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Berlin Brandenburg

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  • HAL (CCSd)  (183)
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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 19 January 2010, Vol.107(3), pp.1201-6
    Description: After their generation and specification in periventricular regions, neuronal precursors maintain an immature and migratory state until their arrival in the respective target structures. Only here are terminal differentiation and synaptic integration induced. Although the molecular control of neuronal specification has started to be elucidated, little is known about the factors that control the latest maturation steps. We aimed at identifying factors that induce terminal differentiation during postnatal and adult neurogenesis, thereby focusing on the generation of periglomerular interneurons in the olfactory bulb. We isolated neuronal precursors and mature neurons from the periglomerular neuron lineage and analyzed their gene expression by microarray. We found that expression of the bHLH transcription factor NeuroD1 strikingly coincides with terminal differentiation. Using brain electroporation, we show that overexpression of NeuroD1 in the periventricular region in vivo leads to the rapid appearance of cells with morphological and molecular characteristics of mature neurons in the subventricular zone and rostral migratory stream. Conversely, shRNA-induced knockdown of NeuroD1 inhibits terminal neuronal differentiation. Thus, expression of a single transcription factor is sufficient to induce neuronal differentiation of neural progenitors in regions that normally do not show addition of new neurons. These results suggest a considerable potential of NeuroD1 for use in cell-therapeutic approaches in the nervous system.
    Keywords: Basic Helix-Loop-Helix Transcription Factors -- Physiology ; Cell Differentiation -- Physiology ; Interneurons -- Chemistry ; Olfactory Bulb -- Cytology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    Language: English
    In: Intensive Care Medicine, 2011, Vol.37(10), pp.1648-1655
    Description: Byline: Robin Cremer (1,2), Philippe Hubert (3,6), Bruno Grandbastien (4,7), Gregoire Moutel (5,6), Francis Leclerc (1,8) Keywords: Withdrawing treatments; Guideline adherence; Intensive care unit; Ethics; Child; Uncompensated care; Patient care management; Hospital costs Abstract: Purpose Our goal is to assess the prevalence of questioning about the appropriateness of initiating or maintaining life-sustaining treatments (LST) in French-speaking paediatric intensive care units (PICUs) and to evaluate time utilisation related to decision-making processes (DMP). Methods 18-month, multicentre, prospective, descriptive, observational study in 15 French-speaking PICUs. Results Among the 5,602 children admitted, 410 died (7.3%), including 175 after forgoing LST (42.7% of deaths). LST was questioned in 308 children (5.5%) with a prevalence of 13.3 per 100 patient-days. More than 30% of children survived despite the appropriateness of LST being questioned (23% despite a decision to forgo treatment). Median caregiver time spent on making and presenting the decisions was 11 h per child. Conclusions In this study, on any given day in each 10-bed PICU, there was more than one child for whom a DMP was underway. Of children, 23% survived despite a decision to forgo LST being made, which underlines the need to elaborate a care plan for these children. Also, DMP represented a large amount of staff time that is undervalued but necessary to ensure optimal palliative practice in PICU. Author Affiliation: (1) Reanimation Pediatrique, Hopital Jeanne de Flandre, CHU de Lille, 59037, Lille Cedex, France (2) Espace Ethique Hospitalier et Universitaire de Lille, 1 place de Verdun, 59045, Lille Cedex, France (3) Reanimation Pediatrique, Hopital Necker-Enfants Malades, Rue de Sevres, 75007, Paris, France (6) Universite Paris V - Descartes, 12 rue de l'ecole de medecine, 75006, Paris, France (4) Service d'Epidemiologie Regional, Hopital Calmette, CHU de Lille, 59037, Lille Cedex, France (7) Universite Lille Nord de France, 1 bis rue Georges Lefebvre, 59800, Lille, France (5) Reseau de Recherche en Ethique de l'INSERM, Laboratoire d'Ethique Medicale, Faculte de Medecine Paris-Descartes, 75270, Paris, France (8) Universite Lille Nord de France, UDSL, EA 2694, 1 bis rue Georges Lefebvre, 59800, Lille, France Article History: Registration Date: 09/07/2011 Received Date: 21/10/2010 Accepted Date: 12/04/2011 Online Date: 16/08/2011
    Keywords: Withdrawing treatments ; Guideline adherence ; Intensive care unit ; Ethics ; Child ; Uncompensated care ; Patient care management ; Hospital costs
    ISSN: 0342-4642
    E-ISSN: 1432-1238
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  • 3
    Language: English
    In: Journal of Experimental Social Psychology, 2011, Vol.47(1), pp.139-146
    Description: In two studies we investigated the impact of degree of collective failure in a public good dilemma (near miss vs. large miss) on group members' negative reactions (negative affect, attributions of responsibility for the failure, and intention to leave the group). The results show that upward counterfactual thinking has more impact on members' negative responses when experiencing a near miss rather than a large miss. In Experiment 1, the results show that in the case of a near miss (and not a large miss), negative affect and attributions of responsibility were higher when other-focused counterfactuals rather than self-focused counterfactuals were elicited. Negative affect was found to mediate the effect on attributions of responsibility. Experiment 2 replicates these findings on a wider range of negative responses and reveals that the effect of counterfactual thought on willingness to leave the group in the case of a near miss is mediated by attributions of responsibility.
    Keywords: Public Good Dilemmas ; Counterfactuals ; Negative Affect ; Exit ; Near Miss Effect ; Sociology & Social History ; Psychology
    ISSN: 0022-1031
    E-ISSN: 1096-0465
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  • 4
    Language: English
    In: Journal of Experimental Social Psychology, January 2010, Vol.46(1), pp.85-96
    Description: This research explored why strongly identifying followers endorse prototypical leaders by addressing the role of procedural fairness in this process. We introduced the distinction between procedural fairness rules relating to leader benevolence (i.e., whether the leader supports the group’s interests) and follower control (i.e., whether followers can influence the leader’s decisions). We predicted that strongly identifying group members endorse prototypical leaders because they perceive such leaders as acting in line with benevolence related fairness rules rather than because such leaders are perceived as giving followers control. An organizational field study and a laboratory experiment revealed support for these ideas. Our results thus provide insights into why prototypical leaders are endorsed among strongly identifying followers. They also have implications for the procedural fairness literature in showing that frequently studied procedural fairness rules (e.g., voice) do not explain endorsement of leaders believed to support the group’s interests.
    Keywords: Leadership ; Prototypicality ; Identification ; Procedural Fairness ; Justice ; Legitimacy ; Sociology & Social History ; Psychology
    ISSN: 0022-1031
    E-ISSN: 1096-0465
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  • 5
    Language: English
    In: The New England journal of medicine, 28 July 2011, Vol.365(4), pp.375; author reply 376
    Description: To the Editor: On behalf of the Section on Neurotrauma and Critical Care of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons, we register our concern with the recently published article “Decompressive Craniectomy in Diffuse Traumatic Brain Injury” by Cooper...
    Keywords: Decompressive Craniectomy ; Brain Injuries -- Surgery ; Edema -- Etiology ; Intracranial Hypertension -- Surgery
    ISSN: 00284793
    E-ISSN: 1533-4406
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  • 6
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 29 July 2014, Vol.111(30), pp.E3129-38
    Description: In the nervous system, cilia dysfunction perturbs the circulation of the cerebrospinal fluid, thus affecting neurogenesis and brain homeostasis. A role for planar cell polarity (PCP) signaling in the orientation of cilia (rotational polarity) and ciliogenesis is established. However, whether and how PCP regulates cilia positioning in the apical domain (translational polarity) in radial progenitors and ependymal cells remain unclear. By analysis of a large panel of mutant mice, we show that two PCP signals are operating in ciliated cells. The first signal, controlled by cadherin, EGF-like, laminin G-like, seven-pass, G-type receptor (Celsr) 2, Celsr3, Frizzled3 (Fzd3) and Van Gogh like2 (Vangl2) organizes multicilia in individual cells (single-cell polarity), whereas the second signal, governed by Celsr1, Fzd3, and Vangl2, coordinates polarity between cells in both radial progenitors and ependymal cells (tissue polarity). Loss of either of these signals is associated with specific defects in the cytoskeleton. Our data reveal unreported functions of PCP and provide an integrated view of planar polarization of the brain ciliated cells.
    Keywords: Cell Polarity -- Physiology ; Cytoskeleton -- Metabolism ; Ependyma -- Metabolism ; Nerve Tissue Proteins -- Metabolism ; Neurogenesis -- Physiology ; Signal Transduction -- Physiology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 7
    Language: English
    In: The Journal of neuroscience : the official journal of the Society for Neuroscience, 21 November 2012, Vol.32(47), pp.16892-905
    Description: In the postnatal forebrain, the subventricular zone (SVZ) contains a pool of undifferentiated cells, which proliferate and migrate along the rostral migratory stream (RMS) to the olfactory bulb and differentiate into granule cells and periglomerular cells. Plexin-B2 is a semaphorin receptor previously known to act on neuronal proliferation in the embryonic brain and neuronal migration in the cerebellum. We show here that, in the postnatal and adult CNS, Plexin-B2 is expressed in the subventricular zone lining the telencephalic ventricles and in the rostral migratory stream. We analyzed Plxnb2(-/-) mice and found that there is a marked reduction in the proliferation of SVZ cells in the mutant. Plexin-B2 expression is downregulated in the olfactory bulb as interneurons initiate radial migration. BrdU labeling and GFP electroporation into postnatal SVZ, in addition to time-lapse videomicroscopy, revealed that neuroblasts deficient for Plexin-B2 migrate faster than control ones and leave the RMS more rapidly. Overall, these results show that Plexin-B2 plays a role in postnatal neurogenesis and in the migration of SVZ-derived neuroblasts.
    Keywords: Cell Movement -- Physiology ; Nerve Tissue Proteins -- Physiology ; Neurogenesis -- Physiology ; Neurons -- Physiology ; Prosencephalon -- Physiology
    E-ISSN: 1529-2401
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  • 8
    In: Nature Neuroscience, 2012, Vol.15(8), p.1120
    Description: In the postnatal and adult mouse forebrain, a mosaic of spatially separated neural stem cells along the lateral wall of the ventricles generates defined types of olfactory bulb neurons. To understand the mechanisms underlying the regionalization of the stem cell pool, we focused on the transcription factor Pax6, a determinant of the dopaminergic phenotype in this system. We found that, although Pax6 mRNA was transcribed widely along the ventricular walls, Pax6 protein was restricted to the dorsal aspect. This dorsal restriction was a result of inhibition of protein expression by miR-7a, a microRNA (miRNA) that was expressed in a gradient opposing Pax6. In vivo inhibition of miR-7a in Pax6-negative regions of the lateral wall induced Pax6 protein expression and increased dopaminergic neurons in the olfactory bulb. These findings establish miRNA-mediated fine-tuning of protein expression as a mechanism for controlling neuronal stem cell diversity and, consequently, neuronal phenotype.
    Keywords: Dopaminergic Neurons -- Physiology ; Eye Proteins -- Metabolism ; Homeodomain Proteins -- Metabolism ; Micrornas -- Physiology ; Neural Stem Cells -- Physiology ; Paired Box Transcription Factors -- Metabolism ; Prosencephalon -- Physiology ; Repressor Proteins -- Metabolism;
    ISSN: 1097-6256
    E-ISSN: 15461726
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  • 9
    Language: English
    In: The Journal of neuroscience : the official journal of the Society for Neuroscience, 11 June 2014, Vol.34(24), pp.8318-23
    Description: The heparan sulfate proteoglycan Glypican 4 (Gpc4) is strongly expressed in mouse embryonic stem (ES) cells where it controls the maintenance of self-renewal by modulating Wnt/β-catenin signaling activities. Here we show that mouse ES cells carrying a hypomorphic Gpc4 allele, in a single-step neuronal differentiation protocol, show increased differentiation into dopaminergic neurons expressing tyrosine hydroxylase (TH) and nuclear receptor related-1 protein (Nurr1) 1. In contrast to wild-type cells, these differentiating Gpc4-mutant cells expressed high levels of DOPA decarboxylase and the dopamine transporter, two markers expressed by fully mature dopaminergic neurons. Intrastriatal transplantation of Gpc4 hypomorphic cells into a 6-OHDA rat model for Parkinson's disease improved motor behavior in the cylinder test and amphetamine-induced rotations at a higher level than transplanted wild-type cells. Importantly, Gpc4 hypomorphic cell grafts, in contrast to wild-type cells, did not generate teratomas in the host brains, leading to strongly enhanced animal survival. Therefore, control of Gpc4 activity level represents a new potential strategy to reduce ES cell tumorigenic features while at the same time increasing neuronal differentiation and integration.
    Keywords: Dopaminergic Neurons -- Physiology ; Embryonic Stem Cells -- Transplantation ; Glypicans -- Metabolism ; Parkinson Disease -- Physiopathology ; Teratoma -- Prevention & Control
    E-ISSN: 1529-2401
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  • 10
    Language: English
    In: The Journal of neuroscience : the official journal of the Society for Neuroscience, 14 March 2012, Vol.32(11), pp.3759-64
    Description: In the adult forebrain, new interneurons are continuously generated and integrated into the existing circuitry of the olfactory bulb (OB). In an attempt to identify signals that regulate this synaptic integration process, we found strong expression of agrin in adult generated neuronal precursors that arrive in the olfactory bulb after their generation in the subventricular zone. While the agrin receptor components MuSK and Lrp4 were below detection level in neuron populations that represent synaptic targets for the new interneurons, the alternative receptor α3-Na(+)K(+)-ATPase was strongly expressed in mitral cells. Using a transplantation approach, we demonstrate that agrin-deficient interneuron precursors migrate correctly into the OB. However, in contrast to wild-type neurons, which form synapses and survive for prolonged periods, mutant neurons do not mature and are rapidly eliminated. Using in vivo brain electroporation of the olfactory system, we show that the transmembrane form of agrin alone is sufficient to mediate integration and demonstrate that excess transmembrane agrin increases the number of dendritic spines. Last, we provide in vivo evidence that an interaction between agrin and α3-Na(+)K(+)-ATPase is of functional importance in this system.
    Keywords: Agrin -- Physiology ; Neurogenesis -- Physiology ; Neurons -- Metabolism ; Olfactory Bulb -- Metabolism ; Signal Transduction -- Physiology ; Sodium-Potassium-Exchanging Atpase -- Physiology
    ISSN: 02706474
    E-ISSN: 1529-2401
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