bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-Dependent Cerebrovascular Abnormalities and Blood Flow Disturbances in APP23 Mice Modeling Alzheimer's Disease
Authors: Beckmann Nicolau , Schuler Alexandra , Mueggler Thomas , Meyer Eric P. , Wiederhold Karl-Heinz , Staufenbiel Matthias , Krucker Thomas
Published: April 2018

Neuropathological changes associated with Alzheimer's disease (AD) such as amyloidplaques, cerebral amyloid angiopathy, and related pathologies are reproduced in APP23 transgenic mice overexpressing amyloid precursor protein (APP) with the Swedish mutation. Magnetic resonance angiography (MRA) was applied to probe,in vivo, the cerebral arterial hemodynamics of these mice. Flow voids were detected at the internal carotid artery of 11-month-old APP23 mice. At the age of 20 months, additional flow disturbances were observed in large arteries at the circle of Willis. Vascular corrosion casts obtained from the same mice revealed that vessel elimination, deformation, or both had taken place at the sites where flow voids were detected by MRA. The detailed three-dimensional architecture of the vasculature visible in the casts assisted the identification of smaller vessels most likely formed as substitution or anastomosis within the circle of Willis. Angiograms and corrosion casts from nontransgenic, age-matched mice manifested no major abnormalities in the cerebrovascular arterial flow pattern. Because no transgene overexpression has been found in the cerebrovasculature of APP23 mice and no deposits of amyloid-β (Aβ) were observed in large arteries in the region of the circle of Willis, the present results suggest that soluble Aβ may exert deleterious effects on the vasculature. Our findings support the idea that cerebral circulatory abnormalities evolving progressively could contribute to AD pathogenesis. The study also shows the power of MRA to identify changes of vascular function in genetically engineered mice. MRA as a noninvasive technique could be applied to test new therapeutic concepts in animal models of AD and in humans.
Reduced Inhibition and Increased Output of Layer II Neurons in the Medial Entorhinal Cortex in a Model of Temporal Lobe Epilepsy
Authors: Kobayashi Masayuki , Wen Xiling , Buckmaster Paul S.
Published: April 2018

Temporal lobe epilepsy is the most common type of epilepsy in adults, and its underlying mechanisms are unclear. To investigate how the medial entorhinal cortex might contribute to temporal lobe epilepsy, we evaluated the histology and electrophysiology of slices from rats 3–7 d after an epileptogenic injury (pilocarpine-induced status epilepticus). Nissl staining, NeuN immunocytochemistry, andin situhybridization for GAD65 mRNA were used to verify the preferential loss of glutamatergic neurons and the relative sparing of GABAergic interneurons in layer III. From slices adjacent to those that were used for anatomy, we obtained whole-cell patch recordings from layer II medial entorhinal cortical neurons. Recordings under current-clamp conditions revealed similar intrinsic electrophysiological properties (resting membrane potential, input resistance, single spike, and repetitive firing properties) to those of controls. Spontaneous IPSCs were less frequent (68% of controls), smaller in amplitude (57%), and transferred less charge (51%) than in controls. However, the frequency, amplitude, and rise time of miniature IPSCs were normal. These findings suggest that after epileptogenic injuries the layer II entorhinal cortical neurons receive less GABAAreceptor-mediated synaptic input because presynaptic inhibitory interneurons become less active. To investigate the possible consequences of reduced spontaneous inhibitory input to layer II neurons, we recorded field potentials in the dentate gyrus, their major synaptic target. At 5 d after pilocarpine-induced status epilepticus the spontaneous field potentials recordedin vivowere over three times more frequent than in controls. These findings suggest that an epileptogenic injury reduces inhibition of layer II neurons and results in excessive synaptic input to the dentate gyrus.
Mitogen-Activated Protein Kinase Regulates Dopamine Transporter Surface Expression and Dopamine Transport Capacity
Authors: Morón José A. , Zakharova Irina , Ferrer Jasmine V. , Merrill Gerald A. , Hope Bruce , Lafer Eileen M. , Lin Zhi Cheng , Wang Jia Bei , Javitch Jonathan A. , Galli Aurelio , Shippenberg Toni S.
Published: April 2018

The dopamine transporter (DAT) regulates the clearance of dopamine (DA) released into the extracellular space and is an important site on which psychostimulants act to produce their effects. Here, we show that mitogen-activated protein kinase (MAPK) regulates the transport capacity and intracellular trafficking of DAT. Incubation of striatal synaptosomes or epitope-tagged human DAT (hDAT) human embryonic kidney (HEK) 293 cells with the MAPK kinase (MEK) inhibitors 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto) butadiene and 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one decreased DA uptake in a concentration- and time-dependent manner. Kinetic studies revealed a decrease in the capacity of transport (Vmax) but no change inKm. Immunoblotting confirmed labeling of p42 and p44 MAPK in untreated striatal synaptosomes and HEK 293 cells, consistent with constitutive MAPK activation, and the inhibitors used decreased MAPK phosphorylation. Biotinylation and confocal imaging studies showed that MAPK inhibition promoted the clathrin-associated redistribution of hDAT from the plasma membrane to the cytosol. In contrast, transient transfection of hDAT-expressing cells with constitutively active MEK increased theVmaxof DA transport without alteringKm. However, only a small increase in hDAT cell surface expression was seen. These data demonstrate an involvement of the MAPK cascade in regulating DAT transport capacity in striatum and that inhibition of this cascade decreases DAT cell surface expression in HEK 293 cells. Furthermore, they highlight the potential role of MAPK as a presynaptic mechanism that regulates DA signaling.
Fas/Tumor Necrosis Factor Receptor Death Signaling Is Required for Axotomy-Induced Death of MotoneuronsIn Vivo
Authors: Ugolini Gabriele , Raoul Cédric , Ferri Anna , Haenggeli Christine , Yamamoto Yoichi , Salaün Danièle , Henderson Christopher E. , Kato Ann C. , Pettmann Brigitte , Hueber Anne-Odile
Published: April 2018

Activation of the Fas death receptor leads to the death of motoneurons in culture. To investigate the role of Fas in programmed cell death and pathological situations, we used several mutant mice deficient for Fas signaling and made a novel transgenicFADD-DN(FAS-associated death domain-dominant-negative) strain.In vitro, motoneurons from all of these mice were found to be resistant to Fas activation and to show a delay in trophic deprivation-induced death. During normal developmentin vivo, no changes in motoneuron survival were observed. However, the number of surviving motoneurons was twofold higher in animals deficient for Fas signaling after facial nerve transection in neonatal mice. These results reveal a novel role for Fas as a trigger of axotomy-induced death and suggest that the Fas pathway may be activated in pathological degeneration of motoneurons.
Functional Coupling between Sulfonylurea Receptor Type 1 and a Nonselective Cation Channel in Reactive Astrocytes from Adult Rat Brain
Authors: Chen Mingkui , Dong Yafeng , Simard J. Marc
Published: April 2018

We previously identified a novel, nonselective cation channel in native reactive (type R1) astrocytes (NR1As) from injured rat brain that is regulated by cytoplasmic Ca2+and ATP (NCCa-ATP) and exhibits sensitivity to block by adenine nucleotides similar to that of sulfonylurea receptor type 1 (SUR1). Here we show that SUR1 is involved in regulation of this channel. NR1As within the site of injury and after isolation exhibited specific binding of FITC-tagged glibenclamide and were immunolabeled with anti-SUR1 antibody, but not with anti-SUR2, anti-Kir6.1 or anti-Kir6.2 antibodies, indicating absence of ATP-sensitive K+(KATP) channels. RT-PCR confirmed transcription of mRNA for SUR1 but not SUR2. Several properties previously associated exclusively with SUR1-regulated KATPchannels were observed in patch-clamp experiments using Cs+as the charge carrier: (1) the sulfonylureas, glibenclamide and tolbutamide, inhibited NCCa-ATPchannels with EC50values of 48 nmand 16.1 μm, respectively; (2) inhibition by sulfonylureas was lost after exposure of the intracellular face to trypsin or anti-SUR1 antibody; (3) channel inhibition was caused by a change in kinetics of channel closing, with no change in channel amplitude or open-channel dwell times; and (4) the SUR activator (“KATPchannel opener”), diazoxide, activated the NCCa-ATPchannel, whereas pinacidil and cromakalin did not. Also, glibenclamide prevented cell blebbing after ATP depletion, whereas blebbing was produced by exposure to diazoxide. Our data indicate that SUR1 is functionally coupled to the pore-forming portion of the NCCa-ATPchannel, providing the first demonstration of promiscuity of SUR1 outside of the K+inward rectifier family of channels.
A Role for Extracellular Na+in the Channel Gating of Native and Recombinant Kainate Receptors
Authors: Paternain Ana V. , Cohen Adir , Stern-Bach Yael , Lerma Juan
Published: April 2018

Ionotropic glutamate receptors of the kainate and AMPA subtypes share a number of structural features, both topographical and in terms of stoichiometry. In addition, AMPA and kainate receptors share similar pharmacological and biophysical properties in that they are activated by common agonists and display rapid activation and desensitization characteristics. However, we show here that in contrast to AMPA receptor-mediated responses (native or recombinant GluR3 receptor), the response of native and recombinant (GluR6) kainate receptors to glutamate was drastically reduced in the absence of extracellular Na+(i.e., when replaced by Cs+). Removal of Na+increases the rate of desensitization, indicating that external Na+modulates channel gating. Whereas the size of the substituting cation is important in mimicking the action of Na+(Li+>K+>Cs+), modulation was voltage independent. These results indicate the existence of different gating mechanisms for AMPA and kainate receptors. By using chimeric AMPA-kainate receptors derived from GluR3 and GluR6, we have identified a key residue in the S2 segment of GluR6 (M770) that is largely responsible for the sensitivity of the receptor to external Na+. Thus, these results show the existence of a specific kainate receptor gating mechanism that requires external Na+to be operative.
Development of Columnar Topography in the Excitatory Layer 4 to Layer 2/3 Projection in Rat Barrel Cortex
Authors: Bender Kevin J. , Rangel Juliana , Feldman Daniel E.
Published: April 2018

The excitatory feedforward projection from layer (L) 4 to L2/3 in rat primary somatosensory (S1) cortex exhibits precise, columnar topography that is critical for columnar processing of whisker inputs. Here, we characterize the development of axonal topography in this projection using single-cell reconstructions in S1 slices. In the mature projection [postnatal day (P) 14-26], axons of L4 cells extending into L2/3 were confined almost entirely to the home barrel column, consistent with previous results. At younger ages (P8-11), however, axonal topography was significantly less columnar, with a large proportion of branches innervating neighboring barrel columns representing adjacent whisker rows. Mature topography developed from this initial state by targeted axonal growth within the home column and by growth of barrel columns themselves. Raising rats with all or a subset of whiskers plucked from P8-9, manipulations that induce reorganization of functional whisker maps and synaptic depression at L4 to L2/3 synapses, did not alter normal anatomical development of L4 to L2/3 axons. Thus, development of this projection does not require normal sensory experience after P8, and deprivation-induced reorganization of whisker maps at this age is unlikely to involve physical remodeling of L4 to L2/3 axons.
Vaccination with Dendritic Cells Pulsed with Peptides of Myelin Basic Protein Promotes Functional Recovery from Spinal Cord Injury
Authors: Hauben Ehud , Gothilf Amalia , Cohen Avi , Butovsky Oleg , Nevo Uri , Smirnov Igor , Yoles Eti , Akselrod Solange , Schwartz Michal
Published: April 2018

Injury-induced self-destructive processes cause significant functional loss after incomplete spinal cord injury (SCI). Cellular elements of both the innate (macrophage) and the adaptive (T-cell) immune response can, if properly activated and controlled, promote post-traumatic regrowth and protection after SCI. Dendritic cells (DCs) trigger activation of effector and regulatory T-cells, providing a link between the functions of the innate and the adaptive immune systems. They also initiate and control the body's response to pathogenic agents and regulate immune responses to both foreign and self-antigens. Here we show that post-injury injection of bone marrow-derived DCs pulsed with encephalitogenic or nonencephalitogenic peptides derived from myelin basic protein, when administered (either systemically or locally by injection into the lesion site) up to 12 d after the injury, led to significant and pronounced recovery from severe incomplete SCI. No significant protection was seen in DC recipients deprived of mature T-cells. Flow cytometry, RT-PCR, and proliferation assays indicated that the DCs prepared and used here were mature and immunogenic. Taken together, the results suggest that the DC-mediated neuroprotection was achieved via the induction of a systemic T-cell-dependent immune response. Better preservation of neural tissue and diminished formation of cysts and scar tissue accompanied the improved functional recovery in DC-treated rats. The use of antigen-specific DCs may represent an effective way to obtain, via transient induction of an autoimmune response, the maximal benefit of immune-mediated repair and maintenance as well as protection against self-destructive compounds.
Calbindin Influences Response to Photic Input in Suprachiasmatic Nucleus
Authors: Hamada Toshiyuki , LeSauter Joseph , Lokshin Maria , Romero Maria-Teresa , Yan Lily , Venuti Judith M. , Silver Rae
Published: April 2018

It is well known that light resets the circadian clock only at specific times of day. The mechanisms mediating such gating of environmental input to the CNS are not well understood. We show that calbindinD28K(CalB)-containing cells of the suprachiasmatic nucleus (SCN), which are directly retinorecipient, gate photic entrainment of cellular circadian oscillators and thereby determine the timing of locomotor rhythmicity. Specifically, we demonstrate a circadian rhythm of subcellular localization of CalB: whereas the protein is detected at all times in the cytoplasm, it is low or absent in the nucleus during the night. Under normal circumstances, light-induced behavioral phase shifts andPeriod(Per) gene expression in the SCN occur only during the subjective night. Surprisingly, both behavioral phase shifts and light-inducedPerare blocked during the subjective night and enhanced during the subjective day after administration of CalB antisense oligodeoxynucleotides. These results suggest a cellular basis for temporal gating of photic input to the circadian clock.
Upregulation of Sodium Channel Nav1.3 and Functional Involvement in Neuronal Hyperexcitability Associated with Central Neuropathic Pain after Spinal Cord Injury
Authors: Hains Bryan C. , Klein Joshua P. , Saab Carl Y. , Craner Matthew J. , Black Joel A. , Waxman Stephen G.
Published: April 2018

Spinal cord injury (SCI) can result in hyperexcitability of dorsal horn neurons and central neuropathic pain. We hypothesized that these phenomena are consequences, in part, of dysregulated expression of voltage-gated sodium channels. Because the rapidly repriming TTX-sensitive sodium channel Nav1.3 has been implicated in peripheral neuropathic pain, we investigated its role in central neuropathic pain after SCI. In this study, adult male Sprague Dawley rats underwent T9 spinal contusion injury. Four weeks after injury when extracellular recordings demonstrated hyperexcitability of L3-L5 dorsal horn multireceptive nociceptive neurons, and when pain-related behaviors were evident, quantitative RT-PCR,in situhybridization, and immunocytochemistry revealed an upregulation of Nav1.3 in dorsal horn nociceptive neurons. Intrathecal administration of antisense oligodeoxynucleotides (ODNs) targeting Nav1.3 resulted in decreased expression of Nav1.3 mRNA and protein, reduced hyperexcitability of multireceptive dorsal horn neurons, and attenuated mechanical allodynia and thermal hyperalgesia after SCI. Expression of Nav1.3 protein and hyperexcitability in dorsal horn neurons as well as pain-related behaviors returned after cessation of antisense delivery. Responses to normally noxious stimuli and motor function were unchanged in SCI animals administered Nav1.3 antisense, and administration of mismatch ODNs had no effect. These results demonstrate for the first time that Nav1.3 is upregulated in second-order dorsal horn sensory neurons after nervous system injury, showing that SCI can trigger changes in sodium channel expression, and suggest a functional link between Nav1.3 expression and neuronal hyperexcitability associated with central neuropathic pain.
Fine Structure and Biochemical Mechanisms Underlying Nigrostriatal Inclusions and Cell Death after Proteasome Inhibition
Authors: Fornai Francesco , Lenzi Paola , Gesi Marco , Ferrucci Michela , Lazzeri Gloria , Busceti Carla L. , Ruffoli Riccardo , Soldani Paola , Ruggieri Stefano , Alessandrì Maria G. , Paparelli Antonio
Published: April 2018

Mutation of genes encoding for various components of a metabolic pathway named the ubiquitin-proteasome system (UP) leads to inherited forms of Parkinson's disease (PD), whereas various components of the UP are constantly present within neuronal inclusions, Lewy bodies, that characterize most genetic and sporadic forms of PD. It has been hypothesized that impairment of this metabolic pathway might be a common mechanism for the onset of PD, and a recent study demonstrated a dysfunction of the UP system within the substantia nigra of patients affected by sporadic PD. In search for the mechanisms underlying the selective toxicity for nigral neurons after inhibition of the UP system, we explored the selective effects after striatal microinfusions of lactacystin or epoxomycin and potential retrograde changes within the ipsilateral substantia nigra. We found that neurotoxicity was selective for striatal dopamine (DA) components and led to retrograde apoptosis within nigral DA cells, which developed neuronal inclusions staining for antigens of the UP system. We found the same ultrastructural features characterizing inclusions obtainedin vivoandin vitroafter UP inhibition.In vivo, lactacystin-epoxomycin-induced toxicity was suppressed by inhibiting DA synthesis. Similarly,in vitroinclusions and apoptosis were prevented by reducing endogenous DA. On the other hand, toxicity of proteasome inhibition was enhanced by drugs augmenting DA availability:l-3,4-dihydroxyphenylalanine, monoamine oxidase blockers, and DA β-hydroxylase blockers.

These findings demonstrate that impairment of the UP system produces cell death and neuronal inclusions selectively for DA-containing neurons that depend on the occurrence of endogenous DA.
Modulation of the Innate Immune Response by NMDA Receptors Has Neuropathological Consequences
Authors: Glezer Isaias , Zekki Hakima , Scavone Cristoforo , Rivest Serge
Published: April 2018

The aim of this study was to determine whether glutamate receptors modulate the innate immune response in the brain of C3H/HeN and C3H/HeJ mice; the latter bear a loss of function in the toll-like receptor (TLR) 4 gene. Mice received an intrastriatal (IS) infusion of lipopolysaccharide (LPS), the exogenous ligand forTLR4, and were killed at several times thereafter. This treatment activated the transcription of a wide variety of genes involved in the control of the innate immune response. MK-801, an antagonist of NMDA glutamate receptor subtype, exacerbated the effects of the endotoxin in the brain of C3H/HeN mice but not inTLR4-deficient animals. The ipsilateral side of C3H/HeN mice exhibited stronger hybridization signals for the mRNA encoding TLR2, CD14, tumor necrosis factor-α, and inhibitory factor-κBα at various times after the treatment combining MK-801 and LPS. This robust inflammatory response in the brain of C3H/HeN mice was not associated with any convincing signs of neurodegeneration or demyelination that was verified via numerous approaches and at time up to 2 weeks after injection. However, animals that received long-term IS infusion of LPS, together with MK-801, exhibited a significant increase in demyelination levels within the ipsilateral side. Our results demonstrate that binding of glutamate to its cognate NMDA receptor modulates LPS-induced innate immune reaction in aTLR4-dependent manner. This acute response may be crucial to eliminate bacterial cell wall components and minimizing tissue injury. However, sustained deregulation of proinflammatory signaling involving NMDA receptors leads to demyelination and is likely to be a mechanism participating in such pathological conditions.
Circadian Gene Expression Regulates Pulsatile Gonadotropin-Releasing Hormone (GnRH) Secretory Patterns in the Hypothalamic GnRH-Secreting GT1-7 Cell Line
Authors: Chappell Patrick E. , White Rachel S. , Mellon Pamela L.
Published: April 2018

Although it has long been established that episodic secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus is required for normal gonadotropin release, the molecular and cellular mechanisms underlying the synchronous release of GnRH are primarily unknown. We used the GT1-7 mouse hypothalamic cell line as a model for GnRH secretion, because these cells release GnRH in a pulsatile pattern similar to that observedin vivo. To explore possible molecular mechanisms governing secretory timing, we investigated the role of the molecular circadian clock in regulation of GnRH secretion. GT1-7 cells express many known core circadian clock genes, and we demonstrate that oscillations of these components can be induced by stimuli such as serum and the adenylyl cyclase activator forskolin, similar to effects observed in fibroblasts. Strikingly, perturbation of circadian clock function in GT1-7 cells by transient expression of the dominant-negativeClock-Δ19 gene disrupts normal ultradian patterns of GnRH secretion, significantly decreasing mean pulse frequency. Additionally, overexpression of the negative limb clock gene mCry1 in GT1-7 cells substantially increases GnRH pulse amplitude without a commensurate change in pulse frequency, demonstrating that an endogenous biological clock is coupled to the mechanism of neurosecretion in these cells and can regulate multiple secretory parameters. Finally, mice harboring a somatic mutation in theClockgene are subfertile and exhibit a substantial increase in estrous cycle duration as revealed by examination of vaginal cytology. This effect persists in normal light/dark (LD) cycles, suggesting that a suprachiasmatic nucleus-independent endogenous clock in GnRH neurons is required for eliciting normal pulsatile patterns of GnRH secretion.
Selective Encoding of Cocaine versus Natural Rewards by Nucleus Accumbens Neurons Is Not Related to Chronic Drug Exposure
Authors: Carelli Regina M. , Wondolowski Joyce
Published: April 2018

We reported previously that subsets of nucleus accumbens (Acb) neurons differentially encode information about goal-directed behaviors for “natural” (food and water) versus cocaine reward in animals well trained to self-administer the drug (Carelli et al., 2000). Here, we examined whether repeated exposure to cocaine is the crucial determinate of the selective encoding of cocaine versus water reinforcement by Acb neurons. Acb cells were recorded during a water-cocaine multiple schedule from the first day of cocaine exposure as well as during repeated sessions. Specifically, animals were initially trained to press a lever for water and were then surgically prepared for extracellular recording in the Acb. After 1 week, Acb cells were recorded during acquisition of the water-cocaine multiple schedule. Because behavioral responding for water was already established, training on the multiple schedule was divided into three components corresponding to acquisition of self-administration: (1) “initial” (day 1 of self-administration), (2) “reliable” (self-administration behavior was present but erratic), and (3) “stable” (cocaine responding was stable). During the initial component, the percentage of water-selective neurons was high compared with cocaine neurons. However, this became approximately equal with repeated self-administration experience (i.e., during the stable component). Remarkably, the percentage of neurons showing overlapping (similar) neuronal firing patterns during initial exposure to cocaine was low (<8%) and remained low during reliable and stable components. These findings support the view that separate neural circuits in the Acb differentially encode information about cocaine versus natural reward, and that this functional organization is not a direct consequence of chronic drug exposure.
Angiotensin II Blocks Nicotine-Mediated Neuroprotection against β-Amyloid (1-42) via Activation of the Tyrosine Phosphatase SHP-1
Authors: Shaw Seán , Bencherif Merouane , Marrero Mario B.
Published: April 2018

We showed recently that nicotine activates the growth-promoting enzyme Janus kinase 2 (JAK2) in PC12 cells and that preincubation of these cells with the JAK2-specific inhibitor AG-490 blocked the nicotine-induced neuroprotection against β-amyloid (1-42) [Aβ (1-42)]. These results provided direct evidence for linkage between JAK2 and the α7 nicotinic acetylcholine receptor-induced neuroprotection in PC12 cells. We also showed that preincubation with angiotensin II (Ang II), functioning via the angiotensin II type 2 (AT2) receptor, blocked both the nicotine-induced activation of JAK2 and its neuroprotection against Aβ (1-42). Recently growth-inhibitory effects of the AT2receptor have been reported to be mediated by the activation of protein tyrosine phosphatases (PTPases) and that AT2receptor stimulation is associated with a rapid activation of the PTPase SHP-1 (the cytoplasmic tyrosine phosphatase that contains Src homology 2 domains), a negative regulator of JAK2 signaling. Therefore, the potential biological significance of AT2receptor-induced effects on both the nicotine-induced activation of JAK2 and its neuroprotection against Aβ (1-42) led us to investigate whether SHP-1 activation could be involved in this process. We found that Ang II induced the activation of SHP-1 and that an antisense against SHP-1 not only augmented the nicotine-induced tyrosine phosphorylation of JAK2 but also blocked the Ang II neutralization of the nicotine-induced neuroprotection. These results demonstrate that nicotine-induced tyrosine phosphorylation of JAK2 and neuroprotection against Aβ (1-42) in PC12 cells are blocked by Ang II via AT2receptor-induced activation of SHP-1.
Next-Generation Sequencing of the Complete Mitochondrial Genome of the Endangered Species Black Lion Tamarin Leontopithecus chrysopygus (Primates) and Mitogenomic Phylogeny Focusing on the Callitrichidae Family
Authors: de Freitas Patrícia Domingues , Mendez Fernando Luis , Chávez-Congrains Karla , Galetti Pedro Manoel , Coutinho Luiz Lehmann , Pissinatti Alcides , Bustamante Carlos Daniel
Published: April 2018

We describe the complete mitochondrial genome sequence of the Black Lion Tamarin, an endangered primate species endemic to the Atlantic Rainforest of Brazil. We assembled the Leontopithecus chrysopygus mitogenome, through analysis of 523M base pairs (bp) of short reads produced by next-generation sequencing (NGS) on the Illumina Platform, and investigated the presence of nuclear mitochondrial pseudogenes and heteroplasmic sites. Additionally, we conducted phylogenetic analyses using all complete mitogenomes available for primates until June 2017. The single circular mitogenome of BLT showed organization and arrangement that are typical for other vertebrate species, with a total of 16618 bp, containing 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 non-coding region (D-loop region). Our full phylogenetic tree is based on the most comprehensive mitogenomic dataset for Callitrichidae species to date, adding new data for the Leontopithecus genus, and discussing previous studies performed on primates. Moreover, the mitochondrial genome reported here consists of a robust mitogenome with 3000X coverage, which certainly will be useful for further phylogenetic and evolutionary analyses of Callitrichidae and higher taxa.
Evaluación del pensamiento crítico y científico en estudiantes de pedagogía de una universidad chilena
Authors: Ossa-Cornejo Carlos , Palma-Luengo Maritza , Lagos-San Martín Nelly , Díaz-Larenas Claudio
Published: April 2018

This paper describes a research project focused on identifying student-teachers’ critical thinking performance levels in scientific reasoning and, secondly, on analyzing the reliability level of the Critical Thinking Tasks test (CTT). As part of the methodology, a non-probabilistic sample of 129 teacher education students from different majors at Bio-Bio University was considered, and the Critical Thinking Task test was applied to collect data. The data analysis was conducted using descriptive statistics, reliability measures and mean score differences. The data showed that the instrument is reliable (α=0,79); there is also a relatively low performance in the global test and its dimensions; and there are differences between the different teacher education programs. It is concluded that the instrument is reliable, and findings support the idea that knowledge-based areas influence critical thinking. Finally, it is necessary to strengthen specific sub-skills to enhance critical thinking as a contribution for scientific reasoning.
Para pensar la educación política en la educación formal
Authors: Fernández Alatorre Ana Corina
Published: April 2018

The purpose of this essay is to share the reflections about the meaning of politics to be able to think, from there, of the potential of a kind of education capable of giving back to the subject the right to take the floor and act, to exercise the politicization in the best possible way. From what is currently observed in countries of different continents, especially those with great inequalities, high levels of corruption and vulnerable sovereignty, the texts of Hannah Arendt (1997) are taken as a source of theoretical reflection in order to bring her into dialogue with more contemporary authors, like Bauman (2001), who invite us to recognize the many devastating faces of fear and their consequent paralyzing effect. After arguing the need to restore politics, reflection is opened to think about the implications of this need for the meaning of education.
Repensando la educación rural en una zona transfronteriza entre Costa Rica y Nicaragua: El caso de la Región Huetar Norte (RHN)
Authors: Salas-Acuña Erick Francisco
Published: April 2018

This essay discusses education in a rural cross-border area of Costa Rica, the Región Huetar Norte (Northern Huetar Region). It aims to raise the need of promoting educational processes that respond to the conditions of this territory. To do this, concepts such as rurality, border, and interculturality are problematized. Later comes a description of the historical conformation of this region, emphasizing the important role of Nicaraguan populations in the colonization of the northern territories; these territories constitute a space of cultural identity favored by the interconnection between both countries. Under the assumption that the inclusion of this “cross-border culture” constitutes a pending challenge for national educational policies, the essay argues for an intercultural education that contemplates the binational experiences of this territory in order to contribute to the exchange, the interaction and cooperation between both borders.
Aspectos pedagógicos y curriculares por considerar en el rediseño de un plan de estudios de posgrado con énfasis en docencia universitaria
Authors: Alvarado-Herrera Sindy Susana , González-Sandoval German Eduardo , Paniagua-Cortés Yarina
Published: April 2018

This project addresses the publications of a group of renowned authors in order to highlight important aspects to be considered by the Education Master’s Program in Higher Education and Teaching of the National University of Costa Rica as part of its improvement strategies in teacher education, taking into account the most recent tendencies related to internationalization, mobility, accreditation, academic management and shared leadership in higher education. The paper aims to portray a proposal that fulfills the needs of the Costa Rican master’s programs in higher education and teaching by approaching this country’s reality in terms of what the programs offer. It is a bibliographic research paper, which sources have been published for no longer than 10 years and are truly groundbreaking in regard to the graduate program trends that guide this production. Moreover, as part of the contextualization needed, all master’s degrees in higher education and teaching offered in the country are taken into consideration. As a result of this research, it can be concluded that these programs are pertinent, especially the one offered by the National University of Costa Rica, and it is evident that disseminating the program’s highlights and achievements through processes that respond to quality criteria for graduate programs truly needs to be encouraged.
The draft provisions on antitrust fines in the Commission’s ECN+ Proposal
Authors: Thomas Stefan , Dueñas Manuel
Published: April 2018

On 22 March 2017, the Commission released its Proposal for a directive to empower the competition authorities of the Member States to be more effective enforcers (COM(2017) 142 final). With this effort to harmonise national public enforcement regimes, the Commission enters uncharted territory. Effectiveness is deemed to be fostered by the introduction of the economic entity doctrine as a unitary sanctioning concept throughout the Member States. As a complementing measure, the Proposal prescribes a more coherent standard for leniency in the European Competition Network. The present article ventures to evaluate these remedies. A preliminary hypothesis is that the Commission’s conviction of the economic entity doctrine to become the gold standard for antitrust enforcement is possibly based on tenuous ideas of effectiveness. Moreover, the introduction of a 10 % fine cap for any National Competition Authority irrespective of the size of the Member State can lead to highly disparate relative fining powers throughout the internal market. As to the leniency aspect, the present article will attempt to assess whether the Proposal taps the full potential for enhancement. As an alternative to the Commission’s suggestions the article elaborates on a one-stop-shop leniency principle. Such would go beyond the current Proposal in that it would render multiple leniency filings obsolete within the EU.
Sawing off the branch you are sitting on
Authors: Pöchtrager Markus A.
Published: April 2018

This article argues that vowel reduction can be insightfully understood by reinterpreting openness as structural instead of melodic (i.e., mediated by an element). This allows for a unified account of various reduction phenomena in different languages and also extends to lenition in consonants. The proposal made here is couched within Government Phonology 2.0, a further development of Government Phonology.
The role of phonological processes in determining the vowel inventory of Brazilian Portuguese
Authors: Santana Arthur Pereira
Published: April 2018

This article deals with the non-final posttonic vowel subsystem of Brazilian Portuguese, specifically it questions if the high-mid vowels /e, o/ have undergone neutralization in this position. Three accounts have been provided so far to answer this question. Câmara Jr. (1999) proposes that the nonfinal posttonic subsystem is composed of four vowels /i, e, a, u/; Bisol (2003) advocates for a three-vowel subsystem /i, a, u/, and Ribeiro (2007) defends a five-vowel subsystem /i, e, a, o, u/. In this paper, I show that mid-vowel alternation in nonfinal posttonic context is the key to defining what the vowel subsystem is, which must be composed of five vowels /i, e, a, o, u/; however, differently to what has been proposed by Ribeiro (2007) for whom mid-vowel alternation is a case of lexical diffusion, I show that a rule-based approach is more explanatory of the phenomena.
Scope domains Toward a Dependency Grammar account of the syntactic distribution of negative polarity items
Authors: Osborne Timothy , Reeve Matthew
Published: April 2018

A widely assumed limitation on the distribution of negative polarity items (NPIs) is that they must be c-commanded by a trigger. Scrutiny of this limitation reveals, however, that c-command by a trigger is neither a necessary nor a sufficient condition on the distribution of NPIs. The failure of ccommand to serve as the basis for an account of the syntactic distribution of NPIs is taken here as the impetus to pursue an alternative approach, one in terms of scope and linear order instead of c-command. A particular concept of scope is established that serves as the key notion for characterizing the syntactic relationship between NPIs and their triggers. Scope is defined in a dependency grammar (DG) theory of syntax in terms ofscope domains. Thecatenaunit plays an important role. Given the notions of scope put forward, it is possible to discern two conditions on the syntactic distribution of NPIs.
Creating a culture of lifelong learning among Med-Peds Residents
Authors: O'Keefe Siobhán , Turner Mary Catherine , Brinn Nathan Andrew , Newton Dale
Published: April 2018

This article was migrated. The article was not marked as recommended. IntroductionInstitutional Culture is difficult to change but is imperative to the quality of physicians at an institution and its trainees.Background/RationaleNot all physicians practice life-long learning. Barriers include emphasis on clinical productivity, ineffective online searching, inadequate personal initiative and institutional culture. We were concerned that our institutional culture did not routinely stimulate the dynamic discussion of recent literature. To impact this culture, we implemented a lifelong learning lecture series for combined medicine-pediatrics (Med-Peds) physicians.MethodsArticles were selected from the American Academy of Pediatrics Grand Rounds and American College of Physicians Journal Clubs. 8-10 Articles were reviewed in "rapid fire' style and heated discussion was encouraged. Participants completed tests assessing knowledge pertaining to the articles to quantify their engagement.Results120 articles were reviewed during 15 lectures. 37 out of a potential 40 physicians participated. Participants answered a mean of 11% more questions correctly on short term recall (p=0.0026) and on long term recall (p= 0.0600) when compared to their baseline knowledge. When comparing the questions that pertained to lectures the participants attended versus those they did not attend participants answered 7% more questions correctly on short term recall ( p=0.0800) and long term recall ( p=0.1200).ConclusionsCulture is difficult to measure. The improved correct responses to questions about the papers presented suggests that the participants did engage in the discussion of the articles. Given the nature of Med-Peds training, culture change has the potential to affect the culture within both departments.
Os caixeiros viajantes como agentes formadores de redes sociais no Rio Grande do Sul
Authors: Von Mühlen Caroline , Dos Santos Rodrigo Luis
Published: April 2018

Este trabalho tem por objetivo apresentar alguns apontamentos acerca do projeto de pesquisa intitulado “Homens de negócios e de relações: os caixeiros viajantes como agentes formadores de redes sociais no Rio Grande do Sul (segunda metade do século XIX e primeira metade do século XX)”.Este projeto encontra-se em fase de desenvolvimento e visa empreender uma análise da formação de redes sociais, econômicas e políticas estabelecidas pelos caixeiros viajantes no Rio Grande do Sul, contemplando o recorte temporal que inicia na segunda metade do século XIX até a primeira metade do século XX, período em que essa profissão passa a sofrer um declínio. Percebemos que estes agentes sociais são analisados de forma ainda muito precária pela historiografia, sobretudo no Rio Grande do Sul. Tendo em vista que os caixeiros viajantes desempenharam um papel de considerável importância econômica e, em decorrência disso, também se ocuparam de estabelecerem vínculos diversos e formas de sociabilidade, almejamos dar maior visibilidade para estes agentes históricos e, concomitantemente, visibilizar as estratégias utilizadas por eles, a partir de uma apreciação crítica de suas trajetórias pessoais, embasados em robusto embasamento teórico e metodológico, coerente com os avanços recentes da historiografia na área das relações sociais.
Memória e conflitos étnico-raciais a partir de uma trajetória de abandono no século XX
Authors: Freitas Denize Terezinha Leal , Silva Jonathan Fachini da
Published: April 2018

O presente trabalho aborda a história de um abandono infantil resultado de um conflito étnico ocorrido na década de 50 do século XX. Trata-se da história de vida de uma mulher que descobriu depois de adulta sua verdadeira origem familiar e étnica. Nossa personagem é filha biológica de uma mãe de abastada família de imigrantes alemães e de um pai curandeiro e descendente de africanos, todos do pequeno vilarejo de Alto Sampaio, no Rio Grande do Sul. Desde a tenra idade e por muitos anos, viveu com uma família adotiva que a resgatou após o nascimento, no munícipio de Lajeado, no dia 04 de novembro de 1952. Através da metodologia da História Oral a partir de entrevistas e o cruzamento de fontes do período, do aporte teórico e discussões acerca da racialidade e condição feminina, pretendemos resgatar e compreender os caminhos e descaminhos que levaram a omissão e ao mesmo tempo sobrevivência destas memórias veladas por mais de sessenta anos.
DETERMINATION OF CONCRETE VAULT THICKNESS OF NEAR SURFACE DISPOSAL FOR RADIOACTIVE WASTE AT SERPONG NUCLEAR AREA
Authors: Sucipta Sucipta , Suhartono Suhartono
Published: April 2018

In order to support and complement the radioactive waste management facilities in Indonesia, BATAN will build a demonstration disposal facility in Serpong Nuclear Area (SNA). Demonstration disposal that will be built is Near Surface Disposal (NSD) type. Engineered vault for NSD is reinforced concrete. The calculations for determining the thickness of NSD concrete vault is based on the conceptual design as the result of the placement optimization of  demonstration disposal that takes into account the inventory of radioactive waste and environmental geology conditions of the site at Serpong Nuclear Area. The thickness of the vault in this paper is focused on its ability to withstand radiation from stored waste so that workers or people who are around the disposal facility is safe with maximum radiation dose limit rate of 0.3 μSv / h. The calculation is performed with the aid of MicroShield 7:02 and Rad Pro Calculator Version 3:26 software. From the calculation so that the dose rate at the outer surface of the vault to be 0.3 μSv / h, required walls made of concrete with a density of 2:35 g / cm3 is 62.8 cm thickness.
EVALUASI KEMAMPUAN SISTEM MENARA PENDINGIN REAKTOR RSG-GAS
Authors: Sihombing Edison Edison
Published: April 2018

EVALUASI KEMAMPUAN SISTEM MENARA PENDINGIN REAKTOR RSG-GAS. Saat ini, pengoperasian reaktor telah berlangsung selama 29 tahun. Meskipun selama ini masih dapat beroperasi secara aman. Namun analisis terkini kemampuan sistem pendingin reaktor RSG-GAS sangat penting untuk dilakukan. Hal ini perlu disampaikan kepada badan pengawas untuk mendapatkan persetujuan perpanjangan izin operasi RSG-GAS. Sistem pendingin RSG-GAS adalah pendingin primer dan sekunder. Unit komponen operasi yang berperan mentransfer panas adalah pompa penukar panas dan menara pendingin, dari 7 unit menara pendingin yang ada, dapat dioperasikan sesuai dengan beban panas dari reaktor. Tujuan makalah ini adalah menganalisis kemampuan sistem menara pendingin RSG-GAS pada daya operasi reaktor 20 MWt, 25 MWt dan 30 MWt. Uji verifikasi dikerjakan dengan mengukur temperatur pendingin keluar menara pendingin dan masuk ke reaktor pada operasi reaktor daya 15 MWt dengan moda operasi 4, 5 dan 6 unit menara pendingin. Selanjutnya analisis kemampuan menara pendingin pada daya reaktor 20 MWt, 25 MWt dan 30 MWt dianalisis menggunakan software ChemCAD. Hasil evaluasi menunjukkan bahwa dari aspek keselamatan, reaktor RSG-GAS daya 15 MWt dapat dioperasikan secara aman. Dari analisis operasi 4 dan 5 menara pendingin pada daya 30 MWt mengindikasikan bahwa temperatur pendingin ke reaktor mendekati batas sistem proteksi reaktor yang sebaiknya dihindari, oleh karena itu dianjurkan penggunaan 6 menara pendingin untuk operasi steady state pada daya 30 MWt.Kata kunci: RSG-GAS, temperatur pendingin, evaluasi, analisis, kemampuan menara pendingin.
Pemodelan Perhitungan Indeks Lost of Load Probability untuk N Unit Pembangkit pada Sistem Kelistrikan Opsi Nuklir
Authors: Setya Budi Rizki Firmansyah , Birmano Moch. Djoko , - Imam Bastori
Published: April 2018

Perhitungan LOLP dapat dilakukan secara manual ataupun dengan bantuan program. Perhitungan secara manual membutuhkan waktu yang lebih lama dan ketelitian dibandingkan dengan menggunakan bantuan program. Tujuan penelitian ini adalah untuk membuat sebuah model perhitungan indeks LOLP yang lebih sederhana, fleksibel (dapat digunakan untuk N jumlah pembangkit), dan waktu perhitungan yang lebih cepat. Program perhitungan LOLP menggunakan bantuan program Matlab. Penelitian dilakukan dengan langkah sebagai berikut: pembuatan source code pada Matlab, perhitungan indeks LOLP dengan data masukkan yang digunakan, dan validasi hasil perhitungan. Validasi dilakukan dengan cara bencmarking terhadap hasil perhitungan penelitian sebelumnya. Hasil penelitian menunjukkan bahwa model perhitungan indeks LOLP untuk N unit pembangkit pada sistem kelistrikan opsi nuklir telah berhasil dibuat dengan mempertimbangkan aspek kesederhanaan data masukkan, fleksibilitas, dan waktu yang lebih cepat. Hasil perhitungan dapat dinyatakan valid dengan selisih yang kurang dari 1% jika dibandingkan dengan hasil pada penelitian sebelumnya yang telah menghitung indeks LOLP dengan cara manual.
DAMPAK PERALIHAN MASSAL TRANSPORTASI JALAN RAYA KE MOBIL LISTRIK.
Authors: Liun Edwaren
Published: April 2018

Pertumbuhan penduduk Indonesia masih terus berlangsung dan kebutuhan energi untuk transportasi terus meningkat dari tahun ke tahun. Pasokan bahan bakar minyak diprediksi akan menurun sehingga energi untuk transportasi membutuhkan langkah-langkah inovatif ke masa depan, yang salah satu alternatif utamanya adalah menggunakan tenaga listrik. Makalah bertujuan untuk mengu­raikan perspektif ke depan sistem energi dalam kaitannya memenuhi permintaan di sektor transportasi serta meramalkan indikator yang terkait permintaan energi transportasi selama empat dekade ke depan menggunakan teknik smoothing trendline. Analisis dilakukan menggunakan Model MESSAGE untuk optimasi keseluruhan sistem energi. Di dalam model ini, dengan adanya vektor permintaan untuk barang atau jasa terhadap energi tertentu, pasokan harus menjamin jumlah yang sesuai dengan manfaat teknologi dan sumber daya yang dikonteskan. Permintaan energi sektor transportasi akan mencapai angka 300 ribu MWy energi tergambar pada tahun 2055. Untuk kendaraan listrik nilai aktualnya adalah 81 ribu MWy dalam bentuk energi listrik sebagai hasil perhitungan konversi energi. Demikian juga untuk tahun-tahun selainnya nilai aktual energi listriknya dikalikan dengan angka 0,27 – sebagai faktor konversi dari besaran nominal ke besaran aktual. Biaya energi untuk kendaraan listrik dengan perbedaan tipis lebih murah daripada kendaraan berbahan bakar minyak.