A Fate Map of the Murine Pancreas Buds Reveals a Multipotent Ventral Foregut Organ Progenitor
Angelo, Jesse R.; Guerrero-Zayas, Mara-Isel; Tremblay, Kimberly D.
2012-01-01
The definitive endoderm is the embryonic germ layer that gives rise to the budding endodermal organs including the thyroid, lung, liver and pancreas as well as the remainder of the gut tube. DiI fate mapping and whole embryo culture were used to determine the endodermal origin of the 9.5 days post coitum (dpc) dorsal and ventral pancreas buds. Our results demonstrate that the progenitors of each bud occupy distinct endodermal territories. Dorsal bud progenitors are located in the medial endoderm overlying somites 2–4 between the 2 and 11 somite stage (SS). The endoderm forming the ventral pancreas bud is found in 2 distinct regions. One territory originates from the left and right lateral endoderm caudal to the anterior intestinal portal by the 6 SS and the second domain is derived from the ventral midline of the endoderm lip (VMEL). Unlike the laterally located ventral foregut progenitors, the VMEL population harbors a multipotent progenitor that contributes to the thyroid bud, the rostral cap of the liver bud, ventral midline of the liver bud and the midline of the ventral pancreas bud in a temporally restricted manner. This data suggests that the midline of the 9.5 dpc thyroid, liver and ventral pancreas buds originates from the same progenitor population, demonstrating a developmental link between all three ventral foregut buds. Taken together, these data define the location of the dorsal and ventral pancreas progenitors in the prespecified endodermal sheet and should lead to insights into the inductive events required for pancreas specification. PMID:22815796
Directory of Open Access Journals (Sweden)
Han-Seop Kim
2014-01-01
Full Text Available The direct lineage reprogramming of somatic cells to other lineages by defined factors has led to innovative cell-fate-change approaches for providing patient-specific cells. Recent reports have demonstrated that four pluripotency factors (Oct4, Sox2, Klf4, and c-Myc are sufficient to directly reprogram fibroblasts to other specific cells, including induced neural stem cells (iNSCs. Here, we show that mouse fibroblasts can be directly reprogrammed into midbrain dopaminergic neuronal progenitors (DPs by temporal expression of the pluripotency factors and environment containing sonic hedgehog and fibroblast growth factor 8. Within thirteen days, self-renewing and functional induced DPs (iDPs were generated. Interestingly, the inhibition of both Jak and Gsk3β notably enhanced the iDP reprogramming efficiency. We confirmed the functionality of the iDPs by showing that the dopaminergic neurons generated from iDPs express midbrain markers, release dopamine, and show typical electrophysiological profiles. Our results demonstrate that the pluripotency factors-mediated direct reprogramming is an invaluable strategy for supplying functional and proliferating iDPs and may be useful for other neural progenitors required for disease modeling and cell therapies for neurodegenerative disorders.
Ventral medullary neurones excited from the hypothalamic and mid-brain defence areas.
Hilton, S M; Smith, P R
1984-07-01
In cats anaesthetised with chloralose, the ventral medulla was explored in and around the strip previously identified as the location of the efferent pathway from the hypothalamic and mid-brain defence areas to the spinal cord, in a search for neurones excited by electrical stimulation of the defence areas. Such units were found mostly in the caudal part of this strip, at a depth of not more than 500 microns from the surface. Nearly all were located in the ventral part of nucleus paragigantocellularis lateralis (PGL) at the level of the rostral pole of the inferior olive. There was evidence of temporal and spatial facilitation, indicating a convergent excitatory input from the defence areas onto neurones in PGL. This is consistent with earlier evidence of a synaptic relay in the efferent pathway at this site. When the pathway is blocked at this site, arterial blood pressure falls profoundly, so activity in these neurones may be essential for the normal level of sympathetic nerve activity.
Czech Academy of Sciences Publication Activity Database
Andersson, E.R.; Prakash, N.; Čajánek, L.; Minina, E.; Bryja, Vítězslav; Bryjová, Lenka; Yamaguchi, T.P.; Hall, A.C.; Wurst, W.; Arenas, E.
2008-01-01
Roč. 3, č. 10 (2008), s. 1-14 E-ISSN 1932-6203 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : Wnt 5a deficient mouse * ventral midbrain * planar cell polarity Subject RIV: BO - Biophysics
Subramaniam, Mahalakshmi; Kern, Beatrice; Vogel, Simone; Klose, Verena; Schneider, Gaby; Roeper, Jochen
2014-09-01
The impairment of protein degradation via the ubiquitin-proteasome system (UPS) is present in sporadic Parkinson's disease (PD), and might play a key role in selective degeneration of vulnerable dopamine (DA) neurons in the substantia nigra pars compacta (SN). Further evidence for a causal role of dysfunctional UPS in familial PD comes from mutations in parkin, which results in a loss of function of an E3-ubiquitin-ligase. In a mouse model, genetic inactivation of an essential component of the 26S proteasome lead to widespread neuronal degeneration including DA midbrain neurons and the formation of alpha-synuclein-positive inclusion bodies, another hallmark of PD. Studies using pharmacological UPS inhibition in vivo had more mixed results, varying from extensive degeneration to no loss of DA SN neurons. However, it is currently unknown whether UPS impairment will affect the neurophysiological functions of DA midbrain neurons. To answer this question, we infused a selective proteasome inhibitor into the ventral midbrain in vivo and recorded single DA midbrain neurons 2 weeks after the proteasome challenge. We found a selective increase in the mean in vivo firing frequencies of identified DA SN neurons in anesthetized mice, while those in the ventral tegmental area (VTA) were unaffected. Our results demonstrate that a single-hit UPS inhibition is sufficient to induce a stable and selective hyperexcitability phenotype in surviving DA SN neurons in vivo. This might imply that UPS dysfunction sensitizes DA SN neurons by enhancing 'stressful pacemaking'. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
DEFF Research Database (Denmark)
Bauer, Matthias; Szulc, Jolanta; Meyer, Morten
2008-01-01
function of Dlk1 in VM neuron development, we investigated the effect of soluble Dlk1 protein as well as the intrinsic Dlk1 function in the course of VM progenitor expansion and dopaminergic (DA) neuron differentiation in vitro. Dlk1 treatment during expansion increased DA progenitor proliferation...
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Angela Anderegg
Full Text Available MicroRNAs regulate gene expression in diverse physiological scenarios. Their role in the control of morphogen related signaling pathways has been less studied, particularly in the context of embryonic Central Nervous System (CNS development. Here, we uncover a role for microRNAs in limiting the spatiotemporal range of morphogen expression and function. Wnt1 is a key morphogen in the embryonic midbrain, and directs proliferation, survival, patterning and neurogenesis. We reveal an autoregulatory negative feedback loop between the transcription factor Lmx1b and a newly characterized microRNA, miR135a2, which modulates the extent of Wnt1/Wnt signaling and the size of the dopamine progenitor domain. Conditional gain of function studies reveal that Lmx1b promotes Wnt1/Wnt signaling, and thereby increases midbrain size and dopamine progenitor allocation. Conditional removal of Lmx1b has the opposite effect, in that expansion of the dopamine progenitor domain is severely compromised. Next, we provide evidence that microRNAs are involved in restricting dopamine progenitor allocation. Conditional loss of Dicer1 in embryonic stem cells (ESCs results in expanded Lmx1a/b+ progenitors. In contrast, forced elevation of miR135a2 during an early window in vivo phenocopies the Lmx1b conditional knockout. When En1::Cre, but not Shh::Cre or Nes::Cre, is used for recombination, the expansion of Lmx1a/b+ progenitors is selectively reduced. Bioinformatics and luciferase assay data suggests that miR135a2 targets Lmx1b and many genes in the Wnt signaling pathway, including Ccnd1, Gsk3b, and Tcf7l2. Consistent with this, we demonstrate that this mutant displays reductions in the size of the Lmx1b/Wnt1 domain and range of canonical Wnt signaling. We posit that microRNA modulation of the Lmx1b/Wnt axis in the early midbrain/isthmus could determine midbrain size and allocation of dopamine progenitors. Since canonical Wnt activity has recently been recognized as a key
DEFF Research Database (Denmark)
Parish, Clare L; Castelo-Branco, Gonçalo; Rawal, Nina
2008-01-01
have prevented their clinical application. We present here a method for generating large numbers of DA neurons based on expanding and differentiating ventral midbrain (VM) neural stem cells/progenitors in the presence of key signals necessary for VM DA neuron development. Mouse VM neurospheres (VMNs......Dopamine (DA) cell replacement therapy in Parkinson disease (PD) can be achieved using human fetal mesencephalic tissue; however, limited tissue availability has hindered further developments. Embryonic stem cells provide a promising alternative, but poor survival and risk of teratoma formation......) expanded with FGF2, differentiated with sonic hedgehog and FGF8, and transfected with Wnt5a (VMN-Wnt5a) generated 10-fold more DA neurons than did conventional FGF2-treated VMNs. VMN-Wnt5a cells exhibited the transcriptional and biochemical profiles and intrinsic electrophysiological properties of midbrain...
Aizawa, Hidenori; Bianco, Isaac H; Hamaoka, Takanori; Miyashita, Toshio; Uemura, Osamu; Concha, Miguel L; Russell, Claire; Wilson, Stephen W; Okamoto, Hitoshi
2005-02-08
The habenulae are part of an evolutionarily highly conserved limbic-system conduction pathway that connects telencephalic nuclei to the interpeduncular nucleus (IPN) of the midbrain . In zebrafish, unilateral activation of the Nodal signaling pathway in the left brain specifies the laterality of the asymmetry of habenular size . We show "laterotopy" in the habenulo-interpeduncular projection in zebrafish, i.e., the stereotypic, topographic projection of left-sided habenular axons to the dorsal region of the IPN and of right-sided habenular axons to the ventral IPN. This asymmetric projection is accounted for by a prominent left-right (LR) difference in the size ratio of the medial and lateral habenular sub-nuclei, each of which specifically projects either to ventral or dorsal IPN targets. Asymmetric Nodal signaling directs the orientation of laterotopy but is dispensable for the establishment of laterotopy itself. Our results reveal a mechanism by which information distributed between left and right sides of the brain can be transmitted bilaterally without loss of LR coding, which may play a crucial role in functional lateralization of the vertebrate brain .
Joutsa, Juho; Johansson, Jarkko; Seppänen, Marko; Noponen, Tommi; Kaasinen, Valtteri
2015-07-01
Loss of nigrostriatal neurons leading to dopamine depletion in the dorsal striatum is the pathologic hallmark of Parkinson disease contributing to the primary motor symptoms of the disease. However, Parkinson pathology is more widespread in the brain, affecting also other dopaminergic pathways and neurotransmitter systems, but these changes are less well characterized. This study aimed to investigate the mesencephalic striatal and extrastriatal dopaminergic projections together with extrastriatal serotonin transporter binding in Parkinson disease. Two hundred sixteen patients with Parkinson disease and 204 control patients (patients without neurodegenerative parkinsonism syndromes and normal SPECT imaging) were investigated with SPECT using the dopamine/serotonin transporter ligand (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ((123)I-FP-CIT) in the clinical setting. The group differences and midbrain correlations were analyzed voxel by voxel over the entire brain. We found that Parkinson patients had lower (123)I-FP-CIT uptake in the striatum and ventral midbrain but higher uptake in the thalamus and raphe nuclei than control patients. In patients with Parkinson disease, the correlation of the midbrain tracer uptake was shifted from the putamen to widespread corticolimbic areas. All findings were highly significant at the voxel level familywise error-corrected P value of less than 0.05. Our findings show that Parkinson disease is associated not only with the degeneration of the nigrostriatal dopamine neurotransmission, but also with a parallel shift toward mesolimbic and mesocortical function. Furthermore, Parkinson disease patients seem to have upregulation of brain serotonin transporter function at the early phase of the disease. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
International Nuclear Information System (INIS)
Edman, Linda C.; Mira, Helena; Arenas, Ernest
2008-01-01
β-chemokines are secreted factors that regulate diverse functions in the adult brain, such as neuro-immune responses and neurotransmission, but their function in the developing brain is largely unknown. We recently found that the orphan nuclear receptor, Nurr1, up regulates CCL2 and CCL7 in neural stem cells, suggesting a possible function of β-chemokines in midbrain development. Here we report that two β-chemokines, CCL2 and CCL7, and two of their receptors, CCR1 and CCR2, are expressed and developmentally regulated in the ventral midbrain (VM). Moreover, we found that the expression of CCL7 was down regulated in the Nurr1 knockout mice, linking CCL7 to dopamine (DA) neuron development. When the function of CCL2 and CCL7 was examined, we found that they selectively enhanced the differentiation of Nurr1+ precursors into DA neurons, but not their survival or progenitor proliferation in primary precursor cultures. Moreover, both CCL2 and CCL7 promoted neuritogenesis in midbrain DA neuron cultures. Thus, our results show for the first time a function of β-chemokines in the developing brain and identify β-chemokines as novel class of pro-differentiation factors for midbrain DA neurons. These data also suggest that β-chemokines may become useful tools to enhance the differentiation of DA cell preparations for cell replacement therapy and drug discovery in Parkinson's disease (PD)
Chung, Chee Yeun; Licznerski, Pawel; Alavian, Kambiz N.; Simeone, Antonio; Lin, Zhicheng; Martin, Eden; Vance, Jeffery; Isacson, Ole
2010-01-01
Two adjacent groups of midbrain dopaminergic neurons, A9 (substantia nigra pars compacta) and A10 (ventral tegmental area), have distinct projections and exhibit differential vulnerability in Parkinson's disease. Little is known about transcription factors that influence midbrain dopaminergic subgroup phenotypes or their potential role in disease.…
Directory of Open Access Journals (Sweden)
Agnete Kirkeby
2012-06-01
Full Text Available To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.
Schott, Bjorn H.; Sellner, Daniela B.; Lauer, Corinna-J.; Habib, Reza; Frey, Julietta U.; Guderian, Sebastian; Heinze, Hans-Jochen; Duzel, Emrah
2004-01-01
Recent evidence suggests a close functional relationship between memory formation in the hippocampus and dopaminergic neuromodulation originating in the ventral tegmental area and medial substantia nigra of the midbrain. Here we report midbrain activation in two functional MRI studies of visual memory in healthy young adults. In the first study,…
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Florian Wegner
Full Text Available BACKGROUND: Human fetal midbrain-derived neural progenitor cells (NPCs may deliver a tissue source for drug screening and regenerative cell therapy to treat Parkinson's disease. While glutamate and GABA(A receptors play an important role in neurogenesis, the involvement of glycine receptors during human neurogenesis and dopaminergic differentiation as well as their molecular and functional characteristics in NPCs are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated NPCs in respect to their glycine receptor function and subunit expression using electrophysiology, calcium imaging, immunocytochemistry, and quantitative real-time PCR. Whole-cell recordings demonstrate the ability of NPCs to express functional strychnine-sensitive glycine receptors after differentiation for 3 weeks in vitro. Pharmacological and molecular analyses indicate a predominance of glycine receptor heteromers containing α2β subunits. Intracellular calcium measurements of differentiated NPCs suggest that glycine evokes depolarisations mediated by strychnine-sensitive glycine receptors and not by D-serine-sensitive excitatory glycine receptors. Culturing NPCs with additional glycine, the glycine-receptor antagonist strychnine, or the Na(+-K(+-Cl(- co-transporter 1 (NKCC1-inhibitor bumetanide did not significantly influence cell proliferation and differentiation in vitro. CONCLUSIONS/SIGNIFICANCE: These data indicate that NPCs derived from human fetal midbrain tissue acquire essential glycine receptor properties during neuronal maturation. However, glycine receptors seem to have a limited functional impact on neurogenesis and dopaminergic differentiation of NPCs in vitro.
Schott, Björn H; Sellner, Daniela B; Lauer, Corinna-J; Habib, Reza; Frey, Julietta U; Guderian, Sebastian; Heinze, Hans-Jochen; Düzel, Emrah
2004-01-01
Recent evidence suggests a close functional relationship between memory formation in the hippocampus and dopaminergic neuromodulation originating in the ventral tegmental area and medial substantia nigra of the midbrain. Here we report midbrain activation in two functional MRI studies of visual memory in healthy young adults. In the first study, participants distinguished between familiar and novel configurations of pairs of items which had been studied together by either learning the location or the identity of the items. In the second study, participants studied words by either rating the words' pleasantness or counting syllables. The ventral tegmental area and medial substantia nigra showed increased activation by associative novelty (first study) and subsequent free recall performance (second study). In both studies, this activation accompanied hippocampal activation, but was unaffected by the study task. Thus midbrain regions seem to participate selectively in hippocampus-dependent processes of associative novelty and explicit memory formation, but appear to be unaffected by other task-relevant aspects.
Fukusumi, Yoshiyasu; Meier, Florian; Götz, Sebastian; Matheus, Friederike; Irmler, Martin; Beckervordersandforth, Ruth; Faus-Kessler, Theresa; Minina, Eleonora; Rauser, Benedict; Zhang, Jingzhong; Arenas, Ernest; Andersson, Elisabet; Niehrs, Christof; Beckers, Johannes; Simeone, Antonio; Wurst, Wolfgang; Prakash, Nilima
2015-09-30
Wingless-related MMTV integration site 1 (WNT1)/β-catenin signaling plays a crucial role in the generation of mesodiencephalic dopaminergic (mdDA) neurons, including the substantia nigra pars compacta (SNc) subpopulation that preferentially degenerates in Parkinson's disease (PD). However, the precise functions of WNT1/β-catenin signaling in this context remain unknown. Stem cell-based regenerative (transplantation) therapies for PD have not been implemented widely in the clinical context, among other reasons because of the heterogeneity and incomplete differentiation of the transplanted cells. This might result in tumor formation and poor integration of the transplanted cells into the dopaminergic circuitry of the brain. Dickkopf 3 (DKK3) is a secreted glycoprotein implicated in the modulation of WNT/β-catenin signaling. Using mutant mice, primary ventral midbrain cells, and pluripotent stem cells, we show that DKK3 is necessary and sufficient for the correct differentiation of a rostrolateral mdDA neuron subset. Dkk3 transcription in the murine ventral midbrain coincides with the onset of mdDA neurogenesis and is required for the activation and/or maintenance of LMX1A (LIM homeobox transcription factor 1α) and PITX3 (paired-like homeodomain transcription factor 3) expression in the corresponding mdDA precursor subset, without affecting the proliferation or specification of their progenitors. Notably, the treatment of differentiating pluripotent stem cells with recombinant DKK3 and WNT1 proteins also increases the proportion of mdDA neurons with molecular SNc DA cell characteristics in these cultures. The specific effects of DKK3 on the differentiation of rostrolateral mdDA neurons in the murine ventral midbrain, together with its known prosurvival and anti-tumorigenic properties, make it a good candidate for the improvement of regenerative and neuroprotective strategies in the treatment of PD. Significance statement: We show here that Dickkopf 3 (DKK3), a
Grison, Alice; Gaiser, Carine; Bieder, Andrea; Baranek, Constanze; Atanasoski, Suzana
2018-03-23
Little is known about the molecular players driving proliferation of neural progenitor cells (NPCs) during embryonic mouse development. Here, we demonstrate that proliferation of NPCs in the developing forebrain depends on a particular combination of cell cycle regulators. We have analyzed the requirements for members of the cyclin-dependent kinase (cdk) family using cdk-deficient mice. In the absence of either cdk4 or cdk6, which are both regulators of the G1 phase of the cell cycle, we found no significant effects on the proliferation rate of cortical progenitor cells. However, concomitant loss of cdk4 and cdk6 led to a drastic decrease in the proliferation rate of NPCs, specifically the basal progenitor cells of both the dorsal and ventral forebrain at embryonic day 13.5 (E13.5). Moreover, basal progenitors in the forebrain of Cdk4;Cdk6 double mutant mice exhibited altered cell cycle characteristics. Cdk4;cdk6 deficiency led to an increase in cell cycle length and cell cycle exit of mutant basal progenitor cells in comparison to controls. In contrast, concomitant ablation of cdk2 and cdk6 had no effect on the proliferation of NCPs. Together, our data demonstrate that the expansion of the basal progenitor pool in the developing telencephalon is dependent on the presence of distinct combinations of cdk molecules. Our results provide further evidence for differences in the regulation of proliferation between apical and basal progenitors during cortical development. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.
Opioid receptors in midbrain dopaminergic regions of the rat. 1. Mu receptor autoradiography
International Nuclear Information System (INIS)
German, D.C.; Speciale, S.G.; Manaye, K.F.; Sadeq, M.
1993-01-01
Several lines of evidence indicate that an interaction exists between opioid peptides and midbrain dopaminergic neurons. The purpose of this study was to map and quantify the density of the mu opioid receptor subtype relative to the location of the dopaminergic (DA) neurons in the retrorubral field (nucleus A8), substantia nigra (nucleus A9), and ventral tegmental area and related nuclei (nucleus A10) in the rat. Sections through the rostral-caudal extent of the midbrain were stained with an antibody against tyrosine hydroxylase, as a DA cell marker, and comparable sections were processed for in vitro receptor autoradiography using the mu-selective ligand, 3 H-Tyr-D-Ala-N-MePhe-Gyl-ol enkephalin. In the nucleus A8 region, there were low levels of mu binding. In the rostral portion of nucleus A9, there was prominent mu binding both in the ventral pars compacta, which contains numerous DA neurons, and in regions that correspond to the location of the DA dendrites which project ventrally into the underlying substantia nigra pars reticulata. In the caudal portion of nucleus A9, mu binding was greatest in the substantia nigra pars reticulata, but also in the same region that contains DA neurons. In nucleus A10, mu receptor densities differed depending upon the nucleus A10 subdivision, and the rostral-caudal position in the nucleus. Low receptor densities were observed in rostral portions of the ventral tegmental area and interfascicular nucleus, and there was negligible binding in the parabrachial pigmented nucleus and paranigral nucleus at the level of the interpeduncular nucleus; all regions where there are high densities of DA somata. Mu binding was relatively high in the central linear nucleus, and in the dorsal and medial divisions of the medial terminal nucleus of the accessory optic system, which has been shown to contain DA dendrites. These data indicate that mu opioid receptors are located in certain regions occupied by all three midbrain DA nuclei, but in a
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Hideaki Yamamoto
Full Text Available Adherens junctions (AJs play a role in mechanically connecting adjacent cells to maintain tissue structure, particularly in epithelial cells. The major cell-cell adhesion molecules at AJs are cadherins and nectins. Afadin binds to both nectins and α-catenin and recruits the cadherin-β-catenin complex to the nectin-based cell-cell adhesion site to form AJs. To explore the role of afadin in radial glial and ependymal cells in the brain, we generated mice carrying a nestin-Cre-mediated conditional knockout (cKO of the afadin gene. Newborn afadin-cKO mice developed hydrocephalus and died neonatally. The afadin-cKO brain displayed enlarged lateral ventricles and cerebral aqueduct, resulting from stenosis of the caudal end of the cerebral aqueduct and obliteration of the ventral part of the third ventricle. Afadin deficiency further caused the loss of ependymal cells from the ventricular and aqueductal surfaces. During development, radial glial cells, which terminally differentiate into ependymal cells, scattered from the ventricular zone and were replaced by neurons that eventually covered the ventricular and aqueductal surfaces of the afadin-cKO midbrain. Moreover, the denuded ependymal cells were only occasionally observed in the third ventricle and the cerebral aqueduct of the afadin-cKO midbrain. Afadin was co-localized with nectin-1 and N-cadherin at AJs of radial glial and ependymal cells in the control midbrain, but these proteins were not concentrated at AJs in the afadin-cKO midbrain. Thus, the defects in the afadin-cKO midbrain most likely resulted from the destruction of AJs, because AJs in the midbrain were already established before afadin was genetically deleted. These results indicate that afadin is essential for the maintenance of AJs in radial glial and ependymal cells in the midbrain and is required for normal morphogenesis of the cerebral aqueduct and ventral third ventricle in the midbrain.
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Christine Esslinger
Full Text Available INTRODUCTION: Metacognition, i.e. critically reflecting on and monitoring one's own reasoning, has been linked behaviorally to the emergence of delusions and is a focus of cognitive therapy in patients with schizophrenia. However, little is known about the neural processing underlying metacognitive function. To address this issue, we studied brain activity during a modified beads task which has been used to measure a "Jumping to Conclusions" (JTC bias in schizophrenia patients. METHODS: We used functional magnetic resonance imaging to identify neural systems active in twenty-five healthy subjects when solving a modified version of the "beads task", which requires a probabilistic decision after a variable amount of data has been requested by the participants. We assessed brain activation over the duration of a trial and at the time point of decision making. RESULTS: Analysis of activation during the whole process of probabilistic reasoning showed an extended network including the prefronto-parietal executive functioning network as well as medial parieto-occipital regions. During the decision process alone, activity in midbrain and ventral striatum was detected, as well as in thalamus, medial occipital cortex and anterior insula. CONCLUSIONS: Our data show that probabilistic reasoning shares neural substrates with executive functions. In addition, our finding that brain regions commonly associated with salience processing are active during probabilistic reasoning identifies a candidate mechanism that could underlie the behavioral link between dopamine-dependent aberrant salience and JTC in schizophrenia. Further studies with delusional schizophrenia patients will have to be performed to substantiate this link.
Reward and aversion in a heterogeneous midbrain dopamine system.
Lammel, Stephan; Lim, Byung Kook; Malenka, Robert C
2014-01-01
The ventral tegmental area (VTA) is a heterogeneous brain structure that serves a central role in motivation and reward processing. Abnormalities in the function of VTA dopamine (DA) neurons and the targets they influence are implicated in several prominent neuropsychiatric disorders including addiction and depression. Recent studies suggest that the midbrain DA system is composed of anatomically and functionally heterogeneous DA subpopulations with different axonal projections. These findings may explain a number of previously confusing observations that suggested a role for DA in processing both rewarding as well as aversive events. Here we will focus on recent advances in understanding the neural circuits mediating reward and aversion in the VTA and how stress as well as drugs of abuse, in particular cocaine, alter circuit function within a heterogeneous midbrain DA system. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.
Drumming with dopamine neurons : Resonance and synchronization in the Ventral Tegmental Area
van der Velden, L.J.J.
2018-01-01
The ventral tegmental area (VTA) is a dopaminergic nucleus in the midbrain with the propensity to exhibit spontaneous intrinsic rhythmic activity in the 1-5 Hz frequency range (ex vivo). Here, we combine in-vitro simultaneous action potential recording from a 60 channel multi-electro-array with
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Moeller, Scott J.; Tomasi, Dardo; Woicik, Patricia A.; Maloney, Thomas; Alia-Klein, Nelly; Honorio, Jean; Telang, Frank; Wang, Gene-Jack; Wang, Ruiliang; Sinha, Rajita; Carise, Deni; Astone-Twerell, Janetta; Bolger, Joy; Volkow, Nora D.; Goldstein, Rita Z.
2012-03-28
Drug addiction is characterized by dysregulated dopamine neurotransmission. Although dopamine functioning appears to partially recover with abstinence, the specific regions that recover and potential impact on drug seeking remain to be determined. Here we used functional magnetic resonance imaging (fMRI) to study an ecologically valid sample of 15 treatment-seeking cocaine addicted individuals at baseline and 6-month follow-up. At both study sessions, we collected fMRI scans during performance of a drug Stroop task, clinical self-report measures of addiction severity and behavioral measures of cocaine seeking (simulated cocaine choice); actual drug use in between the two study sessions was also monitored. At 6-month follow-up (compared with baseline), we predicted functional enhancement of dopaminergically innervated brain regions, relevant to the behavioral responsiveness toward salient stimuli. Consistent with predictions, whole-brain analyses revealed responses in the midbrain (encompassing the ventral tegmental area/substantia nigra complex) and thalamus (encompassing the mediodorsal nucleus) that were higher (and more positively correlated) at follow-up than baseline. Increased midbrain activity from baseline to follow-up correlated with reduced simulated cocaine choice, indicating that heightened midbrain activations in this context may be marking lower approach motivation for cocaine. Normalization of midbrain function at follow-up was also suggested by exploratory comparisons with active cocaine users and healthy controls (who were assessed only at baseline). Enhanced self-control at follow-up was suggested by a trend for the commonly hypoactive dorsal anterior cingulate cortex to increase response during a drug-related context. Together, these results suggest that fMRI could be useful in sensitively tracking follow-up outcomes in drug addiction.
Perez, Yvan; Rieger, Verena; Martin, Elise; Müller, Carsten H G; Harzsch, Steffen
2013-05-01
Emerging evidence suggests that Chaetognatha represent an evolutionary lineage that is the sister group to all other Protostomia thus promoting these animals as a pivotal model for our understanding of bilaterian evolutionary history. We have analyzed the proliferation of neuronal progenitor cells in the developing ventral nerve center (VNC) of Spadella cephaloptera hatchlings. To that end, for the first time in Chaetognatha, we performed in vivo incorporation experiments with the S-phase specific mitosis marker bromodeoxyuridine (BrdU). Our experiments provide evidence for a high level of mitotic activity in the VNC for ca. 3 days after hatching. Neurogenesis is carried by presumptive neuronal progenitor cells that cycle rapidly and most likely divide asymmetrically. These progenitors are arranged in a distinct grid-like geometrical pattern including about 35 transverse rows. Considering Chaetognaths to be an early offshoot of the protostome lineage we conclude that the presence of neuronal progenitor cells with asymmetric division seems to be a feature that is rooted deeply in the Metazoa. In the light of previous evidence indicating the presence of serially iterated peptidergic neurons with individual identities in the chaetognath VNC, we discuss if these neuronal progenitor cells give rise to distinct lineages. Furthermore, we evaluate the serially iterated arrangement of the progenitor cells in the light of evolution of segmentation. Copyright © 2013 Wiley Periodicals, Inc.
DEFF Research Database (Denmark)
Christophersen, Nicolai S.; Gronborg, Mette; Petersen, Thomas Nordahl
2007-01-01
upregulation with increased positive staining of cell bodies in the SNc and fibers in the striatum. Analysis of the developmental regulation of Dlk1 in the murine ventral midbrain showed that the upregulation of Dlk1 mRNA correlated with the generation of tyrosine hydroxylase (TH)-positive neurons. Furthermore...
Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions
Directory of Open Access Journals (Sweden)
Alvarez-Bolado Gonzalo
2012-01-01
Full Text Available Abstract Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E9.5 contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia. Progenitors labeled at later stages (after E9.5 give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly
Directory of Open Access Journals (Sweden)
Daisuke Doi
2014-03-01
Full Text Available Human induced pluripotent stem cells (iPSCs can provide a promising source of midbrain dopaminergic (DA neurons for cell replacement therapy for Parkinson’s disease. However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. Here, we show that human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, CORIN. We induced DA neurons using scalable culture conditions on human laminin fragment, and the sorted CORIN+ cells expressed the midbrain DA progenitor markers, FOXA2 and LMX1A. When transplanted into 6-OHDA-lesioned rats, the CORIN+ cells survived and differentiated into midbrain DA neurons in vivo, resulting in significant improvement of the motor behavior, without tumor formation. In particular, the CORIN+ cells in a NURR1+ cell-dominant stage exhibited the best survival and function as DA neurons. Our method is a favorable strategy in terms of scalability, safety, and efficiency and may be advantageous for clinical application.
Čajánek, Lukáš; Ganji, Ranjani Sri; Henriques-Oliveira, Catarina; Theofilopoulos, Spyridon; Koník, Peter
2013-01-01
Understanding the mechanisms that drive the differentiation of dopaminergic (DA) neurons is crucial for successful development of novel therapies for Parkinson's disease, in which DA neurons progressively degenerate. However, the mechanisms underlying the differentiation-promoting effects of Wnt5a on DA precursors are poorly understood. Here, we present the molecular and functional characterization of a signaling pathway downstream of Wnt5a, the Wnt/Dvl/Rac1 pathway. First, we characterize the interaction between Rac1 and Dvl and identify the N-terminal part of Dvl3 as necessary for Rac1 binding. Next, we show that Tiam1, a Rac1 guanosine exchange factor (GEF), is expressed in the ventral midbrain, interacts with Dvl, facilitates Dvl-Rac1 interaction, and is required for Dvl- or Wnt5a-induced activation of Rac1. Moreover, we show that Wnt5a promotes whereas casein kinase 1 (CK1), a negative regulator of the Wnt/Dvl/Rac1 pathway, abolishes the interactions between Dvl and Tiam1. Finally, using ventral midbrain neurosphere cultures, we demonstrate that the generation of DA neurons in culture is impaired after Tiam1 knockdown, indicating that Tiam1 is required for midbrain DA differentiation. In summary, our data identify Tiam1 as a novel regulator of DA neuron development and as a Dvl-associated and Rac1-specific GEF acting in the Wnt/Dvl/Rac1 pathway. PMID:23109420
Azimi, Sayyed M; Sheridan, Steven D; Ghannad-Rezaie, Mostafa; Eimon, Peter M; Yanik, Mehmet Fatih
2018-05-01
Identification of optimal transcription-factor expression patterns to direct cellular differentiation along a desired pathway presents significant challenges. We demonstrate massively combinatorial screening of temporally-varying mRNA transcription factors to direct differentiation of neural progenitor cells using a dynamically-reconfigurable magnetically-guided spotting technology for localizing mRNA, enabling experiments on millimetre size spots. In addition, we present a time-interleaved delivery method that dramatically reduces fluctuations in the delivered transcription-factor copy-numbers per cell. We screened combinatorial and temporal delivery of a pool of midbrain-specific transcription factors to augment the generation of dopaminergic neurons. We show that the combinatorial delivery of LMX1A, FOXA2 and PITX3 is highly effective in generating dopaminergic neurons from midbrain progenitors. We show that LMX1A significantly increases TH -expression levels when delivered to neural progenitor cells either during proliferation or after induction of neural differentiation, while FOXA2 and PITX3 increase expression only when delivered prior to induction, demonstrating temporal dependence of factor addition. © 2018, Azimi et al.
Kutejova, Eva; Sasai, Noriaki; Shah, Ankita; Gouti, Mina; Briscoe, James
2016-03-21
In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
L’Episcopo, Francesca; Tirolo, Cataldo; Testa, Nunzio; Caniglia, Salvatore; Morale, Maria Concetta; Serapide, Maria Francesca; Pluchino, Stefano; Marchetti, Bianca
2014-01-01
SUMMARY Wnt/β-catenin signaling is required for specification and neurogenesis of midbrain dopaminergic (mDA) neurons, the pivotal neuronal population that degenerates in Parkinson’s disease (PD) and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Wnt/β-catenin signaling plays a vital role in adult neurogenesis but whether it might engage DA neurogenesis/neurorepair in the affected PD brain is yet unresolved. Recently, the adult midbrain aqueduct periventricular regions (Aq-PVRs) were shown to harbor neural stem/progenitor cells (mNPCs) with DA potential in vitro, but restrictive mechanisms in vivo are believed to limit their DA regenerative capacity. Using in vitro mNPC culture systems we herein demonstrate that aging is one most critical factor restricting mNPC neurogenic potential via dysregulation of Wnt/β-catenin signaling. Cococulture paradigms between young/aged (Y/A) mNPCs and Y/A astrocytes identified glial age and a decline of glial-derived factors including Wnts as key determinants of impaired neurogenic potential, whereas Wnt activation regimens efficiently reversed the diminished proliferative, neuronal and DA differentiation potential of A-mNPCs. Next, in vivo studies in wild (Wt) and transgenic β-catenin reporter mice uncovered Wnt/β-catenin signaling activation and remarkable astrocyte remodeling of Aq-PVR in response to MPTP-induced DA neuron death. Spatio-temporal analyses unveiled β-catenin signaling in predopaminergic (Nurr1+/TH−) and imperiled or rescuing DAT+ neurons during MPTP-induced DA neuron injury and self-repair. Aging inhibited Wnt signaling, whereas β-catenin activation in situ with a specific GSK-3β antagonist promoted a significant degree of DA neurorestoration associated with reversal of motor deficit, with implications for neurorestorative approaches in PD. PMID:24648001
Czech Academy of Sciences Publication Activity Database
Andersson, E.R.; Salto, C.; Villaescusa, J.C.; Cajanek, L.; Yang, S.; Bryjová, Lenka; Nagy, I.I.; Vainio, S.J.; Ramírez, C.; Bryja, Vítězslav; Arenas, E.
2013-01-01
Roč. 110, č. 7 (2013), E602-E610 ISSN 0027-8424 Grant - others:GA ČR(CZ) GA204/09/0498; GA ČR(CZ) GAP301/11/0747 Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : VENTRAL MIDBRAIN * PARKINSONS-DISEASE * BETA-CATENIN Subject RIV: BO - Biophysics Impact factor: 9.809, year: 2013
Lovrics, Anna; Gao, Yu; Juhá sz, Bianka; Bock, Istvá n; Byrne, Helen M; Dinnyé s, Andrá s; Ková cs, Krisztiá n A
2014-01-01
with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where
Evidence of functional duplicity of Nestin expression in the adult mouse midbrain
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Parisa Farzanehfar
2017-03-01
Full Text Available Whether or not neurogenesis occurs in the adult substantia nigra pars compacta (SNc is an important question relevant for developing better treatments for the motor symptoms of Parkinson's disease (PD. Although controversial, it is generally believed that dividing cells here remain undifferentiated or differentiate into glia, not neurons. However, there is a suggestion that Nestin-expressing neural precursor cells (NPCs in the adult SNc have a propensity to differentiate into neurons, which we sought to confirm in the present study. Adult (>8-weeks old transgenic NesCreERT2/GtROSA or NesCreERT2/R26eYFP mice were used to permanently label Nestin-expressing cells and their progeny with β-galactosidase (β-gal or enhanced yellow fluorescent protein (eYFP, respectively. Most β-gal+ or eYFP+ cells were found in the ependymal lining of the midbrain aqueduct (Aq and in the midline ventral to Aq. Smaller but significant numbers were in the periaqueductal gray (PAG, the ventral tegmental area (VTA, and in SNc. Low-level basal proliferation was evidenced by a modest increase in number of β-gal+ or eYFP+ cells over time, fewer β-gal+ or eYFP+ cells when mice were administered the anti-mitotic agent Cytarabine, and incorporation of the proliferation marker bromodeoxyuridine (BrdU in a very small number of β-gal+ cells. No evidence of migration was found, including no immunoreactivity against the migration markers doublecortin (DCX or polysialic acid neural cell adhesion molecule (PSA-NCAM, and no dispersal of β-gal+ or eYFP+ cells through the midbrain parenchyma over time. However, β-gal+ or eYFP+ cells did increase in size and express higher levels of mature neuronal genes over time, indicating growth and neuronal differentiation. In mice whose SNc dopamine neurons had been depleted with 6-hydroxy-dopamine, a model of PD, there were ~2-fold more β-gal+ cells in SNc specifically, although the proportion that were also NeuN+ was not affected
Viereckel, Thomas; Dumas, Sylvie; Smith-Anttila, Casey J A; Vlcek, Bianca; Bimpisidis, Zisis; Lagerström, Malin C; Konradsson-Geuken, Åsa; Wallén-Mackenzie, Åsa
2016-10-20
The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) of the midbrain are associated with Parkinson's disease (PD), schizophrenia, mood disorders and addiction. Based on the recently unraveled heterogeneity within the VTA and SNc, where glutamate, GABA and co-releasing neurons have been found to co-exist with the classical dopamine neurons, there is a compelling need for identification of gene expression patterns that represent this heterogeneity and that are of value for development of human therapies. Here, several unique gene expression patterns were identified in the mouse midbrain of which NeuroD6 and Grp were expressed within different dopaminergic subpopulations of the VTA, and TrpV1 within a small heterogeneous population. Optogenetics-coupled in vivo amperometry revealed a previously unknown glutamatergic mesoaccumbal pathway characterized by TrpV1-Cre-expression. Human GRP was strongly detected in non-melanized dopaminergic neurons within the SNc of both control and PD brains, suggesting GRP as a marker for neuroprotected neurons in PD. This study thus unravels markers for distinct subpopulations of neurons within the mouse and human midbrain, defines unique anatomical subregions within the VTA and exposes an entirely new glutamatergic pathway. Finally, both TRPV1 and GRP are implied in midbrain physiology of importance to neurological and neuropsychiatric disorders.
Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation.
Ravindran, Ethiraj; Hu, Hao; Yuzwa, Scott A; Hernandez-Miranda, Luis R; Kraemer, Nadine; Ninnemann, Olaf; Musante, Luciana; Boltshauser, Eugen; Schindler, Detlev; Hübner, Angela; Reinecker, Hans-Christian; Ropers, Hans-Hilger; Birchmeier, Carmen; Miller, Freda D; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M
2017-04-01
Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures. Rho guanine nucleotide exchange factor (ARHGEF) family members are key for controlling the spatiotemporal activation of Rho GTPase, to modulate cytoskeleton dynamics, cell division, and cell migration. We identified, by means of whole exome sequencing, a homozygous frameshift mutation in the ARHGEF2 as a cause of intellectual disability, a midbrain-hindbrain malformation, and mild microcephaly in a consanguineous pedigree of Kurdish-Turkish descent. We show that loss of ARHGEF2 perturbs progenitor cell differentiation and that this is associated with a shift of mitotic spindle plane orientation, putatively favoring more symmetric divisions. The ARHGEF2 mutation leads to reduction in the activation of the RhoA/ROCK/MLC pathway crucial for cell migration. We demonstrate that the human brain malformation is recapitulated in Arhgef2 mutant mice and identify an aberrant migration of distinct components of the precerebellar system as a pathomechanism underlying the midbrain-hindbrain phenotype. Our results highlight the crucial function of ARHGEF2 in human brain development and identify a mutation in ARHGEF2 as novel cause of a neurodevelopmental disorder.
Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation
Yuzwa, Scott A.; Hernandez-Miranda, Luis R.; Musante, Luciana; Boltshauser, Eugen; Schindler, Detlev; Hübner, Angela; Reinecker, Hans-Christian; Ropers, Hans-Hilger; Miller, Freda D.; Hübner, Christoph; Kaindl, Angela M.
2017-01-01
Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures. Rho guanine nucleotide exchange factor (ARHGEF) family members are key for controlling the spatiotemporal activation of Rho GTPase, to modulate cytoskeleton dynamics, cell division, and cell migration. We identified, by means of whole exome sequencing, a homozygous frameshift mutation in the ARHGEF2 as a cause of intellectual disability, a midbrain-hindbrain malformation, and mild microcephaly in a consanguineous pedigree of Kurdish-Turkish descent. We show that loss of ARHGEF2 perturbs progenitor cell differentiation and that this is associated with a shift of mitotic spindle plane orientation, putatively favoring more symmetric divisions. The ARHGEF2 mutation leads to reduction in the activation of the RhoA/ROCK/MLC pathway crucial for cell migration. We demonstrate that the human brain malformation is recapitulated in Arhgef2 mutant mice and identify an aberrant migration of distinct components of the precerebellar system as a pathomechanism underlying the midbrain-hindbrain phenotype. Our results highlight the crucial function of ARHGEF2 in human brain development and identify a mutation in ARHGEF2 as novel cause of a neurodevelopmental disorder. PMID:28453519
Viereckel, Thomas; Dumas, Sylvie; Smith-Anttila, Casey J. A.; Vlcek, Bianca; Bimpisidis, Zisis; Lagerström, Malin C.; Konradsson-Geuken, Åsa; Wallén-Mackenzie, Åsa
2016-01-01
The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) of the midbrain are associated with Parkinson’s disease (PD), schizophrenia, mood disorders and addiction. Based on the recently unraveled heterogeneity within the VTA and SNc, where glutamate, GABA and co-releasing neurons have been found to co-exist with the classical dopamine neurons, there is a compelling need for identification of gene expression patterns that represent this heterogeneity and that are of value for development of human therapies. Here, several unique gene expression patterns were identified in the mouse midbrain of which NeuroD6 and Grp were expressed within different dopaminergic subpopulations of the VTA, and TrpV1 within a small heterogeneous population. Optogenetics-coupled in vivo amperometry revealed a previously unknown glutamatergic mesoaccumbal pathway characterized by TrpV1-Cre-expression. Human GRP was strongly detected in non-melanized dopaminergic neurons within the SNc of both control and PD brains, suggesting GRP as a marker for neuroprotected neurons in PD. This study thus unravels markers for distinct subpopulations of neurons within the mouse and human midbrain, defines unique anatomical subregions within the VTA and exposes an entirely new glutamatergic pathway. Finally, both TRPV1 and GRP are implied in midbrain physiology of importance to neurological and neuropsychiatric disorders. PMID:27762319
Heimovics, Sarah A; Salvante, Katrina G; Sockman, Keith W; Riters, Lauren V
2011-01-01
Individuals display dramatic differences in social communication even within similar social contexts. Across vertebrates dopaminergic projections from the ventral tegmental area (VTA) and midbrain central gray (GCt) strongly influence motivated, reward-directed behaviors. Norepinephrine is also rich in these areas and may alter dopamine neuronal activity. The present study was designed to provide insight into the roles of dopamine and norepinephrine in VTA and GCt and their efferent striatal ...
Viereckel, Thomas; Dumas, Sylvie; Smith-Anttila, Casey J. A.; Vlcek, Bianca; Bimpisidis, Zisis; Lagerstr?m, Malin C.; Konradsson-Geuken, ?sa; Wall?n-Mackenzie, ?sa
2016-01-01
The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) of the midbrain are associated with Parkinson's disease (PD), schizophrenia, mood disorders and addiction. Based on the recently unraveled heterogeneity within the VTA and SNc, where glutamate, GABA and co-releasing neurons have been found to co-exist with the classical dopamine neurons, there is a compelling need for identification of gene expression patterns that represent this heterogeneity and that are of value for ...
Hierarchical prediction errors in midbrain and septum during social learning.
Diaconescu, Andreea O; Mathys, Christoph; Weber, Lilian A E; Kasper, Lars; Mauer, Jan; Stephan, Klaas E
2017-04-01
Social learning is fundamental to human interactions, yet its computational and physiological mechanisms are not well understood. One prominent open question concerns the role of neuromodulatory transmitters. We combined fMRI, computational modelling and genetics to address this question in two separate samples (N = 35, N = 47). Participants played a game requiring inference on an adviser's intentions whose motivation to help or mislead changed over time. Our analyses suggest that hierarchically structured belief updates about current advice validity and the adviser's trustworthiness, respectively, depend on different neuromodulatory systems. Low-level prediction errors (PEs) about advice accuracy not only activated regions known to support 'theory of mind', but also the dopaminergic midbrain. Furthermore, PE responses in ventral striatum were influenced by the Met/Val polymorphism of the Catechol-O-Methyltransferase (COMT) gene. By contrast, high-level PEs ('expected uncertainty') about the adviser's fidelity activated the cholinergic septum. These findings, replicated in both samples, have important implications: They suggest that social learning rests on hierarchically related PEs encoded by midbrain and septum activity, respectively, in the same manner as other forms of learning under volatility. Furthermore, these hierarchical PEs may be broadcast by dopaminergic and cholinergic projections to induce plasticity specifically in cortical areas known to represent beliefs about others. © The Author (2017). Published by Oxford University Press.
Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation.
Directory of Open Access Journals (Sweden)
Ethiraj Ravindran
2017-04-01
Full Text Available Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures. Rho guanine nucleotide exchange factor (ARHGEF family members are key for controlling the spatiotemporal activation of Rho GTPase, to modulate cytoskeleton dynamics, cell division, and cell migration. We identified, by means of whole exome sequencing, a homozygous frameshift mutation in the ARHGEF2 as a cause of intellectual disability, a midbrain-hindbrain malformation, and mild microcephaly in a consanguineous pedigree of Kurdish-Turkish descent. We show that loss of ARHGEF2 perturbs progenitor cell differentiation and that this is associated with a shift of mitotic spindle plane orientation, putatively favoring more symmetric divisions. The ARHGEF2 mutation leads to reduction in the activation of the RhoA/ROCK/MLC pathway crucial for cell migration. We demonstrate that the human brain malformation is recapitulated in Arhgef2 mutant mice and identify an aberrant migration of distinct components of the precerebellar system as a pathomechanism underlying the midbrain-hindbrain phenotype. Our results highlight the crucial function of ARHGEF2 in human brain development and identify a mutation in ARHGEF2 as novel cause of a neurodevelopmental disorder.
Focal midbrain tumors in children
Vandertop, W. P.; Hoffman, H. J.; Drake, J. M.; Humphreys, R. P.; Rutka, J. T.; Amstrong, D. C.; Becker, L. E.
1992-01-01
The clinical and neuroradiological features of focal midbrain tumors in 12 children are described, and the results of their surgical management are presented. Patients with a focal midbrain tumor usually exhibit either symptoms and signs of raised intracranial pressure caused by an obstructive
Directory of Open Access Journals (Sweden)
Marcy A Kingsbury
Full Text Available In mammals, rostrocaudal columns of the midbrain periaqueductal gray (PAG regulate diverse behavioral and physiological functions, including sexual and fight-or-flight behavior, but homologous columns have not been identified in non-mammalian species. In contrast to mammals, in which the PAG lies ventral to the superior colliculus and surrounds the cerebral aqueduct, birds exhibit a hypertrophied tectum that is displaced laterally, and thus the midbrain central gray (CG extends mediolaterally rather than dorsoventrally as in mammals. We therefore hypothesized that the avian CG is organized much like a folded open PAG. To address this hypothesis, we conducted immunohistochemical comparisons of the midbrains of mice and finches, as well as Fos studies of aggressive dominance, subordinance, non-social defense and sexual behavior in territorial and gregarious finch species. We obtained excellent support for our predictions based on the folded open model of the PAG and further showed that birds possess functional and anatomical zones that form longitudinal columns similar to those in mammals. However, distinguishing characteristics of the dorsal/dorsolateral PAG, such as a dense peptidergic innervation, a longitudinal column of neuronal nitric oxide synthase neurons, and aggression-induced Fos responses, do not lie within the classical avian CG, but in the laterally adjacent intercollicular nucleus (ICo, suggesting that much of the ICo is homologous to the dorsal PAG.
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.
Eisch, A.J.; Bolanos, C.A.; de Wit, J.; Simonak, R.D.; Pudiak, C.M.; Barrot, M.; Verhaagen, J.; Nestler, E.J.
2003-01-01
Background: Previous work has shown that brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), are involved in appetitive behavior. Here we show that BDNF in the ventral tegmental area-nucleus accumbens (VTA-NAc) pathway is also involved in the development of
Pathological Laughter as a Symptom of Midbrain Infarction
Dabby, Ron; Watemberg, Nathan; Lampl, Yair; Eilam, Anda; Rapaport, Abraham; Sadeh, Menachem
2004-01-01
Pathological laughter is an uncommon symptom usually caused by bilateral, diffuse cerebral lesions. It has rarely been reported in association with isolated cerebral lesions. Midbrain involvement causing pathological laughter is extremely unusual. We describe three patients who developed pathological laughter after midbrain and pontine-midbrain infarction. In two patients a small infarction in the left paramedian midbrain was detected, whereas the third one sustained a massive bilateral pontine infarction extending to the midbrain. Laughter heralded stroke by one day in one patient and occurred as a delayed phenomenon three months after stroke in another. Pathological laughter ceased within a few days in two patients and was still present at a two year follow-up in the patient with delayed-onset laughter. Pathological laughter can herald midbrain infarction or follow stroke either shortly after onset of symptoms or as a delayed phenomenon. Furthermore, small unilateral midbrain infarctions can cause this rare complication. PMID:15706050
MRI characteristics of midbrain tumours
International Nuclear Information System (INIS)
Sun, B.; Wang, C.C.; Wang, J.
1999-01-01
We diagnosed 60 cases of midbrain tumours by MRI between 1993 to 1997. There were 39 males and 21 females, aged 2-64 years, mean 25.6 years. We found 38 patients with true intramedullary midbrain tumours, 11 predominantly in the tectum, 20 in the tegmentum and 7 with a downward extension to the pons; there were 7 within the cerebral aqueduct. There were 22 patients with infiltrating midbrain tumours extending from adjacent structures, 11 cases each from the thalamus and pineal region. All patients received surgical treatment. Gross total resection was achieved in 42 cases, subtotal (> 75 %) resection in 18. Pathological diagnoses included 16 low-grade and 15 high-grade astrocytomas; 5 oligodendroastrocytomas; 2 ependymomas; 11 glioblastomas; and 11 pineal parenchymal or germ-cell tumours. Midbrain tumours are a heterogeneous group of neoplasms, with wide variation in clinical and MRI features, related to the site and type of tumour. MRI not only allows precise analysis of their growth pattern, but also can lead to a correct preoperative diagnosis in the majority of cases. (orig.) (orig.)
DEFF Research Database (Denmark)
Rice, M E; Richards, C D; Nedergaard, S
1994-01-01
Fast-scan cyclic voltammetry with carbon fibre microelectrodes was used to detect endogenous dopamine (DA) and 5-hydroxytryptamine (5-HT) release from three distinct regions of guinea-pig mid-brain in vitro: rostral and caudal substantia nigra (SN) and the ventral tegmental area (VTA). Previous...... these regions with in situ electrodes and demonstrates the utility of fast-scan cyclic voltammetry to investigate the mechanisms and possible non-classical functions of somato-dendritic DA release....
Isolated trochlear nerve palsy with midbrain hemorrhage
Directory of Open Access Journals (Sweden)
Raghavendra S
2010-01-01
Full Text Available Midbrain hemorrhage causing isolated fourth nerve palsy is extremely rare. Idiopathic, traumatic and congenital abnormalities are the most common causes of fourth nerve palsy. We report acute isolated fourth nerve palsy in an 18-year-old lady due to a midbrain hemorrhage probably due to a midbrain cavernoma. The case highlights the need for neuroimaging in selected cases of isolated trochlear nerve palsy.
Lovrics, Anna
2014-11-14
We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.
DEFF Research Database (Denmark)
Christiansen, Mia Apuschkin; Stilling, Sara; Rahbek-Clemmensen, Troels
2015-01-01
Midbrain dopaminergic (DAergic) neurons are a heterogeneous cell group, composed of functionally distinct cell populations projecting to the basal ganglia, prefrontal cortex and limbic system. Despite their functional significance, the midbrain population of DAergic neurons is sparse, constituting...... of the dopamine transporter (DAT) promoter was characterized. Confocal microscopy analysis of brain sections showed strong eGFP signal reporter in midbrain regions and striatal terminals that co-localized with the DAergic markers DAT and tyrosine hydroxylase (TH). Thorough quantification of co...
Identification of distinct telencephalic progenitor pools for neuronal diversity in the amygdala.
Hirata, Tsutomu; Li, Peijun; Lanuza, Guillermo M; Cocas, Laura A; Huntsman, Molly M; Corbin, Joshua G
2009-02-01
The development of the amygdala, a central structure of the limbic system, remains poorly understood. We found that two spatially distinct and early-specified telencephalic progenitor pools marked by the homeodomain transcription factor Dbx1 are major sources of neuronal cell diversity in the mature mouse amygdala. We found that Dbx1-positive cells of the ventral pallium generate the excitatory neurons of the basolateral complex and cortical amygdala nuclei. Moreover, Dbx1-derived cells comprise a previously unknown migratory stream that emanates from the preoptic area (POA), a ventral telencephalic domain adjacent to the diencephalic border. The Dbx1-positive, POA-derived population migrated specifically to the amygdala and, as defined by both immunochemical and electrophysiological criteria, generated a unique subclass of inhibitory neurons in the medial amygdala nucleus. Thus, this POA-derived population represents a previously unknown progenitor pool dedicated to the limbic system.
Directory of Open Access Journals (Sweden)
Angela Jinsook Oh
2018-06-01
Full Text Available Purpose: Midline structural defects in the neural axis can give rise to neuro-ophthalmic symptoms. We report a rare case of keyhole aqueduct syndrome presenting after two years of severe cough due to gastroesophageal reflux disease. Observations: A 58-year-old woman with a 2-year history of daily, severe cough presented to the neuro-ophthalmology clinic with progressive diplopia and oscillopsia. Examination revealed a 1–2 Hz down-beating nystagmus in primary gaze that worsened with left, right, and down gazes. Gaze evoked nystagmus and mild paresis were also seen with up gaze. There was an incomitant left hypertropia due to skew deviation that worsened with right and up gazes and improved with down gaze. She also had a right-sided ptosis and a 3 mm anisocoria not due to cranial nerve 3 paresis or Horner's syndrome. Brain magnetic resonance imaging showed a 1.5 mm × 11.7 mm × 6 mm midline cleft in the ventral midbrain communicating with the cerebral aqueduct, consistent with keyhole aqueduct syndrome. Her nystagmus and diplopia improved with oral acetazolamide treatment, at high doses of 2500–3000 mg per day. Conclusions and importance: We report the first case of midbrain keyhole aqueduct syndrome with ocular motor and other neuro-ophthalmic manifestations associated with severe cough. Although her cough was effectively treated and intracranial pressure measurement was normal, her ophthalmic symptoms continued to progress, which is common in previous cases reported. Treatment with acetazolamide led to significant improvement, supporting the use of acetazolamide in this rare condition. Keywords: Keyhole aqueduct syndrome, Midbrain cleft, Mesencephalic cleft, Syrinx, Syringobulbia, Down-beating nystagmus, Cerebrospinal fluid
Interneuron progenitor transplantation to treat CNS dysfunction
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Muhammad O Chohan
2016-08-01
Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.
Safety and tolerability of MRI-guided infusion of AAV2-hAADC into the mid-brain of nonhuman primate
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Waldy San Sebastian
2014-01-01
Full Text Available Aromatic L-amino acid decarboxylase (AADC deficiency is a rare, autosomal-recessive neurological disorder caused by mutations in the DDC gene that leads to an inability to synthesize catecholamines and serotonin. As a result, patients suffer compromised development, particularly in motor function. A recent gene replacement clinical trial explored putaminal delivery of recombinant adeno-associated virus serotype 2 vector encoding human AADC (AAV2-hAADC in AADC-deficient children. Unfortunately, patients presented only modest amelioration of motor symptoms, which authors acknowledged could be due to insufficient transduction of putamen. We hypothesize that, with the development of a highly accurate MRI-guided cannula placement technology, a more effective approach might be to target the affected mid-brain neurons directly. Transduction of AADC-deficient dopaminergic neurons in the substantia nigra and ventral tegmental area with locally infused AAV2-hAADC would be expected to lead to restoration of normal dopamine levels in affected children. The objective of this study was to assess the long-term safety and tolerability of bilateral AAV2-hAADC MRI-guided pressurized infusion into the mid-brain of nonhuman primates. Animals received either vehicle, low or high AAV2-hAADC vector dose and were euthanized 1, 3, or 9 months after surgery. Our data indicate that effective mid-brain transduction was achieved without untoward effects.
Thawani, Ankita; Sirohi, Devika; Kuhn, Richard J; Fekete, Donna M
2018-04-17
Zika virus (ZIKV) is associated with severe neurodevelopmental impairments in human fetuses, including microencephaly. Previous reports examining neural progenitor tropism of ZIKV in organoid and animal models did not address whether the virus infects all neural progenitors uniformly. To explore this, ZIKV was injected into the neural tube of 2-day-old chicken embryos, resulting in nonuniform periventricular infection 3 days later. Recurrent foci of intense infection were present at specific signaling centers that influence neuroepithelial patterning at a distance through secretion of morphogens. ZIKV infection reduced transcript levels for 3 morphogens, SHH, BMP7, and FGF8 expressed at the midbrain basal plate, hypothalamic floor plate, and isthmus, respectively. Levels of Patched1, a SHH-pathway downstream gene, were also reduced, and a SHH-dependent cell population in the ventral midbrain was shifted in position. Thus, the diminishment of signaling centers through ZIKV-mediated apoptosis may yield broader, non-cell-autonomous changes in brain patterning. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Glutamate neurons are intermixed with midbrain dopamine neurons in nonhuman primates and humans
Root, David H.; Wang, Hui-Ling; Liu, Bing; Barker, David J.; Mód, László; Szocsics, Péter; Silva, Afonso C.; Maglóczky, Zsófia; Morales, Marisela
2016-01-01
The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. Here, we revealed VGluT2 neurons within the VTA and SNC of nonhuman primates and humans by simultaneous detection of VGluT2 mRNA and tyrosine hydroxylase (TH; for identification of dopamine neurons). We found that several VTA subdivisions share similar cellular compositions in nonhuman primates and humans; their rostral linear nuclei have a high prevalence of VGluT2 neurons lacking TH; their paranigral and parabrachial pigmented nuclei have mostly TH neurons, and their parabrachial pigmented nuclei have dual VGluT2-TH neurons. Within nonhuman primates and humans SNC, the vast majority of neurons are TH neurons but VGluT2 neurons were detected in the pars lateralis subdivision. The demonstration that midbrain dopamine neurons are intermixed with glutamate or glutamate-dopamine neurons from rodents to humans offers new opportunities for translational studies towards analyzing the roles that each of these neurons play in human behavior and in midbrain-associated illnesses such as addiction, depression, schizophrenia, and Parkinson’s disease. PMID:27477243
Midbrain morphology reflects extent of brain damage in Krabbe disease
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Zuccoli, Giulio; Narayanan, Srikala; Panigrahy, Ashok; Poe, Michele D.; Escolar, Maria L.
2015-01-01
To study the relationships between midbrain morphology, Loes score, gross motor function, and cognitive function in infantile Krabbe disease. Magnetic resonance imaging (MRI) scans were evaluated by two neuroradiologists blinded to clinical status and neurodevelopmental function of children with early or late infantile Krabbe disease. A simplified qualitative 3-point scoring system based on midbrain morphology on midsagittal MRI was used. A score of 0 represented normal convex morphology of the midbrain, a score of 1 represented flattening of the midbrain, and a score of 3 represented concave morphology of the midbrain (hummingbird sign). Spearman correlations were estimated between this simplified MRI scoring system and the Loes score, gross motor score, and cognitive score. Forty-two MRIs of 27 subjects were reviewed. Analysis of the 42 scans showed normal midbrain morphology in 3 (7.1 %) scans, midbrain flattening in 11 (26.2 %) scans, and concave midbrain morphology (hummingbird sign) in 28 (66.7 %) scans. Midbrain morphology scores were positively correlated with the Loes score (r = 0.81, p < 0.001) and negatively correlated with both gross motor and cognitive scores (r = -.84, p < 0.001; r = -0.87, p < 0.001, respectively). The inter-rater reliability for the midbrain morphology scale was κ =.95 (95 % CI: 0.86-1.0), and the inter-rater reliability for the Loes scale was κ =.58 (95 % CI: 0.42-0.73). Midbrain morphology scores of midsagittal MRI images correlates with cognition and gross motor function in children with Krabbe disease. This MRI scoring system represents a simple but reliable method to assess disease progression in patients with infantile Krabbe disease. (orig.)
Midbrain morphology reflects extent of brain damage in Krabbe disease
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Zuccoli, Giulio; Narayanan, Srikala; Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Section of Neuroradiology, Pittsburgh, PA (United States); Poe, Michele D.; Escolar, Maria L. [University of Pittsburgh, Program for the Study of Neurodevelopment in Rare Disorders, Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA (United States)
2015-07-15
To study the relationships between midbrain morphology, Loes score, gross motor function, and cognitive function in infantile Krabbe disease. Magnetic resonance imaging (MRI) scans were evaluated by two neuroradiologists blinded to clinical status and neurodevelopmental function of children with early or late infantile Krabbe disease. A simplified qualitative 3-point scoring system based on midbrain morphology on midsagittal MRI was used. A score of 0 represented normal convex morphology of the midbrain, a score of 1 represented flattening of the midbrain, and a score of 3 represented concave morphology of the midbrain (hummingbird sign). Spearman correlations were estimated between this simplified MRI scoring system and the Loes score, gross motor score, and cognitive score. Forty-two MRIs of 27 subjects were reviewed. Analysis of the 42 scans showed normal midbrain morphology in 3 (7.1 %) scans, midbrain flattening in 11 (26.2 %) scans, and concave midbrain morphology (hummingbird sign) in 28 (66.7 %) scans. Midbrain morphology scores were positively correlated with the Loes score (r = 0.81, p < 0.001) and negatively correlated with both gross motor and cognitive scores (r = -.84, p < 0.001; r = -0.87, p < 0.001, respectively). The inter-rater reliability for the midbrain morphology scale was κ =.95 (95 % CI: 0.86-1.0), and the inter-rater reliability for the Loes scale was κ =.58 (95 % CI: 0.42-0.73). Midbrain morphology scores of midsagittal MRI images correlates with cognition and gross motor function in children with Krabbe disease. This MRI scoring system represents a simple but reliable method to assess disease progression in patients with infantile Krabbe disease. (orig.)
Tlx controls proliferation and patterning of lateral telencephalic progenitor domains.
Stenman, Jan M; Wang, Bei; Campbell, Kenneth
2003-11-19
We showed previously that the orphan nuclear receptor Tlx is required for the correct establishment of the pallio-subpallial boundary. Loss of Tlx results in a dorsal expansion of ventral markers (e.g., the homeodomain protein GSH2) into the ventralmost pallial region, i.e., the ventral pallium. We also observed a disproportionate reduction in the size of the Tlx mutant lateral ganglionic eminence (LGE) from embryonic day 14.5 onward. Here we show that this reduction is caused, at least in large part, by a proliferation defect. Interestingly, in Tlx mutants, the LGE derivatives are differentially affected. Although the development of the Tlx mutant striatum is compromised, an apparently normal number of olfactory bulb interneurons are observed. Consistent with this observation, we found that Tlx is required for the normal establishment of the ventral LGE that gives rise to striatal projection neurons. This domain is reduced by the dorsal and ventral expansion of molecular markers normally confined to progenitor domains flanking the ventral LGE. Finally, we investigated possible genetic interactions between Gsh2 and Tlx in lateral telencephalic development. Our results show that, although Gsh2 and Tlx have additive effects on striatal development, they differentially regulate the establishment of ventral pallial identity.
Directory of Open Access Journals (Sweden)
Daniela Lehnen
2017-10-01
Full Text Available Human pluripotent stem cell (hPSC-derived mesencephalic dopaminergic (mesDA neurons can relieve motor deficits in animal models of Parkinson's disease (PD. Clinical translation of differentiation protocols requires standardization of production procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-associated protein (IAP is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP+ mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA neurons in vitro. Intrastriatal transplantation of IAP+ cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP+ mesDA progenitors were more homogeneous in size and DA neuron density. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clinical cell replacement strategies.
Martínez, Constanza; Cornejo, Víctor Hugo; Lois, Pablo; Ellis, Tammy; Solis, Natalia P; Wainwright, Brandon J; Palma, Verónica
2013-01-01
The Sonic Hedgehog (Shh) pathway is responsible for critical patterning events early in development and for regulating the delicate balance between proliferation and differentiation in the developing and adult vertebrate brain. Currently, our knowledge of the potential role of Shh in regulating neural stem cells (NSC) is largely derived from analyses of the mammalian forebrain, but for dorsal midbrain development it is mostly unknown. For a detailed understanding of the role of Shh pathway for midbrain development in vivo, we took advantage of mouse embryos with cell autonomously activated Hedgehog (Hh) signaling in a conditional Patched 1 (Ptc1) mutant mouse model. This animal model shows an extensive embryonic tectal hypertrophy as a result of Hh pathway activation. In order to reveal the cellular and molecular origin of this in vivo phenotype, we established a novel culture system to evaluate neurospheres (nsps) viability, proliferation and differentiation. By recreating the three-dimensional (3-D) microenvironment we highlight the pivotal role of endogenous Shh in maintaining the stem cell potential of tectal radial glial cells (RGC) and progenitors by modulating their Ptc1 expression. We demonstrate that during late embryogenesis Shh enhances proliferation of NSC, whereas blockage of endogenous Shh signaling using cyclopamine, a potent Hh pathway inhibitor, produces the opposite effect. We propose that canonical Shh signaling plays a central role in the control of NSC behavior in the developing dorsal midbrain by acting as a niche factor by partially mediating the response of NSC to epidermal growth factor (EGF) and fibroblast growth factor (FGF) signaling. We conclude that endogenous Shh signaling is a critical mechanism regulating the proliferation of stem cell lineages in the embryonic dorsal tissue.
Ascending Midbrain Dopaminergic Axons Require Descending GAD65 Axon Fascicles for Normal Pathfinding
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Claudia Marcela Garcia-Peña
2014-06-01
Full Text Available The Nigrostriatal pathway (NSP is formed by dopaminergic axons that project from the ventral midbrain to the dorsolateral striatum as part of the medial forebrain bundle. Previous studies have implicated chemotropic proteins in the formation of the NSP during development but little is known of the role of substrate-anchored signals in this process. We observed in mouse and rat embryos that midbrain dopaminergic axons ascend in close apposition to descending GAD65-positive axon bundles throughout their trajectory to the striatum. To test whether such interaction is important for dopaminergic axon pathfinding, we analyzed transgenic mouse embryos in which the GAD65 axon bundle was reduced by the conditional expression of the diphtheria toxin. In these embryos we observed dopaminergic misprojection into the hypothalamic region and abnormal projection in the striatum. In addition, analysis of Robo1/2 and Slit1/2 knockout embryos revealed that the previously described dopaminergic misprojection in these embryos is accompanied by severe alterations in the GAD65 axon scaffold. Additional studies with cultured dopaminergic neurons and whole embryos suggest that NCAM and Robo proteins are involved in the interaction of GAD65 and dopaminergic axons. These results indicate that the fasciculation between descending GAD65 axon bundles and ascending dopaminergic axons is required for the stereotypical NSP formation during brain development and that known guidance cues may determine this projection indirectly by instructing the pathfinding of the axons that are part of the GAD65 axon scaffold.
Taniguchi, Daisuke; Hatano, Taku; Kamagata, Koji; Okuzumi, Ayami; Oji, Yutaka; Mori, Akio; Hori, Masaaki; Aoki, Shigeki; Hattori, Nobutaka
2018-05-14
Background Nigral degeneration patterns differ between PSP and PD. However, the relationship between nigral degeneration and midbrain atrophy in PSP remains unclear. Objective We analyzed differences and relationships between nigral degeneration and midbrain atrophy in PSP and PD. Methods Neuromelanin-sensitive MRI and midbrain volumetry were performed in 11 PSP patients, 24 PD patients, and 10 controls to measure the neuromelanin-sensitive SNpc area and midbrain volume. Results The neuromelanin-sensitive SNpc area and midbrain volume were significantly smaller in PSP patients compared with PD patients and controls. Motor deficits were inversely correlated with neuromelanin-sensitive SNpc area in PD, but not PSP patients. There was no significant correlation between neuromelanin-sensitive SNpc area and midbrain volume in either disease group. Midbrain volumetry discriminated PSP from PD. Diagnostic accuracy was improved when neuromelanin-sensitive MRI analysis was added. Conclusions Neuromelanin-sensitive MRI and midbrain volumetry may reflect the clinical and pathological characteristics of PSP and PD. Combining neuromelanin-sensitive MRI and midbrain volumetry may be useful for differentiating PSP from PD. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.
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Palminteri, Enzo; Berdondini, Elisa; Fusco, Ferdinando; De Nunzio, Cosimo; Giannitsas, Kostas; Shokeir, Ahmed A
2012-06-01
To investigate the versatility of the ventral urethrotomy approach in bulbar reconstruction with buccal mucosa (BM) grafts placed on the dorsal, ventral or dorsal plus ventral urethral surface. Between 1999 and 2008, 216 patients with bulbar strictures underwent BM graft urethroplasty using the ventral-sagittal urethrotomy approach. Of these patients, 32 (14.8%; mean stricture 3.2 cm, range 1.5-5) had a dorsal graft urethroplasty (DGU), 121 (56%; mean stricture 3.7, range 1.5-8) a ventral graft urethroplasty (VGU), and 63 (29.2%; mean stricture 3.4, range 1.5-10) a dorsal plus ventral graft urethroplasty (DVGU). The strictured urethra was opened by a ventral-sagittal urethrotomy and BM graft was inserted dorsally or ventrally or dorsal plus ventral to augment the urethral plate. The median follow-up was 37 months. The overall 5-year actuarial success rate was 91.4%. The 5-year actuarial success rates were 87.8%, 95.5% and 86.3% for the DGU, VGU and DVGU, respectively. There were no statistically significant differences among the three groups. Success rates decreased significantly only with a stricture length of >4 cm. In BM graft bulbar urethroplasties the ventral urethrotomy access is simple and versatile, allowing an intraoperative choice of dorsal, ventral or combined dorsal and ventral grafting, with comparable success rates.
Electrical stimulation of the midbrain excites the auditory cortex asymmetrically.
Quass, Gunnar Lennart; Kurt, Simone; Hildebrandt, Jannis; Kral, Andrej
2018-05-17
Auditory midbrain implant users cannot achieve open speech perception and have limited frequency resolution. It remains unclear whether the spread of excitation contributes to this issue and how much it can be compensated by current-focusing, which is an effective approach in cochlear implants. The present study examined the spread of excitation in the cortex elicited by electric midbrain stimulation. We further tested whether current-focusing via bipolar and tripolar stimulation is effective with electric midbrain stimulation and whether these modes hold any advantage over monopolar stimulation also in conditions when the stimulation electrodes are in direct contact with the target tissue. Using penetrating multielectrode arrays, we recorded cortical population responses to single pulse electric midbrain stimulation in 10 ketamine/xylazine anesthetized mice. We compared monopolar, bipolar, and tripolar stimulation configurations with regard to the spread of excitation and the characteristic frequency difference between the stimulation/recording electrodes. The cortical responses were distributed asymmetrically around the characteristic frequency of the stimulated midbrain region with a strong activation in regions tuned up to one octave higher. We found no significant differences between monopolar, bipolar, and tripolar stimulation in threshold, evoked firing rate, or dynamic range. The cortical responses to electric midbrain stimulation are biased towards higher tonotopic frequencies. Current-focusing is not effective in direct contact electrical stimulation. Electrode maps should account for the asymmetrical spread of excitation when fitting auditory midbrain implants by shifting the frequency-bands downward and stimulating as dorsally as possible. Copyright © 2018 Elsevier Inc. All rights reserved.
VMAT2-mediated neurotransmission from midbrain leptin receptor neurons in feeding regulation
Leptin receptors (LepRs) expressed in the midbrain contribute to the action of leptin on feeding regulation. The midbrain neurons release a variety of neurotransmitters including dopamine (DA), glutamate and GABA. However, which neurotransmitter mediates midbrain leptin action on feeding remains unc...
Lehnen, Daniela; Barral, Serena; Cardoso, Tiago; Grealish, Shane; Heuer, Andreas; Smiyakin, Andrej; Kirkeby, Agnete; Kollet, Jutta; Cremer, Harold; Parmar, Malin; Bosio, Andreas; Knöbel, Sebastian
2017-10-10
Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clinical translation of differentiation protocols requires standardization of production procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-associated protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP + mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA) neurons in vitro. Intrastriatal transplantation of IAP + cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP + mesDA progenitors were more homogeneous in size and DA neuron density. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clinical cell replacement strategies. Copyright © 2017 Miltenyi Biotec GmbH. Published by Elsevier Inc. All rights reserved.
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File list: NoD.Neu.50.AllAg.Midbrain [Chip-atlas[Archive
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Oh, Angela Jinsook; Lanzman, Bryan Alexander; Liao, Yaping Joyce
2018-06-01
Midline structural defects in the neural axis can give rise to neuro-ophthalmic symptoms. We report a rare case of keyhole aqueduct syndrome presenting after two years of severe cough due to gastroesophageal reflux disease. A 58-year-old woman with a 2-year history of daily, severe cough presented to the neuro-ophthalmology clinic with progressive diplopia and oscillopsia. Examination revealed a 1-2 Hz down-beating nystagmus in primary gaze that worsened with left, right, and down gazes. Gaze evoked nystagmus and mild paresis were also seen with up gaze. There was an incomitant left hypertropia due to skew deviation that worsened with right and up gazes and improved with down gaze. She also had a right-sided ptosis and a 3 mm anisocoria not due to cranial nerve 3 paresis or Horner's syndrome. Brain magnetic resonance imaging showed a 1.5 mm × 11.7 mm × 6 mm midline cleft in the ventral midbrain communicating with the cerebral aqueduct, consistent with keyhole aqueduct syndrome. Her nystagmus and diplopia improved with oral acetazolamide treatment, at high doses of 2500-3000 mg per day. We report the first case of midbrain keyhole aqueduct syndrome with ocular motor and other neuro-ophthalmic manifestations associated with severe cough. Although her cough was effectively treated and intracranial pressure measurement was normal, her ophthalmic symptoms continued to progress, which is common in previous cases reported. Treatment with acetazolamide led to significant improvement, supporting the use of acetazolamide in this rare condition.
Lüer, Karin; Technau, Gerhard M
2009-08-03
The Drosophila embryonic central nervous system (CNS) develops from two sets of progenitor cells, neuroblasts and ventral midline progenitors, which behave differently in many respects. Neuroblasts derive from the neurogenic region of the ectoderm and form the lateral parts of the CNS. Ventral midline precursors are formed by two rows of mesectodermal cells and build the CNS midline. There is plenty of evidence that individual identities are conferred to precursor cells by positional information in the ectoderm. It is unclear, however, how far the precursors can maintain their identities and developmental properties in the absence of normal external signals. To separate the respective contributions of autonomous properties versus extrinsic signals during their further development, we isolated individual midline precursors and neuroectodermal precursors at the pre-mitotic gastrula stage, traced their development in vitro, and analyzed the characteristics of their lineages in comparison with those described for the embryo. Although individually cultured mesectodermal cells exhibit basic characteristics of CNS midline progenitors, the clones produced by these progenitors differ from their in situ counterparts with regard to cell numbers, expression of molecular markers, and the separation of neuronal and glial fate. In contrast, clones derived from individually cultured precursors taken from specific dorsoventral zones of the neuroectoderm develop striking similarities to the lineages of neuroblasts that normally delaminate from these zones and develop in situ. This in vitro analysis allows for the first time a comparison of the developmental capacities in situ and in vitro of individual neural precursors of defined spatial and temporal origin. The data reveal that cells isolated at the pre-mitotic and pre-delamination stage express characteristics of the progenitor type appropriate to their site of origin in the embryo. However, presumptive neuroblasts, once
Lecca, Salvatore; Melis, Miriam; Luchicchi, Antonio; Ennas, Maria Grazia; Castelli, Maria Paola; Muntoni, Anna Lisa; Pistis, Marco
2011-02-01
Recent findings have underlined the rostromedial tegmental nucleus (RMTg), a structure located caudally to the ventral tegmental area, as an important site involved in the mechanisms of aversion. RMTg contains γ-aminobutyric acid neurons responding to noxious stimuli, densely innervated by the lateral habenula and providing a major inhibitory projection to reward-encoding midbrain dopamine (DA) neurons. One of the key features of drug addiction is the perseverance of drug seeking in spite of negative and unpleasant consequences, likely mediated by response suppression within neural pathways mediating aversion. To investigate whether the RMTg has a function in the mechanisms of addicting drugs, we studied acute effects of morphine, cocaine, the cannabinoid agonist WIN55212-2 (WIN), and nicotine on putative RMTg neurons. We utilized single unit extracellular recordings in anesthetized rats and whole-cell patch-clamp recordings in brain slices to identify and characterize putative RMTg neurons and their responses to drugs of abuse. Morphine and WIN inhibited both firing rate in vivo and excitatory postsynaptic currents (EPSCs) evoked by stimulation of rostral afferents in vitro, whereas cocaine inhibited discharge activity without affecting EPSC amplitude. Conversely, nicotine robustly excited putative RMTg neurons and enhanced EPSCs, an effect mediated by α7-containing nicotinic acetylcholine receptors. Our results suggest that activity of RMTg neurons is profoundly influenced by drugs of abuse and, as important inhibitory afferents to midbrain DA neurons, they might take place in the complex interplay between the neural circuits mediating aversion and reward.
Rausch, Vanessa H; Bauch, Eva M; Bunzeck, Nico
2014-07-01
In neural systems, information processing can be facilitated by adding an optimal level of white noise. Although this phenomenon, the so-called stochastic resonance, has traditionally been linked with perception, recent evidence indicates that white noise may also exert positive effects on cognitive functions, such as learning and memory. The underlying neural mechanisms, however, remain unclear. Here, on the basis of recent theories, we tested the hypothesis that auditory white noise, when presented during the encoding of scene images, enhances subsequent recognition memory performance and modulates activity within the dopaminergic midbrain (i.e., substantia nigra/ventral tegmental area, SN/VTA). Indeed, in a behavioral experiment, we can show in healthy humans that auditory white noise-but not control sounds, such as a sinus tone-slightly improves recognition memory. In an fMRI experiment, white noise selectively enhances stimulus-driven phasic activity in the SN/VTA and auditory cortex. Moreover, it induces stronger connectivity between SN/VTA and right STS, which, in addition, exhibited a positive correlation with subsequent memory improvement by white noise. Our results suggest that the beneficial effects of auditory white noise on learning depend on dopaminergic neuromodulation and enhanced connectivity between midbrain regions and the STS-a key player in attention modulation. Moreover, they indicate that white noise could be particularly useful to facilitate learning in conditions where changes of the mesolimbic system are causally related to memory deficits including healthy and pathological aging.
Glucose modulates food-related salience coding of midbrain neurons in humans.
Ulrich, Martin; Endres, Felix; Kölle, Markus; Adolph, Oliver; Widenhorn-Müller, Katharina; Grön, Georg
2016-12-01
Although early rat studies demonstrated that administration of glucose diminishes dopaminergic midbrain activity, evidence in humans has been lacking so far. In the present functional magnetic resonance imaging study, glucose was intravenously infused in healthy human male participants while seeing images depicting low-caloric food (LC), high-caloric food (HC), and non-food (NF) during a food/NF discrimination task. Analysis of brain activation focused on the ventral tegmental area (VTA) as the origin of the mesolimbic system involved in salience coding. Under unmodulated fasting baseline conditions, VTA activation was greater during HC compared with LC food cues. Subsequent to infusion of glucose, this difference in VTA activation as a function of caloric load leveled off and even reversed. In a control group not receiving glucose, VTA activation during HC relative to LC cues remained stable throughout the course of the experiment. Similar treatment-specific patterns of brain activation were observed for the hypothalamus. The present findings show for the first time in humans that glucose infusion modulates salience coding mediated by the VTA. Hum Brain Mapp 37:4376-4384, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Cognitive Neurostimulation: Learning to Volitionally Sustain Ventral Tegmental Area Activation.
MacInnes, Jeff J; Dickerson, Kathryn C; Chen, Nan-Kuei; Adcock, R Alison
2016-03-16
Activation of the ventral tegmental area (VTA) and mesolimbic networks is essential to motivation, performance, and learning. Humans routinely attempt to motivate themselves, with unclear efficacy or impact on VTA networks. Using fMRI, we found untrained participants' motivational strategies failed to consistently activate VTA. After real-time VTA neurofeedback training, however, participants volitionally induced VTA activation without external aids, relative to baseline, Pre-test, and control groups. VTA self-activation was accompanied by increased mesolimbic network connectivity. Among two comparison groups (no neurofeedback, false neurofeedback) and an alternate neurofeedback group (nucleus accumbens), none sustained activation in target regions of interest nor increased VTA functional connectivity. The results comprise two novel demonstrations: learning and generalization after VTA neurofeedback training and the ability to sustain VTA activation without external reward or reward cues. These findings suggest theoretical alignment of ideas about motivation and midbrain physiology and the potential for generalizable interventions to improve performance and learning. Copyright © 2016 Elsevier Inc. All rights reserved.
Palminteri, Enzo; Berdondini, Elisa; Fusco, Ferdinando; Nunzio, Cosimo De; Giannitsas, Kostas; Shokeir, Ahmed A.
2012-01-01
Objectives To investigate the versatility of the ventral urethrotomy approach in bulbar reconstruction with buccal mucosa (BM) grafts placed on the dorsal, ventral or dorsal plus ventral urethral surface. Patients and methods Between 1999 and 2008, 216 patients with bulbar strictures underwent BM graft urethroplasty using the ventral-sagittal urethrotomy approach. Of these patients, 32 (14.8%; mean stricture 3.2?cm, range 1.5?5) had a dorsal graft urethroplasty (DGU), 121 (56%; mean stricture...
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Ksenija Zega
2017-11-01
Full Text Available Hydrocephalus can occur in children alone or in combination with other neurodevelopmental disorders that are often associated with brain overgrowth. Despite the severity of these disorders, the molecular and cellular mechanisms underlying these pathologies and their comorbidity are poorly understood. Here, we studied the consequences of genetically inactivating in mice dual-specificity phosphatase 16 (Dusp16, which is known to negatively regulate mitogen-activated protein kinases (MAPKs and which has never previously been implicated in brain development and disorders. Mouse mutants lacking a functional Dusp16 gene (Dusp16−/− developed fully-penetrant congenital obstructive hydrocephalus together with brain overgrowth. The midbrain aqueduct in Dusp16−/− mutants was obstructed during mid-gestation by an expansion of neural progenitors, and during later gestational stages by neurons resulting in a blockage of cerebrospinal fluid (CSF outflow. In contrast, the roof plate and ependymal cells developed normally. We identified a delayed cell cycle exit of neural progenitors in Dusp16−/− mutants as a cause of progenitor overproliferation during mid-gestation. At later gestational stages, this expanded neural progenitor pool generated an increased number of neurons associated with enlarged brain volume. Taken together, we found that Dusp16 plays a critical role in neurogenesis by balancing neural progenitor cell proliferation and neural differentiation. Moreover our results suggest that a lack of functional Dusp16 could play a central role in the molecular mechanisms linking brain overgrowth and hydrocephalus.
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Glenda E. Gillies
2016-12-01
Full Text Available Glucocorticoid hormones (GCs released from the fetal/maternal glands during late gestation are required for normal development of mammalian organs and tissues. Accordingly, synthetic glucocorticoids have proven to be invaluable in perinatal medicine where they are widely used to accelerate fetal lung maturation when there is risk of pre-term birth and to promote infant survival. However, clinical and pre-clinical studies have demonstrated that inappropriate exposure of the developing brain to elevated levels of GCs, either as a result of clinical over-use or after stress-induced activation of the fetal/maternal adrenal cortex, is linked with significant effects on brain structure, neurological function and behaviour in later life. In order to understand the underlying neural processes, particular interest has focused on the midbrain dopaminergic systems, which are critical regulators of normal adaptive behaviours, cognitive and sensorimotor functions. Specifically, using a rodent model of GC exposure in late gestation (approximating human brain development at late second/early third trimester, we demonstrated enduring effects on the shape and volume of the ventral tegmental area (VTA and substantia nigra pars compacta (SNc (origins of the mesocorticolimbic and nigrostriatal dopaminergic pathways on the topographical organisation and size of the dopaminergic neuronal populations and astrocytes within these nuclei and on target innervation density and neurochemical markers of dopaminergic transmission (receptors, transporters, basal and amphetamine-stimulated dopamine release at striatal and prefrontal cortical sites that impact on the adult brain. The effects of antenatal GC treatment (AGT were both profound and sexually-dimorphic, not only in terms of quantitative change but also qualitatively, with several parameters affected in the opposite direction in males and females. Although such substantial neurobiological changes might presage marked
Obstructive sleep apnea is associated with altered midbrain chemical concentrations.
Macey, Paul M; Sarma, Manoj K; Prasad, Janani P; Ogren, Jennifer A; Aysola, Ravi; Harper, Ronald M; Thomas, M Albert
2017-11-05
Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age±SD:54.6±10.6years; AHI:35.0±19.4; SAO 2 min:83±7%) and 26 healthy control (50.7±8.5years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting (ProFit) algorithm. The midbrain in OSA showed decreased N-acetylaspartate (NAA; OSA:1.24±0.43, Control:1.47±0.41; p=0.03; independent samples t-test), a marker of neuronal viability. Increased levels in OSA over control subjects appeared in glutamate (Glu; OSA:1.23±0.57, Control:0.98±0.33; p=0.03), ascorbate (Asc; OSA:0.56±0.28, Control:0.42±0.20; (50.7±8.5years; p=0.03), and myo-inositol (mI; OSA:0.96±0.48, Control:0.72±0.35; p=0.03). No differences between groups appeared in γ-aminobutyric acid (GABA) or taurine. The midbrain in OSA patients shows decreased NAA, indicating neuronal injury or dysfunction. Higher Glu levels may reflect excitotoxic processes and astrocyte activation, and higher mI is also consistent with glial activation. Higher Asc levels may result from oxidative stress induced by intermittent hypoxia in OSA. Additionally, Asc and Glu are involved with glutamatergic processes, which are likely upregulated in the midbrain nuclei of OSA patients. The altered metabolite levels help explain dysfunction and structural deficits in
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Technau Gerhard M
2009-08-01
Full Text Available Abstract Background The Drosophila embryonic central nervous system (CNS develops from two sets of progenitor cells, neuroblasts and ventral midline progenitors, which behave differently in many respects. Neuroblasts derive from the neurogenic region of the ectoderm and form the lateral parts of the CNS. Ventral midline precursors are formed by two rows of mesectodermal cells and build the CNS midline. There is plenty of evidence that individual identities are conferred to precursor cells by positional information in the ectoderm. It is unclear, however, how far the precursors can maintain their identities and developmental properties in the absence of normal external signals. Results To separate the respective contributions of autonomous properties versus extrinsic signals during their further development, we isolated individual midline precursors and neuroectodermal precursors at the pre-mitotic gastrula stage, traced their development in vitro, and analyzed the characteristics of their lineages in comparison with those described for the embryo. Although individually cultured mesectodermal cells exhibit basic characteristics of CNS midline progenitors, the clones produced by these progenitors differ from their in situ counterparts with regard to cell numbers, expression of molecular markers, and the separation of neuronal and glial fate. In contrast, clones derived from individually cultured precursors taken from specific dorsoventral zones of the neuroectoderm develop striking similarities to the lineages of neuroblasts that normally delaminate from these zones and develop in situ. Conclusion This in vitro analysis allows for the first time a comparison of the developmental capacities in situ and in vitro of individual neural precursors of defined spatial and temporal origin. The data reveal that cells isolated at the pre-mitotic and pre-delamination stage express characteristics of the progenitor type appropriate to their site of origin in
Pera, Edgar M; Kim, James I; Martinez, Sarah L; Brechner, Mariel; Li, Su Yu; Wessely, Oliver; De Robertis, E M
2002-08-01
Patterning of the central nervous system is regulated by a signaling center located at the midbrain-hindbrain boundary (MHB), or isthmus organizer. Fibroblast growth factors secreted from the MHB are required and sufficient to direct the ordered growth and regionalization of the midbrain and anterior hindbrain. In an unbiased secretion cloning screen of Xenopus gastrula embryos we identified a novel gene, which we designated as Isthmin (xIsm) due to its prominent expression at the MHB. xIsm encodes a secreted protein of 449 amino acids containing one copy of the thrombospondin type 1 repeat (TSR). We also found orthologous Isthmin genes in human (hIsm) and mouse (mIsm), as well as a gene encoding an Isthmin-like human unknown protein (hIsm-l). The conservation of a unique carboxy-terminal region between hIsm and hIsm-l suggests that Isthmin is the founding member of a new family of secreted proteins. xIsm was strongly expressed maternally in the Xenopus egg and showed zygotic expression in the ventral blastopore lip, notochord, and MHB. Additional expression domains were detected in neural crest, ear vesicle, and developing blood islands. Interestingly, xIsm was co-expressed with Fibroblast growth factor-8 (xFgf-8) at multiple sites including the MHB, indicating that these two genes are part of a synexpression group which also includes sprouty and sef homologs.
Specificity and impact of adrenergic projections to the midbrain dopamine system
Mejias-Aponte, Carlos A.
2016-01-01
Dopamine (DA) is a neuromodulator that regulates different brain circuits involved in cognitive functions, motor coordination, and emotions. Dysregulation of DA is associated with many neurological and psychiatric disorders such as Parkinson’s disease and substance abuse. Several lines of research have shown that the midbrain DA system is regulated by the central adrenergic system. This review focuses on adrenergic interactions with midbrain DA neurons. It discusses the current neuroanatomy including source of adrenergic innervation, type of synapses, and adrenoceptors expression. It also discusses adrenergic regulation of DA cell activity and neurotransmitter release. Finally, it reviews several neurological and psychiatric disorders where changes in adrenergic system are associated with dysregulation of the midbrain DA system. PMID:26820641
Comparison of gene expression profile in embryonic mesencephalon and neuronal primary cultures.
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Dario Greco
Full Text Available In the mammalian central nervous system (CNS an important contingent of dopaminergic neurons are localized in the substantia nigra and in the ventral tegmental area of the ventral midbrain. They constitute an anatomically and functionally heterogeneous group of cells involved in a variety of regulatory mechanisms, from locomotion to emotional/motivational behavior. Midbrain dopaminergic neuron (mDA primary cultures represent a useful tool to study molecular mechanisms involved in their development and maintenance. Considerable information has been gathered on the mDA neurons development and maturation in vivo, as well as on the molecular features of mDA primary cultures. Here we investigated in detail the gene expression differences between the tissue of origin and ventral midbrain primary cultures enriched in mDA neurons, using microarray technique. We integrated the results based on different re-annotations of the microarray probes. By using knowledge-based gene network techniques and promoter sequence analysis, we also uncovered mechanisms that might regulate the expression of CNS genes involved in the definition of the identity of specific cell types in the ventral midbrain. We integrate bioinformatics and functional genomics, together with developmental neurobiology. Moreover, we propose guidelines for the computational analysis of microarray gene expression data. Our findings help to clarify some molecular aspects of the development and differentiation of DA neurons within the midbrain.
Mileykovskiy, Boris; Morales, Marisela
2011-05-18
It is widely accepted that midbrain dopamine (DA) neurons encode actual and expected reward values by phasic alterations in firing rate. However, how DA neurons encode negative events in the environment is still unclear because some DA neurons appear to be depressed and others excited by aversive stimuli. Here, we show that exposing fear-conditioned rats to stimuli predicting electrical shock elicited three types of biphasic responses, each of which contained an inhibitory pause, in neurochemically identified ventral tegmental area (VTA) DA neurons. The duration of the inhibitory pause in these responses of VTA DA neurons was in direct proportion to the increase in respiratory rate reflecting the level of conditioned fear. Our results suggest that the duration of inhibition of VTA DA neurons encodes negative emotional values of signals predicting aversive events in the environment.
Wei, Luqing; Hu, Xiao; Yuan, Yonggui; Liu, Weiguo; Chen, Hong
2018-07-16
Neuropathology suggests that Parkinson's disease (PD) with depression may involve a progressive degeneration of the nigrostriatal and mesocorticolimbic dopaminergic systems. Previous positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have shown that dopamine changes in individual brain regions constituting the nigrostriatal and mesocorticolimbic circuits are associated with depression in PD. However, few studies have been conducted on the circuit-level alterations in this disease. The present study used resting-state fMRI and seed-based functional connectivity of putative dopaminergic midbrain regions (i.e., substantia nigra (SN) and ventral tegmental area (VTA)) to investigate the circuit-related abnormalities in PD with depression. The results showed that depressed PD (DPD) patients relative to healthy controls (HC) and non-depressed PD (NDPD) patients had increased functional connectivity between VTA and anterior cingulate cortex (ACC), demonstrating that dysfunctional mesocorticolimbic dopaminergic neurotransmission may be associated with depression in PD. Compared with HC, DPD and NDPD patients showed increased functional connectivity from SN to sensorimotor cortex, validating that alterations in the nigrostriatal circuitry could be responsible for cardinal motor features in PD. In addition, aberrant connectivity between VTA and ACC was correlated with the severity of depression in PD patients, further supporting that abnormal mesocorticolimbic system may account for depressive symptoms in PD. These results have provided potential circuit-level biomarkers of depression in PD, and suggested that resting state functional connectivity of midbrain dopaminergic nuclei may be useful for understanding the underlying pathology in PD with depression. Copyright © 2018 Elsevier B.V. All rights reserved.
Khaira, S K; Nefzger, C M; Beh, S J; Pouton, C W; Haynes, J M
2011-09-01
Neurons differentiated in vitro from embryonic stem cells (ESCs) have the potential to serve both as models of disease states and in drug discovery programs. In this study, we use sonic hedgehog (SHH) and fibroblast growth factor 8 (FGF-8) to enrich for forebrain and midbrain phenotypes from mouse ESCs. We then investigate, using Ca(2+) imaging and [(3)H]-GABA release studies, whether the GABAergic neurons produced exhibit distinct functional phenotypes. At day 24 of differentiation, reverse transcriptase-PCR showed the presence of both forebrain (Bf-1, Hesx1, Pgc-1α, Six3) and midbrain (GATA2, GATA3) selective mRNA markers in developing forebrain-enriched cultures. All markers were present in midbrain cultures except for Bf-1 and Pgc-1α. Irrespective of culture conditions all GABA immunoreactive neurons were also immunoreactive to neuropeptide Y (NPY) antibodies. Forebrain and midbrain GABAergic neurons responded to ATP (1 mM), L-glutamate (30 μM), noradrenaline (30 μM), acetylcholine (30 μM) and dopamine (30 μM), with similar elevations of intracellular Ca(2+)([Ca(2+)](i)). The presence of GABA(A) and GABA(B) antagonists, bicuculline (30 μM) and CGP55845 (1 μM), increased the elevation of [Ca(2+)](i) in response to dopamine (30 μM) in midbrain, but not forebrain GABAergic neurons. All agonists, except dopamine, elicited similar [(3)H]-GABA release from forebrain and midbrain cultures. Dopamine (30 μM) did not stimulate significant [(3)H]-GABA release in midbrain cultures, although it was effective in forebrain cultures. This study shows that differentiating neurons toward a midbrain fate restricts the expression of forebrain markers. Forebrain differentiation results in the expression of forebrain and midbrain markers. All GABA(+) neurons contain NPY, and show similar agonist-induced elevations of [Ca(2+)](i) and [(3)H]-GABA release. This study indicates that the pharmacological phenotype of these particular neurons may be independent of the addition of
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Iria G Dopeso-Reyes
2014-12-01
Full Text Available Calbindin (CB is a calcium binding protein reported to protect dopaminergic neurons from degeneration. Although a direct link between CB content and differential vulnerability of dopaminergic neurons has long been accepted, factors other than CB have also been suggested, particularly those related to the dopamine transporter. Indeed, several studies have reported that CB levels are not causally related to the differential vulnerability of dopaminergic neurons against neurotoxins. Here we have used dual stains for tyrosine hydroxylase (TH and CB in 3 control and 3 MPTP-treated monkeys to visualize dopaminergic neurons in the ventral tegmental area (VTA and in the dorsal and ventral tiers of the substantia nigra pars compacta (SNcd and SNcv co-expressing TH and CB. In control animals, the highest percentages of co-localization were found in VTA (58.2%, followed by neurons located in the SNcd (34.7%. As expected, SNcv neurons lacked CB expression. In MPTP-treated animals, the percentage of CB-ir/TH-ir neurons in the VTA was similar to control monkeys (62.1%, whereas most of the few surviving neurons in the SNcd were CB-ir/TH-ir (88.6%. Next, we have elucidated the presence of CB within identified nigrostriatal and nigroextrastriatal midbrain dopaminergic projection neurons. For this purpose, two control monkeys received one injection of Fluoro-Gold into the caudate nucleus and one injection of cholera toxin (CTB into the postcommissural putamen, whereas two more monkeys were injected with CTB into the internal division of the globus pallidus. As expected, all the nigrocaudate- and nigroputamen-projecting neurons were TH-ir, although surprisingly, all of these nigrostriatal-projecting neurons were negative for CB. Furthermore, all the nigropallidal-projecting neurons co-expressed both TH and CB. In summary, although CB-ir dopaminergic neurons seem to be less prone to MPTP-induced degeneration, our data clearly demonstrated that these neurons are not
Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure.
Tang, Suk Peng; Kuttulebbai Nainamohamed Salam, Sirajudeen; Jaafar, Hasnan; Gan, Siew Hua; Muzaimi, Mustapha; Sulaiman, Siti Amrah
2017-01-01
Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ ( p honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.
Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure
Sulaiman, Siti Amrah
2017-01-01
Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung. PMID:28127418
International Nuclear Information System (INIS)
Kang, Ji Hoon; Im, Joo Hyuk; Kim, Jae Seung; Lee, Myoung Chong
2001-01-01
Midbrain lesion may produce a variety of movement disorders including tremor, dystonia, and parkinsonism. The anatomical and functional basis of the movement disorder associated with the midbrain lesion is still unclear. The purpose of this study was to correlate focal midbrain lesions with clinical and I-123 IPT SPECT findings. Five patients (aged 25 to 69 years, 3 men and 2 women) who presented with movement disorder associated with discrete focal midbrain lesion on the brain MRI were included. We reviewed the clinical characteristics of movement disorders and the brain MRI findings in all patients. I-123 IPT SPECT was performed in all patients and 9 normal controls to evaluate the integrity of the nigrostriatal dopaminergic system and specific binding ratios were also calculated. Patients consisted of 2 with parkinsonism, 1 with midbrain tremor, 1 with hemidystonia, and 1 with micrographia as the only manifestation. In all patients, movement disorders were confined to the limbs contralateral to the focal midbrain lesions. The causes of midbrain lesion were trauma (n=2), rupture of AVM (n=1), cerebral infarction (n=1), and encephalitis (n=1). The latency between the midbrain injury and the onset of movement disorder varied from 1.5 months to 2 years (mean 6.7 months). Specific binding ratios of ipsilateral striatum (1.6±1.4) were significantly lower than that of contralateral side (3.3±0.99) and normal control (3.5±0.5)(p<0.05). All of six patients had lesions involving substantia nigra on MRI and two of these with resting tremor had also lesions involving the red nucleus. Bradykinesia and rigidity were mild or absent in these two patients, despite severely decreased specific binding ratios (mean 0.55) of ipsilateral striatum. Movement disorders associated with focal midbrain lesion were partially related to the damage in the nigrostriatal dopaminergic system. However, the severity and nature of movement disorder were variable and not directly related to the
Encoding of natural and artificial stimuli in the auditory midbrain
Lyzwa, Dominika
How complex acoustic stimuli are encoded in the main center of convergence in the auditory midbrain is not clear. Here, the representation of neural spiking responses to natural and artificial sounds across this subcortical structure is investigated based on neurophysiological recordings from the mammalian midbrain. Neural and stimulus correlations of neuronal pairs are analyzed with respect to the neurons' distance, and responses to different natural communication sounds are discriminated. A model which includes linear and nonlinear neural response properties of this nucleus is presented and employed to predict temporal spiking responses to new sounds. Supported by BMBF Grant 01GQ0811.
Parkinson's disease-like midbrain hyperechogenicity is frequent in amyotrophic lateral sclerosis.
Fathinia, Panteha; Hermann, Andreas; Reuner, Ulrike; Kassubek, Jan; Storch, Alexander; Ludolph, Albert C
2013-02-01
Clinical and neuroimaging data suggest impairment of the nigrostriatal system in amyotrophic lateral sclerosis (ALS). We thus hypothesized whether Parkinson's disease (PD)-like midbrain sonography findings are also present in ALS. Eighty-six patients with the diagnosis of possible or definite ALS according to revised El Escorial criteria were examined by transcranial B-mode sonography compared to 76 age- and gender-matched controls and 33 PD patients. Hyperechogenic areas of the midbrain representing the substantia nigra were measured planimetrically using standard protocols. In subjects with sufficient temporal acoustic bone windows, mean midbrain hyperechogenic areas were significantly higher in ALS (0.251 ± 0.104 cm(2)) and PD patients (0.286 ± 0.078 cm(2)) compared to controls (0.091 ± 0.054 cm(2)) with no significant difference between ALS and PD patients (one-way ANOVA: F value = 94.3; P diagnosis and differential diagnosis of PD and ALS alike.
Allodi, Ilary; Hedlund, Eva
2014-01-01
Induction of specific neuronal fates is restricted in time and space in the developing CNS through integration of extrinsic morphogen signals and intrinsic determinants. Morphogens impose regional characteristics on neural progenitors and establish distinct progenitor domains. Such domains are defined by unique expression patterns of fate determining transcription factors. These processes of neuronal fate specification can be recapitulated in vitro using pluripotent stem cells. In this review, we focus on the generation of dopamine neurons and motor neurons, which are induced at ventral positions of the neural tube through Sonic hedgehog (Shh) signaling, and defined at anteroposterior positions by fibroblast growth factor (Fgf) 8, Wnt1, and retinoic acid (RA). In vitro utilization of these morphogenic signals typically results in the generation of multiple neuronal cell types, which are defined at the intersection of these signals. If the purpose of in vitro neurogenesis is to generate one cell type only, further lineage restriction can be accomplished by forced expression of specific transcription factors in a permissive environment. Alternatively, cell-sorting strategies allow for selection of neuronal progenitors or mature neurons. However, modeling development, disease and prospective therapies in a dish could benefit from structured heterogeneity, where desired neurons are appropriately synaptically connected and thus better reflect the three-dimensional structure of that region. By modulating the extrinsic environment to direct sequential generation of neural progenitors within a domain, followed by self-organization and synaptic establishment, a reductionist model of that brain region could be created. Here we review recent advances in neuronal fate induction in vitro, with a focus on the interplay between cell intrinsic and extrinsic factors, and discuss the implications for studying development and disease in a dish.
Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure
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Suk Peng Tang
2017-01-01
Full Text Available Paraquat (PQ is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day, Tualang honey (1.0 g/kg/day, or ubiquinol (0.2 g/kg/day throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week or PQ (10 mg/kg/week once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p<0.05. The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase and glutathione-S-transferase. Treatment with Tualang honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.
Increased Fos expression among midbrain dopaminergic cell groups during birdsong tutoring.
Nordeen, E J; Holtzman, D A; Nordeen, K W
2009-08-01
During avian vocal learning, birds memorize conspecific song patterns and then use auditory feedback to match their vocal output to this acquired template. Some models of song learning posit that during tutoring, conspecific visual, social and/or auditory cues activate neuromodulatory systems that encourage acquisition of the tutor's song and attach incentive value to that specific acoustic pattern. This hypothesis predicts that stimuli experienced during social tutoring activate cell populations capable of signaling reward. Using immunocytochemistry for the protein product of the immediate early gene c-Fos, we found that brief exposure of juvenile male zebra finches to a live familiar male tutor increased the density of Fos+ cells within two brain regions implicated in reward processing: the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). This activation of Fos appears to involve both dopaminergic and non-dopaminergic VTA/SNc neurons. Intriguingly, a familiar tutor was more effective than a novel tutor in stimulating Fos expression within these regions. In the periaqueductal gray, a dopamine-enriched cell population that has been implicated in emotional processing, Fos labeling also was increased after tutoring, with a familiar tutor again being more effective than a novel conspecific. As several neural regions implicated in song acquisition receive strong dopaminergic projections from these midbrain nuclei, their activation in conjunction with hearing the tutor's song could help to establish sensory representations that later guide motor sequence learning.
Weise, Christopher M; Thiyyagura, Pradeep; Reiman, Eric M; Chen, Kewei; Krakoff, Jonathan
2015-06-01
Little is known on how sensing of energy needs is centrally represented, integrated, and translated into the behavioral aspects of energy homeostasis. Fat free mass (FFM) is the major determinant of energy expenditure. We investigated how interindividual variances in FFM relate to neuronal activity in humans. Healthy adults (n = 64, 21F/43M; age 31.3 ± 9.1y; percentage of body fat [PFAT] 25.6 ± 10.7%; BMI 30.4 ± 9) underwent a 36h fast and subsequent H(2) (15) O positron emission tomographic (PET) measurement of regional cerebral blood flow (rCBF). Multiple variable regression analysis revealed significant associations of FFM with rCBF within the midbrain [including parts of the periaqueductal gray (PAG), ventral tegmental area (VTA), thalamic and hypothalamic regions], the bilateral parahippocampal region, left anterior cingulate, left insular cortex, right cerebellum, and distinct regions within the temporal and occipital cortex. In contrast, no significant associations were found for fat mass (FM). We investigated the potential functional-anatomical link between FFM and central regulation of food intake by performing a conjunction analysis of FFM and the perceived hunger feelings. This showed a significant overlap within the midbrain PAG. Mediation analysis demonstrated a significant indirect effect of FFM on hunger with PAG rCBF as mediator. Most regions we found to be associated with FFM form part in ascending homeostatic pathways and cortical circuitries implicated in the regulation of basic bodily functions indicating a potential role of these central networks in the integration of FFM determined energy needs. © 2015 Wiley Periodicals, Inc.
Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety
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Brenes, J.C.; Broiz, A.C.; Bassi, G.S.; Schwarting, R.K.W.; Brandão, M.L.
2012-01-01
Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by Y -aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG
Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety
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Brenes, J.C. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Broiz, A.C.; Bassi, G.S. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Schwarting, R.K.W. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Brandão, M.L. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)
2012-03-09
Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by {sub Y}-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.
Lin, Yong; Zhang, Hao; Wang, Wen-dong; Wu, De-sheng; Jiang, Song-hui; Qu, Wei-dong
2006-07-01
To investigate the mechanism and effect of rat perinatal exposure to bisphenol A (BPA) resulting in midbrain dopaminergic neuronal cell apoptosis and tyrosine hydroxylase expression of male offspring. Rat dams were randomLy divided into 4 groups on gestational day(GD) 10 and given orally the bisphenol A doses as 0, 0.5, 5, 50 mg/kg x d from GD10 to weaning. The brains of male offspring were obtained for detecting, with immunohistochemistry protocol, the Caspase-3, Bcl-2 and tyrosine hydroxylase expression in the midbrain on postnatal day 21 or 30 respectively, and the midbrain apoptotic neuronal cell were detected by TUNEL on PND21. The expression of Caspase-3 in the midbrain of rat male offspring were increased but bcl-2 were decreased on PND21 and 30, respectively. On PND21, apoptotic neuronal cell were found in the midbrain of high and medium doses groups. TH protein expression was decreased. Perinatal exposure to bisphenol A can induce the apoptosis of midbrain dopaminergic neuron in the male rat offspring even after weaning, and concomitantly decrease the midbrain TH immunoreactivity, this may cause the abnormal function of dopaminergic pathway of rat male offspring.
Wnt5a regulates midbrain dopaminergic axon growth and guidance.
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Brette D Blakely
2011-03-01
Full Text Available During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM the cues that guide dopaminergic (DA axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway. Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in Wnt5a-/- mice, where fasciculation of the medial forebrain bundle (MFB as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance.
Ventral pallidum roles in reward and motivation.
Smith, Kyle S; Tindell, Amy J; Aldridge, J Wayne; Berridge, Kent C
2009-01-23
In recent years the ventral pallidum has become a focus of great research interest as a mechanism of reward and incentive motivation. As a major output for limbic signals, the ventral pallidum was once associated primarily with motor functions rather than regarded as a reward structure in its own right. However, ample evidence now suggests that ventral pallidum function is a major mechanism of reward in the brain. We review data indicating that (1) an intact ventral pallidum is necessary for normal reward and motivation, (2) stimulated activation of ventral pallidum is sufficient to cause reward and motivation enhancements, and (3) activation patterns in ventral pallidum neurons specifically encode reward and motivation signals via phasic bursts of excitation to incentive and hedonic stimuli. We conclude that the ventral pallidum may serve as an important 'limbic final common pathway' for mesocorticolimbic processing of many rewards.
Chillura, Antonino; Naro, Antonino; Micchia, Katia; Bramanti, Alessia; Bramanti, Placido; Calabrò, Rocco Salvatore
2017-09-15
Transcranial sonography (TCS) of the brainstem is currently used to support the clinical diagnosis of movement disorders. The aim of the study was to assess the usefulness of midbrain TCS in assessing outcome in patients with Chronic Disorders of Consciousness (DOC). Eleven patients with Minimally Conscious State (MCS) and Unresponsive Wakefulness Syndrome (UWS) were included in the study. We measured the area and echogenicity of the midbrain by encoding and digitally analyzing the corresponding images from the orbitomeatal plane, the morphology of brain parenchyma from the thalamic and cella media plane, and the intracranial circulation. All the patients showed an increase of pulsatility index and numerous morphological alterations on all the scan planes. In particular, we found a loss of the characteristic butterfly-shape of the midbrain, which appeared hypoechoic in the UWS but not in the MCS patients. After six months, the patients were clinically assessed by using Glasgow Outcome Scale Extended (GOSE). We found that a higher increase in GOSE scoring at follow-up was correlated with larger area and higher echogenicity of the midbrain at baseline. The present study suggests that TCS data of the midbrain may support clinical assessment of patients with chronic DOC to estimate their outcome. Copyright © 2017 Elsevier B.V. All rights reserved.
Shishkina, Galina T; Kalinina, Tatyana S; Bulygina, Veta V; Lanshakov, Dmitry A; Babluk, Ekaterina V; Dygalo, Nikolay N
2015-01-01
Anti-apoptotic proteins are suggested to be important for the normal health of neurons and synapses as well as for resilience to stress. In order to determine whether stressful events may influence the expression of anti-apoptotic protein Bcl-xL in the midbrain and specifically in the midbrain serotonergic (5-HT) neurons involved in neurobehavioral responses to adverse stimuli, adult male rats were subjected to short-term or chronic forced swim stress. A short-term stress rapidly increased the midbrain bcl-xl mRNA levels and significantly elevated Bcl-xL immunoreactivity in the midbrain 5-HT cells. Stress-induced increase in glucocorticoid secretion was implicated in the observed effect. The levels of bcl-xl mRNA were decreased after stress when glucocorticoid elevation was inhibited by metyrapone (MET, 150 mg/kg), and this decrease was attenuated by glucocorticoid replacement with dexamethasone (DEX; 0.2 mg/kg). Both short-term stress and acute DEX administration, in parallel with Bcl-xL, caused a significant increase in tph2 mRNA levels and slightly enhanced tryptophan hydroxylase immunoreactivity in the midbrain. The increasing effect on the bcl-xl expression was specific to the short-term stress. Forced swim repeated daily for 2 weeks led to a decrease in bcl-xl mRNA in the midbrain without any effects on the Bcl-xL protein expression in the 5-HT neurons. In chronically stressed animals, an increase in tph2 gene expression was not associated with any changes in tryptophan hydroxylase protein levels. Our findings are the first to demonstrate that both short-term stress and acute glucocorticoid exposures induce Bcl-xL protein expression in the midbrain 5-HT neurons concomitantly with the activation of the 5-HT synthesis pathway in these neurons.
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Galina T Shishkina
Full Text Available Anti-apoptotic proteins are suggested to be important for the normal health of neurons and synapses as well as for resilience to stress. In order to determine whether stressful events may influence the expression of anti-apoptotic protein Bcl-xL in the midbrain and specifically in the midbrain serotonergic (5-HT neurons involved in neurobehavioral responses to adverse stimuli, adult male rats were subjected to short-term or chronic forced swim stress. A short-term stress rapidly increased the midbrain bcl-xl mRNA levels and significantly elevated Bcl-xL immunoreactivity in the midbrain 5-HT cells. Stress-induced increase in glucocorticoid secretion was implicated in the observed effect. The levels of bcl-xl mRNA were decreased after stress when glucocorticoid elevation was inhibited by metyrapone (MET, 150 mg/kg, and this decrease was attenuated by glucocorticoid replacement with dexamethasone (DEX; 0.2 mg/kg. Both short-term stress and acute DEX administration, in parallel with Bcl-xL, caused a significant increase in tph2 mRNA levels and slightly enhanced tryptophan hydroxylase immunoreactivity in the midbrain. The increasing effect on the bcl-xl expression was specific to the short-term stress. Forced swim repeated daily for 2 weeks led to a decrease in bcl-xl mRNA in the midbrain without any effects on the Bcl-xL protein expression in the 5-HT neurons. In chronically stressed animals, an increase in tph2 gene expression was not associated with any changes in tryptophan hydroxylase protein levels. Our findings are the first to demonstrate that both short-term stress and acute glucocorticoid exposures induce Bcl-xL protein expression in the midbrain 5-HT neurons concomitantly with the activation of the 5-HT synthesis pathway in these neurons.
International Nuclear Information System (INIS)
Reimold, M.; Bares, R.; Reischl, G.; Solbach, C.; Machulla, H.-J.; Smolka, M.N.; Mann, K.; Schumann, G.; Zimmer, A.; Wrase, J.; Hu, X.-Z.; Goldman, D.; Heinz, A.
2007-01-01
Homozygote carriers of two long (L) alleles of the serotonin transporter (5-HTT) regulatory region displayed in vitro a twofold increase in 5-HTT expression compared with carriers of one or two short (S) alleles. However, in vivo imaging studies yielded contradictory results. Recently, an A > G exchange leading to differential transcriptional activation of 5-HTT mRNA in lymphobalstoid cell lines was discovered in the 5-HTT regulatory region. In vitro and in vivo evidence suggests that [ 11 C]DASB, a new 5-HTT ligand offers some advantages over the ligands used in previous studies in measuring 5-HTT density independent of synaptic levels of serotonin. We assessed 5-HTT binding potential (BP 2) in the midbrain of 19 healthy subjects with positron emission tomography and [ 11 C]DASB. Accounting for the hypothesized functional similarity of L G and S in driving 5-HTT transcription, we assessed whether L A L A homozygotes display increased midbrain BP 2 compared with carriers of at least one S allele. BP 2 in the midbrain was significantly increased in L A L A homozygotes compared with carriers of at least one S allele. Interestingly, the genotype effect on the midbrain was significantly different from that on the thalamus and the amygdala where no group differences were detected. This in vivo study provides further evidence that subjects homozygous for the L A allele display increased expression of 5-HTT in the midbrain, the origin of central serotonergic projections. (author)
Fos expression in the midbrain periaqueductal grey after trigeminovascular stimulation
Hoskin, KL; Bulmer, DCE; Lasalandra, M; Jonkman, A; Goadsby, PJ
There is an accumulating body of evidence suggesting that the periaqueductal grey (PAG) is involved in the pathophysiology of migraine. Positron emission tomography (PET) studies in humans have shown that the caudal ventrolateral midbrain, encompassing the ventrolateral PAG, has activations during
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Ran eYe
2016-01-01
Full Text Available The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT modulates many key brain functions including those subserving sensation, emotion, reward and cognition. Efficient clearance of 5-HT after release is achieved by the antidepressant-sensitive 5-HT transporter (SERT, SLC6A4. To identify novel SERT regulators, we pursued a proteomic analysis of mouse midbrain SERT complexes, evaluating findings in the context of prior studies that established a SERT-linked transcriptome. Remarkably, both efforts converged on a relationship of SERT with the synaptic adhesion protein neuroligin 2 (NLGN2, a postsynaptic partner for presynaptic neurexins, and a protein well known to organize inhibitory GABAergic synapses. Western blots of midbrain reciprocal immunoprecipitations confirmed SERT/NLGN2 associations, and also extended to other NLGN2 associated proteins (e.g. -neurexin (NRXN, gephyrin. Midbrain SERT/NLGN2 interactions were found to be Ca2+-independent, supporting cis versus trans-synaptic interactions, and were absent in hippocampal preparations, consistent with interactions arising in somatodendritic compartments. Dual color in situ hybridization confirmed co-expression of Tph2 and Nlgn2 mRNA in the dorsal raphe, with immunocytochemical studies confirming SERT:NLGN2 co-localization in raphe cell bodies but not axons. Consistent with correlative mRNA expression studies, loss of NLGN2 expression in Nlgn2 null mice produced significant reductions in midbrain and hippocampal SERT expression and function. Additionally, dorsal raphe 5-HT neurons from Nlgn2 null mice exhibit reduced excitability, a loss of GABAA receptor-mediated IPSCs, and increased 5-HT1A autoreceptor sensitivity. Finally, Nlgn2 null mice display significant changes in behaviors known to be responsive to SERT and/or 5-HT receptor manipulations. We discuss our findings in relation to the possible coordination of intrinsic and extrinsic regulation afforded by somatodendritic SERT:NLGN2
International Nuclear Information System (INIS)
Khan, Zahidul; Akhtar, Monira; Asklund, Thomas; Juliusson, Bengt; Almqvist, Per M.; Ekstroem, Tomas J.
2007-01-01
Enzyme prodrug therapy using neural progenitor cells (NPCs) as delivery vehicles has been applied in animal models of gliomas and relies on gap junction communication (GJC) between delivery and target cells. This study investigated the effects of histone deacetylase (HDAC) inhibitors on GJC for the purpose of facilitating transfer of therapeutic molecules from recombinant NPCs. We studied a novel immortalized midbrain cell line, NGC-407 of embryonic human origin having neural precursor characteristics, as a potential delivery vehicle. The expression of gap junction protein connexin 43 (C x 43) was analyzed by western blot and immunocytochemistry. While C x 43 levels were decreased in untreated differentiating NGC-407 cells, the HDAC inhibitor 4-phenylbutyrate (4-PB) increased C x 43 expression along with increased membranous deposition in both proliferating and differentiating cells. Simultaneously, Ser 279/282-phosphorylated form of C x 43 was declined in both culture conditions by 4-PB. The 4-PB effect in NGC-407 cells was verified by using HNSC.100 human neural progenitors and Trichostatin A. Improved functional GJC is of imperative importance for therapeutic strategies involving intercellular transport of low molecular-weight compounds. We show here an enhancement by 4-PB, of the functional GJC among NGC-407 cells, as well as between NGC-407 and human glioma cells, as indicated by increased fluorescent dye transfer
Torakal Ventral Cord Herniation
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Sermin Tok
2015-11-01
Full Text Available Ventral cord herniation is a rare cause of focal myelopathy due to herniation of the thoracic cord through a dural defect.It is also known by a variety of other terms such as spontaneous thoracic cord herniation or idiopathic spinal cord herniation.The key feature is focal distortion and rotation of the cord with no CSF seen between it and the ventral theca.
DEFF Research Database (Denmark)
Jensen, Pia; Gramsbergen, Jan-Bert; Zimmer, Jens
2011-01-01
Effective numerical expansion of dopaminergic precursors might overcome the limited availability of transplantable cells in replacement strategies for Parkinson's disease. Here we investigated the effect of fibroblast growth factor-2 (FGF2) and FGF8 on expansion and dopaminergic differentiation o...... enzyme activity, which may explain the elevated dopamine levels. Our findings demonstrate that modulation of oxygen tension is a recognizable factor for in vitro expansion and dopaminergic differentiation of rat embryonic midbrain precursor cells....... of rat embryonic ventral mesencephalic neuroblasts cultured at high (20%) and low (3%) oxygen tension. More cells incorporated bromodeoxyuridine in cultures expanded at low as compared to high oxygen tension, and after 6 days of differentiation there were significantly more neuronal cells in low than......, switching FGF2-expanded cultures from low to high oxygen tension during the last two days of differentiation significantly enhanced dopamine release and intracellular dopamine levels as compared to all other treatment groups. In addition, the short-term exposure to high oxygen enhanced in situ assessed TH...
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Christensen-Dalsgaard, J; Jørgensen, M B
1989-01-01
European grassfrogs (Rana temporaria) were stimulated with pulsed sinusoidal, vertical vibrations (10-300 Hz) and the responses of 46 single midbrain neurons were recorded in awake, immobilized animals. Most units (40) had simple V-shaped excitatory vibrational tuning curves. The distribution of ...... stimuli probably play a role in communication and detection of predators and the vibration-sensitive midbrain neurons may be involved in the central processing of such behaviorally significant stimuli.......European grassfrogs (Rana temporaria) were stimulated with pulsed sinusoidal, vertical vibrations (10-300 Hz) and the responses of 46 single midbrain neurons were recorded in awake, immobilized animals. Most units (40) had simple V-shaped excitatory vibrational tuning curves. The distribution...... of best frequencies (BF's) was bimodal with peaks at 10 and 100 Hz and the thresholds ranged from 0.02 to 1.28 cm/s2 at the BF. Twenty-three neurons showed phasic-tonic and 11 neurons phasic responses. The dynamic range of seismic intensity for most neurons was 20-30 dB. In contrast to the sharp phase...
Development and function of the midbrain dopamine system: what we know and what we need to.
Bissonette, G B; Roesch, M R
2016-01-01
The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson's disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, including drug addiction, autism and schizophrenia. Understanding dopamine neuron ontogeny and how dopamine connections and circuitry develops may provide us with key insights into potentially important avenues of research for other dopamine-related disorders. This review will provide a brief overview of the major molecular and genetic players throughout the development of midbrain dopamine neurons and what we know about the behavioral- and disease-related implications associated with perturbations to midbrain dopamine neuron development. We intend to combine the knowledge of two broad fields of neuroscience, both developmental and behavioral, with the intent on fostering greater discussion between branches of neuroscience in the service of addressing complex cognitive questions from a developmental perspective and identifying important gaps in our knowledge for future study. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
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Martinat, Cecile; Bacci, Jean-Jacques; Leete, Thomas
2006-01-01
's disease. We sought to identify genes that can potentiate maturation of ES cell cultures to the midbrain DA neuron phenotype. A number of transcription factors have been implicated in the development of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1......Midbrain dopamine (DA) neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson's disease. Cell replacement therapies, and in particular embryonic stem (ES) cell-derived DA neurons, offer a potential therapeutic venue for Parkinson......, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2. However, none of these factors appear sufficient alone to induce the mature midbrain DA neuron phenotype in ES cell cultures in vitro, suggesting a more complex regulatory network. Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation...
Development and function of the midbrain dopamine system: what we know and what we need to
Bissonette, G. B.; Roesch, M. R.
2015-01-01
The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson’s disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, in...
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Marcela Perrone-Bertolotti
2017-06-01
Full Text Available It has been suggested that dorsal and ventral pathways support distinct aspects of language processing. Yet, the full extent of their involvement and their inter-regional connectivity in visual word recognition is still unknown. Studies suggest that they might reflect the dual-route model of reading, with the dorsal pathway more involved in grapho-phonological conversion during phonological tasks, and the ventral pathway performing lexico-semantic access during semantic tasks. Furthermore, this subdivision is also suggested at the level of the inferior frontal cortex, involving ventral and dorsal parts for lexico-semantic and phonological processing, respectively. In the present study, we assessed inter-regional brain connectivity and task-induced modulations of brain activity during a phoneme detection and semantic categorization tasks, using fMRI in healthy subject. We used a dynamic causal modeling approach to assess inter-regional connectivity and task demand modulation within the dorsal and ventral pathways, including the following network components: the ventral occipito-temporal cortex (vOTC; dorsal and ventral, the superior temporal gyrus (STG; dorsal, the dorsal inferior frontal gyrus (dIFG; dorsal, and the ventral IFG (vIFG; ventral. We report three distinct inter-regional interactions supporting orthographic information transfer from vOTC to other language regions (vOTC -> STG, vOTC -> vIFG and vOTC -> dIFG regardless of task demands. Moreover, we found that (a during semantic processing (direct ventral pathway the vOTC -> vIFG connection strength specifically increased and (b a lack of modulation of the vOTC -> dIFG connection strength by the task that could suggest a more general involvement of the dorsal pathway during visual word recognition. Results are discussed in terms of anatomo-functional connectivity of visual word recognition network.
Hierarchical prediction errors in midbrain and basal forebrain during sensory learning.
Iglesias, Sandra; Mathys, Christoph; Brodersen, Kay H; Kasper, Lars; Piccirelli, Marco; den Ouden, Hanneke E M; Stephan, Klaas E
2013-10-16
In Bayesian brain theories, hierarchically related prediction errors (PEs) play a central role for predicting sensory inputs and inferring their underlying causes, e.g., the probabilistic structure of the environment and its volatility. Notably, PEs at different hierarchical levels may be encoded by different neuromodulatory transmitters. Here, we tested this possibility in computational fMRI studies of audio-visual learning. Using a hierarchical Bayesian model, we found that low-level PEs about visual stimulus outcome were reflected by widespread activity in visual and supramodal areas but also in the midbrain. In contrast, high-level PEs about stimulus probabilities were encoded by the basal forebrain. These findings were replicated in two groups of healthy volunteers. While our fMRI measures do not reveal the exact neuron types activated in midbrain and basal forebrain, they suggest a dichotomy between neuromodulatory systems, linking dopamine to low-level PEs about stimulus outcome and acetylcholine to more abstract PEs about stimulus probabilities. Copyright © 2013 Elsevier Inc. All rights reserved.
Isolated Medial Rectus Nuclear Palsy as a Rare Presentation of Midbrain Infarction.
Al-Sofiani, Mohammed; Lee Kwen, Peterkin
2015-10-08
Diplopia is a common subjective complaint that can be the first manifestation of a serious pathology. Here, we report a rare case of midbrain infarction involving the lateral subnucleus of the oculomotor nuclear complex presenting as diplopia, with no other stroke manifestations. An 83-year-old right-handed white man with past medical history of diabetes mellitus, hypertension, dyslipidemia, and coronary artery disease presented to the emergency department (ED) with diplopia and unsteadiness. Two days prior to admission, the patient woke up with constant horizontal diplopia and unsteadiness, which limited his daily activities and led to a fall at home. He denied any weakness, clumsiness, nausea, vomiting, photophobia, fever, or chills. Ocular exam showed a disconjugate gaze at rest, weakness of the left medial rectus muscle, impaired convergence test, and bilateral 3-mm reactive pupils. The diplopia resolved by closing either eye. The remaining extraocular muscles and other cranial nerves were normal. There was no nystagmus, ptosis, or visual field deficit. Sensation, muscle tone, and strength were normal in all extremities. Magnetic resonance imaging (MRI) of the brain revealed a tiny focus of restricted diffusion in the left posterior lateral midbrain. A thorough history and physical examination is essential to diagnose and manage diplopia. Isolated extraocular palsy is usually thought to be caused by orbital lesions or muscular diseases. Here, we report a case of midbrain infarction manifested as isolated medial rectus palsy.
Ripollés, Pablo; Marco-Pallarés, Josep; Alicart, Helena; Tempelmann, Claus; Rodríguez-Fornells, Antoni; Noesselt, Toemme
2016-09-20
Humans constantly learn in the absence of explicit rewards. However, the neurobiological mechanisms supporting this type of internally-guided learning (without explicit feedback) are still unclear. Here, participants who completed a task in which no external reward/feedback was provided, exhibited enhanced fMRI-signals within the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop) when successfully grasping the meaning of new-words. Importantly, new-words that were better remembered showed increased activation and enhanced functional connectivity between the midbrain, hippocampus, and ventral striatum. Moreover, enhanced emotion-related physiological measures and subjective pleasantness ratings during encoding were associated with remembered new-words after 24 hr. Furthermore, increased subjective pleasantness ratings were also related to new-words remembered after seven days. These results suggest that intrinsic-potentially reward-related-signals, triggered by self-monitoring of correct performance, can promote the storage of new information into long-term memory through the activation of the SN/VTA-Hippocampal loop, possibly via dopaminergic modulation of the midbrain.
The complexity of the calretinin-expressing progenitors in the human cerebral cortex
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Nevena V Radonjic
2014-08-01
Full Text Available The complex structure and function of the cerebral cortex critically depend on the balance of excitation and inhibition provided by the pyramidal projection neurons and GABAergic interneurons, respectively. The calretinin-expressing (CalR+ cell is a subtype of GABAergic cortical interneurons that is more prevalent in humans than in rodents. In rodents, CalR+ interneurons originate in the caudal ganglionic eminence (CGE from Gsx2+ progenitors, but in humans it has been suggested that a subpopulation of CalR+ cells can also be generated in the cortical ventricular/subventricular zone (VZ/SVZ. The progenitors for cortically generated CalR+ subpopulation in primates are not yet characterized. Hence, the aim of this study was to identify patterns of expression of the transcription factors (TFs that commit cortical stem cells to the CalR fate, with a focus on Gsx2. First, we studied the expression of Gsx2 and its downstream effectors, Ascl1 and Sp8 in the cortical regions of the fetal human forebrain at midgestation. Next, we established that a subpopulation of cells expressing these TFs are proliferating in the cortical SVZ, and can be co-labeled with CalR. The presence and proliferation of Gsx2+ cells, not only in the ventral telencephalon (GE as previously reported, but also in the cerebral cortex suggests cortical origin of a subpopulation of CalR+ neurons in humans. In vitro treatment of human cortical progenitors with Sonic hedgehog (Shh, an important morphogen in the specification of interneurons, decreased levels of Ascl1 and Sp8 proteins, but did not affect Gsx2 levels. Taken together, our ex-vivo and in vitro results on human fetal brain suggest complex endogenous and exogenous regulation of TFs implied in the specification of different subtypes of CalR+ cortical interneurons.
Vomeronasal inputs to the rodent ventral striatum.
Ubeda-Bañon, I; Novejarque, A; Mohedano-Moriano, A; Pro-Sistiaga, P; Insausti, R; Martinez-Garcia, F; Lanuza, E; Martinez-Marcos, A
2008-03-18
Vertebrates sense chemical signals through the olfactory and vomeronasal systems. In squamate reptiles, which possess the largest vomeronasal system of all vertebrates, the accessory olfactory bulb projects to the nucleus sphericus, which in turn projects to a portion of the ventral striatum known as olfactostriatum. Characteristically, the olfactostriatum is innervated by neuropeptide Y, tyrosine hydroxylase and serotonin immunoreactive fibers. In this study, the possibility that a structure similar to the reptilian olfactostriatum might be present in the mammalian brain has been investigated. Injections of dextran-amines have been aimed at the posteromedial cortical amygdaloid nucleus (the putative mammalian homologue of the reptilian nucleus sphericus) of rats and mice. The resulting anterograde labeling includes the olfactory tubercle, the islands of Calleja and sparse terminal fields in the shell of the nucleus accumbens and ventral pallidum. This projection has been confirmed by injections of retrograde tracers into the ventral striato-pallidum that render retrograde labeling in the posteromedial cortical amygdaloid nucleus. The analysis of the distribution of neuropeptide Y, tyrosine hydroxylase, serotonin and substance P in the ventral striato-pallidum of rats, and the anterograde tracing of the vomeronasal amygdaloid input in the same material confirm that, similar to reptiles, the ventral striatum of mammals includes a specialized vomeronasal structure (olfactory tubercle and islands of Calleja) displaying dense neuropeptide Y-, tyrosine hydroxylase- and serotonin-immunoreactive innervations. The possibility that parts of the accumbens shell and/or ventral pallidum could be included in the mammalian olfactostriatum cannot be discarded.
... incarcerated) in the hernia and become impossible to push back in. This is usually painful. The blood supply ... you are lying down or that you cannot push back in. Risks The risks of ventral hernia repair ...
Primary ventral or groin hernia in pregnancy
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Oma, E; Bay-Nielsen, M; Jensen, K K
2017-01-01
BACKGROUND: Prevalence, management, and risk of emergency operation for primary ventral or groin hernia in pregnancy are unknown. The objective of this study was to estimate the prevalences of primary ventral or groin hernia in pregnancy and the potential risks for elective and emergency repair...... was conducted to identify patients registered with a primary ventral or groin hernia in pregnancy. Follow-up was conducted by review of medical record notes within the Capital Region of Denmark supplemented with structured telephone interviews on indication. RESULTS: In total, 20,714 pregnant women were...... included in the study cohort. Seventeen (0.08%) and 25 (0.12%) women were registered with a primary ventral and groin hernia, respectively. None underwent elective or emergency repair in pregnancy, and all had uncomplicated childbirth. In 10 women, the groin bulge disappeared spontaneously after delivery...
Directory of Open Access Journals (Sweden)
Tim D Aumann
Full Text Available Recent evidence indicates the number of dopaminergic neurons in the adult rodent hypothalamus and midbrain is regulated by environmental cues, including photoperiod, and that this occurs via up- or down-regulation of expression of genes and proteins that are important for dopamine (DA synthesis in extant neurons ('DA neurotransmitter switching'. If the same occurs in humans, it may have implications for neurological symptoms associated with DA imbalances. Here we tested whether there are differences in the number of tyrosine hydroxylase (TH, the rate-limiting enzyme in DA synthesis and DA transporter (DAT immunoreactive neurons in the midbrain of people who died in summer (long-day photoperiod, n = 5 versus winter (short-day photoperiod, n = 5. TH and DAT immunoreactivity in neurons and their processes was qualitatively higher in summer compared with winter. The density of TH immunopositive (TH+ neurons was significantly (~6-fold higher whereas the density of TH immunonegative (TH- neurons was significantly (~2.5-fold lower in summer compared with winter. The density of total neurons (TH+ and TH- combined was not different. The density of DAT+ neurons was ~2-fold higher whereas the density of DAT- neurons was ~2-fold lower in summer compared with winter, although these differences were not statistically significant. In contrast, midbrain nuclear volume, the density of supposed glia (small TH- cells, and the amount of TUNEL staining were the same in summer compared with winter. This study provides the first evidence of an association between environmental stimuli (photoperiod and the number of midbrain DA neurons in humans, and suggests DA neurotransmitter switching underlies this association.
Elevated midbrain serotonin transporter availability in mixed mania: a case report
Directory of Open Access Journals (Sweden)
Kuikka Jyrki
2004-09-01
Full Text Available Abstract Background Results obtained from brain imaging studies indicate that serotonin transporter (SERT and dopamine transporter (DAT densities are altered in major depression. However, no such studies have been published on current mania or hypomania. Case presentation In this single photon emission computed tomography (SPECT study with [123I]nor-β-CIT we present a case with simultaneous symptoms of major depression and hypomania. She had an elevated serotonin transporter availability (SERT in the midbrain and elevated dopamine transporter availability (DAT in the striatum, which normalised in a one-year follow-up period during which she received eight months of psychodynamic psychotherapy. Conclusions To our knowledge, this is the first report on SERT and DAT associated with mania. In our case the availability of both SERT in the midbrain and DAT in the striatum were elevated at baseline and declined during psychotherapy, while the SERT and DAT of the depressed controls increased during psychotherapy. Symptoms of hypomania in the case were alleviated during psychotherapy. Clinical recovery was also reflected in the Hamilton Depression Rating Scale (HDRS scores.
Mesenchymal progenitor cells for the osteogenic lineage.
Ono, Noriaki; Kronenberg, Henry M
2015-09-01
Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment. Although heterogeneity of cell populations of interest marked by a promoter-based approach complicates overall interpretation, an emerging complexity of mesenchymal progenitors has been revealed. Current literatures suggest two distinct types of bone progenitor cells; growth-associated mesenchymal progenitors contribute to explosive growth of bone in early life, whereas bone marrow mesenchymal progenitors contribute to the much slower remodeling process and response to injury that occurs mainly in adulthood. More detailed relationships of these progenitors need to be studied through further experimentation.
Midbrain adaptation may set the stage for the perception of musical beat.
Rajendran, Vani G; Harper, Nicol S; Garcia-Lazaro, Jose A; Lesica, Nicholas A; Schnupp, Jan W H
2017-11-15
The ability to spontaneously feel a beat in music is a phenomenon widely believed to be unique to humans. Though beat perception involves the coordinated engagement of sensory, motor and cognitive processes in humans, the contribution of low-level auditory processing to the activation of these networks in a beat-specific manner is poorly understood. Here, we present evidence from a rodent model that midbrain preprocessing of sounds may already be shaping where the beat is ultimately felt. For the tested set of musical rhythms, on-beat sounds on average evoked higher firing rates than off-beat sounds, and this difference was a defining feature of the set of beat interpretations most commonly perceived by human listeners over others. Basic firing rate adaptation provided a sufficient explanation for these results. Our findings suggest that midbrain adaptation, by encoding the temporal context of sounds, creates points of neural emphasis that may influence the perceptual emergence of a beat. © 2017 The Authors.
Midbrain adaptation may set the stage for the perception of musical beat
2017-01-01
The ability to spontaneously feel a beat in music is a phenomenon widely believed to be unique to humans. Though beat perception involves the coordinated engagement of sensory, motor and cognitive processes in humans, the contribution of low-level auditory processing to the activation of these networks in a beat-specific manner is poorly understood. Here, we present evidence from a rodent model that midbrain preprocessing of sounds may already be shaping where the beat is ultimately felt. For the tested set of musical rhythms, on-beat sounds on average evoked higher firing rates than off-beat sounds, and this difference was a defining feature of the set of beat interpretations most commonly perceived by human listeners over others. Basic firing rate adaptation provided a sufficient explanation for these results. Our findings suggest that midbrain adaptation, by encoding the temporal context of sounds, creates points of neural emphasis that may influence the perceptual emergence of a beat. PMID:29118141
International Nuclear Information System (INIS)
Adachi, Michito; Ohshima, Fumi; Kawanami, Toru; Kato, Takeo
2006-01-01
On magnetic resonance imaging (MRI) sagittal sections, we sometimes encounter abnormal aspects of the superior profile of the midbrain and the cingulate sulcus in patients with dementia. In this preliminary study, we refer to these findings as the ''upper midbrain profile sign'' and the cingulate sulcus sign.'' We prospectively evaluated the usefulness of these signs for the diagnosis of idiopathic normal-pressure hydrocephalus (iNPH), Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). We evaluated the upper midbrain profile sign and the cingulate sulcus sign on MRI sagittal images obtained from 21 people with headaches but no neurological deficit (controls), 10 iNPH patients, 11 AD patients, and 5 PSP patients. The upper midbrain profile sign indicated a concave shape to the superior profile of the midbrain on mid-sagittal images, and the cingulate sulcus sign indicated a narrow, tight aspect of the posterior part of the cingulate sulcus on paramedian-sagittal images. These signs were never seen in any images from the controls. The upper midbrain profile sign was seen in 7 of 10 patients with iNPH, 5 of 11 with AD, and 3 of 5 with PSP. The cingulate sulcus sign was seen in all 10 patients with iNPH but was never seen in any patient with AD or PSP. The upper midbrain profile sign could support a diagnosis of PSP but cannot discriminate among iNPH, AD, and PSP. In contrast, the cingulate sulcus sign has a very high sensitivity for iNPH and should facilitate the distinction of iNPH from other dementias. In the clinical setting, it is momentous to evaluate these signs easily by one simple MRI sequence. (author)
FUSIMOTOR EFFECTS OF MIDBRAIN STIMULATION ON JAW MUSCLE-SPINDLES OF THE ANESTHETIZED CAT
TAYLOR, A; JUCH, PJW
The effects of electrical stimulation within the midbrain on fusimotor output to the jaw elevator muscles were studied in anaesthetized cats. Muscle spindle afferents recorded in the mesencephalic trigeminal nucleus were categorised as primary or secondary by their responses to succinylcholine
Late onset arginase deficiency presenting with encephalopathy and midbrain hyperintensity
Directory of Open Access Journals (Sweden)
Boby Varkey Maramattom
2016-01-01
Full Text Available Urea cycle disorders (UCD are very rare metabolic disorders that present with encephalopathy and hyperammonemia. Of the UCDs, Arginase deficiency (ARD is the rarest and presents in childhood with a progressive spastic diplegia or seizures. Acute presentation in adulthood is extremely unusual. [1] We present the first case of adult onset ARD presenting with encephalopathy and diffusion weighted MRI findings that resembled a moustache in the midbrain.
Selective updating of working memory content modulates meso-cortico-striatal activity.
Murty, Vishnu P; Sambataro, Fabio; Radulescu, Eugenia; Altamura, Mario; Iudicello, Jennifer; Zoltick, Bradley; Weinberger, Daniel R; Goldberg, Terry E; Mattay, Venkata S
2011-08-01
Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating. Analyses revealed a functionally coupled network consisting of a midbrain region encompassing the substantia nigra/ventral tegmental area, caudate, and dorsolateral prefrontal cortex that was selectively engaged during working memory updating compared to the overwriting and maintenance of working memory content. Further analysis revealed differential midbrain-dorsolateral prefrontal interactions during selective updating between low-performing and high-performing individuals. These findings highlight the role of this meso-cortico-striatal circuitry during the selective updating of working memory in humans, which complements previous research in behavioral neuroscience and computational modeling. Published by Elsevier Inc.
Ripollés, Pablo; Marco-Pallarés, Josep; Alicart, Helena; Tempelmann, Claus; Rodríguez-Fornells, Antoni; Noesselt, Toemme
2016-01-01
Humans constantly learn in the absence of explicit rewards. However, the neurobiological mechanisms supporting this type of internally-guided learning (without explicit feedback) are still unclear. Here, participants who completed a task in which no external reward/feedback was provided, exhibited enhanced fMRI-signals within the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop) when successfully grasping the meaning of new-words. Importantly, new-words that were better remembered showed increased activation and enhanced functional connectivity between the midbrain, hippocampus, and ventral striatum. Moreover, enhanced emotion-related physiological measures and subjective pleasantness ratings during encoding were associated with remembered new-words after 24 hr. Furthermore, increased subjective pleasantness ratings were also related to new-words remembered after seven days. These results suggest that intrinsic—potentially reward-related—signals, triggered by self-monitoring of correct performance, can promote the storage of new information into long-term memory through the activation of the SN/VTA-Hippocampal loop, possibly via dopaminergic modulation of the midbrain. DOI: http://dx.doi.org/10.7554/eLife.17441.001 PMID:27644419
Aparicio, M-Auxiliadora; Saldaña, Enrique
2014-03-01
The tectal longitudinal column (TLC) is a longitudinally oriented, long and narrow nucleus that spans the paramedian region of the midbrain tectum of a large variety of mammals (Saldaña et al. in J Neurosci 27:13108-13116, 2007). Recent analysis of the organization of this region revealed another novel nucleus located immediately dorsal, and parallel, to the TLC. Because the name "tectal longitudinal column" also seems appropriate for this novel nucleus, we suggest the TLC described in 2007 be renamed the "ventral tectal longitudinal column (TLCv)", and the newly discovered nucleus termed the "dorsal tectal longitudinal column (TLCd)". This work represents the first characterization of the rat TLCd. A constellation of anatomical techniques was used to demonstrate that the TLCd differs from its surrounding structures (TLCv and superior colliculus) cytoarchitecturally, myeloarchitecturally, neurochemically and hodologically. The distinct expression of vesicular amino acid transporters suggests that TLCd neurons are GABAergic. The TLCd receives major projections from various areas of the cerebral cortex (secondary visual mediomedial area, and granular and dysgranular retrosplenial cortices) and from the medial pretectal nucleus. It densely innervates the ipsilateral lateral posterior and laterodorsal nuclei of the thalamus. Thus, the TLCd is connected with vision-related neural centers. The TLCd may be unique as it constitutes the only known nucleus made of GABAergic neurons dedicated to providing massive inhibition to higher order thalamic nuclei of a specific sensory modality.
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Tristan Aumentado-Armstrong
2015-10-01
Full Text Available Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems. Such responses emerge in higher brain areas, thereby suggesting that they occur by integrating afferent input. However, the mechanisms by which such integration occurs are poorly understood. Here we show that midbrain electrosensory neurons can respond selectively and in an invariant manner to heterogeneity in behaviorally relevant stimulus waveforms. Such invariant responses were not seen in hindbrain electrosensory neurons providing afferent input to these midbrain neurons, suggesting that response invariance results from nonlinear integration of such input. To test this hypothesis, we built a model based on the Hodgkin-Huxley formalism that received realistic afferent input. We found that multiple combinations of parameter values could give rise to invariant responses matching those seen experimentally. Our model thus shows that there are multiple solutions towards achieving invariant responses and reveals how subthreshold membrane conductances help promote robust and invariant firing in response to heterogeneous stimulus waveforms associated with behaviorally relevant stimuli. We discuss the implications of our findings for the electrosensory and other systems.
Aumentado-Armstrong, Tristan; Metzen, Michael G; Sproule, Michael K J; Chacron, Maurice J
2015-10-01
Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems. Such responses emerge in higher brain areas, thereby suggesting that they occur by integrating afferent input. However, the mechanisms by which such integration occurs are poorly understood. Here we show that midbrain electrosensory neurons can respond selectively and in an invariant manner to heterogeneity in behaviorally relevant stimulus waveforms. Such invariant responses were not seen in hindbrain electrosensory neurons providing afferent input to these midbrain neurons, suggesting that response invariance results from nonlinear integration of such input. To test this hypothesis, we built a model based on the Hodgkin-Huxley formalism that received realistic afferent input. We found that multiple combinations of parameter values could give rise to invariant responses matching those seen experimentally. Our model thus shows that there are multiple solutions towards achieving invariant responses and reveals how subthreshold membrane conductances help promote robust and invariant firing in response to heterogeneous stimulus waveforms associated with behaviorally relevant stimuli. We discuss the implications of our findings for the electrosensory and other systems.
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Pluchino Stefano
2011-07-01
Full Text Available Abstract Background Dopamine-synthesizing (dopaminergic, DA neurons in the ventral midbrain (VM constitute a pivotal neuronal population controlling motor behaviors, cognitive and affective brain functions, which generation critically relies on the activation of Wingless-type MMTV integration site (Wnt/β-catenin pathway in their progenitors. In Parkinson's disease, DA cell bodies within the substantia nigra pars compacta (SNpc progressively degenerate, with causes and mechanisms poorly understood. Emerging evidence suggests that Wnt signaling via Frizzled (Fzd receptors may play a role in different degenerative states, but little is known about Wnt signaling in the adult midbrain. Using in vitro and in vivo model systems of DA degeneration, along with functional studies in both intact and SN lesioned mice, we herein highlight an intrinsic Wnt1/Fzd-1/β-catenin tone critically contributing to the survival and protection of adult midbrain DA neurons. Results In vitro experiments identifie Fzd-1 receptor expression at a mRNA and protein levels in dopamine transporter (DAT expressing neurons, and demonstrate the ability of exogenous Wnt1 to exert robust neuroprotective effects against Caspase-3 activation, the loss of tyrosine hydroxylase-positive (TH+ neurons and [3H] dopamine uptake induced by different DA-specific insults, including serum and growth factor deprivation, 6-hydroxydopamine and MPTP/MPP+. Co-culture of DA neurons with midbrain astrocytes phenocopies Wnt1 neuroprotective effects, whereas RNA interference-mediated knockdown of Wnt1 in midbrain astrocytes markedly reduces astrocyte-induced TH+ neuroprotection. Likewise, silencing β-catenin mRNA or knocking down Fzd-1 receptor expression in mesencephalic neurons counteract astrocyte-induced TH+ neuroprotection. In vivo experiments document Fzd-1 co-localization with TH+ neurons within the intact SNpc and blockade of Fzd/β-catenin signaling by unilateral infusion of a Fzd
The role of the ventral dentate gyrus in olfactory pattern separation.
Weeden, Christy S S; Hu, Nathan J; Ho, Liana U N; Kesner, Raymond P
2014-05-01
Dorsoventral lesion studies of the hippocampus have indicated that the dorsal axis of the hippocampus is important for spatial processing and the ventral axis of the hippocampus is important for olfactory learning and memory and anxiety. There is some evidence to suggest that the ventral CA3 and ventral CA1 conduct parallel processes for pattern completion and temporal processing, respectively. Studies have indicated that the dorsal dentate gyrus (DG) is importantly involved in processes reflecting underlying pattern separation activity for spatial information. However, the ventral DG is less understood. The current study investigated the less-understood role of the ventral DG in olfactory pattern separation. A series of odor stimuli that varied on only one level, number of carbon chains (methyl groups), was used in a matching-to-sample paradigm in order to investigate ventral DG involvement in working memory for similar and less similar odors. Rats with ventral DG lesions were impaired at delays of 60 sec, but not at delays of 15 sec. A memory-based pattern separation effect was observed performance was poorest with only one carbon chain separation between trial odors and was highest for trials with four separations. The present study indicates that the ventral DG plays an important role in olfactory learning and memory processes for highly similar odors. The results also indicate a role for the ventral DG in pattern separation for odor information, which may have further implications for parallel processing across the dorsoventral axis for the DG in spatial (dorsal) and olfactory (ventral) pattern separation. Copyright © 2014 Wiley Periodicals, Inc.
Goutel, C; Kishimoto, Y; Schulte-Merker, S; Rosa, F
2000-12-01
In Xenopus and zebrafish, BMP2, 4 and 7 have been implicated, after the onset of zygotic expression, in inducing and maintaining ventro-lateral cell fate during early development. We provide evidence here that a maternally expressed bone morphogenetic protein (BMP), Radar, may control early ventral specification in zebrafish. We show that Radar ventralizes zebrafish embryos and induces the early expression of bmp2b and bmp4. The analysis of Radar overexpression in both swirl/bmp2b mutants and embryos expressing truncated BMP receptors shows that Radar-induced ventralization is dependent on functional BMP2/4 pathways, and may initially rely on an Alk6-related signaling pathway. Finally, we show that while radar-injected swirl embryos still exhibit a strongly dorsalized phenotype, the overexpression of Radar into swirl/bmp2b mutant embryos restores ventral marker expression, including bmp4 expression. Our results suggest that a complex regulation of different BMP pathways controls dorso-ventral (DV) patterning from early cleavage stages until somitogenesis.
DEFF Research Database (Denmark)
Berrevoet, Frederik; Doerhoff, Carl; Muysoms, Filip
2017-01-01
PURPOSE: This study assessed the recurrence rate and other safety and efficacy parameters following ventral hernia repair with a polyester composite prosthesis (Parietex™ Composite Ventral Patch [PCO-VP]). PATIENTS AND METHODS: A single-arm, multicenter prospective study of 126 patients undergoing...
Becker-Bense, Sandra; Buchholz, Hans-Georg; Baier, Bernhard; Schreckenberger, Mathias; Bartenstein, Peter; Zwergal, Andreas; Brandt, Thomas; Dieterich, Marianne
2016-01-01
The aim of the study was to uncover mechanisms of central compensation of vestibular function at brainstem, cerebellar, and cortical levels in patients with acute unilateral midbrain infarctions presenting with an acute vestibular tone imbalance. Eight out of 17 patients with unilateral midbrain infarctions were selected on the basis of signs of a vestibular tone imbalance, e.g., graviceptive (tilts of perceived verticality) and oculomotor dysfunction (skew deviation, ocular torsion) in F18-fluordeoxyglucose (FDG)-PET at two time points: A) in the acute stage, and B) after recovery 6 months later. Lesion-behavior mapping analyses with MRI verified the exact structural lesion sites. Group subtraction analyses and comparisons with healthy controls were performed with Statistic Parametric Mapping for the PET data. A comparison of PET A of acute-stage patients with that of healthy controls showed increases in glucose metabolism in the cerebellum, motion-sensitive visual cortex areas, and inferior temporal lobe, but none in vestibular cortex areas. At the supratentorial level bilateral signal decreases dominated in the thalamus, frontal eye fields, and anterior cingulum. These decreases persisted after clinical recovery in contrast to the increases. The transient activations can be attributed to ocular motor and postural recovery (cerebellum) and sensory substitution of vestibular function for motion perception (visual cortex). The persisting deactivation in the thalamic nuclei and frontal eye fields allows alternative functional interpretations of the thalamic nuclei: either a disconnection of ascending sensory input occurs or there is a functional mismatch between expected and actual vestibular activity. Our data support the view that both thalami operate separately for each hemisphere but receive vestibular input from ipsilateral and contralateral midbrain integration centers. Normally they have gatekeeper functions for multisensory input to the cortex and automatic
Diversity of bilateral synaptic assemblies for binaural computation in midbrain single neurons.
He, Na; Kong, Lingzhi; Lin, Tao; Wang, Shaohui; Liu, Xiuping; Qi, Jiyao; Yan, Jun
2017-11-01
Binaural hearing confers many beneficial functions but our understanding of its underlying neural substrates is limited. This study examines the bilateral synaptic assemblies and binaural computation (or integration) in the central nucleus of the inferior colliculus (ICc) of the auditory midbrain, a key convergent center. Using in-vivo whole-cell patch-clamp, the excitatory and inhibitory postsynaptic potentials (EPSPs/IPSPs) of single ICc neurons to contralateral, ipsilateral and bilateral stimulation were recorded. According to the contralateral and ipsilateral EPSP/IPSP, 7 types of bilateral synaptic assemblies were identified. These include EPSP-EPSP (EE), E-IPSP (EI), E-no response (EO), II, IE, IO and complex-mode (CM) neurons. The CM neurons showed frequency- and/or amplitude-dependent EPSPs/IPSPs to contralateral or ipsilateral stimulation. Bilateral stimulation induced EPSPs/IPSPs that could be larger than (facilitation), similar to (ineffectiveness) or smaller than (suppression) those induced by contralateral stimulation. Our findings have allowed our group to characterize novel neural circuitry for binaural computation in the midbrain. Copyright © 2017 Elsevier B.V. All rights reserved.
Marty-Santos, Leilani
2015-01-01
Insulin-producing β cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell–cell interactions that might constitute a niche for the developing β cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which β cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to β cells and other pancreatic lineages. PMID:26216134
Progenitor cells in pulmonary vascular remodeling
Yeager, Michael E.; Frid, Maria G.; Stenmark, Kurt R.
2011-01-01
Pulmonary hypertension is characterized by cellular and structural changes in the walls of pulmonary arteries. Intimal thickening and fibrosis, medial hypertrophy and fibroproliferative changes in the adventitia are commonly observed, as is the extension of smooth muscle into the previously non-muscularized vessels. A majority of these changes are associated with the enhanced presence of α-SM-actin+ cells and inflammatory cells. Atypical abundances of functionally distinct endothelial cells, particularly in the intima (plexiform lesions), and also in the perivascular regions, are also described. At present, neither the origin(s) of these cells nor the molecular mechanisms responsible for their accumulation, in any of the three compartments of the vessel wall, have been fully elucidated. The possibility that they arise from either resident vascular progenitors or bone marrow–derived progenitor cells is now well established. Resident vascular progenitor cells have been demonstrated to exist within the vessel wall, and in response to certain stimuli, to expand and express myofibroblastic, endothelial or even hematopoietic markers. Bone marrow–derived or circulating progenitor cells have also been shown to be recruited to sites of vascular injury and to assume both endothelial and SM-like phenotypes. Here, we review the data supporting the contributory role of vascular progenitors (including endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and fibrocytes) in vascular remodeling. A more complete understanding of the processes by which progenitor cells modulate pulmonary vascular remodeling will undoubtedly herald a renaissance of therapies extending beyond the control of vascular tonicity and reduction of pulmonary artery pressure. PMID:22034593
Directory of Open Access Journals (Sweden)
Dennis E Coyle
Full Text Available The NTERA2 cl D1 (NT2 cell line, derived from human teratocarcinoma, exhibits similar properties as embryonic stem (ES cells or very early neuroepithelial progenitors. NT2 cells can be induced to become postmitotic central nervous system neurons (NT2N with retinoic acid. Although neurons derived from pluripotent cells, such as NT2N, have been characterized for their neurotransmitter phenotypes, their potential suitability as a donor source for neural transplantation also depends on their ability to respond to localized environmental cues from a specific region of the CNS. Therefore, our study aimed to characterize the regional transcription factors that define the rostocaudal and dorsoventral identity of NT2N derived from a monolayer differentiation paradigm using quantitative PCR (qPCR. Purified NT2N mainly expressed both GABAergic and glutamatergic phenotypes and were electrically active but did not form functional synapses. The presence of immature astrocytes and possible radial glial cells was noted. The NT2N expressed a regional transcription factor code consistent with forebrain, hindbrain and spinal cord neural progenitors but showed minimal expression of midbrain phenotypes. In the dorsoventral plane NT2N expressed both dorsal and ventral neural progenitors. Of major interest was that even under the influence of retinoic acid, a known caudalization factor, the NT2N population maintained a rostral phenotype subpopulation which expressed cortical regional transcription factors. It is proposed that understanding the regional differentiation bias of neurons derived from pluripotent stem cells will facilitate their successful integration into existing neuronal networks within the CNS.
Directory of Open Access Journals (Sweden)
Aaron McMurtray
2014-01-01
Full Text Available Acute onset of psychosis in an older or elderly individual without history of previous psychiatric disorders should prompt a thorough workup for neurologic causes of psychiatric symptoms. This report compares and contrasts clinical features of new onset of psychotic symptoms between two patients, one with an acute basal ganglia hemorrhagic stroke and another with an acute mid-brain ischemic stroke. Delusions and hallucinations due to basal ganglia lesions are theorized to develop as a result of frontal lobe dysfunction causing impairment of reality checking pathways in the brain, while visual hallucinations due to mid-brain lesions are theorized to develop due to dysregulation of inhibitory control of the ponto-geniculate-occipital system. Psychotic symptoms occurring due to stroke demonstrate varied clinical characteristics that depend on the location of the stroke within the brain. Treatment with antipsychotic medications may provide symptomatic relief.
International Nuclear Information System (INIS)
Hirose, Yoshikazu; Itoh, Tohru; Miyajima, Atsushi
2009-01-01
Hedgehog (Hh) signaling plays crucial roles in development and homeostasis of various organs. In the adult liver, it regulates proliferation and/or viability of several types of cells, particularly under injured conditions, and is also implicated in stem/progenitor cell maintenance. However, the role of this signaling pathway during the normal developmental process of the liver remains elusive. Although Sonic hedgehog (Shh) is expressed in the ventral foregut endoderm from which the liver derives, the expression disappears at the onset of the liver bud formation, and its possible recurrence at the later stages has not been investigated. Here we analyzed the activation and functional relevance of Hh signaling during the mouse fetal liver development. At E11.5, Shh and an activation marker gene for Hh signaling, Gli1, were expressed in Dlk + hepatoblasts, the fetal liver progenitor cells, and the expression was rapidly decreased thereafter as the development proceeded. In the culture of Dlk + hepatoblasts isolated from the E11.5 liver, activation of Hh signaling stimulated their proliferation and this effect was cancelled by a chemical Hh signaling inhibitor, cyclopamine. In contrast, hepatocyte differentiation of Dlk + hepatoblasts in vitro as manifested by the marker gene expression and acquisition of ammonia clearance activity was significantly inhibited by forced activation of Hh signaling. Taken together, these results demonstrate the temporally restricted manner of Hh signal activation and its role in promoting the hepatoblast proliferation, and further suggest that the pathway needs to be shut off for the subsequent hepatic differentiation of hepatoblasts to proceed normally.
Transplanting oligodendrocyte progenitors into the adult CNS
International Nuclear Information System (INIS)
Franklin, R.J.M.; Blakemore, W.F.; Cambridge Univ.
1997-01-01
This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author)
Origin of hemopoietic stromal progenitor cells in chimeras
International Nuclear Information System (INIS)
Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.
1985-01-01
Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice
Directory of Open Access Journals (Sweden)
Sharyn L Rossi
2010-07-01
Full Text Available Motor neuron loss is characteristic of cervical spinal cord injury (SCI and contributes to functional deficit.In order to investigate the amenability of the injured adult spinal cord to motor neuron differentiation, we transplanted spinal cord injured animals with a high purity population of human motor neuron progenitors (hMNP derived from human embryonic stem cells (hESCs. In vitro, hMNPs displayed characteristic motor neuron-specific markers, a typical electrophysiological profile, functionally innervated human or rodent muscle, and secreted physiologically active growth factors that caused neurite branching and neuronal survival. hMNP transplantation into cervical SCI sites in adult rats resulted in suppression of intracellular signaling pathways associated with SCI pathogenesis, which correlated with greater endogenous neuronal survival and neurite branching. These neurotrophic effects were accompanied by significantly enhanced performance on all parameters of the balance beam task, as compared to controls. Interestingly, hMNP transplantation resulted in survival, differentiation, and site-specific integration of hMNPs distal to the SCI site within ventral horns, but hMNPs near the SCI site reverted to a neuronal progenitor state, suggesting an environmental deficiency for neuronal maturation associated with SCI.These findings underscore the barriers imposed on neuronal differentiation of transplanted cells by the gliogenic nature of the injured spinal cord, and the physiological relevance of transplant-derived neurotrophic support to functional recovery.
Norton, Will H; Mangoli, Maryam; Lele, Zsolt; Pogoda, Hans-Martin; Diamond, Brianne; Mercurio, Sara; Russell, Claire; Teraoka, Hiroki; Stickney, Heather L; Rauch, Gerd-Jörg; Heisenberg, Carl-Philipp; Houart, Corinne; Schilling, Thomas F; Frohnhoefer, Hans-Georg; Rastegar, Sepand; Neumann, Carl J; Gardiner, R Mark; Strähle, Uwe; Geisler, Robert; Rees, Michelle; Talbot, William S; Wilson, Stephen W
2005-02-01
In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol-/- embryos, we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol-/- mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves. Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphenucleus and the trochlear motor nucleus are absent in mol-/- embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins.
Aberg, Kristoffer Carl; Doell, Kimberly C; Schwartz, Sophie
2015-10-28
Some individuals are better at learning about rewarding situations, whereas others are inclined to avoid punishments (i.e., enhanced approach or avoidance learning, respectively). In reinforcement learning, action values are increased when outcomes are better than predicted (positive prediction errors [PEs]) and decreased for worse than predicted outcomes (negative PEs). Because actions with high and low values are approached and avoided, respectively, individual differences in the neural encoding of PEs may influence the balance between approach-avoidance learning. Recent correlational approaches also indicate that biases in approach-avoidance learning involve hemispheric asymmetries in dopamine function. However, the computational and neural mechanisms underpinning such learning biases remain unknown. Here we assessed hemispheric reward asymmetry in striatal activity in 34 human participants who performed a task involving rewards and punishments. We show that the relative difference in reward response between hemispheres relates to individual biases in approach-avoidance learning. Moreover, using a computational modeling approach, we demonstrate that better encoding of positive (vs negative) PEs in dopaminergic midbrain regions is associated with better approach (vs avoidance) learning, specifically in participants with larger reward responses in the left (vs right) ventral striatum. Thus, individual dispositions or traits may be determined by neural processes acting to constrain learning about specific aspects of the world. Copyright © 2015 the authors 0270-6474/15/3514491-10$15.00/0.
Directory of Open Access Journals (Sweden)
Liang Cheng
2017-01-01
Full Text Available Most citizen people are exposed daily to environmental noise at moderate levels with a short duration. The aim of the present study was to determine the effects of daily short-term exposure to moderate noise on sound level processing in the auditory midbrain. Sound processing properties of auditory midbrain neurons were recorded in anesthetized mice exposed to moderate noise (80 dB SPL, 2 h/d for 6 weeks and were compared with those from age-matched controls. Neurons in exposed mice had a higher minimum threshold and maximum response intensity, a longer first spike latency, and a higher slope and narrower dynamic range for rate level function. However, these observed changes were greater in neurons with the best frequency within the noise exposure frequency range compared with those outside the frequency range. These sound processing properties also remained abnormal after a 12-week period of recovery in a quiet laboratory environment after completion of noise exposure. In conclusion, even daily short-term exposure to moderate noise can cause long-term impairment of sound level processing in a frequency-specific manner in auditory midbrain neurons.
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Juliana Alves Brandão
2015-04-01
Full Text Available Cortical GABAergic interneurons constitute an extremely diverse population of cells organized in a well-defined topology of precisely interconnected cells. They play a crucial role regulating inhibitory-excitatory balance in brain circuits, gating sensory perception and regulating spike timing to brain oscillations during distinct behaviors. Dysfunctions in the establishment of proper inhibitory circuits have been associated to several brain disorders such as autism, epilepsy and schizophrenia. In the rodent adult cortex, inhibitory neurons are generated during the second gestational week from distinct progenitor lineages located in restricted domains of the ventral telencephalon. However, only recently, studies have revealed some of the mechanisms generating the heterogeneity of neuronal subtypes and their modes of integration in brain networks. Here we will discuss some the events involved in the production of cortical GABAergic neuron diversity with focus on the interaction between intrinsically driven genetic programs and environmental signals during development.
Liu, Zhiqiang; Han, Jing; Jia, Lintao; Maillet, Jean-Christian; Bai, Guang; Xu, Lin; Jia, Zhengping; Zheng, Qiaohua; Zhang, Wandong; Monette, Robert; Merali, Zul; Zhu, Zhou; Wang, Wei; Ren, Wei; Zhang, Xia
2010-12-20
Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.
Directory of Open Access Journals (Sweden)
Zhiqiang Liu
2010-12-01
Full Text Available Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP and long-term depression (LTD. Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses of the midbrain ventral tegmental area (VTA following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids, the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction.
Liu, Zhiqiang; Han, Jing; Jia, Lintao; Maillet, Jean-Christian; Bai, Guang; Xu, Lin; Jia, Zhengping; Zheng, Qiaohua; Zhang, Wandong; Monette, Robert; Merali, Zul; Zhu, Zhou; Wang, Wei; Ren, Wei; Zhang, Xia
2010-01-01
Drug addiction is an association of compulsive drug use with long-term associative learning/memory. Multiple forms of learning/memory are primarily subserved by activity- or experience-dependent synaptic long-term potentiation (LTP) and long-term depression (LTD). Recent studies suggest LTP expression in locally activated glutamate synapses onto dopamine neurons (local Glu-DA synapses) of the midbrain ventral tegmental area (VTA) following a single or chronic exposure to many drugs of abuse, whereas a single exposure to cannabinoid did not significantly affect synaptic plasticity at these synapses. It is unknown whether chronic exposure of cannabis (marijuana or cannabinoids), the most commonly used illicit drug worldwide, induce LTP or LTD at these synapses. More importantly, whether such alterations in VTA synaptic plasticity causatively contribute to drug addictive behavior has not previously been addressed. Here we show in rats that chronic cannabinoid exposure activates VTA cannabinoid CB1 receptors to induce transient neurotransmission depression at VTA local Glu-DA synapses through activation of NMDA receptors and subsequent endocytosis of AMPA receptor GluR2 subunits. A GluR2-derived peptide blocks cannabinoid-induced VTA synaptic depression and conditioned place preference, i.e., learning to associate drug exposure with environmental cues. These data not only provide the first evidence, to our knowledge, that NMDA receptor-dependent synaptic depression at VTA dopamine circuitry requires GluR2 endocytosis, but also suggest an essential contribution of such synaptic depression to cannabinoid-associated addictive learning, in addition to pointing to novel pharmacological strategies for the treatment of cannabis addiction. PMID:21187978
vox homeobox gene: a novel regulator of midbrain-hindbrain boundary development in medaka fish?
Czech Academy of Sciences Publication Activity Database
Fabian, Peter; Pantzartzi, Chrysoula; Kozmiková, Iryna; Kozmik, Zbyněk
2016-01-01
Roč. 226, č. 2 (2016), s. 99-107 ISSN 0949-944X R&D Projects: GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : Midbrain-hindbrain boundary * vox * medaka * Heat shock element * fgf8 * Gene regulatory network Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.422, year: 2016
Long-term polarization of microglia upon alpha-synuclein overexpression in nonhuman primates
DEFF Research Database (Denmark)
Barkholt, Pernille; Sanchez-Guajardo, Vanesa Maria; Kirik, Denis
2012-01-01
We have previously shown that persistent ﰇ-sy- nuclein overexpression in ventral midbrain of marmoset leads to a distinctive neurodegenerative process and motor defects. The neurodegeneration was confined to caudate putamen dopaminergic fibers in animals overexpressing wild-type (wt) ﰇ-synuclein....
Single-minded and the evolution of the ventral midline in arthropods.
Linne, Viktoria; Eriksson, Bo Joakim; Stollewerk, Angelika
2012-04-01
In insects and crustaceans, ventral midline cells are present that subdivide the CNS into bilateral symmetric halves. In both arthropod groups unpaired midline neurons and glial cells have been identified that contribute to the embryonic patterning mechanisms. In the fruitfly Drosophila melanogaster, for example, the midline cells are involved in neural cell fate specification along the dorso-ventral axis but also in axonal pathfinding and organisation of the axonal scaffold. Both in insects and malacostracan crustaceans, the bHLH-PAS transcription factor single-minded is the master regulator of ventral midline development and homology has been suggested for individual midline precursors in these groups. The conserved arrangement of the axonal scaffold as well as the regular pattern of neural precursors in all euarthropod groups raises the question whether the ventral midline system is conserved in this phylum. In the remaining euarthropod groups, the chelicerates and myriapods, a single-minded homologue has been identified in the spider Achaearanea tepidariorum (chelicerate), however, the gene is not expressed in the ventral midline but in the median area of the ventral neuroectoderm. Here we show that At-sim is not required for ventral midline development. Furthermore, we identify sim homologues in representatives of arthropods that have not yet been analysed: the myriapod Strigamia maritima and a representative of an outgroup to the euarthropods, the onychophoran Euperipatoides kanangrensis. We compare the expression patterns to the A. tepidariorum sim homologue expression and furthermore analyse the nature of the arthropod midline cells. Our data suggest that in arthropods unpaired midline precursors evolved from the bilateral median domain of the ventral neuroectoderm in the last common ancestor of Mandibulata (insects, crustaceans, myriapods). We hypothesize that sim was expressed in this domain and recruited to ventral midline development. Subsequently, sim
Opposing dorsal/ventral stream dynamics during figure-ground segregation.
Wokke, Martijn E; Scholte, H Steven; Lamme, Victor A F
2014-02-01
The visual system has been commonly subdivided into two segregated visual processing streams: The dorsal pathway processes mainly spatial information, and the ventral pathway specializes in object perception. Recent findings, however, indicate that different forms of interaction (cross-talk) exist between the dorsal and the ventral stream. Here, we used TMS and concurrent EEG recordings to explore these interactions between the dorsal and ventral stream during figure-ground segregation. In two separate experiments, we used repetitive TMS and single-pulse TMS to disrupt processing in the dorsal (V5/HMT⁺) and the ventral (lateral occipital area) stream during a motion-defined figure discrimination task. We presented stimuli that made it possible to differentiate between relatively low-level (figure boundary detection) from higher-level (surface segregation) processing steps during figure-ground segregation. Results show that disruption of V5/HMT⁺ impaired performance related to surface segregation; this effect was mainly found when V5/HMT⁺ was perturbed in an early time window (100 msec) after stimulus presentation. Surprisingly, disruption of the lateral occipital area resulted in increased performance scores and enhanced neural correlates of surface segregation. This facilitatory effect was also mainly found in an early time window (100 msec) after stimulus presentation. These results suggest a "push-pull" interaction in which dorsal and ventral extrastriate areas are being recruited or inhibited depending on stimulus category and task demands.
Arterial blood supply to the thalamus and midbrain on CT sections, 2
International Nuclear Information System (INIS)
Takeshita, Gen; Ottomo, Michinori; Satoh, Nobuko; Yokoyama, Yoshiaki.
1984-01-01
The selective injection of a dyestuff into thalamoperforating arteries from the posterior part of the circle of Willis, using five postmortem brains, was performed. After fixation, sections parallel to the orbito-meatal line were obtained. In cases which showed a standard development of the posterior communicating arteries, the usual patterns were as follows: the area supplied by perforators of the posterior communicating artery (anterior thalamoperforating artery) was visualized in the hypothalamus and the antero-lateral part of the thalamus; the area supplied by perforators of the proximal segment of the posterior cerebral artery (interpeduncular thalamoperforating artery) was visualized in the midbrain and the medial part of thalamus; the area supplied by perforators of the ambient segment of the posterior cerebral artery (thalamogeniculate artery) was visualized in the medial part of the geniculate body and the posterior part of the thalamus. According to the development of the posterior communicating artery, the area supplied by each perforator was quite variable. Three CT sections were obtained containing three different patterns of the posterior communicating artery: 1) well-developed; 2) moderately developed; and 3) poorly developed. The identification of the area supplied by thalamoperforating arteries on CT sections was quite useful in the CT diagnosis of cerebrovascular disorders which involved the thalamus and the midbrain. (author)
Dopamine release in ventral striatum of pathological gamblers losing money
DEFF Research Database (Denmark)
Linnet, J; Peterson, E; Doudet, D J
2010-01-01
Linnet J, Peterson E, Doudet DJ, Gjedde A, Møller A. Dopamine release in ventral striatum of pathological gamblers losing money. Objective: To investigate dopaminergic neurotransmission in relation to monetary reward and punishment in pathological gambling. Pathological gamblers (PG) often continue...... gambling despite losses, known as 'chasing one's losses'. We therefore hypothesized that losing money would be associated with increased dopamine release in the ventral striatum of PG compared with healthy controls (HC). Method: We used Positron Emission Tomography (PET) with [(11)C]raclopride to measure...... dopamine release in the ventral striatum of 16 PG and 15 HC playing the Iowa Gambling Task (IGT). Results: PG who lost money had significantly increased dopamine release in the left ventral striatum compared with HC. PG and HC who won money did not differ in dopamine release. Conclusion: Our findings...
Subramanian, Hari H.; Holstege, Gert
Subramanian HH, Holstege G. Midbrain and medullary control of postinspiratory activity of the crural and costal diaphragm in vivo. J Neurophysiol 105: 2852-2862, 2011. First published March 30, 2011; doi:10.1152/jn.00168.2011.-Studies on brain stem respiratory neurons suggest that eupnea consists of
Ott, Christian D.; Roberts, Luke F.; da Silva Schneider, André; Fedrow, Joseph M.; Haas, Roland; Schnetter, Erik
2018-03-01
We present a first study of the progenitor star dependence of the three-dimensional (3D) neutrino mechanism of core-collapse supernovae. We employ full 3D general-relativistic multi-group neutrino radiation-hydrodynamics and simulate the postbounce evolutions of progenitors with zero-age main sequence masses of 12, 15, 20, 27, and 40 M ⊙. All progenitors, with the exception of the 12 M ⊙ star, experience shock runaway by the end of their simulations. In most cases, a strongly asymmetric explosion will result. We find three qualitatively distinct evolutions that suggest a complex dependence of explosion dynamics on progenitor density structure, neutrino heating, and 3D flow. (1) Progenitors with massive cores, shallow density profiles, and high post-core-bounce accretion rates experience very strong neutrino heating and neutrino-driven turbulent convection, leading to early shock runaway. Accretion continues at a high rate, likely leading to black hole formation. (2) Intermediate progenitors experience neutrino-driven, turbulence-aided explosions triggered by the arrival of density discontinuities at the shock. These occur typically at the silicon/silicon–oxygen shell boundary. (3) Progenitors with small cores and density profiles without strong discontinuities experience shock recession and develop the 3D standing-accretion shock instability (SASI). Shock runaway ensues late, once declining accretion rate, SASI, and neutrino-driven convection create favorable conditions. These differences in explosion times and dynamics result in a non-monotonic relationship between progenitor and compact remnant mass.
Human V4 and ventral occipital retinotopic maps
Winawer, Jonathan; Witthoft, Nathan
2016-01-01
The ventral surface of the human occipital lobe contains multiple retinotopic maps. The most posterior of these maps is considered a potential homolog of macaque V4, and referred to as human V4 (‘hV4’). The location of the hV4 map, its retinotopic organization, its role in visual encoding, and the cortical areas it borders have been the subject of considerable investigation and debate over the last 25 years. We review the history of this map and adjacent maps in ventral occipital cortex, and consider the different hypotheses for how these ventral occipital maps are organized. Advances in neuroimaging, computational modeling, and characterization of the nearby anatomical landmarks and functional brain areas have improved our understanding of where human V4 is and what kind of visual representations it contains. PMID:26241699
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Anupama Dey
2017-08-01
Full Text Available The birth of new neurons, or neurogenesis, in the adult midbrain is important for progressing dopamine cell-replacement therapies for Parkinson's disease. Most studies suggest newborn cells remain undifferentiated or differentiate into glia within the adult midbrain. However, some studies suggest nestin + neural precursor cells (NPCs have a propensity to generate new neurons here. We sought to confirm this by administering tamoxifen to adult NesCreERT2/R26eYFP transgenic mice, which permanently labelled adult nestin-expressing cells and their progeny with enhanced yellow fluorescent protein (eYFP. eYFP+ midbrain cells were then characterized 1–32 weeks later in acutely prepared brain slices using whole-cell patch clamp electrophysiology combined with single-cell RT-qPCR. Most eYFP+ cells exhibited a mature neuronal phenotype with large amplitude fast action potentials (APs, spontaneous post-synaptic currents (sPSCs, and expression of ‘mature’ neuronal genes (NeuN, Gad1, Gad2 and/or VGLUT2. This was the case even at the earliest time-point following tamoxifen (i.e. 1 week. In comparison to neighboring eYFP− (control cells, eYFP+ cells discharged more APs per unit current injection, and had faster AP time-to-peak, hyperpolarized resting membrane potential, smaller membrane capacitance and shorter duration sPSCs. eYFP+ cells were also differentiated from eYFP− cells by increased expression of ‘immature’ pro-neuronal genes (Pax6, Ngn2 and/or Msx1. However, further analyses failed to reveal evidence of a place of birth, neuronal differentiation, maturation and integration indicative of classical neurogenesis. Thus our findings do not support the notion that nestin + NPCs in the adult SNc and midbrain generate new neurons via classical neurogenesis. Rather, they raise the possibility that mature neurons express nestin under unknown circumstances, and that this is associated with altered physiology and gene expression.
Modified semitendinosus muscle transposition to repair ventral perineal hernia in 14 dogs.
Morello, E; Martano, M; Zabarino, S; Piras, L A; Nicoli, S; Bussadori, R; Buracco, P
2015-06-01
To describe a modified technique of semitendinosus muscle transposition for the repair of ventral perineal hernia. Retrospective review of case records of dogs with ventral perineal hernia that were treated by transposing the medial half of the longitudinally split semitendinosus muscle of one limb. The transposition of the internal obturator muscle was used when uni- or bilateral rectal sacculation was also present in addition to ventral perineal hernia; colopexy and vas deferens pexy were also performed. Fourteen dogs were included. In addition to ventral perineal hernia, unilateral and bilateral perineal hernia was also present in five and six of the dogs, respectively. The mean follow-up time was 890 days. Ventral perineal hernia was successfully managed by the modified semitendinosus muscle transposition with minor complications in all the dogs included in the study. Despite the small number of dogs included, the unilateral transposition of the medial half of the longitudinally split semitendinosus muscle consistently supported the ventral rectal enlargement in perineal hernia without obvious adverse effects. © 2015 British Small Animal Veterinary Association.
International Nuclear Information System (INIS)
Gonzales-Lima, F.
1986-01-01
The autoradiographic ( 14 C)2-deoxyglucose (2-DG) method was used to map the descending effects of midbrain reticular stimulation on the rat cervical spinal cord. The stimulation evoked consistently a defensive 'freezing' reaction as well as a large and highly localized increase in 2-DG uptake in the substantia gelatinosa (SG)(Rexed laminae 2-3). No stimulus-induced changes in 2-DG uptake were produced in the other regions of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of midbrain reticular stimulation on the spinal cord. They also support the concept of an integrative role for the SG in descending reticular mechanisms at the spinal cord level. (author)
Energy Technology Data Exchange (ETDEWEB)
Gonzales-Lima, F
1986-04-24
The autoradiographic (/sup 14/C)2-deoxyglucose (2-DG) method was used to map the descending effects of midbrain reticular stimulation on the rat cervical spinal cord. The stimulation evoked consistently a defensive 'freezing' reaction as well as a large and highly localized increase in 2-DG uptake in the substantia gelatinosa (SG)(Rexed laminae 2-3). No stimulus-induced changes in 2-DG uptake were produced in the other regions of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of the spinal cord. The findings represent the first anatomical demonstration of the activating effects of midbrain reticular stimulation on the spinal cord. They also support the concept of an integrative role for the SG in descending reticular mechanisms at the spinal cord level. 12 refs.
Establishment and initial experiences from the Danish Ventral Hernia Database
DEFF Research Database (Denmark)
Helgstrand, F; Rosenberg, J; Bay-Nielsen, M
2010-01-01
, use of mesh or no mesh, type of suture material, and placement of the mesh. A total of 5,629 elective and 661 acute ventral hernia repairs were registered. After the first 2 years the registration rate was 70%. CONCLUSION: The first national ventral hernia database has been established. Preliminary...... of the Danish Ventral Hernia Database (DVHD). Furthermore, the first 2-year data from 2007 to 2008 are presented. METHODS: Registrations were based on surgeons' web registrations and validated by cross checking with data from the Danish National Patient Register. RESULTS: The DVHD was established in June 2006...... and is based on prospective online web-registration of perioperative data, and individualised tracking of follow up data. During the first 2 years (2007-2008) data showed a large variation in almost all aspects of ventral hernia repair regarding surgical technique, use of open versus laparoscopic technique...
The role of human ventral visual cortex in motion perception
Saygin, Ayse P.; Lorenzi, Lauren J.; Egan, Ryan; Rees, Geraint; Behrmann, Marlene
2013-01-01
Visual motion perception is fundamental to many aspects of visual perception. Visual motion perception has long been associated with the dorsal (parietal) pathway and the involvement of the ventral ‘form’ (temporal) visual pathway has not been considered critical for normal motion perception. Here, we evaluated this view by examining whether circumscribed damage to ventral visual cortex impaired motion perception. The perception of motion in basic, non-form tasks (motion coherence and motion detection) and complex structure-from-motion, for a wide range of motion speeds, all centrally displayed, was assessed in five patients with a circumscribed lesion to either the right or left ventral visual pathway. Patients with a right, but not with a left, ventral visual lesion displayed widespread impairments in central motion perception even for non-form motion, for both slow and for fast speeds, and this held true independent of the integrity of areas MT/V5, V3A or parietal regions. In contrast with the traditional view in which only the dorsal visual stream is critical for motion perception, these novel findings implicate a more distributed circuit in which the integrity of the right ventral visual pathway is also necessary even for the perception of non-form motion. PMID:23983030
Impairment of circulating endothelial progenitors in Down syndrome
Directory of Open Access Journals (Sweden)
Costa Valerio
2010-09-01
Full Text Available Abstract Background Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome. Methods Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis. Results We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells. Conclusions Our data provide evidences for a reduced number and altered
Development of the ventral body wall in the human embryo
Mekonen, Hayelom K.; Hikspoors, Jill P. J. M.; Mommen, Greet; Köhler, S. Eleonore; Lamers, Wouter H.
2015-01-01
Migratory failure of somitic cells is the commonest explanation for ventral body wall defects. However, the embryo increases ~ 25-fold in volume in the period that the ventral body wall forms, so that differential growth may, instead, account for the observed changes in topography. Human embryos
Financial implications of ventral hernia repair: a hospital cost analysis.
Reynolds, Drew; Davenport, Daniel L; Korosec, Ryan L; Roth, J Scott
2013-01-01
Complicated ventral hernias are often referred to tertiary care centers. Hospital costs associated with these repairs include direct costs (mesh materials, supplies, and nonsurgeon labor costs) and indirect costs (facility fees, equipment depreciation, and unallocated labor). Operative supplies represent a significant component of direct costs, especially in an era of proprietary synthetic meshes and biologic grafts. We aim to evaluate the cost-effectiveness of complex abdominal wall hernia repair at a tertiary care referral facility. Cost data on all consecutive open ventral hernia repairs (CPT codes 49560, 49561, 49565, and 49566) performed between 1 July 2008 and 31 May 2011 were analyzed. Cases were analyzed based upon hospital status (inpatient vs. outpatient) and whether the hernia repair was a primary or secondary procedure. We examined median net revenue, direct costs, contribution margin, indirect costs, and net profit/loss. Among primary hernia repairs, cost data were further analyzed based upon mesh utilization (no mesh, synthetic, or biologic). Four-hundred and fifteen patients underwent ventral hernia repair (353 inpatients and 62 outpatients); 173 inpatients underwent ventral hernia repair as the primary procedure; 180 inpatients underwent hernia repair as a secondary procedure. Median net revenue ($17,310 vs. 10,360, p costs for cases performed without mesh were $5,432; median direct costs for those using synthetic and biologic mesh were $7,590 and 16,970, respectively (p financial loss was $8,370. Outpatient ventral hernia repairs, with and without synthetic mesh, resulted in median net losses of $1,560 and 230, respectively. Ventral hernia repair is associated with overall financial losses. Inpatient synthetic mesh repairs are essentially budget neutral. Outpatient and inpatient repairs without mesh result in net financial losses. Inpatient biologic mesh repairs result in a negative contribution margin and striking net financial losses. Cost
Cataclysmic Variables as Supernova Ia Progenitors
Directory of Open Access Journals (Sweden)
Stella Kafka
2012-06-01
Full Text Available Although the identification of the progenitors of type Ia supernovae (SNeIa remains controversial, it is generally accepted that they originate from binary star systems in which at least one component is a carbon-oxygen white dwarf (WD; those systems are grouped under the wide umbrella of cataclysmic variables. Current theories for SNeIa progenitors hold that, either via Roche lobe overflow of the companion or via a wind, the WD accumulates hydrogen or helium rich material which is then burned to C and O onto the WD’s surface. However, the specifics of this scenario are far from being understood or defined, allowing for a wealth of theories fighting for attention and a dearth of observations to support them. I discuss the latest attempts to identify and study those controversial SNeIa progenitors. I also introduce the most promising progenitor in hand and I present observational diagnostics that can reveal more members of the category.
Heimovics, Sarah A; Salvante, Katrina G; Sockman, Keith W; Riters, Lauren V
2011-11-01
Individuals display dramatic differences in social communication even within similar social contexts. Across vertebrates dopaminergic projections from the ventral tegmental area (VTA) and midbrain central gray (GCt) strongly influence motivated, reward-directed behaviors. Norepinephrine is also rich in these areas and may alter dopamine neuronal activity. The present study was designed to provide insight into the roles of dopamine and norepinephrine in VTA and GCt and their efferent striatal target, song control region area X, in the regulation of individual differences in the motivation to sing. We used high pressure liquid chromatography with electrochemical detection to measure dopamine, norepinephrine and their metabolites in micropunched samples from VTA, GCt, and area X in male European starlings (Sturnus vulgaris). We categorized males as sexually motivated or non-sexually motivated based on individual differences in song produced in response to a female. Dopamine markers and norepinephrine in VTA and dopamine in area X correlated positively with sexually-motivated song. Norepinephrine in area X correlated negatively with non-sexually-motivated song. Dopamine in GCt correlated negatively with sexually-motivated song, and the metabolite DOPAC correlated positively with non-sexually-motivated song. Results highlight a role for evolutionarily conserved dopaminergic projections from VTA to striatum in the motivation to communicate and highlight novel patterns of catecholamine activity in area X, VTA, and GCt associated with individual differences in sexually-motivated and non-sexually-motivated communication. Correlations between dopamine and norepinephrine markers also suggest that norepinephrine may contribute to individual differences in communication by modifying dopamine neuronal activity in VTA and GCt. Copyright © 2011. Published by Elsevier Inc.
Maternal control of the Drosophila dorsal–ventral body axis
Stein, David S.; Stevens, Leslie M.
2016-01-01
The pathway that generates the dorsal–ventral (DV) axis of the Drosophila embryo has been the subject of intense investigation over the previous three decades. The initial asymmetric signal originates during oogenesis by the movement of the oocyte nucleus to an anterior corner of the oocyte, which establishes DV polarity within the follicle through signaling between Gurken, the Drosophila Transforming Growth Factor (TGF)-α homologue secreted from the oocyte, and the Drosophila Epidermal Growth Factor Receptor (EGFR) that is expressed by the follicular epithelium cells that envelop the oocyte. Follicle cells that are not exposed to Gurken follow a ventral fate and express Pipe, a sulfotransferase that enzymatically modifies components of the inner vitelline membrane layer of the eggshell, thereby transferring DV spatial information from the follicle to the egg. These ventrally sulfated eggshell proteins comprise a localized cue that directs the ventrally restricted formation of the active Spätzle ligand within the perivitelline space between the eggshell and the embryonic membrane. Spätzle activates Toll, a transmembrane receptor in the embryonic membrane. Transmission of the Toll signal into the embryo leads to the formation of a ventral-to-dorsal gradient of the transcription factor Dorsal within the nuclei of the syncytial blastoderm stage embryo. Dorsal controls the spatially specific expression of a large constellation of zygotic target genes, the Dorsal gene regulatory network, along the embryonic DV circumference. This article reviews classic studies and integrates them with the details of more recent work that has advanced our understanding of the complex pathway that establishes Drosophila embryo DV polarity. PMID:25124754
The Danish ventral hernia database
DEFF Research Database (Denmark)
Helgstrand, Frederik; Jorgensen, Lars Nannestad
2016-01-01
Aim: The Danish Ventral Hernia Database (DVHD) provides national surveillance of current surgical practice and clinical postoperative outcomes. The intention is to reduce postoperative morbidity and hernia recurrence, evaluate new treatment strategies, and facilitate nationwide implementation of ...... of operations and is an excellent tool for observing changes over time, including adjustment of several confounders. This national database registry has impacted on clinical practice in Denmark and led to a high number of scientific publications in recent years.......Aim: The Danish Ventral Hernia Database (DVHD) provides national surveillance of current surgical practice and clinical postoperative outcomes. The intention is to reduce postoperative morbidity and hernia recurrence, evaluate new treatment strategies, and facilitate nationwide implementation...... to the surgical repair are recorded. Data registration is mandatory. Data may be merged with other Danish health registries and information from patient questionnaires or clinical examinations. Descriptive data: More than 37,000 operations have been registered. Data have demonstrated high agreement with patient...
Directory of Open Access Journals (Sweden)
Chenguang Zhou
2017-08-01
Full Text Available Wernekink commissure syndrome secondary to caudal paramedian midbrain infarction (CPMI is a rare midbrain syndrome involving the decussation of the superior cerebellar peduncle in the caudal paramedian midbrain tegmentum. The central characteristics are constant bilateral cerebellar dysfunction, variable eye movement disorders, and rare delayed palatal myoclonus. Following is a description of the case of a 60-year-old man who presented with dizziness, slurred speech, and difficulty walking. Neurological examination revealed bilateral cerebellar dysfunction and bilateral internuclear ophthalmoplegia (bilateral INO. Serial magnetic resonance imaging (MRI revealed a lesion in the caudal paramedian midbrain with a “heart-shaped” sign on fluid-attenuation inversion recovery images and a “V-shaped” appearance on diffusion-weighted imaging (DWI. An acute CPMI with a “heart or V” appearance sign was diagnosed. Upon follow-up evaluation 3 months later, a palatal tremor accompanied by involuntary head tremor was discovered. Hypertrophy and increased signal of the bilateral inferior olivary nucleus, compatible with hypertropic olivary degeneration (HOD were revealed during a subsequent MRI study.
Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure
Tang, Suk Peng; Kuttulebbai Nainamohamed Salam, Sirajudeen; Jaafar, Hasnan; Gan, Siew Hua; Muzaimi, Mustapha; Sulaiman, Siti Amrah
2017-01-01
Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2?mL/kg/day), Tualang honey (1.0?g/kg/day), or ubiquinol (0.2?g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were i...
Functional organization and visual representations in human ventral lateral prefrontal cortex
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Annie Wai Yiu Chan
2013-07-01
Full Text Available Recent neuroimaging studies in both human and non-human primates have identified face selective activation in the ventral lateral prefrontal cortex even in the absence of working memory demands. Further, research has suggested that this face-selective response is largely driven by the presence of the eyes. However, the nature and origin of visual category responses in the ventral lateral prefrontal cortex remain unclear. Further, in a broader sense, how do these findings relate to our current understandings of lateral prefrontal cortex? What do these findings tell us about the underlying function and organization principles of the ventral lateral prefrontal cortex? What is the future direction for investigating visual representations in this cortex? This review focuses on the function, topography, and circuitry of the ventral lateral prefrontal cortex to enhance our understanding of the evolution and development of this cortex.
Radiographic identification of the equine ventral conchal bulla.
Finnegan, C M; Townsend, N B; Barnett, T P; Barakzai, S Z
Involvement of the ventral conchal sinus (VCS) is an important diagnostic and prognostic feature in cases of the equine sinus disease. The authors aimed to ascertain if the caudo-dorsal extension of the VCS, the ventral conchal bulla (VCB) is identifiable on plain radiographs of cadaver skulls without sinus disease. Bilateral frontonasal sinus flaps were made in 10 equine cadaver skulls. Plain lateral, lateral oblique and dorso-ventral radiographs were then obtained followed by the same views taken with stainless steel wire outlining the caudal border of the VCB. Plain radiographs were randomised and blindly evaluated by two observers who marked where they believed the VCB to be positioned. This was then correlated with the true position of the VCB using radiographs with wires in place. The ease of identification of the VCB was classified as 'easy' or 'difficult'. The VCB was correctly identified in 70 per cent of lateral radiographs, but only 45 per cent of lateral oblique radiographs and 17 per cent of dorso-ventral radiographs. If a clinician was confident that he or she could identify the VCB, they were usually correct. Conversely if the clinician judged VCB identification as 'difficult', they usually identified it incorrectly. In the authors' clinical experience, the VCB of horses with sinusitis involving this compartment is more radiologically evident than in clinically normal horses. Knowledge of the normal radiographic anatomy of this structure should aid clinicians in identifying horses with sinusitis affecting the VCS.
The issue of ventral versus dorsal approach in bulbar urethral ...
African Journals Online (AJOL)
E. Palminteri
From surgical point of view, the Barbagli Dorsal Grafting by Dor- sal approach [8] gives a good support for the graft; Barbagli stated that his technique offers a wider augmentation than ventral or dorsal grafting using the ventral approach. The good spongiosum covering seems reduce the risk of fistula; in reality there is a ...
Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass
Menegas, William; Bergan, Joseph F; Ogawa, Sachie K; Isogai, Yoh; Umadevi Venkataraju, Kannan; Osten, Pavel; Uchida, Naoshige; Watabe-Uchida, Mitsuko
2015-01-01
Combining rabies-virus tracing, optical clearing (CLARITY), and whole-brain light-sheet imaging, we mapped the monosynaptic inputs to midbrain dopamine neurons projecting to different targets (different parts of the striatum, cortex, amygdala, etc) in mice. We found that most populations of dopamine neurons receive a similar set of inputs rather than forming strong reciprocal connections with their target areas. A common feature among most populations of dopamine neurons was the existence of dense ‘clusters’ of inputs within the ventral striatum. However, we found that dopamine neurons projecting to the posterior striatum were outliers, receiving relatively few inputs from the ventral striatum and instead receiving more inputs from the globus pallidus, subthalamic nucleus, and zona incerta. These results lay a foundation for understanding the input/output structure of the midbrain dopamine circuit and demonstrate that dopamine neurons projecting to the posterior striatum constitute a unique class of dopamine neurons regulated by different inputs. DOI: http://dx.doi.org/10.7554/eLife.10032.001 PMID:26322384
Aversive counterconditioning attenuates reward signalling in the ventral striatum
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Anne Marije Kaag
2016-08-01
Full Text Available Appetitive conditioning refers to the process of learning cue-reward associations and is mediated by the mesocorticolimbic system. Appetitive conditioned responses are difficult to extinguish, especially for highly salient rewards such as food and drugs. We investigate whether aversive counterconditioning can alter reward reinstatement in the ventral striatum in healthy volunteers using functional Magnetic Resonance Imaging (fMRI. In the initial conditioning phase, two different stimuli were reinforced with a monetary reward. In the subsequent counterconditioning phase, one of these stimuli was paired with an aversive shock to the wrist. In the following extinction phase, none of the stimuli were reinforced. In the final reinstatement phase, reward was reinstated by informing the participants that the monetary gain could be doubled. Our fMRI data revealed that reward signalling in the ventral striatum and ventral tegmental area following reinstatement was smaller for the stimulus that was counterconditioned with an electrical shock, compared to the non-counterconditioned stimulus. A functional connectivity analysis showed that aversive counterconditioning strengthened striatal connectivity with the hippocampus and insula. These results suggest that reward signalling in the ventral striatum can be attenuated through aversive counterconditioning, possibly by concurrent retrieval of the aversive association through enhanced connectivity with hippocampus and insula.
Kesavan, Gokul; Chekuru, Avinash; Machate, Anja; Brand, Michael
2017-01-01
The midbrain-hindbrain boundary (MHB) acts as an organizer and controls the fate of neighboring cells to develop into either mesencephalic (midbrain) or metencephalic (hindbrain) cells by secreting signaling molecules like Wnt1 and Fgf8. The zebrafish is an excellent vertebrate model for studying MHB development due to the ease of gene manipulation and the possibility of following cellular dynamics and morphogenetic processes using live imaging. Currently, only very few reporter and/or Cre-driver lines are available to study gene expression at the MHB, hampering the understanding of MHB development, and traditional transgenic technologies using promoter/enhancer fragments or bacterial artificial chromosome (BAC)-mediated transgenesis often do not faithfully recapitulate endogenous expression patterns. In contrast, CRISPR/Cas9-mediated genome editing technology now provides a great opportunity to efficiently knock-in or knock-out genes. We have generated four CRISPR/Cas9-based knock-in fluorescent reporter lines for two crucial genes involved in MHB development, namely otx2 and pax2a . The coding sequences of the reporters were knocked-in upstream of the corresponding ATG and are, thus, under the control of the endogenous promoter/enhancer elements. Interestingly, this strategy does not disturb endogenous gene expression. Using the fast maturing fluorescent protein reporter, Venus, enabled us to follow MHB development using cell tracking and live imaging. In addition, we show that these reporter lines label various neuronal and glial cell types in the adult zebrafish brain, making them highly suitable for investigating embryonic and adult midbrain, hindbrain, and MHB development.
Sizzled controls dorso-ventral polarity by repressing cleavage of the Chordin protein.
Muraoka, Osamu; Shimizu, Takashi; Yabe, Taijiro; Nojima, Hideaki; Bae, Young-Ki; Hashimoto, Hisashi; Hibi, Masahiko
2006-04-01
The Bone morphogenetic protein (Bmp) signalling gradient has a major function in the formation of the dorso-ventral axis. The zebrafish ventralized mutant, ogon, encodes Secreted Frizzled (Sizzled). sizzled is ventrally expressed in a Bmp-dependent manner and is required for the suppression of Bmp signalling on the ventral side of zebrafish embryos. However, it remains unclear how Sizzled inhibits Bmp signalling and controls ventro-lateral cell fate. We found that Sizzled stabilizes Chordin, a Bmp antagonist, by binding and inhibiting the Tolloid-family metalloproteinase, Bmp1a, which cleaves and inactivates Chordin. The cysteine-rich domain of Sizzled is required for inhibition of Bmp1a activity. Loss of both Bmp1a and Tolloid-like1 (Tll1; another Tolloid-family metalloproteinase) function leads to a complete suppression and reversal of the ogon mutant phenotype. These results indicate that Sizzled represses the activities of Tolloid-family proteins, thereby creating the Chordin-Bmp activity gradient along the dorso-ventral axis. Here, we describe a previously unrecognized role for a secreted Frizzled-related protein.
Requirement of Xmsx-1 in the BMP-triggered ventralization of Xenopus embryos.
Yamamoto, T S; Takagi, C; Ueno, N
2000-03-01
Signaling triggered by polypeptide growth factors leads to the activation of their target genes. Several homeobox genes are known to be induced in response to polypeptide growth factors in early Xenopus development. In particular, Xmsx-1, an amphibian homologue of vertebrate Msx-1, is well characterized as a target gene of bone morphogenetic protein (BMP). Here, using a dominant-negative form of Xmsx-1 (VP-Xmsx-1), which is a fusion protein made with the virus-derived VP16 activation domain, we have examined whether Xmsx-1 activity is required in the endogenous ventralizing pathway. VP-Xmsx-1 induced a secondary body axis, complete with muscle and neural tissues, when overexpressed in ventral blastomeres, suggesting that Xmsx-1 activity is necessary for both mesoderm and ectoderm to be ventralized. We have also examined the epistatic relationship between Xmsx-1 and another ventralizing homeobox protein, Xvent-1, and show that Xmsx-1 is likely to be acting upstream of Xvent-1. We propose that Xmsx-1 is required in the BMP-stimulated ventralization pathway that involves the downstream activation of Xvent-1.
The Role of Microglial Subsets in Regulating Brain Injury
2009-07-01
oil. White scale bars represent a 10 lm distance. For histology, mice were killed and subjected to cardiac perfusion. Harvested brains and spinal cord...isolating ventral midbrain neurons, and we thank Dr Daniel Cua and Dr Barbara Shaikh (Schering- Plough , Palo Alto, CA, USA) and Dr Monica Carson (UC
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Ugliano, Marcella; Janka, Hans-Thomas; Marek, Andreas [Max-Planck-Institut fuer Astrophysik, Karl-Schwarzschild-Str. 1, D-85748 Garching (Germany); Arcones, Almudena [Institut fuer Kernphysik, Technische Universitaet Darmstadt, Schlossgartenstr. 2, D-64289 Darmstadt (Germany)
2012-09-20
We perform hydrodynamic supernova (SN) simulations in spherical symmetry for over 100 single stars of solar metallicity to explore the progenitor-explosion and progenitor-remnant connections established by the neutrino-driven mechanism. We use an approximative treatment of neutrino transport and replace the high-density interior of the neutron star (NS) by an inner boundary condition based on an analytic proto-NS core-cooling model, whose free parameters are chosen such that explosion energy, nickel production, and energy release by the compact remnant of progenitors around 20 M{sub Sun} are compatible with SN 1987A. Thus, we are able to simulate the accretion phase, initiation of the explosion, subsequent neutrino-driven wind phase for 15-20 s, and the further evolution of the blast wave for hours to days until fallback is completed. Our results challenge long-standing paradigms. We find that remnant mass, launch time, and properties of the explosion depend strongly on the stellar structure and exhibit large variability even in narrow intervals of the progenitors' zero-age main-sequence mass. While all progenitors with masses below {approx}15 M{sub Sun} yield NSs, black hole (BH) as well as NS formation is possible for more massive stars, where partial loss of the hydrogen envelope leads to weak reverse shocks and weak fallback. Our NS baryonic masses of {approx}1.2-2.0 M{sub Sun} and BH masses >6 M{sub Sun} are compatible with a possible lack of low-mass BHs in the empirical distribution. Neutrino heating accounts for SN energies between some 10{sup 50} erg and {approx}2 Multiplication-Sign 10{sup 51} erg but can hardly explain more energetic explosions and nickel masses higher than 0.1-0.2 M{sub Sun }. These seem to require an alternative SN mechanism.
DEFF Research Database (Denmark)
Stasiulewicz, Magdalena; Gray, Shona; Mastromina, Ioanna
2015-01-01
Notochord-derived Sonic Hedgehog (SHH) is essential for dorso-ventral patterning of the overlying neural tube. Increasing concentration and duration of Shh signal induces progenitors to acquire progressively more ventral fates. We show Notch signalling augments the response of neuroepithelial cells...
Heterogeneity of limbal basal epithelial progenitor cells.
Hayashida, Yasutaka; Li, Wei; Chen, Ying-Ting; He, Hua; Chen, Szu-yu; Kheirkah, Ahmad; Zhu, Ying-Tien; Matsumoto, Yukihiro; Tseng, Scheffer C G
2010-11-01
Although corneal epithelial stem cells (SCs) are located at the limbus between the cornea and the conjunctiva, not all limbal basal epithelial cells are SCs. Using 2 dispase digestions to remove different amounts of limbal basal epithelial cells for cross-sections, flat mounts, and cytospin preparations, double immunostaining to pancytokeratins (PCK) and vimentin (Vim) identified 3 p63+ epithelial progenitors such as PCK-/Vim+, PCK/Vim, and PCK-/Vim+ and 1 p63+ mesenchymal cell, PCK-/Vim+. PCK-/Vim- progenitors had the smallest cell size were 10-20 times more enriched on collagen I-coated dishes in the 5-minute rapid adherent fraction that contained the highest percentage of p63+ cells but the lowest percentage of cytokeratin12+ cells, and gave rise to high Ki67 labeling and vivid clonal growth. In contrast, PCK+/Vim+ and PCK+/Vim- progenitors were found more in the slow-adherent fraction and yielded poor clonal growth. PCK/Vim progenitors and clusters of PCK-/Vim+ mesenchymal cells, which were neither melanocytes nor Langerhans cells, were located in the limbal basal region. Therefore, differential expression of PCK and Vim helps identify small PCK-/Vim- cells as the most likely candidate for SCs among a hierarchy of heterogeneous limbal basal progenitors, and their close association with PCK-/Vim+ presumed "niche" cells.
Biology and flow cytometry of proangiogenic hematopoietic progenitors cells.
Rose, Jonathan A; Erzurum, Serpil; Asosingh, Kewal
2015-01-01
During development, hematopoiesis and neovascularization are closely linked to each other via a common bipotent stem cell called the hemangioblast that gives rise to both hematopoietic cells and endothelial cells. In postnatal life, this functional connection between the vasculature and hematopoiesis is maintained by a subset of hematopoietic progenitor cells endowed with the capacity to differentiate into potent proangiogenic cells. These proangiogenic hematopoietic progenitors comprise a specific subset of bone marrow (BM)-derived cells that homes to sites of neovascularization and possess potent paracrine angiogenic activity. There is emerging evidence that this subpopulation of hematopoietic progenitors plays a critical role in vascular health and disease. Their angiogenic activity is distinct from putative "endothelial progenitor cells" that become structural cells of the endothelium by differentiation into endothelial cells. Proangiogenic hematopoietic progenitor cell research requires multidisciplinary expertise in flow cytometry, hematology, and vascular biology. This review provides a comprehensive overview of proangiogenic hematopoietic progenitor cell biology and flow cytometric methods to detect these cells in the peripheral blood circulation and BM. © 2014 International Society for Advancement of Cytometry.
Nationwide analysis of prolonged hospital stay and readmission after elective ventral hernia repair
DEFF Research Database (Denmark)
Helgstrand, Frederik; Rosenberg, Jacob; Kehlet, Henrik
2011-01-01
Early outcome after elective ventral hernia repair is unsatisfactory, but detailed analyses are lacking. The aim of this study was to describe the aetiology of prolonged hospital stay (LOS), readmission and death <30 days after elective ventral hernia repair.......Early outcome after elective ventral hernia repair is unsatisfactory, but detailed analyses are lacking. The aim of this study was to describe the aetiology of prolonged hospital stay (LOS), readmission and death
Novel structural components of the ventral disc and lateral crest in Giardia intestinalis.
Directory of Open Access Journals (Sweden)
Kari D Hagen
2011-12-01
Full Text Available Giardia intestinalis is a ubiquitous parasitic protist that is the causative agent of giardiasis, one of the most common protozoan diarrheal diseases in the world. Giardia trophozoites attach to the intestinal epithelium using a specialized and elaborate microtubule structure, the ventral disc. Surrounding the ventral disc is a less characterized putatively contractile structure, the lateral crest, which forms a continuous perimeter seal with the substrate. A better understanding of ventral disc and lateral crest structure, conformational dynamics, and biogenesis is critical for understanding the mechanism of giardial attachment to the host. To determine the components comprising the ventral disc and lateral crest, we used shotgun proteomics to identify proteins in a preparation of isolated ventral discs. Candidate disc-associated proteins, or DAPs, were GFP-tagged using a ligation-independent high-throughput cloning method. Based on disc localization, we identified eighteen novel DAPs, which more than doubles the number of known disc-associated proteins. Ten of the novel DAPs are associated with the lateral crest or outer edge of the disc, and are the first confirmed components of this structure. Using Fluorescence Recovery After Photobleaching (FRAP with representative novel DAP::GFP strains we found that the newly identified DAPs tested did not recover after photobleaching and are therefore structural components of the ventral disc or lateral crest. Functional analyses of the novel DAPs will be central toward understanding the mechanism of ventral disc-mediated attachment and the mechanism of disc biogenesis during cell division. Since attachment of Giardia to the intestine via the ventral disc is essential for pathogenesis, it is possible that some proteins comprising the disc could be potential drug targets if their loss or disruption interfered with disc biogenesis or function, preventing attachment.
Reporter-Based Isolation of Developmental Myogenic Progenitors
Directory of Open Access Journals (Sweden)
Eyemen Kheir
2018-04-01
Full Text Available The formation and activity of mammalian tissues entail finely regulated processes, involving the concerted organization and interaction of multiple cell types. In recent years the prospective isolation of distinct progenitor and stem cell populations has become a powerful tool in the hands of developmental biologists and has rendered the investigation of their intrinsic properties possible. In this protocol, we describe how to purify progenitors with different lineage history and degree of differentiation from embryonic and fetal skeletal muscle by fluorescence-activated cell sorting (FACS. The approach takes advantage of a panel of murine strains expressing fluorescent reporter genes specifically in the myogenic progenitors. We provide a detailed description of the dissection procedures and of the enzymatic dissociation required to maximize the yield of mononucleated cells for subsequent FACS-based purification. The procedure takes ~6–7 h to complete and allows for the isolation and the subsequent molecular and phenotypic characterization of developmental myogenic progenitors.
MicroRNA-326 acts as a molecular switch in the regulation of midbrain urocortin 1 expression
Aschrafi, Armaz; Verheijen, Jan M.; Gordebeke, Peter M.; Olde Loohuis, Nikkie F.; Menting, Kelly; Jager, Amanda; Palkovits, Miklos; Geenen, Bram; Kos, Aron; Martens, Gerard J.M.; Glennon, Jeffrey C.; Kaplan, Barry B.; Gaszner, Balázs; Kozicz, Tamas
2016-01-01
Background Altered levels of urocortin 1 (Ucn1) in the centrally projecting Edinger–Westphal nucleus (EWcp) of depressed suicide attempters or completers mediate the brain’s response to stress, while the mechanism regulating Ucn1 expression is unknown. We tested the hypothesis that microRNAs (miRNAs), which are vital fine-tuners of gene expression during the brain’s response to stress, have the capacity to modulate Ucn1 expression. Methods Computational analysis revealed that the Ucn1 3′ untranslated region contained a conserved binding site for miR-326. We examined miR-326 and Ucn1 levels in the EWcp of depressed suicide completers. In addition, we evaluated miR-326 and Ucn1 levels in the serum and the EWcp of a chronic variable mild stress (CVMS) rat model of behavioural despair and after recovery from CVMS, respectively. Gain and loss of miR-326 function experiments examined the regulation of Ucn1 by this miRNA in cultured midbrain neurons. Results We found reduced miR-326 levels concomitant with elevated Ucn1 levels in the EWcp of depressed suicide completers as well as in the EWcp of CVMS rats. In CVMS rats fully recovered from stress, both serum and EWcp miR-326 levels rebounded to nonstressed levels. While downregulation of miR-326 levels in primary midbrain neurons enhanced Ucn1 expression levels, miR-326 overexpression selectively reduced the levels of this neuropeptide. Limitations This study lacked experiments showing that in vivo alteration of miR-326 levels alleviate depression-like behaviours. We show only correlative data for miR-325 and cocaine- and amphetamine-regulated transcript levels in the EWcp. Conclusion We identified miR-326 dysregulation in depressed suicide completers and characterized this miRNA as an upstream regulator of the Ucn1 neuropeptide expression in midbrain neurons. PMID:27045550
SUPERNOVA REMNANT PROGENITOR MASSES IN M31
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Jennings, Zachary G.; Williams, Benjamin F.; Dalcanton, Julianne J.; Gilbert, Karoline M.; Fouesneau, Morgan; Weisz, Daniel R. [Department of Astronomy, University of Washington Seattle, Box 351580, WA 98195 (United States); Murphy, Jeremiah W. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Dolphin, Andrew E., E-mail: zachjenn@uw.edu, E-mail: adolphin@raytheon.com [Raytheon, 1151 East Hermans Road, Tucson, AZ 85706 (United States)
2012-12-10
Using Hubble Space Telescope photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main-sequence masses (M{sub ZAMS}) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and employ CMD fitting to measure the recent star formation history of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star, then assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the M{sub ZAMS} from this age. Because our technique is not contingent on identification or precise location of the progenitor star, it can be applied to the location of any known SNRs. We identify significant young star formation around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of {approx}2 increase over currently measured progenitor masses. We consider the remaining six SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped their birth sites. In general, the distribution of recovered progenitor masses is bottom-heavy, showing a paucity of the most massive stars. If we assume a single power-law distribution, dN/dM{proportional_to}M{sup {alpha}}, then we find a distribution that is steeper than a Salpeter initial mass function (IMF) ({alpha} = -2.35). In particular, we find values of {alpha} outside the range -2.7 {>=} {alpha} {>=} -4.4 to be inconsistent with our measured distribution at 95% confidence. If instead we assume a distribution that follows a Salpeter IMF up to some maximum mass, then we find that values of M{sub Max} > 26 are inconsistent with the measured distribution at 95% confidence. In either scenario, the data suggest that some fraction of massive stars may not explode. The result is preliminary and requires more SNRs and further analysis. In addition, we use our distribution to estimate a
Apc1 is required for maintenance of local brain organizers and dorsal midbrain survival.
Paridaen, Judith T M L; Danesin, Catherine; Elas, Abu Tufayal; van de Water, Sandra; Houart, Corinne; Zivkovic, Danica
2009-07-15
The tumor suppressor Apc1 is an intracellular antagonist of the Wnt/beta-catenin pathway, which is vital for induction and patterning of the early vertebrate brain. However, its role in later brain development is less clear. Here, we examined the mechanisms underlying effects of an Apc1 zygotic-effect mutation on late brain development in zebrafish. Apc1 is required for maintenance of established brain subdivisions and control of local organizers such as the isthmic organizer (IsO). Caudal expansion of Fgf8 from IsO into the cerebellum is accompanied by hyperproliferation and abnormal cerebellar morphogenesis. Loss of apc1 results in reduced proliferation and apoptosis in the dorsal midbrain. Mosaic analysis shows that Apc is required cell-autonomously for maintenance of dorsal midbrain cell fate. The tectal phenotype occurs independently of Fgf8-mediated IsO function and is predominantly caused by stabilization of beta-catenin and subsequent hyperactivation of Wnt/beta-catenin signalling, which is mainly mediated through LEF1 activity. Chemical activation of the Wnt/beta-catenin in wild-type embryos during late brain maintenance stages phenocopies the IsO and tectal phenotypes of the apc mutants. These data demonstrate that Apc1-mediated restriction of Wnt/beta-catenin signalling is required for maintenance of local organizers and tectal integrity.
Directory of Open Access Journals (Sweden)
Sollars Vincent E
2009-03-01
Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.
Progenitor's Signatures in Type Ia Supernova Remnants
Chiotellis, A.; Kosenko, D.; Schure, K.M.; Vink, J.
2013-01-01
The remnants of Type Ia supernovae (SNe Ia) can provide important clues about their progenitor histories. We discuss two well-observed supernova remnants (SNRs) that are believed to have resulted from SNe Ia, and use various tools to shed light on the possible progenitor histories. We find that
Behavioral Specifications of Reward-Associated Long-Term Memory Enhancement in Humans
Wittmann, Bianca C.; Dolan, Raymond J.; Duzel, Emrah
2011-01-01
Recent functional imaging studies link reward-related activation of the midbrain substantia nigra-ventral tegmental area (SN/VTA), the site of origin of ascending dopaminergic projections, with improved long-term episodic memory. Here, we investigated in two behavioral experiments how (1) the contingency between item properties and reward, (2) the…
Gerrits, P.O.; Kortekaas, R.; de Weerd, Heleen; Luiten, P.G.M.; van der Want, J.J.L.; Veening, Jan
2013-01-01
Spumiform basement membrane degeneration (sbmd) is a specific kind of aberration present in the capillaries of the midbrain periaqueductal gray (PAG) region of the senescent hamster. These capillaries, separated by the ependymal cell layer, are bordering the Sylvian cerebral aqueduct. The aqueduct,
Gerrits, P.O.; Kortekaas, R.; Weerd, H. de; Luiten, P.G.M.; Want, J.J. van der; Veening, J.G.
2013-01-01
Spumiform basement membrane degeneration (sbmd) is a specific kind of aberration present in the capillaries of the midbrain periaqueductal gray (PAG) region of the senescent hamster. These capillaries, separated by the ependymal cell layer, are bordering the Sylvian cerebral aqueduct. The aqueduct,
Hippocampal projections to the ventral striatum: from spatial memory to motivated behavior
van der Meer, M.M.A; Ito, R.; Lansink, C.S.; Pennartz, C.M.A.; Derdikman, D.; Knierim, J.J.
2014-01-01
Multiple regions of the hippocampal formation project to the ventral striatum, a central node in brain circuits that subserve aspects of motivation. These projections emphasize information flow from the ventral (temporal) pole of the hippocampus and interact with converging projections and
Progress of stem/progenitor cell-based therapy for retinal degeneration.
Tang, Zhimin; Zhang, Yi; Wang, Yuyao; Zhang, Dandan; Shen, Bingqiao; Luo, Min; Gu, Ping
2017-05-10
Retinal degeneration (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa, is one of the leading causes of blindness. Presently, no satisfactory therapeutic options are available for these diseases principally because the retina and retinal pigmented epithelium (RPE) do not regenerate, although wet AMD can be prevented from further progression by anti-vascular endothelial growth factor therapy. Nevertheless, stem/progenitor cell approaches exhibit enormous potential for RD treatment using strategies mainly aimed at the rescue and replacement of photoreceptors and RPE. The sources of stem/progenitor cells are classified into two broad categories in this review, which are (1) ocular-derived progenitor cells, such as retinal progenitor cells, and (2) non-ocular-derived stem cells, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stromal cells. Here, we discuss in detail the progress in the study of four predominant stem/progenitor cell types used in animal models of RD. A short overview of clinical trials involving the stem/progenitor cells is also presented. Currently, stem/progenitor cell therapies for RD still have some drawbacks such as inhibited proliferation and/or differentiation in vitro (with the exception of the RPE) and limited long-term survival and function of grafts in vivo. Despite these challenges, stem/progenitor cells represent the most promising strategy for RD treatment in the near future.
Selective uptake of boronophenylalanine by glioma stem/progenitor cells
International Nuclear Information System (INIS)
Sun, Ting; Zhou, Youxin; Xie, Xueshun; Chen, Guilin; Li, Bin; Wei, Yongxin; Chen, Jinming; Huang, Qiang; Du, Ziwei
2012-01-01
The success of boron neutron capture therapy (BNCT) depends on the amount of boron in cells and the tumor/blood and tumor/(normal tissue) boron concentration ratios. For the first time, measurements of boron uptake in both stem/progenitor and differentiated glioma cells were performed along with measurements of boron biodistribution in suitable animal models. In glioma stem/progenitor cells, the selective accumulation of boronophenylalanine (BPA) was lower, and retention of boron after BPA removal was longer than in differentiated glioma cells in vitro. However, boron biodistribution was not statistically significantly different in mice with xenografts. - Highlights: ► Uptake of BPA was analyzed in stem/progenitor and differentiated glioma cells. ► Selective accumulation of BPA was lower in glioma stem/progenitor cells. ► Retention of boron after BPA removal was longer in glioma stem/progenitor cells. ► Boron biodistribution was not statistically different in mice with xenografts.
Crossmodal Recruitment of the Ventral Visual Stream in Congenital Blindness
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Maurice Ptito
2012-01-01
Full Text Available We used functional MRI (fMRI to test the hypothesis that blind subjects recruit the ventral visual stream during nonhaptic tactile-form recognition. Congenitally blind and blindfolded sighted control subjects were scanned after they had been trained during four consecutive days to perform a tactile-form recognition task with the tongue display unit (TDU. Both groups learned the task at the same rate. In line with our hypothesis, the fMRI data showed that during nonhaptic shape recognition, blind subjects activated large portions of the ventral visual stream, including the cuneus, precuneus, inferotemporal (IT, cortex, lateral occipital tactile vision area (LOtv, and fusiform gyrus. Control subjects activated area LOtv and precuneus but not cuneus, IT and fusiform gyrus. These results indicate that congenitally blind subjects recruit key regions in the ventral visual pathway during nonhaptic tactile shape discrimination. The activation of LOtv by nonhaptic tactile shape processing in blind and sighted subjects adds further support to the notion that this area subserves an abstract or supramodal representation of shape. Together with our previous findings, our data suggest that the segregation of the efferent projections of the primary visual cortex into a dorsal and ventral visual stream is preserved in individuals blind from birth.
Identification of Different Classes of Luminal Progenitor Cells within Prostate Tumors
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Supreet Agarwal
2015-12-01
Full Text Available Primary prostate cancer almost always has a luminal phenotype. However, little is known about the stem/progenitor properties of transformed cells within tumors. Using the aggressive Pten/Tp53-null mouse model of prostate cancer, we show that two classes of luminal progenitors exist within a tumor. Not only did tumors contain previously described multipotent progenitors, but also a major population of committed luminal progenitors. Luminal cells, sorted directly from tumors or grown as organoids, initiated tumors of adenocarcinoma or multilineage histological phenotypes, which is consistent with luminal and multipotent differentiation potentials, respectively. Moreover, using organoids we show that the ability of luminal-committed progenitors to self-renew is a tumor-specific property, absent in benign luminal cells. Finally, a significant fraction of luminal progenitors survived in vivo castration. In all, these data reveal two luminal tumor populations with different stem/progenitor cell capacities, providing insight into prostate cancer cells that initiate tumors and can influence treatment response.
Strategies to reverse endothelial progenitor cell dysfunction in diabetes.
Petrelli, Alessandra; Di Fenza, Raffaele; Carvello, Michele; Gatti, Francesca; Secchi, Antonio; Fiorina, Paolo
2012-01-01
Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial), their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs). Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.
Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes
Directory of Open Access Journals (Sweden)
Alessandra Petrelli
2012-01-01
Full Text Available Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial, their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs. Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications.
Ionizing radiation induces apoptosis in hematopoietic stem and progenitor cells
International Nuclear Information System (INIS)
Meng, A.; Zhou, D.; Geiger, H.; Zant, G.V.
2003-01-01
The aims of this study was to determine if ionizing radiation (IR) induces apoptosis in hematopoietic stem (HSC) and progenitor cells. Lin-cells were isolated from mouse bone marrow (BM) and pretreated with vehicle or 100 μM z-VAD 1 h prior to exposure to 4 Gy IR. The apoptotic and/or necrotic responses of these cells to IR were analyzed by measuring the annexin V and/or 7-AAD staining in HSC and progenitor populations using flow cytometry, and hematopoietic function of these cells was determined by CAFC assay. Exposure of Lin-cells to IR selectively decreased the numbers of HSC and progenitors in association with an increase in apoptosis in a time-dependent manner. Pretreatment of Lin- cells with z-VAD significantly inhibited IR-induced apoptosis and the decrease in the numbers of HSC and progenitors. However, IR alone or in combination with z-VAD did not lead to a significant increase in necrotic cell death in either HSC or progenitors. In addition, pretreatment of BM cells with z-VAD significantly attenuated IR-induced reduction in the frequencies of day-7, -28 and -35 CAFC. Exposure of HSC and progenitors to IR induces apoptosis. The induction of HSC and progenitor apoptosis contributes to IR-induced suppression of their hematopoietic function
THE PROGENITOR OF THE TYPE IIb SN 2008ax REVISITED
International Nuclear Information System (INIS)
Folatelli, Gastón; Bersten, Melina C.; Benvenuto, Omar G.; Kuncarayakti, Hanindyo; Maeda, Keiichi; Nomoto, Ken’ichi
2015-01-01
Hubble Space Telescope observations of the site of the supernova (SN) SN 2008ax obtained in 2011 and 2013 reveal that the possible progenitor object detected in pre-explosion images was in fact multiple. Four point sources are resolved in the new, higher-resolution images. We identify one of the sources with the fading SN. The other three objects are consistent with single supergiant stars. We conclude that their light contaminated the previously identified progenitor candidate. After subtraction of these stars, the progenitor appears to be significantly fainter and bluer than previously measured. Post-explosion photometry at the SN location indicates that the progenitor object has disappeared. If single, the progenitor is compatible with a supergiant star of B to mid-A spectral type, while a Wolf–Rayet (W-R) star would be too luminous in the ultraviolet to account for the observations. Moreover, our hydrodynamical modeling shows that the pre-explosion mass was 4–5 M ⊙ and the radius was 30–50 R ⊙ , which is incompatible with a W-R progenitor. We present a possible interacting binary progenitor computed with our evolutionary models that reproduces all the observational evidence. A companion star as luminous as an O9–B0 main-sequence star may have remained after the explosion
Retinal progenitor cell xenografts to the pig retina
DEFF Research Database (Denmark)
Warfvinge, Karin; Kiilgaard, Jens Folke; Lavik, Erin B
2005-01-01
To investigate the survival, integration, and differentiation of mouse retinal progenitor cells after transplantation to the subretinal space of adult pigs.......To investigate the survival, integration, and differentiation of mouse retinal progenitor cells after transplantation to the subretinal space of adult pigs....
Zhang, Tie-Yuan; Keown, Christopher L; Wen, Xianglan; Li, Junhao; Vousden, Dulcie A; Anacker, Christoph; Bhattacharyya, Urvashi; Ryan, Richard; Diorio, Josie; O'Toole, Nicholas; Lerch, Jason P; Mukamel, Eran A; Meaney, Michael J
2018-01-19
Early life experience influences stress reactivity and mental health through effects on cognitive-emotional functions that are, in part, linked to gene expression in the dorsal and ventral hippocampus. The hippocampal dentate gyrus (DG) is a major site for experience-dependent plasticity associated with sustained transcriptional alterations, potentially mediated by epigenetic modifications. Here, we report comprehensive DNA methylome, hydroxymethylome and transcriptome data sets from mouse dorsal and ventral DG. We find genome-wide transcriptional and methylation differences between dorsal and ventral DG, including at key developmental transcriptional factors. Peripubertal environmental enrichment increases hippocampal volume and enhances dorsal DG-specific differences in gene expression. Enrichment also enhances dorsal-ventral differences in DNA methylation, including at binding sites of the transcription factor NeuroD1, a regulator of adult neurogenesis. These results indicate a dorsal-ventral asymmetry in transcription and methylation that parallels well-known functional and anatomical differences, and that may be enhanced by environmental enrichment.
Amiragova, M G; Arakhangel'skaia, M I
1983-08-01
Chronic animal experiments were made to study the endocrine and electroencephalographic responses of the cortico-subcortical structures to stress before and after coagulation of the midbrain reticular formation. The operation entailed dramatic changes in both the bioelectrical responses and thyroid and adrenal responses, which were found to be differentiated.
The ventral visual pathway: an expanded neural framework for the processing of object quality.
Kravitz, Dwight J; Saleem, Kadharbatcha S; Baker, Chris I; Ungerleider, Leslie G; Mishkin, Mortimer
2013-01-01
Since the original characterization of the ventral visual pathway, our knowledge of its neuroanatomy, functional properties, and extrinsic targets has grown considerably. Here we synthesize this recent evidence and propose that the ventral pathway is best understood as a recurrent occipitotemporal network containing neural representations of object quality both utilized and constrained by at least six distinct cortical and subcortical systems. Each system serves its own specialized behavioral, cognitive, or affective function, collectively providing the raison d'être for the ventral visual pathway. This expanded framework contrasts with the depiction of the ventral visual pathway as a largely serial staged hierarchy culminating in singular object representations and more parsimoniously incorporates attentional, contextual, and feedback effects. Published by Elsevier Ltd.
Binocular depth processing in the ventral visual pathway.
Verhoef, Bram-Ernst; Vogels, Rufin; Janssen, Peter
2016-06-19
One of the most powerful forms of depth perception capitalizes on the small relative displacements, or binocular disparities, in the images projected onto each eye. The brain employs these disparities to facilitate various computations, including sensori-motor transformations (reaching, grasping), scene segmentation and object recognition. In accordance with these different functions, disparity activates a large number of regions in the brain of both humans and monkeys. Here, we review how disparity processing evolves along different regions of the ventral visual pathway of macaques, emphasizing research based on both correlational and causal techniques. We will discuss the progression in the ventral pathway from a basic absolute disparity representation to a more complex three-dimensional shape code. We will show that, in the course of this evolution, the underlying neuronal activity becomes progressively more bound to the global perceptual experience. We argue that these observations most probably extend beyond disparity processing per se, and pertain to object processing in the ventral pathway in general. We conclude by posing some important unresolved questions whose answers may significantly advance the field, and broaden its scope.This article is part of the themed issue 'Vision in our three-dimensional world'. © 2016 The Author(s).
Visualization of nitric oxide production in the earthworm ventral nerve cord.
Kitamura, Y; Naganoma, Y; Horita, H; Tsuji, N; Shimizu, R; Ogawa, H; Oka, K
2001-06-01
Distribution of nitric oxide (NO)-producible neurons in the ventral nerve cord (VNC) of the earthworm was investigated by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry. Some neurons (20-30 microm in diameter) were intensely stained and were localized in areas between the 1st and 2nd lateral nerves in the ventral side of VNC. In contrast, no neurons including giant fibers were stained in the dorsal side. Endogenous NO production from VNC was visualized using a fluorescent dye, diaminofluorescein-2 diacethyl (DAF-2 DA). When VNC was incubated in a saline, a relative high level of NO was produced from the ventral side, especially from NADPH-d-positive neurons. Under high-K+ stimulation, NO was also detected in the giant fibers in the dorsal side of VNC. Our results suggest that the earthworm VNC constantly and relative highly produces NO as a neuromodulator, and that NO produced from the ventral side sometimes reaches and affects the giant fibers. In conclusion, we successfully visualized NO in the earthworm VNC by clarifying both the distribution of NO-producible neurons and the endogenous NO production.
Mesh versus non-mesh repair of ventral abdominal hernias
International Nuclear Information System (INIS)
Jawaid, M.A.; Talpur, A.H.
2008-01-01
To investigate the relative effectiveness of mesh and suture repair of ventral abdominal hernias in terms of clinical outcome, quality of life and rate of recurrence in both the techniques. This is a retrospective descriptive analysis of 236 patients with mesh and non-mesh repair of primary ventral hernias performed between January 2000 to December 2004 at Surgery Department, Liaquat University of Medical and Health Sciences, Jamshoro. The record sheets of the patients were analyzed and data retrieved to compare the results of both techniques for short-term and long-term results. The data retrieved is statistically analyzed on SPSS version 11. There were 43 (18.22%) males and 193 (81.77%) females with a mean age of 51.79 years and a range of 59 (81-22). Para-umbilical hernia was the commonest of ventral hernia and accounted for 49.8% (n=118) of the total study population followed by incisional hernia comprising 24% (n=57) of the total number. There was a significant difference in the recurrent rate at 3 years interval with 23/101 (22.77%) recurrences in suture-repaired subjects compared to 10/135 (7.40%) in mesh repair group. Chronic pain lasting up to 1-2 years was noted in 14 patients with suture repair. Wound infection is comparatively more common (8.14%) in mesh group. The other variables such as operative and postoperative complications, total hospital stay and quality of life is also discussed. Mesh repair of ventral hernia is much superior to non-mesh suture repair in terms of recurrence and overall outcome. (author)
A Case of Midbrain and Thalamic Infarction Involving Artery of Percheron
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Muhammad Almamun
2015-03-01
Full Text Available Blood supply to the thalamus and brainstem have frequent anatomic variations. One of these is where all the perforators to the above areas arise from a single branch of the posterior cerebral artery commonly known as the artery of Percheron. Infarction involving this artery leading to bilateral thalamic and midbrain lesions is not uncommon, but can cause diagnostic difficulties due to the varying clinical presentations possible and the wide differentials. Early brain imaging and diagnosis is important for initiating appropriate treatment. In this case report, we discuss a patient who presented with an artery of Percheron related stroke affecting the mid brain and paramedian thalamic areas. We also discuss the differentials of presentations with similar symptoms.
Cocaine exposure shifts the balance of associative encoding from ventral to dorsolateral striatum
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Yuji Takahashi
2007-12-01
Full Text Available Both dorsal and ventral striatum are implicated in the "habitization" of behavior that occurs in addiction. Here we examined the effect of cocaine exposure on associative encoding in these two regions. Neural activity was recorded during go/no-go discrimination learning and reversal. Activity in ventral striatum developed and reversed rapidly, tracking the valence of the predicted outcome, whereas activity in dorsolateral striatum developed and reversed more slowly, tracking discriminative responding. This difference is consistent with the putative roles of these two areas in promoting habit-like behavior. Dorsolateral striatum has been directly implicated in habit or stimulus response learning, whereas ventral striatum appears to be involved indirectly by allowing cues associated with reward to exert a general motivational influence on responding. Interestingly cocaine exposure did not uniformly enhance processing across both regions. Instead cocaine reduced the degree and flexibility of cue-evoked firing in ventral striatum while marginally enhanced cue-selective firing in dorsolateral striatum. Thus cocaine exposure causes regionally specific effects on neural processing in striatum; these effects may promote the habitization of behavior by shifting control from ventral to dorsolateral regions.
Gastric dilatation volvulus: a retrospective study of 203 dogs with ventral midline gastropexy.
Ullmann, B; Seehaus, N; Hungerbühler, S; Meyer-Lindenberg, A
2016-01-01
To evaluate the recurrence rate of gastric dilatation volvulus and the incidence of complications in subsequent coeliotomies following ventral midline gastropexy. The medical records of dogs treated for gastric dilatation volvulus by ventral midline gastropexy were retrospectively reviewed. Owners were contacted and invited to complete a questionnaire and to return to the clinic for ultrasonographic and radiographic follow-up. The questionnaire was completed by 203 owners 2 to 123 months postoperatively, 24 of whom attended the follow-up examination. Of the 203 dogs, 13 (6 · 4%) underwent subsequent ventral midline coeliotomy and none developed complications related to the gastropexy site. In 23 of the 24 re-evaluated dogs, the stomach was closely associated with the abdominal on radiography and/or ultrasound. The recurrence rate for clinical signs of gastric dilatation or gastric dilatation volvulus after ventral midline gastropexy was 6 · 4%. This study shows that the recurrence of gastric dilatation volvulus after ventral midline gastropexy is low and adhesion of the stomach to the abdominal wall is persistent in almost all dogs that were re-examined. The gastropexy site did not appear to interfere with subsequent coeliotomy. © 2015 British Small Animal Veterinary Association.
Evolutionary plasticity of habenular asymmetry with a conserved efferent connectivity pattern.
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Aldo Villalón
Full Text Available The vertebrate habenulae (Hb is an evolutionary conserved dorsal diencephalic nuclear complex that relays information from limbic and striatal forebrain regions to the ventral midbrain. One key feature of this bilateral nucleus is the presence of left-right differences in size, cytoarchitecture, connectivity, neurochemistry and/or gene expression. In teleosts, habenular asymmetry has been associated with preferential innervation of left-right habenular efferents into dorso-ventral domains of the midbrain interpeduncular nucleus (IPN. However, the degree of conservation of this trait and its relation to the structural asymmetries of the Hb are currently unknown. To address these questions, we performed the first systematic comparative analysis of structural and connectional asymmetries of the Hb in teleosts. We found striking inter-species variability in the overall shape and cytoarchitecture of the Hb, and in the frequency, strength and to a lesser degree, laterality of habenular volume at the population level. Directional asymmetry of the Hb was either to the left in D. rerio, E. bicolor, O. latipes, P. reticulata, B. splendens, or to the right in F. gardneri females. In contrast, asymmetry was absent in P. scalare and F. gardneri males at the population level, although in these species the Hb displayed volumetric asymmetries at the individual level. Inter-species variability was more pronounced across orders than within a single order, and coexisted with an overall conserved laterotopic representation of left-right habenular efferents into dorso-ventral domains of the IPN. These results suggest that the circuit design involving the Hb of teleosts promotes structural flexibility depending on developmental, cognitive and/or behavioural pressures, without affecting the main midbrain connectivity output, thus unveiling a key conserved role of this connectivity trait in the function of the circuit. We propose that ontogenic plasticity in habenular
LPXRFa peptide system in the European sea bass: A molecular and immunohistochemical approach.
Paullada-Salmerón, José A; Cowan, Mairi; Aliaga-Guerrero, María; Gómez, Ana; Zanuy, Silvia; Mañanos, Evaristo; Muñoz-Cueto, José A
2016-01-01
Gonadotropin-inhibitory hormone (GnIH) is a neuropeptide that suppresses reproduction in birds and mammals by inhibiting GnRH and gonadotropin secretion. GnIH orthologs with a C-terminal LPXRFamide (LPXRFa) motif have been identified in teleost fish. Although recent work also suggests its role in fish reproduction, studies are scarce and controversial, and have mainly focused on cyprinids. In this work we cloned a full-length cDNA encoding an LPXRFa precursor in the European sea bass, Dicentrarchus labrax. In contrast to other teleosts, the sea bass LPXRFa precursor contains only two putative RFamide peptides, termed sbLPXRFa1 and sbLPXRFa2. sblpxrfa transcripts were expressed predominantly in the olfactory bulbs/telencephalon, diencephalon, midbrain tegmentum, retina, and gonads. We also developed a specific antiserum against sbLPXRFa2, which revealed sbLPXRFa-immunoreactive (ir) perikarya in the olfactory bulbs-terminal nerve, ventral telencephalon, caudal preoptic area, dorsal mesencephalic tegmentum, and rostral rhombencephalon. These sbLPXRFa-ir cells profusely innervated the preoptic area, hypothalamus, optic tectum, semicircular torus, and caudal midbrain tegmentum, but conspicuous projections also reached the olfactory bulbs, ventral/dorsal telencephalon, habenula, ventral thalamus, pretectum, rostral midbrain tegmentum, posterior tuberculum, reticular formation, and viscerosensory lobe. The retina, pineal, vascular sac, and pituitary were also targets of sbLPXRFa-ir cells. In the pituitary, this innervation was observed close to follicle-stimulating hormone (FSH), luteinizing hormone (LH) and growth hormone (GH) cells. Tract-tracing retrograde labeling suggests that telencephalic and preoptic sbLPXRFa cells might represent the source of pituitary innervation. The immunohistochemical distribution of sbLPXRFa cells and fibers suggest that LPXRFa peptides might be involved in some functions as well as reproduction, such as feeding, growth, and behavior.
Mazzulli, Joseph R; Zunke, Friederike; Isacson, Ole; Studer, Lorenz; Krainc, Dimitri
2016-02-16
Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the accumulation of protein aggregates comprised of α-synuclein (α-syn). A major barrier in treatment discovery for PD is the lack of identifiable therapeutic pathways capable of reducing aggregates in human neuronal model systems. Mutations in key components of protein trafficking and cellular degradation machinery represent important risk factors for PD; however, their precise role in disease progression and interaction with α-syn remains unclear. Here, we find that α-syn accumulation reduced lysosomal degradation capacity in human midbrain dopamine models of synucleinopathies through disrupting hydrolase trafficking. Accumulation of α-syn at the cell body resulted in aberrant association with cis-Golgi-tethering factor GM130 and disrupted the endoplasmic reticulum-Golgi localization of rab1a, a key mediator of vesicular transport. Overexpression of rab1a restored Golgi structure, improved hydrolase trafficking and activity, and reduced pathological α-syn in patient neurons. Our work suggests that enhancement of lysosomal hydrolase trafficking may prove beneficial in synucleinopathies and indicates that human midbrain disease models may be useful for identifying critical therapeutic pathways in PD and related disorders.
THE PROGENITOR OF THE TYPE IIb SN 2008ax REVISITED
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Folatelli, Gastón; Bersten, Melina C.; Benvenuto, Omar G. [Instituto de Astrofísica de La Plata (Argentina); Kuncarayakti, Hanindyo [Millennium Institute of Astrophysics (MAS), Casilla 36-D, Santiago (Chile); Maeda, Keiichi; Nomoto, Ken’ichi, E-mail: gaston@fcaglp.unlp.edu.ar [Kavli Institute for the Physics and Mathematics of the Universe (WPI), The University of Tokyo, Kashiwa, Chiba 277-8583 (Japan)
2015-10-01
Hubble Space Telescope observations of the site of the supernova (SN) SN 2008ax obtained in 2011 and 2013 reveal that the possible progenitor object detected in pre-explosion images was in fact multiple. Four point sources are resolved in the new, higher-resolution images. We identify one of the sources with the fading SN. The other three objects are consistent with single supergiant stars. We conclude that their light contaminated the previously identified progenitor candidate. After subtraction of these stars, the progenitor appears to be significantly fainter and bluer than previously measured. Post-explosion photometry at the SN location indicates that the progenitor object has disappeared. If single, the progenitor is compatible with a supergiant star of B to mid-A spectral type, while a Wolf–Rayet (W-R) star would be too luminous in the ultraviolet to account for the observations. Moreover, our hydrodynamical modeling shows that the pre-explosion mass was 4–5 M{sub ⊙} and the radius was 30–50 R{sub ⊙}, which is incompatible with a W-R progenitor. We present a possible interacting binary progenitor computed with our evolutionary models that reproduces all the observational evidence. A companion star as luminous as an O9–B0 main-sequence star may have remained after the explosion.
Arterial blood supply to midbrain, thalamus and internal capsule on CT, 3
International Nuclear Information System (INIS)
Takeshita, Gen; Ottomo, Michinori; Sasaki, Taisuke; Fukuda, Eiko.
1984-01-01
The selective injection of dye into the anterior choroidal artery (blue), the medial posterior choroidal artery (green), and the lateral posterior choroidal artery (red), using seven post-mortem brains, was performed. After fixation, sections parallel with the orbito-meatal line were obtained. The distribution of the anterior choroidal artery was visualized in the uncal region of the temporal lobe and the cerebral peduncle below the slice of the third ventricle. On the slice of the third ventricle, the lateral part of the geniculate region, the globus pallidus, and the posterior limb of the internal capsule were supplied by the anterior choroidal artery. The blood supply of the posterior limb of the internal capsule was also demonstrated on the slice of the anterior horn and on the body of the lateral ventricle. The distribution of the medial posterior choroidal artery was visualized in the tegmentum of the midbrain below the slice of the third ventricle, and on the slice of the anterior horn, the pineal body and the posterior part of the thalamus were also supplied. The distribution of the lateral posterior choroidal artery was visualized in the lateral part of the midbrain, around the red nucleus, below the slice of the third ventricle, and on the slice of the third ventricle, the upper part of the cerebral peduncle, the posterior part of the hypothalamus, and the medial part of the geniculate region were also supplied. Also, distribution to the medial and posterior parts of the thalamus was noted on the slice of the anterior horn. It was quite useful to identify the distribution of each choroidal artery on CT sections for the CT diagnosis of cerebrovascular disorders. (author)
Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema
Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham
2017-01-01
Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826
X Inactivation and Progenitor Cancer Cells
Directory of Open Access Journals (Sweden)
Ruben Agrelo
2011-04-01
Full Text Available In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing.
Crossmodal recruitment of the ventral visual stream in congenital blindness
DEFF Research Database (Denmark)
Ptito, Maurice; Matteau, Isabelle; Zhi Wang, Arthur
2012-01-01
We used functional MRI (fMRI) to test the hypothesis that blind subjects recruit the ventral visual stream during nonhaptic tactile-form recognition. Congenitally blind and blindfolded sighted control subjects were scanned after they had been trained during four consecutive days to perform......, inferotemporal (IT), cortex, lateral occipital tactile vision area (LOtv), and fusiform gyrus. Control subjects activated area LOtv and precuneus but not cuneus, IT and fusiform gyrus. These results indicate that congenitally blind subjects recruit key regions in the ventral visual pathway during nonhaptic...
Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; McKinney, Sheri; Lester, Henry A
2017-11-01
Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.
Representation of Gravity-Aligned Scene Structure in Ventral Pathway Visual Cortex.
Vaziri, Siavash; Connor, Charles E
2016-03-21
The ventral visual pathway in humans and non-human primates is known to represent object information, including shape and identity [1]. Here, we show the ventral pathway also represents scene structure aligned with the gravitational reference frame in which objects move and interact. We analyzed shape tuning of recently described macaque monkey ventral pathway neurons that prefer scene-like stimuli to objects [2]. Individual neurons did not respond to a single shape class, but to a variety of scene elements that are typically aligned with gravity: large planes in the orientation range of ground surfaces under natural viewing conditions, planes in the orientation range of ceilings, and extended convex and concave edges in the orientation range of wall/floor/ceiling junctions. For a given neuron, these elements tended to share a common alignment in eye-centered coordinates. Thus, each neuron integrated information about multiple gravity-aligned structures as they would be seen from a specific eye and head orientation. This eclectic coding strategy provides only ambiguous information about individual structures but explicit information about the environmental reference frame and the orientation of gravity in egocentric coordinates. In the ventral pathway, this could support perceiving and/or predicting physical events involving objects subject to gravity, recognizing object attributes like animacy based on movement not caused by gravity, and/or stabilizing perception of the world against changes in head orientation [3-5]. Our results, like the recent discovery of object weight representation [6], imply that the ventral pathway is involved not just in recognition, but also in physical understanding of objects and scenes. Copyright © 2016 Elsevier Ltd. All rights reserved.
LINKING TYPE Ia SUPERNOVA PROGENITORS AND THEIR RESULTING EXPLOSIONS
International Nuclear Information System (INIS)
Foley, Ryan J.; Kirshner, Robert P.; Simon, Joshua D.; Burns, Christopher R.; Gal-Yam, Avishay; Hamuy, Mario; Morrell, Nidia I.; Phillips, Mark M.; Shields, Gregory A.; Sternberg, Assaf
2012-01-01
Comparing the ejecta velocities at maximum brightness and narrow circumstellar/interstellar Na D absorption line profiles of a sample of 23 Type Ia supernovae (SNe Ia), we determine that the properties of SN Ia progenitor systems and explosions are intimately connected. As demonstrated by Sternberg et al., half of all SNe Ia with detectable Na D absorption at the host-galaxy redshift in high-resolution spectroscopy have Na D line profiles with significant blueshifted absorption relative to the strongest absorption component, which indicates that a large fraction of SN Ia progenitor systems have strong outflows. In this study, we find that SNe Ia with blueshifted circumstellar/interstellar absorption systematically have higher ejecta velocities and redder colors at maximum brightness relative to the rest of the SN Ia population. This result is robust at a 98.9%-99.8% confidence level, providing the first link between the progenitor systems and properties of the explosion. This finding is further evidence that the outflow scenario is the correct interpretation of the blueshifted Na D absorption, adding additional confirmation that some SNe Ia are produced from a single-degenerate progenitor channel. An additional implication is that either SN Ia progenitor systems have highly asymmetric outflows that are also aligned with the SN explosion or SNe Ia come from a variety of progenitor systems where SNe Ia from systems with strong outflows tend to have more kinetic energy per unit mass than those from systems with weak or no outflows.
Differentiation of Mouse Embryonic Stem Cells into Ventral Foregut Precursors
DEFF Research Database (Denmark)
Rothová, Michaela; Hölzenspies, Jurriaan J; Livigni, Alessandra
2016-01-01
Anterior definitive endoderm (ADE), the ventral foregut precursor, is both an important embryonic signaling center and a unique multipotent precursor of liver, pancreas, and other organs. Here, a method is described for the differentiation of mouse embryonic stem cells (mESCs) to definitive...... endoderm with pronounced anterior character. ADE-containing cultures can be produced in vitro by suspension (embryoid body) culture or in a serum-free adherent monolayer culture. ESC-derived ADE cells are committed to endodermal fates and can undergo further differentiation in vitro towards ventral foregut...
Kovell, Robert Caleb; Terlecki, Ryan Patrick
2015-02-01
To describe the novel technique of ventral inlay substitution urethroplasty for the management of male anterior urethral stricture disease. A 58-year-old gentleman with multifocal bulbar stricture disease measuring 7 cm in length was treated using a ventral inlay substitution urethroplasty. A dorsal urethrotomy was created, and the ventral urethral plated was incised. The edges of the urethral plate were mobilized without violation of the ventral corpus spongiosum. A buccal mucosa graft was harvested and affixed as a ventral inlay to augment the caliber of the urethra. The dorsal urethrotomy was closed over a foley catheter. No intraoperative or postoperative complications occurred. Postoperative imaging demonstrated a widely patent urethra. After three years of follow-up, the patient continues to do well with no voiding complaints and low postvoid residuals. Ventral inlay substitution urethroplasty appears to be a safe and feasible technique for the management of bulbar urethral strictures.
Haemopoietic progenitor cells in human peripheral blood
International Nuclear Information System (INIS)
Zwaan, F.E.
1980-01-01
The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)
Constraints on the Progenitor System of SN 2016gkg from a Comprehensive Statistical Analysis
Sravan, Niharika; Marchant, Pablo; Kalogera, Vassiliki; Margutti, Raffaella
2018-01-01
Type IIb supernovae (SNe) present a unique opportunity for understanding the progenitors of stripped-envelope SNe because the stellar progenitor of several SNe IIb have been identified in pre-explosion images. In this paper, we use Bayesian inference and a large grid of non-rotating solar-metallicity single and binary stellar models to derive the associated probability distributions of single and binary progenitors of the SN IIb 2016gkg using existing observational constraints. We find that potential binary star progenitors have smaller pre-SN hydrogen-envelope and helium-core masses than potential single-star progenitors typically by 0.1 M ⊙ and 2 M ⊙, respectively. We find that, a binary companion, if present, is a main-sequence or red-giant star. Apart from this, we do not find strong constraints on the nature of the companion star. We demonstrate that the range of progenitor helium-core mass inferred from observations could help improve constraints on the progenitor. We find that the probability that the progenitor of SN 2016gkg was a binary is 22% when we use constraints only on the progenitor luminosity and effective temperature. Imposing the range of pre-SN progenitor hydrogen-envelope mass and radius inferred from SN light curves, the probability that the progenitor is a binary increases to 44%. However, there is no clear preference for a binary progenitor. This is in contrast to binaries being the currently favored formation channel for SNe IIb. Our analysis demonstrates the importance of statistical inference methods to constrain progenitor channels.
Correlation between early surgical complications and readmission rate after ventral hernia repair
DEFF Research Database (Denmark)
Kokotovic, D; Sjølander, H; Gögenur, I
2017-01-01
PURPOSE: Postoperative surgical complications arising from ventral hernia repair have been assessed by a variety of outcome measures. The objective of this study was to correlate the Clavien Dindo Classification (CDC) graded complications with the 30-day readmission rate as early outcome measures...... in ventral hernia repair. Secondarily, we wanted to investigate whether the risk factors for Clavien Dindo class ≥1 and 30-day readmission were comparable. METHODS: Single-centre retrospective study including all patients (≥18 years) who underwent ventral hernia repair between January 1, 2009 and September 1......). There was a significant association between a complication graded by the CDC ≥1 and 30-day readmission for both incisional and umbilical/epigastric hernia repair (p readmission. Recurrent...
Concurrent TMS-fMRI Reveals Interactions between Dorsal and Ventral Attentional Systems
DEFF Research Database (Denmark)
Leitao, Joana; Thielscher, Axel; Tuennerhoff, Johannes
2015-01-01
interactively in this process. This fMRI study used concurrent transcranial magnetic stimulation (TMS) as a causal perturbation approach to investigate the interactions between dorsal and ventral attentional systems and sensory processing areas. In a sustained spatial attention paradigm, human participants......Adaptive behavior relies on combining bottom-up sensory inputs with top-down control signals to guide responses in line with current goals and task demands. Over the past decade, accumulating evidence has suggested that the dorsal and ventral frontoparietal attentional systems are recruited......-TMS relative to Sham-TMS increased activation in the parietal cortex regardless of sensory stimulation, confirming the neural effectiveness of TMS stimulation. Visual targets increased activations in the anterior insula, a component of the ventral attentional system responsible for salience detection...
Pain and convalescence following laparoscopic ventral hernia repair
DEFF Research Database (Denmark)
Eriksen, Jens Ravn
2011-01-01
Severe pain is usual after laparoscopic ventral hernia repair (LVHR). Mesh fixation with titanium tacks may play a key role in the development of acute and chronic pain and alternative fixation methods should therefore be investigated. This PhD thesis was based on three studies and aimed too: 1...... abdominal wall. A mechanical peel test was performed for each tissue sample. The secondary outcome parameters were grade and strength of adhesions to the mesh, shrinkage and displacement/folding of the mesh and histological parameters. All nine pigs survived without complications until sacrifice. No meshes...... satisfaction. This issue must have first priority in future ventral hernia repair research. It is now documented, that the simple application of fibrin glue instead of titanium tacks for mesh fixation in LVHR of defects
Pain and convalescence following laparoscopic ventral hernia repair
DEFF Research Database (Denmark)
Eriksen, Jens Ravn
Severe pain is usual after laparoscopic ventral hernia repair (LVHR). Mesh fixation with titanium tacks may play a key role in the development of acute and chronic pain and alternative fixation methods should therefore be investigated. This PhD thesis was based on three studies and aimed too: 1...... abdominal wall. A mechanical peel test was performed for each tissue sample. The secondary outcome parameters were grade and strength of adhesions to the mesh, shrinkage and displacement/folding of the mesh and histological parameters. All nine pigs survived without complications until sacrifice. No meshes...... satisfaction. This issue must have first priority in future ventral hernia repair research. It is now documented, that the simple application of fibrin glue instead of titanium tacks for mesh fixation in LVHR of defects
Brand, Matthias; Snagowski, Jan; Laier, Christian; Maderwald, Stefan
2016-04-01
One type of Internet addiction is excessive pornography consumption, also referred to as cybersex or Internet pornography addiction. Neuroimaging studies found ventral striatum activity when participants watched explicit sexual stimuli compared to non-explicit sexual/erotic material. We now hypothesized that the ventral striatum should respond to preferred pornographic compared to non-preferred pornographic pictures and that the ventral striatum activity in this contrast should be correlated with subjective symptoms of Internet pornography addiction. We studied 19 heterosexual male participants with a picture paradigm including preferred and non-preferred pornographic materials. Subjects had to evaluate each picture with respect to arousal, unpleasantness, and closeness to ideal. Pictures from the preferred category were rated as more arousing, less unpleasant, and closer to ideal. Ventral striatum response was stronger for the preferred condition compared to non-preferred pictures. Ventral striatum activity in this contrast was correlated with the self-reported symptoms of Internet pornography addiction. The subjective symptom severity was also the only significant predictor in a regression analysis with ventral striatum response as dependent variable and subjective symptoms of Internet pornography addiction, general sexual excitability, hypersexual behavior, depression, interpersonal sensitivity, and sexual behavior in the last days as predictors. The results support the role for the ventral striatum in processing reward anticipation and gratification linked to subjectively preferred pornographic material. Mechanisms for reward anticipation in ventral striatum may contribute to a neural explanation of why individuals with certain preferences and sexual fantasies are at-risk for losing their control over Internet pornography consumption. Copyright © 2016 Elsevier Inc. All rights reserved.
Ventral aspect of the visual form pathway is not critical for the perception of biological motion
Gilaie-Dotan, Sharon; Saygin, Ayse Pinar; Lorenzi, Lauren J.; Rees, Geraint; Behrmann, Marlene
2015-01-01
Identifying the movements of those around us is fundamental for many daily activities, such as recognizing actions, detecting predators, and interacting with others socially. A key question concerns the neurobiological substrates underlying biological motion perception. Although the ventral “form” visual cortex is standardly activated by biologically moving stimuli, whether these activations are functionally critical for biological motion perception or are epiphenomenal remains unknown. To address this question, we examined whether focal damage to regions of the ventral visual cortex, resulting in significant deficits in form perception, adversely affects biological motion perception. Six patients with damage to the ventral cortex were tested with sensitive point-light display paradigms. All patients were able to recognize unmasked point-light displays and their perceptual thresholds were not significantly different from those of three different control groups, one of which comprised brain-damaged patients with spared ventral cortex (n > 50). Importantly, these six patients performed significantly better than patients with damage to regions critical for biological motion perception. To assess the necessary contribution of different regions in the ventral pathway to biological motion perception, we complement the behavioral findings with a fine-grained comparison between the lesion location and extent, and the cortical regions standardly implicated in biological motion processing. This analysis revealed that the ventral aspects of the form pathway (e.g., fusiform regions, ventral extrastriate body area) are not critical for biological motion perception. We hypothesize that the role of these ventral regions is to provide enhanced multiview/posture representations of the moving person rather than to represent biological motion perception per se. PMID:25583504
Neuronal Progenitor Maintenance Requires Lactate Metabolism and PEPCK-M-Directed Cataplerosis.
Álvarez, Zaida; Hyroššová, Petra; Perales, José Carlos; Alcántara, Soledad
2016-03-01
This study investigated the metabolic requirements for neuronal progenitor maintenance in vitro and in vivo by examining the metabolic adaptations that support neuronal progenitors and neural stem cells (NSCs) in their undifferentiated state. We demonstrate that neuronal progenitors are strictly dependent on lactate metabolism, while glucose induces their neuronal differentiation. Lactate signaling is not by itself capable of maintaining the progenitor phenotype. The consequences of lactate metabolism include increased mitochondrial and oxidative metabolism, with a strict reliance on cataplerosis through the mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) pathway to support anabolic functions, such as the production of extracellular matrix. In vivo, lactate maintains/induces populations of postnatal neuronal progenitors/NSCs in a PEPCK-M-dependent manner. Taken together, our data demonstrate that, lactate alone or together with other physical/biochemical cues maintain NSCs/progenitors with a metabolic signature that is classically found in tissues with high anabolic capacity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Stark, Adam J; Smith, Christopher T; Lin, Ya-Chen; Petersen, Kalen J; Trujillo, Paula; van Wouwe, Nelleke C; Kang, Hakmook; Donahue, Manus J; Kessler, Robert M; Zald, David H; Claassen, Daniel O
2018-03-28
The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D 2/3 receptor expression are described in drug-seeking and addiction disorders. Parkinson's disease (PD) patients are frequently prescribed D 2 -like dopamine agonist (DAgonist) therapy for motor symptoms, yet a proportion develop clinically significant behavioral addictions characterized by impulsive and compulsive behaviors (ICBs). Until now, changes in D 2/3 receptor binding in both striatal and extrastriatal regions have not been concurrently quantified in this population. We identified 35 human PD patients (both male and female) receiving DAgonist therapy, with ( n = 17) and without ( n = 18) ICBs, matched for age, disease duration, disease severity, and dose of dopamine therapy. In the off-dopamine state, all completed PET imaging with [ 18 F]fallypride, a high affinity D 2 -like receptor ligand that can measure striatal and extrastriatal D 2/3 nondisplaceable binding potential (BP ND ). Striatal differences between ICB+/ICB- patients localized to the ventral striatum and putamen, where ICB+ subjects had reduced BP ND In this group, self-reported severity of ICB symptoms positively correlated with midbrain D 2/3 receptor BP ND Group differences in regional D 2/3 BP ND relationships were also notable: ICB+ (but not ICB-) patients expressed positive correlations between midbrain and caudate, putamen, globus pallidus, and amygdala BP ND s. These findings support the hypothesis that compulsive behaviors in PD are associated with reduced ventral and dorsal striatal D 2/3 expression, similar to changes in comparable behavioral disorders. The data also suggest that relatively preserved ventral midbrain dopaminergic projections throughout nigrostriatal and mesolimbic networks are characteristic of ICB+ patients, and may account for differential DAgonist therapeutic response. SIGNIFICANCE STATEMENT The biologic determinants of
DEFF Research Database (Denmark)
Christensen, T.; Bisgaard, C.F.; Nielsen, Henrik Bjørn
2010-01-01
Several findings suggest a functional and anatomical differentiation along the dorso-ventral axis of the hippocampus. Lesion studies in rats have indicated that the dorsal hippocampus preferentially plays a role in spatial learning and memory, while the ventral hippocampus is involved in anxiety...... and ventral granular cell layer with a false discovery rate below 5% and with a relative change in gene expression level of 20% or more. From this pool of genes 45 genes were more than two-fold regulated, 13 genes being dorsally enriched and 32 genes being ventrally enriched. Moreover, cluster analysis based...
Topography and collateralization of dopaminergic projections to primary motor cortex in rats.
Hosp, Jonas A; Nolan, Helen E; Luft, Andreas R
2015-05-01
Dopaminergic signaling within the primary motor cortex (M1) is necessary for successful motor skill learning. Dopaminergic neurons projecting to M1 are located in the ventral tegmental area (VTA, nucleus A10) of the midbrain. It is unknown which behavioral correlates are encoded by these neurons. The objective here is to investigate whether VTA-M1 fibers are collaterals of projections to prefrontal cortex (PFC) or nucleus accumbens (NAc) or if they form a distinct pathway. In rats, multiple-site retrograde fluorescent tracers were injected into M1, PFC and the core region of the NAc and VTA sections investigated for concomitant labeling of different tracers. Dopaminergic neurons projecting to M1, PFC and NAc were found in nucleus A10 and to a lesser degree in the medial nucleus A9. Neurons show high target specificity, minimal collateral branching to other than their target area and hardly cross the midline. Whereas PFC- and NAc-projecting neurons are indistinguishably intermingled within the ventral portion of dopaminergic nuclei in middle and caudal midbrain, M1-projecting neurons are only located within the dorsal part of the rostral midbrain. Within M1, the forelimb representation receives sevenfold more dopaminergic projections than the hindlimb representation. This strong rostro-caudal gradient as well as the topographical preference to dorsal structures suggest that projections to M1 emerged late in the development of the dopaminergic systems in and form a functionally distinct system.
VANDERPLAS, J; WIERSINGAPOST, JEC; MAES, FW; BOHUS, B
1995-01-01
The effects of low-intensity electrical stimulation of sites in the hypothalamus and zona incerta (ZI) on mean blood pressure (MBP), heart rate (HR), and neuronal activity in the midbrain periaqueductal gray (FAG) were investigated in rats. Longlasting depressor responses were elicited from 67 sites
α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation
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Jing Song
2018-03-01
Full Text Available A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG, a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133+ and CD133− cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133+ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet. αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.
α-Ketoglutarate Promotes Pancreatic Progenitor-Like Cell Proliferation.
Song, Jing; Ma, Dongshen; Xing, Yun; Tang, Shanshan; Alahdal, Murad; Guo, Jiamin; Pan, Yi; Zhang, Yanfeng; Shen, Yumeng; Wu, Qiong; Lu, Zhou; Jin, Liang
2018-03-22
A major source of β cell generation is pancreatic progenitor-like cell differentiation. Multiple studies have confirmed that stem cell metabolism plays important roles in self-renewal and proliferation. In the absence of glucose, glutamine provides the energy for cell division and growth. Furthermore, α-ketoglutarate (αKG), a precursor for glutamine synthesis, is sufficient for enabling glutamine-independent cell proliferation. We have demonstrated that αKG contributes to the large-scale proliferation of pancreatic progenitor-like cells that can provide an ample amount of clinically relevant β cells. We compared the mRNA expression of a subset of genes, the abundance of ATP, reactive oxide species, mitochondrial number, and the colony-forming frequency between mouse pancreatic CD133⁺ and CD133 - cells. We employed Real-Time PCR, immunostaining and passage assays to investigate self-renewal and proliferation of pancreatic progenitor-like cells in a 3D culture system in the presence and absence of αKG. The energy metabolism of CD133⁺ cells was more prone to oxidative phosphorylation. However, in the 3D culture system, when αKG was supplemented to the culture medium, the proliferation of the pancreatic progenitor-like cells was significantly elevated. We confirmed that the presence of αKG correlated with the up-regulation of Ten-Eleven Translocation (Tet). αKG can promote the proliferation of pancreatic progenitor-like cells via the up-regulation of Tet.
Imaging findings in patients with ventral dural defects and herniation of neural tissue
International Nuclear Information System (INIS)
Baur, A.; Staebler, A.; Reiser, M.; Psenner, K.; Hamburger, C.
1997-01-01
The aim of this paper is to describe clinical and imaging findings in three patients with ventral dural defects and herniation of the spinal cord or cauda equina. The literature is reviewed and the clinical, radiological and operative findings are compared. Three patients with ventral dural defects of different etiologies are presented. One patient gave a longstanding history of ankylosing spondylitis, the second patient presents 37 years after spinal trauma, and the third patient presents with spontaneous spinal cord herniation. All patients had typically slowly progressive neurological symptoms with multiple hospitalizations until diagnosis was made. Characteristic findings in postmyelographic CT included a ventral or ventrolateral displacement with deformation of the spinal cord or the cauda equina. Sagittal MRI showed this abrupt and localized anterior deviation of the spinal cord or the cauda equina to the posterior portions of a vertebral body with or without a bony vertebral defect optimally. Additionally, due to the ventral displacement of the spinal cord, the dorsal subarachnoid space was relatively enlarged without evidence of an arachnoid cyst, in all patients. Magnetic resonance imaging and postmyelographic CT can diagnose ventral dural defects with spinal cord herniation or nerve root entrapment. Dural defects must be considered in the presence of neurological symptoms in cases of longstanding ankylosing spondylitis, late sequelae of fractures of vertebral bodies, and without history of spinal trauma or surgery. (orig.). With 3 figs
Development and molecular composition of the hepatic progenitor cell niche.
Vestentoft, Peter Siig
2013-05-01
End-stage liver diseases represent major health problems that are currently treated by liver transplantation. However, given the world-wide shortage of donor livers novel strategies are needed for therapeutic treatment. Adult stem cells have the ability to self-renew and differentiate into the more specialized cell types of a given organ and are found in tissues throughout the body. These cells, whose progeny are termed progenitor cells in human liver and oval cells in rodents, have the potential to treat patients through the generation of hepatic parenchymal cells, even from the patient's own tissue. Little is known regarding the nature of the hepatic progenitor cells. Though they are suggested to reside in the most distal part of the biliary tree, the canal of Hering, the lack of unique surface markers for these cells has hindered their isolation and characterization. Upon activation, they proliferate and form ductular structures, termed "ductular reactions", which radiate into the hepatic parenchyma. The ductular reactions contain activated progenitor cells that not only acquire a phenotype resembling that observed in developing liver but also display markers of differentiation shared with the cholangiocytic or hepatocytic lineages, the two parenchymal hepatic cell types. Interactions between the putative progenitor cells, the surrounding support cells and the extracellular matrix scaffold, all constituting the progenitor cell niche, are likely to be important for regulating progenitor cell activity and differentiation. Therefore, identifying novel progenitor cell markers and deciphering their microenvironment could facilitate clinical use. The aims of the present PhD thesis were to expand knowledge of the hepatic progenitor cell niche and characterize it both during development and in disease. Several animal models of hepatic injury are known to induce activation of the progenitor cells. In order to identify possible progenitor cell markers and niche components
Context Dependent Effects of Ventral Tegmental Area Inactivation on Spatial Working Memory
Martig, Adria K.; Jones, Graham L.; Smith, Kelsey E.; Mizumori, Sheri J.Y.
2009-01-01
Rats were tested on a hippocampus dependent win-shift working memory task in familiar or novel environments after receiving bilateral ventral tegmental area infusions of baclofen. Baclofen infusion disrupted working memory performance in both familiar and novel environments. In addition, baclofen infusion selectively disrupted short-term working memory in the novel environment. This experiment confirms selective ventral tegmental area support of accurate performance during a context dependent...
Ultrastructural changes of compressed lumbar ventral nerve roots following decompression
International Nuclear Information System (INIS)
El-Barrany, Wagih G.; Hamdy, Raid M.; Al-Hayani, Abdulmonem A.; Jalalah, Sawsan M.; Al-Sayyad, Mohammad J.
2006-01-01
To study whether there will be permanent lumbar nerve rot scanning or degeneration secondary to continuous compression followed by decompression on the nerve roots, which can account for postlaminectomy leg weakness or back pain. The study was performed at the Department of Anatomy, Faulty of Medicine, king Abdulaziz University, Jeddah, Kingdom of Saudi Arabia during 2003-2005. Twenty-six adult male New Zealand rabbits were used in the present study. The ventral roots of the left fourth lumbar nerve were clamped for 2 weeks then decompression was allowed by removal of the clips. The left ventral roots of the fourth lumbar nerve were excised for electron microscopic study. One week after nerve root decompression, the ventral root peripheral to the site of compression showed signs of Wallerian degeneration together with signs of regeneration. Schwann cells and myelinated nerve fibers showed severe degenerative changes. Two weeks after decompression, the endoneurium of the ventral root showed extensive edema with an increase in the regenerating myelinated and unmyentilated nerve fibers, and fibroblasts proliferation. Three weeks after decompression, the endoneurium showed an increase in the regenerating myelinated and unmyelinated nerve fibers with diminution of the endoneurial edema, and number of macrophages and an increase in collagen fibrils. Five and 6 weeks after decompression, the endoneurium showed marked diminution of the edema, macrophages, mast cells and fibroblasts. The enoneurium was filed of myelinated and unmyelinated nerve fibers and collagen fibrils. Decompression of the compressed roots of a spinal nerve is followed by regeneration of the nerve fibers and nerve and nerve recovery without endoneurial scarring. (author)
NFIX Regulates Neural Progenitor Cell Differentiation During Hippocampal Morphogenesis
Heng, Yee Hsieh Evelyn; McLeay, Robert C.; Harvey, Tracey J.; Smith, Aaron G.; Barry, Guy; Cato, Kathleen; Plachez, Céline; Little, Erica; Mason, Sharon; Dixon, Chantelle; Gronostajski, Richard M.; Bailey, Timothy L.; Richards, Linda J.; Piper, Michael
2014-01-01
Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix−/− mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix−/− mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix−/− mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure. PMID:23042739
Avelar, Alicia J; Cao, Jianjing; Newman, Amy Hauck; Beckstead, Michael J
2017-09-01
Abuse of psychostimulants like cocaine that inhibit dopamine (DA) reuptake through the dopamine transporter (DAT) represents a major public health issue, however FDA-approved pharmacotherapies have yet to be developed. Recently a class of ligands termed "atypical DAT inhibitors" has gained attention due to their range of effectiveness in increasing extracellular DA levels without demonstrating significant abuse liability. These compounds not only hold promise as therapeutic agents to treat stimulant use disorders but also as experimental tools to improve our understanding of DAT function. Here we used patch clamp electrophysiology in mouse brain slices to explore the effects of two atypical DAT inhibitors (R-modafinil and JHW 007) on the physiology of single DA neurons in the substantia nigra and ventral tegmental area. Despite their commonalities of being DAT inhibitors that lack cocaine-like behavioral profiles, these compounds exhibited surprisingly divergent cellular effects. Similar to cocaine, R-modafinil slowed DA neuron firing in a D2 receptor-dependent manner and rapidly enhanced the amplitude and duration of D2 receptor-mediated currents in the midbrain. In contrast, JHW 007 exhibited little effect on firing, slow DAT blockade, and an unexpected inhibition of D2 receptor-mediated currents that may be due to direct D2 receptor antagonism. Furthermore, pretreatment with JHW 007 blunted the cellular effects of cocaine, suggesting that it may be valuable to investigate similar DAT inhibitors as potential therapeutic agents. Further exploration of these and other atypical DAT inhibitors may reveal important cellular effects of compounds that will have potential as pharmacotherapies for treating cocaine use disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.
Cook, Jason B; Hendrickson, Linzy M; Garwood, Grant M; Toungate, Kelsey M; Nania, Christina V; Morikawa, Hitoshi
2017-01-01
Similar to drugs of abuse, the hedonic value of food is mediated, at least in part, by the mesostriatal dopamine (DA) system. Prolonged intake of either high calorie diets or drugs of abuse both lead to a blunting of the DA system. Most studies have focused on DAergic alterations in the striatum, but little is known about the effects of high calorie diets on ventral tegmental area (VTA) DA neurons. Since high calorie diets produce addictive-like DAergic adaptations, it is possible these diets may increase addiction susceptibility. However, high calorie diets consistently reduce psychostimulant intake and conditioned place preference in rodents. In contrast, high calorie diets can increase or decrease ethanol drinking, but it is not known how a junk food diet (cafeteria diet) affects ethanol drinking. In the current study, we administered a cafeteria diet consisting of bacon, potato chips, cheesecake, cookies, breakfast cereals, marshmallows, and chocolate candies to male Wistar rats for 3-4 weeks, producing an obese phenotype. Prior cafeteria diet feeding reduced homecage ethanol drinking over 2 weeks of testing, and transiently reduced sucrose and chow intake. Importantly, cafeteria diet had no effect on ethanol metabolism rate or blood ethanol concentrations following 2g/kg ethanol administration. In midbrain slices, we showed that cafeteria diet feeding enhances DA D2 receptor (D2R) autoinhibition in VTA DA neurons. These results show that junk food diet-induced obesity reduces ethanol drinking, and suggest that increased D2R autoinhibition in the VTA may contribute to deficits in DAergic signaling and reward hypofunction observed with obesity.
DISAPPEARANCE OF THE PROGENITOR OF SUPERNOVA iPTF13bvn
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Folatelli, Gastón; Bersten, Melina C. [Facultad de Ciencias Astronómicas y Geofísicas, Universidad Nacional de La Plata, Instituto de Astrofísica de La Plata (IALP), CONICET, Paseo del Bosque S/N, B1900FWA La Plata (Argentina); Van Dyk, Schuyler D. [IPAC/Caltech, Mailcode 100-22, Pasadena, CA 91125 (United States); Kuncarayakti, Hanindyo; Pignata, Giuliano; Hamuy, Mario [Millennium Institute of Astrophysics (MAS), Santiago (Chile); Maeda, Keiichi; Nomoto, Ken’ichi; Quimby, Robert M. [Kavli Institute for the Physics and Mathematics of the Universe (WPI), The University of Tokyo, Kashiwa, Chiba 277-8583 (Japan); Zheng, WeiKang; Filippenko, Alexei V.; Clubb, Kelsey I. [Department of Astronomy, University of California, Berkeley, CA 94720-3411 (United States); Smith, Nathan [Steward Observatory, University of Arizona, 933 N. Cherry Avenue, Tucson, AZ 85721 (United States); Elias-Rosa, Nancy [INAF-Osservatorio Astronomico di Padova, Vicolo dell’Osservatorio 5, I-35122 Padova (Italy); Foley, Ryan J. [Astronomy Department, University of Illinois at Urbana-Champaign, 1002 W. Green Street, Urbana, IL 61801 (United States); Miller, Adam A., E-mail: gaston.folatelli@ipmu.jp [Jet Propulsion Laboratory, 4800 Oak Grove Drive, MS 169-506, Pasadena, CA 91109 (United States)
2016-07-10
Supernova (SN) iPTF13bvn in NGC 5806 was the first Type Ib SN to have been tentatively associated with a progenitor in pre-explosion images. We performed deep ultraviolet (UV) and optical Hubble Space Telescope observations of the SN site ∼740 days after explosion. We detect an object in the optical bands that is fainter than the pre-explosion object. This dimming is likely not produced by dust absorption in the ejecta; thus, our finding confirms the connection of the progenitor candidate with the SN. The object in our data is likely dominated by the fading SN, implying that the pre-SN flux is mostly due to the progenitor. We compare our revised pre-SN photometry with previously proposed models. Although binary progenitors are favored, models need to be refined. In particular, to comply with our deep UV detection limit, any companion star must be less luminous than a late-O star or substantially obscured by newly formed dust. A definitive progenitor characterization will require further observations to disentangle the contribution of a much fainter SN and its environment.
Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins
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Suzanne R. Kalb
2017-06-01
Full Text Available Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs, toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC, alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH, and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC, but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.
Characterization of Proliferating Neural Progenitors after Spinal Cord Injury in Adult Zebrafish.
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Subhra Prakash Hui
Full Text Available Zebrafish can repair their injured brain and spinal cord after injury unlike adult mammalian central nervous system. Any injury to zebrafish spinal cord would lead to increased proliferation and neurogenesis. There are presences of proliferating progenitors from which both neuronal and glial loss can be reversed by appropriately generating new neurons and glia. We have demonstrated the presence of multiple progenitors, which are different types of proliferating populations like Sox2+ neural progenitor, A2B5+ astrocyte/ glial progenitor, NG2+ oligodendrocyte progenitor, radial glia and Schwann cell like progenitor. We analyzed the expression levels of two common markers of dedifferentiation like msx-b and vimentin during regeneration along with some of the pluripotency associated factors to explore the possible role of these two processes. Among the several key factors related to pluripotency, pou5f1 and sox2 are upregulated during regeneration and associated with activation of neural progenitor cells. Uncovering the molecular mechanism for endogenous regeneration of adult zebrafish spinal cord would give us more clues on important targets for future therapeutic approach in mammalian spinal cord repair and regeneration.
Werkman, T.R.; McCreary, A.C.; Kruse, C.G.; Wadman, W.J.
2011-01-01
This in vitro study investigates and compares the effects of NK3 receptor ligands on the firing rate of rat and guinea pig midbrain dopamine neurons. The findings are discussed in the light of choosing suitable animal models for investigating pharmacological properties of NK3 receptor antagonists,
Uncovering the Number and Clonal Dynamics of Mesp1 Progenitors during Heart Morphogenesis
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Samira Chabab
2016-01-01
Full Text Available The heart arises from distinct sources of cardiac progenitors that independently express Mesp1 during gastrulation. The precise number of Mesp1 progenitors that are specified during the early stage of gastrulation, and their clonal behavior during heart morphogenesis, is currently unknown. Here, we used clonal and mosaic tracing of Mesp1-expressing cells combined with quantitative biophysical analysis of the clonal data to define the number of cardiac progenitors and their mode of growth during heart development. Our data indicate that the myocardial layer of the heart derive from ∼250 Mesp1-expressing cardiac progenitors born during gastrulation. Despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. These results provide insights into the number of cardiac progenitors and their mode of growth and open up avenues to decipher the clonal dynamics of progenitors in other organs and tissues.
Suzuki, Takumi; Sato, Makoto
2017-11-15
Diversification of neuronal types is key to establishing functional variations in neural circuits. The first critical step to generate neuronal diversity is to organize the compartmental domains of developing brains into spatially distinct neural progenitor pools. Neural progenitors in each pool then generate a unique set of diverse neurons through specific spatiotemporal specification processes. In this review article, we focus on an additional mechanism, 'inter-progenitor pool wiring', that further expands the diversity of neural circuits. After diverse types of neurons are generated in one progenitor pool, a fraction of these neurons start migrating toward a remote brain region containing neurons that originate from another progenitor pool. Finally, neurons of different origins are intermingled and eventually form complex but precise neural circuits. The developing cerebral cortex of mammalian brains is one of the best examples of inter-progenitor pool wiring. However, Drosophila visual system development has revealed similar mechanisms in invertebrate brains, suggesting that inter-progenitor pool wiring is an evolutionarily conserved strategy that expands neural circuit diversity. Here, we will discuss how inter-progenitor pool wiring is accomplished in mammalian and fly brain systems. Copyright © 2017 Elsevier Inc. All rights reserved.
Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.
Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L
2016-01-06
Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly. Copyright © 2016 Elsevier Inc. All rights reserved.
APC sets the Wnt tone necessary for cerebral cortical progenitor development.
Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E S
2017-08-15
Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. © 2017 Nakagawa et al.; Published by Cold Spring Harbor Laboratory Press.
Hmga2 regulates self-renewal of retinal progenitors.
Parameswaran, Sowmya; Xia, Xiaohuan; Hegde, Ganapati; Ahmad, Iqbal
2014-11-01
In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here, we demonstrate that cell-extrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs). We observed that a small subset of RPCs was capable of clonal propagation and retained multipotentiality of parents in the presence of endothelial cells (ECs), known self-renewal regulators in various stem cell niches. The self-renewing effects, also observed in vivo, involve multiple intercellular signaling pathways, engaging Hmga2. As progenitors exhaust during retinal development, expression of Hmga2 progressively decreases. Analyses of Hmga2-expression perturbation, in vitro and in vivo, revealed that Hmga2 functionally helps to mediate cell-extrinsic influences on late-retinal progenitor self-renewal. Our results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina. © 2014. Published by The Company of Biologists Ltd.
Tournier, Benjamin B; Tsartsalis, Stergios; Dimiziani, Andrea; Millet, Philippe; Ginovart, Nathalie
2016-09-15
This study examined the time-course of alterations in levels and functional sensitivities of dopamine D2/3 receptors (D2/3R) during the course and up to 6 weeks following cessation of chronic treatment with Delta(9)-Tetrahydrocannabinol (THC) in rats. THC treatment led to an increase in D2/3R levels in striatum, as assessed using [(3)H]-(+)-PHNO, that was readily observable after one week of treatment, remained stably elevated during the subsequent 2 weeks of treatment, but fully reversed within 2 weeks of THC discontinuation. THC-induced D2/3R alterations were more pronounced and longer lasting in the dopamine cell body regions of the midbrain, wherein [(3)H]-(+)-PHNO binding was still elevated at 2 weeks but back to control values at 6 weeks after THC cessation. Parallel analyses of the psychomotor effects of pre- and post-synaptic doses of quinpirole also showed a pattern of D2/3R functional supersensitivity indicative of more rapid subsidence in striatum than in midbrain following drug cessation. These results indicate that chronic THC is associated with a biochemical and functional sensitization of D2/3R signaling, that these responses show a region-specific temporal pattern and are fully reversible following drug discontinuation. These results suggest that an increased post-synaptic D2/3R function and a decreased DA presynaptic signaling, mediated by increased D2/3R autoinhibition, may predominate during distinct phases of withdrawal and may contribute both to the mechanisms leading to relapse and to cannabinoid withdrawal symptoms. The different rates of normalization of D2/3R function in striatum and midbrain may be critical information for the development of new pharmacotherapies for cannabis dependence. Copyright © 2016 Elsevier B.V. All rights reserved.
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Harumichi Itoh
2017-03-01
Full Text Available Craniocervical junction abnormalities with atlantoaxial subluxation caused by ventral subluxation of C2 were diagnosed in a 6-month-old female Pomeranian with tetraplegia as a clinical sign. Lateral survey radiography of the neck with flexion revealed atlantoaxial subluxation with ventral subluxation of C2. Computed tomography revealed absence of dens and atlanto-occipital overlapping. Magnetic resonance imaging showed compression of the spinal cord and indentation of caudal cerebellum. The diagnosis was Chiari-like malformation, atlantoaxial subluxation with ventral displacement of C2, atlanto-occipital overlapping, and syringomyelia. The dog underwent foramen magnum decompression, dorsal laminectomy of C1, and ventral fixation of the atlantoaxial joint. Soon after the operation, voluntary movements of the legs were recovered. Finally, the dog could stand and walk without assistance. The dog had complicated malformations at the craniocervical junction but foramen magnum decompression and dorsal laminectomy for Chiari-like malformation, and ventral fixation for atlantoaxial subluxation resulted in an excellent clinical outcome.
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Renal blood flow and oxygenation drive nephron progenitor differentiation.
Rymer, Christopher; Paredes, Jose; Halt, Kimmo; Schaefer, Caitlin; Wiersch, John; Zhang, Guangfeng; Potoka, Douglas; Vainio, Seppo; Gittes, George K; Bates, Carlton M; Sims-Lucas, Sunder
2014-08-01
During kidney development, the vasculature develops via both angiogenesis (branching from major vessels) and vasculogenesis (de novo vessel formation). The formation and perfusion of renal blood vessels are vastly understudied. In the present study, we investigated the regulatory role of renal blood flow and O2 concentration on nephron progenitor differentiation during ontogeny. To elucidate the presence of blood flow, ultrasound-guided intracardiac microinjection was performed, and FITC-tagged tomato lectin was perfused through the embryo. Kidneys were costained for the vasculature, ureteric epithelium, nephron progenitors, and nephron structures. We also analyzed nephron differentiation in normoxia compared with hypoxia. At embryonic day 13.5 (E13.5), the major vascular branches were perfused; however, smaller-caliber peripheral vessels remained unperfused. By E15.5, peripheral vessels started to be perfused as well as glomeruli. While the interior kidney vessels were perfused, the peripheral vessels (nephrogenic zone) remained unperfused. Directly adjacent and internal to the nephrogenic zone, we found differentiated nephron structures surrounded and infiltrated by perfused vessels. Furthermore, we determined that at low O2 concentration, little nephron progenitor differentiation was observed; at higher O2 concentrations, more differentiation of the nephron progenitors was induced. The formation of the developing renal vessels occurs before the onset of blood flow. Furthermore, renal blood flow and oxygenation are critical for nephron progenitor differentiation. Copyright © 2014 the American Physiological Society.
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Invited review: mesenchymal progenitor cells in intramuscular connective tissue development.
Miao, Z G; Zhang, L P; Fu, X; Yang, Q Y; Zhu, M J; Dodson, M V; Du, M
2016-01-01
The abundance and cross-linking of intramuscular connective tissue contributes to the background toughness of meat, and is thus undesirable. Connective tissue is mainly synthesized by intramuscular fibroblasts. Myocytes, adipocytes and fibroblasts are derived from a common pool of progenitor cells during the early embryonic development. It appears that multipotent mesenchymal stem cells first diverge into either myogenic or non-myogenic lineages; non-myogenic mesenchymal progenitors then develop into the stromal-vascular fraction of skeletal muscle wherein adipocytes, fibroblasts and derived mesenchymal progenitors reside. Because non-myogenic mesenchymal progenitors mainly undergo adipogenic or fibrogenic differentiation during muscle development, strengthening progenitor proliferation enhances the potential for both intramuscular adipogenesis and fibrogenesis, leading to the elevation of both marbling and connective tissue content in the resulting meat product. Furthermore, given the bipotent developmental potential of progenitor cells, enhancing their conversion to adipogenesis reduces fibrogenesis, which likely results in the overall improvement of marbling (more intramuscular adipocytes) and tenderness (less connective tissue) of meat. Fibrogenesis is mainly regulated by the transforming growth factor (TGF) β signaling pathway and its regulatory cascade. In addition, extracellular matrix, a part of the intramuscular connective tissue, provides a niche environment for regulating myogenic differentiation of satellite cells and muscle growth. Despite rapid progress, many questions remain in the role of extracellular matrix on muscle development, and factors determining the early differentiation of myogenic, adipogenic and fibrogenic cells, which warrant further studies.
DNMT1 maintains progenitor function in self-renewing somatic tissue.
Sen, George L; Reuter, Jason A; Webster, Daniel E; Zhu, Lilly; Khavari, Paul A
2010-01-28
Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation. DNA methylation provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1) maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintenance, the role for DNMT1 in maintaining the progenitor state in constantly replenished somatic tissues, such as mammalian epidermis, is unclear. Here we show that DNMT1 is essential for epidermal progenitor cell function. DNMT1 protein was found enriched in undifferentiated cells, where it was required to retain proliferative stamina and suppress differentiation. In tissue, DNMT1 depletion led to exit from the progenitor cell compartment, premature differentiation and eventual tissue loss. Genome-wide analysis showed that a significant portion of epidermal differentiation gene promoters were methylated in self-renewing conditions but were subsequently demethylated during differentiation. Furthermore, UHRF1 (refs 9, 10), a component of the DNA methylation machinery that targets DNMT1 to hemi-methylated DNA, is also necessary to suppress premature differentiation and sustain proliferation. In contrast, Gadd45A and B, which promote active DNA demethylation, are required for full epidermal differentiation gene induction. These data demonstrate that proteins involved in the dynamic regulation of DNA methylation patterns are required for progenitor maintenance and self-renewal in mammalian somatic tissue.
Correction of distal hypospadias: ventral adaption of the prepuce and meatal advancement.
Persson-Jünemann, C; Seemann, O; Köhrmann, K U; Potempa, D; Jünemann, K P; Alken, P
1993-01-01
In distal hypospadias without chordee, surgical correction has a purely cosmetic character. In contrast to standard techniques focusing on meatal position, parents often regard the redundant dorsal prepuce and its missing ventral fusion as the essential constituent of this malformation. The operative technique, presented in detail, emphasizes on foreskin reconstruction. The ventral adaption of the prepuce (VAP procedure) results in a penis with normal appearance. Complications presented reveal the importance of proper patient selection.
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Lifescience Database Archive (English)
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File list: Oth.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available Oth.Adp.50.AllAg.Adipose_progenitor_cells mm9 TFs and others Adipocyte Adipose progeni...tor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Adp.50.AllAg.Adipose_progenitor_cells.bed ...
File list: Oth.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available Oth.Adp.10.AllAg.Adipose_progenitor_cells mm9 TFs and others Adipocyte Adipose progeni...tor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Adp.10.AllAg.Adipose_progenitor_cells.bed ...
Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain.
Ono, Munenori; Bishop, Deborah C; Oliver, Douglas L
2016-02-12
Different forms of plasticity are known to play a critical role in the processing of information about sound. Here, we report a novel neural plastic response in the inferior colliculus, an auditory center in the midbrain of the auditory pathway. A vigorous, long-lasting sound-evoked afterdischarge (LSA) is seen in a subpopulation of both glutamatergic and GABAergic neurons in the central nucleus of the inferior colliculus of normal hearing mice. These neurons were identified with single unit recordings and optogenetics in vivo. The LSA can continue for up to several minutes after the offset of the sound. LSA is induced by long-lasting, or repetitive short-duration, innocuous sounds. Neurons with LSA showed less adaptation than the neurons without LSA. The mechanisms that cause this neural behavior are unknown but may be a function of intrinsic mechanisms or the microcircuitry of the inferior colliculus. Since LSA produces long-lasting firing in the absence of sound, it may be relevant to temporary or chronic tinnitus or to some other aftereffect of long-duration sound.
File list: His.Neu.20.AllAg.Induced_neural_progenitors [Chip-atlas[Archive
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Full Text Available His.Neu.10.AllAg.Induced_neural_progenitors mm9 Histone Neural Induced neural proge...nitors SRX667381,SRX668240 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.10.AllAg.Induced_neural_progenitors.bed ...
Ventral hernia repair with poly-4-hydroxybutyrate mesh.
Plymale, Margaret A; Davenport, Daniel L; Dugan, Adam; Zachem, Amanda; Roth, John Scott
2018-04-01
Biomaterial research has made available a biologically derived fully resorbable poly-4-hydroxybutyrate (P4HB) mesh for use in ventral and incisional hernia repair (VIHR). This study evaluates outcomes of patients undergoing VIHR with P4HB mesh. An IRB-approved prospective pilot study was conducted to assess clinical and quality of life (QOL) outcomes for patients undergoing VIHR with P4HB mesh. Perioperative characteristics were defined. Clinical outcomes, employment status, QOL using 12-item short form survey (SF-12), and pain assessments were followed for 24 months postoperatively. 31 patients underwent VIHR with bioresorbable mesh via a Rives-Stoppa approach with retrorectus mesh placement. The median patient age was 52 years, median body mass index was 33 kg/m 2 , and just over half of the patients were female. Surgical site occurrences occurred in 19% of patients, most of which were seroma. Hernia recurrence rate was 0% (median follow-up = 414 days). Patients had significantly improved QOL at 24 months compared to baseline for SF-12 physical component summary and role emotional (p < 0.05). Ventral hernia repair with P4HB bioresorbable mesh results in favorable outcomes. Early hernia recurrence was not identified among the patient cohort. Quality of life improvements were noted at 24 months versus baseline for this cohort of patients with bioresorbable mesh. Use of P4HB mesh for ventral hernia repair was found to be feasible in this patient population. (ClinicalTrials.gov Identifier: NCT01863030).
Role of miRNA-9 in Brain Development
Directory of Open Access Journals (Sweden)
Balachandar Radhakrishnan
2016-01-01
Full Text Available MicroRNAs (miRNAs are a class of small regulatory RNAs involved in gene regulation. The regulation is effected by either translational inhibition or transcriptional silencing. In vertebrates, the importance of miRNA in development was discovered from mice and zebrafish dicer knockouts. The miRNA-9 (miR-9 is one of the most highly expressed miRNAs in the early and adult vertebrate brain. It has diverse functions within the developing vertebrate brain. In this article, the role of miR-9 in the developing forebrain (telencephalon and diencephalon, midbrain, hindbrain, and spinal cord of vertebrate species is highlighted. In the forebrain, miR-9 is necessary for the proper development of dorsoventral telencephalon by targeting marker genes expressed in the telencephalon. It regulates proliferation in telencephalon by regulating Foxg1, Pax6, Gsh2 , and Meis2 genes. The feedback loop regulation between miR-9 and Nr2e1/Tlx helps in neuronal migration and differentiation. Targeting Foxp1 and Foxp2 , and Map1b by miR-9 regulates the radial migration of neurons and axonal development. In the organizers, miR-9 is inversely regulated by hairy1 and Fgf8 to maintain zona limitans interthalamica and midbrain-hindbrain boundary (MHB. It maintains the MHB by inhibiting Fgf signaling genes and is involved in the neurogenesis of the midbrain-hindbrain by regulating Her genes. In the hindbrain, miR-9 modulates progenitor proliferation and differentiation by regulating Her genes and Elav3. In the spinal cord, miR-9 modulates the regulation of Foxp1 and Onecut1 for motor neuron development. In the forebrain, midbrain, and hindbrain, miR-9 is necessary for proper neuronal progenitor maintenance, neurogenesis, and differentiation. In vertebrate brain development, miR-9 is involved in regulating several region-specific genes in a spatiotemporal pattern.
Cowell, Rosemary A.; Bussey, Timothy J.; Saksida, Lisa M.
2010-01-01
We examined the organization and function of the ventral object processing pathway. The prevailing theoretical approach in this field holds that the ventral object processing stream has a modular organization, in which visual perception is carried out in posterior regions and visual memory is carried out, independently, in the anterior temporal…
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File list: Pol.Oth.50.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive
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File list: Oth.Neu.20.AllAg.Induced_neural_progenitors [Chip-atlas[Archive
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Full Text Available Oth.Neu.20.AllAg.Induced_neural_progenitors mm9 TFs and others Neural Induced neural... progenitors SRX323564,SRX323573 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.20.AllAg.Induced_neural_progenitors.bed ...
Rausch, Franziska; Mier, Daniela; Eifler, Sarah; Esslinger, Christine; Schilling, Claudia; Schirmbeck, Frederike; Englisch, Susanne; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias
2014-07-01
Patients with schizophrenia suffer from deficits in monitoring and controlling their own thoughts. Within these so-called metacognitive impairments, alterations in probabilistic reasoning might be one cognitive phenomenon disposing to delusions. However, so far little is known about alterations in associated brain functionality. A previously established task for functional magnetic resonance imaging (fMRI), which requires a probabilistic decision after a variable amount of stimuli, was applied to 23 schizophrenia patients and 28 healthy controls matched for age, gender and educational levels. We compared activation patterns during decision-making under conditions of certainty versus uncertainty and evaluated the process of final decision-making in ventral striatum (VS) and ventral tegmental area (VTA). We replicated a pre-described extended cortical activation pattern during probabilistic reasoning. During final decision-making, activations in several fronto- and parietocortical areas, as well as in VS and VTA became apparent. In both of these regions schizophrenia patients showed a significantly reduced activation. These results further define the network underlying probabilistic decision-making. The observed hypo-activation in regions commonly associated with dopaminergic neurotransmission fits into current concepts of disrupted prediction error signaling in schizophrenia and suggests functional links to reward anticipation. Forthcoming studies with patients at risk for psychosis and drug-naive first episode patients are necessary to elucidate the development of these findings over time and the interplay with associated clinical symptoms. Copyright © 2014 Elsevier B.V. All rights reserved.
TYPE IIb SUPERNOVAE WITH COMPACT AND EXTENDED PROGENITORS
International Nuclear Information System (INIS)
Chevalier, Roger A.; Soderberg, Alicia M.
2010-01-01
The classic example of a Type IIb supernova is SN 1993J, which had a cool extended progenitor surrounded by a dense wind. There is evidence for another category of Type IIb supernova that has a more compact progenitor with a lower density, probably fast, wind. Distinguishing features of the compact category are weak optical emission from the shock heated envelope at early times, nonexistent or very weak H emission in the late nebular phase, rapidly evolving radio emission, rapid expansion of the radio shell, and expected nonthermal as opposed to thermal X-ray emission. Type IIb supernovae that have one or more of these features include SNe 1996cb, 2001ig, 2003bg, 2008ax, and 2008bo. All of these with sufficient radio data (the last four) show evidence for presupernova wind variability. We estimate a progenitor envelope radius ∼1 x 10 11 cm for SN 2008ax, a value consistent with a compact Wolf-Rayet progenitor. Supernovae in the SN 1993J extended category include SN 2001gd and probably the Cas A supernova. We suggest that the compact Type IIb events be designated Type cIIb and the extended ones Type eIIb. The H envelope mass dividing these categories is ∼0.1 M sun .
Amer, Mohammed S; Hassan, Elham A; Torad, Faisal A
2018-02-20
Five female egg-laying pigeons presented with painless, reducible, ventral abdominal swellings located between the keel and the pubis, or close to the cloaca. Based on clinical, radiographic, and ultrasonographic examination, these pigeons were diagnosed with ventral abdominal hernia requiring surgical interference. Reduction was successfully performed under general anesthesia. Radiographic and ultrasonographic examinations were beneficial for confirming the diagnosis and visualizing the hernial content for surgical planning. Lateral radiographs were more helpful than ventrodorsal radiographs for identification of the hernial content and its continuation with the abdominal muscles. Ultrasonographic examination offered a non-invasive diagnostic tool that allowed for the differentiation of hernia from other abdominal swellings. In addition, it played a beneficial role in identification of the hernial content and follow up after surgical interference. In conclusion, radiographic and ultrasonographic examinations were beneficial in the diagnosis, surgical planning, and follow up after surgical interference of ventral abdominal hernia in pigeons.
Risk-Assessment Score and Patient Optimization as Cost Predictors for Ventral Hernia Repair.
Saleh, Sherif; Plymale, Margaret A; Davenport, Daniel L; Roth, John Scott
2018-04-01
Ventral hernia repair (VHR) is associated with complications that significantly increase healthcare costs. This study explores the associations between hospital costs for VHR and surgical complication risk-assessment scores, need for cardiac or pulmonary evaluation, and smoking or obesity counseling. An IRB-approved retrospective study of patients having undergone open VHR over 3 years was performed. Ventral Hernia Risk Score (VHRS) for surgical site occurrence and surgical site infection, and the Ventral Hernia Working Group grade were calculated for each case. Also recorded were preoperative cardiology or pulmonary evaluations, smoking cessation and weight reduction counseling, and patient goal achievement. Hospital costs were obtained from the cost accounting system for the VHR hospitalization stratified by major clinical cost drivers. Univariate regression analyses were used to compare the predictive power of the risk scores. Multivariable analysis was performed to develop a cost prediction model. The mean cost of index VHR hospitalization was $20,700. Total and operating room costs correlated with increasing CDC wound class, VHRS surgical site infection score, VHRS surgical site occurrence score, American Society of Anesthesiologists class, and Ventral Hernia Working Group (all p variance in costs (p optimization significantly reduced direct and operating room costs (p < 0.05). Cardiac evaluation was associated with increased costs. Ventral hernia repair hospital costs are more accurately predicted by CDC wound class than VHR risk scores. A straightforward 6-factor model predicted most cost variation for VHR. Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
Directory of Open Access Journals (Sweden)
Shunsuke Tanigawa
2016-04-01
Full Text Available Nephron progenitors in the embryonic kidney propagate while generating differentiated nephrons. However, in mice, the progenitors terminally differentiate shortly after birth. Here, we report a method for selectively expanding nephron progenitors in vitro in an undifferentiated state. Combinatorial and concentration-dependent stimulation with LIF, FGF2/9, BMP7, and a WNT agonist is critical for expansion. The purified progenitors proliferated beyond the physiological limits observed in vivo, both for cell numbers and lifespan. Neonatal progenitors were maintained for a week, while progenitors from embryonic day 11.5 expanded 1,800-fold for nearly 20 days and still reconstituted 3D nephrons containing glomeruli and renal tubules. Furthermore, progenitors generated from mouse embryonic stem cells and human induced pluripotent cells could be expanded with retained nephron-forming potential. Thus, we have established in vitro conditions for promoting the propagation of nephron progenitors, which will be essential for dissecting the mechanisms of kidney organogenesis and for regenerative medicine.
Neural Correlates of Hostile Jokes: Cognitive and Motivational Processes in Humor Appreciation.
Chan, Yu-Chen; Liao, Yi-Jun; Tu, Cheng-Hao; Chen, Hsueh-Chih
2016-01-01
Hostile jokes (HJs) provide aggressive catharsis and a feeling of superiority. Behavioral research has found that HJs are perceived as funnier than non-hostile jokes (NJs). The purpose of the present study was to identify the neural correlates of the interaction between type and humor by comparing HJs, NJs, and their corresponding hostile sentences (HSs) and non-hostile sentences (NSs). HJs primarily showed activation in the dorsomedial prefrontal cortex (dmPFC) and midbrain compared with the corresponding hostile baseline. Conversely, NJs primarily revealed activation in the ventromedial PFC (vmPFC), amygdala, midbrain, ventral anterior cingulate cortex, and nucleus accumbens (NAcc) compared with the corresponding non-hostile baseline. These results support the critical role of the medial PFC (mPFC) for the neural correlates of social cognition and socio-emotional processing in response to different types of jokes. Moreover, the processing of HJs showed increased activation in the dmPFC, which suggested cognitive operations of social motivation, whereas the processing of NJs displayed increased activation in the vmPFC, which suggested social-affective engagement. HJs versus NJs primarily showed increased activation in the dmPFC and midbrain, whereas NJs versus HJs primarily displayed greater activation in the amygdala and midbrain. The psychophysiological interaction (PPI) analysis demonstrated functional coupling of the dmPFC-dlPFC and midbrain-dmPFC for HJs and functional coupling of the vmPFC-midbrain and amygdala-midbrain-NAcc for NJs. Surprisingly, HJs were not perceived as funnier than NJs. Future studies could further investigate the neural correlates of potentially important traits of high-hostility tendencies in humor appreciation based on the psychoanalytic and superiority theories of humor.
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Full Text Available Oth.Neu.20.AllAg.Neural_progenitor_cells mm9 TFs and others Neural Neural progenito...r cells SRX109472,SRX315274,SRX802060,SRX109471 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.20.AllAg.Neural_progenitor_cells.bed ...
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File list: Oth.Oth.10.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive
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Full Text Available His.Neu.05.AllAg.Neural_progenitor_cells mm9 Histone Neural Neural progenitor cells... SRX315277,SRX667383,SRX668241,SRX315278,SRX315276 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.05.AllAg.Neural_progenitor_cells.bed ...
Proof of region-specific multipotent progenitors in human breast epithelia
DEFF Research Database (Denmark)
Fridriksdottir, Agla J; Villadsen, René; Morsing, Mikkel
2017-01-01
in luminal progenitors to interrogate the differentiation repertoire of candidate stem cells in TDLUs. We show that stem-like activity in serial passage culture and in vivo breast morphogenesis relies on the preservation of a myoepithelial phenotype. By enrichment for region-specific progenitors, we identify...
THE TYPE IIb SUPERNOVA 2011dh FROM A SUPERGIANT PROGENITOR
International Nuclear Information System (INIS)
Bersten, Melina C.; Nomoto, Ken'ichi; Folatelli, Gastón; Maeda, Keiichi; Benvenuto, Omar G.; Ergon, Mattias; Sollerman, Jesper; Benetti, Stefano; Ochner, Paolo; Tomasella, Lina; Botticella, Maria Teresa; Fraser, Morgan; Kotak, Rubina
2012-01-01
A set of hydrodynamical models based on stellar evolutionary progenitors is used to study the nature of SN 2011dh. Our modeling suggests that a large progenitor star—with R ∼ 200 R ☉ —is needed to reproduce the early light curve (LC) of SN 2011dh. This is consistent with the suggestion that the yellow super-giant star detected at the location of the supernova (SN) in deep pre-explosion images is the progenitor star. From the main peak of the bolometric LC and expansion velocities, we constrain the mass of the ejecta to be ≈2 M ☉ , the explosion energy to be E = (6-10) × 10 50 erg, and the 56 Ni mass to be approximately 0.06 M ☉ . The progenitor star was composed of a helium core of 3-4 M ☉ and a thin hydrogen-rich envelope of ≈0.1M ☉ with a main-sequence mass estimated to be in the range of 12-15 M ☉ . Our models rule out progenitors with helium-core masses larger than 8 M ☉ , which correspond to M ZAMS ∼> 25M ☉ . This suggests that a single star evolutionary scenario for SN 2011dh is unlikely.
EVOLUTION OF PROGENITORS FOR ELECTRON CAPTURE SUPERNOVAE
International Nuclear Information System (INIS)
Takahashi, Koh; Umeda, Hideyuki; Yoshida, Takashi
2013-01-01
We provide progenitor models for electron capture supernovae (ECSNe) with detailed evolutionary calculation. We include minor electron capture nuclei using a large nuclear reaction network with updated reaction rates. For electron capture, the Coulomb correction of rates is treated and the contribution from neutron-rich isotopes is taken into account in each nuclear statistical equilibrium (NSE) composition. We calculate the evolution of the most massive super asymptotic giant branch stars and show that these stars undergo off-center carbon burning and form ONe cores at the center. These cores become heavier up to the critical mass of 1.367 M ☉ and keep contracting even after the initiation of O+Ne deflagration. Inclusion of minor electron capture nuclei causes convective URCA cooling during the contraction phase, but the effect on the progenitor evolution is small. On the other hand, electron capture by neutron-rich isotopes in the NSE region has a more significant effect. We discuss the uniqueness of the critical core mass for ECSNe and the effect of wind mass loss on the plausibility of our models for ECSN progenitors.
Mapping a lateralisation gradient within the ventral stream for auditory speech perception
Karsten eSpecht
2013-01-01
Recent models on speech perception propose a dual stream processing network, with a dorsal stream, extending from the posterior temporal lobe of the left hemisphere through inferior parietal areas into the left inferior frontal gyrus, and a ventral stream that is assumed to originate in the primary auditory cortex in the upper posterior part of the temporal lobe and to extend towards the anterior part of the temporal lobe, where it may connect to the ventral part of the inferior frontal gyrus...
Mapping a lateralization gradient within the ventral stream for auditory speech perception
Specht, Karsten
2013-01-01
Recent models on speech perception propose a dual-stream processing network, with a dorsal stream, extending from the posterior temporal lobe of the left hemisphere through inferior parietal areas into the left inferior frontal gyrus, and a ventral stream that is assumed to originate in the primary auditory cortex in the upper posterior part of the temporal lobe and to extend toward the anterior part of the temporal lobe, where it may connect to the ventral part of the inferior frontal gyrus....
File list: His.Adp.10.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive
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File list: His.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available His.Adp.05.AllAg.Adipose_progenitor_cells mm9 Histone Adipocyte Adipose progenitor ...cells SRX127409,SRX127407,SRX127394,SRX127396,SRX127383,SRX127381 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Adp.05.AllAg.Adipose_progenitor_cells.bed ...
Jin, Hao; Sood, Raman; Xu, Jin; Zhen, Fenghua; English, Milton A; Liu, P Paul; Wen, Zilong
2009-02-01
One unique feature of vertebrate definitive hematopoiesis is the ontogenic switching of hematopoietic stem cells from one anatomical compartment or niche to another. In mice, hematopoietic stem cells are believed to originate in the aorta-gonad-mesonephros (AGM), subsequently migrate to the fetal liver (FL) and finally colonize the bone marrow (BM). Yet, the differentiation potential of hematopoietic stem cells within early niches such as the AGM and FL remains incompletely defined. Here, we present in vivo analysis to delineate the differentiation potential of definitive hematopoietic stem/progenitor cells (HSPCs) in the zebrafish AGM and FL analogies, namely the ventral wall of dorsal aorta (VDA) and the posterior blood island (PBI), respectively. Cell fate mapping and analysis of zebrafish runx1(w84x) and vlad tepes (vlt(m651)) mutants revealed that HSPCs in the PBI gave rise to both erythroid and myeloid lineages. However, we surprisingly found that HSPCs in the VDA were not quiescent but were uniquely adapted to generate myeloid but not erythroid lineage cells. We further showed that such distinct differentiation output of HSPCs was, at least in part, ascribed to the different micro-environments present in these two niches. Our results highlight the importance of niche in shaping the differentiation output of developing HSPCs.
Involvement of serotonin in the ventral tegmental area in thermoregulation of freely moving rats.
Ishiwata, Takayuki; Hasegawa, Hiroshi; Greenwood, Benjamin N
2017-07-13
We have recently reported that the serotonin (5-HT) projections from the midbrain's raphe nuclei that contains 5-HT cell bodies may play a role both in heat production and in heat loss. The purpose of the present study was to clarify the involvement of 5-HT in the ventral tegmental area (VTA), where 5-HT is suggested to participate in thermoregulation, using the combined methods of telemetry, microdialysis, and high performance liquid chromatography, with a special emphasis on regulation of the body temperature (T b ) in freely moving rats. First, we measured changes in T b , tail skin temperature (T tail ; an index of heat loss), heart rate (HR; an index of heat production), locomotor activity (Act), and levels of extracellular monoamines in the VTA during cold (5°C) or heat (35°C) exposure. Subsequently, we perfused citalopram (5-HT re-uptake inhibitor) into the VTA and measured the thermoregulatory parameters and monoamines release. Although T b , T tail , and HR changed during both exposures, significant changes in extracellular level of 5-HT (138.7±12.7% baseline, p<0.01), but not dopamine (DA) or noradrenaline (NA) were noted in the VTA only during heat exposure. In addition, perfusion of citalopram into the VTA increased extracellular 5-HT levels (221.0±52.2% baseline, p<0.01), but not DA or NA, while T b decreased from 37.4±0.1°C to 36.8±0.2°C (p<0.001),T tail increased from 26.3±0.4°C to 28.4±0.4°C (p<0.001), and HR and Act remained unchanged. Our results suggest that the VTA is a key area for thermoregulation, and 5-HT, but not DA or NA, modulates the heat loss system through action in the VTA. Copyright © 2017 Elsevier B.V. All rights reserved.
Directory of Open Access Journals (Sweden)
François Lapraz
2009-11-01
Full Text Available Formation of the dorsal-ventral axis of the sea urchin embryo relies on cell interactions initiated by the TGFbeta Nodal. Intriguingly, although nodal expression is restricted to the ventral side of the embryo, Nodal function is required for specification of both the ventral and the dorsal territories and is able to restore both ventral and dorsal regions in nodal morpholino injected embryos. The molecular basis for the long-range organizing activity of Nodal is not understood. In this paper, we provide evidence that the long-range organizing activity of Nodal is assured by a relay molecule synthesized in the ventral ectoderm, then translocated to the opposite side of the embryo. We identified this relay molecule as BMP2/4 based on the following arguments. First, blocking BMP2/4 function eliminated the long-range organizing activity of an activated Nodal receptor in an axis rescue assay. Second, we demonstrate that BMP2/4 and the corresponding type I receptor Alk3/6 functions are both essential for specification of the dorsal region of the embryo. Third, using anti-phospho-Smad1/5/8 immunostaining, we show that, despite its ventral transcription, the BMP2/4 ligand triggers receptor mediated signaling exclusively on the dorsal side of the embryo, one of the most extreme cases of BMP translocation described so far. We further report that the pattern of pSmad1/5/8 is graded along the dorsal-ventral axis and that two BMP2/4 target genes are expressed in nested patterns centered on the region with highest levels of pSmad1/5/8, strongly suggesting that BMP2/4 is acting as a morphogen. We also describe the very unusual ventral co-expression of chordin and bmp2/4 downstream of Nodal and demonstrate that Chordin is largely responsible for the spatial restriction of BMP2/4 signaling to the dorsal side. Thus, unlike in most organisms, in the sea urchin, a single ventral signaling centre is responsible for induction of ventral and dorsal cell fates. Finally
Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors
Doulatov, Sergei; Vo, Linda T.; Macari, Elizabeth R.; Wahlster, Lara; Kinney, Melissa A.; Taylor, Alison M.; Barragan, Jessica; Gupta, Manav; McGrath, Katherine; Lee, Hsiang-Ying; Humphries, Jessica M.; DeVine, Alex; Narla, Anupama; Alter, Blanche P.; Beggs, Alan H.; Agarwal, Suneet; Ebert, Benjamin L.; Gazda, Hanna T.; Lodish, Harvey F.; Sieff, Colin A.; Schlaeger, Thorsten M.; Zon, Leonard I.; Daley, George Q.
2017-01-01
Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small-molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and up-regulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA. PMID:28179501
Luminal progenitors restrict their lineage potential during mammary gland development.
Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia
2015-02-01
The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.
Braisted, Janet E.; Ringstedt, Thomas; O'Leary, Dennis D. M.
2009-01-01
Thalamocortical axons (TCAs) originate in dorsal thalamus, extend ventrally along the lateral thalamic surface, and as they approach hypothalamus make a lateral turn into ventral telencephalon. In vitro studies show that hypothalamus releases a chemorepellent for TCAs, and analyses of knockout mice indicate that Slit chemorepellents and their receptor Robo2 influence TCA pathfinding. We show that Slit chemorepellents are the hypothalamic chemorepellent and act through Robos to steer TCAs into...
Pain and convalescence following laparoscopic ventral hernia repair
DEFF Research Database (Denmark)
Eriksen, Jens Ravn
Severe pain is usual after laparoscopic ventral hernia repair (LVHR). Mesh fixation with titanium tacks may play a key role in the development of acute and chronic pain and alternative fixation methods should therefore be investigated. This PhD thesis was based on three studies and aimed too: 1) ...
Effects of combined BDNF and GDNF treatment on cultured dopaminergic midbrain neurons
DEFF Research Database (Denmark)
Sautter, J; Meyer, Morten; Spenger, C
1998-01-01
Neural transplantation is an experimental therapy for Parkinson's disease. Pretreatment of fetal donor tissue with neurotrophic factors may improve survival of grafted dopaminergic neurons. Free-floating roller tube cultures of fetal rat ventral mesencephalon were treated with brain-derived neuro......Neural transplantation is an experimental therapy for Parkinson's disease. Pretreatment of fetal donor tissue with neurotrophic factors may improve survival of grafted dopaminergic neurons. Free-floating roller tube cultures of fetal rat ventral mesencephalon were treated with brain......-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), or a combination of both. Dopamine content of the culture medium, the number of tyrosine hydroxylase-immunoreactive neurons, and culture volumes were moderately increased in the BDNF- and GDNF-treated cultures but significantly...... increased by 6.8-, 3.2- and 2.4-fold, respectively after treatment with the combination of both factors. We conclude that pretreatment of dopaminergic tissue in culture with a combination of BDNF and GDNF may be an effective means to improve the quality of tissue prior to grafting....
Hoebeke, P B; De Kuyper, P; Van Laecke, E
2002-11-01
In the hypospadiac penis the ventral skin is poorly developed, while dorsal skin is redundant. The classical Byars' flaps are a way to use the excess dorsal skin to cover the penile shaft. The appearance after Byars' flaps however is not natural. We use a more natural looking skin allocation with superior aesthetic results. The clue in this reconstruction is an inverted triangle shaped excision of ventral skin expanding over the edges of the hooded prepuce (which makes it look like Batman). After excision of the ventral skin it is possible to close the penile skin in the midline, thus mimicking the natural raphe. In case of preputial reconstruction the excised ventral skin makes the prepuce look more natural. The trend of further refining aesthetic appearance of the hypospadiac penis often neglects the penile skin reconstruction. A technique is presented by which the total penile appearances after surgery ameliorates due to better skin reconstruction.
Polyester composite versus PTFE in laparoscopic ventral hernia repair.
Colon, Modesto J; Telem, Dana A; Chin, Edward; Weber, Kaare; Divino, Celia M; Nguyen, Scott Q
2011-01-01
Both polyester composite (POC) and polytetrafluoroethylene (PTFE) mesh are commonly used for laparoscopic ventral hernia repair. However, sparse information exists comparing perioperative and long-term outcome by mesh repair. A prospective database was utilized to identify 116 consecutive patients who underwent laparoscopic ventral hernia repair at The Mount Sinai Hospital from 2004-2009. Patients were grouped by type of mesh used, PTFE versus POC, and retrospectively compared. Follow-up at a mean of 12 months was achieved by telephone interview and office visit. Of the 116 patients, 66 underwent ventral hernia repair with PTFE and 50 with POC mesh. Patients were well matched by patient demographics. No difference in mean body mass index (BMI) was demonstrated between the PTFE and POC group (31.8 vs. 32.5, respectively; P=NS). Operative time was significantly longer in the PTFE group (136 vs.106 minutes, PPTFE group and none in the POC group (P NS). No other major complications occurred in the immediate postoperative period (30 days). At a mean follow-up of 12 months, no significant difference was demonstrated between the PTFE and POC groups in hernia recurrence (3% vs. 2%), wound complications (1% vs. 0%), mesh infection, requiring removal (3% vs. 0%), bowel obstruction (3% vs. 2%), or persistent pain or discomfort (28% vs. 32%), respectively (P=NS). Our study demonstrated no significant association between types of mesh used and postoperative complications. In the 12-month follow-up, no differences were noted in hernia recurrence.
Tanigawa, Shunsuke; Taguchi, Atsuhiro; Sharma, Nirmala; Perantoni, Alan O; Nishinakamura, Ryuichi
2016-04-26
Nephron progenitors in the embryonic kidney propagate while generating differentiated nephrons. However, in mice, the progenitors terminally differentiate shortly after birth. Here, we report a method for selectively expanding nephron progenitors in vitro in an undifferentiated state. Combinatorial and concentration-dependent stimulation with LIF, FGF2/9, BMP7, and a WNT agonist is critical for expansion. The purified progenitors proliferated beyond the physiological limits observed in vivo, both for cell numbers and lifespan. Neonatal progenitors were maintained for a week, while progenitors from embryonic day 11.5 expanded 1,800-fold for nearly 20 days and still reconstituted 3D nephrons containing glomeruli and renal tubules. Furthermore, progenitors generated from mouse embryonic stem cells and human induced pluripotent cells could be expanded with retained nephron-forming potential. Thus, we have established in vitro conditions for promoting the propagation of nephron progenitors, which will be essential for dissecting the mechanisms of kidney organogenesis and for regenerative medicine. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
File list: Unc.Neu.10.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available Unc.Neu.10.AllAg.Fetal_neural_progenitor_cells hg19 Unclassified Neural Fetal neural... progenitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Neu.10.AllAg.Fetal_neural_progenitor_cells.bed ...
File list: NoD.Neu.20.AllAg.Induced_neural_progenitors [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available NoD.Neu.20.AllAg.Induced_neural_progenitors mm9 No description Neural Induced neural... progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Neu.20.AllAg.Induced_neural_progenitors.bed ...
File list: NoD.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available NoD.Neu.05.AllAg.Induced_neural_progenitors mm9 No description Neural Induced neural... progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Neu.05.AllAg.Induced_neural_progenitors.bed ...
File list: Unc.Neu.05.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available Unc.Neu.05.AllAg.Fetal_neural_progenitor_cells hg19 Unclassified Neural Fetal neural... progenitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Neu.05.AllAg.Fetal_neural_progenitor_cells.bed ...
File list: NoD.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available NoD.Neu.10.AllAg.Induced_neural_progenitors mm9 No description Neural Induced neural... progenitors http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Neu.10.AllAg.Induced_neural_progenitors.bed ...
Adaptive remodeling of the biliary tree: the essence of liver progenitor cell expansion.
Kok, Cindy Yuet-Yin; Miyajima, Atsushi; Itoh, Tohru
2015-07-01
The liver progenitor cell population has long been thought to exist within the liver. However, there are no standardized criteria for defining the liver progenitor cells, and there has been intense debate about the origin of these cells in the adult liver. The characteristics of such cells vary depending on the disease model used and also on the method of analysis. Visualization of three-dimensional biliary structures has revealed that the emergence of liver progenitor cells essentially reflects the adaptive remodeling of the hepatic biliary network in response to liver injury. We propose that the progenitor cell exists as a subpopulation in the biliary tree and show that the appearance of liver progenitor cells in injured parenchyma is reflective of extensive remodeling of the biliary structure. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
Boekhoudt, Linde; Omrani, Azar; Luijendijk, Mieneke C M; Wolterink-Donselaar, Inge G; Wijbrans, Ellen C; van der Plasse, Geoffrey; Adan, Roger A H
2016-01-01
Hyperactivity is a core symptom in various psychiatric disorders, including attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorders, and anorexia nervosa. Although hyperactivity has been linked to dopaminergic signalling, the causal relationship between midbrain dopamine neuronal
The Progenitors of Local Ultra-massive Galaxies Across Cosmic Time
DEFF Research Database (Denmark)
Marchesini, Danilo; Muzzin, Adam; Stefanon, Mauro
2014-01-01
in age of $z=0$ UMGs as derived from their fossil records. The progenitors of local UMGs, including the star-forming ones, never lived on the blue cloud since $z=3$. We propose an alternative path for the formation of local UMGs that refines previously proposed pictures and that is fully consistent......-forming galaxies progressively increases, with the progenitors at $2z 1$, whereas the remaining was assembled via merging from $z\\sim 1$ to the present. Most of the quenching of the star-forming progenitors happened between $z=2.75$ and $z=1.25$, in good agreement with the typical formation redshift and scatter...
File list: NoD.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available NoD.Adp.20.AllAg.Adipose_progenitor_cells mm9 No description Adipocyte Adipose progeni...tor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Adp.20.AllAg.Adipose_progenitor_cells.bed ...
File list: Pol.Neu.05.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
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File list: DNS.Neu.20.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
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File list: Unc.Neu.50.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available Unc.Neu.50.AllAg.Fetal_neural_progenitor_cells hg19 Unclassified Neural Fetal neural progeni...tor cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Neu.50.AllAg.Fetal_neural_progenitor_cells.bed ...
File list: Pol.Neu.10.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available Pol.Neu.10.AllAg.Fetal_neural_progenitor_cells hg19 RNA polymerase Neural Fetal neural progeni...tor cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Neu.10.AllAg.Fetal_neural_progenitor_cells.bed ...
File list: NoD.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive
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Full Text Available NoD.Adp.50.AllAg.Adipose_progenitor_cells mm9 No description Adipocyte Adipose progeni...tor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Adp.50.AllAg.Adipose_progenitor_cells.bed ...
File list: NoD.Adp.05.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available NoD.Adp.05.AllAg.Adipose_progenitor_cells mm9 No description Adipocyte Adipose progeni...tor cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Adp.05.AllAg.Adipose_progenitor_cells.bed ...
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Full Text Available NoD.Oth.05.AllAg.Multipotent_otic_progenitor mm9 No description Others Multipotent otic progeni...tor http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Oth.05.AllAg.Multipotent_otic_progenitor.bed ...
File list: DNS.Neu.50.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
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File list: Pol.Neu.50.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available Pol.Neu.50.AllAg.Fetal_neural_progenitor_cells hg19 RNA polymerase Neural Fetal neural... progenitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Neu.50.AllAg.Fetal_neural_progenitor_cells.bed ...
File list: His.Neu.50.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available His.Neu.50.AllAg.Fetal_neural_progenitor_cells hg19 Histone Neural Fetal neural pro...genitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.50.AllAg.Fetal_neural_progenitor_cells.bed ...
File list: His.Neu.20.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available His.Neu.20.AllAg.Fetal_neural_progenitor_cells hg19 Histone Neural Fetal neural pro...genitor cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Neu.20.AllAg.Fetal_neural_progenitor_cells.bed ...
Panuganti, Swapna; Papoutsakis, Eleftherios T; Miller, William M
2010-10-01
Megakaryopoiesis encompasses hematopoietic stem and progenitor cell (HSPC) commitment to the megakaryocytic cell (Mk) lineage, expansion of Mk progenitors and mature Mks, polyploidization and platelet release. pH and pO2 increase from the endosteum to sinuses, and different cytokines are important for various stages of differentiation. We hypothesized that mimicking the changing conditions during Mk differentiation in the bone marrow would facilitate expansion of progenitors that could generate many high-ploidy Mks. CD34+ HSPCs were cultured at pH 7.2 and 5% O2 with stem cell factor (SCF), thrombopoietin (Tpo) and all combinations of Interleukin (IL)-3, IL-6, IL-11 and Flt-3 ligand to promote Mk progenitor expansion. Cells cultured with selected cytokines were shifted to pH 7.4 and 20% O2 to generate mature Mks, and treated with nicotinamide (NIC) to enhance polyploidization. Using Tpo + SCF + IL-3 + IL-11, we obtained 3.5 CD34+ CD41+ Mk progenitors per input HSPC, while increasing purity from 1% to 17%. Cytokine cocktails with IL-3 yielded more progenitors and mature Mks, although the purities were lower. Mk production was much greater at higher pH and pO2. Although fewer progenitors were present, shifting to 20% O2 /pH 7.4 at day 5 (versus days 7 or 9) yielded the greatest mature Mk production, 14 per input HSPC. NIC more than doubled the percentage of high-ploidy Mks to 40%. We obtained extensive Mk progenitor expansion, while ensuring that the progenitors could produce high-ploidy Mks. We anticipate that subsequent optimization of cytokines for mature Mk production and delayed NIC addition will greatly increase high-ploidy Mk production.
Energy Technology Data Exchange (ETDEWEB)
LaBarge, Mark A; Nelson, Celeste M; Villadsen, Rene; Fridriksdottir, Agla; Ruth, Jason R; Stampfer, Martha R; Petersen, Ole W; Bissell, Mina J
2008-09-19
In adult tissues, multi-potent progenitor cells are some of the most primitive members of the developmental hierarchies that maintain homeostasis. That progenitors and their more mature progeny share identical genomes, suggests that fate decisions are directed by interactions with extrinsic soluble factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells. Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well as constellations of signaling molecules; and these were used in conjunction with physiologically relevant 3 dimensional human breast cultures. Both immortalized and primary human breast progenitors were analyzed. We report on the functional ability of those proteins of the mammary gland that maintain quiescence, maintain the progenitor state, and guide progenitor differentiation towards myoepithelial and luminal lineages.
Single progenitor model for GW150914 and GW170104
D'Orazio, Daniel J.; Loeb, Abraham
2018-04-01
The merger of stellar-mass black holes (BHs) is not expected to generate detectable electromagnetic (EM) emission. However, the gravitational wave (GW) events GW150914 and GW170104, detected by the Laser Interferometer Gravitational Wave Observatory to be the result of merging, ˜60 M⊙ binary black holes (BBHs), each have claimed coincident gamma-ray emission. Motivated by the intriguing possibility of an EM counterpart to BBH mergers, we construct a model that can reproduce the observed EM and GW signals for GW150914- and GW170104-like events, from a single-star progenitor. Following Loeb [Astrophys. J. Lett. 819, L21 (2016), 10.3847/2041-8205/819/2/L21], we envision a massive, rapidly rotating star within which a rotating-bar instability fractures the core into two overdensities that fragment into clumps which merge to form BHs in a tight binary with arbitrary spin-orbit alignment. Once formed, the BBH inspirals due to gas and gravitational-wave drag until tidal forces trigger strong feeding of the BHs with the surrounding stellar-density gas about 10 sec before merger. The resulting giga-Eddington accretion peak launches a jet that breaks out of the progenitor star and drives a powerful outflow that clears the gas from the orbit of the binary within 1 sec, preserving the vacuum GW waveform in the Laser Interferometer Gravitational Wave Observatory band. The single-progenitor scenario predicts the existence of variability of the gamma-ray burst, modulated at the ˜0.2 sec chirping period of the BBH due to relativistic Doppler boost. The jet breakout should be accompanied by a low-luminosity supernova. Finally, because the BBHs of the single-progenitor model do not exist at large separations, they will not be detectable in the low-frequency gravitational-wave band of the Laser Interferometer Space Antenna. Hence, the single-progenitor BBHs will be unambiguously discernible from BBHs formed through alternate, double-progenitor evolution scenarios.
Biomimetic collagen/elastin meshes for ventral hernia repair in a rat model.
Minardi, Silvia; Taraballi, Francesca; Wang, Xin; Cabrera, Fernando J; Van Eps, Jeffrey L; Robbins, Andrew B; Sandri, Monica; Moreno, Michael R; Weiner, Bradley K; Tasciotti, Ennio
2017-03-01
Ventral hernia repair remains a major clinical need. Herein, we formulated a type I collagen/elastin crosslinked blend (CollE) for the fabrication of biomimetic meshes for ventral hernia repair. To evaluate the effect of architecture on the performance of the implants, CollE was formulated both as flat sheets (CollE Sheets) and porous scaffolds (CollE Scaffolds). The morphology, hydrophylicity and in vitro degradation were assessed by SEM, water contact angle and differential scanning calorimetry, respectively. The stiffness of the meshes was determined using a constant stretch rate uniaxial tensile test, and compared to that of native tissue. CollE Sheets and Scaffolds were tested in vitro with human bone marrow-derived mesenchymal stem cells (h-BM-MSC), and finally implanted in a rat ventral hernia model. Neovascularization and tissue regeneration within the implants was evaluated at 6weeks, by histology, immunofluorescence, and q-PCR. It was found that CollE Sheets and Scaffolds were not only biomechanically sturdy enough to provide immediate repair of the hernia defect, but also promoted tissue restoration in only 6weeks. In fact, the presence of elastin enhanced the neovascularization in both sheets and scaffolds. Overall, CollE Scaffolds displayed mechanical properties more closely resembling those of native tissue, and induced higher gene expression of the entire marker genes tested, associated with de novo matrix deposition, angiogenesis, adipogenesis and skeletal muscles, compared to CollE Sheets. Altogether, this data suggests that the improved mechanical properties and bioactivity of CollE Sheets and Scaffolds make them valuable candidates for applications of ventral hernia repair. Due to the elevated annual number of ventral hernia repair in the US, the lack of successful grafts, the design of innovative biomimetic meshes has become a prime focus in tissue engineering, to promote the repair of the abdominal wall, avoid recurrence. Our meshes (Coll
Correlation between early surgical complications and readmission rate after ventral hernia repair.
Kokotovic, D; Sjølander, H; Gögenur, I; Helgstrand, F
2017-08-01
Postoperative surgical complications arising from ventral hernia repair have been assessed by a variety of outcome measures. The objective of this study was to correlate the Clavien Dindo Classification (CDC) graded complications with the 30-day readmission rate as early outcome measures in ventral hernia repair. Secondarily, we wanted to investigate whether the risk factors for Clavien Dindo class ≥1 and 30-day readmission were comparable. Single-centre retrospective study including all patients (≥18 years) who underwent ventral hernia repair between January 1, 2009 and September 1, 2014 at Zealand University Hospital. Data were obtained from hospital files and the Danish National Patient Registry. A 100% follow-up was obtained. In total, the study included 700 patients (261 patients with incisional hernia repair and 439 patients with umbilical or epigastric hernia repair). There was a significant association between a complication graded by the CDC ≥1 and 30-day readmission for both incisional and umbilical/epigastric hernia repair (p readmission. Recurrent (vs. primary) hernia repair was an independent risk factors for both CDC ≥1 and 30-day readmission in umbilical/epigastric hernia repair. Furthermore, hernia size 2-7 cm (vs. >2 cm) was a risk factor for CDC ≥1 but not for 30-day readmission in umbilical/epigastric hernia repair. Reports on 30-day readmission can be used as a general outcome measure in ventral hernia repair, however CDC provides a more precise and detailed registration of postoperative complications.
PROGENITORS OF RECOMBINING SUPERNOVA REMNANTS
Energy Technology Data Exchange (ETDEWEB)
Moriya, Takashi J., E-mail: takashi.moriya@ipmu.jp [Kavli Institute for the Physics and Mathematics of the Universe, Todai Institutes for Advanced Study, University of Tokyo, Kashiwanoha 5-1-5, Kashiwa, Chiba 277-8583 (Japan)
2012-05-01
Usual supernova remnants have either ionizing plasma or plasma in collisional ionization equilibrium, i.e., the ionization temperature is lower than or equal to the electron temperature. However, the existence of recombining supernova remnants, i.e., supernova remnants with ionization temperature higher than the electron temperature, has been recently confirmed. One suggested way to have recombining plasma in a supernova remnant is to have a dense circumstellar medium at the time of the supernova explosion. If the circumstellar medium is dense enough, collisional ionization equilibrium can be established in the early stage of the evolution of the supernova remnant and subsequent adiabatic cooling, which occurs after the shock wave gets out of the dense circumstellar medium, makes the electron temperature lower than the ionization temperature. We study the circumstellar medium around several supernova progenitors and show which supernova progenitors can have a circumstellar medium dense enough to establish collisional ionization equilibrium soon after the explosion. We find that the circumstellar medium around red supergiants (especially massive ones) and the circumstellar medium dense enough to make Type IIn supernovae can establish collisional ionization equilibrium soon after the explosion and can evolve to become recombining supernova remnants. Wolf-Rayet stars and white dwarfs have the possibility to be recombining supernova remnants but the fraction is expected to be very small. As the occurrence rate of the explosions of red supergiants is much higher than that of Type IIn supernovae, the major progenitors of recombining supernova remnants are likely to be red supergiants.
International Nuclear Information System (INIS)
Sakurai, Keita; Tokumaru, Aya M.; Shimoji, Keigo; Murayama, Shigeo; Kanemaru, Kazutomi; Morimoto, Satoru; Aiba, Ikuko; Nakagawa, Motoo; Ozawa, Yoshiyuki; Shimohira, Masashi; Shibamoto, Yuta; Matsukawa, Noriyuki; Hashizume, Yoshio
2017-01-01
Recently, it has been recognized that pathologically proven progressive supranuclear palsy (PSP) cases are classified into various clinical subtypes with non-uniform symptoms and imaging findings. This article reviews essential imaging findings, general information, and advanced magnetic resonance imaging (MRI) techniques for PSP and presents these MRI findings of pathologically proven typical and atypical PSP cases for educational purposes. With the review of literatures, notably including atypical pathologically proven PSP cases, MRI and clinical information of 15 pathologically proven typical and atypical PSP cases were retrospectively evaluated. In addition to typical symptoms, PSP patients can exhibit atypical symptoms including levodopa-responsive parkinsonism, pure akinesia, non-fluent aphasia, corticobasal syndrome, and predominant cerebellar ataxia. As well as clinical symptoms, the degree of midbrain atrophy, a well-known imaging hallmark, is not consistent in atypical PSP cases. This fact has important implications for the limitation of midbrain atrophy as a diagnostic imaging biomarker of PSP pathology. Additional evaluation of other imaging findings including various regional atrophies of the globus pallidus, frontal lobe, cerebral peduncle, and superior cerebellar peduncle is essential for the diagnosis of atypical PSP cases. It is necessary for radiologists to recognize the wide clinical and radiological spectra of typical and atypical PSP cases. (orig.)
Energy Technology Data Exchange (ETDEWEB)
Sakurai, Keita; Tokumaru, Aya M.; Shimoji, Keigo [Tokyo Metropolitan Medical Center of Gerontology, Department of Diagnostic Radiology, Tokyo (Japan); Murayama, Shigeo; Kanemaru, Kazutomi; Morimoto, Satoru [Tokyo Metropolitan Geriatric Hospital, Department of Neurology, Tokyo (Japan); Aiba, Ikuko [National Hospital Organization Higashi Nagoya National Hospital, Department of Neurology, Nagoya (Japan); Nakagawa, Motoo; Ozawa, Yoshiyuki; Shimohira, Masashi; Shibamoto, Yuta [Nagoya City University Graduate School of Medical Sciences, Department of Radiology, Nagoya (Japan); Matsukawa, Noriyuki [Nagoya City University Graduate School of Medical Sciences, Department of Neurology and Neuroscience, Nagoya (Japan); Hashizume, Yoshio [Fukushimura Hospital, Choju Medical Institute, Toyohashi (Japan)
2017-05-15
Recently, it has been recognized that pathologically proven progressive supranuclear palsy (PSP) cases are classified into various clinical subtypes with non-uniform symptoms and imaging findings. This article reviews essential imaging findings, general information, and advanced magnetic resonance imaging (MRI) techniques for PSP and presents these MRI findings of pathologically proven typical and atypical PSP cases for educational purposes. With the review of literatures, notably including atypical pathologically proven PSP cases, MRI and clinical information of 15 pathologically proven typical and atypical PSP cases were retrospectively evaluated. In addition to typical symptoms, PSP patients can exhibit atypical symptoms including levodopa-responsive parkinsonism, pure akinesia, non-fluent aphasia, corticobasal syndrome, and predominant cerebellar ataxia. As well as clinical symptoms, the degree of midbrain atrophy, a well-known imaging hallmark, is not consistent in atypical PSP cases. This fact has important implications for the limitation of midbrain atrophy as a diagnostic imaging biomarker of PSP pathology. Additional evaluation of other imaging findings including various regional atrophies of the globus pallidus, frontal lobe, cerebral peduncle, and superior cerebellar peduncle is essential for the diagnosis of atypical PSP cases. It is necessary for radiologists to recognize the wide clinical and radiological spectra of typical and atypical PSP cases. (orig.)
Opposing dorsal/ventral stream dynamics during figure-ground segregation
Wokke, M.E.; Scholte, H.S.; Lamme, V.A.F.
2014-01-01
The visual system has been commonly subdivided into two segregated visual processing streams: The dorsal pathway processes mainly spatial information, and the ventral pathway specializes in object perception. Recent findings, however, indicate that different forms of interaction (cross-talk) exist
File list: Oth.Neu.20.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available Oth.Neu.20.AllAg.Fetal_neural_progenitor_cells hg19 TFs and others Neural Fetal neural... progenitor cells SRX109477 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Neu.20.AllAg.Fetal_neural_progenitor_cells.bed ...
File list: Oth.Neu.50.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available Oth.Neu.50.AllAg.Fetal_neural_progenitor_cells hg19 TFs and others Neural Fetal neural... progenitor cells SRX109477 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Neu.50.AllAg.Fetal_neural_progenitor_cells.bed ...
PRMT5 is essential for the maintenance of chondrogenic progenitor cells in the limb bud.
Norrie, Jacqueline L; Li, Qiang; Co, Swanie; Huang, Bau-Lin; Ding, Ding; Uy, Jann C; Ji, Zhicheng; Mackem, Susan; Bedford, Mark T; Galli, Antonella; Ji, Hongkai; Vokes, Steven A
2016-12-15
During embryonic development, undifferentiated progenitor cells balance the generation of additional progenitor cells with differentiation. Within the developing limb, cartilage cells differentiate from mesodermal progenitors in an ordered process that results in the specification of the correct number of appropriately sized skeletal elements. The internal pathways by which these cells maintain an undifferentiated state while preserving their capacity to differentiate is unknown. Here, we report that the arginine methyltransferase PRMT5 has a crucial role in maintaining progenitor cells. Mouse embryonic buds lacking PRMT5 have severely truncated bones with wispy digits lacking joints. This novel phenotype is caused by widespread cell death that includes mesodermal progenitor cells that have begun to precociously differentiate into cartilage cells. We propose that PRMT5 maintains progenitor cells through its regulation of Bmp4 Intriguingly, adult and embryonic stem cells also require PRMT5 for maintaining pluripotency, suggesting that similar mechanisms might regulate lineage-restricted progenitor cells during organogenesis. © 2016. Published by The Company of Biologists Ltd.
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Lifescience Database Archive (English)
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Lifescience Database Archive (English)
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File list: ALL.Neu.10.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
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Lifescience Database Archive (English)
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File list: InP.Adp.20.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
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File list: InP.Adp.50.AllAg.Adipose_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available InP.Adp.50.AllAg.Adipose_progenitor_cells mm9 Input control Adipocyte Adipose progeni...tor cells SRX127370,SRX127367 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Adp.50.AllAg.Adipose_progenitor_cells.bed ...
File list: ALL.Neu.05.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available ALL.Neu.05.AllAg.Fetal_neural_progenitor_cells hg19 All antigens Neural Fetal neural... progenitor cells SRX109477,SRX109478 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Neu.05.AllAg.Fetal_neural_progenitor_cells.bed ...
Ens, Bruno J.; Alting, D
1996-01-01
We studied prey choice of a captive Oystercatcher:hat hammered Mussels from the ventral side. The results replicate previous findings that ventral hammerers select Mussels of intermediate size, select against thick-shelled Mussels, abandon an increasing proportion of Mussels with increasing size and
Intersections of lung progenitor cells, lung disease and lung cancer.
Kim, Carla F
2017-06-30
The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.
Intersections of lung progenitor cells, lung disease and lung cancer
Directory of Open Access Journals (Sweden)
Carla F. Kim
2017-06-01
Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.
Cooch, Nisha K; Stalnaker, Thomas A; Wied, Heather M; Bali-Chaudhary, Sheena; McDannald, Michael A; Liu, Tzu-Lan; Schoenbaum, Geoffrey
2015-05-21
The ventral striatum has long been proposed as an integrator of biologically significant associative information to drive actions. Although inputs from the amygdala and hippocampus have been much studied, the role of prominent inputs from orbitofrontal cortex (OFC) are less well understood. Here, we recorded single-unit activity from ventral striatum core in rats with sham or ipsilateral neurotoxic lesions of lateral OFC, as they performed an odour-guided spatial choice task. Consistent with prior reports, we found that spiking activity recorded in sham rats during cue sampling was related to both reward magnitude and reward identity, with higher firing rates observed for cues that predicted more reward. Lesioned rats also showed differential activity to the cues, but this activity was unbiased towards larger rewards. These data support a role for OFC in shaping activity in the ventral striatum to represent the biological significance of associative information in the environment.
Bhat, Amilal; Gandhi, Ajay; Saxena, Gajendra; Choudhary, Gautam Ram
2010-01-01
Aims : Objective of this study was to assess the feasibility and results of preputial reconstruction and tubularized incised plate urethroplasty (TIP) in patients of proximal hypospadias with ventral penile curvature. Materials and Methods : Twenty-seven patients of proximal hypospadias who underwent preputioplasty with TIP were evaluated retrospectively. Ventral curvature was corrected by mobilization of the urethral plate with the corpus spongiosum and the proximal urethra; dorsal plica...
File list: InP.Neu.20.AllAg.Induced_neural_progenitors [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available InP.Neu.20.AllAg.Induced_neural_progenitors mm9 Input control Neural Induced neural... progenitors SRX323563,SRX323574,SRX667380,SRX668238 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.20.AllAg.Induced_neural_progenitors.bed ...
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Full Text Available InP.Neu.50.AllAg.Induced_neural_progenitors mm9 Input control Neural Induced neural... progenitors SRX323563,SRX323574,SRX667380,SRX668238 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.50.AllAg.Induced_neural_progenitors.bed ...
File list: InP.Neu.10.AllAg.Induced_neural_progenitors [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available InP.Neu.10.AllAg.Induced_neural_progenitors mm9 Input control Neural Induced neural... progenitors SRX668238,SRX667380,SRX323563,SRX323574 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.10.AllAg.Induced_neural_progenitors.bed ...
File list: InP.Neu.05.AllAg.Induced_neural_progenitors [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available InP.Neu.05.AllAg.Induced_neural_progenitors mm9 Input control Neural Induced neural... progenitors SRX667380,SRX668238,SRX323563,SRX323574 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.05.AllAg.Induced_neural_progenitors.bed ...
Directory of Open Access Journals (Sweden)
Aline Carolina Giardini
2017-01-01
Full Text Available Background. Glial cells are implicated in the development of chronic pain and brain-derived neurotropic factor (BDNF released from activated microglia contributes to the nociceptive transmission. Neural mobilization (NM technique is a method clinically effective in reducing pain sensitivity. Here we examined the involvement of glial cells and BDNF expression in the thalamus and midbrain after NM treatment in rats with chronic constriction injury (CCI. CCI was induced and rats were subsequently submitted to 10 sessions of NM, every other day, beginning 14 days after CCI. Thalamus and midbrain were analyzed for glial fibrillary acidic protein (GFAP, microglial cell OX-42, and BDNF using Immunohistochemistry and Western blot assays. Results. Thalamus and midbrain of CCI group showed increases in GFAP, OX-42, and BDNF expression compared with control group and, in contrast, showed decreases in GFAP, OX-42, and BDNF after NM when compared with CCI group. The decreased immunoreactivity for GFAP, OX-42, and BDNF in ventral posterolateral nucleus in thalamus and the periaqueductal gray in midbrain was shown by immunohistochemistry. Conclusions. These findings may improve the knowledge about the involvement of astrocytes, microglia, and BDNF in the chronic pain and show that NM treatment, which alleviates neuropathic pain, affects glial cells and BDNF expression.
Pulpal progenitors and dentin repair.
Harichane, Y; Hirata, A; Dimitrova-Nakov, S; Granja, I; Goldberg, A; Kellermann, O; Poliard, A
2011-07-01
Mesenchymal stem cells are present in the dental pulp. They have been shown to contribute to dentin-like tissue formation in vitro and to participate in bone repair after a mandibular lesion. However, their capacity to contribute efficiently to reparative dentin formation after pulp lesion has never been explored. After pulp exposure, we have identified proliferative cells within 3 zones. In the crown, zone I is near the cavity, and zone II corresponds to the isthmus between the mesial and central pulp. In the root, zone III, near the apex, at a distance from the inflammatory site, contains mitotic stromal cells which may represent a source of progenitor cells. Stem-cell-based strategies are promising treatments for tissue injury in dentistry. Our experiments focused on (1) location of stem cells induced to leave their quiescent state early after pulp injury and (2) implantation of pulp progenitors, a substitute for classic endodontic treatments, paving the way for pulp stem-cell-based therapies.
DEFF Research Database (Denmark)
Deserno, Lorenz; Beck, Anne; Huys, Quentin J. M.
2015-01-01
Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug......-related stimuli towards drug-related stimuli. Such ‘hijacked’ dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs......) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N = 27). All participants also underwent 6-[18F]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation...
Smeets, Bart; Angelotti, Maria Lucia; Rizzo, Paola; Dijkman, Henry; Lazzeri, Elena; Mooren, Fieke; Ballerini, Lara; Parente, Eliana; Sagrinati, Costanza; Mazzinghi, Benedetta; Ronconi, Elisa; Becherucci, Francesca; Benigni, Ariela; Steenbergen, Eric; Lasagni, Laura; Remuzzi, Giuseppe; Wetzels, Jack; Romagnani, Paola
2009-12-01
Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner surface of Bowman's capsule can regenerate podocytes, but whether dysregulated proliferation of these progenitors contributes to crescent formation is unknown. In this study, we used confocal microscopy, laser capture microdissection, and real-time quantitative reverse transcriptase-PCR to demonstrate that hypercellular lesions of different podocytopathies and crescentic glomerulonephritis consist of three distinct populations: CD133(+)CD24(+)podocalyxin (PDX)(-)nestin(-) renal progenitors, CD133(+)CD24(+)PDX(+)nestin(+) transitional cells, and CD133(-)CD24(-)PDX(+)nestin(+) differentiated podocytes. In addition, TGF-beta induced CD133(+)CD24(+) progenitors to produce extracellular matrix, and these were the only cells to express the proliferation marker Ki67. Taken together, these results suggest that glomerular hyperplastic lesions derive from the proliferation of renal progenitors at different stages of their differentiation toward mature podocytes, providing an explanation for the pathogenesis of hyperplastic lesions in podocytopathies and crescentic glomerulonephritis.
International Nuclear Information System (INIS)
Cashman, J.; Eaves, A.C.; Eaves, C.J.
1985-01-01
We have examined the cycling status of various classes of erythroid and granulopoietic progenitor populations maintained for many weeks in standard normal long-term human marrow cultures. These were initiated with a single inoculum of marrow aspirate and were routinely fed by weekly removal of half of the nonadherent cells and replacement of half of the growth medium. Progenitors of large erythroid colonies (more than eight erythroblast clusters) present in the nonadherent fraction and progenitors of small granulocyte/macrophage colonies (fewer than 500 cells) present in both the nonadherent and adherent fractions were found to be actively cycling at all times examined (28% to 63% kill following a 20-minute exposure to 20 microCi/mL of high specific activity 3 H-thymidine). In contrast, progenitors of large granulocyte/macrophage colonies (more than 500 cells) and progenitors of large erythroid colonies (more than eight erythroblast clusters), present in the adherent layer, consistently alternated between a quiescent state at the time of each weekly medium change and a proliferating state two to three days later (0% to 13% kill and 21% to 49% kill, respectively). Additional experiments revealed that the activation of primitive progenitors in the adherent layer was not dependent on the addition of fresh glutamine or hydrocortisone, nor on the physical manipulations involved in changing the growth medium. These studies provide the first direct evidence that normal long-term human marrow cultures support the continued turnover of a variety of early hematopoietic progenitor cell types. Further, they indicate that the proliferative activity of the most primitive of these progenitors is regulated by stage-specific cell-cell interactions that are subject to manipulation
Blindness alters the microstructure of the ventral but not the dorsal visual stream.
Reislev, Nina L; Kupers, Ron; Siebner, Hartwig R; Ptito, Maurice; Dyrby, Tim B
2016-07-01
Visual deprivation from birth leads to reorganisation of the brain through cross-modal plasticity. Although there is a general agreement that the primary afferent visual pathways are altered in congenitally blind individuals, our knowledge about microstructural changes within the higher-order visual streams, and how this is affected by onset of blindness, remains scant. We used diffusion tensor imaging and tractography to investigate microstructural features in the dorsal (superior longitudinal fasciculus) and ventral (inferior longitudinal and inferior fronto-occipital fasciculi) visual pathways in 12 congenitally blind, 15 late blind and 15 normal sighted controls. We also studied six prematurely born individuals with normal vision to control for the effects of prematurity on brain connectivity. Our data revealed a reduction in fractional anisotropy in the ventral but not the dorsal visual stream for both congenitally and late blind individuals. Prematurely born individuals, with normal vision, did not differ from normal sighted controls, born at term. Our data suggest that although the visual streams are structurally developing without normal visual input from the eyes, blindness selectively affects the microstructure of the ventral visual stream regardless of the time of onset. We suggest that the decreased fractional anisotropy of the ventral stream in the two groups of blind subjects is the combined result of both degenerative and cross-modal compensatory processes, affecting normal white matter development.
Ventral impressions on the hypopharynx
International Nuclear Information System (INIS)
Daschner, H.; Hannig, C.
1991-01-01
Two impressions can be seen on the ventral aspect of the hypopharynx and upper oesophagus; on static images it is difficult to differentiate these from small tumours. In order to evaluate this region more accurately, we have examined 150 patients by means of rapid rate cinematography. In 52.6% we found a constant irregular or convex impression formed by the cricoid; in the other cases this was not seen or was quite minimal. In 93% a sub-cricoid impression could be demonstrated which was due to lax mucosa. Characteristically this showed a variable appearance during the passage of a bolus. Only the cricoid impression was associated with dysphagia. (orig.) [de
Cho, Yong Suk; Stevens, Leslie M; Stein, David
2010-06-22
The establishment of Drosophila embryonic dorsal-ventral (DV) polarity relies on serine proteolytic activity in the perivitelline space between the embryonic membrane and the eggshell. Gastrulation Defective cleaves and activates Snake, which processes and activates Easter, which cleaves Spätzle to form the activating ligand for the Toll receptor. Ventral restriction of ligand formation depends on the Pipe sulfotransferase, which is expressed in ventral cells of the follicular epithelium surrounding the developing oocyte. Pipe modifies components of the developing eggshell to produce a ventral cue embedded in the vitelline membrane. This ventral cue is believed to promote one or more of the proteolysis steps in the perivitelline space. By examining the processing of transgenic, tagged versions of the perivitelline proteins during DV patterning, we find that the proteolysis of Easter by Snake is the first Pipe-dependent step and therefore the key ventrally restricted event in the protease cascade. We also find that Snake and Easter associate together in a complex in both wild-type and pipe mutant-derived embryos. This observation suggests a mechanism in which the sulfated target of Pipe promotes a productive interaction between Snake and Easter, perhaps by facilitating conformational changes in a complex containing the two proteins. Copyright 2010 Elsevier Ltd. All rights reserved.
Neural Correlates of Hostile Jokes: Cognitive and Motivational Processes in Humor Appreciation
Directory of Open Access Journals (Sweden)
Yu-Chen Chan
2016-10-01
Full Text Available Hostile jokes provide aggressive catharsis and a feeling of superiority. Behavioral research has found that hostile jokes are perceived as funnier than non-hostile jokes. The purpose of the present study was to identify the neural correlates of the interaction between type and humor by comparing hostile jokes (HJs, non-hostile jokes (NJs, and their corresponding hostile sentences (HSs and non-hostile sentences (NSs. Hostile jokes primarily showed activation in the dorsomedial prefrontal cortex (dmPFC and midbrain compared with the corresponding hostile baseline. Conversely, non-hostile jokes primarily revealed activation in the ventromedial PFC (vmPFC, amygdala, midbrain, ventral anterior cingulate cortex, and nucleus accumbens (NAcc compared with the corresponding non-hostile baseline. These results support the critical role of the medial prefrontal cortex (mPFC for the neural correlates of social cognition and socio-emotional processing in response to different types of jokes. Moreover, the processing of hostile jokes showed increased activation in the dmPFC, which suggested cognitive operations of social motivation, whereas the processing of non-hostile jokes displayed increased activation in the vmPFC, which suggested social-affective engagement. Hostile jokes versus non-hostile jokes primarily showed increased activation in the dmPFC and midbrain, whereas non-hostile jokes versus hostile jokes primarily displayed greater activation in the amygdala and midbrain. The psychophysiological interaction (PPI analysis demonstrated functional coupling of the dmPFC-dlPFC and midbrain-dmPFC for hostile jokes and functional coupling of the vmPFC-midbrain and amygdala-midbrain-NAcc for non-hostile jokes. Surprisingly, the neural correlates of hostile jokes were not perceived as funnier than non-hostile jokes. Future studies could further investigate the neural correlates of potentially important traits of high-hostility tendencies in humor appreciation
File list: InP.Neu.20.AllAg.Neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available InP.Neu.20.AllAg.Neural_progenitor_cells mm9 Input control Neural Neural progenitor... cells SRX109476,SRX315272,SRX315273,SRX109475,SRX668239,SRX667382 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.20.AllAg.Neural_progenitor_cells.bed ...
File list: InP.Neu.10.AllAg.Neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available InP.Neu.10.AllAg.Neural_progenitor_cells mm9 Input control Neural Neural progenitor... cells SRX109476,SRX315272,SRX315273,SRX109475,SRX667382,SRX668239 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.10.AllAg.Neural_progenitor_cells.bed ...
File list: InP.Neu.05.AllAg.Neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
Full Text Available InP.Neu.05.AllAg.Neural_progenitor_cells mm9 Input control Neural Neural progenitor... cells SRX109476,SRX667382,SRX109475,SRX315272,SRX315273,SRX668239 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.05.AllAg.Neural_progenitor_cells.bed ...
Gadziola, Marie A.
2016-01-01
The ventral striatum is critical for evaluating reward information and the initiation of goal-directed behaviors. The many cellular, afferent, and efferent similarities between the ventral striatum's nucleus accumbens and olfactory tubercle (OT) suggests the distributed involvement of neurons within the ventral striatopallidal complex in motivated behaviors. Although the nucleus accumbens has an established role in representing goal-directed actions and their outcomes, it is not known whether this function is localized within the nucleus accumbens or distributed also within the OT. Answering such a fundamental question will expand our understanding of the neural mechanisms underlying motivated behaviors. Here we address whether the OT encodes natural reinforcers and serves as a substrate for motivational information processing. In recordings from mice engaged in a novel water-motivated instrumental task, we report that OT neurons modulate their firing rate during initiation and progression of the instrumental licking behavior, with some activity being internally generated and preceding the first lick. We further found that as motivational drive decreases throughout a session, the activity of OT neurons is enhanced earlier relative to the behavioral action. Additionally, OT neurons discriminate the types and magnitudes of fluid reinforcers. Together, these data suggest that the processing of reward information and the orchestration of goal-directed behaviors is a global principle of the ventral striatum and have important implications for understanding the neural systems subserving addiction and mood disorders. SIGNIFICANCE STATEMENT Goal-directed behaviors are widespread among animals and underlie complex behaviors ranging from food intake, social behavior, and even pathological conditions, such as gambling and drug addiction. The ventral striatum is a neural system critical for evaluating reward information and the initiation of goal-directed behaviors. Here we
Sex differences in morphology of the brain stem and cerebellum with normal ageing
International Nuclear Information System (INIS)
Oguro, H.; Okada, K.; Yamaguchi, S.; Kobayashi, S.
1998-01-01
The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the crebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women. (orig.)
Sex differences in morphology of the brain stem and cerebellum with normal ageing
Energy Technology Data Exchange (ETDEWEB)
Oguro, H.; Okada, K.; Yamaguchi, S.; Kobayashi, S. [Internal Medicine III, Shimane Medical University, Izumo (Japan)
1998-12-01
The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the crebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women. (orig.) With 4 figs., 3 tabs., 16 refs.
Güçlü, Umut; van Gerven, Marcel A J
2015-07-08
Converging evidence suggests that the primate ventral visual pathway encodes increasingly complex stimulus features in downstream areas. We quantitatively show that there indeed exists an explicit gradient for feature complexity in the ventral pathway of the human brain. This was achieved by mapping thousands of stimulus features of increasing complexity across the cortical sheet using a deep neural network. Our approach also revealed a fine-grained functional specialization of downstream areas of the ventral stream. Furthermore, it allowed decoding of representations from human brain activity at an unsurpassed degree of accuracy, confirming the quality of the developed approach. Stimulus features that successfully explained neural responses indicate that population receptive fields were explicitly tuned for object categorization. This provides strong support for the hypothesis that object categorization is a guiding principle in the functional organization of the primate ventral stream. Copyright © 2015 the authors 0270-6474/15/3510005-10$15.00/0.
Blumenfeld, Robert S; Nomura, Emi M; Gratton, Caterina; D'Esposito, Mark
2013-10-01
Anatomical connectivity differences between the dorsal and ventral lateral prefrontal cortex (PFC) of the non-human primate strongly suggests that these regions support different functions. However, after years of study, it remains unclear whether these regions are functionally distinct. In contrast, there has been a groundswell of recent studies providing evidence for a rostro-caudal functional organization, along the lateral as well as dorsomedial frontal cortex. Thus, it is not known whether dorsal and ventral regions of lateral PFC form distinct functional networks and how to reconcile any dorso-ventral organization with the medio-lateral and rostro-caudal axes. Here, we used resting-state connectivity data to identify parallel dorsolateral and ventrolateral streams of intrinsic connectivity with the dorsomedial frontal cortex. Moreover, we show that this connectivity follows a rostro-caudal gradient. Our results provide evidence for a novel framework for the intrinsic organization of the frontal cortex that incorporates connections between medio-lateral, dorso-ventral, and rostro-caudal axes.
DEFF Research Database (Denmark)
Fordham, Robert P; Yui, Shiro; Hannan, Nicholas R F
2013-01-01
Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can...... be expanded in vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can be established during intestinal differentiation of human induced pluripotent stem cells. Established cultures of mouse fetal intestinal progenitors express lower levels of Lgr5 than mature progenitors and propagate...... in the presence of the Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal organoids by exposure to Wnt3a. Following transplantation in a colonic injury model, FEnS contribute to regeneration of colonic epithelium by forming epithelial crypt-like structures expressing region...
Effects of hematopoietic growth factors on purified bone marrow progenitor cells
F.J. Bot (Freek)
1992-01-01
textabstractWe have used highly enriched hematopoietic progenitor cells and in-vitro culture to examine the following questions: 1. The effects of recombinant lL-3 and GM-CSF on proliferation and differentiation of enriched hematopoietic progenitor cells have not been clearly defined: - how do IL~3
PLZF regulates fibroblast growth factor responsiveness and maintenance of neural progenitors.
Gaber, Zachary B; Butler, Samantha J; Novitch, Bennett G
2013-10-01
Distinct classes of neurons and glial cells in the developing spinal cord arise at specific times and in specific quantities from spatially discrete neural progenitor domains. Thus, adjacent domains can exhibit marked differences in their proliferative potential and timing of differentiation. However, remarkably little is known about the mechanisms that account for this regional control. Here, we show that the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF) plays a critical role shaping patterns of neuronal differentiation by gating the expression of Fibroblast Growth Factor (FGF) Receptor 3 and responsiveness of progenitors to FGFs. PLZF elevation increases FGFR3 expression and STAT3 pathway activity, suppresses neurogenesis, and biases progenitors towards glial cell production. In contrast, PLZF loss reduces FGFR3 levels, leading to premature neuronal differentiation. Together, these findings reveal a novel transcriptional strategy for spatially tuning the responsiveness of distinct neural progenitor groups to broadly distributed mitogenic signals in the embryonic environment.
Can pancreatic duct-derived progenitors be a source of islet regeneration?
International Nuclear Information System (INIS)
Xia, Bing; Zhan, Xiao-Rong; Yi, Ran; Yang, Baofeng
2009-01-01
The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing β-cells. The functional mass of β-cells is decreased in type 1 diabetes, so replacing missing β-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the β-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding β-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated. In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet β-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the 'gold standard' of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal cells as an in vivo progenitor for
Can pancreatic duct-derived progenitors be a source of islet regeneration?
Energy Technology Data Exchange (ETDEWEB)
Xia, Bing [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Zhan, Xiao-Rong, E-mail: xiaorongzhan@sina.com [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Yi, Ran [Department of Endocrinology, First Hospital of Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China); Yang, Baofeng [Department of Pharmacology, State Key Laboratory of Biomedicine and Pharmacology, Harbin Medical University, Harbin, Hei Long Jiang Province 150001 (China)
2009-06-12
The regenerative process of the pancreas is of interest because the main pathogenesis of diabetes mellitus is an inadequate number of insulin-producing {beta}-cells. The functional mass of {beta}-cells is decreased in type 1 diabetes, so replacing missing {beta}-cells or triggering their regeneration may allow for improved type 1 diabetes treatment. Therefore, expansion of the {beta}-cell mass from endogenous sources, either in vivo or in vitro, represents an area of increasing interest. The mechanism of islet regeneration remains poorly understood, but the identification of islet progenitor sources is critical for understanding {beta}-cell regeneration. One potential source is the islet proper, via the dedifferentiation, proliferation, and redifferentiation of facultative progenitors residing within the islet. Neogenesis, or that the new pancreatic islets can derive from progenitor cells present within the ducts has been reported, but the existence and identity of the progenitor cells have been debated. In this review, we focus on pancreatic ductal cells, which are islet progenitors capable of differentiating into islet {beta}-cells. Islet neogenesis, seen as budding of hormone-positive cells from the ductal epithelium, is considered to be one mechanism for normal islet growth after birth and in regeneration, and has suggested the presence of pancreatic stem cells. Numerous results support the neogenesis hypothesis, the evidence for the hypothesis in the adult comes primarily from morphological studies that have in common the production of damage to all or part of the pancreas, with consequent inflammation and repair. Although numerous studies support a ductal origin for new islets after birth, lineage-tracing experiments are considered the 'gold standard' of proof. Lineage-tracing experiments show that pancreatic duct cells act as progenitors, giving rise to new islets after birth and after injury. The identification of differentiated pancreatic ductal
The Type IIb Supernova 2013df and its Cool Supergiant Progenitor
VanDyk, Schuyler D.; Zeng, Weikang; Fox, Ori D.; Cenko, S. Bradley; Clubb, Kelsey I.; Filippenko, Alexei; Foley, Ryan J.; Miller, Adam A.; Smith, Nathan; Kelly, Patrick L.;
2014-01-01
We have obtained early-time photometry and spectroscopy of supernova (SN) 2013df in NGC 4414. The SN is clearly of Type II b, with notable similarities to SN 1993J. From its luminosity at secondary maximum light, it appears that less Ni-56 (is approximately less than 0.06M) was synthesized in the SN 2013df explosion than was the case for the SNe II b 1993J, 2008ax, and 2011dh. Based on a comparison of the light curves, the SN 2013df progenitor must have been more extended in radius prior to explosion than the progenitor of SN 1993J. The total extinction for SN 2013dfis estimated to be A(sub V) = 0.30 mag. The metallicity at the SN location is likely to be solar. We have conducted Hubble Space Telescope(HST) Target of Opportunity observations of the SN with the Wide Field Camera 3, and from a precise comparison of these new observations to archival HST observations of the host galaxy obtained 14 yr prior to explosion, we have identified the progenitor of SN 2013df to be a yellow supergiant, somewhat hotter than a red supergiant progenitor for a normal Type II-Plateau SN. From its observed spectral energy distribution, assuming that the light is dominated by one star, the progenitor had effective temperature T(sub eff) = 4250+/-100 K and a bolometric luminosity L(sub bol) =10(exp 4.94+/-0.06) Solar Luminosity. This leads to an effective radius Reff = 545+/-65 Solar Radius. The star likely had an initial mass in the range of 13-17Solar Mass; however, if it was a member of an interacting binary system, detailed modeling of the system is required to estimate this mass more accurately. The progenitor star of SN 2013df appears to have been relatively similar to the progenitor of SN 1993J.
The type IIb supernova 2013df and its cool supergiant progenitor
Energy Technology Data Exchange (ETDEWEB)
Van Dyk, Schuyler D. [Spitzer Science Center/Caltech, Mail Code 220-6, Pasadena, CA 91125 (United States); Zheng, WeiKang; Fox, Ori D.; Clubb, Kelsey I.; Filippenko, Alexei V.; Kelly, Patrick L. [Department of Astronomy, University of California, Berkeley, CA 94720-3411 (United States); Cenko, S. Bradley [Astrophysics Science Division, NASA Goddard Space Flight Center, Mail Code 661, Greenbelt, MD 20771 (United States); Foley, Ryan J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Miller, Adam A. [Jet Propulsion Laboratory, MS 169-506, Pasadena, CA 91109 (United States); Smith, Nathan [Steward Observatory, University of Arizona, Tucson, AZ 85720 (United States); Lee, William H. [Instituto de Astronomía, Universidad Nacional Autónoma de México, Apdo. Postal 70-264, Cd. Universitaria, México DF 04510 (Mexico); Ben-Ami, Sagi; Gal-Yam, Avishay, E-mail: vandyk@ipac.caltech.edu [Benoziyo Center for Astrophysics, The Weizmann Institute of Science, Rehovot 76100 (Israel)
2014-02-01
We have obtained early-time photometry and spectroscopy of supernova (SN) 2013df in NGC 4414. The SN is clearly of Type IIb, with notable similarities to SN 1993J. From its luminosity at secondary maximum light, it appears that less {sup 56}Ni (≲ 0.06 M {sub ☉}) was synthesized in the SN 2013df explosion than was the case for the SNe IIb 1993J, 2008ax, and 2011dh. Based on a comparison of the light curves, the SN 2013df progenitor must have been more extended in radius prior to explosion than the progenitor of SN 1993J. The total extinction for SN 2013df is estimated to be A{sub V} = 0.30 mag. The metallicity at the SN location is likely to be solar. We have conducted Hubble Space Telescope (HST) Target of Opportunity observations of the SN with the Wide Field Camera 3, and from a precise comparison of these new observations to archival HST observations of the host galaxy obtained 14 yr prior to explosion, we have identified the progenitor of SN 2013df to be a yellow supergiant, somewhat hotter than a red supergiant progenitor for a normal Type II-Plateau SN. From its observed spectral energy distribution, assuming that the light is dominated by one star, the progenitor had effective temperature T {sub eff} = 4250 ± 100 K and a bolometric luminosity L {sub bol} = 10{sup 4.94±0.06} L {sub ☉}. This leads to an effective radius R {sub eff} = 545 ± 65 R {sub ☉}. The star likely had an initial mass in the range of 13-17 M {sub ☉}; however, if it was a member of an interacting binary system, detailed modeling of the system is required to estimate this mass more accurately. The progenitor star of SN 2013df appears to have been relatively similar to the progenitor of SN 1993J.
Observational Investigations of the Progenitors of Supernovae
Lyman, J. D.
2014-03-01
Supernovae (SNe) are the spectacular deaths of stars and have shaped the universe we see today. Their far-reaching influence affects the chemical and dynamical evolution of galaxies, star formation, neutron star and black hole formation, and they are largely responsible for most of the heavy elements that make up the universe, including around 90 per cent of the reader. They also provide laboratories of nuclear and particle physics far beyond what we can construct on Earth and act as probes of extreme density and energy. This thesis presents new research into understanding the nature of the progenitor systems of various types of SNe, as well as presenting results that will allow their study to be more productive in the future, through use of automated pipelines and methods to increase the science value of discovered SNe. An environmental study of two peculiar types of transients ('Calcium-rich' and '2002cx-like'), which may not be true SNe, reveals extremely different ages of the exploding systems that will constrain the current theoretical effort into discovering the progenitor systems. The GRB-SN 120422A/2012bz is investigated and found to be an extremely luminous and energetic SN, even amongst the infamously bright GRB-SNe. A method is presented that allows an accurate reconstruction of the bolometric light curve of a core-collapse SN, which relies on only two optical filter observations - this will hugely reduce the observational cost of constructing bolometric light curves, a tool of great importance when hoping to constrain the nature of a SN explosion and hence its progenitor. Finally, this method is utilised to construct the largest bolometric CCSN bolometric light curve sample to date, and these are analytically modelled to reveal population statistics of the explosions, thus informing on the nature of the progenitors.
Aihara, Eitaro; Mahe, Maxime M; Schumacher, Michael A; Matthis, Andrea L; Feng, Rui; Ren, Wenwen; Noah, Taeko K; Matsu-ura, Toru; Moore, Sean R; Hong, Christian I; Zavros, Yana; Herness, Scott; Shroyer, Noah F; Iwatsuki, Ken; Jiang, Peihua; Helmrath, Michael A; Montrose, Marshall H
2015-11-24
Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5(+)) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5(+) cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration.
Directory of Open Access Journals (Sweden)
Anne-Marike Schiffer
Full Text Available Influential concepts in neuroscientific research cast the brain a predictive machine that revises its predictions when they are violated by sensory input. This relates to the predictive coding account of perception, but also to learning. Learning from prediction errors has been suggested for take place in the hippocampal memory system as well as in the basal ganglia. The present fMRI study used an action-observation paradigm to investigate the contributions of the hippocampus, caudate nucleus and midbrain dopaminergic system to different types of learning: learning in the absence of prediction errors, learning from prediction errors, and responding to the accumulation of prediction errors in unpredictable stimulus configurations. We conducted analyses of the regions of interests' BOLD response towards these different types of learning, implementing a bootstrapping procedure to correct for false positives. We found both, caudate nucleus and the hippocampus to be activated by perceptual prediction errors. The hippocampal responses seemed to relate to the associative mismatch between a stored representation and current sensory input. Moreover, its response was significantly influenced by the average information, or Shannon entropy of the stimulus material. In accordance with earlier results, the habenula was activated by perceptual prediction errors. Lastly, we found that the substantia nigra was activated by the novelty of sensory input. In sum, we established that the midbrain dopaminergic system, the hippocampus, and the caudate nucleus were to different degrees significantly involved in the three different types of learning: acquisition of new information, learning from prediction errors and responding to unpredictable stimulus developments. We relate learning from perceptual prediction errors to the concept of predictive coding and related information theoretic accounts.
Schiffer, Anne-Marike; Ahlheim, Christiane; Wurm, Moritz F; Schubotz, Ricarda I
2012-01-01
Influential concepts in neuroscientific research cast the brain a predictive machine that revises its predictions when they are violated by sensory input. This relates to the predictive coding account of perception, but also to learning. Learning from prediction errors has been suggested for take place in the hippocampal memory system as well as in the basal ganglia. The present fMRI study used an action-observation paradigm to investigate the contributions of the hippocampus, caudate nucleus and midbrain dopaminergic system to different types of learning: learning in the absence of prediction errors, learning from prediction errors, and responding to the accumulation of prediction errors in unpredictable stimulus configurations. We conducted analyses of the regions of interests' BOLD response towards these different types of learning, implementing a bootstrapping procedure to correct for false positives. We found both, caudate nucleus and the hippocampus to be activated by perceptual prediction errors. The hippocampal responses seemed to relate to the associative mismatch between a stored representation and current sensory input. Moreover, its response was significantly influenced by the average information, or Shannon entropy of the stimulus material. In accordance with earlier results, the habenula was activated by perceptual prediction errors. Lastly, we found that the substantia nigra was activated by the novelty of sensory input. In sum, we established that the midbrain dopaminergic system, the hippocampus, and the caudate nucleus were to different degrees significantly involved in the three different types of learning: acquisition of new information, learning from prediction errors and responding to unpredictable stimulus developments. We relate learning from perceptual prediction errors to the concept of predictive coding and related information theoretic accounts.
Endothelial Progenitor Cells as Shuttle of Anticancer Agents.
Laurenzana, Anna; Margheri, Francesca; Chillà, Anastasia; Biagioni, Alessio; Margheri, Giancarlo; Calorini, Lido; Fibbi, Gabriella; Del Rosso, Mario
2016-10-01
Cell therapies are treatments in which stem or progenitor cells are stimulated to differentiate into specialized cells able to home to and repair damaged tissues. After their discovery, endothelial progenitor cells (EPCs) stimulated worldwide interest as possible vehicles to perform autologous cell therapy of tumors. Taking into account the tumor-homing properties of EPCs, two different approaches to control cancer progression have been pursued by combining cell-based therapy with gene therapy or with nanomedicine. The first approach is based on the possibility of engineering EPCs to express different transgenes, and the second is based on the capacity of EPCs to take up nanomaterials. Here we review the most important progress covering the following issues: the characterization of bona fide endothelial progenitor cells, their role in tumor vascularization and metastasis, and preclinical data about their use in cell-based tumor therapy, considering antiangiogenic, suicide, immune-stimulating, and oncolytic virus gene therapy. The mixed approach of EPC cell therapy and nanomedicine is discussed in terms of plasmonic-dependent thermoablation and molecular imaging.
Panuganti, Swapna; Papoutsakis, Eleftherios T.; Miller, William M.
2010-01-01
Background Megakaryopoiesis encompasses hematopoietic stem and progenitor cell (HSPC) commitment to the megakaryocytic cell (Mk) lineage, expansion of Mk progenitors and mature Mks, polyploidization, and platelet release. pH and pO2 increase from the endosteum to sinuses, and different cytokines are important for various stages of differentiation. We hypothesized that mimicking the changing conditions during Mk differentiation in the bone marrow would facilitate expansion of progenitors that could generate many high-ploidy Mks. Methods CD34+ HSPCs were cultured at pH 7.2 and 5% O2 with stem cell factor (SCF), thrombopoietin (Tpo), and all combinations of Interleukin (IL)-3, IL-6, IL-11, and Flt-3 ligand to promote Mk progenitor expansion. Cells cultured with selected cytokines were shifted to pH 7.4 and 20% O2 to generate mature Mks, and treated with nicotinamide to enhance polyploidization. Results Using Tpo+SCF+IL-3+IL-11, we obtained 3.5 CD34+CD41+ Mk progenitors per input HSPC, while increasing purity from 1% to 17%. Cytokine cocktails with IL-3 yielded more progenitors and mature Mks, although the purities were lower. Mk production was much greater at higher pH and pO2. Although fewer progenitors were present, shifting to 20% O2/pH 7.4 at day 5 (versus days 7 or 9) yielded the greatest mature Mk production, 14 per input HSPC. Nicotinamide more than doubled the percentage of high-ploidy Mks to 40%. Discussion We obtained extensive Mk progenitor expansion, while ensuring that the progenitors could produce high-ploidy Mks. We anticipate that subsequent optimization of cytokines for mature Mk production and delayed nicotinamide addition will greatly increase high-ploidy Mk production. PMID:20482285
Violencia Filio Parental: Comparando lo que informan los adolescentes y sus progenitores
Calvete, Esther; Orue, Izaskun; González-Cabrera, Joaquín
2017-01-01
El objetivo principal del presente estudio fue examinar la consistencia de los informes de progenitores e hijos a la hora de informar sobre la violencia filio-parental en una muestra comunitaria. Como objetivo secundario, se exploraron las propiedades psicométricas de la versión para progenitores del Cuestionario de Violencia Filio-Parental (Calvete, Gámez-Guadix et al., 2013). Participaron en el estudio un total de 880 adolescentes (51.70% chicas, entre 13 y 19 años) y sus progenitores (76....
The functional anatomy of speech perception: Dorsal and ventral processing pathways
Hickok, Gregory
2003-04-01
Drawing on recent developments in the cortical organization of vision, and on data from a variety of sources, Hickok and Poeppel (2000) have proposed a new model of the functional anatomy of speech perception. The model posits that early cortical stages of speech perception involve auditory fields in the superior temporal gyrus bilaterally (although asymmetrically). This cortical processing system then diverges into two broad processing streams, a ventral stream, involved in mapping sound onto meaning, and a dorsal stream, involved in mapping sound onto articulatory-based representations. The ventral stream projects ventrolaterally toward inferior posterior temporal cortex which serves as an interface between sound and meaning. The dorsal stream projects dorsoposteriorly toward the parietal lobe and ultimately to frontal regions. This network provides a mechanism for the development and maintenance of ``parity'' between auditory and motor representations of speech. Although the dorsal stream represents a tight connection between speech perception and speech production, it is not a critical component of the speech perception process under ecologically natural listening conditions. Some degree of bi-directionality in both the dorsal and ventral pathways is also proposed. A variety of recent empirical tests of this model have provided further support for the proposal.
DNA microarray unravels rapid changes in transcriptome of MK-801 treated rat brain
Kobayashi, Yuka; Kulikova, Sofya P; Shibato, Junko; Rakwal, Randeep; Satoh, Hiroyuki; Pinault, Didier; Masuo, Yoshinori
2015-01-01
AIM: To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS: Rats were treated with an intraperitoneal injection of MK-801 [0.08 (low-dose) and 0.16 (high-dose) mg/kg] or NaCl (vehicle control). In a first series of experiment, the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments, the whole brain of each animal was rapidly removed at 40 min post-injection, and different regions were separated: amygdala, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum on ice followed by DNA microarray (4 × 44 K whole rat genome chip) analysis. RESULTS: Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency (30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose (0.08 mg/kg) of MK-801. Under high-dose (0.16 mg/kg), ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. CONCLUSION: Acute MK-801 treatment increases synchrony of baseline gamma oscillations, and causes very early changes in gene expressions in six individual rat brain regions, a first report. PMID:26629322
File list: NoD.Neu.50.AllAg.Fetal_neural_progenitor_cells [Chip-atlas[Archive
Lifescience Database Archive (English)
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Henry, Curtis J; Casás-Selves, Matias; Kim, Jihye; Zaberezhnyy, Vadym; Aghili, Leila; Daniel, Ashley E; Jimenez, Linda; Azam, Tania; McNamee, Eoin N; Clambey, Eric T; Klawitter, Jelena; Serkova, Natalie J; Tan, Aik Choon; Dinarello, Charles A; DeGregori, James
2015-12-01
The incidence of cancer is higher in the elderly; however, many of the underlying mechanisms for this association remain unexplored. Here, we have shown that B cell progenitors in old mice exhibit marked signaling, gene expression, and metabolic defects. Moreover, B cell progenitors that developed from hematopoietic stem cells (HSCs) transferred from young mice into aged animals exhibited similar fitness defects. We further demonstrated that ectopic expression of the oncogenes BCR-ABL, NRAS(V12), or Myc restored B cell progenitor fitness, leading to selection for oncogenically initiated cells and leukemogenesis specifically in the context of an aged hematopoietic system. Aging was associated with increased inflammation in the BM microenvironment, and induction of inflammation in young mice phenocopied aging-associated B lymphopoiesis. Conversely, a reduction of inflammation in aged mice via transgenic expression of α-1-antitrypsin or IL-37 preserved the function of B cell progenitors and prevented NRAS(V12)-mediated oncogenesis. We conclude that chronic inflammatory microenvironments in old age lead to reductions in the fitness of B cell progenitor populations. This reduced progenitor pool fitness engenders selection for cells harboring oncogenic mutations, in part due to their ability to correct aging-associated functional defects. Thus, modulation of inflammation--a common feature of aging--has the potential to limit aging-associated oncogenesis.
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Characteristics of meniscus progenitor cells migrated from injured meniscus.
Seol, Dongrim; Zhou, Cheng; Brouillette, Marc J; Song, Ino; Yu, Yin; Choe, Hyeong Hun; Lehman, Abigail D; Jang, Kee W; Fredericks, Douglas C; Laughlin, Barbara J; Martin, James A
2017-09-01
Serious meniscus injuries seldom heal and increase the risk for knee osteoarthritis; thus, there is a need to develop new reparative therapies. In that regard, stimulating tissue regeneration by autologous stem/progenitor cells has emerged as a promising new strategy. We showed previously that migratory chondrogenic progenitor cells (CPCs) were recruited to injured cartilage, where they showed a capability in situ tissue repair. Here, we tested the hypothesis that the meniscus contains a similar population of regenerative cells. Explant studies revealed that migrating cells were mainly confined to the red zone in normal menisci: However, these cells were capable of repopulating defects made in the white zone. In vivo, migrating cell numbers increased dramatically in damaged meniscus. Relative to non-migrating meniscus cells, migrating cells were more clonogenic, overexpressed progenitor cell markers, and included a larger side population. Gene expression profiling showed that the migrating population was more similar to CPCs than other meniscus cells. Finally, migrating cells equaled CPCs in chondrogenic potential, indicating a capacity for repair of the cartilaginous white zone of the meniscus. These findings demonstrate that, much as in articular cartilage, injuries to the meniscus mobilize an intrinsic progenitor cell population with strong reparative potential. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1966-1972, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Long-term Results of Ventral Penile Curvature Repair in Childhood.
Golomb, Dor; Sivan, Bezalel; Livne, Pinhas M; Nevo, Amihay; Ben-Meir, David
2018-02-01
To assess the postpubertal outcome of ventral penile curvature repaired in infancy in terms of recurrence and aesthetics. Postpubertal patients treated for hypospadias and ventral penile curvature in infancy at a tertiary medical center were invited to undergo assessment of the quality of the repair. Findings were compared between patients with a straight penis after skin release and patients who required dorsal plication. The cohort included 27 patients of mean age 16.5 years who were reported with straight penis after surgery. Postpubertal curvature was found in 6 of 14 patients (43%) successfully treated by skin release and 10 of 13 patients (77%) who underwent dorsal plication (P = .087). Significant curvature (≥30 degrees) was found in 1 of 14 patients in the skin-release group and 4 of 13 in the dorsal plication group (P = .16). Rates of redo urethroplasty were 2 of 14 (14%) and 5 of 10 (50%), respectively. Patient satisfaction with the appearance of the penis did not differ significantly. Ventral penile curvature repaired in infancy often recurs after puberty. The need for dorsal plication has a trend-level association with recurrence of penile curvature in puberty. It might also be related to the degree of postpubertal penile curvature and the need for redo urethroplasty. Procedure type does not affect patient satisfaction with the postpubertal appearance of the penis. Copyright © 2017 Elsevier Inc. All rights reserved.
Lipoma of the midbrain: post-mortem finding in a patient with breast cancer
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Verônica Maia Gouvea
1989-09-01
Full Text Available Intracranial lipomas are rare, usually do not have clinical expression and are located mare frequently in the corpus callosum. Other locations include the spinal cord, midbrain tectum, superior vermis, tuber cinereum, infundibulum and more rarely cerebellopontine angle, hypothalamus, superior medullary velum and insula. We report the case of a lipoma of the left inferior colliculus which was a post-mortem finding in a woman who died of breast cancer. Although there are reports of intracranial lipomas in patients with malignant tumors there is no explanation for the co-existence of the two tumors. The present tumor also includes a segment of a nerve which is not uncommon, but a less common finding was the presence of nests of Schwann cells within it, shown by immunohistochemistry.
International Nuclear Information System (INIS)
Drilling, J.S.; Schoenberner, D.
1985-01-01
Direct observational evidence is presented which indicates that the immediate progenitors of white dwarfs are the central stars of planetary nebulae (approximately 70%), other post-AGB objects (approximately 30%), and post-HB objects not massive enough to climb the AGB (approximately 0.3%). The combined birth rate for these objects is in satisfactory agreement with the death rate of main-sequence stars and the birth rate of white dwarfs
Biochemistry and biology: heart-to-heart to investigate cardiac progenitor cells.
Chimenti, Isotta; Forte, Elvira; Angelini, Francesco; Messina, Elisa; Giacomello, Alessandro
2013-02-01
Cardiac regenerative medicine is a rapidly evolving field, with promising future developments for effective personalized treatments. Several stem/progenitor cells are candidates for cardiac cell therapy, and emerging evidence suggests how multiple metabolic and biochemical pathways strictly regulate their fate and renewal. In this review, we will explore a selection of areas of common interest for biology and biochemistry concerning stem/progenitor cells, and in particular cardiac progenitor cells. Numerous regulatory mechanisms have been identified that link stem cell signaling and functions to the modulation of metabolic pathways, and vice versa. Pharmacological treatments and culture requirements may be exploited to modulate stem cell pluripotency and self-renewal, possibly boosting their regenerative potential for cell therapy. Mitochondria and their many related metabolites and messengers, such as oxygen, ROS, calcium and glucose, have a crucial role in regulating stem cell fate and the balance of their functions, together with many metabolic enzymes. Furthermore, protein biochemistry and proteomics can provide precious clues on the definition of different progenitor cell populations, their physiology and their autocrine/paracrine regulatory/signaling networks. Interdisciplinary approaches between biology and biochemistry can provide productive insights on stem/progenitor cells, allowing the development of novel strategies and protocols for effective cardiac cell therapy clinical translation. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.
Expanding the spectrum of congenital anomalies of the diencephalic-mesencephalic junction
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Severino, Mariasavina; Tortora, Domenico; Rossi, Andrea [Istituto Giannina Gaslini, Neuroradiology Unit, Genova (Italy); Pistorio, Angela [Istituto Giannina Gaslini, Epidemiology and Biostatistics Unit, Genoa (Italy); Ramenghi, Luca Antonio [Istituto Giannina Gaslini, Neonatal Intensive Care Unit, Genoa (Italy); Napoli, Flavia [Istituto Giannina Gaslini, Endocrinology Unit, Genoa (Italy); Mancardi, Maria Margherita [Istituto Giannina Gaslini, Neuropsychiatry Unit, Genoa (Italy); Striano, Pasquale [Istituto Giannina Gaslini, Paediatric Neurology and Muscular Diseases Unit, Genoa (Italy); Capra, Valeria [Istituto Giannina Gaslini, Genetic Unit, Genoa (Italy)
2016-01-15
We aimed to describe the clinico-radiological findings of patients with disorders of diencephalic-mesencephalic junction (DMJ) formation and midbrain anteroposterior patterning. We reviewed the DMJ anatomy of 445 patients with brain malformations. Associated supra/infratentorial abnormalities and clinical findings were noted. Craniocaudal and anteroposterior diameters of midbrain, pons, medulla, vermis, and transverse cerebellar diameter were compared with age-matched controls. Post hoc tests were corrected according to Bonferroni (p{sub B}). Two patterns of DMJ anomaly were identified in 12 patients (7 females, mean age 41 months). Type A was characterized by hypothalamic-mesencephalic fusion on axial plane, with possible midbrain ventral cleft (7 patients). Anteroposterior (p{sub B} =.006) and craniocaudal (p{sub B} =.027) diameters of the pons, craniocaudal diameter of the vermis (p{sub B} =.015), and transverse cerebellar diameter (p{sub B} =.011) were smaller than the controls. Corticospinal tract, basal ganglia, and commissural anomalies were also associated. Clinical findings included spastic-dystonic tetraparesis, hypothalamic dysfunction, epilepsy, and severe developmental delay. Type B was characterized by incomplete thalamic-mesencephalic cleavage on sagittal plane, with parenchymal bands connecting the interthalamic adhesion with the midbrain (five patients). Anteroposterior diameters of midbrain (p{sub B} =.002), pons (p{sub B} =.0004), and medulla (p{sub B} =.002) as well as the vermian anteroposterior (p{sub B} =.040) and craniocaudal diameters (p{sub B} =.014) were smaller than the controls. These patients were less neurologically impaired, most presenting mild developmental delay. The spectrum of DMJ patterning defects is wide and may be associated with several brain malformations. Infratentorial brain structures should be carefully evaluated to better define the type of associated midbrain-hindbrain anomalies. (orig.)
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Sakurada, O.; Kobayashi, M.; Ueno, H.; Ishii, S. (Juntendo Univ., Tokyo (Japan). School of Medicine)
1982-01-01
Bilateral lesions made in the midbrain reticular formation of the rat produced behavioral akinesia. These animals neither ate nor drank. EEGs of these animals usually showed high voltage slow waves at rest. Slight EEG arousal response was demonstrated by clapping, touching and pinching only in rats with moderate impairment. Concerning the rates of local cerebral glucose utilization (LCGU) measured by means of the autoradiographic (/sup 14/C) deoxyglucose method, 13 structures exhibited significant reductions in 28 gray structures examined when compared with sham operated rats. Lesions in the midbrain reticular formation resulted in reduction of LCGU in the neocortex, ventral nucleus of the thalamus, subthalamic nucleus, and medial and lateral geniculated bodies, mamillary body, septal nucleus and caudateputamen. Structures which did not show any significant change in LCGU were those related to the paleo and archi-cortices. These findings suggest the existence of two types of ascending activating systems. Administration of 30 mg/kg of pentobarbital reduced LCGU diffusely throughout the brain. When thyrotropin releasing hormone (TRH) was administered to rats with lesions in the midbrain reticular formation, reversal of the reduction of LCGU was observed in the dorsomedial nucleus of the thalamus and the mamillary body. Reversal of LCGU in the dorsomedial nucleus of thalamus was especially significant and its level exceeded the level of the sham control value. This suggests TRH might exert its function through the dorsomedial nucleus of the thalamus and mamillary body. When TRH was administered to rats treated with pentobarbital, significant reversal was observed in the following structures: the lateral and ventral nucleus of the thalamus, dentate gyrus, caudate-putamen, nucleus accumbens, pontine gray matter, and raphe nucleus.
Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.
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Teruyo Oishi
Full Text Available Heterotopic ossification (HO is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+ and PDGFRα(+ cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+ cells and PDGFRα(+ cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+ cells formed bone-like tissue and showed successful engraftment, while CD56(+ cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+ cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+ cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+ cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+ cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+ cells. Our results suggest that PDGFRα(+ cells may be the major source of HO and that the newly identified mi
Ukita, Kanako; Hirahara, Shino; Oshima, Naoko; Imuta, Yu; Yoshimoto, Aki; Jang, Chuan-Wei; Oginuma, Masayuki; Saga, Yumiko; Behringer, Richard R; Kondoh, Hisato; Sasaki, Hiroshi
2009-10-01
The notochord develops from notochord progenitor cells (NPCs) and functions as a major signaling center to regulate trunk and tail development. NPCs are initially specified in the node by Wnt and Nodal signals at the gastrula stage. However, the underlying mechanism that maintains the NPCs throughout embryogenesis to contribute to the posterior extension of the notochord remains unclear. Here, we demonstrate that Wnt signaling in the NPCs is essential for posterior extension of the notochord. Genetic labeling revealed that the Noto-expressing cells in the ventral node contribute the NPCs that reside in the tail bud. Robust Wnt signaling in the NPCs was observed during posterior notochord extension. Genetic attenuation of the Wnt signal via notochord-specific beta-catenin gene ablation resulted in posterior truncation of the notochord. In the NPCs of such mutant embryos, the expression of notochord-specific genes was down-regulated, and an endodermal marker, E-cadherin, was observed. No significant alteration of cell proliferation or apoptosis of the NPCs was detected. Taken together, our data indicate that the NPCs are derived from Noto-positive node cells, and are not fully committed to a notochordal fate. Sustained Wnt signaling is required to maintain the NPCs' notochordal fate.
ON THE PROGENITOR OF THE TYPE II-PLATEAU SN 2008cn in NGC 4603
International Nuclear Information System (INIS)
Elias-Rosa, Nancy; Van Dyk, Schuyler D.; Li, Weidong; Filippenko, Alexei V.; Foley, Ryan J.; Smith, Nathan; Morrell, Nidia; Gonzalez, Sergio; Hamuy, Mario; Cuillandre, Jean-Charles
2009-01-01
A trend is emerging regarding the progenitor stars that give rise to the most common core-collapse supernovae (SNe), those of Type II-Plateau (II-P): they generally appear to be red supergiants with a limited range of initial masses, ∼8-16 M sun . Here, we consider another example, SN 2008cn, in the nearly face-on spiral galaxy NGC 4603. Even with limited photometric data, it appears that SN 2008cn is not a normal SN II-P, but is of the high-luminosity subclass. Through comparison of pre- and post-explosion images obtained with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope, we have isolated a supergiant star prior to explosion at nearly the same position as the SN. We provide evidence that this supergiant may well be the progenitor of the SN, although this identification is not entirely unambiguous. This is exacerbated by the distance to the host galaxy, 33.3 Mpc, making SN 2008cn the most distant SN II-P yet for which an attempt has been made to identify a progenitor star in pre-SN images. The progenitor candidate has a more yellow color ([V - I] 0 = 0.98 mag and T eff = 5200 ± 300 K) than generally would be expected and, if a single star, would require that it exploded during a 'blue loop' evolutionary phase, which is theoretically not expected to occur. Nonetheless, we estimate an initial mass of M ini = 15 ± 2 M sun for this star, which is within the expected mass range for SN II-P progenitors. The yellower color could also arise from the blend of two or more stars, such as a red supergiant and a brighter, blue supergiant. Such a red supergiant hidden in this blend could instead be the progenitor and would also have an initial mass within the expected progenitor mass range. Furthermore, the yellow supergiant could be in a massive, interacting binary system, analogous to the possible yellow supergiant progenitor of the high-luminosity SN II-P 2004et. Finally, if the yellow supergiant is not the progenitor, or is not a stellar
Mapping a lateralisation gradient within the ventral stream for auditory speech perception
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Karsten eSpecht
2013-10-01
Full Text Available Recent models on speech perception propose a dual stream processing network, with a dorsal stream, extending from the posterior temporal lobe of the left hemisphere through inferior parietal areas into the left inferior frontal gyrus, and a ventral stream that is assumed to originate in the primary auditory cortex in the upper posterior part of the temporal lobe and to extend towards the anterior part of the temporal lobe, where it may connect to the ventral part of the inferior frontal gyrus. This article describes and reviews the results from a series of complementary functional magnetic imaging (fMRI studies that aimed to trace the hierarchical processing network for speech comprehension within the left and right hemisphere with a particular focus on the temporal lobe and the ventral stream. As hypothesised, the results demonstrate a bilateral involvement of the temporal lobes in the processing of speech signals. However, an increasing leftward asymmetry was detected from auditory-phonetic to lexico-semantic processing and along the posterior-anterior axis, thus forming a lateralisation gradient. This increasing leftward lateralisation was particularly evident for the left superior temporal sulcus (STS and more anterior parts of the temporal lobe.
Mapping a lateralization gradient within the ventral stream for auditory speech perception.
Specht, Karsten
2013-01-01
Recent models on speech perception propose a dual-stream processing network, with a dorsal stream, extending from the posterior temporal lobe of the left hemisphere through inferior parietal areas into the left inferior frontal gyrus, and a ventral stream that is assumed to originate in the primary auditory cortex in the upper posterior part of the temporal lobe and to extend toward the anterior part of the temporal lobe, where it may connect to the ventral part of the inferior frontal gyrus. This article describes and reviews the results from a series of complementary functional magnetic resonance imaging studies that aimed to trace the hierarchical processing network for speech comprehension within the left and right hemisphere with a particular focus on the temporal lobe and the ventral stream. As hypothesized, the results demonstrate a bilateral involvement of the temporal lobes in the processing of speech signals. However, an increasing leftward asymmetry was detected from auditory-phonetic to lexico-semantic processing and along the posterior-anterior axis, thus forming a "lateralization" gradient. This increasing leftward lateralization was particularly evident for the left superior temporal sulcus and more anterior parts of the temporal lobe.
Dendritic Cell Lineage Potential in Human Early Hematopoietic Progenitors
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Julie Helft
2017-07-01
Full Text Available Conventional dendritic cells (cDCs are thought to descend from a DC precursor downstream of the common myeloid progenitor (CMP. However, a mouse lymphoid-primed multipotent progenitor has been shown to generate cDCs following a DC-specific developmental pathway independent of monocyte and granulocyte poiesis. Similarly, here we show that, in humans, a large fraction of multipotent lymphoid early progenitors (MLPs gives rise to cDCs, in particular the subset known as cDC1, identified by co-expression of DNGR-1 (CLEC9A and CD141 (BDCA-3. Single-cell analysis indicates that over one-third of MLPs have the potential to efficiently generate cDCs. cDC1s generated from CMPs or MLPs do not exhibit differences in transcriptome or phenotype. These results demonstrate an early imprinting of the cDC lineage in human hematopoiesis and highlight the plasticity of developmental pathways giving rise to human DCs.
Martin-Soelch, Chantal; Szczepanik, Joanna; Nugent, Allison; Barhaghi, Krystle; Rallis, Denise; Herscovitch, Peter; Carson, Richard E; Drevets, Wayne C
2011-05-01
Electrophysiological studies have shown that mesostriatal dopamine (DA) neurons increase activity in response to unpredicted rewards. With respect to other functions of the mesostriatal dopaminergic system, dopamine's actions show prominent laterality effects. Whether changes in DA transmission elicited by rewards also are lateralized, however, has not been investigated. Using [¹¹C]raclopride-PET to assess the striatal DA response to unpredictable monetary rewards, we hypothesized that such rewards would induce an asymmetric reduction in [¹¹C]raclopride binding in the ventral striatum, reflecting lateralization of endogenous dopamine release. In 24 healthy volunteers, differences in the regional D₂/₃ receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition were measured using the bolus-plus-constant-infusion [¹¹C]raclopride method. During the reward condition subjects randomly received monetary awards while performing a 'slot-machine' task. The ΔBP between conditions was assessed in striatal regions-of-interest and compared between left and right sides. We found a significant condition × lateralization interaction in the ventral striatum. A significant reduction in binding potential (BP(ND) ) in the reward condition vs. the control condition was found only in the right ventral striatum, and the ΔBP was greater in the right than the left ventral striatum. Unexpectedly, these laterality effects appeared to be partly accounted for by gender differences, as our data showed a significant bilateral BP(ND) reduction in women while in men the reduction reached significance only in the right ventral striatum. These data suggest that DA release in response to unpredictable reward is lateralized in the human ventral striatum, particularly in males. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
Lansink, Carien S; Meijer, Guido T; Lankelma, Jan V; Vinck, Martin A; Jackson, Jadin C; Pennartz, Cyriel M A
2016-10-12
The use of information from the hippocampal memory system in motivated behavior depends on its communication with the ventral striatum. When an animal encounters cues that signal subsequent reward, its reward expectancy is raised. It is unknown, however, how this process affects hippocampal dynamics and their influence on target structures, such as ventral striatum. We show that, in rats, reward-predictive cues result in enhanced hippocampal theta and beta band rhythmic activity during subsequent action, compared with uncued goal-directed navigation. The beta band component, also labeled theta's harmonic, involves selective hippocampal CA1 cell groups showing frequency doubling of firing periodicity relative to theta rhythmicity and it partitions the theta cycle into segments showing clear versus poor spike timing organization. We found that theta phase precession occurred over a wider range than previously reported. This was apparent from spikes emitted near the peak of the theta cycle exhibiting large "phase precessing jumps" relative to spikes in foregoing cycles. Neither this phenomenon nor the regular manifestation of theta phase precession was affected by reward expectancy. Ventral striatal neuronal firing phase-locked not only to hippocampal theta, but also to beta band activity. Both hippocampus and ventral striatum showed increased synchronization between neuronal firing and local field potential activity during cued compared with uncued goal approaches. These results suggest that cue-triggered reward expectancy intensifies hippocampal output to target structures, such as the ventral striatum, by which the hippocampus may gain prioritized access to systems modulating motivated behaviors. Here we show that temporally discrete cues raising reward expectancy enhance both theta and beta band activity in the hippocampus once goal-directed navigation has been initiated. These rhythmic activities are associated with increased synchronization of neuronal firing
Dangaria, Smit J.
2011-12-01
Stem/progenitor cells are a population of cells capable of providing replacement cells for a given differentiated cell type. We have applied progenitor cell-based technologies to generate novel tissue-engineered implants that use biomimetic strategies with the ultimate goal of achieving full regeneration of lost periodontal tissues. Mesenchymal periodontal tissues such as cementum, alveolar bone (AB), and periodontal ligament (PDL) are neural crest-derived entities that emerge from the dental follicle (DF) at the onset of tooth root formation. Using a systems biology approach we have identified key differences between these periodontal progenitors on the basis of global gene expression profiles, gene cohort expression levels, and epigenetic modifications, in addition to differences in cellular morphologies. On an epigenetic level, DF progenitors featured high levels of the euchromatin marker H3K4me3, whereas PDL cells, AB osteoblasts, and cementoblasts contained high levels of the transcriptional repressor H3K9me3. Secondly, we have tested the influence of natural extracellular hydroxyapatite matrices on periodontal progenitor differentiation. Dimension and structure of extracellular matrix surfaces have powerful influences on cell shape, adhesion, and gene expression. Here we show that natural tooth root topographies induce integrin-mediated extracellular matrix signaling cascades in tandem with cell elongation and polarization to generate physiological periodontium-like tissues. In this study we replanted surface topography instructed periodontal ligament progenitors (PDLPs) into rat alveolar bone sockets for 8 and 16 weeks, resulting in complete attachment of tooth roots to the surrounding alveolar bone with a periodontal ligament fiber apparatus closely matching physiological controls along the entire root surface. Displacement studies and biochemical analyses confirmed that progenitor-based engineered periodontal tissues were similar to control teeth and
Parras, Carlos M.; Schuurmans, Carol; Scardigli, Raffaella; Kim, Jaesang; Anderson, David J.; Guillemot, François
2002-01-01
The neural bHLH genes Mash1 and Ngn2 are expressed in complementary populations of neural progenitors in the central and peripheral nervous systems. Here, we have systematically compared the activities of the two genes during neural development by generating replacement mutations in mice in which the coding sequences of Mash1 and Ngn2 were swapped. Using this approach, we demonstrate that Mash1 has the capacity to respecify the identity of neuronal populations normally derived from Ngn2-expressing progenitors in the dorsal telencephalon and ventral spinal cord. In contrast, misexpression of Ngn2 in Mash1-expressing progenitors does not result in any overt change in neuronal phenotype. Taken together, these results demonstrate that Mash1 and Ngn2 have divergent functions in specification of neuronal subtype identity, with Mash1 having the characteristics of an instructive determinant whereas Ngn2 functions as a permissive factor that must act in combination with other factors to specify neuronal phenotypes. Moreover, the ectopic expression of Ngn2 can rescue the neurogenesis defects of Mash1 null mutants in the ventral telencephalon and sympathetic ganglia but not in the ventral spinal cord and the locus coeruleus, indicating that Mash1 contribution to the specification of neuronal fates varies greatly in different lineages, presumably depending on the presence of other determinants of neuronal identity. PMID:11825874
Fractalkine expression induces endothelial progenitor cell lysis by natural killer cells.
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Dilyana Todorova
Full Text Available BACKGROUND: Circulating CD34(+ cells, a population that includes endothelial progenitors, participate in the maintenance of endothelial integrity. Better understanding of the mechanisms that regulate their survival is crucial to improve their regenerative activity in cardiovascular and renal diseases. Chemokine-receptor cross talk is critical in regulating cell homeostasis. We hypothesized that cell surface expression of the chemokine fractalkine (FKN could target progenitor cell injury by Natural Killer (NK cells, thereby limiting their availability for vascular repair. METHODOLOGY/PRINCIPAL FINDINGS: We show that CD34(+-derived Endothelial Colony Forming Cells (ECFC can express FKN in response to TNF-α and IFN-γ inflammatory cytokines and that FKN expression by ECFC stimulates NK cell adhesion, NK cell-mediated ECFC lysis and microparticles release in vitro. The specific involvement of membrane FKN in these processes was demonstrated using FKN-transfected ECFC and anti-FKN blocking antibody. FKN expression was also evidenced on circulating CD34(+ progenitor cells and was detected at higher frequency in kidney transplant recipients, when compared to healthy controls. The proportion of CD34(+ cells expressing FKN was identified as an independent variable inversely correlated to CD34(+ progenitor cell count. We further showed that treatment of CD34(+ circulating cells isolated from adult blood donors with transplant serum or TNF-α/IFN-γ can induce FKN expression. CONCLUSIONS: Our data highlights a novel mechanism by which FKN expression on CD34(+ progenitor cells may target their NK cell mediated killing and participate to their immune depletion in transplant recipients. Considering the numerous diseased contexts shown to promote FKN expression, our data identify FKN as a hallmark of altered progenitor cell homeostasis with potential implications in better evaluation of vascular repair in patients.
Fu, Juan; Xing, Xiaoli; Han, Mengfi; Xu, Na; Piao, Chengji; Zhang, Yue; Zheng, Xigeng
2016-02-01
The return of learned fear is an important issue in anxiety disorder research since an analogous process may contribute to long-term fear maintenance or clinical relapse. A number of studies demonstrate that mPFC and hippocampus are important in the modulation of post-extinction re-expression of fear memory. However, the region-specific role of these structures in the fear return evoked by a sub-threshold conditioning (SC) is not known. In the present experiments, we first examined specific roles of the prelimbic cortex (PL), the dorsal hippocampus (DH, the dorsal CA1 area in particular), the ventral hippocampus (the ventral dentate gyrus (vDG) and the ventral CA1 area in particular) in this fear return process. Then we examined the role of connections between PL and vCA1 with this behavioral approach. Rats were subjected to five tone-shock pairings (1.0-mA shock) to induce conditioned fear (freezing), followed by three fear extinction sessions (25 tone-alone trials each session). After a post-test for extinction memory, some rats were retrained with the SC procedure to reinstate tone-evoked freezing. Rat groups were injected with low doses of the GABAA agonist muscimol to selectively inactivate PL, DH, vDG, or vCA1 120 min before the fear return test. A disconnection paradigm with ipsilateral or contralateral muscimol injection of the PL and the vCA1 was used to examine the role of this pathway in the fear return. We found that transient inactivation of these areas significantly impaired fear return (freezing): inactivation of the prelimbic cortex blocked SC-evoked fear return in particular but did not influence fear expression in general; inactivation of the DH area impaired fear return, but had no effect on the extinction retrieval process; both ventral DG and ventral CA1 are required for the return of extinguished fear whereas only ventral DG is required for the extinction retrieval. These findings suggest that PL, DH, vDG, and vCA1 all contribute to the fear
DNMT1 Maintains Progenitor Function in Self-Renewing Somatic Tissue
Sen, George L.; Reuter, Jason A.; Webster, Daniel E.; Zhu, Lilly; Khavari, Paul A.
2010-01-01
Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation1,2. DNA methylation3,4,5 provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1)6,7 maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintena...
Directory of Open Access Journals (Sweden)
Charles eDucrot
2013-10-01
Full Text Available Previous studies have shown that blockade of ventral midbrain (VM glutamate N-Methyl-D-Aspartate (NMDA receptors induces reward, stimulates forward locomotion and enhances brain stimulation reward. Glutamate induces two types of excitatory response on VM neurons, a fast and short lasting depolarisation mediated by a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA receptors and a longer lasting depolarization mediated by NMDA receptors. A role for the two glutamate receptors in modulation of VM neuronal activity is evidenced by the functional change in AMPA and NMDA synaptic responses that result from repeated exposure to reward. Since both receptors contribute to the action of glutamate on VM neuronal activity, we studied the effects of VM AMPA and NMDA receptor blockade on reward induced by electrical brain stimulation. Experiments were performed on rats trained to self-administer electrical pulses in the medial posterior mesencephalon. Reward thresholds were measured with the curve-shift paradigm before and for two hours after bilateral VM microinjections of the AMPA antagonist, NBQX (2,3,-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(fquinoxaline-7-sulfonamide, 0, 80, and 800 pmol/0.5ul/side and of a single dose (0.825 nmol/0.5ul/side of the NMDA antagonist, PPPA (2R,4S-4-(3-Phosphonopropyl-2-piperidinecarboxylic acid. NBQX produced a dose-dependent increase in reward threshold with no significant change in maximum rate of responding. Whereas PPPA injected at the same VM sites produced a significant time dependent decrease in reward threshold and increase in maximum rate of responding. We found a negative correlation between the magnitude of the attenuation effect of NBQX and the enhancement effect of PPPA; moreover, NBQX and PPPA were most effective when injected respectively into the anterior and posterior VM. These results suggest that glutamate acts on different receptor sub-types, most likely located on different VM neurons, to modulate
Dorsolateral Prefrontal Cortex Drives Mesolimbic Dopaminergic Regions to Initiate Motivated Behavior
Ballard, Ian C.; Murty, Vishnu P.; Carter, R. McKell; MacInnes, Jeffrey J.; Huettel, Scott A.; Adcock, R. Alison
2011-01-01
How does the brain translate information signaling potential rewards into motivation to get them? Motivation to obtain reward is thought to depend on the midbrain, (particularly the ventral tegmental area, VTA), the nucleus accumbens (NAcc), and the dorsolateral prefrontal cortex (dlPFC), but it is not clear how the interactions amongst these regions relate to reward-motivated behavior. To study the influence of motivation on these reward-responsive regions and on their interactions, we used ...
Boons, P; Collinson, R; Cunningham, C; Lindsey, I
2010-06-01
Abdominal rectopexy is ideal for otherwise healthy patients with rectal prolapse because of low recurrence, yet after posterior rectopexy, half of the patients complain of severe constipation. Resection mitigates this dysfunction but risks a pelvic anastomosis. The novel nerve-sparing ventral rectopexy appears to avoid postero-lateral rectal dissection denervation and thus postoperative constipation. We aimed to evaluate our functional results with laparoscopic ventral rectopexy. Consecutive rectal prolapse patients undergoing laparoscopic ventral rectopexy were prospectively assessed (Wexner Constipation and Faecal Incontinence Severity Index scores) pre-, 3 months postoperatively, and late (> 12 months). Sixty-five consecutive patients with external rectal prolapse (median age 72 years, 34% > 80 years, median follow up 19 months) underwent laparoscopic ventral rectopexy. There was one recurrence (2%) and one conversion. Morbidity (17%) and mortality (0%) were low. Median operating time was 140 min and median length of stay 2 days. At 3 months, constipation was improved in 72% and mildly induced in 2% (median pre-and postoperative Wexner scores 9 vs 4, P constipation and incontinence (P constipation and avoidance of de novo constipation appear superior to historical functional results of posterior rectopexy. A laparoscopic approach allows low morbidity and short hospital stay, even in those patients over 80 years of age in whom a perineal approach is usually preferred for safety.
Opposing Amygdala and Ventral Striatum Connectivity during Emotion Identification
Satterthwaite, Theodore D.; Wolf, Daniel H.; Pinkham, Amy E.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey N.; Overton, Eve; Seubert, Janina; Gur, Raquel E.; Gur, Ruben C.; Loughead, James
2011-01-01
Lesion and electrophysiological studies in animals provide evidence of opposing functions for subcortical nuclei such as the amygdala and ventral striatum, but the implications of these findings for emotion identification in humans remain poorly described. Here we report a high-resolution fMRI study in a sample of 39 healthy subjects who performed…
Effects of Substrate and Co-Culture on Neural Progenitor Cell Differentiation
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Jones, Erin Boote [Iowa State Univ., Ames, IA (United States)
2008-01-01
In recent years the study of stem and progenitor cells has moved to the forefront of research. Since the isolation of human hematopoietic stem cells in 1988 and the subsequent discovery of a self renewing population of multipotent cells in many tissues, many researchers have envisioned a better understanding of development and potential clinical usage in intractable diseases. Both these goals, however, depend on a solid understanding of the intracellular and extracellular forces that cause stem cells to differentiate to a specific cell fate. Many diseases of large scale cell loss have been suggested as candidates for stem cell based treatments. It is proposed that replacing the function of the damaged or defective cells by specific differentiation of stem or progenitor cells could treat the disease. Before cells can be directed to specific lineages, the mechanisms of differentiation must be better understood. Differentiation in vivo is an intensively complex system that is difficult to study. The goal of this research is to develop further understanding of the effects of soluble and extracellular matrix (ECM) cues on the differentiation of neural progenitor cells with the use of a simplified in vitro culture system. Specific research objectives are to study the differentiation of neural progenitor cells in response to astrocyte conditioned medium and protein substrate composition and concentration. In an effort to reveal the mechanism of the conditioned medium interaction, a test for the presence of a feedback loop between progenitor cells and astrocytes is presented along with an examination of conditioned medium storage temperature, which can reveal enzymatic dependencies. An examination of protein substrate composition and concentration will help to reveal the role of any ECM interactions on differentiation. This thesis is organized into a literature review covering recent advances in use of external modulators of differentiation such as surface coatings, co
Progenitors mobilized by gamma-tocotrienol as an effective radiation countermeasure.
Directory of Open Access Journals (Sweden)
Vijay K Singh
Full Text Available The purpose of this study was to elucidate the role of gamma-tocotrienol (GT3-mobilized progenitors in mitigating damage to mice exposed to a supralethal dose of cobalt-60 gamma-radiation. CD2F1 mice were transfused 24 h post-irradiation with whole blood or isolated peripheral blood mononuclear cells (PBMC from donors that had received GT3 72 h prior to blood collection and recipient mice were monitored for 30 days. To understand the role of GT3-induced granulocyte colony-stimulating factor (G-CSF in mobilizing progenitors, donor mice were administered a neutralizing antibody specific to G-CSF or its isotype before blood collection. Bacterial translocation from gut to heart, spleen and liver of irradiated recipient mice was evaluated by bacterial culture on enriched and selective agar media. Endotoxin in serum samples also was measured. We also analyzed the colony-forming units in the spleens of irradiated mice. Our results demonstrate that whole blood or PBMC from GT3-administered mice mitigated radiation injury when administered 24 h post-irradiation. Furthermore, administration of a G-CSF antibody to GT3-injected mice abrogated the efficacy of blood or PBMC obtained from such donors. Additionally, GT3-mobilized PBMC inhibited the translocation of intestinal bacteria to the heart, spleen, and liver, and increased colony forming unit-spleen (CFU-S numbers in irradiated mice. Our data suggests that GT3 induces G-CSF, which mobilizes progenitors and these progenitors mitigate radiation injury in recipient mice. This approach using mobilized progenitor cells from GT3-injected donors could be a potential treatment for humans exposed to high doses of radiation.
Dorsal and ventral streams across sensory modalities
Institute of Scientific and Technical Information of China (English)
Anna Sedda; Federica Scarpina
2012-01-01
In this review,we describe the current models of dorsal and ventral streams in vision,audition and touch.Available theories take their first steps from the model of Milner and Goodale,which was developed to explain how human actions can be efficiently carried out using visual information.Since then,similar concepts have also been applied to other sensory modalities.We propose that advances in the knowledge of brain functioning can be achieved through models explaining action and perception patterns independently from sensory modalities.
Progenitor outgrowth from the niche in Drosophila trachea is guided by FGF from decaying branches.
Chen, Feng; Krasnow, Mark A
2014-01-10
Although there has been progress identifying adult stem and progenitor cells and the signals that control their proliferation and differentiation, little is known about the substrates and signals that guide them out of their niche. By examining Drosophila tracheal outgrowth during metamorphosis, we show that progenitors follow a stereotyped path out of the niche, tracking along a subset of tracheal branches destined for destruction. The embryonic tracheal inducer branchless FGF (fibroblast growth factor) is expressed dynamically just ahead of progenitor outgrowth in decaying branches. Knockdown of branchless abrogates progenitor outgrowth, whereas misexpression redirects it. Thus, reactivation of an embryonic tracheal inducer in decaying branches directs outgrowth of progenitors that replace them. This explains how the structure of a newly generated tissue is coordinated with that of the old.
Mass ejection in failed supernovae: variation with stellar progenitor
Fernández, Rodrigo; Quataert, Eliot; Kashiyama, Kazumi; Coughlin, Eric R.
2018-05-01
We study the ejection of mass during stellar core-collapse when the stalled shock does not revive and a black hole forms. Neutrino emission during the protoneutron star phase causes a decrease in the gravitational mass of the core, resulting in an outward going sound pulse that steepens into a shock as it travels out through the star. We explore the properties of this mass ejection mechanism over a range of stellar progenitors using spherically symmetric, time-dependent hydrodynamic simulations that treat neutrino mass-loss parametrically and follow the shock propagation over the entire star. We find that all types of stellar progenitor can eject mass through this mechanism. The ejected mass is a decreasing function of the surface gravity of the star, ranging from several M⊙ for red supergiants to ˜0.1 M⊙ for blue supergiants and ˜10-3 M⊙ for Wolf-Rayet stars. We find that the final shock energy at the surface is a decreasing function of the core-compactness, and is ≲ 1047-1048 erg in all cases. In progenitors with a sufficiently large envelope, high core-compactness, or a combination of both, the sound pulse fails to unbind mass. Successful mass ejection is accompanied by significant fallback accretion that can last from hours to years. We predict the properties of shock breakout and thermal plateau emission produced by the ejection of the outer envelope of blue supergiant and Wolf-Rayet progenitors in otherwise failed supernovae.
Schneider, David M; Woolley, Sarah M N
2010-06-01
Many social animals including songbirds use communication vocalizations for individual recognition. The perception of vocalizations depends on the encoding of complex sounds by neurons in the ascending auditory system, each of which is tuned to a particular subset of acoustic features. Here, we examined how well the responses of single auditory neurons could be used to discriminate among bird songs and we compared discriminability to spectrotemporal tuning. We then used biologically realistic models of pooled neural responses to test whether the responses of groups of neurons discriminated among songs better than the responses of single neurons and whether discrimination by groups of neurons was related to spectrotemporal tuning and trial-to-trial response variability. The responses of single auditory midbrain neurons could be used to discriminate among vocalizations with a wide range of abilities, ranging from chance to 100%. The ability to discriminate among songs using single neuron responses was not correlated with spectrotemporal tuning. Pooling the responses of pairs of neurons generally led to better discrimination than the average of the two inputs and the most discriminating input. Pooling the responses of three to five single neurons continued to improve neural discrimination. The increase in discriminability was largest for groups of neurons with similar spectrotemporal tuning. Further, we found that groups of neurons with correlated spike trains achieved the largest gains in discriminability. We simulated neurons with varying levels of temporal precision and measured the discriminability of responses from single simulated neurons and groups of simulated neurons. Simulated neurons with biologically observed levels of temporal precision benefited more from pooling correlated inputs than did neurons with highly precise or imprecise spike trains. These findings suggest that pooling correlated neural responses with the levels of precision observed in the
File list: ALL.Oth.50.AllAg.Multipotent_otic_progenitor [Chip-atlas[Archive
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Chua, Chee Wai; Epsi, Nusrat J; Leung, Eva Y; Xuan, Shouhong; Lei, Ming; Li, Bo I; Bergren, Sarah K; Hibshoosh, Hanina; Mitrofanova, Antonina
2018-01-01
Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important in cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated. We have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing cells), a luminal stem/progenitor cell that functions in prostate regeneration. Using genetically--engineered mouse models and novel prostate epithelial cell lines, we find that progenitor properties of CARNs are largely unaffected by AR deletion, apart from decreased proliferation in vivo. Furthermore, AR loss suppresses tumor formation after deletion of the Pten tumor suppressor in CARNs; however, combined Pten deletion and activation of oncogenic Kras in AR-deleted CARNs result in tumors with focal neuroendocrine differentiation. Our findings show that AR modulates specific progenitor properties of CARNs, including their ability to serve as a cell of origin for prostate cancer. PMID:29334357
Parekh, Chintan; Sahaghian, Arineh; Kim, William; Scholes, Jessica; Ge, Shundi; Zhu, Yuhua; Asgharzadeh, Shahab; Hollis, Roger; Kohn, Donald; Ji, Lingyun; Malvar, Jemily; Wang, Xiaoyan; Crooks, Gay
2012-04-01
The cytokine thrombopoietin (Tpo) plays a critical role in hematopoiesis by binding to the extracellular domain and inducing homodimerization of the intracellular signaling domain of its receptor, c-Mpl. Mpl homodimerization can also be accomplished by binding of a synthetic ligand to a constitutively expressed fusion protein F36VMpl consisting of a ligand binding domain (F36V) and the intracellular signaling domain of Mpl. Unexpectedly, in contrast to Tpo stimulation, robust erythropoiesis is induced after dimerization of F36VMpl in human CD34+ progenitor cells. The goal of this study was to define the hematopoietic progenitor stages at which dimerization of intracellular Mpl induces erythropoiesis and the downstream molecular events that mediate this unanticipated effect. Dimerization (in the absence of erythropoietin and other cytokines) in human common myeloid progenitors and megakaryocytic erythroid progenitors caused a significant increase in CD34+ cells (p Mpl in human myeloerythroid progenitors induces progenitor expansion and erythropoiesis through molecular mechanisms that are not shared by Tpo stimulation of endogenous Mpl. Copyright © 2012 AlphaMed Press.
Directory of Open Access Journals (Sweden)
Nicolas Christoforou
Full Text Available The mammalian heart has little capacity to regenerate, and following injury the myocardium is replaced by non-contractile scar tissue. Consequently, increased wall stress and workload on the remaining myocardium leads to chamber dilation, dysfunction, and heart failure. Cell-based therapy with an autologous, epigenetically reprogrammed, and cardiac-committed progenitor cell source could potentially reverse this process by replacing the damaged myocardium with functional tissue. However, it is unclear whether cardiac progenitor cell-derived cardiomyocytes are capable of attaining levels of structural and functional maturity comparable to that of terminally-fated cardiomyocytes. Here, we first describe the derivation of mouse induced pluripotent stem (iPS cells, which once differentiated allow for the enrichment of Nkx2-5(+ cardiac progenitors, and the cardiomyocyte-specific expression of the red fluorescent protein. We show that the cardiac progenitors are multipotent and capable of differentiating into endothelial cells, smooth muscle cells and cardiomyocytes. Moreover, cardiac progenitor selection corresponds to cKit(+ cell enrichment, while cardiomyocyte cell-lineage commitment is concomitant with dual expression of either cKit/Flk1 or cKit/Sca-1. We proceed to show that the cardiac progenitor-derived cardiomyocytes are capable of forming electrically and mechanically coupled large-scale 2D cell cultures with mature electrophysiological properties. Finally, we examine the cell progenitors' ability to form electromechanically coherent macroscopic tissues, using a physiologically relevant 3D culture model and demonstrate that following long-term culture the cardiomyocytes align, and form robust electromechanical connections throughout the volume of the biosynthetic tissue construct. We conclude that the iPS cell-derived cardiac progenitors are a robust cell source for tissue engineering applications and a 3D culture platform for pharmacological
Guo, Rong; Böhmer, Wendelin; Hebart, Martin; Chien, Samson; Sommer, Tobias; Obermayer, Klaus; Gläscher, Jan
2016-12-14
Goal-directed and instrumental learning are both important controllers of human behavior. Learning about which stimulus event occurs in the environment and the reward associated with them allows humans to seek out the most valuable stimulus and move through the environment in a goal-directed manner. Stimulus-response associations are characteristic of instrumental learning, whereas response-outcome associations are the hallmark of goal-directed learning. Here we provide behavioral, computational, and neuroimaging results from a novel task in which stimulus-response and response-outcome associations are learned simultaneously but dominate behavior at different stages of the experiment. We found that prediction error representations in the ventral striatum depend on which type of learning dominates. Furthermore, the amygdala tracks the time-dependent weighting of stimulus-response versus response-outcome learning. Our findings suggest that the goal-directed and instrumental controllers dynamically engage the ventral striatum in representing prediction errors whenever one of them is dominating choice behavior. Converging evidence in human neuroimaging studies has shown that the reward prediction errors are correlated with activity in the ventral striatum. Our results demonstrate that this region is simultaneously correlated with a stimulus prediction error. Furthermore, the learning system that is currently dominating behavioral choice dynamically engages the ventral striatum for computing its prediction errors. This demonstrates that the prediction error representations are highly dynamic and influenced by various experimental context. This finding points to a general role of the ventral striatum in detecting expectancy violations and encoding error signals regardless of the specific nature of the reinforcer itself. Copyright © 2016 the authors 0270-6474/16/3612650-11$15.00/0.
Caillé, S.; Guillem, K.; Cador, M.; Manzoni, O.; Georges, F.
2009-01-01
Active response to either natural or pharmacological reward causes synaptic modifications to excitatory synapses on dopamine (DA) neurons of the ventral tegmental area (VTA). Here, we examine these modifications using nicotine, the main addictive component of tobacco, which is a potent regulator of
International Nuclear Information System (INIS)
Winton, E.F.; Colenda, K.W.
1987-01-01
The continued retrieval of progenitor cells (CFU-GEMM, BFU-E, CFU-E, CFU-GM) from human long-term marrow cultures (LTMC) is not uncommonly used as evidence that proliferation and differentiation are occurring in more primitive hematopoietic stem cells (HSC) in these cultures. Alternatively, the continued presence of progenitors in LTMC could be the result of survival and/or limited self-renewal of progenitor cells present when the culture was initiated, and such progenitors would have little relevance to the parent HSC. The following studies were designed to determine the relative contributions of precursors of progenitor cells to the total progenitor cells present in LTMC using a two-stage regeneration model. The adherent layer in LTMC was established over 3 weeks, irradiated (875 rad) to permanently eliminate resident hematopoietic cells, and recharged with autologous cryo-preserved marrow that was either treated or not treated (control) with 4-hydroperoxycyclophosphamide (4-HC, 100 micrograms/ml for 30 min). The 4-HC-treated marrow contained no progenitor cells, yet based on clinical autologous bone marrow transplant experience, has intact HSC. Within 1-3 weeks, progenitor cells reappeared in the irradiated LTMC recharged with 4-HC-treated marrow, and were preferentially located in the adherent layer. By 2-6 weeks, the number of progenitor cells in the adherent layer of LTMC recharged with 4-HC marrow was equivalent to control LTMC. The progenitors regenerating in the irradiated LTMC recharged with 4-HC-treated marrow appear to originate from precursors of progenitor cells, perhaps HSC. We propose this model may be useful in elucidating cellular and molecular correlates of progenitor cell regeneration from precursors
Ultrasonographic evaluation of the healing of ventral midline abdominal incisions in the horse.
Wilson, D A; Badertscher, R R; Boero, M J; Baker, G J; Foreman, J H
1989-06-01
Ultrasonography was used to evaluate the ventral midline incisions of 21 ponies following exploratory laparotomy. The incisions were evaluated before surgery and at weekly intervals from one to seven weeks after surgery. Both 5.0 and 7.5 MHz linear array and 7.5 MHz sector transducers were used for the evaluations. The incisional complications observed were drainage, oedema, suture sinus formation, suture abscess, superficial dehiscence and incisional hernia. Ultrasonographic imaging of the ventral midline incision was an easy, reliable and objective method for detecting and monitoring the progression of incisional complications in a non-invasive manner.
van Hulst, Branko M; de Zeeuw, Patrick; Lupas, Kellina; Bos, Dienke J; Neggers, Sebastiaan F W; Durston, Sarah
2015-01-01
Reward processing has been implicated in developmental disorders. However, the classic task to probe reward anticipation, the monetary incentive delay task, has an abstract coding of reward and no storyline and may therefore be less appropriate for use with developmental populations. We modified the task to create a version appropriate for use with children. We investigated whether this child-friendly version could elicit ventral striatal activation during reward anticipation in typically developing children and young adolescents (aged 9.5-14.5). In addition, we tested whether our performance-based measure of reward sensitivity was associated with anticipatory activity in ventral striatum. Reward anticipation was related to activity in bilateral ventral striatum. Moreover, we found an association between individual reward sensitivity and activity in ventral striatum. We conclude that this task assesses ventral striatal activity in a child-friendly paradigm. The combination with a performance-based measure of reward sensitivity potentially makes the task a powerful tool for developmental imaging studies of reward processing.
Grace, Anthony A
2010-11-01
The dopamine system is under multiple forms of regulation, and in turn provides effective modulation of system responses. Dopamine neurons are known to exist in several states of activity. The population activity, or the proportion of dopamine neurons firing spontaneously, is controlled by the ventral subiculum of the hippocampus. In contrast, burst firing, which is proposed to be the behaviorally salient output of the dopamine system, is driven by the brainstem pedunculopontine tegmentum (PPTg). When an animal is exposed to a behaviorally salient stimulus, the PPTg elicits a burst of action potentials in the dopamine neurons. However, this bursting only occurs in the portion of the dopamine neuron population that is firing spontaneously. This proportion is regulated by the ventral subiculum. Therefore, the ventral subiculum provides the gain, or the amplification factor, for the behaviorally salient stimulus. The ventral subiculum itself is proposed to carry information related to the environmental context. Thus, the ventral subiculum will adjust the responsivity of the dopamine system based on the needs of the organism and the characteristics of the environment. However, this finely tuned system can be disrupted in disease states. In schizophrenia, a disruption of interneuronal regulation of the ventral subiculum is proposed to lead to an overdrive of the dopamine system, rendering the system in a constant hypervigilant state. Moreover, amphetamine sensitization and stressors also appear to cause an abnormal dopaminergic drive. Such an interaction could underlie the risk factors of drug abuse and stress in the precipitation of a psychotic event. On the other hand, this could point to the ventral subiculum as an effective site of therapeutic intervention in the treatment or even the prevention of schizophrenia.
International Nuclear Information System (INIS)
Hirsch, Cordula; Campano, Louise M.; Woehrle, Simon; Hecht, Andreas
2007-01-01
Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of β-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/β-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity
Dorsal and ventral changes of the occipital vertebrae
International Nuclear Information System (INIS)
Banki, Z.
1981-01-01
Based on his own observation and on the literature, the author discusses various types of calcification in the occipital-cervical region, beginning with those situated dorsally and followed by ventral forms. An attempt is made to classify these changes, depending on their morphology and situation, from an embryological point of view. The pro-atlantal and ante pro-atlanto origin of the occipital vertebrae is discussed. Differentiation depends on appearances. (orig.) [de
Rausch, Franziska; Mier, Daniela; Eifler, Sarah; Fenske, Sabrina; Schirmbeck, Frederike; Englisch, Susanne; Schilling, Claudia; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias
2015-01-01
Patients with schizophrenia display metacognitive impairments, such as hasty decision-making during probabilistic reasoning - the "jumping to conclusion" bias (JTC). Our recent fMRI study revealed reduced activations in the right ventral striatum (VS) and the ventral tegmental area (VTA) to be
Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders.
Lazzeri, Elena; Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura; Romagnani, Paola
2015-08-01
The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. Copyright © 2015 by the American Society of Nephrology.
THE PROGENITOR OF SUPERNOVA 2011dh/PTF11eon IN MESSIER 51
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Van Dyk, Schuyler D. [Spitzer Science Center/Caltech, Pasadena CA 91125 (United States); Li, Weidong; Cenko, S. Bradley; Silverman, Jeffrey M.; Filippenko, Alexei V. [Department of Astronomy, University of California, Berkeley, CA 94720-3411 (United States); Kasliwal, Mansi M.; Horesh, Assaf; Ofek, Eran O.; Quimby, Robert M.; Kulkarni, Shrinivas R. [Astronomy Department, California Institute of Technology, Pasadena, CA 91125 (United States); Kraus, Adam L. [Institute for Astronomy, University of Hawaii, Honolulu, HI 96822 (United States); Arcavi, Iair; Gal-Yam, Avishay; Yaron, Ofer; Polishook, David, E-mail: vandyk@ipac.caltech.edu [Department of Particle Physics and Astrophysics, Weizmann Institute of Science, 76100 Rehovot (Israel)
2011-11-10
We have identified a luminous star at the position of supernova (SN) 2011dh/PTF11eon, in pre-SN archival, multi-band images of the nearby, nearly face-on galaxy Messier 51 (M51) obtained by the Hubble Space Telescope with the Advanced Camera for Surveys. This identification has been confirmed, to the highest available astrometric precision, using a Keck-II adaptive-optics image. The available early-time spectra and photometry indicate that the SN is a stripped-envelope, core-collapse Type IIb, with a more compact progenitor (radius {approx} 10{sup 11} cm) than was the case for the well-studied SN IIb 1993J. We infer that the extinction to SN 2011dh and its progenitor arises from a low Galactic foreground contribution, and that the SN environment is of roughly solar metallicity. The detected object has absolute magnitude M{sup 0}{sub V} Almost-Equal-To -7.7 and effective temperature {approx}6000 K. The star's radius, {approx}10{sup 13} cm, is more extended than what has been inferred for the SN progenitor. We speculate that the detected star is either an unrelated star very near the position of the actual progenitor, or, more likely, the progenitor's companion in a mass-transfer binary system. The position of the detected star in a Hertzsprung-Russell diagram is consistent with an initial mass of 17-19 M{sub Sun }. The light of this star could easily conceal, even in the ultraviolet, the presence of a stripped, compact, very hot ({approx}10{sup 5} K), nitrogen-rich Wolf-Rayet star progenitor.
Psaltis, Peter J; Puranik, Amrutesh S; Spoon, Daniel B; Chue, Colin D; Hoffman, Scott J; Witt, Tyra A; Delacroix, Sinny; Kleppe, Laurel S; Mueske, Cheryl S; Pan, Shuchong; Gulati, Rajiv; Simari, Robert D
2014-07-18
Macrophages regulate blood vessel structure and function in health and disease. The origins of tissue macrophages are diverse, with evidence for local production and circulatory renewal. We identified a vascular adventitial population containing macrophage progenitor cells and investigated their origins and fate. Single-cell disaggregates from adult C57BL/6 mice were prepared from different tissues and tested for their capacity to form hematopoietic colony-forming units. Aorta showed a unique predilection for generating macrophage colony-forming units. Aortic macrophage colony-forming unit progenitors coexpressed stem cell antigen-1 and CD45 and were adventitially located, where they were the predominant source of proliferating cells in the aortic wall. Aortic Sca-1(+)CD45(+) cells were transcriptionally and phenotypically distinct from neighboring cells lacking stem cell antigen-1 or CD45 and contained a proliferative (Ki67(+)) Lin(-)c-Kit(+)CD135(-)CD115(+)CX3CR1(+)Ly6C(+)CD11b(-) subpopulation, consistent with the immunophenotypic profile of macrophage progenitors. Adoptive transfer studies revealed that Sca-1(+)CD45(+) adventitial macrophage progenitor cells were not replenished via the circulation from bone marrow or spleen, nor was their prevalence diminished by depletion of monocytes or macrophages by liposomal clodronate treatment or genetic deficiency of macrophage colony-stimulating factor. Rather adventitial macrophage progenitor cells were upregulated in hyperlipidemic ApoE(-/-) and LDL-R(-/-) mice, with adventitial transfer experiments demonstrating their durable contribution to macrophage progeny particularly in the adventitia, and to a lesser extent the atheroma, of atherosclerotic carotid arteries. The discovery and characterization of resident vascular adventitial macrophage progenitor cells provides new insight into adventitial biology and its participation in atherosclerosis and provokes consideration of the broader existence of local macrophage
Nf2-Yap signaling controls the expansion of DRG progenitors and glia during DRG development.
Serinagaoglu, Yelda; Paré, Joshua; Giovannini, Marco; Cao, Xinwei
2015-02-01
Molecular mechanisms governing the maintenance and proliferation of dorsal root ganglia (DRG) progenitors are largely unknown. Here we reveal that the Hippo pathway regulates the expansion of DRG progenitors and glia during mammalian DRG development. The key effectors of this pathway, transcriptional coactivators Yap and Taz, are expressed in DRG progenitors and glia during DRG development but are at least partially inhibited from activating transcription. Aberrant YAP activation leads to overexpansion of DRG progenitor and glial populations. We further show that the Neurofibromatosis 2 (Nf2) tumor suppressor inhibits Yap during DRG development. Loss of Nf2 leads to similar phenotypes as does YAP hyperactivation, and deleting Yap suppresses these phenotypes. Our study demonstrates that Nf2-Yap signaling plays important roles in controlling the expansion of DRG progenitors and glia during DRG development. Copyright © 2014 Elsevier Inc. All rights reserved.
Asymmetric development of dorsal and ventral attention networks in the human brain
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Kristafor Farrant
2015-04-01
Full Text Available Two neural systems for goal-directed and stimulus-driven attention have been described in the adult human brain; the dorsal attention network (DAN centered in the frontal eye fields (FEF and intraparietal sulcus (IPS, and the ventral attention network (VAN anchored in the temporoparietal junction (TPJ and ventral frontal cortex (VFC. Little is known regarding the processes governing typical development of these attention networks in the brain. Here we use resting state functional MRI data collected from thirty 7 to 12 year-old children and thirty 18 to 31 year-old adults to examine two key regions of interest from the dorsal and ventral attention networks. We found that for the DAN nodes (IPS and FEF, children showed greater functional connectivity with regions within the network compared with adults, whereas adults showed greater functional connectivity between the FEF and extra-network regions including the posterior cingulate cortex. For the VAN nodes (TPJ and VFC, adults showed greater functional connectivity with regions within the network compared with children. Children showed greater functional connectivity between VFC and nodes of the salience network. This asymmetric pattern of development of attention networks may be a neural signature of the shift from over-representation of bottom-up attention mechanisms to greater top-down attentional capacities with development.