bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Activation during Human Male Ejaculation
Authors: Holstege Gert , Georgiadis Janniko R. , Paans Anne M. J. , Meiners Linda C. , van der Graaf Ferdinand H. C. E. , Reinders A. A. T. Simone
Published: April 2018

Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation in heterosexual male volunteers. Manual penile stimulation was performed by the volunteer's female partner. Primary activation was found in the mesodiencephalic transition zone, including the ventral tegmental area, which is involved in a wide variety of rewarding behaviors. Parallels are drawn between ejaculation and heroin rush. Other activated mesodiencephalic structures are the midbrain lateral central tegmental field, zona incerta, subparafascicular nucleus, and the ventroposterior, midline, and intralaminar thalamic nuclei. Increased activation was also present in the lateral putamen and adjoining parts of the claustrum.

Neocortical activity was only found in Brodmann areas 7/40, 18, 21, 23, and 47, exclusively on the right side. On the basis of studies in rodents, the medial preoptic area, bed nucleus of the stria terminalis, and amygdala are thought to be involved in ejaculation, but increased rCBF was not found in any of these regions. Conversely, in the amygdala and adjacent entorhinal cortex, a decrease in activation was observed.

Remarkably strong rCBF increases were observed in the cerebellum. These findings corroborate the recent notion that the cerebellum plays an important role in emotional processing. The present study for the first time provides insight into which regions in the human brain play a primary role in ejaculation, and the results might have important implications for our understanding of how human ejaculation is brought about, and for our ability to improve sexual function and satisfaction in men.
A Receptor-Like Inositol Lipid Phosphatase Is Required for the Maturation of Developing Cochlear Hair Bundles
Authors: Goodyear R. J. , Legan P. K. , Wright M. B. , Marcotti W. , Oganesian A. , Coats S. A. , Booth C. J. , Kros C. J. , Seifert R. A. , Bowen-Pope D. F. , Richardson G. P.
Published: April 2018

A screen for protein tyrosine phosphatases (PTPs) expressed in the chick inner ear yielded a high proportion of clones encoding an avian ortholog of protein tyrosine phosphatase receptor Q (Ptprq), a receptor-like PTP. Ptprq was first identified as a transcript upregulated in rat kidney in response to glomerular nephritis and has recently been shown to be active against inositol phospholipids. An antibody to the intracellular domain of Ptprq, anti-Ptprq, stains hair bundles in mice and chicks. In the chick ear, the distribution of Ptprq is almost identical to that of the 275 kDa hair-cell antigen (HCA), a component of hair-bundle shaft connectors recognized by a monoclonal antibody (mAb) that stains inner-ear hair bundles and kidney glomeruli. Furthermore, anti-Ptprq immunoblots a 275 kDa polypeptide immunoprecipitated by the anti-HCA mAb from the avian inner ear, indicating that the HCA and Ptprq are likely to be the same molecule. In two transgenic mouse strains with different mutations in Ptprq, anti-Ptprq immunoreactivity cannot be detected in the ear. Shaft connectors are absent from mutant vestibular hair bundles, but the stereocilia forming the hair bundle are not splayed, indicating that shaft connectors are not necessary to hold the stereocilia together; however, the mice show rapid postnatal deterioration in cochlear hair-bundle structure, associated with smaller than normal transducer currents with otherwise normal adaptation properties, a progressive loss of basal-coil cochlear hair cells, and deafness. These results reveal that Ptprq is required for formation of the shaft connectors of the hair bundle, the normal maturation of cochlear hair bundles, and the long-term survival of high-frequency auditory hair cells.
Fast Synaptic Currents inDrosophilaMushroom Body Kenyon Cells Are Mediated by α-Bungarotoxin-Sensitive Nicotinic Acetylcholine Receptors and Picrotoxin-Sensitive GABA Receptors
Authors: Su Hailing , O'Dowd Diane K.
Published: April 2018

The mushroom bodies, bilaterally symmetric regions in the insect brain, play a critical role in olfactory associative learning. Genetic studies inDrosophilasuggest that plasticity underlying acquisition and storage of memory occurs at synapses on the dendrites of mushroom body Kenyon cells (Dubnau et al., 2001). Additional exploration of the mechanisms governing synaptic plasticity contributing to these aspects of olfactory associative learning requires identification of the receptors that mediate fast synaptic transmission in Kenyon cells. To this end, we developed a culture system that supports the formation of excitatory and inhibitory synaptic connections between neurons harvested from the central brain region of late-stageDrosophilapupae. Mushroom body Kenyon cells are identified as small-diameter, green fluorescent protein-positive (GFP+) neurons in cultures from OK107-GAL4;UAS-GFP pupae. In GFP+ Kenyon cells, fast EPSCs are mediated by α-bungarotoxin-sensitive nicotinic acetylcholine receptors (nAChRs). The miniature EPSCs have rapid rise and decay kinetics and a broad, positively skewed amplitude distribution. Fast IPSCs are mediated by picrotoxin-sensitive chloride conducting GABA receptors. The miniature IPSCs also have a rapid rate of rise and decay and a broad amplitude distribution. The vast majority of spontaneous synaptic currents in the cultured Kenyon cells are mediated byα-bungarotoxin-sensitive nAChRs or picrotoxin-sensitive GABA receptors. Therefore, these receptors are also likely to mediate synaptic transmission in Kenyon cellsin vivoand to contribute to plasticity during olfactory associative learning.
Receptive Field Plasticity Profoundly Alters the Cutaneous Parallel Fiber Synaptic Input to Cerebellar InterneuronsIn Vivo
Authors: Jörntell Henrik , Ekerot Carl-Fredrik
Published: April 2018

The cutaneous parallel fiber (PF) receptive fields of cerebellar stellate and basket cells in the cerebellar C3 zonein vivoare normally very small but can be dramatically enlarged by climbing fiber (CF)-dependent plasticity. To analyze the effects of this receptive field plasticity, we present for the first time whole-cell patch-clamp recordings from these interneurons during natural and electrical activation of cutaneously driven synaptic input. In “naive” interneurons, peripheral input nearly exclusively activated a few (two to eight) large PF EPSPs from a specific small skin area that overlapped the receptive field of the local CF input. After conjunctive PF and CF stimulation, numerous small and large EPSPs and ramp-like depolarizations could be activated from the entire forelimb skin. These findings therefore confirm previous suggestions that conjunctive PF and CF activation leads to a long-lasting potentiation of PF synaptic input to interneurons. The CF response, which is crucial for the induction of the PF synaptic potentiation, was strong but variable and very different from the conventional EPSPs evoked by PFs.
Ionic Mechanisms of Burst Firing in Dissociated Purkinje Neurons
Authors: Swensen Andrew M. , Bean Bruce P.
Published: April 2018

Cerebellar Purkinje neurons have intrinsic membrane properties that favor burst firing, seen not only during complex spikes elicited by climbing fiber input but also with direct electrical stimulation of cell bodies. We examined the ionic conductances that underlie all-or-none burst firing elicited in acutely dissociated mouse Purkinje neurons by short depolarizing current injections. Blocking voltage-dependent calcium entry by cadmium or replacement of external calcium by magnesium enhanced burst firing, but it was blocked by cobalt replacement of calcium, probably reflecting block of sodium channels. In voltage-clamp experiments, we used the burst waveform of each cell as a voltage command and used ionic substitutions and pharmacological manipulations to isolate tetrodotoxin (TTX)-sensitive sodium current, P-type and T-type calcium current, hyperpolarization-activated cation current (Ih), voltage-activated potassium current, large-conductance calcium-activated potassium current, and small-conductance calcium-activated potassium (SK) current. Measured near the middle of the first interspike interval, TTX-sensitive sodium current carried the largest inward current, and T-type calcium current was also substantial. Current through P-type channels was large immediately after a spike but decayed rapidly. These inward currents were opposed by substantial components of voltage-dependent and calcium-dependent potassium current. Termination of the burst is caused partly by decay of sodium current, together with a progressive buildup of SK current after the first interspike interval. Although burst firing depends on the net balance between multiple large currents flowing after a spike, it is surprisingly robust, probably reflecting complex interactions between the exact voltage waveform and voltage and calcium dependence of the various currents.
Neural Correlates of Rewarded and Unrewarded Eye Movements in the Primate Caudate Nucleus
Authors: Watanabe Katsumi , Lauwereyns Johan , Hikosaka Okihide
Published: April 2018

The prospect of immediate reward elicits goal-oriented behavior. However, animals often have to perform actions that do not immediately lead to reward in the pursuit of a long-term goal. Here we identify neural activity in monkey caudate nucleus that specifically correlates with rewarded and unrewarded eye movements. The monkey performed a visually guided saccade task in which only one position was associated with positive reinforcement. To advance in the experimental session, however, the monkey had no choice but to complete a saccade to an unrewarded position as well as to a rewarded position. Some caudate saccadic neurons showed enhanced activity around the time of the saccade in rewarded trials (rewarded-saccade neurons). Another subset of neurons discharged selectively around the execution of the saccade in unrewarded trials (unrewarded-saccade neurons). In both rewarded and unrewarded trials, stronger activity of these neurons was associated with reduced saccade latency. These results suggest that both rewarded and unrewarded saccades are facilitated by caudate saccadic activity. The neuronal activity of unrewarded-saccade neurons might reflect the required execution of unrewarded eye movements on the way to future reward.
Capsazepine Protects against Neuronal Injury Caused by Oxygen Glucose Deprivation by InhibitingIh
Authors: Ray Alison M. , Benham Ceri D. , Roberts Jenny C. , Gill Catherine H. , Lanneau Christophe , Gitterman Danniel P. , Harries Mark , Davis John B. , Davies Christopher H.
Published: April 2018

Cell death mechanisms frequently involve the influx of extracellular calcium through voltage- and ligand-gated ion channels, e.g., the NMDA receptor (Greene, 1999). The vanilloid receptor (VR1) is present in regions of the brain (Mezey et al., 2000) that are highly susceptible to neurodegenerative insults, suggesting that this ion channel might contribute to the cellular processes involved in neuronal death. We tested the effects of VR1 ligands in the oxygen glucose deprivation (OGD) model of cell death in organotypic hippocampal slice cultures. The VR1agonist capsaicin at concentrations that are selective for VR1did not affect cell viability per se or the extent of neurodegeneration induced by the OGD insult. In contrast, the VR1antagonist capsazepine (0.1-10 μm) significantly reduced the amount of OGD-induced cell death. However, capsazepine was still neuroprotective in slices prepared from VR1knock-out mice, which exhibited the same degree of neurodegeneration to that observed in slices prepared from wild-type mice, excluding the possibility that it afforded neuroprotection through inhibition of VR1. Instead, capsazepine inhibited the hyperpolarization-activated nonspecific cation channel generated currentIhin a concentration range similar to that which was neuroprotective. Furthermore, the specificIhblocker ZD-7288 was also neuroprotective, mirroring the effects of capsazepine, in that it was effective at preventing cell death when applied either during or after the OGD insult. These results demonstrate that capsazepine affords neuroprotection through inhibition ofIhrather than inhibition of VR1.
Different Roles for Simple-Cell and Complex-Cell Inhibition in V1
Authors: Lauritzen Thomas Z. , Miller Kenneth D.
Published: April 2018

Previously, we proposed a model of the circuitry underlying simple-cell responses in cat primary visual cortex (V1) layer 4. We argued that the ordered arrangement of lateral geniculate nucleus inputs to a simple cell must be supplemented by a component of feedforward inhibition that is untuned for orientation and responds to high temporal frequencies to explain the sharp contrast-invariant orientation tuning and low-pass temporal frequency tuning of simple cells. The temporal tuning also requires a significant NMDA component in geniculocortical synapses. Recent experiments have revealed cat V1 layer 4 inhibitory neurons with two distinct types of receptive fields (RFs): complex RFs with mixed ON/OFF responses lacking in orientation tuning, and simple RFs with normal, sharp-orientation tuning (although, some respond to all orientations). We show that complex inhibitory neurons can provide the inhibition needed to explain simple-cell response properties. Given this complex cell inhibition, antiphase or “push-pull” inhibition from tuned simple inhibitory neurons acts to sharpen spatial frequency tuning, lower responses to low temporal frequency stimuli, and increase the stability of cortical activity.
μ-Opioid Receptor Desensitization in Mature Rat Neurons: Lack of Interaction between DAMGO and Morphine
Authors: Bailey Christopher P. , Couch Daniel , Johnson Elizabeth , Griffiths Katie , Kelly Eamonn , Henderson Graeme
Published: April 2018

μ-Opioid receptors (MORs) exhibit rapid desensitization and internalization during exposure to various opioid agonists. In some studies, however, morphine has been observed to produce little MOR desensitization or internalization. We examined desensitization in mature rat locus ceruleus (LC) neurons and confirmed that morphine is a very poor desensitizing agent, whereas [d-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAMGO), a high-efficacy agonist, and methadone, an agonist we observed to be of equivalent efficacy to morphine, produced profound rapid desensitization. Similarly, by measuring plasma membrane receptor levels in HEK293 cells stably expressing T7-epitope-tagged rat MOR1 at near physiological levels (HEK293-MOR1 cells), DAMGO and methadone but not morphine caused rapid MOR internalization. It has been reported that a low concentration of DAMGO, coapplied with morphine, caused morphine to induce MOR internalization. We examined whether this interaction occurred in mature mammalian neurons at the level of receptor desensitization. Coapplication of low concentrations of DAMGO did not increase morphine-induced desensitization in LC neurons but caused a lesser degree of desensitization than DAMGO alone. We also failed to observe an enhancement by DAMGO of morphine-induced desensitization in the electrically stimulated guinea pig ileum myenteric plexus-longitudinal muscle preparation. In HEK293-MOR1 cells, low concentrations of DAMGO did not convert morphine into a receptor-internalizing agent. The data presented here fail to support the theory that low concentrations of DAMGO can increase morphine-induced MOR desensitization or internalization.
Pathogenesis of X-Linked Charcot-Marie-Tooth Disease: Differential Effects of Two Mutations in Connexin 32
Authors: Abrams Charles K. , Freidin Mona , Bukauskas Feliksas , Dobrenis Kostantin , Bargiello Thaddeus A. , Verselis Vytas K. , Bennett Michael V. L. , Chen Lei , Sahenk Zarife
Published: April 2018

X-Linked Charcot-Marie-Tooth disease is an inherited peripheral neuropathy arising in patients with mutations in the gene encoding connexin 32 (Cx32). Cx32 is expressed at the paranodes and Schmidt-Lantermann incisures of myelinating Schwann cells in which it is believed to form a reflexive pathway between the abaxonal and adaxonal cytoplasmic domains. Patients with the Val181Ala (V181A) mutation have a severe peripheral neuropathy. Experiments using a nude mouse xenograft system show that Schwann cells expressing only this mutant form of Cx32 are profoundly impaired in their ability to support the earliest stages of regeneration of myelinated fibers. Coupling between pairedXenopusoocytes expressing V181A is reduced compared with the coupling between oocytes expressing wild-type human Cx32 (32WT), and protein levels assayed by Western blot are substantially lower. Immunocytochemisty shows thatNeuro2a cells expressing the V181A mutant have very few gap junction plaques compared with cells expressing 32WT; Cx32 protein levels are lower in these cells than in those expressing 32WT. Because failure of normal regeneration is evident before formation of myelin, loss of function of Cx32 may impact on the function of precursors of the myelinating Schwann cell before the formation of the hypothesized reflexive pathway. The Glu102Gly (E102G) mutation leads to a milder phenotype. Early regeneration is normal in grafts with Schwann cells expressing the E102G mutant. The only abnormality detected in the behavior of its channel is increased sensitivity to acidification-induced closure, a property that may lead to reduced gap junction coupling during periods of metabolic stress. This restricted functional abnormality may explain the relatively mild phenotype seen in the xenograft model and in E102G patients.
Hypoglycemic Neuronal Death and Cognitive Impairment Are Prevented by Poly(ADP-Ribose) Polymerase Inhibitors Administered after Hypoglycemia
Authors: Suh Sang Won , Aoyama Koji , Chen Yongmei , Garnier Philippe , Matsumori Yasuhiko , Gum Elizabeth , Liu Jialing , Swanson Raymond A.
Published: April 2018

Severe hypoglycemia causes neuronal death and cognitive impairment. Evidence suggests that hypoglycemic neuronal death involves excitotoxicity and DNA damage. Poly(ADP-ribose) polymerase-1 (PARP-1) normally functions in DNA repair, but promotes cell death when extensively activated by DNA damage. Cortical neuron cultures were subjected to glucose deprivation to assess the role of PARP-1 in hypoglycemic neuronal death. PARP-1-/-neurons and wild-type, PARP-1+/+neurons treated with the PARP inhibitor 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone both showed increased resistance to glucose deprivation. A rat model of insulin-induced hypoglycemia was used to assess the therapeutic potential of PARP inhibitors after hypoglycemia. Rats subjected to severe hypoglycemia (30 min EEG isoelectricity) accumulated both nitrotyrosine and the PARP-1 product, poly(ADP-ribose), in vulnerable neurons. Treatment with PARP inhibitors immediately after hypoglycemia blocked production of poly(ADP-ribose) and reduced neuronal death by >80% in most brain regions examined. Increased neuronal survival was also achieved when PARP inhibitors were administered up to 2 hr after blood glucose correction. Behavioral and histological assessments performed 6 weeks after hypoglycemia confirmed a sustained salutary effect of PARP inhibition. These results suggest that PARP-1 activation is a major factor mediating hypoglycemic neuronal death and that PARP-1 inhibitors can rescue neurons that would otherwise die after severe hypoglycemia.
Distinct Populations of Forebrain Neural Stem and Progenitor Cells Can Be Isolated Using Side-Population Analysis
Authors: Kim Mina , Morshead Cindi M.
Published: April 2018

The absence of stem cell-specific markers has posed challenges to the identification and isolation of stem cells. We report the isolation of a discrete and highly enriched population of neural stem cells from clonally derived colonies of neural stem cell and progenitor cells (neurospheres) after exposure to the fluorescent DNA binding dye Hoeschst 33342 and subsequent analysis via dual wavelength flow cytometry. The low fluorescent side population comprised only 3.6% of all live cells sorted yet contained >99% of all the neural stem cells as assayed by the formation of neurospheres in culture. Most neurosphere-derived cells are progenitor cells, and these are found within the higher fluorescence (non-side population) fraction. The isolation of a highly enriched population of self-renewing, multipotential neural stem cells was seen from both adult- and embryonic-derived neurospheres; however, the relative percentage of cells comprising the side-population and the mechanism of dye efflux varied between adult and embryonic donor tissue. Combining the side-population analysis with markers recently shown to enrich for neural stem cells afforded no further enrichment in the case of peanut agglutinin expression and size criteria; however, when the side-population analysis was combined with Lewis X (LeX) expression, a slight enrichment was seen over side-population analysis alone.
Primordial Hematopoietic Stem Cells Generate Microglia But Not Myelin-Forming Cells in a Neural Environment
Authors: Vitry Sandrine , Bertrand Julien Y. , Cumano Ana , Dubois-Dalcq Monique
Published: April 2018

Finding ways to enhance remyelination is a major challenge in treating demyelinating diseases. Recent studies have suggested that circulating bone marrow cells can home in brain and transdifferentiate into neural cells. To ask whether hematopoietic precursors can form myelinating cells, we investigated the neuropoietic potential of embryonic precursors sorted from the mouse aorta-gonads-mesonephros (AGM) region. This cell fraction is capable of long-term hematopoietic reconstitution and generates colonies containing multipotential precursors and lymphoid or erythro-myeloid progenies. When cultured in hematopoietic growth conditions, a fraction of CD45-positive AGM cells coexpress neural markers such as nestin, the polysialylated form of neural cell adhesion molecule, the βIII tubulin isoform, and glial fibrillary acidic protein. However, when hematopoietic precursors containing green fluorescent protein were cocultured with embryonic striatal precursors into neurospheres, they maintained their hematopoietic phenotype without undergoing differentiation into neurons, astrocytes, or oligodendrocytes. After intraventricular grafting, hematopoietic precursors integrated into the brain of wild-type or hypomyelinated newbornshiverermice and gave rise to microglia but not neurons or glia. In contrast, when wild-type embryonic striatal neurospheres were grafted inshiverer, they formed numerous myelin internode patches. Even when neural and hematopoietic precursors were grafted together intoshiverermice, only neural precursors generated myelin-forming cells and synthesized myelin. Thus, embryonic neurospheres have myelin repair properties not shown by embryonic hematopoietic precursors. This suggests that the use of multipotential neural precursors to generate myelin-forming cells remains one of the most promising avenues toward remyelination therapies.
Opioid Modulation of Scratching and Spinal c-fosExpression Evoked by Intradermal Serotonin
Authors: Nojima Hiroshi , Simons Christopher T. , Cuellar Jason M. , Carstens Mirela Iodi , Moore Justin A. , Carstens Earl
Published: April 2018

We investigated a spinal site for opioid modulation of itch-related scratching behavior in rats. Intradermal 5-HT (2%, 10 μl) elicited intermittent bouts of hindlimb scratching directed toward the injection site (nape of neck) beginning within minutes and lasting >1 hr. 5-HT-evoked scratching was significantly reduced by systemic administration of the opiate antagonist naltrexone but was not affected by systemic morphine at a dosage (3 mg/kg) that induces analgesia. Intradermal 5-HT elicited a significant increase in c-fos-like immunoreactivity (FLI) in superficial laminas I-III at the lateral aspect of the cervical C3-C6 dorsal horn compared with controls receiving intradermal saline. Neither systemic morphine nor naltrexone significantly affected counts of 5-HT-evoked FLI. The lack of effect of morphine suggests that intradermal 5-HT activates dorsal horn neurons, signaling itch but not pain. Attenuation of 5-HT-evoked scratching but not spinal FLI by naltrexone suggests a supraspinal site for its antipruritic action. In contrast, morphine significantly attenuated FLI elicited by intradermal capsaicin, a chemical that induces pain but not scratching.
Gene Profile of Electroconvulsive Seizures: Induction of Neurotrophic and Angiogenic Factors
Authors: Newton Samuel S. , Collier Emily F. , Hunsberger Joshua , Adams David , Terwilliger Rose , Selvanayagam Emmanuel , Duman Ronald S.
Published: April 2018

Electroconvulsive seizure therapy (ECS) is a clinically proven treatment for depression and is often effective even in patients resistant to chemical antidepressants. However, the molecular mechanisms underlying the therapeutic efficacy of ECS are not fully understood. One theory that has gained attention is that ECS and other antidepressants increase the expression of select neurotrophic factors that could reverse or block the atrophy and cell loss resulting from stress and depression. To further address this topic, we examined the expression of other neurotrophic-growth factors and related signaling pathways in the hippocampus in response to ECS using a custom growth factor microarray chip. We report the regulation of several genes that are involved in growth factor and angiogenic-endothelial signaling, including neuritin, stem cell factor, vascular endothelial growth factor (VEGF), VGF (nonacronymic), cyclooxygenase-2, and tissue inhibitor of matrix metalloproteinase-1. Some of these, as well as other growth factors identified, including VEGF, basic fibroblast growth factor, and brain-derived neurotrophic factor, have roles in mediating neurogenesis and cell proliferation in the adult brain. We also examined gene expression in the choroid plexus and found several growth factors that are enriched in this vascular tissue as well as regulated by ECS. These data suggest that an amplification of growth factor signaling combined with angiogenic mechanisms could have an important role in the molecular action of ECS. This study demonstrates the applicability of custom-focused microarray technology in addressing hypothesis-driven questions regarding the action of antidepressants.
Priming Stimulation Enhances the Depressant Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation
Authors: Iyer Meenakshi B. , Schleper Nicole , Wassermann Eric M.
Published: April 2018

Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) can depress the excitability of the cortex locally and has been proposed for the treatment of disorders such as schizophrenia and epilepsy. Some have speculated that the depressant effect is related to long-term depression (LTD) of cortical synapses. Becausein vitroLTD can be enhanced by pretreatment of synapses with higher-frequency stimulation, we hypothesized that if rTMS depression had mechanisms in common with LTD, higher-frequency priming would increase it also. In 25 healthy volunteers in two experiments, we measured motor-evoked potentials (MEPs) from TMS of the motor cortex to define the baseline response. Subthreshold rTMS (6 Hz, fixed rate or frequency modulated) was used to prime the motor cortex, followed by suprathreshold 1 Hz stimulation for 10 min at just above the MEP threshold. Over the next 60 min, we recorded MEPs every 10 sec and found significant increases in the amount of cortical depression with both types of 6 Hz priming rTMS relative to sham. The MEP depression from 6 Hz-primed 1 Hz rTMS showed no evidence of decay after 60 min. Pretreatment with 6 Hz primes both 1 Hz rTMS depression and LTD. Although not conclusive evidence, this strengthens the case for overlapping mechanisms and suggests a potent new technique for enhancing low-frequency rTMS depression that may have experimental and clinical applications.
Sustained Ca2+Entry Elicits Transient Postsynaptic Currents at a Retinal Ribbon Synapse
Authors: Singer Joshua H. , Diamond Jeffrey S.
Published: April 2018

Night (scotopic) vision is mediated by a distinct retinal circuit in which the light responses of rod-driven neurons are faster than those of the rods themselves. To investigate the dynamics of synaptic transmission at the second synapse in the rod pathway, we made paired voltage-clamp recordings from rod bipolar cells (RBCs) and postsynaptic AII and A17 amacrine cells in rat retinal slices. Depolarization of RBCs from -60 mV elicited sustained Ca2+currents and evoked AMPA receptor (AMPAR)-mediated EPSCs in synaptically coupled amacrine cells that exhibited large, rapidly rising initial peaks that decayed rapidly to smaller, steady-state levels. The transient component persisted in the absence of feedback inhibition to the RBC terminal and when postsynaptic AMPA receptor desensitization was blocked with cyclothiazide, indicating that it reflects a time-dependent decrease in the rate of exocytosis from the presynaptic terminal. The EPSC waveform was similar when RBCs were recorded in perforated-patch or whole-cell configurations, but asynchronous release from RBCs was enhanced when the intraterminal Ca2+buffer capacity was reduced. When RBCs were depolarized from -100 mV, inactivating, low voltage-activated (T-type channel-mediated) Ca2+currents were evident. Although Ca2+influx through T-type channels boosted vesicle release, as reflected by larger EPSCs, it did not make the EPSCs faster, indicating that activation of T-type channels is not necessary to generate a transient phase of exocytosis. We conclude that the time course of vesicle release from RBCs is inherently transient and, together with the fast kinetics of postsynaptic AMPARs, speeds transmission at this synapse.
Apoptosis Induced by p75NTR Overexpression Requires Jun Kinase-Dependent Phosphorylation of Bad
Authors: Bhakar Asha L. , Howell Jenny L. , Paul Christine E. , Salehi Amir H. , Becker Esther B. E. , Said Farid , Bonni Azad , Barker Philip A.
Published: April 2018

The p75 neurotrophin receptor (p75NTR), a member of the tumor necrosis factor receptor superfamily, facilitates apoptosis during development and after injury to the CNS. The signaling cascades activated by p75NTR that result in apoptosis remain poorly understood. In this study, we show that overexpression of p75NTR in primary cortical neurons, in pheochromocytoma cell line (PC12) cells, and in glioma cells results in activation of Jun kinase (JNK), accumulation of cytochromecwithin the cytosol, and activation of caspases 9, 6, and 3. To link p75NTR-dependent JNK activation to mitochondrial cytochromecrelease, regulation of BH3-domain-only family members was examined. Transcription of BH3-domain-only family members was not induced by p75NTR, but p75NTR-dependent JNK activation resulted in phosphorylation and oligomerization of the BH3-domain-only family member Bad. Loss of function experiments using Bad dominant negatives or RNA interference demonstrated a requirement for Bad in p75NTR-induced apoptosis. Together, these studies provide the first data linking apoptosis induced by p75NTR to the phosphorylation of BH3-domain-only family members.
Imaging Reveals Synaptic Targets of a Swim-Terminating Neuron in the Leech CNS
Authors: Taylor Adam L. , Cottrell Garrison W. , Kleinfeld David , Kristan William B.
Published: April 2018

In the leech, the command-like neuron called cell Tr2 is known to stop swimming, but the connections from cell Tr2 to the swim central pattern generator have not been identified. We used fluorescence resonance energy transfer voltage-sensitive dyes to identify three neurons that are synaptic targets of cell Tr2. We then used electrophysiological techniques to show that these connections are monosynaptic, chemical, and excitatory. Two of the novel targets, cell 256 and cell 54, terminate swimming when stimulated. These neurons are likely to mediate swim cessation caused by cell Tr2 activity, and thus play the role of intermediate control cells in the leech CNS.
Oxidative Stress Is Responsible for Deficient Survival and Dendritogenesis in Purkinje Neurons from Ataxia-Telangiectasia Mutated Mutant Mice
Authors: Chen Philip , Peng Cheng , Luff John , Spring Kevin , Watters Dianne , Bottle Steven , Furuya Shigeki , Lavin Martin F.
Published: April 2018

Atmgene-disrupted mice recapitulate the majority of characteristics observed in patients with the genetic disorder ataxia-telangiectasia (A-T). However, although they exhibit defects in neuromotor function and a distinct neurological phenotype, they do not show the progressive neurodegeneration seen in human patients, but there is evidence that ataxia-telangiectasia mutated (Atm)-deficient animals have elevated levels of oxidized macromolecules and some neuropathology. We report here thatin vitrosurvival of cerebellar Purkinje cells from bothAtm“knock-out” andAtm“knock-in” mice was significantly reduced compared with their wild-type littermates. Although most of the Purkinje neurons from wild-type mice exhibited extensive dendritic elongation and branching under these conditions, most neurons fromAtm-deficient mice had dramatically reduced dendritic branching. An antioxidant (isoindoline nitroxide) prevented Purkinje cell death inAtm-deficient mice and enhanced dendritogenesis to wild-type levels. Furthermore, administration of the antioxidant throughout pregnancy had a small enhancing effect on Purkinje neuron survival inAtmgene-disrupted animals and protected against oxidative stress in older animals. These data provide strong evidence for a defect in the cerebellum ofAtm-deficient mice and suggest that oxidative stress contributes to this phenotype.
Mirror Neuron Populations Represent Sequences of Behavioral Epochs During Both Execution and Observation
Authors: Mazurek Kevin A. , Rouse Adam G. , Schieber Marc H.
Published: April 2018

Mirror neurons (MNs) have the distinguishing characteristic of modulating during both execution and observation of an action. Although most studies of MNs have focused on various features of the observed movement, MNs also may monitor the behavioral circumstances in which the movement is embedded, including time periods preceding and following the observed movement. Here, we recorded multiple MNs simultaneously from implanted electrode arrays as two male monkeys executed and observed a reach, grasp, and manipulate task involving different target objects. MNs were recorded from premotor cortex (PM-MNs) and primary motor cortex (M1-MNs). During execution trials, hidden Markov models (HMMs) applied to the activity of either PM-MN or M1-MN populations most often detected sequences of four hidden states, which we named according to the behavioral epoch during which each state began: initial, reaction, movement, and final. The hidden states of MN populations thus reflected not only the movement, but also three behavioral epochs during which no movement occurred. HMMs trained on execution trials could decode similar sequences of hidden states in observation trials, with complete hidden state sequences decoded more frequently from PM-MN populations than from M1-MN populations. Moreover, population trajectories projected in a 2D plane defined by execution trials were preserved in observation trials more for PM-MN than for M1-MN populations. These results suggest that MN populations represent entire behavioral sequences, including both movement and non-movement. PM-MN populations showed greater similarity than M1-MN populations in their representation of behavioral sequences during execution versus observation.

SIGNIFICANCE STATEMENTMirror neurons (MNs) are thought to provide a neural mechanism for understanding the actions of others. However, for an action to be understood, both the movement per se and the non-movement context before and after the movement need to be represented. We found that simultaneously recorded MN populations encoded sequential hidden neural states corresponding approximately to sequential behavioral epochs of a reach, grasp, and manipulate task. During observation trials, hidden state sequences were similar to those identified in execution trials. Hidden state similarity was stronger for MN populations in premotor cortex than for those in primary motor cortex. Execution/observation similarity of hidden state sequences may contribute to understanding the actions of others without actually performing the action oneself.
VAKUM KURUTMA YÖNTEMİ KULLANILARAK ÜRETİLEN SADE VE MEYVELİ BAL TOZLARININ BAZI FİZİKSEL, KİMYASAL VE DUYUSAL ÖZELLİKLERİNİN BELİRLENMESİ
Authors: ERBAS Mustafa , MUTLU Ceren
Published: April 2018

Araştırmada; vakum kurutma yöntemi ile balın biyoaktif
bileşenlerini koruyarak sade ve meyveli bal tozu (karadut, çilek ve portakal)
üretimi ve üretilen bal tozlarının soğuk içecek hazırlamak için bal tozu
karışımlarına dönüştürülmesi amaçlanmıştır. Bal tozu örneklerine; fiziksel,
kimyasal ve duyusal analizler yapılmıştır. Bal tozu örneklerinin sıkıştırılmış
yığın yoğunluğu ve hacim ağırlıklı ortalama partikül boyutu değerlerinin
sırasıyla 0.60-0.85 g/cm3 ve 79.99-198.88 µm ve çözünürlüklerin ise
%90 değerinin üzerinde olduğu belirlenmiştir. Bal tozu örneklerinin nem içeriği
ve su aktivitesi değerlerinin sırasıyla %2.77-4.30 ve 0.27-0.33 olduğu tespit
edilmiştir. Üretimde kullanılan balın ve sade bal tozunun diastaz sayılarının
sırasıyla 10.51 ve 9.58 olduğu belirlenmiştir. Duyusal analiz sonucunda, genel
beğeni parametresinin 5 puanlık hedonik skala üzerinden 3 değerinin üzerinde
puan aldığı ve çilek suyu içeren örneklerin daha çok beğenildiği
belirlenmiştir.
Komputasi Grid Menggunakan Globus untuk Menghitung Opsi Put Amerika dengan Simulasi Monte Carlo
Authors: Purwinarko Aji , Pulungan Reza
Published: April 2018

Internet dan teknologi komputasi grid mengubah cara kita mengatasi masalah yang kompleks. Komputasi grid terus menjanjikan untuk memberikan kemampuan yang tinggi dari berbagai sistem dan teknik komputasi. Kemampuan mendistribusikan aplikasi pada beberapa mesin adalah salah satu aspek kunci dari komputasi grid. Salah satu penyedia librari komputasi grid adalah Globus Toolkit. Komputasi grid ini dapat dimanfaatkan untuk menjalankan aplikasi opsi put Amerika dengan menggunakan simulasi Monte Carlo. Simulasi Monte Carlo dapat meramalkan harga saham yang akan terjadi. Dari hasil penelitian yang dilakukan, menunjukkan bahwa semakin banyak simulasi yang dilakukan maka semakin akurat nilai rata-rata harga saham. Hasil penelitian ini menunjukkan bahwa semakin banyak simulasi yang dilakukan, akan menghasilkan nilai opsi put yang konvergen dengan standard error yang kecil dan proses komputasi dengan menggunakan jumlah prosesor yang besar akan lebih cepat.
Pengembangan E-Stats Berbasis Web (Studi Kasus Universitas Negeri Semarang)
Authors: Arini Florentina Yuni
Published: April 2018

Saat ini, pengembangan e-learning berbasis web menjadi tren dalam dunia pendidikan. Oleh karena itu, dalam penelitian ini penulis mengembangkan E-Stats berbasis web bidang ilmu statistik yang secara khusus dikembangkan di Universitas Negeri Semarang (UNNES). E-Stats menyediakan layanan akses artikel, jurnal dan materi tentang statistik. Artikel dan abstrak jurnal statistik dapat diakses oleh umum. Sedangkan jika menjadi member memiliki prevelege untuk mendownload jurnal dan materi yang sudah di-upload. Bagi member dapat mendaftar melalui form registrasi yang disediakan di halaman registrasi web. Desain E-Stats melalui tahap prototype (analisis, perancangan, desain sistem, ERD dan desain skema database), pemrograman, pengujian dan pemeliharaan. Melalui E-Stats, pembelajaran statistika dapat diakses online tanpa batas ruang dan waktu.
Model Expertise Management System di Universitas Negeri Semarang
Authors: Purwinarko Aji , Sukestiyarno YL
Published: April 2018

Pemanfaatan sistem informasi sebagai penopang organisasi tidak dapat dipungkiri lagi, dimana setiap bagian dari organisasi diharapkan mampu memberikan pelayanan yang cepat dan akurat kepada setiap end user. Salah satu bentuk layanan sistem informasi tersebut adalah Expertise Management System (EMS). EMS dikembangkan di Universitas Negeri Semarang (UNNES) memiliki kemampuan untuk menyajikan data tentang pakar-pakar yang telah dimiliki UNNES kepada end user. Desain EMS melalui tahap prototype (analisis, perancangan, desain sistem, DFD, ERD, dan desain skema database), pemrograman, pengujian dan pemeliharaan. Melalui EMS ini pula, UNNES dapat menawarkan pakar-pakarnya untuk berkolaborasi dalam penelitian maupun kegiatan lainnya, sehingga dengan sendirinya akan memperkuat posisi UNNES di dalam persaingan tingkat regional maupun global.
Model Delone and Mclean Untuk Mengukur Kesuksesan E-Government Kota Pekalongan
Authors: Saputro Pujo Hari , Budiyanto Djoko , Santoso Joko
Published: April 2018

Pemerintah Kota Pekalongan saat ini sudah menjadi salah satu kota percontohan dalam penggunaan E-government di Indonesia, banyak sistem sudah diterapkan dan berhasil membantu dalam pelayanan pemerintah kota kepada masyarakat dan juga mempermudah dalam pekerjaan pegawai pemerintahan. Metode DeLone and McLean yaitu metode yang mempunyai 6 variabel evaluasi yaitu: information quality, system quality, service quality, use, user satisfaction dan net benefit. Metode DeLone and McLean akan digunakan sebagai model mengukur kesuksesan E- government dalam penggunaannya untuk membantu kinerja pegawai pemerintahan kota pekalongan. Dengan model ini diharapkan dapat diketahui komponen-komponen yang mendukung atau menghambat dalam penggunaan E-government, sehingga ke depan diharapkan dapat menjadi bahan evaluasi untuk perbaikan.
Análisis de las dinámicas socio-económicas campesinas colombianas en torno a la educación, 2006 – 2016
Authors: Bedoya Franco Paula Andrea , Cristancho Giraldo Laura Andrea
Published: April 2018

La educación, como instrumento que mejora la calidad de vida, se encuentra atada a las dinámicas socio-económicas en las que viven los individuos de una sociedad, ello determinará su ingreso y permanencia en el sistema escolar y por ende, la posterior formación en capital humano. En este artículo se expone dicha relación para las áreas rurales colombianas en la educación básica y media, a través de la revisión de la literatura, la caracterización del entorno rural y la evaluación de las políticas públicas para el periodo 2006-2016 como herramienta que contribuye al alcance educativo de los habitantes rurales. Se concluye que este vínculo entre el origen socio-económico y el logro educativo aún marca diferencias significativas entre los habitantes urbanos y rurales del país, y que se requieren esfuerzos por parte del sector público para el impulso de la educación como transformador de vida.
Inversión en infraestructura y crecimiento económico, relevancia de factores institucionales
Authors: Esquivel Monge Manfred , Loaiza Marín Kerry
Published: April 2018

Se cuantifica el efecto que tiene la inversión en infraestructura sobre el crecimiento económico y si está condicionado por factores de índole institucional mediante modelos dinámicos de panel con variables instrumentales y técnica GMM. Los resultados son coherentes con estudios previos en cuanto a la magnitud del efecto de la infraestructura sobre el crecimiento. Se halla evidencia de que factores institucionales inciden significativamente en el potencial efecto expansivo de la infraestructura. Se encuentra que países de América Latina estarían limitando el potencial expansivo de su inversión en infraestructura al presentar indicadores de desempeño institucional desfavorables. Lo mismo estaría sucediendo con países de ingreso medio y bajo.
Gestiones de la (a)sexualidad infantil: una lectura del campo de investigaciones de las ciencias sociales en el ámbito latinoamericano
Authors: González Pilar Anastasía
Published: April 2018

La (a)sexualidad infantil ha sido emplazada en discursos complejos yheterogéneos a lo largo de la historia. Actualmente contamos con un consenso de aparatos gubernamentales que reconoce una definición de sexualidad integral, positiva y amplia para la sexualidad adulta – tal es el caso de la definición de sexualidad de la OMS –, y sin embargo, cuando se refiere la sexualidad infantil, generalmente se la reduce a la prevención, restringiendo al mismo tiempo la noción de sexualidad a una sexualidad peligrosa. Esta operación que detectamos en una amplia variedad de discursos sociales se corresponde con enunciaciones del derecho internacional y a su vez con el estado de investigaciones sociales y humanas relativas a la infancia. El objetivo del presente artículo es poner en funcionamiento algunos significados dela estratificación de la sexualidad por edad, explicitando operaciones específicas del discurso social que la constituyen y (re)producen, especialmente en el campo de los discursos de derechos sexuales y reproductivos.
Successful treatment of herpes simplex-associated erythema multiforme with a combination of acyclovir and prednisone
Authors: Muryah Arny E. , Sufiawati Irna
Published: April 2018

Objective: Erythema Multiforme (EM) is an acute mucocutaneous hypersensitivity reaction triggered by certain infections and medications. EM induced by virus infection termed as Herpes- associated Erythema Multiforme (HAEM). The use of corticosteroids for treating HAEM has been a long debate issue. The aim of this case report is to present a patient with HAEM who was successfully treated with acyclovir combined with prednisone.Methods:A 31-years-old female, presented with a complaint of pain and diffuse ulcers in mouth. The patient reported recurrent episode of the ulcers of the mouth during the last two years. On extra oral examination, lips were crusted and bleeding. Intraoral examination revealed multiple diffuse ulcerations on mucosa. Nolesions were seen in other part of the body. Laboratory investigation revealed normal complete blood count and positive HSV-1 serology. The patient was diagnosed as HAEM.The patient was treated with acyclovir (1000 mg/day) and prednisone (10mg/day), topical mixture corticosteroid, chlorhexidine gluconate 0.2% and multivitaminduring seven days.Results:All lesions healed without any further clinical sequelae within 7 days.The clinical success of corticosteroids as effective anti-inflammatory agents is largely attributed to their ability to reduce the expression of pro-inflammatory genes, help to maintain vascular integrity and decrease the expression of leukocyte adhesion molecules.Conclusions:The addition of prednisone to acyclovir for HAEM resulted in a significant reduction of clinical signs and symptoms during the first week. The combination of acyclovir and corticosteroids may play an important role in the standard care for HAEM.
Emergency management of Ludwig’s angina: a case report
Authors: Alimin Nur H. , Syamsuddin Endang
Published: April 2018

Objective: Ludwig’s angina is a severe diffuse cellulitis in mandibular region that commonly caused by odontogenic infection. Due to its acute on onset, spread rapidly, involving the submandibular, sublingual region bilaterally and submental region, this condition consider as an emergency because it can cause airway obstruction.Methods: A 40 years old male patient came to Dr. Hasan Sadikin hospital emergency room with pain and swelling at lower jaw, drooling, hard to breath and limitation in opening his mouth. He was diagnosed with sepsis and Ludwig’s angina. Tracheostomy was performed to secure the airway, continued with teeth extraction, incision and drainage to eliminate the source of infection. Combination of intravenous antimicrobial was administered.Results: An advanced case of Ludwig’s angina and its management was reported. The patient showed a good response to the treatment and the condition was improved.Conclusion: Ludwig’s angina is a rare emergency condition which potentially life-threatening. Patient showed a significant recovery due to immediate and rapid management in securing airway patency and infection source control to prevent the spread of infection and further complications.