bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Phosphatase-1 Regulation in the Induction of Long-Term Potentiation: Heterogeneous Molecular Mechanisms
Authors: Allen Patrick B. , Hvalby Øivind , Jensen Vidar , Errington Michael L. , Ramsay Mark , Chaudhry Farrukh A. , Bliss Timothy V. P. , Storm-Mathisen Jon , Morris Richard G. M. , Andersen Per , Greengard Paul
Published: April 2018

Protein phosphatase inhibitor-1 (I-1) has been proposed as a regulatory element in the signal transduction cascade that couples postsynaptic calcium influx to long-term changes in synaptic strength. We have evaluated this model using mice lacking I-1. Recordings made in slices prepared from mutant animals and also in anesthetized mutant animals indicated that long-term potentiation (LTP) is deficient at perforant path–dentate granule cell synapses.In vitro, this deficit was restricted to synapses of the lateral perforant path. LTP at Schaffer collateral–CA1 pyramidal cell synapses remained normal. Thus, protein phosphatase-1-mediated regulation of NMDA receptor-dependent synaptic plasticity involves heterogeneous molecular mechanisms, in both different dendritic subregions and different neuronal subtypes. Examination of the performance of I-1 mutants in spatial learning tests indicated that intact LTP at lateral perforant path–granule cell synapses is either redundant or is not involved in this form of learning.
Differential Expression of Group I Metabotropic Glutamate Receptors in Functionally Distinct Hippocampal Interneurons
Authors: van Hooft Johannes A. , Giuffrida Raffaella , Blatow Maria , Monyer Hannah
Published: April 2018

Metabotropic glutamate receptors (mGluRs) have been proposed to be involved in oscillatory rhythmic activity in the hippocampus. However, the subtypes of mGluRs involved and their precise distribution in different populations of interneurons is unclear. In this study, we combined functional analysis of mGluR-mediated inward currents in CA1 oriens–alveus interneurons with anatomical and immunocytochemical identification of these interneurons and expression analysis of group I mGluR using single-cell reverse transcription-PCR (RT-PCR). Four major interneuron subtypes could be distinguished based on the mGluR-mediated inward current induced by the application of 100 μmtrans-(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) under voltage-clamp conditions and the action potential firing pattern under current-clamp conditions. Type I interneurons responded with a large inward current of ∼224 pA, were positive for somatostatin, and the majority expressed both mGluR1 and mGluR5. Type II interneurons responded with an inward current of ∼80 pA, contained calbindin, and expressed mainly mGluR1. Type III interneurons responded with an inward current of ∼60 pA. These interneurons were fast-spiking, contained parvalbumin, and expressed mainly mGluR5. Type IV interneurons did not respond with an inward current upon application of ACPD, yet they expressed group I mGluRs. Activation of group I mGluRs under current-clamp conditions increased spike frequency and resulted in rhythmic firing activity in type I and II, but not in type III and IV, interneurons. RT-PCR results suggest that activation of mGluR1 in the subsets of GABAergic interneurons, classified here as type I and II, may play an important role in mediating synchronous activity.
The Mechanisms of hsp27 Antibody-Mediated Apoptosis in Retinal Neuronal Cells
Authors: Tezel Gülgün , Wax Martin B.
Published: April 2018

Although elevated titers of serum antibodies to hsp27 accompany human diseases such as cancer and glaucoma, evidence of their pathogenic effects is lacking. Here we present novel evidence that exogenously applied hsp27 antibody enters neuronal cells in human retina by an endocytic mechanism. Subsequent to internalization, hsp27 antibody facilitates apoptotic cell death as characterized by morphological assessment, DNA fragmentation, and the activation of cysteine aspartic acid proteases. In addition, we demonstrate that after internalization, hsp27 antibody is detected in discrete cytoplasmic and nuclear structures and colocalizes to actin cytoskeleton. Hsp27 antibody binding to actin results in depolymerization and proteolytic cleavage of actin in a dose-dependent manner. These results suggest that exogenous hsp27 antibody may induce neuronal apoptosis by inactivating or attenuating the ability of native hsp27 to stabilize actin cytoskeleton, thereby providing a novel mechanism by which autoantibodies to hsp27 may impair cell survival in selective human diseases.
Pregnenolone Sulfate Modulates Inhibitory Synaptic Transmission by Enhancing GABAAReceptor Desensitization
Authors: Shen Weixing , Mennerick Steven , Covey Douglas F. , Zorumski Charles F.
Published: April 2018

We examined the effects of the neurosteroid pregnenolone sulfate (PS) on GABAAreceptor-mediated synaptic currents and currents elicited by rapid applications of GABA onto nucleated outside-out patches in cultured postnatal rat hippocampal neurons. At 10 μm, PS significantly depressed peak responses and accelerated the decay of evoked inhibitory synaptic currents.

In nucleated outside-out patches, PS depressed peak currents and speeded deactivation after 5 msec applications of a saturating concentration of GABA. PS also increased the rate and degree of macroscopic GABA receptor desensitization during prolonged GABA applications. In a paired GABA application paradigm, PS slowed the rate of recovery from desensitization.

In contrast to its prominent effects on currents produced by saturating GABA concentrations, PS had only small effects on peak currents and failed to alter deactivation after brief applications of the weakly desensitizing GABAAreceptor agonists taurine and β-alanine. However, when β-alanine was applied for a sufficient duration to promote receptor desensitization, PS augmented macroscopic desensitization and slowed deactivation.

These results suggest that PS inhibits GABA-gated chloride currents by enhancing receptor desensitization and stabilizing desensitized states. This contention is supported by kinetic modeling studies in which increases in the rate of entry into doubly liganded desensitized states mimic most effects of PS.
An Intramolecular Interaction between Src Homology 3 Domain and Guanylate Kinase-Like Domain Required for Channel Clustering by Postsynaptic Density-95/SAP90
Authors: Shin Hyewon , Hsueh Yi-Ping , Yang Fu-Chia , Kim Eunjoon , Sheng Morgan
Published: April 2018

Members of the postsynaptic density-95 (PSD-95)/SAP90 family of membrane-associated guanylate kinase (MAGUK) proteins function as multimodular scaffolds that organize protein-signaling complexes at neuronal synapses. MAGUK proteins contain PDZ, Src homology 3 (SH3), and guanylate kinase (GK)-like domains, all of which can function as sites for specific protein–protein interactions. We report here a direct protein–protein interaction between the SH3 domain and the GK region in the PSD-95 family of MAGUKs. The SH3 domain of the PSD-95 family appears to have an atypical binding specificity, because the classical SH3 binding (-P-X-X-P-) motif is absent from the GK domain. Although SH3–GK binding can occur in either an intramolecular or intermolecular manner, the intramolecular mode is preferred, possibly because of additional tertiary interactions available when the SH3 and GK domains are adjacent in the same polypeptide. Mutations disrupting the intramolecular SH3–GK interaction do not interfere with PSD-95 association with the K+channel Kv1.4 or with the GK domain-binding protein GKAP. The same mutations, however, inhibit the clustering of Kv1.4 by PSD-95, suggesting that the intramolecular SH3–GK interaction may modulate the clustering activity of PSD-95.
IFNγ Enhances Microglial Reactions to Hippocampal Axonal Degeneration
Authors: Jensen Michael B. , Hegelund Iørn V. , Lomholt Nina D. , Finsen Bente , Owens Trevor
Published: April 2018

Glial reactivity is implicated in CNS repair and regenerative responses. Microglia, the cells responding earliest to axonal injury, produce tumor necrosis factor-α (TNFα), a cytokine with both cytopathic and neuroprotective effects. We have studied activation of hippocampal microglia to produce TNFα in response to transection of perforant path axons in SJL/J mice. TNFα mRNA was produced in a transient manner, peaking at 2 d and falling again by 5 d after lesioning. This was unlike other markers of glial reactivity, such as Mac-1 upregulation, which were sustained over longer time periods. Message for the immune cytokine interferon-γ (IFNγ) was undetectable, and glial reactivity to axonal lesions occurred as normal in IFNγ-deficient mice. Microglial responses to lesion-induced neuronal injury were markedly enhanced in myelin basic protein promoter-driven transgenic mice, in which IFNγ was endogenously produced in hippocampus. The kinetics of TNFα downregulation 5 d after lesion was not affected by transgenic IFNγ, indicating that IFNγ acts as an amplifier and not an inducer of response. These results are discussed in the context of a regenerative role for TNFα in the CNS, which is innately regulated and potentiated by IFNγ.
N-CAM Binding Inhibits the Proliferation of Hippocampal Progenitor Cells and Promotes Their Differentiation to a Neuronal Phenotype
Authors: Amoureux Marie-Claude , Cunningham Bruce A. , Edelman Gerald M. , Crossin Kathryn L.
Published: April 2018

Cell adhesion molecules (CAMs) play important roles during the development of the nervous system. On the basis of our previous observations that binding of the neural CAM (N-CAM) inhibits astrocyte proliferation and alters gene expression, we hypothesized that N-CAM may influence the balance between the proliferation and the differentiation of neural progenitor cells. Rat and mouse hippocampal progenitor cells were cultured and showed dependence on basic FGF for proliferation, immunoreactivity for nestin, the presence of limited numbers of differentiated cells, and the ability to generate glial cells and neurons under different culture conditions. Addition of soluble N-CAM reduced cell proliferation in a dose-dependent manner with no evidence of apoptosis. The inhibition of proliferation by N-CAM was accompanied by an induction of differentiation to the neuronal lineage, as indicated by a twofold increase in the percentage of microtubule-associated protein 2-positive cells even in the presence of mitogenic growth factors. Experiments using hippocampal cells from N-CAM knock-out mice indicated that N-CAM on the cell surface is not required for these effects, suggesting the existence of heterophilic signaling. These results support a role for N-CAM and N-CAM ligands in the inhibition of proliferation and the induction of neural differentiation of hippocampal neural progenitor cells.
Caspase-Mediated Degradation of AMPA Receptor Subunits: A Mechanism for Preventing Excitotoxic Necrosis and Ensuring Apoptosis
Authors: Glazner Gordon W. , Chan Sic L. , Lu Chengbiao , Mattson Mark P.
Published: April 2018

Activation of ionotropic glutamate receptors of the AMPA and NMDA subtypes likely contributes to neuronal injury and death in various neurodegenerative disorders. Excitotoxicity can manifest as either apoptosis or necrosis, but the mechanisms that determine the mode of cell death are not known. We now report that levels of AMPA receptor subunits GluR-1 and GluR-4 are rapidly decreased in cultured rat hippocampal neurons undergoing apoptosis in response to withdrawal of trophic support (WTS), whereas levels of NMDA receptor subunits NR1, NR2A, and NR2B are unchanged. Exposure of isolated synaptosomal membranes to “apoptotic” cytosolic extracts resulted in rapid degradation of AMPA receptor subunits. Treatment of cells and synaptosomal membranes with the caspase inhibitors prevented degradation of AMPA receptor subunits, demonstrating a requirement for caspases in the process. Calcium responses to AMPA receptor activation were reduced after withdrawal of trophic support and enhanced after treatment with caspase inhibitors. Vulnerability of neurons to excitotoxic necrosis was decreased after withdrawal of trophic support and potentiated by treatment with caspase inhibitors. Our data indicate that caspase-mediated degradation of AMPA receptor subunits occurs during early periods of cell stress and may serve to ensure apoptosis by preventing excitotoxic necrosis.
From Plaque to Pretzel: Fold Formation and Acetylcholine Receptor Loss at the Developing Neuromuscular Junction
Authors: Marques Maria Julia , Conchello José-Angel , Lichtman Jeff W.
Published: April 2018

Although there has been progress in understanding the initial steps in the formation of synapses, less is known about their subsequent maturation (Sanes and Lichtman, 1999). Two alterations on the postsynaptic side of the mammalian neuromuscular junction occur during early postnatal life: acetylcholine receptors (AChRs) disappear from parts of the developing junction as all but one axonal inputs are removed, and the topography of the postsynaptic membrane becomes more complicated as gutters and folds are established. We have studied the maturation of the AChR distribution and postsynaptic topography simultaneously by imaging labeled AChRs at the mouse neuromuscular junction in a new way, using reflected light confocal microscopy. At birth postsynaptic receptors were localized in irregular patches within a spoon-shaped plaque. Beginning several days later, receptor regions within a single endplate were divided into differentiated and less organized compartments. Folds generally oriented orthogonal to the long axis of the muscle fiber were seen in developing gutters, although the orientation of the gutters seemed to be imposed by the branching pattern of the nerve. Eventually, superficial regions lacking AChR labeling were apparent in all junctions. In junctions denervated in the neonatal period both gutter formation and the disappearance of superficial receptors regions were prevented. We suggest that tension between growing muscle fibers and the relatively inelastic synaptic terminals that adhere to them causes the topographic features of the postsynaptic membrane. This view provides a mechanical explanation for gutters, folds, and the location of folds at sites of neurotransmitter release.
Recycling of the Cell Adhesion Molecule L1 in Axonal Growth Cones
Authors: Kamiguchi Hiroyuki , Lemmon Vance
Published: April 2018

The cell adhesion molecule (CAM) L1 plays crucial roles in axon growthin vitroand in the formation of major axonal tractsin vivo. It is generally thought that CAMs link extracellular immobile ligands with retrogradely moving actin filaments to transmit force that pulls the growth cone forward. However, relatively little is known about the fate of CAMs that have been translocated into the central (C)-domain of the growth cone. We have shown previously that L1 is preferentially endocytosed at the C-domain. In the present study, we further analyze the subcellular distribution of endocytic organelles containing L1 at different time points and demonstrate that internalized L1 is transported into the peripheral (P)-domain of growth cones advancing via an L1-dependent mechanism. Internalized L1 is found in vesicles positioned along microtubules, and the centrifugal transport of these L1-containing vesicles is dependent on dynamic microtubules in the P-domain. Furthermore, we show that endocytosed L1 is reinserted into the plasma membrane at the leading edge of the P-domain. Monitoring recycled L1 reveals that it moves retrogradely on the cell surface into the C-domain. In contrast, the growth cone advancing independently of L1 internalizes and recycles L1 within the C-domain. For the growth cone to advance, the leading edge needs to establish strong adhesive interactions with the substrate while attachments at the rear are released. Recycling L1 from the C-domain to the leading edge provides an effective way to create asymmetric L1-mediated adhesion and therefore would be critical for L1-based growth cone motility.
Wild-Type Huntingtin Protects from Apoptosis Upstream of Caspase-3
Authors: Rigamonti Dorotea , Bauer Johannes H. , De-Fraja Claudio , Conti Luciano , Sipione Simonetta , Sciorati Clara , Clementi Emilio , Hackam Abigail , Hayden Michael R. , Li Yong , Cooper Jillian K. , Ross Christopher A. , Govoni Stefano , Vincenz Claudius , Cattaneo Elena
Published: April 2018

Expansion of a polyglutamine sequence in the N terminus of huntingtin is the gain-of-function event that causes Huntington's disease. This mutation affects primarily the medium-size spiny neurons of the striatum. Huntingtin is expressed in many neuronal and non-neuronal cell types, implying a more general function for the wild-type protein. Here we report that wild-type huntingtin acts by protecting CNS cells from a variety of apoptotic stimuli, including serum withdrawal, death receptors, and pro-apoptotic Bcl-2 homologs. This protection may take place at the level of caspase-9 activation. The full-length protein also modulates the toxicity of the poly-Q expansion. Cells expressing full-length mutant protein are susceptible to fewer death stimuli than cells expressing truncated mutant huntingtin.
Encoding of Tactile Stimulus Location by Somatosensory Thalamocortical Ensembles
Authors: Ghazanfar Asif A. , Stambaugh Christopher R. , Nicolelis Miguel A. L.
Published: April 2018

The exquisite modular anatomy of the rat somatosensory system makes it an excellent model to test the potential coding strategies used to discriminate the location of a tactile stimulus. Here, we investigated how ensembles of simultaneously recorded single neurons in layer V of primary somatosensory (SI) cortex and in the ventral posterior medial (VPM) nucleus of the thalamus of the anesthetized rat may encode the location of a single whisker stimulus on a single trial basis. An artificial neural network based on a learning vector quantization algorithm, was used to identify putative coding mechanisms. Our data suggest that these neural ensembles may rely on a distributed coding scheme to represent the location of single whisker stimuli. Within this scheme, the temporal modulation of neural ensemble firing rate, as well as the temporal interactions between neurons, contributed significantly to the representation of stimulus location. The relative contribution of these temporal codes increased with the number of whiskers that the ensembles must discriminate among. Our results also indicated that the SI cortex and the VPM nucleus may function as a single entity to encode stimulus location. Overall, our data suggest that the representation of somatosensory features in the rat trigeminal system may arise from the interactions of neurons within and between the SI cortex and VPM nucleus. Furthermore, multiple coding strategies may be used simultaneously to represent the location of tactile stimuli.
Amphetamine Blocks Long-Term Synaptic Depression in the Ventral Tegmental Area
Authors: Jones Susan , Kornblum Johanna L. , Kauer Julie A.
Published: April 2018

The mesolimbic dopamine system is essential for reward-seeking behavior, and drugs of abuse are thought to usurp the normal functioning of this pathway. A growing body of evidence suggests that glutamatergic synapses on dopamine neurons in the ventral tegmental area (VTA) are modified during exposure to addictive drugs, producing sensitization, a progressive augmentation in the rewarding properties of psychostimulant drugs with repeated exposure. We have tested the hypothesis that psychostimulant exposure interferes with the synaptic plasticity of glutamatergic inputs to the VTA. We find that excitatory synapses onto VTA dopamine neurons exhibit long-term depression (LTD) in response to low-frequency stimulation and modest depolarization. LTD in the VTA is NMDA receptor-independent but is dependent on intracellular Ca2+and can be induced by driving Ca2+into the dopamine neuron. Brief exposure to amphetamine entirely blocks LTD at glutamatergic synapses in the VTA, by releasing endogenous dopamine that acts at D2 dopamine receptors. The block of LTD is selective, because amphetamine has no effect on hippocampal LTD. The LTD we have discovered in the VTA is likely to be an important component of excitatory control of the reward pathway; amphetamine will inhibit LTD, removing this normal brake on the glutamatergic drive to dopamine neurons. This effect of amphetamine represents an important mechanism by which normal function of the brain reward system may be impaired during substance abuse.
Facilitation of Recovery from Inactivation by External Na+and Location of the Activation Gate in Neuronal Na+Channels
Authors: Kuo Chung-Chin , Liao Shu-Yuan
Published: April 2018

Fast inactivation of the Na+channel presumably is produced by binding of the inactivating peptide (the “hinged lid”) to the internal pore mouth of the activated channel. It has been shown that recovery from inactivation in Na+channels begins with a delay, which corresponds to deactivation of the channel, and is then followed by an exponential phase, which corresponds to unbinding of the inactivating peptide. We found that the exponential phase is ∼1.6-fold faster in 150 mmthan in 0 mmexternal Na+, but the initial delays are the same. External Na+also increases the late steady-state Na+current during a step depolarization and shifts the inactivation curve accordingly but has no effect on the activation and deactivation kinetics of the current. Quantitative analysis of the data reveals that external Na+has the same facilitation effect on the unbinding of the bound inactivating peptide whether the channel is activated or deactivated but has no effect on the other gating processes of the channel. These findings suggest that permeating Na+ions directly knock off the bound inactivating peptide and that channel activation or deactivation does not affect the accessibility of the bound inactivation peptide to external Na+. The activation gate (the key gating change transforming a Na+-nonconducting pore into a Na+-conducting one) therefore should not be located external to the inactivation gate, which presumably is already located close to the internal end of the pore.
Metabolic Stress Reversibly Activates theDrosophilaLight-Sensitive Channels TRP and TRPLIn Vivo
Authors: Agam Keren , von Campenhausen Mark , Levy Simon , Ben-Ami Hagit Cohen , Cook Boaz , Kirschfeld Kuno , Minke Baruch
Published: April 2018

Drosophilatransient receptor potential (TRP) is a prototypical member of a novel family of channel proteins underlying phosphoinositide-mediated Ca2+entry. Although the initial stages of this signaling cascade are well known, downstream events leading to the opening of the TRP channels are still obscure. In the present study we applied patch-clamp whole-cell recordings and measurements of Ca2+concentration by ion-selective microelectrodes in eyes of normal and mutantDrosophilato isolate the TRP and TRP-like (TRPL)-dependent currents. We report that anoxia rapidly and reversibly depolarizes the photoreceptors and induces Ca2+influx into these cells in the dark. We further show that openings of the light-sensitive channels, which mediate these effects, can be obtained by mitochondrial uncouplers or by depletion of ATP in photoreceptor cells, whereas the effects of illumination and all forms of metabolic stress were additive. Effects similar to those found in wild-type flies were also found in mutants with strong defects in rhodopsin, Gq-protein, or phospholipase C, thus indicating that the metabolic stress operates at a late stage of the phototransduction cascade. Genetic elimination of both TRP and TRPL channels prevented the effects of anoxia, mitochondrial uncouplers, and depletion of ATP, thus demonstrating that the TRP and TRPL channels are specific targets of metabolic stress. These results shed new light on the properties of the TRP and TRPL channels by showing that a constitutive ATP-dependent process is required to keep these channels closed in the dark, a requirement that would make them sensitive to metabolic stress.
Prominence of Direct Entorhinal–CA1 Pathway Activation in Sensorimotor and Cognitive Tasks Revealed by 2-DG Functional Mapping in Nonhuman Primate
Authors: Sybirska Elzbieta , Davachi Lila , Goldman-Rakic Patricia S.
Published: April 2018

The trisynaptic pathway from entorhinal cortex to the hippocampus has long been regarded as the major route of information transfer underlying memory consolidation. Most physiological studies of this pathway involve recording from hippocampal slices. We have used both single- and double-label 2-deoxyglucose autoradiographic methods to image the pattern of activation in the hippocampal formation of 14 rhesus monkeys performing cognitive tasks, varying in content (spatial or nonspatial), process (working memory or associative memory), and mode of response (oculomotor or manual). These studies revealed a highly differentiated pattern of metabolic activation throughout the rostrocaudal extent of the hippocampal formation that was common to all behavioral conditions examined. This pattern consisted of intense activation of the stratum lacunosum-moleculare of CA1 and the subiculum, contrasting with barely detectable activity in CA3 and modest activation in the dentate gyrus, which did not include its molecular layer. These findings indicate a remarkable invariance in hippocampal activation under conditions of varied content, varied process, and varied mode of response and an heretofore-unappreciated preferential engagement of the direct rather than the trisynaptic pathway during performance of a wide range of behavioral tasks.
Malformation of the Functional Organization of Somatosensory Cortex in Adult Ephrin-A5 Knock-Out Mice Revealed byIn VivoFunctional Imaging
Authors: Prakash Neal , Vanderhaeghen Pierre , Cohen-Cory Susana , Frisén Jonas , Flanagan John G. , Frostig Ron D.
Published: April 2018

The molecular mechanisms that coordinate the functional organization of the mammalian neocortex are largely unknown. We tested the involvement of a putative guidance label, ephrin-A5, in the functional organization of the somatosensory cortex by quantifying the functional representations of individual whiskersin vivoin adult ephrin-A5 knock-out mice, using intrinsic signal optical imaging. In wild-type mice ephrin-A5 is expressed in a gradient in the somatosensory cortex during development. In adult ephrin-A5 knock-out mice, we found a spatial gradient of change in the amount of cortical territory shared by individual whisker functional representations across the somatosensory cortex, as well as a gradient of change in the distance between the functional representations. Both gradients of change were in correspondence with the developmental expression gradient of ephrin-A5 in wild-type mice. These changes involved malformations of the cortical spacing of the thalamocortical components, without concurrent malformations of the intracortical components of individual whisker functional representations. Overall, these results suggest that a developmental guidance label, such as ephrin-A5, is involved in establishing certain spatial relationships of the functional organization of the adult neocortex, and they underscore the advantage of investigating gene manipulation usingin vivofunctional imaging.
κ-Opioid Receptor Agonists Modulate Visceral Nociception at a Novel, Peripheral Site of Action
Authors: Joshi S. K. , Su Xin , Porreca Frank , Gebhart G. F.
Published: April 2018

κ-opioid receptor agonists (κ-ORAs) have been shown to modulate visceral nociception through an interaction with a peripheral, possibly novel, κ-opioid-like receptor. We used in the present experiments an antisense strategy to further explore the hypothesis that κ-ORA effects in the colon are produced at a site different from the cloned κ-opioid receptor (KOR). An antisense oligodeoxynucleotide (ODN) to the cloned rat KOR was administered intrathecally (12.5 μg, twice daily for 4 d) to specifically knock-down the cloned KOR. Efficacy of the KOR antisense ODN treatment was behaviorally evaluated by assessing the antinociceptive effects of peripherally administered κ- (EMD 61,753 and U 69,593), μ- (DAMGO) and δ- (deltorphin) ORAs in the formalin test. Intrathecal antisense, but not mismatch ODN blocked the actions of EMD 61,753 and U 69,593 without affecting the actions of DAMGO or deltorphin; a complete recovery of antinociceptive actions of the κ-ORA EMD 61,753 was observed 10 d after the termination of antisense ODN treatment. In contrast, the ability of EMD 61,753 to dose-dependently attenuate responses of pelvic nerve afferent fibers to noxious colonic distension was unaffected in the same rats in which the antisense ODN effectively knocked-down the KOR as assessed in the formalin test. Additionally, Western blot analysis demonstrated a significant downregulation of KOR protein in the L4-S1 dorsal root ganglia of antisense, but not mismatch ODN-treated rats. The present results support the existence of a non-κ-opioid receptor site of action localized in the colon.
c-fosReduces Corticosterone-Mediated Effects on Neurotrophic Factor Expression in the Rat Hippocampal CA1 Region
Authors: Hansson A. C. , Sommer W. , Rimondini R. , Andbjer B. , Strömberg I. , Fuxe K.
Published: April 2018

The transcription of neurotrophic factors, i.e., basic fibroblast growth factor (bFGF) and brain-derived neurotrophic factor (BDNF) is regulated by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation despite the lack of a classical glucocorticoid response element in their promoter region.

A time course for corticosterone (10 mg/kg, s.c.) in adrenalectomized rats revealed a peak hormone effect at the 4 hr time interval forbFGF(110–204% increase),BDNF(53–67% decrease),GR(53–64% decrease), andMR(34–56% decrease) mRNA levels in all hippocampal subregions usingin situhybridization.c-fosmRNA levels were affected exclusively in the dentate gyrus after 50 min to 2 hr (38–46% decrease).

Furthermore, it was evaluated whether corticosterone regulation of these genes depends on interactions with the transcription factor complex activator protein-1.c-fosantisense oligodeoxynucleotides were injected into the dorsal hippocampus of adrenalectomized rats. Corticosterone was given 2 hr later, and the effects on gene expression were measured 4 hr later. In CA1, antisense treatment significantly and selectively enhanced the hormone action on the expression ofbFGF(44% enhanced increase) andBDNF(38% enhanced decrease) versus control oligodeoxynucleotide treatment. In addition, an upregulation ofc-fosexpression (89% increase) was found. There were no effects ofc-fosantisense on hippocampalGRandMRexpression. Thus it seems that a tonicc-fosmechanism exists within CA1, which reducesGR- andMR-mediated effects on expression ofbFGFandBDNF.
Tropospheric ozone assessment report: Global ozone metrics for climate change, human health, and crop/ecosystem research
Authors: Lefohn Allen S. , Malley Christopher S. , Smith Luther , Wells Benjamin , Hazucha Milan , Simon Heather , Naik Vaishali , Mills Gina , Schultz Martin G. , Paoletti Elena , De Marco Alessandra , Xu Xiaobin , Zhang Li , Wang Tao , Neufeld Howard S. , Musselman Robert C. , Tarasick David , Brauer Michael , Feng Zhaozhong , Tang Haoye , Kobayashi Kazuhiko , Sicard Pierre , Solberg Sverre , Gerosa Giacomo
Published: April 2018

Assessment of spatial and temporal variation in the impacts of ozone on human health, vegetation, and climate requires appropriate metrics. A key component of the Tropospheric Ozone Assessment Report (TOAR) is the consistent calculation of these metrics at thousands of monitoring sites globally. Investigating temporal trends in these metrics required that the same statistical methods be applied across these ozone monitoring sites. The nonparametric Mann-Kendall test (for significant trends) and the Theil-Sen estimator (for estimating the magnitude of trend) were selected to provide robust methods across all sites. This paper provides the scientific underpinnings necessary to better understand the implications of and rationale for selecting a specific TOAR metric for assessing spatial and temporal variation in ozone for a particular impact. The rationale and underlying research evidence that influence the derivation of specific metrics are given. The form of 25 metrics (4 for model-measurement comparison, 5 for characterization of ozone in the free troposphere, 11 for human health impacts, and 5 for vegetation impacts) are described. Finally, this study categorizes health and vegetation exposure metrics based on the extent to which they are determined only by the highest hourly ozone levels, or by a wider range of values. The magnitude of the metrics is influenced by both the distribution of hourly average ozone concentrations at a site location, and the extent to which a particular metric is determined by relatively low, moderate, and high hourly ozone levels. Hence, for the same ozone time series, changes in the distribution of ozone concentrations can result in different changes in the magnitude and direction of trends for different metrics. Thus, dissimilar conclusions about the effect of changes in the drivers of ozone variability (e.g., precursor emissions) on health and vegetation exposure can result from the selection of different metrics.
DEVELOPMENT OF SCIENCE TEXTBOOK BASED ON SCIENTIFIC LITERACY FOR SECONDARY SCHOOL
Authors: Rusilowati A. , Nugroho S. E. , Susilowati S. M.
Published: April 2018

The purpose of this research is to develop scientific literacy-based science text books and to determine the characteristics, validity, readability, as well as the effectiveness of the textbooks.The study started with product development and then continued by feasibility test and readability test. Feasibility test was done with the respondent of lecturer and science teachers of VII, VIII, IX grade at SMP N at Central Java. Readability test used cloze test that filled by VII, VIII, and IX grade students at that schools. The data analysis was done with percentage discription and t-test. The study results in feasibility test showed that the developed literacy science textbook has average score 90,74%. It means the literacy science textbook is suitable. Based on the readability test result, science literacy textbook is easy to learn. The average of score of cloze test was 88,14%. The effectiveness of the developed science textbook was classified as an effective stimulant to increase students scientific literacy.Tujuan penelitian ini adalah mengembangkan buku ajar IPA berbasis literasi sains, menentukan karakteristik, kevalidannya, tingkat keterbacaan, dan keefektifannya. Penelitian pengembangan ini dimulai dengan analisis kebutuhan, penyusunan tema, pengembangan buku ajar, uji kevalidan dan keterbacaan buku yang telah dikembangkan. Validasi dilakukan oleh dosen dan guru IPA kelas VII, VII, IX. Uji validitas, tingkat keterbacaan dan keefektifan buku dilakukan di SMP N di Jawa Tengah. Subjek ujicoba adalah siswa kelas VII, VIII, IX. Teknik analisis data menggunakan deskriptif persentase untuk uji kevalidan dan keterbacaan, dan uji t untuk keefektifan. Hasil validasi menunjukkan seluruh buku yang dikembangkan adalah valid dengan rata-rata skor 90,74% berada pada kategori sangat valid. Skor rata-rata tingkat keterbacaan sebesar 88,14% beradapada kategori mudah dipahami. Buku ajar yang dikembangkan efektif untuk meningkatkan kemampuan literasi sains.
STUDY ON PHYSICAL-CHEMICAL PROPERTIES OF FURNACE-NICKEL-SLAG POWDER FOR GEOPOLYMER APPLICATION
Authors: Samnur S. , Husain H. , Zulfi A. , Sujiono E. H.
Published: April 2018

This research aims to prepare powder of nickel slag from furnace machine, identify, and analyze of the elements or compounds containing in the sample. The data retrieval was done with the analysis of elemental composition, phase microstructures, crystal size, distribution, and composition mapping of the samples by using XRD, Rigaku Miniflex II, and SEM-EDS, Tescan Vega-3. XRD result indicates that the formation which the similar to amorphous phase was identified and the formation at peak 2? = 28.01 is identified as the low quartz (SiO2). FWHM 0.18 was obtained using microcal origin 6.0 and average crystal size 53.37 nm was obtained by applying Scherer equation. SEM results show average grain size of samples which is less than 1?m and maximum to 4?m. Based on EDS result, the main constituent elements are Si 32.86 wt%, Mg 19.40 wt%, and Fe 32.03 wt%, respectively.Penelitian ini bertujuan untuk menyiapkan bubuk slag nikel yang berasal dari furnace, yang dilanjutkan dengan mengidentifikasi dan menganalisis unsur atau paduan yang terkandung di dalamnya. Data diperoleh dengan melakukan analisis terhadap komposisi unsur, fasa mikrostruktur, ukuran Kristal, distribusi dan komposisi paduan dari sampel bubuk slag nikel furnace dengan menggunakan XRD tipe Rigaku Miniflex II dan SEM-EDS tipe Tescan Vega-3. Hasil analisis XRD menunjukkan bahwa formasi yang dihasilkan menyerupai fase amorf dan formasi yang terbentuk pada puncak 2? = 28.01 diidentifikasi sebagai low quartz (SiO2). Dengan menggunakan microcal origin 6.0 diperoleh FWHM 0.18 dan menggunakan persamaan Scherer diperoleh rata-rata ukuran kristal 53.37 nm. Hasil pengukuan SEM menunjukkan bahwa rata-rata ukuran butir dari sampel bubuk slag nikel furnace bervariasi antara minimal 1?m dan maksimum 4 ?m. Berdasarkan pengukuran EDS diperoleh secara berturut-turut bahwa unsur utama penyusun paduan slag nikel furnace adalah Si 32.86 wt%, Mg 19.40 wt%, dan Fe 32.03 wt%.
PENINGKATAN HASIL BELAJAR FISIKA DENGAN MENERAPKAN MODEL PEMBELAJARAN ADVANCE ORGANIZER BERBANTU ANIMASI KOMPUTER
Authors: Hatika R. G.
Published: April 2018

Dalam usaha mendapatkan hasil belajar siswa yang baik maka tenaga pendidikan harus mempunyai strategi dalam melakukan pembelajaran. Salah satu model pembelajaran yang dapat digunakan yaitu Advance Organizer. Dalam hal menunjang penggunaan suatu model, maka diperlukannya penggunaan media pembelajaran tertentu, salah satu media yang dapat digunakan yaitu media animasi komputer. Sampel penelitian diambil berdasarkan Sampling Jenuh. Desain penelitian yang digunakan dalam penelitian ini adalah desain kelompok Two group posttest only. Hasil analisis daya serap dalam kategori baik, ketuntasan belajar secara klasikal sudah tuntas dan efektivitas pembelajaran adalah efektif. Ini berarti bahwa penggunaan model Advance Organizer berbantu animasi komputer adalah efektif digunakan dalam melihat hasil belajar fisika siswa SMA Rambah Hilir baik ditinjau melalui daya serap, ketuntasan belajar dan efektivitas pembelajarannya.In an effort to get the good results of student learning the teacher must have strategies for learning. One model of learning that can be used is Advance Organizer. In terms of supporting the use of a single model, there is a need for the use of specific instructional media. The media that can be used is computer animation media. The design used in this research was the group design of two group posttest only. The results of the analysis of absorption was in good, classical learning completeness has been completed and the effectiveness of learning was effective. This means that the use of model Advance Organizer assested computer animation is effective in view student learning outcomes of physics at SMA Rambah Hilir well reviewed through absorption, mastery learning and learning effectiveness.
THE IMPLEMENTATION OF LEARNING DEVICES WITH SCIENTIFIC APPROACH TO IMPROVE STUDENT LIFE SKILLS
Authors: Hikmawati H. , Rokhmat J. , Sutrio S.
Published: April 2018

The purpose of this study was to test the effectiveness of the implementation of learning device with scientific approach to improve student life skills. The research uses one group pre testpost test design. Subjects in this study were students of grade ten (class X). Implementation of learning device supports effectively in learning activities if the implementation of a lesson plan by teachers, student social skills and student academic skills at least in a good category. The results showed that the implementation of lesson plan by teachers to get the average value of 3.38 are in the very good category, gain value of the student social skill at average value of 3.03 is in the very good category, and gain of student academic skill at average value of 76 is in the good category. It concludes that the implementation of learning tools with scientific approach support effectively in learning activities.
ANALYSIS OF PROSPECTIVE PHYSICS TEACHERS� FEEDBACK ON ONLINE PEER-ASSESSMENT IMPLEMENTATION
Authors: Khusaini K.
Published: April 2018

This study aimed to analyse prospective physics teachers feedback during the implementation of online peer-assessment in Teaching Physics in English course. Twenty prospective physics teachers participated in this study. They were familiar with the use of smart phone in their daily life. They tend to communicate using social media such as WhatsApp application. The students have practiced in using paper based peer-assessment in other courses, but they have not applied it in online method providing real time feedback and score. The implementation of online peer-assessment challenged the students to assess their peer objectively. The lecturers feedback influence students skills how to evaluate their peer performance. Several factors may influence the quality of students online peer-assessment such as students culture back ground, implementation of the online peer-assessment, and practicants performance.
DETERMINANTS FACTORS ANALYSIS OF INDONESIAN STUDENTS� PHYSICS ACHIEVEMENT IN TIMSS 2011
Authors: Susongko P. , Fatkhurrahman M. A.
Published: April 2018

This study aimed to find the structure of the theoretical model that can illustrate the achievements of Indonesian students in the field of physics. This study also examines the variables that directly or indirectly influence the physics achievement of Indonesian students. The data in this study are data of TIMSS 2011 on physics test with population involved were 4572 Indonesian students grade 8. This research used path analysis from LISREL 8.30. The physics achievement model of Indonesian students based on TIMSS 2011 results are as follows: (1) physics achievement is directly influenced by self-confidence, interest in learning, and students 'attitudes toward the importance of physics; (2) physics achievement indirectly influenced by students' involvement in physics learning indicated from their interest and confidence in physics learning; (3) attitudes toward the importance of physics have an indirectly positive impact on physics achievement. Students' self-confidence in physics learning has a stronger direct influence on their achievements than their interest in physics.
As antoloxías consultadas da poesía galega: da Escolma de poesía galega IV. Os contemporáneos de Francisco Fernández del Riego aos Novísimos da poesía galega de María Victoria Moreno
Authors: Acuña Trabazo Ana
Published: April 2018

Este artigo pretende volver sobre a importancia da Escolma da poesía galega contemporánea (IV), publicada en 1955 por Francisco Fernández del Riego. A súa relevancia exemplificarase ao comparala con outras antoloxías consultadas e ao tratar a polémica suscitada entre os escritores galegos do momento.
Literatura timorense em língua portuguesa: os caminhos da consolidação
Authors: Ramos Ana Margarida
Published: April 2018

Pretende-se, com este estudo, traçar os rumos contemporâneos da literatura timorense em língua portuguesa nas últimas décadas, caracterizando o seu processo de emergência e primeiras tentativas de consolidação no contexto das literaturas pós-coloniais. Este estudo centrar-se-á na análise das produções mais recentes de Luís Cardoso e João Aparício, as duas vozes que, de forma mais consolidada, respetivamente no romance e na lírica, espelham as tendências da literatura timorense contemporânea.
O mundo de pernas para o ar ou da carnavalização no álbum de Manuela Bacelar
Authors: Rodrigues Carina
Published: April 2018

O presente estudo visa uma leitura breve das representações do tópico da carnavalização no álbum escrito e ilustrado por Manuela Bacelar ? criadora pioneira na edição deste segmento em Portugal. Refletindo sobre aspetos ligados ao tratamento narrativo e visual das obras da premiada artista plástica, procuraremos demonstrar como, com base no humor, no cómico e/ou na ironia, recorre à inversão do mundo ou à do próprio estereótipo, nas suas mais diversas variantes.
Análisis financiero-presupuestario en la provisión pública local, un caso práctico: Cercedo y Cotobade
Authors: Del Campo Villares Manuel Octavio , Ferreiro-Seoane Francisco Jesús , Camino-Santos Marta
Published: April 2018

La Administración Local, al ser la más próxima al ciudadano, es la que mejor conoce sus necesidades por lo que su eficiencia al prestar servicios básicos colectivos es alta. Sin embargo, para garantizar una óptima provisión de esos servicios requiere de una suficiencia financiera. Por ello, el estudio del estado financiero de nuestras Corporaciones Locales es prioritario, tarea donde además de las cuestiones financieras inciden otros múltiples aspectos. Este trabajo aborda la cuestión financiera a partir de los estados contables y ratios financieros aplicados a las entidades locales, midiendo así la capacidad evaluadora de estos indicadores financieros en relación a la situación económico-financiera de las entidades locales. El estudio, se basa en un análisis comparado acerca de la centralidad y dispersión de esos instrumentos, siendo las referencias utilizadas tanto las establecidas a partir de reglas empíricas como en los valores alcanzados por los indicadores de otras Corporaciones Locales de similar tamaño a nivel provincial y autonómico. Concluyendo con la proyección de los ratios del municipio investigado sobre las distintas referencias espaciales disponibles, obteniendo así una información relevante de la dirección a seguir para garantizar la provisión local.
Neocorporativismo y calidad en la educación superior pública mexicana
Authors: Dautrey Philippe Louis Charles
Published: April 2018

En el presente trabajo se aborda la relación entre el neocorporativismo –o sea, la transformación del antiguo corporativismo bajo la tutela del neoliberalismo– y la educación superior pública (centros de investigación, universidades federales y estatales) en México. En particular se considera el impacto del marco institucional y del contexto ideológico en la calidad, por la cual en los últimos años se incrementó la preocupación. Tanto la diseminación extrapolítica del poder de los directivos de las instituciones públicas, que circunscribe la autonomía de los docentes, como los programas federales, inspirados en la Nueva Gestión Pública de índole neoliberal, no remedian el legado del pasado, esto es, la tradicional orientación utilitarista de la educación superior. En todo ello el tema de la calidad está todavía pendiente. El avance hacia una burocracia legal-racional y el fortalecimiento de criterios cualitativos enfocados en mejorar el nivel académico del conocimiento producido y transmitido sigue representando un desafío cuya solución permitiría colmar la brecha cognitiva respecto al mundo desarrollado.
Los intelectuales en América Latina: la falta de ejemplaridad, el relativismo de valores y las ambivalencias del poder
Authors: Mansilla H. C. F.
Published: April 2018

El breve ensayo intenta criticar los valores de orientación y las pautas repetitivas del comportamiento práctico de los intelectuales progresistas en América Latina.  El texto enfatiza la falta de ejemplaridad de los intelectuales con respecto a los otros estratos sociales en los campos de la ética y de la praxis política. Los intelectuales actúan según valores convencionales (como dinero, poder, prestigio), pero reiteran discursos retóricos rutinarios, como la construcción de un modelo igualitario, cuando en realidad se hallan inmersos en estructuras jerárquicas piramidales.