRNA to primary neurosphere cultures. Neurospheres derived from the subventricular zone of adult mice or from human embryonic stem cells were transfected with EGFP mRNA by lipofection and electroporation. Transfection efficiency and expression levels were monitored by flow cytometry. Cell survival following transfection was examined using live cell counting and the MTT assay. Both lipofection and electroporation provided high efficiency transfection of neurospheres. In comparison with lipofection, electroporation resulted in increased transfection efficiencies, but lower expression per cell and shorter durations of expression. Additional rounds of lipofection renewed EGFP expression in neurospheres, suggesting this method may be suitable for reprogramming applications. In summary, we have developed a protocol for achieving high efficiency transfection rates in mouse and human neurosphere cell culture that can be applied for future studies of gene function studies in neural stem cells, such as defining efficient differentiation protocols for glial and neuronal linages.

  4. mRNA Transfection of Mouse and Human Neural Stem Cell Cultures

    Science.gov (United States)

    McLenachan, Samuel; Zhang, Dan; Palomo, Ana Belén Alvarez; Edel, Michael J.; Chen, Fred K.

    2013-01-01

    The use of synthetic mRNA as an alternative gene delivery vector to traditional DNA-based constructs provides an effective method for inducing transient gene expression in cell cultures without genetic modification. Delivery of mRNA has been proposed as a safer alternative to viral vectors in the induction of pluripotent cells for regenerative therapies. Although mRNA transfection of fibroblasts, dendritic and embryonic stem cells has been described, mRNA delivery to neurosphere cultures has not been previously reported. Here we sought to establish an efficient method for delivering mRNA to primary neurosphere cultures. Neurospheres derived from the subventricular zone of adult mice or from human embryonic stem cells were transfected with EGFP mRNA by lipofection and electroporation. Transfection efficiency and expression levels were monitored by flow cytometry. Cell survival following transfection was examined using live cell counting and the MTT assay. Both lipofection and electroporation provided high efficiency transfection of neurospheres. In comparison with lipofection, electroporation resulted in increased transfection efficiencies, but lower expression per cell and shorter durations of expression. Additional rounds of lipofection renewed EGFP expression in neurospheres, suggesting this method may be suitable for reprogramming applications. In summary, we have developed a protocol for achieving high efficiency transfection rates in mouse and human neurosphere cell culture that can be applied for future studies of gene function studies in neural stem cells, such as defining efficient differentiation protocols for glial and neuronal linages. PMID:24386231

  5. mRNA transfection of mouse and human neural stem cell cultures.

    Science.gov (United States)

    McLenachan, Samuel; Zhang, Dan; Palomo, Ana Belén Alvarez; Edel, Michael J; Chen, Fred K

    2013-01-01

    The use of synthetic mRNA as an alternative gene delivery vector to traditional DNA-based constructs provides an effective method for inducing transient gene expression in cell cultures without genetic modification. Delivery of mRNA has been proposed as a safer alternative to viral vectors in the induction of pluripotent cells for regenerative therapies. Although mRNA transfection of fibroblasts, dendritic and embryonic stem cells has been described, mRNA delivery to neurosphere cultures has not been previously reported. Here we sought to establish an efficient method for delivering mRNA to primary neurosphere cultures. Neurospheres derived from the subventricular zone of adult mice or from human embryonic stem cells were transfected with EGFP mRNA by lipofection and electroporation. Transfection efficiency and expression levels were monitored by flow cytometry. Cell survival following transfection was examined using live cell counting and the MTT assay. Both lipofection and electroporation provided high efficiency transfection of neurospheres. In comparison with lipofection, electroporation resulted in increased transfection efficiencies, but lower expression per cell and shorter durations of expression. Additional rounds of lipofection renewed EGFP expression in neurospheres, suggesting this method may be suitable for reprogramming applications. In summary, we have developed a protocol for achieving high efficiency transfection rates in mouse and human neurosphere cell culture that can be applied for future studies of gene function studies in neural stem cells, such as defining efficient differentiation protocols for glial and neuronal linages.

  6. Ex vivo study of dentate gyrus neurogenesis in human pharmacoresistant temporal lobe epilepsy.

    Science.gov (United States)

    Paradisi, M; Fernández, M; Del Vecchio, G; Lizzo, G; Marucci, G; Giulioni, M; Pozzati, E; Antonelli, T; Lanzoni, G; Bagnara, G P; Giardino, L; Calzà, L

    2010-10-01

    Neurogenesis in adult humans occurs in at least two areas of the brain, the subventricular zone of the telencephalon and the subgranular layer of the dentate gyrus in the hippocampal formation. We studied dentate gyrus subgranular layer neurogenesis in patients subjected to tailored antero-mesial temporal resection including amygdalohippocampectomy due to pharmacoresistant temporal lobe epilepsy (TLE) using the in vitro neurosphere assay. Sixteen patients were enrolled in the study; mesial temporal sclerosis (MTS) was present in eight patients. Neurogenesis was investigated by ex vivo neurosphere expansion in the presence of mitogens (epidermal growth factor + basic fibroblast growth factor) and spontaneous differentiation after mitogen withdrawal. Growth factor synthesis was investigated by qRT-PCR in neurospheres. We demonstrate that in vitro proliferation of cells derived from dentate gyrus of TLE patients is dependent on disease duration. Moreover, the presence of MTS impairs proliferation. As long as in vitro proliferation occurs, neurogenesis is maintained, and cells expressing a mature neurone phenotype (TuJ1, MAP2, GAD) are spontaneously formed after mitogen withdrawal. Finally, formed neurospheres express mRNAs encoding for growth (vascular endothelial growth factor) as well as neurotrophic factors (brain-derived neurotrophic factor, ciliary neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor). We demonstrated that residual neurogenesis in the subgranular layer of the dentate gyrus in TLE is dependent on diseases duration and absent in MTS. © 2010 The Authors. Neuropathology and Applied Neurobiology © 2010 British Neuropathological Society.

  7. Seismotectonic zoning of Azerbaijan territory

    Science.gov (United States)

    Kangarli, Talat; Aliyev, Ali; Aliyev, Fuad; Rahimov, Fuad

    2017-04-01

    Studying of the space-time correlation and consequences effect between tectonic events and other geological processes that have created modern earth structure still remains as one of the most important problems in geology. This problem is especially important for the East Caucasus-South Caspian geodynamic zone. Being situated at the eastern part of the Caucasian strait, this zone refers to a center of Alpine-Himalayan active folded belt, and is known as a complex tectonic unit with jointing heterogeneous structural-substantial complexes arising from different branches of the belt (Doburja-Caucasus-Kopetdag from the north and Pyrenean-Alborz from the south with Kura and South Caspian zone). According to GPS and precise leveling data, activity of regional geodynamic processes shows intensive horizontal and vertical movements of the Earth's crust as conditioned by collision of the Arabian and Eurasian continental plates continuing since the end of Miocene. So far studies related to the regional of geology-geophysical data, periodically used for the geological and tectonic modeling of the environment mainly based on the fixing ideology. There still remains a number of uncertainties in solution of issues related to regional geology, tectonics and magmatism, structure and interrelation of different structural zones, space-time interrelations between onshore and offshore complexes, etc. At the same time large dataset produced by surface geological surveys, deep geological mapping of on- and offshore areas with the use of seismic and electrical reconnaissance and geophysical field zoning methods, deep well drilling and remote sensing activities. Conducted new studies produced results including differentiation of formerly unknown nappe complexes of the different ages and scales within the structure of mountain-fold zones, identification of new zones containing ophiolites in their section, outlining of currently active faulting areas, geophysical interpretation of the deep

  8. Application of the zone-melting technique to metal chelate systems-VI A new apparatus for zone-melting chromatography.

    Science.gov (United States)

    Maeda, S; Kobayashi, H; Ueno, K

    1973-07-01

    An improved apparatus has been constructed for zone-melting chromatography. An essential feature of the apparatus is that the length of the molten zone can be kept constant during a zone-melting operation, by employing heating and cooling compartments which are separated from each other by double partition plates. Each compartment is heated or cooled with jets of hot or cold air. The apparatus is suitable for organic materials melting in the range between 40 degrees and 180 degrees . The distribution of metal ion along the column after zone melting of copper acetylacetonate in 2-methoxynaphthalene was a smooth curve. The plot of the position of maximum concentration, x(max), against the number of zone passes, n, gave a relationship in accordance with theoretical prediction.

  9. Field observations of climbing behavior and seed predation by adult ground beetles (Coleoptera: Carabidae) in a lowland area of the temperate zone.

    Science.gov (United States)

    Sasakawa, Kôji

    2010-10-01

    Granivory is a specialized food habit in the predominantly carnivorous beetle family Carabidae. Most studies of carabid granivory have been conducted under laboratory conditions; thus, our knowledge of the feeding ecology of granivorous carabids in the field is insufficient. I conducted field observations of climbing behavior and seed predation by adult carabids in a lowland area of eastern Japan, from early October to late November in 2008. This is the first systematic field observation of the feeding ecology of granivorous carabids in the temperate zone. In total, 176 carabid individuals of 11 species were observed, with 108 individuals feeding on plant seeds/flowers. Each carabid species was primarily observed feeding on a particular plant species. Frequently observed combinations were: Amara gigantea Motschulsky on Humulus scandens (Loureiro) Merrill (Moraceae) seed, Amara lucens Baliani on Artemisia indica Willdenow (Asteraceae) flower, and Amara macronota (Solsky) and Harpalus (Pseudoophonus) spp. on Digitaria ciliaris (Retzius) Koeler (Poaceae) seed. In all but one species, the sex ratio of individuals observed feeding was female-biased. In Am. gigantea and Am. macronota, a larger proportion of females than males ate seeds. In the three Amara species, copulations on plants, with the female feeding on its seeds/flowers, were often observed. These observations may indicate that, whereas females climb onto plants to feed on seeds, males climb to seek females for copulation rather than forage. Because granivorous carabids play important roles as weed-control agents in temperate agro-ecosystems, the present results would provide valuable basic information for future studies on this subject.

  10. Explaining the frequency of alcohol consumption in a conflict zone: Jews and Palestinians in Israel.

    Science.gov (United States)

    Massey, Zohar; Chartier, Karen G; Stebbins, Mary B; Canetti, Daphna; Hobfoll, Stevan E; Hall, Brian J; Shuval, Kerem

    2015-07-01

    Experiencing stress and exposure to terrorism may have an adverse effect on health risk behaviors. Few studies have examined alcohol use among adults living in Israel under chronic, stressful terrorism-related conditions. In this study, we examined the relationships of demographics, past stressful events, and terrorism exposure to the frequency of alcohol use and the mediating roles of depressive and post-traumatic stress disorder (PTSD) symptoms. We used three waves of data from a 2007-2008 nationally representative sample of Jewish and Palestinian adults in Israel. We assessed past stressful events, in addition to direct and indirect exposures to terrorism. Results indicated that past stressful events and exposure to terrorism were not directly associated with alcohol use, but were indirectly associated and mediated by depressive and PTSD symptomology. Mental health symptoms were differentially associated with alcohol use. More frequent drinking was mediated by higher levels of depression, including for women and Palestinians; however, PTSD symptom severity was related to less frequent drinking. Mental health may play a prominent role in the frequency of alcohol use among adults exposed to terrorism in Israel. Alcohol use, as a coping mechanism, may differ by demographic characteristics (gender and ethnicity) and psychological symptomology for adults living in a conflict zone in Israel. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Differences in quantitative assessment of myocardial scar and gray zone by LGE-CMR imaging using established gray zone protocols.

    Science.gov (United States)

    Mesubi, Olurotimi; Ego-Osuala, Kelechi; Jeudy, Jean; Purtilo, James; Synowski, Stephen; Abutaleb, Ameer; Niekoop, Michelle; Abdulghani, Mohammed; Asoglu, Ramazan; See, Vincent; Saliaris, Anastasios; Shorofsky, Stephen; Dickfeld, Timm

    2015-02-01

    Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the gold standard for myocardial scar evaluation. Heterogeneous areas of scar ('gray zone'), may serve as arrhythmogenic substrate. Various gray zone protocols have been correlated to clinical outcomes and ventricular tachycardia channels. This study assessed the quantitative differences in gray zone and scar core sizes as defined by previously validated signal intensity (SI) threshold algorithms. High quality LGE-CMR images performed in 41 cardiomyopathy patients [ischemic (33) or non-ischemic (8)] were analyzed using previously validated SI threshold methods [Full Width at Half Maximum (FWHM), n-standard deviation (NSD) and modified-FWHM]. Myocardial scar was defined as scar core and gray zone using SI thresholds based on these methods. Scar core, gray zone and total scar sizes were then computed and compared among these models. The median gray zone mass was 2-3 times larger with FWHM (15 g, IQR: 8-26 g) compared to NSD or modified-FWHM (5 g, IQR: 3-9 g; and 8 g. IQR: 6-12 g respectively, p zone extent (percentage of total scar that was gray zone) also varied significantly among the three methods, 51 % (IQR: 42-61 %), 17 % (IQR: 11-21 %) versus 38 % (IQR: 33-43 %) for FWHM, NSD and modified-FWHM respectively (p zone and scar core. Infarct core and total myocardial scar mass also differ using these methods. Further evaluation of the most accurate quantification method is needed.

  12. Fracture zones constrained by neutral surfaces in a fault-related fold: Insights from the Kelasu tectonic zone, Kuqa Depression

    Science.gov (United States)

    Sun, Shuai; Hou, Guiting; Zheng, Chunfang

    2017-11-01

    Stress variation associated with folding is one of the controlling factors in the development of tectonic fractures, however, little attention has been paid to the influence of neutral surfaces during folding on fracture distribution in a fault-related fold. In this study, we take the Cretaceous Bashijiqike Formation in the Kuqa Depression as an example and analyze the distribution of tectonic fractures in fault-related folds by core observation and logging data analysis. Three fracture zones are identified in a fault-related fold: a tensile zone, a transition zone and a compressive zone, which may be constrained by two neutral surfaces of fold. Well correlation reveals that the tensile zone and the transition zone reach the maximum thickness at the fold hinge and get thinner in the fold limbs. A 2D viscoelastic stress field model of a fault-related fold was constructed to further investigate the mechanism of fracturing. Statistical and numerical analysis reveal that the tensile zone and the transition zone become thicker with decreasing interlimb angle. Stress variation associated with folding is the first level of control over the general pattern of fracture distribution while faulting is a secondary control over the development of local fractures in a fault-related fold.

  13. 76 FR 7107 - Quarterly Listings; Safety Zones, Security Zones, Special Local Regulations, Drawbridge Operation...

    Science.gov (United States)

    2011-02-09

    ... defined boundary for which regulations for vessels navigating within the area have been established by the...)...... 9/19/2008 USCG-2008-0814 San Diego, CA Safety Zones (Part 165)...... 9/6/2008 USCG-2008-0827 Ocean... (Part 165). USCG-2009-0402 Ocean City, NJ Safety Zones (Part 165)...... 10/10/2009 USCG-2009-0403...

  14. Potencial terapêutico das células-tronco de medula óssea no tratamento da epilepsia Therapeutic potential of bone marrow stem cells in epilepsy treatment

    Directory of Open Access Journals (Sweden)

    Maria Julia M. Carrion

    2009-05-01

    Full Text Available Epilepsia é uma patologia bastante prevalente no nosso meio. Há um número significativo de pacientes que não obtém resposta com a terapêutica medicamentosa, o que motivou a pesquisa de novas terapêuticas. O conceito de neurogênese no cérebro adulto, hoje já amplamente conhecida, principalmente a que ocorre na zona subventricular e na zona subgranular do giro denteado, motivou o desenvolvimeto de técnicas que aproveitassem esse mecanismo na tentativa de obtenção de efeitos antiepileptogênicos e reparadores. A maior parte dos estudos em vigência hoje, e que buscam tal finalidade, trabalha o uso de transplante de células progenitoras neurais ou de células fetais em modelos experimentais. No entanto, a terapêutica com células-tronco de medula óssea parece bastante interessante e promissora. Em doenças neurológicas nas quais os danos são frequentemente irreversíveis, as estratégias regenerativas podem representar um novo caminho. Em nosso laboratório, temos estudado o potencial terapêutico de células-tronco da medula óssea no controle de crises espontâneas recorrentes associadas ao modelo da pilocarpina com resultados excelentes. Também já está em andamento o primeiro estudo em humanos utilizando células-tronco de medula óssea para o tratatamento da epilepsia.Epilepsy is a prevalent pathology. A significative number of patients do not achieve an adequate response to pharmacological therapy. This observation has motivated the search for new strategies. The now well known concept of neurogenesis in the adult brain, in particular in the subventricular and dentate gyrus subgranular zones, has encouraged the development of strategies that might control this mechanism in order to obtain either antiepileptogenic or repair effects. Most studies focus on the transplantation of neural progenitor or fetal cells in experimental models, although bone marrow stem cell therapy is promising. In neurological diseases in which damage

  15. Seasonal Ice Zone Reconnaissance Surveys Coordination

    Science.gov (United States)

    2016-03-30

    Chukchi sea seasonal sea ice zone (SIZ) utilizing US Coast Guard Arctic Domain Awareness ( ADA ) flights of opportunity in the summers of 2012- 2014. In...measurements across the Beaufort-Chukchi sea seasonal sea ice zone (SIZ) utilizing US Coast Guard Arctic Domain Awareness ( ADA ) flights of...such, it contains the full range of positions of the marginal ice zone (MIZ) where sea ice interacts with open water. In addition to SIZRS

  16. Environmental Zoning: Some methodological implications

    NARCIS (Netherlands)

    Ike, Paul; Voogd, Henk

    1991-01-01

    The purpose of this article is to discuss some methodological problems of environmental zoning. The principle of environmental zoning will be elaborated. In addition an overview is given of a number of approaches that have been followed in practice to arrive at an integral judgement. Finally some

  17. Growth with Time Zone Differences

    OpenAIRE

    Toru Kikuchi; Sugata Marjit

    2010-01-01

    We propose a two-country growth model of intermediate business-services trade that captures the role of time zone differences. It is shown that a time-saving improvement in intermediate business-services trade involving production in different time zones can have a permanent impact on productivity.

  18. The segmentation of zones with increased autofluorescence in the junctional zone of parapapillary atrophy

    International Nuclear Information System (INIS)

    Kolář, R; Jan, J; Laemmer, R; Mardin, Ch Y

    2009-01-01

    The autofluorescence (AF) derived from the retinal pigment epithelium has the potential to be used as a feature for early glaucoma diagnosis. The aim of this paper is to design and evaluate the method used for semi-automatic segmentation of the zones with increased autofluorescence. A randomized sample of 20 patients (age: 56 ± 10 years) with open angle glaucoma was used. A new method for semi-automatic detection and segmentation of the zones with a higher level of autofluorescence in the junctional zone of parapapillary atrophy has been evaluated. Good agreement has been observed between manually and semi-automatically segmented zones for most of the images, but higher differences may occur for larger hyperfluorescent regions. The data were evaluated using the limits of agreement, with a 2σ border. The described method allows fast and objective evaluation of AF images, preventing undesirable inter-expert variance. A large proportion of AF images could be evaluated successfully by the developed procedure, and the obtained results are comparable to the manual procedure in most cases

  19. Double seismic zone for deep earthquakes in the izu-bonin subduction zone.

    Science.gov (United States)

    Iidaka, T; Furukawa, Y

    1994-02-25

    A double seismic zone for deep earthquakes was found in the Izu-Bonin region. An analysis of SP-converted phases confirms that the deep seismic zone consists of two layers separated by approximately 20 kilometers. Numerical modeling of the thermal structure implies that the hypocenters are located along isotherms of 500 degrees to 550 degrees C, which is consistent with the hypothesis that deep earthquakes result from the phase transition of metastable olivine to a high-pressure phase in the subducting slab.

  20. Purification by using the zone melting technique; Purification par la technique de la zone fondue

    Energy Technology Data Exchange (ETDEWEB)

    Clerc, Michel

    1962-06-22

    The zone melting technique has first been used in metallurgy, and has been developed for the preparation of silicon and germanium for semiconductors, and then for the preparation of organic bodies of high purity. In this research thesis, the author first presents the principle of this technique, and then discusses the influence of agitation in liquid phase, and the influence of the number of passages over the zone. He discusses issues related to matter transport, and some technical details which intervene in the design of an apparatus for purification by zone melting. He finally presents examples.

  1. ZONING DESIGN FOR HAND­WRITTEN NUMERAL RECOGNITION

    NARCIS (Netherlands)

    Lecce Di, V.; Dimauro, G.; Guerriero, A.; Impedovo, S.; Pirlo, G.; Salzo, A.

    2004-01-01

    In the field of Optical Character Recognition (OCR), zoning is used to extract topological information from patterns. In this paper zoning is considered as the result of an optimisation problem and a new technique is presented for automatic zoning. More precisely, local analysis of feature

  2. Neurogenic effects of fingolimod in hippocampus, affecting fear memory.

    Directory of Open Access Journals (Sweden)

    Paschalis Efstathopoulos

    2014-05-01

    Full Text Available Fingolimod (FTY720; Gilenya™,Novartis Pharma AG is a recently developed Sphingosine-1-Phosphate (S1P analogue, orally administered as a new therapeutic agent in Multiple Sclerosis (MS (Brinkmann V. et al. 2010. S1P receptors (S1PRs are expressed in various sites in the CNS including the subventricular zone (Waeber C. et al. 1999; Choi J.W. et al. 2013 while endogenous S1P was shown to induce proliferation and morphological changes in embryonic hippocampal neural progenitors in culture (Harada J. et al. 2004. In this study we investigated the effects of fingolimod on adult rodent hippocampal neurogenesis and their possible functional role. To this aim, thymidine analogue BrdU was injected at the end or before a 2-week i.p. administration of a therapeutic dose of Fingolimod (0,3 mg/kg in young and old mice. Stereological counts of BrdU+ cells revealed significant increase in both proliferation, and survival of neural stem cells (NSC in the area of Dentate Gyrus (DG of the hippocampus, compared to control untreated animals of young but not old ages. In the case of survival assessment, most of the BrdU + cells were also positive for NeuN, suggesting an increase of newly formed neurons. The increase in proliferation rate of NSC was also confirmed by BrdU uptake in hippocampal NSC cultures in vitro, implying that the effects of fingolimod are cell autonomous. Immunohistochemical analysis showed that S1PR was not co-localized with GFAP+ cells in the Subgranular zone (SGZ of the DG, but was strongly co-localized with transcription factor MASH1 and weakly with DcX or PSA-NCAM positive neural progenitors. These findings suggest that expression of S1PR1 in the SGZ is restricted to transit amplifying neural progenitors and maintained also in the stage of neuroblast. In addition, the effects of Fingolimod in DG neurogenesis were positively correlated to enhanced fear memory and increased context discrimination, an established DG-dependent cognitive task

  3. Dynamic expression of the p53 family members p63 and p73 in the mouse and human telencephalon during development and in adulthood.

    Science.gov (United States)

    Hernández-Acosta, N Carolina; Cabrera-Socorro, Alfredo; Morlans, Mercedes Pueyo; Delgado, Francisco J González; Suárez-Solá, M Luisa; Sottocornola, Roberta; Lu, Xin; González-Gómez, Miriam; Meyer, Gundela

    2011-02-04

    p63 and p73, family members of the tumor suppressor p53, are critically involved in the life and death of mammalian cells. They display high homology and may act in concert. The p73 gene is relevant for brain development, and p73-deficient mice display important malformations of the telencephalon. In turn, p63 is essential for the development of stratified epithelia and may also play a part in neuronal survival and aging. We show here that p63 and p73 are dynamically expressed in the embryonic and adult mouse and human telencephalon. During embryonic stages, Cajal-Retzius cells derived from the cortical hem co-express p73 and p63. Comparison of the brain phenotypes of p63- and p73- deficient mice shows that only the loss of p73 function leads to the loss of Cajal-Retzius cells, whereas p63 is apparently not essential for brain development and Cajal-Retzius cell formation. In postnatal mice, p53, p63, and p73 are present in cells of the subventricular zone (SVZ) of the lateral ventricle, a site of continued neurogenesis. The neurogenetic niche is reduced in size in p73-deficient mice, and the numbers of young neurons near the ventricular wall, marked with doublecortin, Tbr1 and calretinin, are dramatically decreased, suggesting that p73 is important for SVZ proliferation. In contrast to their restricted expression during brain development, p73 and p63 are widely detected in pyramidal neurons of the adult human cortex and hippocampus at protein and mRNA levels, pointing to a role of both genes in neuronal maintenance in adulthood. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Radially converging tracer test in a low-angle fracture zone at the Finnsjoen site, central Sweden. The fracture zone project - phase 3

    International Nuclear Information System (INIS)

    Gustafsson, E.; Nordqvist, R.

    1993-10-01

    The performance and results of a radially converging tracer test in a low-angle major fracture zone in crystalline rock are described. The extensive, about 100 m thick, zone 2 was encountered by means of borehole investigations at depths ranging from 100 to 250 metres at the Finnsjon site, central eastern Sweden. The zone studied (zone 2) consists of highly conductive, metre thick interconnected minor shear and fracture zones (sub-zones) with low conductive rock in between. The objective of the tracer test was primarily to determine flow and transport characteristics in a major fracture zone. Secondly new equipment, experimental design and methods of interpretation were developed, tested and improved. The converging flow field was created by pumping in a central borehole from a packed-off interval enclosing the whole thickness of zone 2. Tracer breakthrough was registered from all nine injection points, with first arrivals ranging from 24 to 3200 hours. Evaluated flow and transport parameters included; flow porosity, dispersivity, flow wetted surface, fracture aperture and hydraulic conductivity in fracture flow paths. Directional variations were found in the flow and transport parameters determined, which is concluded to be due to heterogeneity and/or anisotropy. This conditions is more pronounced at depth in zone 2. The results from the tracer test also clearly show that the upper boundary of zone 2 is highly conductive and consistent over hundreds of metres. Within zone 2, and between upper and lower margins, interconnected discrete minor shear and fracture zones (sub-zones) constitute flow paths of considerable variable residence times. The dispersion within the sub-zones of zone 2, expressed as Peclet numbers ranged from 16 to 40. Flow porosity was determined to be 0.001-0.05 in the upper sub-zone and 0.01-0.1 in the intermediate and lower ones and flow wetted surface area per volume of rock was calculated to be within 1-92 m 2 /m 3 . 68 refs, 61 figs, 40 tabs

  5. Drivers׳ merging behavior data in highway work zones

    Directory of Open Access Journals (Sweden)

    Mahmoud Shakouri

    2016-03-01

    Full Text Available There have been growing research interests in finding a suitable work zone layout to improve work zone safety and traffic efficiency. This paper contains data supporting the research article entitled: Effects of work zone configurations and traffic density on performance variables and subjective workload (Shakouri et al., 2014 [1]. A full factorial experiment was conducted to compare the efficiency of two work zone configurations by using a driving simulator with two levels of work zone configuration, two levels of traffic density and three levels of sign placement as fixed factors. Seven female and 23 male participants completed the experiment. In this paper we present the data relating to demographic information of participants, driving simulator data and subjective workload evaluation of participants for each work zone. Keywords: Work zone, Merging behavior, Subjective workload, Safety

  6. Export Processing Zones and Global Class Formation

    NARCIS (Netherlands)

    Neveling, Patrick

    2015-01-01

    This chapter is concerned with one of the most striking developments in the global political economy of capitalism after the Second World War; the rise of export processing zones and special economic zones. Building on long-term ethnohistorical research on the zones’ global spread from one zone in

  7. Nuclear free zone

    International Nuclear Information System (INIS)

    Christoffel, T.

    1987-01-01

    Health professionals have played a leading role in alerting and educating the public regarding the danger of nuclear war which has been described as the last epidemic our civilization will know. Having convinced most people that the use of nuclear weapons would mean intolerable consequences, groups such as Physicians for Social Responsibility have focused on the second critical question how likely is it that these weapons will be used? The oultlook is grim. This article describes the nuclear free zone movement, explores relevant legal questions, and shows how the political potential of nuclear free zones threatens to open a deep rift in the American constitutional system

  8. A geophysical cross-section of the Hockai Fault Zone (Eastern Belgium): imaging an intraplate weak crustal zone.

    Science.gov (United States)

    Lecocq, T.; Camelbeeck, T.

    2016-12-01

    The Hockai Fault Zone (HFZ) is a NNW-SSE trending structure visible in the regional geomorphology in the Ardennes, Eastern-Belgium. It is situated, between the Pays de Herve (Graben de la Minerie) to the North and the Amblève river, to the South. It crosses the Stavelot Massif, almost perpendicular to the Crête de la Vecquée (Vecquée crest), i.e. the highest crest of the Venn. Faults have been identified or suspected on a contour map of the base of the Tertiary cover (Eocene or Oligocene) in the north western and central Rhenish Massif. These faults are necessary to account for the altitude difference of the base of the cover. The deflection or capture of local rivers show a remarkable alignments on more than 42 km N-S. The alignments are mostly trending SSE-NNW, between N140 and N170, with some potential segments with slightly different orientations. This general orientation has been also evidenced from the analyses of Landsat-1 imagery products. At its crossing with the Vecquée Crest, Demoulin locates the HFZ where the Hoëgne river turns sharply towards the north and crosscuts the quarzitic crest. Demoulin identifies three subparallel faults or fault zones on the Hautes-Fagnes plateau, from East to West: the Eupen faulting zone, the Baelen faulting zone and Hockai faulted zone. In this communication, we report on a large-scale geophysical survey that was conducted in order to search of the Hockai fault zone expression at the surface. The locations to search for the Hockai Fault Zone are based on the surface projection of the 1989/1990 seismic swarm that occurred under the Stavelot Massif, geomorphological evidences and past geophysical surveys in the region. Our objective is not to prove a Quaternary movement of faults, but rather to find reliable evidences of their presence and to analyse their lateral extension. In total, 31 ERT profiles were executed almost parallel to the Vecquée Crest, i.e. a total of 10679 meters of profiles. Four zones are imaged

  9. Advanced Vadose Zone Simulations Using TOUGH

    Energy Technology Data Exchange (ETDEWEB)

    Finsterle, S.; Doughty, C.; Kowalsky, M.B.; Moridis, G.J.; Pan,L.; Xu, T.; Zhang, Y.; Pruess, K.

    2007-02-01

    The vadose zone can be characterized as a complex subsurfacesystem in which intricate physical and biogeochemical processes occur inresponse to a variety of natural forcings and human activities. Thismakes it difficult to describe, understand, and predict the behavior ofthis specific subsurface system. The TOUGH nonisothermal multiphase flowsimulators are well-suited to perform advanced vadose zone studies. Theconceptual models underlying the TOUGH simulators are capable ofrepresenting features specific to the vadose zone, and of addressing avariety of coupled phenomena. Moreover, the simulators are integratedinto software tools that enable advanced data analysis, optimization, andsystem-level modeling. We discuss fundamental and computationalchallenges in simulating vadose zone processes, review recent advances inmodeling such systems, and demonstrate some capabilities of the TOUGHsuite of codes using illustrative examples.

  10. Metasomatic zoning at some stratiform rare metal deposits

    International Nuclear Information System (INIS)

    Altyntsev, Yu.V.; Bazhenov, M.I.; Bepeshov, G.V.; Komarnitskij, G.M.; Petrov, I.Ya.; Serykh, A.S.

    1985-01-01

    Metasomatic zoning of stratiform deposits of rare metals (Mo, Pb, As, V, Se, U, etc.) in intermontane depresions, deposited at the postorogenic stage of Paleozoic geosyncline region development, is considered. Geochemical and geophysical characteristics of metasomatic zoning in the case of sloping and steep rock deposition are given. It is established, that in rare metal deposits in variegated deposits of molassoid formation of Middle-Upper Paleozoic the external and internal zones of metasomatic alterations are distinctly separated. The external zone is presented by mineral association: quartz + -albile + -calcite + -epidote; the internal one - by hydromica + -chlorite + -analcite, laumontite + -hematite + -ankerite + -kaolinite. Geochemical zoning is manifested quite regularly at all the deposits and it is subjected to metasomatic zoning. Changes in physical properties of rocks reflect the metasomatic zoning. The character of metasomatic alterations of rocks, geochemical zoning of metasomatites at rare metal deposits in molassoid deposits and spatially contiguous deposits in volcanogenic complexes have common features. A supposition is made on polygenic ore formation in sedimentary rocks of the depressions

  11. High spirituality may be associated with right hemispheric lateralization in Korean adults living with epilepsy.

    Science.gov (United States)

    Lee, Sang-Ahm; Ko, Myung-Ah; Choi, Eun-Ju; Jeon, Ji-Ye; Ryu, Han Uk

    2017-11-01

    Although it is known that epilepsy and spirituality are related, spirituality in epilepsy has received relatively little clinical and scientific attention. Therefore, we investigated which epilepsy-related factors are associated with high spirituality in Korean adults living with epilepsy. This cross-sectional study was conducted in two university hospitals in Korea. Spirituality was assessed using the 6-item Spirituality Self-Rating Scale (SSRS). The participants were categorized into high and low spirituality groups according to the median SSRS score. The presumptive seizure onset zone was determined based on the clinical semiology, electroencephalography, and magnetic resonance imaging findings. Of the 180 participants, 61.7% declared that they had a religious affiliation. The median SSRS score was 15 (interquartile range: 7, 22). The high spirituality subgroup consisted of 92 (51.1%) participants. In the univariate analyses, the high spirituality group was significantly associated with female sex (p<0.05), older age (p<0.01), longer epilepsy duration (p<0.05), polytherapy (p<0.05), complex partial seizure (p<0.05), levetiracetam or topiramate usage (p<0.05), and a right-lateralized seizure onset zone. The multiple logistic regression analysis identified right hemispheric lateralization as the only independent factor associated with high spirituality (odds ratio: 2.410, 95% confidence interval: 1.051-5.528, p<0.05). High spirituality may be associated with right hemispheric lateralization but not with the temporal localization of the seizure onset zone in Korean adults with epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Exploring the Cross-sectional Association between Transit-Oriented Development Zoning and Active Travel and Transit Usage in the United States, 2010-2014

    Directory of Open Access Journals (Sweden)

    Emily eThrun

    2016-06-01

    Full Text Available Background: In response to traditional zoning codes that contribute to car-dependent, sprawling, and disconnected neighborhoods, communities are reforming their land use laws to create pedestrian-friendly areas that promote physical activity. One such reform is the adoption of transit-oriented developments or districts (TODs. TODs are higher-density, compact, mixed use areas located around transit stops that are designed to encourage walking.Purpose: To identify the characteristics of communities that have adopted TODs in their land use laws and examine if communities that have included TODs in their zoning codes are more likely to have adults that commute by any form of active transportation (i.e., walking, biking, or public transportation or by using public transportation specifically.Methods: Zoning codes effective as of 2010 were obtained for a purposeful sample of the largest 3,914 municipal jurisdictions located in 473 of the most populous US counties and consolidated cities within 48 states and the District of Columbia. They were evaluated to determine whether they included TOD districts or regulations using a coding tool developed by the study team. Descriptive statistics together with t-tests and Pearson’s chi-squared independence test were used to compare characteristics of jurisdictions with and without TOD zoning. Multivariate linear regressions were used to compute the adjusted association between TOD zoning and taking public or active transportation to work.Results: Jurisdictions with TOD zoning were located more in the South and West than non-TOD jurisdictions and were more populous, higher income, more racially diverse, and younger. Jurisdictions with TOD zoning had significantly higher percentages of occupied housing with no vehicle than those without TOD zoning. TOD zoning was associated with significantly higher rates of public transportation to work (β=2.10, 95% CI=0.88, 3.32 and active transportation to work (β=2.48, 95

  13. Recent findings relating to firefighter safety zones

    Science.gov (United States)

    Bret Butler; Russ Parsons; William Mell

    2015-01-01

    Designation of safety zones is a primary duty of all wildland firefighters. Unfortunately, information regarding what constitutes an adequate safety zone is inadequately defined. Measurements of energy release from wildland fires have been used to develop an empirically based safety zone guideline. The basis for this work is described here.

  14. 78 FR 15883 - Standard Time Zone Boundaries

    Science.gov (United States)

    2013-03-13

    ...] RIN 2105-AE20 Standard Time Zone Boundaries AGENCY: Office of the Secretary (OST), Department of... time zone boundaries regulations to reflect changes that Congress made to the Uniform Time Act. The... regulations on standard time zone boundaries, 49 CFR Part 71, need to be updated in order to ensure their...

  15. 32 CFR 643.33 - Policy-Coastal zone management.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Policy-Coastal zone management. 643.33 Section... PROPERTY REAL ESTATE Policy § 643.33 Policy—Coastal zone management. (a) The Coastal Zone Management Act of... affecting the coastal zone of a state, to conduct or support those activities in a manner which is, to the...

  16. Zoning Districts, The zoning districts dataset includes the towns in Manitowoc County, WI that have adopted the county's zoning ordinance., Published in 2013, 1:2400 (1in=200ft) scale, Manitowoc County Government.

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Zoning Districts dataset current as of 2013. The zoning districts dataset includes the towns in Manitowoc County, WI that have adopted the county's zoning ordinance..

  17. Radiological impact of drinks intakes of naturally occurring radionuclides on adults of central zone of Malaysia

    International Nuclear Information System (INIS)

    Tawalbeh, A.A.; Samat, S.B.; Muhammad Samudi Yasir; Muhamat Omar

    2012-01-01

    Fifty three samples of different types of imported and locally produced drinks consumed in central zone of Malaysia were analyzed using gamma-ray spectrometry system. The measurement was conducted for 12 hours using a Canberra p-type high purity germanium (HPGe) gamma spectrometer with 30 % relative efficiency resolution of 1.8 keV at 1.33 MeV. The detector was connected to a computer with MCA card (Accuspec B) and Genie-2000 Analysis software of Canberra Industries, USA. The geometric means of daily intakes of 238 U, 232 Th and 40 K were 0.05, 0.08 and 27.23 respectively. Also the values give annual committed effective doses of 0.8, 6.5 and 61.53 μSv yr -1 for 238 U, 232 Th and 40 K, respectively for population in central zone of Malaysia. The net radiological impact of these radionuclides is 68.83 μSv yr -1 . This value gives cancer risk factor of 1.72 x 10 -7 . Also the value of net radiological impact gives loss of life expectancy of 0.43 days only. Whereas ICRP cancer risk factor for general public is 2.5 x 10 -3 and total risk involve from the all natural radiation sources based on global average annual radiation dose of 2.4 mSv yr -1 is 6.0 x 10 -3 . The estimated cancer risk shows that probability of increase of cancer risk from daily Malaysian drinks is only a minor fraction of ICRP values. Therefore the drink samples investigated here does not pose any significant health hazard and is considered radiologically safe for human consumption. (author)

  18. High exhaust temperature, zoned, electrically-heated particulate matter filter

    Science.gov (United States)

    Gonze, Eugene V.; Paratore, Jr., Michael J.; Bhatia, Garima

    2015-09-22

    A system includes a particulate matter (PM) filter, an electric heater, and a control circuit. The electric heater includes multiple zones, which each correspond to longitudinal zones along a length of the PM filter. A first zone includes multiple discontinuous sub-zones. The control circuit determines whether regeneration is needed based on an estimated level of loading of the PM filter and an exhaust flow rate. In response to a determination that regeneration is needed, the control circuit: controls an operating parameter of an engine to increase an exhaust temperature to a first temperature during a first period; after the first period, activates the first zone; deactivates the first zone in response to a minimum filter face temperature being reached; subsequent to deactivating the first zone, activates a second zone; and deactivates the second zone in response to the minimum filter face temperature being reached.

  19. 77 FR 38484 - Safety Zones; Annual Fireworks Events in the Captain of the Port Detroit Zone

    Science.gov (United States)

    2012-06-28

    ... zone will be enforced from 10:00 p.m. to 11:00 p.m. on July 5, 2012. (8) Grosse Isle Yacht Club.... (16) Grosse Pointe Yacht Club 4th of July Fireworks, Grosse Pointe Shores, MI. The safety zone listed...

  20. Fabrication techniques of X-ray spiral zone plates

    International Nuclear Information System (INIS)

    Gao Nan; Zhu Xiaoli; Li Hailiang; Xie Changqing

    2010-01-01

    The techniques to make X-ray spiral zone plates using electron beam and X-ray lithography were studied. A master mask was fabricated on polyimide membrane by E-beam lithography and micro-electroplating. Spiral zone plates were efficiently replicated by X-ray lithography and micro-electroplating. By combining the techniques, spiral zone plates at 1 keV were successfully fabricate. With an outermost zone width of the 200 nm, and the gold absorbers thickness of 700 nm, the high quality zone plates can be used for X-ray phase contrast microscopy.(authors)

  1. United States Stateplane Zones - NAD83

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — U.S. State Plane Zones (NAD 1983) represents the State Plane Coordinate System (SPCS) Zones for the 1983 North American Datum within United States.

  2. United States Stateplane Zones - NAD27

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — U.S. State Plane Zones (NAD 1927) represents the State Plane Coordinate System (SPCS) Zones for the 1927 North American Datum within United States.

  3. Zone Denmark - gasell Taanist / Reet Krause

    Index Scriptorium Estoniae

    Krause, Reet, 1967-

    2006-01-01

    Taanis Viborgis asuva firma Zone Company Denmark, kaubamärgi Zone Denmark ja firma disainerite tutvustus. Ettevõte valmistab disainitooteid roostevabast terasest, klaasist, puidust, kummist jm. Disainer Naja Utzon Popov endast, oma loomingust

  4. Understanding fall meaning and context in marketing balance classes to older adults.

    Science.gov (United States)

    Clark, Lauren; Thoreson, Sallie; Goss, Cynthia W; Zimmer, Lorena Marquez; Marosits, Mark; DiGuiseppi, Carolyn

    2013-02-01

    This study explored older, community-dwelling adults' attitudes and values about proposed church-delivered balance classes for fall prevention. Community observation, group interviews with stakeholders, key informant interviews, and focus groups with church members ≥ 60 years of age were analyzed in two ways: first for inductive themes expressing community sentiment about fall prevention for older adults, then for content useful in creating locally tailored social marketing messages. Four themes expressed perceptions of fall-prevention programming: de-emphasizing fall risk and emphasizing strength and independence, moving older adults out of their "comfort zones" to join classes, identifying relationships to support fall-prevention activities, and considering gender-based differences in approaches to fall prevention. A content analysis of the same dataset yielded information about preferred places in the community, promotion through churches, a tolerable price, and the balance class product itself. The qualitative results will inform the social marketing program to increase intervention delivery success.

  5. U Plant Geographic Zone Cleanup Prototype

    International Nuclear Information System (INIS)

    Romine, L.D.; Leary, K.D.; Lackey, M.B.; Robertson, J.R.

    2006-01-01

    The U Plant geographic zone (UPZ) occupies 0.83 square kilometers on the Hanford Site Central Plateau (200 Area). It encompasses the U Plant canyon (221-U Facility), ancillary facilities that supported the canyon, soil waste sites, and underground pipelines. The UPZ cleanup initiative coordinates the cleanup of the major facilities, ancillary facilities, waste sites, and contaminated pipelines (collectively identified as 'cleanup items') within the geographic zone. The UPZ was selected as a geographic cleanup zone prototype for resolving regulatory, technical, and stakeholder issues and demonstrating cleanup methods for several reasons: most of the area is inactive, sufficient characterization information is available to support decisions, cleanup of the high-risk waste sites will help protect the groundwater, and the zone contains a representative cross-section of the types of cleanup actions that will be required in other geographic zones. The UPZ cleanup demonstrates the first of 22 integrated zone cleanup actions on the Hanford Site Central Plateau to address threats to groundwater, the environment, and human health. The UPZ contains more than 100 individual cleanup items. Cleanup actions in the zone will be undertaken using multiple regulatory processes and decision documents. Cleanup actions will include building demolition, waste site and pipeline excavation, and the construction of multiple, large engineered barriers. In some cases, different cleanup actions may be taken at item locations that are immediately adjacent to each other. The cleanup planning and field activities for each cleanup item must be undertaken in a coordinated and cohesive manner to ensure effective execution of the UPZ cleanup initiative. The UPZ zone cleanup implementation plan (ZCIP) [1] was developed to address the need for a fundamental integration tool for UPZ cleanup. As UPZ cleanup planning and implementation moves forward, the ZCIP is intended to be a living document that will

  6. Problems of Chernobyl exclusion zone

    International Nuclear Information System (INIS)

    1996-01-01

    The collection comprises the results of researches and design activity in the ChNPP exclusion zone with the aim to develop technology, equipment and instruments for RAW management and accident clean-up, studying of the composition and structure of the activity solid bearers in the soil of the exclusion zone and transformation of the radionuclides in the nearest zone of ChNPP. Much attention is paid to medical and biological problems of the accident influence on the flora, fauna and people's health, labour conditions and incidence of the people involved. The collection comprises the information for scientists, experts, postgraduates and students in gaged in ecology, radioecology, nuclear engineering, radiology, radiochemistry and radiobiology

  7. Standardized precipitation index zones for Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Giddings, L.; Soto, M. [Instituto de Ecologia, A.C., Xalapa, Veracruz (Mexico); Rutherford, B.M.; Maarouf, A. [Faculty of Environmental Studies, York University, Toronto, Ontario (Canada)

    2005-01-01

    Precipitation zone systems exists for Mexico based on seasonality, quantity of precipitation, climates and geographical divisions, but none are convenient for the study of the relation of precipitation with phenomena such as El nino. An empirical set of seven exclusively Mexican and six shared zones was derived from three series of Standardized Precipitation Index (SPI) images, from 1940 through 1989: a whole year series (SPI-12) of 582 monthly images, a six month series (SPI-6) of 50 images for winter months (November through April), and a six month series (SPI-6) of 50 images for summer months (May through October). By examination of principal component and unsupervised classification images, it was found that all three series had similar zones. A set of basic training fields chosen from the principal component images was used to classify all three series. The resulting thirteen zones, presented in this article, were found to be approximately similar, varying principally at zones edges. A set of simple zones defined by just a few vertices can be used for practical operations. In general the SPI zones are homogeneous, with almost no mixture of zones and few outliers of one zone in the area of others. They are compared with a previously published map of climatic regions. Potential applications for SPI zones are discussed. [Spanish] Existen varios sistemas de zonificacion de Mexico basados en la estacionalidad, cantidad de precipitacion, climas y divisiones geograficas, pero ninguno es conveniente para el estudio de la relacion de la precipitacion con fenomenos tales como El Nino. En este trabajo se presenta un conjunto de siete zonas empiricas exclusivamente mexicanas y seis compartidas, derivadas de tres series de imagenes de SPI (Indice Estandarizado de la Precipitacion), desde 1940 a 1989: una serie de 582 imagenes mensuales (SPI-12), una series de 50 imagenes (SPI-6) de meses de invierno (noviembre a abril), y otra de 50 imagenes (SPI-6) de meses de verano

  8. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available -of-evidence (WofE) method logistic regression canonical favorability analysis neural networks evidential belief functions Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study... for the following equation: n∑ i=r ( n i ) pi(1− p)n−i = 0.95 . (1) Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study Methodology Results METHODS (cont. . . ): FITNESS FUNCTION...

  9. System zones in capillary zone electrophoresis: Moving boundaries caused by freely migrating hydrogen ions

    Czech Academy of Sciences Publication Activity Database

    Beckers, J. L.; Boček, Petr

    2005-01-01

    Roč. 26, č. 2 (2005), s. 446-452 ISSN 0173-0835 R&D Projects: GA ČR(CZ) GA203/02/0023; GA AV ČR(CZ) IAA4031401; GA AV ČR(CZ) IAA4031103 Institutional research plan: CEZ:AV0Z40310501 Keywords : capillary zone electrophoresis * system zone s Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.850, year: 2005

  10. Spectral zone selection methodology for pebble bed reactors

    International Nuclear Information System (INIS)

    Mphahlele, Ramatsemela; Ougouag, Abderrafi M.; Ivanov, Kostadin N.; Gougar, Hans D.

    2011-01-01

    A methodology is developed for determining boundaries of spectral zones for pebble bed reactors. A spectral zone is defined as a region made up of a number of nodes whose characteristics are collectively similar and that are assigned the same few-group diffusion constants. The spectral zones are selected in such a manner that the difference (error) between the reference transport solution and the diffusion code solution takes a minimum value. This is achieved by choosing spectral zones through optimally minimizing this error. The objective function for the optimization algorithm is the total reaction rate error, which is defined as the sum of the leakage, absorption and fission reaction rates errors in each zone. The selection of these spectral zones is such that the core calculation results based on diffusion theory are within an acceptable tolerance as compared to a proper transport reference solution. Through this work, a consistent approach for identifying spectral zones that yield more accurate diffusion results is introduced.

  11. 33 CFR 165.103 - Safety and Security Zones; LPG Vessel Transits in Portland, Maine, Captain of the Port Zone...

    Science.gov (United States)

    2010-07-01

    ... within a 500-yard radius of any Liquefied Petroleum Gas (LPG) vessel while it is moored at the LPG... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety and Security Zones; LPG... and Security Zones; LPG Vessel Transits in Portland, Maine, Captain of the Port Zone, Portsmouth...

  12. Saturated Zone Colloid-Facilitated Transport

    International Nuclear Information System (INIS)

    Wolfsberg, A.; Reimus, P.

    2001-01-01

    The purpose of the Saturated Zone Colloid-Facilitated Transport Analysis and Modeling Report (AMR), as outlined in its Work Direction and Planning Document (CRWMS MandO 1999a), is to provide retardation factors for colloids with irreversibly-attached radionuclides, such as plutonium, in the saturated zone (SZ) between their point of entrance from the unsaturated zone (UZ) and downgradient compliance points. Although it is not exclusive to any particular radionuclide release scenario, this AMR especially addresses those scenarios pertaining to evidence from waste degradation experiments, which indicate that plutonium and perhaps other radionuclides may be irreversibly attached to colloids. This report establishes the requirements and elements of the design of a methodology for calculating colloid transport in the saturated zone at Yucca Mountain. In previous Total Systems Performance Assessment (TSPA) analyses, radionuclide-bearing colloids were assumed to be unretarded in their migration. Field experiments in fractured tuff at Yucca Mountain and in porous media at other sites indicate that colloids may, in fact, experience retardation relative to the mean pore-water velocity, suggesting that contaminants associated with colloids should also experience some retardation. Therefore, this analysis incorporates field data where available and a theoretical framework when site-specific data are not available for estimating plausible ranges of retardation factors in both saturated fractured tuff and saturated alluvium. The distribution of retardation factors for tuff and alluvium are developed in a form consistent with the Performance Assessment (PA) analysis framework for simulating radionuclide transport in the saturated zone. To improve on the work performed so far for the saturated-zone flow and transport modeling, concerted effort has been made in quantifying colloid retardation factors in both fractured tuff and alluvium. The fractured tuff analysis used recent data

  13. Geometry of the Aegean Benioff zones

    Directory of Open Access Journals (Sweden)

    M. Knapmeyer

    1999-06-01

    Full Text Available The morphology of the Aegean Benioff zone was reconstructed using 1366 hypocentres from the PDE catalogue 1973-1997. Two such zones are identified under the Aegean area, a large one (Main Aegean Subduction, MAS spanning the whole Hellenic arc and a smaller and younger one under the Western Peloponnesus. The geometry of the MAS suggests that it blocks its own subduction and, therefore, causes the development of the smaller western zone as a result of a step back process in the Pliocene.

  14. The habitable zone and extreme planetary orbits.

    Science.gov (United States)

    Kane, Stephen R; Gelino, Dawn M

    2012-10-01

    The habitable zone for a given star describes the range of circumstellar distances from the star within which a planet could have liquid water on its surface, which depends upon the stellar properties. Here we describe the development of the habitable zone concept, its application to our own solar system, and its subsequent application to exoplanetary systems. We further apply this to planets in extreme eccentric orbits and show how they may still retain life-bearing properties depending upon the percentage of the total orbit which is spent within the habitable zone. Key Words: Extrasolar planets-Habitable zone-Astrobiology.

  15. Transcriptional and Genomic Targets of Neural Stem Cells for Functional Recovery after Hemorrhagic Stroke

    Directory of Open Access Journals (Sweden)

    Le Zhang

    2017-01-01

    Full Text Available Hemorrhagic stroke is a life-threatening disease characterized by a sudden rupture of cerebral blood vessels, and it is widely believed that neural cell death occurs after exposure to blood metabolites or subsequently damaged cells. Neural stem cells (NSCs, which maintain neurogenesis and are found in subgranular zone and subventricular zone, are thought to be an endogenous neuroprotective mechanism for these brain injuries. However, due to the complexity of NSCs and their microenvironment, current strategies cannot satisfactorily enhance functional recovery after hemorrhagic stroke. It is well known that transcriptional and genomic pathways play important roles in ensuring the normal functions of NSCs, including proliferation, migration, differentiation, and neural reconnection. Recently, emerging evidence from the use of new technologies such as next-generation sequencing and transcriptome profiling has provided insight into our understanding of genomic function and regulation of NSCs. In the present article, we summarize and present the current data on the control of NSCs at both the transcriptional and genomic levels. Using bioinformatics methods, we sought to predict novel therapeutic targets of endogenous neurogenesis and exogenous NSC transplantation for functional recovery after hemorrhagic stroke, which could also advance our understanding of its pathophysiology.

  16. AUDIT (Alcohol Use Disorders Identification Test) to Estimate the Pattern and Correlates of Alcohol Consumption among the Adult Population of West Bengal, India: A Community Based Cross-sectional Study.

    Science.gov (United States)

    Sau, Arkaprabha

    2017-04-01

    Pattern of alcohol consumption substantially changed in India with in last 20 to 25 years. Excessive alcohol consumption is a major risk factor for various morbidity and mortality. So, scientific study to identify alcohol consumption patterns and its correlates will be helpful to formulate preventive strategies. To estimate the pattern of alcohol consumption and to determine its correlates, among the adult population of the state of West Bengal in India. A community based cross-sectional study was conducted among the adult population of the state of West Bengal at Gram Panchayat (GP) level. Ninety-nine (n=99) adult (≥ 18 years) men and women of Guchati GP at Paschim Medinipur district, was selected using Lot Quality Assurance Sampling (LQAS) technique. The study participants were interviewed using a pre-designed and pre-tested schedule. It was estimated that the prevalence of low risk drinking or abstinence (Zone I) was 65.5% (95% CI 55.5% to 75.5%) and the prevalence of alcohol use in excess of low-risk (Zone II) was 17.6% (95% CI 7.6% to 27.6%), and the prevalence of harmful and hazardous drinking (Zone III) was 8.5% (95% CI 0% to 18.5%) and the prevalence alcohol dependence (Zone-IV) was 8.4% (0% to 18.4%). Logistic regression model shows that "gender" (p = 0.00) and "employment status" (p = 0.01) added significantly to the model with adjusted odds ratio of 82.27 (95% CI 18.17-372.58) and 0.13 (0.03-0.66). There is a need for comprehensive screening and treatment programme to deal with the problems of Alcohol Use Disorders among adults to achieve good health and well being for sustainable development.

  17. 76 FR 38077 - Special Local Regulations and Safety Zones; Recurring Events in Captain of the Port New York Zone

    Science.gov (United States)

    2011-06-29

    ...: All Zone. waters of Long Island Sound in an area bound by the following points: 40[deg]51'43.5'' N 073... Zone. located in approximate position 40[deg]51'52'' N 073[deg]56'24'' W (NAD 1983), approximately 1750...] RIN 1625-AA00; 1625-AA08 Special Local Regulations and Safety Zones; Recurring Events in Captain of...

  18. 49 CFR 222.41 - How does this rule affect Pre-Rule Quiet Zones and Pre-Rule Partial Quiet Zones?

    Science.gov (United States)

    2010-10-01

    ...-Rule Quiet Zone may be established by automatic approval and remain in effect, subject to § 222.51, if... Zone may be established by automatic approval and remain in effect, subject to § 222.51, if the Pre... 49 Transportation 4 2010-10-01 2010-10-01 false How does this rule affect Pre-Rule Quiet Zones and...

  19. Risk-based zoning for urbanizing floodplains.

    Science.gov (United States)

    Porse, Erik

    2014-01-01

    Urban floodplain development brings economic benefits and enhanced flood risks. Rapidly growing cities must often balance the economic benefits and increased risks of floodplain settlement. Planning can provide multiple flood mitigation and environmental benefits by combining traditional structural measures such as levees, increasingly popular landscape and design features (green infrastructure), and non-structural measures such as zoning. Flexibility in both structural and non-structural options, including zoning procedures, can reduce flood risks. This paper presents a linear programming formulation to assess cost-effective urban floodplain development decisions that consider benefits and costs of development along with expected flood damages. It uses a probabilistic approach to identify combinations of land-use allocations (residential and commercial development, flood channels, distributed runoff management) and zoning regulations (development zones in channel) to maximize benefits. The model is applied to a floodplain planning analysis for an urbanizing region in the Baja Sur peninsula of Mexico. The analysis demonstrates how (1) economic benefits drive floodplain development, (2) flexible zoning can improve economic returns, and (3) cities can use landscapes, enhanced by technology and design, to manage floods. The framework can incorporate additional green infrastructure benefits, and bridges typical disciplinary gaps for planning and engineering.

  20. Methylation patterns in marginal zone lymphoma.

    Science.gov (United States)

    Arribas, Alberto J; Bertoni, Francesco

    Promoter DNA methylation is a major regulator of gene expression and transcription. The identification of methylation changes is important for understanding disease pathogenesis, for identifying prognostic markers and can drive novel therapeutic approaches. In this review we summarize the current knowledge regarding DNA methylation in MALT lymphoma, splenic marginal zone lymphoma, nodal marginal zone lymphoma. Despite important differences in the study design for different publications and the existence of a sole large and genome-wide methylation study for splenic marginal zone lymphoma, it is clear that DNA methylation plays an important role in marginal zone lymphomas, in which it contributes to the inactivation of tumor suppressors but also to the expression of genes sustaining tumor cell survival and proliferation. Existing preclinical data provide the rationale to target the methylation machinery in these disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Width of surface rupture zone for thrust earthquakes: implications for earthquake fault zoning

    Science.gov (United States)

    Boncio, Paolo; Liberi, Francesca; Caldarella, Martina; Nurminen, Fiia-Charlotta

    2018-01-01

    The criteria for zoning the surface fault rupture hazard (SFRH) along thrust faults are defined by analysing the characteristics of the areas of coseismic surface faulting in thrust earthquakes. Normal and strike-slip faults have been deeply studied by other authors concerning the SFRH, while thrust faults have not been studied with comparable attention. Surface faulting data were compiled for 11 well-studied historic thrust earthquakes occurred globally (5.4 ≤ M ≤ 7.9). Several different types of coseismic fault scarps characterize the analysed earthquakes, depending on the topography, fault geometry and near-surface materials (simple and hanging wall collapse scarps, pressure ridges, fold scarps and thrust or pressure ridges with bending-moment or flexural-slip fault ruptures due to large-scale folding). For all the earthquakes, the distance of distributed ruptures from the principal fault rupture (r) and the width of the rupture zone (WRZ) were compiled directly from the literature or measured systematically in GIS-georeferenced published maps. Overall, surface ruptures can occur up to large distances from the main fault ( ˜ 2150 m on the footwall and ˜ 3100 m on the hanging wall). Most of the ruptures occur on the hanging wall, preferentially in the vicinity of the principal fault trace ( > ˜ 50 % at distances guidelines). In the absence of such a very detailed study (basic SM, i.e. Level 1 SM of Italian guidelines) a width of ˜ 840 m (90 % probability from "simple thrust" database of distributed ruptures, excluding B-M, F-S and Sy fault ruptures) is suggested to be sufficiently precautionary. For more detailed SM, where the fault is carefully mapped, one must consider that the highest SFRH is concentrated in a narrow zone, ˜ 60 m in width, that should be considered as a fault avoidance zone (more than one-third of the distributed ruptures are expected to occur within this zone). The fault rupture hazard zones should be asymmetric compared to the trace

  2. Zone memories and pseudorandom addressing

    International Nuclear Information System (INIS)

    Marino, D.; Mirizzi, N.; Stella, R.; Visaggio, G.

    1975-01-01

    A quantitative comparison between zone memories, pseudorandom addressed memories and an alternative special purpose memory (spread zone memory) in which the distance between any two transformed descriptors, at first adjacent, is independent of the descriptors pair and results the maximum one is presented. This memory has not been particularly considered at present in spite of its efficiency and its simple implementation

  3. Improving the effectiveness of smart work zone technologies.

    Science.gov (United States)

    2016-11-01

    This project evaluates the effectiveness of sensor network systems for work zone traffic estimation. The comparative analysis is : performed on a work zone modeled in microsimulation and calibrated with field data from two Illinois work zones. Realis...

  4. Shear zones between rock units with no relative movement

    DEFF Research Database (Denmark)

    Koyi, Hemin; Schmeling, Harro; Burchardt, Steffi

    2013-01-01

    Shear zones are normally viewed as relatively narrow deformation zones that accommodate relative displacement between two "blocks" that have moved past each other in opposite directions. This study reports localized zones of shear between adjacent blocks that have not moved past each other. Such ...... given credit for and may be responsible for some reverse kinematics reported in shear zones....... or wakes, elongated bodies (vertical plates or horizontal rod-like bodies) produce tabular shear zones or wakes. Unlike conventional shear zones across which shear indicators usually display consistent symmetries, shear indicators on either side of the shear zone or wake reported here show reverse...... kinematics. Thus profiles exhibit shear zones with opposed senses of movement across their center-lines or -planes.We have used field observations and results from analytical and numerical models to suggest that examples of wakes are the transit paths that develop where denser blocks sink within salt...

  5. The Development Evaluation of Economic Zones in China

    Science.gov (United States)

    Shi, Hong-Bo; Zhang, Zhe; Zhai, Yuming; Chen, Quan; Wang, Jiangtao

    2018-01-01

    After the Chinese reform and opening up, the construction of economic zones, such as Special Economic Zones, Hi-tech Zones and Bonded Zones, has played an irreplaceable role in China’s economic development. Currently, against the background of Chinese economic transition, research on development evaluation of economic zones has become popular and necessary. Similar research usually focuses on one specific field, and the methods that are used to evaluate it are simple. This research aims to analyse the development evaluation of zones by synthesis. A new hybrid multiple criteria decision making (MCDM) model that combines the DEMATEL technique and the DANP method is proposed. After establishing the evaluation criterion system and acquiring data, the influential weights of dimensions and criteria can be calculated, which will be a guide for forming measures of development. Shandong Peninsula Blue Economic Zone is used in the empirical case analysis. The results show that Transportation Conditions, Industrial Structure and Business Climate are the main influencing criteria and measures based on these criteria are proposed. PMID:29301304

  6. Work Zone Intrusion Report Interface Design

    Science.gov (United States)

    2018-02-02

    While necessary for roadways, work zones present a safety risk to crew. Half of road workers deaths between 2005 and 2010 were due to collisions with motorists intruding on the work zone. Therefore, addressing intrusions is an important step for ensu...

  7. Work zone performance measures pilot test.

    Science.gov (United States)

    2011-04-01

    Currently, a well-defined and validated set of metrics to use in monitoring work zone performance do not : exist. This pilot test was conducted to assist state DOTs in identifying what work zone performance : measures can and should be targeted, what...

  8. Health-Promoting Interventions for Persons Aged 80 and Older Are Successful in the Short TermuResults from the Randomized and Three-Armed Elderly Persons in the Risk Zone Study

    DEFF Research Database (Denmark)

    Gustafsson, S.; Wilhelmson, K.; Eklund, K.

    2012-01-01

    OBJECTIVES: To examine the outcomes of the Elderly Persons in the Risk Zone study, which was designed to evaluate whether it is possible to delay deterioration if a health-promoting intervention is made when an older adult (>= 80) is at risk of becoming frail and whether a multiprofessional group...

  9. FIGHT ZONE WITH POINTS OF THE SHOTOKAN KARATE FEMALE COMPETITION

    Directory of Open Access Journals (Sweden)

    Nelson Kautzner Marques Junior

    2014-04-01

    Full Text Available The objective of the study was to determine the fight zone with point during the female kumite of competition. This study used a quantitative research for identify the fight zone with point (ippon or waza-ari or not during the female kumite of competition. Were selected on the Internet several championship of kumite of the JKA and of the ITKF. The study detected a high probability of point in the zone 7 and in the zone 2. The study determined that the most points at the corner occurred when the karateka practiced the attack in fight zone. Kruskal-Wallis ANOVA verified significant difference between the fight zone with points, H (10 = 29,49, p = 0,001. The Mann Whitney U test detected significant difference between the zone 5 with waza-ari versus all the zone. The greatest number of points in the fight zone was in agreement with the size of the fight zone. The central zone or zone 5 has 6x6 m, during the female kumite occurred more points, total of 68 waza-aris and 5 ippons. The study on the fight zone with points of the female kumite permits that the karateka has knowledge about the combat zones and guides the karateka before, during and after the female kumite. However, more studies should be done to confirm these findings.

  10. 75 FR 16370 - Regulated Navigation Areas, Safety Zones, Security Zones; Deepwater Ports in Boston Captain of...

    Science.gov (United States)

    2010-04-01

    ... rule under Executive Order 13045, Protection of Children from Environmental Health Risks and Safety Risks. This rule is not an economically significant rule and would not create an environmental risk to...] RIN 1625-AA00, RIN 1625-AA11 Regulated Navigation Areas, Safety Zones, Security Zones; Deepwater Ports...

  11. Width of surface rupture zone for thrust earthquakes: implications for earthquake fault zoning

    Directory of Open Access Journals (Sweden)

    P. Boncio

    2018-01-01

    Full Text Available The criteria for zoning the surface fault rupture hazard (SFRH along thrust faults are defined by analysing the characteristics of the areas of coseismic surface faulting in thrust earthquakes. Normal and strike–slip faults have been deeply studied by other authors concerning the SFRH, while thrust faults have not been studied with comparable attention. Surface faulting data were compiled for 11 well-studied historic thrust earthquakes occurred globally (5.4 ≤ M ≤ 7.9. Several different types of coseismic fault scarps characterize the analysed earthquakes, depending on the topography, fault geometry and near-surface materials (simple and hanging wall collapse scarps, pressure ridges, fold scarps and thrust or pressure ridges with bending-moment or flexural-slip fault ruptures due to large-scale folding. For all the earthquakes, the distance of distributed ruptures from the principal fault rupture (r and the width of the rupture zone (WRZ were compiled directly from the literature or measured systematically in GIS-georeferenced published maps. Overall, surface ruptures can occur up to large distances from the main fault ( ∼ 2150 m on the footwall and  ∼  3100 m on the hanging wall. Most of the ruptures occur on the hanging wall, preferentially in the vicinity of the principal fault trace ( >   ∼  50 % at distances  <   ∼  250 m. The widest WRZ are recorded where sympathetic slip (Sy on distant faults occurs, and/or where bending-moment (B-M or flexural-slip (F-S fault ruptures, associated with large-scale folds (hundreds of metres to kilometres in wavelength, are present. A positive relation between the earthquake magnitude and the total WRZ is evident, while a clear correlation between the vertical displacement on the principal fault and the total WRZ is not found. The distribution of surface ruptures is fitted with probability density functions, in order to define a criterion to

  12. Expression pattern of thymosin beta 4 in the adult human liver

    Directory of Open Access Journals (Sweden)

    S. Nemolato

    2011-09-01

    Full Text Available Thymosin beta-4 (Tβ4 is a member of beta-thymosins, a family of small peptides involved in polymerization of G-actin, and in many critical biological processes including apoptosis, cell migration, angiogenesis, and fibrosis. Previous studies in the newborn liver did not reveal any significant reactivity for Tβ4 during the intrauterine life. The aim of the present study was to investigate by immunohistochemistry Tβ4 expression in the adult normal liver. Thirty-five human liver samples, including 11 needle liver biopsies and 24 liver specimens obtained at autopsy, in which no pathological change was detected at the histological examination, were immunostained utilizing an anti-Tβ4 commercial antibody. Tβ4 was detected in the hepatocytes of all adult normal livers examined. A zonation of Tβ4 expression was evident in the vast majority of cases. Immunostaining was preferentially detected in zone 3, while a minor degree of reactivity was detected in periportal hepatocytes (zone 1. At higher power, Tβ4-reactive granules appeared mainly localized at the biliary pole of hepatocytes. In cases with a strong immunostaining, even perinuclear areas and the sinusoidal pole of hepatocytes appeared interested by immunoreactivity for Tβ4. The current work first evidences a strong diffuse expression of Tβ4 in the adult human liver, and adds hepatocytes to the list of human cells able to synthesize large amounts of Tβ4 in adulthood. Moreover, Tβ4 should be added to the liver proteins characterized by a zonate expression pattern, in a descending gradient from the terminal vein to the periportal areas of the liver acinus. Identifying the intimate role played by this peptide intracellularly and extracellularly, in physiology and in different liver diseases, is a major challenge for future research focusing on Tβ4.

  13. Presynaptic Active Zone Density during Development and Synaptic Plasticity.

    Science.gov (United States)

    Clarke, Gwenaëlle L; Chen, Jie; Nishimune, Hiroshi

    2012-01-01

    Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density) during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs), the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS), active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and β-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated.

  14. Zones of emotional labour

    DEFF Research Database (Denmark)

    Strøbæk, Pernille Solveig

    2011-01-01

    The paper suggests that due to the difficult nature of their work public family law caseworkers are to be included in the definition of emotional labour even though they are omitted by Hochschild. Based upon a review of the structures involved in emotional labour an explorative qualitative study...... is put forth among 25 Danish public family law caseworkers. The study points to personal, professional, and social zones of emotional labour through which the caseworkers carry out their work. Emotional labour zones mark emotion structures that may be challenging due to complex emotional intersections...

  15. Dike zones on Venus

    Science.gov (United States)

    Markov, M. S.; Sukhanov, A. L.

    1987-01-01

    Venusian dike zone structures were identified from Venera 15 and 16 radar images. These include: a zone of subparallel rows centered at 30 deg N, 7 deg E; a system of intersecting bands centered at 67 deg N, 284 deg E; polygonal systems in lavas covering the structural base uplift centered at 47 deg N, 200 deg E; a system of light bands in the region of the ring structure centered at 43 deg N, 13 deg E; and a dike band centered at 27 deg N, 36 deg E.

  16. ZONE: a finite element mesh generator

    International Nuclear Information System (INIS)

    Burger, M.J.

    1976-05-01

    The ZONE computer program is a finite-element mesh generator which produces the nodes and element description of any two-dimensional geometry. The geometry is subdivided into a mesh of quadrilateral and triangular zones arranged sequentially in an ordered march through the geometry. The order of march can be chosen so that the minimum bandwidth is obtained. The node points are defined in terms of the x and y coordinates in a global rectangular coordinate system. The zones generated are quadrilaterals or triangles defined by four node points in a counterclockwise sequence. Node points defining the outside boundary are generated to describe pressure boundary conditions. The mesh that is generated can be used as input to any two-dimensional as well as any axisymmetrical structure program. The output from ZONE is essentially the input file to NAOS, HONDO, and other axisymmetric finite element programs. 14 figures

  17. 78 FR 11798 - Safety Zones; Annual Fireworks Events in the Captain of the Port Buffalo Zone

    Science.gov (United States)

    2013-02-20

    ... later notice in the Federal Register. B. Regulatory History and Information On June 18, 2008, the Coast... coordinates for the safety zones corresponding with the Browns Football Half time Fireworks and the Lorain... Football Half time and the Lorain Port Fest safety zones, to include changing the format of the coordinates...

  18. 77 FR 35852 - Safety Zones; Multiple Firework Displays in Captain of the Port, Puget Sound Zone

    Science.gov (United States)

    2012-06-15

    ... 13045, Protection of Children from Environmental Health Risks and Safety Risks. This rule is not an economically significant rule and does not create an environmental risk to health or risk to safety that may... 1625-AA00 Safety Zones; Multiple Firework Displays in Captain of the Port, Puget Sound Zone AGENCY...

  19. Effects of radioactive fallout on soil animal populations in the 30 km zone of the Chernobyl atomic power station

    International Nuclear Information System (INIS)

    Krivolutzkij, D.A.; Pokarzhevskij, A.D.

    1992-01-01

    Studies were carried out during July and September 1986, April 1987 and October 1988. Radioactive fallout after the Chernobyl atomic power station (APS) accident induced catastrophic effects on populations of small pine-litter faunae within the 30km zone around the station. Effects on soil faunae were not so marked due to shielding by the soil, or on litter faunae at the edge of the 30km zone due to distance from the source. Thirty-gray doses did not directly affect adult animals in the soil and litter, but impacted their eggs and juveniles. Resident populations recovered slowly during the first year after the accident. Insect migration into the contaminated area was the primary source of soil animal population recovery. After 2-2.5 year, marked differences between populations in the contaminated and control areas were no longer found. (author). 5 refs.; 6 tabs

  20. New insight into the levels, distribution and health risk diagnosis of indoor and outdoor dust-bound FRs in colder, rural and industrial zones of Pakistan.

    Science.gov (United States)

    Khan, Muhammad Usman; Li, Jun; Zhang, Gan; Malik, Riffat Naseem

    2016-09-01

    This is the first robust study designed to probe selected flame retardants (FRs) in the indoor and outdoor dust of industrial, rural and background zones of Pakistan with special emphasis upon their occurrence, distribution and associated health risk. For this purpose, we analyzed FRs such as polybrominated diphenylethers (PBDEs), dechlorane plus (DP), novel brominated flame retardants (NBFRs) and organophosphate flame retardants (OPFRs) in the total of 82 dust samples (indoor and outdoor) collected three from each zone: industrial, rural and background. We found higher concentrations of FRs (PBDEs, DP, NBFRs and OPFRs) in industrial zones as compared to the rural and background zones. Our results reveal that the concentrations of studied FRs are relatively higher in the indoor dust samples being compared with the outdoor dust and they are ranked as: ∑OPFRs > ∑NBFRs > ∑PBDEs > ∑DP. A significant correlation in the FRs levels between the indoor and outdoor dust suggest the potential intermixing of these compounds between them. The principal component analysis/multiple linear regression predicts the percent contribution of FRs from different consumer products in the indoor and outdoor dust of industrial, rural and background zones to trace their source origin. The FRs detected in the background zones reveal the dust-bound FRs suspended in the air might be shifted from different warmer zones or consumers products available/used in the same zones. Hazard quotient (HQ) for FRs via indoor and outdoor dust intake at mean and high dust scenarios to the exposed populations (adults and toddlers) are found free of risk (HQ < 1) in the target zones. Furthermore, our nascent results will provide a baseline record of FRs (PBDEs, DP, NBFRs and OPFRs) concentrations in the indoor and outdoor dust of Pakistan. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. 77 FR 8219 - Coastal Zone Management Program: Illinois

    Science.gov (United States)

    2012-02-14

    ... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Coastal Zone Management... ICMP constitutes an approvable program and that requirements of the Coastal Zone Management Act (CZMA..., submitted a coastal management program to NOAA for approval under the Coastal Zone Management Act (CZMA), 16...

  2. 33 CFR 165.755 - Safety Zone; Guayanilla, Puerto Rico

    Science.gov (United States)

    2010-07-01

    ... Zone; Guayanilla, Puerto Rico (a) The following area is established as a safety zone during the... the Eco-Electrica waterfront facility in Guayanilla Bay, Puerto Rico. The safety zone remains in... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety Zone; Guayanilla, Puerto...

  3. Deficiencies in Vadose Zone Understanding at the INEEL

    Energy Technology Data Exchange (ETDEWEB)

    Wood, Thomas Ronald; Bates, Dona Louise; Bishop, Carolyn Wagoner; Heard, Robert Eugene; Hubbell, Joel Michael; Hull, Laurence Charles; Lehman, Richard Michael; Magnuson, Swen O; Mattson, Earl Douglas; Mccarthy, James Michael; Porro, Indrek; Ritter, Paul David; Roddy, Michael Scott; Singler, Robert Edward; Smith, Richard Paul

    2000-08-01

    Subsurface contamination in the vadose zone, that portion of the subsurface pathway between land surface and an underlying aquifer, poses environmental problems at the Idaho National Engineering and Environmental Laboratory (INEEL) in eastern Idaho and across the U.S. Department of Energy complex. Assessing potential adverse impacts from these contaminated sites requires an understanding of the mechanisms controlling contaminant transport. Currently, vadose zone experts at the INEEL cannot with confidence predict the movement of water and contaminants in the complex, heterogeneous, fractured subsurface at the INEEL, especially within the vadose zone. In the draft version (Revision 1) of the Vadose Zone Deficiencies document, deficiencies in scientific understanding of flow and transport processes in the vadose zone at the INEEL were identified and grouped into 13 categories and recommendations were provided to address each of the deficiencies. The draft document provided the basis for an INEEL Vadose Zone Workshop that was conducted October 20 and 21, 1999, in Idaho Falls, Idaho. The workshop was conducted to group and rank the previously identified deficiencies and for the subsequent development of science plans to address the deficiencies that limit reliable predictions of water and contaminant movement in the subsurface. The workshop participants, comprising INEEL and scientists and project managers and non-INEEL scientists knowledgeable about the vadose zone, developed science- and technology-based recommendations derived through a series of technical sessions at the workshop. In this document, the final version of the Vadose Zone Deficiencies document, the draft document has been incorporated, largely intact, as well as the results from the workshop. The workshop participants grouped the deficiencies in vadose zone understanding at the INEEL into seven categories. These seven categories will be the focus areas of five science plans that are being developed to

  4. Fifty years of shear zones

    Science.gov (United States)

    Graham, Rodney

    2017-04-01

    We are here, of course, because 1967 saw the publication of John Ramsay's famous book. Two years later a memorable field trip from Imperial College to the Outer Hebrides saw John on a bleak headland on the coast of North Uist where a relatively undeformed metadolerite within Lewisian (Precambrian) gneisses contained ductile shear zones with metamorphic fabrics in amphibolite facies. One particular outcrop was very special - a shear zone cutting otherwise completely isotropic, undeformed metadolerite, with an incremental foliation starting to develop at 45° to the deformation zone, and increasing in intensity as it approached the shear direction. Here was proof of the process of simple shear under ductile metamorphic conditions - the principles of simple shear outlined in John Ramsay's 1967 book clearly visible in nature, and verified by Ramsay's mathematical proofs in the eventual paper (Ramsay and Graham, 1970). Later work on the Lewisian on the mainland of Scotland, in South Harris, in Africa, and elsewhere applied Ramsay's simple shear principles more liberally, more imprecisely and on larger scale than at Caisteal Odair, but in retrospect it documented what seems now to be the generality of mid and lower crustal deformation. Deep seismic reflection data show us that on passive margins hyper-stretched continental crust (whether or not cloaked by Seaward Dipping Reflectors) seems to have collapsed onto the mantle. Crustal faults mostly sole out at or above the mantle - so the Moho is a detachment- an 'outer marginal detachment', if you like, and, of course, it must be a ductile shear. On non-volcanic margins this shear zone forms the first formed ocean floor before true sea floor spreading gets going to create real oceanic crust. Gianreto Manatschal, Marcel Lemoine and others realised that the serpentinites described in parts of the Alps are exposed remnants of this ductile shear zone. Associated ophicalcite breccias tell of sea floor exposure, while high

  5. The Devils Mountain Fault zone: An active Cascadia upper plate zone of deformation, Pacific Northwest of North America

    Science.gov (United States)

    Barrie, J. Vaughn; Greene, H. Gary

    2018-02-01

    The Devils Mountain Fault Zone (DMFZ) extends east to west from Washington State to just south of Victoria, British Columbia, in the northern Strait of Juan de Fuca of Canada and the USA. Recently collected geophysical data were used to map this fault zone in detail, which show the main fault trace, and associated primary and secondary (conjugate) strands, and extensive northeast-southwest oriented folding that occurs within a 6 km wide deformation zone. The fault zone has been active in the Holocene as seen in the offset and disrupted upper Quaternary strata, seafloor displacement, and deformation within sediment cores taken close to the seafloor expression of the faults. Data suggest that the present DMFZ and the re-activated Leech River Fault may be part of the same fault system. Based on the length and previously estimated slip rates of the fault zone in Washington State, the DMFZ appears to have the potential of producing a strong earthquake, perhaps as large as magnitude 7.5 or greater, within 2 km of the city of Victoria.

  6. Posttraumatic Mandibular Asymmetry Presenting in a Young Adult

    Directory of Open Access Journals (Sweden)

    Mahnaz Sheikhi, DDS,MS

    2017-03-01

    Full Text Available One of the most common sites of injury of the facial skeleton is mandibular condyle. However, it is the least diagnosed site of trauma in the head and neck regions. A trauma to the mandible and specifically condylar zone during childhood, may lead to asymmetry or mandibular bilateral distortion, which is usually manifested in the second decade of life when the etiology is unknown to most people. This report is about an adult male complaining about facial asymmetry with an unknown source. Obvious clicking at the right side and shorter right ramus and condyle's head deviation directed us to a childhood trauma and fracture.

  7. 76 FR 80342 - Coastal Zone Management Program: Illinois

    Science.gov (United States)

    2011-12-23

    ... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration Coastal Zone Management... program under the Coastal Zone Management Act (CZMA), as amended at 16 U.S.C. 1451-1466, and the...). SUPPLEMENTARY INFORMATION: The Coastal Zone Management Act authorizes the Secretary of Commerce (Secretary) to...

  8. GEODESIC RECONSTRUCTION, SADDLE ZONES & HIERARCHICAL SEGMENTATION

    Directory of Open Access Journals (Sweden)

    Serge Beucher

    2011-05-01

    Full Text Available The morphological reconstruction based on geodesic operators, is a powerful tool in mathematical morphology. The general definition of this reconstruction supposes the use of a marker function f which is not necessarily related to the function g to be built. However, this paper deals with operations where the marker function is defined from given characteristic regions of the initial function f, as it is the case, for instance, for the extrema (maxima or minima but also for the saddle zones. Firstly, we show that the intuitive definition of a saddle zone is not easy to handle, especially when digitised images are involved. However, some of these saddle zones (regional ones also called overflow zones can be defined, this definition providing a simple algorithm to extract them. The second part of the paper is devoted to the use of these overflow zones as markers in image reconstruction. This reconstruction provides a new function which exhibits a new hierarchy of extrema. This hierarchy is equivalent to the hierarchy produced by the so-called waterfall algorithm. We explain why the waterfall algorithm can be achieved by performing a watershed transform of the function reconstructed by its initial watershed lines. Finally, some examples of use of this hierarchical segmentation are described.

  9. Zone-refining of beryllium(II) acetylacetonate

    International Nuclear Information System (INIS)

    Yoshida, Isao; Kobayashi, Hiroshi; Ueno, Keihei

    1975-01-01

    Zone melting was applied to bis (acetylacetonato) beryllium(II), Be(AA) 2 , to remove trace metal constiutents. The effective distribution coefficient, k, of a minor component measured in a binary mixture with the majority of Be(AA) 2 , fell in the range of 0.4 to 0.8, while the value obtained in a multiple component mixture fell in the range of 0.8 to 0.9 except Zn(II)- and Ni(II) chelates. Cr(AA) 3 was concentrated upward in the direction of the zone travelling, and similar results were obtained with Cu(II)-, Co(III)- Fe(III)- and Al(III) acetylacetonates, while Zn(II)-, Ni(II)- and Mn(III) chelates were fractionated in the both ends of the column. On the other hand, when the zone was moved downward, the minor components were concentrated in the lower end of a column. Efficiency in zone refining was compared to each other between the upward- and downward zone travelling modes on the crude beryllium acetylacetonates obtained from a commercial reagent of beryllium nitrate, and the latter mode was found more effective in the concentration of trace components. Discussion was given on possible mechanisms resulting in the difference in the refining efficiency. (author)

  10. 32 CFR 256.7 - Accident potential zone guidelines.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Accident potential zone guidelines. 256.7 Section 256.7 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS AIR INSTALLATIONS COMPATIBLE USE ZONES § 256.7 Accident potential zone guidelines...

  11. 33 CFR 147.801 - Boxer Platform safety zone.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Boxer Platform safety zone. 147.801 Section 147.801 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.801 Boxer Platform safety zone. (a...

  12. Development of the adult neurogenic niche in the hippocampus of mice

    Directory of Open Access Journals (Sweden)

    Zeina eNicola

    2015-05-01

    Full Text Available When does adult hippocampal neurogenesis begin? We describe the development of the neurogenic niche in the subgranular zone (SGZ of the hippocampal dentate gyrus. We did so from the perspective of the situation in the adult.Ontogeny of the dentate gyrus is complex and results in an ectopic neurogenic niche that lifelong generates new granule cells. Neurogenesis during the fetal and early postnatal periods builds the dentate gyrus and gives way to activity-dependent adult neurogenesis. We used markers most relevant to adult neurogenesis research to describe this transition: Nestin, Sox2, BLBP, GFAP, Tbr2, Doublecortin (DCX, NeuroD1 and Prox1. We found that massive changes and a local condensation of proliferating precursor cells occurs between postnatal day 7 (P7, near the peak in proliferation, and P14. Before and around P7, the spatial distribution of cells and the co-localization of markers were distinct from the situation in the adult. Unlike the adult SGZ, the marker pair Nestin/Sox2 and the radial glial marker BLBP were not overlapping during embryonic development, presumably indicating different types of radial glia-like cells. Before P7 GFAP-positive cells in the hilus lacked the radial orientation that is characteristic of the adult type-1 cells. DCX, which is concentrated in type-2b and type-3 progenitor cells and early postmitotic neurons in the adult, showed diffuse expression before P7. Intermediate progenitor cell marker Tbr2 became restricted to the SGZ but was found in the granule cell layer and hilus before. Lineage markers NeuroD1 and Prox1 confirmed this pattern.We conclude that the neurogenic niche of adult neurogenesis is in place well before true adulthood. This might indicate that consistent with the hypothesized function of adult neurogenesis in activity-dependent plasticity, the early transition from postnatal neurogenesis to adult neurogenesis coincides with the time, when the young mice start to become active themselves.

  13. Subspace exclusion zones for damage localization

    DEFF Research Database (Denmark)

    Bernal, Dionisio; Ulriksen, Martin Dalgaard

    2018-01-01

    , this is exploited in the context of structural damage localization to cast the Subspace Exclusion Zone (SEZ) scheme, which locates damage by reconstructing the captured field quantity shifts from analytical subspaces indexed by postulated boundaries, the so-called exclusion zones (EZs), in a model of the structure...

  14. EPA Region 1 No Discharge Zones

    Science.gov (United States)

    This dataset details No Discharge Zones (NDZ) for New England. Boaters may not discharge waste into these areas. Boundaries were determined mostly by Federal Register Environmental Documents in coordination with Massachusetts Coastal Zone Management (MA CZM) and EPA Region 1 Office of Ecosystem Protection (OEP) staff.

  15. Understanding Fluid and Contaminant Movement in the Unsaturated Zone Using the INEEL Vadose Zone Monitoring System

    International Nuclear Information System (INIS)

    Hubbell, J. M.; Mattson, E. D.; Sisson, J. B.; Magnuson, S. O.

    2002-01-01

    DOE has hundreds of contaminated facilities and waste sites requiring cleanup and/or long-term monitoring. These contaminated sites reside in unsaturated soils (i.e. the vadose zone) above the water table. Some of these sites will require active remediation activities or removal while other sites will be placed under institutional controls. In either case, evaluating the effectiveness of the remediation strategy or institutional controls will require monitoring. Classical monitoring strategies implemented at RCRA/CERCLA sites require ground water sampling for 30 years following closure. The overall effectiveness of ground water sampling is diminished due to the fact that by the time you detect chemical transport from a waste site, a major contamination plume likely exists in the vadose zone and the aquifer. This paper suggests a more effective monitoring strategy through monitoring near the contaminant sites within the vadose zone. Vadose zone monitoring allows for quicker detection of potential contaminant transport. The INEEL Vadose Zone Monitoring System (VZMS) is becoming an accepted, cost effective monitoring technology for assessing contaminant transport at DOE facilities. This paper describes the technologies employed in the VZMS and describes how it was used at several DOE facilities. The INEEL VZMS has provided the information in developing and validating both conceptual and risk assessment models of contaminant transport at the Idaho National Engineering and Environmental Laboratory (INEEL), Oak Ridge National Laboratory (ORNL), Savannah River Site (SRS) and the Hanford site. These DOE sites exhibit a broad range of meteorologic, hydrologic and geologic conditions representative of various common geologic environments. The VZMS is comprised of advanced tensiometers, water content sensors, temperature sensors and soil and gas samplers. These instruments are placed at multiple depths in boreholes and allows for the detection of water movement in the

  16. a Cross-Sectional Study on Insomnia among Japanese Adult Women in Relation to Night-Time Road Traffic Noise

    Science.gov (United States)

    Kageyama, T.; Kabuto, M.; Nitta, N.; Kurokawa, Y.; Taira, K.; Suzuki, S.; Takemoto, T.

    1997-08-01

    In an effort to determine the contribution of night-time road traffic noise to insomnia in the general population, 3600 adult Japanese women living in urban residential areas were surveyed. Living near a road with a heavy traffic volume is one of the risk factors for insomnia. The risk for insomnia in the zones 0-20 m from the main roads increased linearly with the night-time traffic volume. This suggests that road traffic noise raises the sound level in bedrooms in such zones, and consequently the prevalence rate of insomnia among the residents, and that noise-induced insomnia is an important public health problem, at least in highly urbanized areas.

  17. The relationship between Anopheles gambiae density and rice cultivation in the savannah zone and forest zone of Côte d'Ivoire.

    Science.gov (United States)

    Briët, Olivier J T; Dossou-Yovo, Joel; Akodo, Elena; van de Giesen, Nick; Teuscher, Thomas M

    2003-05-01

    In 13 villages in the savannah zone and 21 villages in the forest zone of Côte d'Ivoire, the biting density of the principal malaria vector, Anopheles gambiae, was studied as a function of rice cultivation in the inland valleys in a 2-km radius around each village. In the savannah villages, during the main season cropping period, surface water on rice-cultivated and to a lesser extent on uncultivated inland valleys seems to contribute strongly to the A. gambiae population density. For the off-season cropping period (which starts after the first light rains in the savannah zone), correlations were weaker. Breeding sites other than in inland valleys may play an important role in the savannah zone. In the forest zone, however, the A. gambiae population density was strongly correlated with the surface water availability (SWA) in the rice-cultivated inland valleys, whereas the correlation with the SWA in other (uncultivated) inland valleys was weak. The requirement of sunlit breeding sites for A. gambiae might explain this difference between zones. In the forest zone, only inland valleys cleared for rice cultivation meet this requirement, whereas all other inland valleys are covered with dense vegetation. In the savannah zone, however, most undergrowth is burnt during the dry season, which permits sunlight to reach puddles resulting from the first rains.

  18. 27 CFR 28.290 - Receipt in foreign trade zone.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Receipt in foreign trade zone. 28.290 Section 28.290 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... in Foreign-Trade Zone § 28.290 Receipt in foreign trade zone. On receipt at the zone, the shipment...

  19. 49 CFR 1105.9 - Coastal Zone Management Act requirements.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 8 2010-10-01 2010-10-01 false Coastal Zone Management Act requirements. 1105.9... ENVIRONMENTAL LAWS § 1105.9 Coastal Zone Management Act requirements. (a) If the proposed action affects land or water uses within a State coastal zone designated pursuant to the Coastal Zone Management Act (16 U.S.C...

  20. Neural stem cell sparing by linac based intensity modulated stereotactic radiotherapy in intracranial tumors

    International Nuclear Information System (INIS)

    Oehler, Julia; Brachwitz, Tim; Wendt, Thomas G; Banz, Nico; Walther, Mario; Wiezorek, Tilo

    2013-01-01

    Neurocognitive decline observed after radiotherapy (RT) for brain tumors in long time survivors is attributed to radiation exposure of the hippocampus and the subventricular zone (SVZ). The potential of sparing capabilities for both structures by optimized intensity modulated stereotactic radiotherapy (IMSRT) is investigated. Brain tumors were irradiated by stereotactic 3D conformal RT or IMSRT using m3 collimator optimized for PTV and for sparing of the conventional OARs (lens, retina, optic nerve, chiasm, cochlea, brain stem and the medulla oblongata). Retrospectively both hippocampi and SVZ were added to the list of OAR and their dose volume histograms were compared to those from two newly generated IMSRT plans using 7 or 14 beamlets (IMSRT-7, IMSRT-14) dedicated for optimized additional sparing of these structures. Conventional OAR constraints were kept constant. Impact of plan complexity and planning target volume (PTV) topography on sparing of both hippocampi and SVZ, conformity index (CI), the homogeneity index (HI) and quality of coverage (QoC) were analyzed. Limits of agreement were used to compare sparing of stem cell niches with either IMSRT-7 or IMSRT-14. The influence of treatment technique related to the topography ratio between PTV and OARs, realized in group A-D, was assessed by a mixed model. In 47 patients CI (p ≤ 0.003) and HI (p < 0.001) improved by IMSRT-7, IMSRT-14, QoC remained stable (p ≥ 0.50) indicating no compromise in radiotherapy. 90% of normal brain was exposed to a significantly higher dose using IMSRT. IMSRT-7 plans resulted in significantly lower biologically effective doses at all four neural stem cell structures, while contralateral neural stem cells are better spared compared to ipsilateral. A further increase of the number of beamlets (IMSRT-14) did not improve sparing significantly, so IMSRT-7 and IMSRT-14 can be used interchangeable. Patients with tumors contacting neither the subventricular zone nor the cortex benefit

  1. Cited2 Regulates Neocortical Layer II/III Generation and Somatosensory Callosal Projection Neuron Development and Connectivity.

    Science.gov (United States)

    Fame, Ryann M; MacDonald, Jessica L; Dunwoodie, Sally L; Takahashi, Emi; Macklis, Jeffrey D

    2016-06-15

    The neocortex contains hundreds to thousands of distinct subtypes of precisely connected neurons, allowing it to perform remarkably complex tasks of high-level cognition. Callosal projection neurons (CPN) connect the cerebral hemispheres via the corpus callosum, integrating cortical information and playing key roles in associative cognition. CPN are a strikingly diverse set of neuronal subpopulations, and development of this diversity requires precise control by a complex, interactive set of molecular effectors. We have found that the transcriptional coregulator Cited2 regulates and refines two stages of CPN development. Cited2 is expressed broadly by progenitors in the embryonic day 15.5 subventricular zone, during the peak of superficial layer CPN birth, with a progressive postmitotic refinement in expression, becoming restricted to CPN of the somatosensory cortex postnatally. We generated progenitor-stage and postmitotic forebrain-specific Cited2 conditional knock-out mice, using the Emx1-Cre and NEX-Cre mouse lines, respectively. We demonstrate that Cited2 functions in progenitors, but is not necessary postmitotically, to regulate both (1) broad generation of layer II/III CPN and (2) acquisition of precise area-specific molecular identity and axonal/dendritic connectivity of somatosensory CPN. This novel CPN subtype-specific and area-specific control from progenitor action of Cited2 adds yet another layer of complexity to the multistage developmental regulation of neocortical development. This study identifies Cited2 as a novel subtype-specific and area-specific control over development of distinct subpopulations within the broad population of callosal projection neurons (CPN), whose axons connect the two cerebral hemispheres via the corpus callosum (CC). Currently, how the remarkable diversity of CPN subtypes is specified, and how they differentiate to form highly precise and specific circuits, are largely unknown. We found that Cited2 functions within

  2. Introduction to the structures and processes of subduction zones

    Science.gov (United States)

    Zheng, Yong-Fei; Zhao, Zi-Fu

    2017-09-01

    Subduction zones have been the focus of many studies since the advent of plate tectonics in 1960s. Workings within subduction zones beneath volcanic arcs have been of particular interest because they prime the source of arc magmas. The results from magmatic products have been used to decipher the structures and processes of subduction zones. In doing so, many progresses have been made on modern oceanic subduction zones, but less progresses on ancient oceanic subduction zones. On the other hand, continental subduction zones have been studied since findings of coesite in metamorphic rocks of supracrustal origin in 1980s. It turns out that high-pressure to ultrahigh-pressure metamorphic rocks in collisional orogens provide a direct target to investigate the tectonism of subduction zones, whereas oceanic and continental arc volcanic rocks in accretionary orogens provide an indirect target to investigate the geochemistry of subduction zones. Nevertheless, metamorphic dehydration and partial melting at high-pressure to ultrahigh-pressure conditions are tectonically applicable to subduction zone processes at forearc to subarc depths, and crustal metasomatism is the physicochemical mechanism for geochemical transfer from the slab to the mantle in subduction channels. Taken together, these provide us with an excellent opportunity to find how the metamorphic, metasomatic and magmatic products are a function of the structures and processes in both oceanic and continental subduction zones. Because of the change in the thermal structures of subduction zones, different styles of metamorphism, metasomatism and magmatism are produced at convergent plate margins. In addition, juvenile and ancient crustal rocks have often suffered reworking in episodes independent of either accretionary or collisional orogeny, leading to continental rifting metamorphism and thus rifting orogeny for mountain building in intracontinental settings. This brings complexity to distinguish the syn

  3. Integrated seismic interpretation of the Carlsberg Fault zone, Copenhagen, Denmark

    DEFF Research Database (Denmark)

    Nielsen, Lars; Thybo, Hans; Jørgensen, Mette Iwanouw

    2005-01-01

    the fault zone. The fault zone is a shadow zone to shots detonated outside the fault zone. Finite-difference wavefield modelling supports the interpretations of the fan recordings. Our fan recording approach facilitates cost-efficient mapping of fault zones in densely urbanized areas where seismic normal......We locate the concealed Carlsberg Fault zone along a 12-km-long trace in the Copenhagen city centre by seismic refraction, reflection and fan profiling. The Carlsberg Fault is located in a NNW-SSE striking fault system in the border zone between the Danish Basin and the Baltic Shield. Recent...... earthquakes indicate that this area is tectonically active. A seismic refraction study across the Carlsberg Fault shows that the fault zone is a low-velocity zone and marks a change in seismic velocity structure. A normal incidence reflection seismic section shows a coincident flower-like structure. We have...

  4. Turbulent viscosity in natural surf zones

    NARCIS (Netherlands)

    Grasso, F.R.; Ruessink, B.G.

    2012-01-01

    Waves breaking in the shallow surf zone near the shoreline inject turbulence into the water column that may reach the bed to suspend sediment. Breaking-wave turbulence in the surf zone is, however, poorly understood, which is one of the reasons why many process-based coastal-evolution models

  5. Optimization of remediation strategies using vadose zone monitoring systems

    Science.gov (United States)

    Dahan, Ofer

    2016-04-01

    In-situ bio-remediation of the vadose zone depends mainly on the ability to change the subsurface hydrological, physical and chemical conditions in order to enable development of specific, indigenous, pollutants degrading bacteria. As such the remediation efficiency is much dependent on the ability to implement optimal hydraulic and chemical conditions in deep sections of the vadose zone. These conditions are usually determined in laboratory experiments where parameters such as the chemical composition of the soil water solution, redox potential and water content of the sediment are fully controlled. Usually, implementation of desired optimal degradation conditions in deep vadose zone at full scale field setups is achieved through infiltration of water enriched with chemical additives on the land surface. It is assumed that deep percolation into the vadose zone would create chemical conditions that promote biodegradation of specific compounds. However, application of water with specific chemical conditions near land surface dose not necessarily results in promoting of desired chemical and hydraulic conditions in deep sections of the vadose zone. A vadose-zone monitoring system (VMS) that was recently developed allows continuous monitoring of the hydrological and chemical properties of deep sections of the unsaturated zone. The VMS includes flexible time-domain reflectometry (FTDR) probes which allow continuous monitoring of the temporal variation of the vadose zone water content, and vadose-zone sampling ports (VSPs) which are designed to allow frequent sampling of the sediment pore-water and gas at multiple depths. Implementation of the vadose zone monitoring system in sites that undergoes active remediation provides real time information on the actual chemical and hydrological conditions in the vadose zone as the remediation process progresses. Up-to-date the system has been successfully implemented in several studies on water flow and contaminant transport in

  6. Friction of Shear-Fracture Zones

    Science.gov (United States)

    Riikilä, T. I.; Pylväinen, J. I.; Åström, J.

    2017-12-01

    A shear fracture of brittle solids under compression undergoes a substantial evolution from the initial microcracking to a fully formed powder-filled shear zone. Experiments covering the entire process are relatively easy to conduct, but they are very difficult to investigate in detail. Numerically, the large strain limit has remained a challenge. An efficient simulation model and a custom-made experimental device are employed to test to what extent a shear fracture alone is sufficient to drive material to spontaneous self-lubrication. A "weak shear zone" is an important concept in geology, and a large number of explanations, specific for tectonic conditions, have been proposed. We demonstrate here that weak shear zones are far more general, and that their emergence only demands that a microscopic, i.e., fragment-scale, stress relaxation mechanism develops during the fracture process.

  7. 15 CFR 400.41 - Zone operations; general.

    Science.gov (United States)

    2010-01-01

    ... district and is responsible for enforcement, including physical security and access requirements, as... operation. Zone grantees shall ensure that the reasonable zone needs of the business community are served by...

  8. Vadose zone studies at an industrial contaminated site: the vadose zone monitoring system and cross-hole geophysics

    Science.gov (United States)

    Fernandez de Vera, Natalia; Beaujean, Jean; Jamin, Pierre; Nguyen, Frédéric; Dahan, Ofer; Vanclooster, Marnik; Brouyère, Serge

    2014-05-01

    In order to improve risk characterization and remediation measures for soil and groundwater contamination, there is a need to improve in situ vadose zone characterization. However, most available technologies have been developed in the context of agricultural soils. Such methodologies are not applicable at industrial sites, where soils and contamination differ in origin and composition. In addition, most technologies are applicable only in the first meters of soils, leaving deeper vadose zones with lack of information, in particular on field scale heterogeneity. In order to overcome such difficulties, a vadose zone experiment has been setup at a former industrial site in Belgium. Industrial activities carried out on site left a legacy of soil and groundwater contamination in BTEX, PAH, cyanide and heavy metals. The experiment comprises the combination of two techniques: the Vadose Zone Monitoring System (VMS) and cross-hole geophysics. The VMS allows continuous measurements of water content and temperature at different depths of the vadose zone. In addition, it provides the possibility of pore water sampling at different depths. The system is formed by a flexible sleeve containing monitoring units along its depth which is installed in a slanted borehole. The flexible sleeve contains three types of monitoring units in the vadose zone: Time Domain Transmissometry (TDT), which allows water content measurements; Vadose Sampling Ports (VSP), used for collecting water samples coming from the matrix; the Fracture Samplers (FS), which are used for retrieving water samples from the fractures. Cross-hole geophysics techniques consist in the injection of an electrical current using electrodes installed in vertical boreholes. From measured potential differences, detailed spatial patterns about electrical properties of the subsurface can be inferred. Such spatial patterns are related with subsurface heterogeneities, water content and solute concentrations. Two VMS were

  9. Unintentional contaminant transfer from groundwater to the vadose zone during source zone remediation of volatile organic compounds.

    Science.gov (United States)

    Chong, Andrea D; Mayer, K Ulrich

    2017-09-01

    Historical heavy use of chlorinated solvents in conjunction with improper disposal practices and accidental releases has resulted in widespread contamination of soils and groundwater in North America and worldwide. As a result, remediation of chlorinated solvents is required at many sites. For source zone treatment, common remediation strategies include in-situ chemical oxidation (ISCO) using potassium or sodium permanganate, and the enhancement of biodegradation by primary substrate addition. It is well known that these remediation methods tend to generate gas (carbon dioxide (CO 2 ) in the case of ISCO using permanganate, CO 2 and methane (CH 4 ) in the case of bioremediation). Vigorous gas generation in the presence of chlorinated solvents, which are categorized as volatile organic contaminants (VOCs), may cause gas exsolution, ebullition and stripping of the contaminants from the treatment zone. This process may lead to unintentional 'compartment transfer', whereby VOCs are transported away from the contaminated zone into overlying clean sediments and into the vadose zone. To this extent, benchtop column experiments were conducted to quantify the effect of gas generation during remediation of the common chlorinated solvent trichloroethylene (TCE/C 2 Cl 3 H). Both ISCO and enhanced bioremediation were considered as treatment methods. Results show that gas exsolution and ebullition occurs for both remediation technologies. Facilitated by ebullition, TCE was transported from the source zone into overlying clean groundwater and was subsequently released into the column headspace. For the case of enhanced bioremediation, the intermediate degradation product vinyl chloride (VC) was also stripped from the treatment zone. The concentrations measured in the headspace of the columns (TCE ∼300ppm in the ISCO column, TCE ∼500ppm and VC ∼1380ppm in the bioremediation column) indicate that substantial transfer of VOCs to the vadose zone is possible. These findings

  10. Embodied Archives as Contact Zones

    Directory of Open Access Journals (Sweden)

    Judit Vidiella

    2015-02-01

    Full Text Available This article proposes a reflection about affective politics from locating some theoretical and conceptual genealogies like «emotion», «affection», «zones of contact»…, that understand them as action and force fields. These contributions allow us to rethink the relation of affects with politics and strategies of archive linked to performance, and understood as zones of friction, collision, circulation and contact: performative writing, repertoire, memes…

  11. Buffer Zone Requirements for Soil Fumigant Applications

    Science.gov (United States)

    Updated pesticide product labels require fumigant users to establish a buffer zone around treated fields to reduce risks to bystanders. Useful information includes tarp testing guidance and a buffer zone calculator.

  12. Empowering the child and caregiver: yellow zone Asthma Action Plan.

    Science.gov (United States)

    Dinakar, Chitra; Portnoy, Jay M

    2014-11-01

    Current guidelines, both national and international, elegantly describe evidence-based measures to attain and maintain long-term control of asthma. These strategies, typically discussed between the provider and patient, are provided in the form of written (or electronic) instructions as part of the green zone of the color-coded Asthma Action Plan. The red zone of the Asthma Action Plan has directives on when to use systemic corticosteroids and seek medical attention. The transition zone between the green zone of good control and the red zone of asthma exacerbation is the yellow zone. This zone guides the patient on self-management of exacerbations outside a medical setting. Unfortunately, the only recommendation currently available to patients per the current asthma guidelines is the repetitive use of reliever bronchodilators. This approach, while providing modest symptom relief, does not reliably prevent progression to the red zone. In this document, we present new, evidence-based, yellow zone intervention options.

  13. Impact of loudspeaker nonlinear distortion on personal sound zones

    DEFF Research Database (Denmark)

    Ma, Xiaohui; J. Hegarty, Patrick; Abildgaard Pedersen, Jan

    2018-01-01

    Personal sound zone systems aim at creating multiple listening zones within a shared space with minimum interference between zones, but the performance is often poorer than simulations predict and effects of nonlinear distortion are sometimes audible. This paper assesses the impact of nonlinear...... distortion on sound zones through simulations and measurements performed under anechoic conditions. Two sound zones, one bright and one dark, are created with acoustic contrast control using two loudspeaker arrays driven at 250 Hz. Nonlinear distortion is modelled using second or third order nonlinearities....... Simulations show that nonlinear distortion degrades the acoustic contrast, which is confirmed by experimental measurements. The harmonic distortion is audible in the dark zone. Frequency resolved measurements reveal that harmonic distortion contributes to contrast loss, but nonlinear effects...

  14. F-spondin/spon1b expression patterns in developing and adult zebrafish.

    Directory of Open Access Journals (Sweden)

    Veronica Akle

    Full Text Available F-spondin, an extracellular matrix protein, is an important player in embryonic morphogenesis and CNS development, but its presence and role later in life remains largely unknown. We generated a transgenic zebrafish in which GFP is expressed under the control of the F-spondin (spon1b promoter, and used it in combination with complementary techniques to undertake a detailed characterization of the expression patterns of F-spondin in developing and adult brain and periphery. We found that F-spondin is often associated with structures forming long neuronal tracts, including retinal ganglion cells, the olfactory bulb, the habenula, and the nucleus of the medial longitudinal fasciculus (nMLF. F-spondin expression coincides with zones of adult neurogenesis and is abundant in CSF-contacting secretory neurons, especially those in the hypothalamus. Use of this new transgenic model also revealed F-spondin expression patterns in the peripheral CNS, notably in enteric neurons, and in peripheral tissues involved in active patterning or proliferation in adults, including the endoskeleton of zebrafish fins and the continuously regenerating pharyngeal teeth. Moreover, patterning of the regenerating caudal fin following fin amputation in adult zebrafish was associated with F-spondin expression in the blastema, a proliferative region critical for tissue reconstitution. Together, these findings suggest major roles for F-spondin in the CNS and periphery of the developing and adult vertebrate.

  15. Vadose Zone Journal: The first ten years

    NARCIS (Netherlands)

    Vrugt, J.A.; Or, D.; Young, M.H.

    2013-01-01

    Celebrating ten years of publication, the authors introduce a special section commemorating the anniversary of Vadose Zone Journal and reviewing the journal’s role in an evolving understanding of vadose zone science.

  16. Endogenous repair mechanisms enhanced in Parkinson's disease following stem cell therapy

    Directory of Open Access Journals (Sweden)

    Eleonora Napoli

    2017-01-01

    Full Text Available This mini-review highlights the innovative observation that transplanted human neural stem cells can bring about endogenous brain repair through the stimulation of multiple regenerative processes in the neurogenic area (i.e., subventricular zone [SVZ] in an animal model of Parkinson's disease (PD. In addition, we convey that identifying anti-inflammatory cytokines, therapeutic proteomes, and neurotrophic factors within the SVZ may be essential to induce brain repair and behavioral recovery. This work opens up a new area of research for further understanding the pathology and treatment of PD. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

  17. Photobiomodulation and the brain: a new paradigm

    Science.gov (United States)

    Hennessy, Madison; Hamblin, Michael R.

    2017-01-01

    Transcranial photobiomodulation (PBM), also known as low level laser therapy (LLLT), relies on the use of red/NIR light to stimulate, preserve and regenerate cells and tissues. The mechanism of action involves photon absorption in the mitochondria (cytochrome c oxidase), and ion channels in cells leading to activation of signaling pathways, up-regulation of transcription factors and increased expression of protective genes. We have studied PBM for treating traumatic brain injury in mice using a NIR laser spot delivered to the head. Mice had improved memory and learning, increased neuroprogenitor cells in the dentate gyrus and subventricular zone, increased BDNF and more synaptogenesis in the cortex. These highly beneficial effects on the brain suggest that the applications of LLLT are much broader than first conceived. Other groups have studied stroke (animal models and clinical trials), Alzheimer’s disease, Parkinson’s disease, depression and cognitive enhancement in healthy subjects.

  18. Social economic zones as an instrument of regional development

    Directory of Open Access Journals (Sweden)

    Wiesława Lizińska

    2005-01-01

    Full Text Available The goal of the paper was the analysis of the main aspects o f Special Economic Zones (SEZ activity. It refers especially to the goals for establishment, operational models of these zones, SEZ based on examples of selected countries and Poland in the context o f integration with the European Union. The Special Economic Zones to create more attractive conditions for business operations, to contribute mainly to the development of small and medium enterprises and variety of services, consequently to improve employment. However, the consequences of the zones existence can be negative for economy of the region. The Special Economic Zones that are functioning worldwide are different. In Poland, they were first designed by the Irish and based on the example of the zone in Shannon. The existence and principles of the Special Economic Zones operations in Poland are one of the contradiction points in the negotiations with the European Union.

  19. A Radial Glia Fascicle Leads Principal Neurons from the Pallial-Subpallial Boundary into the Developing Human Insula.

    Science.gov (United States)

    González-Arnay, Emilio; González-Gómez, Miriam; Meyer, Gundela

    2017-01-01

    The human insular lobe, in the depth of the Sylvian fissure, displays three main cytoarchitectonic divisions defined by the differentiation of granular layers II and IV. These comprise a rostro-ventral agranular area, an intermediate dysgranular area, and a dorso-caudal granular area. Immunohistochemistry in human embryos and fetuses using antibodies against PCNA, Vimentin, Nestin, Tbr1, and Tb2 reveals that the insular cortex is unique in that it develops far away from the ventricular zone (VZ), with most of its principal neurons deriving from the subventricular zone (SVZ) of the pallial-subpallial boundary (PSB). In human embryos (Carnegie stage 16/17), the rostro-ventral insula is the first cortical region to develop; its Tbr1+ neurons migrate from the PSB along the lateral cortical stream. From 10 gestational weeks (GW) onward, lateral ventricle, ganglionic eminences, and PSB grow forming a C-shaped curvature. The SVZ of the PSB gives rise to a distinct radial glia fiber fascicle (RGF), which courses lateral to the putamen in the external capsule. In the RGF, four components can be established: PF, descending from the prefrontal PSB to the anterior insula; FP, descending from the fronto-parietal PSB toward the intermediate insula; PT, coursing from the PSB near the parieto-temporal junction to the posterior insula, and T, ascending from the temporal PSB and merging with components FP and PT. The RGF fans out at different dorso-ventral and rostro-caudal levels of the insula, with descending fibers predominating over ascending ones. The RGF guides migrating principal neurons toward the future agranular, dysgranular, and granular insular areas, which show an adult-like definition at 32 GW. Despite the narrow subplate, and the absence of an intermediate zone except in the caudal insula, most insular subdivisions develop into a 6-layered isocortex, possibly due to the well developed outer SVZ at the PSB, which is particularly prominent at the level of the dorso

  20. A Radial Glia Fascicle Leads Principal Neurons from the Pallial-Subpallial Boundary into the Developing Human Insula

    Directory of Open Access Journals (Sweden)

    Emilio González-Arnay

    2017-12-01

    Full Text Available The human insular lobe, in the depth of the Sylvian fissure, displays three main cytoarchitectonic divisions defined by the differentiation of granular layers II and IV. These comprise a rostro-ventral agranular area, an intermediate dysgranular area, and a dorso-caudal granular area. Immunohistochemistry in human embryos and fetuses using antibodies against PCNA, Vimentin, Nestin, Tbr1, and Tb2 reveals that the insular cortex is unique in that it develops far away from the ventricular zone (VZ, with most of its principal neurons deriving from the subventricular zone (SVZ of the pallial-subpallial boundary (PSB. In human embryos (Carnegie stage 16/17, the rostro-ventral insula is the first cortical region to develop; its Tbr1+ neurons migrate from the PSB along the lateral cortical stream. From 10 gestational weeks (GW onward, lateral ventricle, ganglionic eminences, and PSB grow forming a C-shaped curvature. The SVZ of the PSB gives rise to a distinct radial glia fiber fascicle (RGF, which courses lateral to the putamen in the external capsule. In the RGF, four components can be established: PF, descending from the prefrontal PSB to the anterior insula; FP, descending from the fronto-parietal PSB toward the intermediate insula; PT, coursing from the PSB near the parieto-temporal junction to the posterior insula, and T, ascending from the temporal PSB and merging with components FP and PT. The RGF fans out at different dorso-ventral and rostro-caudal levels of the insula, with descending fibers predominating over ascending ones. The RGF guides migrating principal neurons toward the future agranular, dysgranular, and granular insular areas, which show an adult-like definition at 32 GW. Despite the narrow subplate, and the absence of an intermediate zone except in the caudal insula, most insular subdivisions develop into a 6-layered isocortex, possibly due to the well developed outer SVZ at the PSB, which is particularly prominent at the level of