bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serotonin Release Evoked by Tail Nerve Stimulation in the CNS ofAplysia: Characterization and Relationship to Heterosynaptic Plasticity
Authors: Marinesco Stéphane , Carew Thomas J. 
Published: April 2018

Considerable experimental evidence suggests that serotonin (5-HT) at sensory neuron→motor neuron (SN→MN) synapses, as well as other neuronal sites, contributes importantly to simple forms of learning such as sensitization and classical conditioning inAplysia. However, the actual release of 5-HT in the CNS induced by sensitizing stimuli such as tail shock has not been directly demonstrated. In this study, we addressed this question by (1) immunohistochemically labeling central 5-HT processes and (2) directly measuring with chronoamperometry the release of 5-HT induced by pedal tail nerve (P9) shock onto tail SNs in the pleural ganglion and their synapses onto tail MNs in the pedal ganglion.We found that numerous 5-HT-immunoreactive fibers surround both the SN cell bodies in the pleural ganglion and SN axons in the pedal ganglion. Chronoamperometric detection of 5-HT performed with carbon fiber electrodes implanted in the vicinity of tail SN somata and synapses revealed an electrochemical 5-HT signal lasting ∼40 sec after a brief shock of P9. 5-HT release was restricted to discrete subregions (modulatory fields) of the CNS, including the vicinity of tail SN soma and synapses ipsilateral to the stimulation. Increasing P9 shock frequency augmented the amplitude of the 5-HT signal and, in parallel, increased SN excitability and SN synaptic transmission onto tail MNs. However, the relationship between the amount of 5-HT release and the two forms of SN plasticity was not uniform: SN excitability increased in a graded manner with increased 5-HT release, whereas synaptic facilitation exhibited a highly nonlinear relationship. The development of chronoamperometric techniques inAplysianow paves the way for a more complete understanding of the contribution of the serotonergic modulatory pathway to memory processing in this system.
Electrotonically Mediated Oscillatory Patterns in Neuronal Ensembles: AnIn VitroVoltage-Dependent Dye-Imaging Study in the Inferior Olive
Authors: Leznik Elena , Makarenko Vladimir , Llinás Rodolfo 
Published: April 2018

Spatiotemporal profiles of ensemble subthreshold neuronal oscillation were studied in brainstem slices using high-speed voltage-sensitive dye imaging. After local electrical stimuli, the overall voltage profile demonstrated coherent oscillatory waves that spread over the inferior olive (IO). These oscillations were also observed in concurrently obtained intracellular recordings from IO neurons. Over the first few seconds after the stimuli, the optically recorded oscillations clustered into coherent groups comprising hundreds of neurons. Statistical analysis of the spatial profiles of these clusters revealed size fluctuation around stable core regions that were surrounded by a rim the diameter of which varied in time during the oscillation period.The neuronal ensemble oscillations were calcium derived and had an average frequency range of 1–7 Hz. This rhythmic response demonstrated a different spatiotemporal distribution in the presence of picrotoxin, which induced the merging of neuronal clusters into larger areas of coherent activity. The possibility that such clustering is a consequence of intrinsic oscillations in ensembles of coupled neurons was tested using mathematical modeling.
D5 (Not D1) Dopamine Receptors Potentiate Burst-Firing in Neurons of the Subthalamic Nucleus by Modulating an L-Type Calcium Conductance
Authors: Baufreton Jérôme , Garret Maurice , Rivera Alicia , de la Calle Adélaïda , Gonon François , Dufy Bernard , Bioulac Bernard , Taupignon Anne 
Published: April 2018

Dopamine is a crucial factor in basal ganglia functioning. In current models of basal ganglia, dopamine is postulated to act on striatal neurons. However, it may also act on the subthalamic nucleus (STN), a key nucleus in the basal ganglia circuit. The data presented here were obtained in brain slices using whole-cell patch clamp. They reveal that D5 dopamine receptors strengthen electrical activity in the subset of subthalamic neurons endowed with burst-firing capacity, resulting in longer discharges of spontaneous or evoked bursts.To distinguish between D1 and D5 subtypes, the action of agonists in the D1/D5 receptor family was first investigated on rat subthalamic neurons. Single-cell reverse transcription-PCR profiling showed that burst-competent neurons only expressed D5 receptors. Accordingly, receptors localized in postsynaptic membranes within the STN were labeled by a D5-specific antibody. Second, agonists in the D1/D5 family were tested in mouse brain slices. It was found that these agonists were active in D1 receptor knock-out mice in a similar way to wild-type mice or rats. This proved that D5 rather than D1 receptors were involved. Pharmacological tools (dihydropyridines, ω-conotoxins, and calciseptine) were used to identify the target of D5 receptors as an L-type channel. This was reached via G-protein and protein kinase A. The action of dopamine on D5 receptors therefore shapes neuronal activity. It contributes to normal information processing in basal ganglia outside striatum. This finding may be useful in drug therapy for various disorders involving changes in STN activity, such as Parkinson's disease and related disorders.
During Fictive Locomotion, Graded Synaptic Currents Drive Bursts of Impulses in Swimmeret Motor Neurons
Authors: Mulloney Brian 
Published: April 2018

During forward swimming, motor neurons that innervate each crayfish swimmeret fire periodic coordinated bursts of impulses. These bursts occur simultaneously in neurons that are functional synergists but alternate with bursts in their antagonists. These impulses ride on periodic oscillations of membrane potential that occur simultaneously in neurons of each type. A model of the local circuit that generates this motor pattern has been proposed. In this model, each motor neuron is driven alternately by excitatory and inhibitory synaptic currents from nonspiking local interneurons. I tested this model by perturbing individual interneurons and recording synaptic currents and changes in input resistance from each class of motor neuron. I also simulated the synaptic currents that would be observed in a cell subject to different patterns of presynaptic input.When the CNS was actively expressing the swimming motor pattern, changes in the membrane potential of individual local interneurons controlled firing of whole sets of motor neurons. Membrane currents in these motor neurons oscillated in phase with the motor output from their own local circuit. The phases of these oscillations differed in different functional classes of motor neurons. In neurons that could be clamped at the reversal potential of their outward currents, the model predicted that large periodic inward currents would be recorded. I observed no signs of periodic inward currents, even when the outward currents clearly had reversed.These results permit a simplification of the cellular model. They are discussed in the context of neural control of locomotion in crustacea and insects.
Receptor Subtypes Involved in the Presynaptic and Postsynaptic Actions of Dopamine on Striatal Interneurons
Authors: Centonze Diego , Grande Cristina , Usiello Alessandro , Gubellini Paolo , Erbs Eric , Martín Ana B. , Pisani Antonio , Tognazzi Nadia , Bernardi Giorgio , Moratalla Rosario , Borrelli Emiliana , Calabresi Paolo 
Published: April 2018

By stimulating distinct receptor subtypes, dopamine (DA) exerts presynaptic and postsynaptic actions on both large aspiny (LA) cholinergic and fast-spiking (FS) parvalbumin-positive interneurons of the striatum. Lack of receptor- and isoform-specific pharmacological agents, however, has hampered the progress toward a detailed identification of the specific DA receptors involved in these actions.To overcome this issue, in the present study we used four different mutant mice in which the expression of specific DA receptors was ablated. In D1 receptor null mice, D1R-/-, DA dose-dependently depolarized both LA and FS interneurons. Interestingly, SCH 233390 (10 μm), a D1-like (D1 and D5) receptor antagonist, but notl-sulpiride (3–10 μm), a D2-like (D2, D3, D4) receptor blocker, prevented this effect, implying D5 receptors in this action. Accordingly, immunohistochemical analyses in both wild-type and D1R-/- mice confirmed the expression of D5 receptors in both cholinergic and parvalbumin-positive interneurons of the striatum.In mice lacking D2 receptors, D2R-/-, the DA-dependent inhibition of GABA transmission was lost in both interneuron populations. Both isoforms of D2 receptor, D2L and D2S, were very likely involved in this inhibitory action, as revealed by the electrophysiological analysis of the effect of the DA D2-like receptor agonist quinpirole in two distinct mutants lacking D2L receptors and expressing variable contents of D2S receptors.The identification of the receptor subtypes involved in the actions of DA on different populations of striatal cells is essential to understand the circuitry of the basal ganglia and to develop pharmacological strategies able to interfere selectively with specific neuronal functions.
3,4-Methylenedioxymethamphetamine (Ecstasy) Inhibits Dyskinesia Expression and Normalizes Motor Activity in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Primates
Authors: Iravani Mahmoud M. , Jackson Michael J. , Kuoppamäki Mikko , Smith Lance A. , Jenner Peter 
Published: April 2018

Ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] was shown to prolong the action ofl-3,4-dihydroxyphenylalanine (l-DOPA) while suppressing dyskinesia in a single patient with Parkinson's disease (PD). The clinical basis of this effect of MDMA is unknown but may relate to its actions on either dopaminergic or serotoninergic systems in brain.In normal, drug-naive common marmosets, MDMA administration suppressed motor activity and exploratory behavior. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated,l-DOPA-primed common marmosets, MDMA transiently relieved motor disability but over a period of 60 min worsened motor symptoms. When given in conjunction withl-DOPA, however, MDMA markedly decreased dyskinesia by reducing chorea and to a lesser extent dystonia and decreased locomotor activity to the level observed in normal animals. MDMA similarly alleviated dyskinesia induced by the selective dopamine D2/3 agonist pramipexole. The actions of MDMA appeared to be mediated through 5-HT mechanisms because its effects were fully blocked by the selective serotonin reuptake inhibitor fluvoxamine. Furthermore, the effect of MDMA onl-DOPA-induced motor activity and dyskinesia was partially inhibited by 5-HT1a/b antagonists. The ability of MDMA to inhibit dyskinesia results from its broad spectrum of action on 5-HT systems. Serotoninergic receptors appear to play an important modulatory role inl-DOPA-induced dyskinesia, and this study may provide a framework for the use of serotoninergic agents in the treatment ofl-DOPA-induced dyskinesia.
Quantitative Estimate of Synaptic Inputs to Striatal Neurons during Up and Down StatesIn Vitro
Authors: Blackwell Kim T. , Czubayko Uwe , Plenz Dietmar 
Published: April 2018

Up states are prolonged membrane potential depolarizations critical for synaptic integration and action potential generation in cortical and striatal neurons. They commonly result from numerous concurrent synaptic inputs, whereas neurons reside in a down state when synaptic inputs are few. By quantifying the composition, frequency, and amplitude of synaptic inputs for both states, we provide important constraints for state transitions in striatal network dynamics.Up and down states occur naturally in cortex-striatum-substantia nigra cocultures, which were used as anin vitromodel in the present study. Spontaneous synaptic inputs during down states were extracted automatically in spiny projection neurons and fast spiking interneurons of the striatum using a newly developed computer algorithm. Consistent with a heterogeneous population of synaptic inputs, PSPs and PSCs showed no correlation in amplitude and rise time and occurred at relatively low frequencies of 10-40 Hz during the down state. The number of synaptic inputs during up states, estimated from the up-state charge and the unitary charge of down-state PSCs, was 217 ± 44. Given the average up-state duration of 284 ± 34 msec, synaptic input frequency was ∼800 Hz during up-states for both neuronal types. Many down-state events reversed at the chloride reversal potential and were blocked by GABAAantagonists. The high correlation between up- and down-state reversal potential suggests that despite these drastic changes in synaptic input frequency, the ratio of inhibitory to excitatory currents is similar during both states.
Lack of Evidence for Sprouting of Aβ Afferents into the Superficial Laminas of the Spinal Cord Dorsal Horn after Nerve Section
Authors: Hughes David I. , Scott Dugald T. , Todd Andrew J. , Riddell John S. 
Published: April 2018

The central arborizations of large myelinated cutaneous afferents normally extend as far dorsally as the ventral part of lamina II in rat spinal cord. Woolf et al. (1992) reported that after nerve injury some of these afferents sprouted into lamina I and the dorsal part of lamina II, and it has been suggested that this could contribute to allodynia associated with neuropathic pain. Part of the evidence for sprouting was on the basis of the use of cholera toxin B subunit as a selective tracer for A-fibers, and the validity of this approach has recently been questioned; however, sprouting was also reported in experiments involving intra-axonal labeling of chronically axotomized afferents.We have used intra-axonal labeling in the rat to examine central terminals of 58 intact sciatic afferents of presumed cutaneous origin and 38 such afferents axotomized 7-10 weeks previously. Both normal and axotomized populations included axons with hair follicle afferent-like morphology and arbors that entered the ventral half of lamina II; however, none of these extended farther dorsally. We also performed bulk labeling of myelinated afferents by injecting biotinylated dextran into the lumbar dorsal columns bilaterally 8-11 weeks after unilateral sciatic nerve section. We observed that both ipsilateral and contralateral to the sectioned nerve, arbors of axons with hair follicle afferent-like morphology in the sciatic territory extended only as far as the ventral half of lamina II. Therefore these results do not support the hypothesis that Aβ afferents sprout into the superficial laminas after nerve section.
Two Modes of Vesicle Recycling in the Rat Calyx of Held
Authors: de Lange R. P. J. , de Roos A. D. G. , Borst J. G. G. 
Published: April 2018

Vesicle recycling was studied in the rat calyx of Held, a giant brainstem terminal involved in sound localization. Stimulation of brain slices containing the calyx-type synapse with a high extracellular potassium ion concentration in the presence of horseradish peroxidase resulted within several minutes in a reduction of the number of neurotransmitter vesicles and in the appearance of labeled endosome-like structures. After returning to normal solution, the endosome-like structures disappeared over a period of several minutes, whereas simultaneously the number of labeled vesicles increased. A comparison with afferent stimulation suggested that the endosome-like structures normally do not participate in the vesicle cycle. Afferent stimulation at 5 Hz resulted in sustained synaptic transmission, without vesicle depletion but with an estimated endocytotic activity of <0.2 synaptic vesicles per active zone per second. At 20 Hz, the presynaptic action potentials generally failed during prolonged stimulation. In identified synapses, the number of vesicles labeled by photoconversion after stimulation at 5 Hz in the presence of the styryl dye RH414 was much lower than the number of vesicles that were released, as determined by measuring EPSCs. No more than ∼5% of the vesicles were labeled after 20 min stimulation at 5 Hz, whereas this stimulation protocol was sufficient to largely destain a terminal after previous loading.The results support a scheme for recycling in which two different modes coexist. At physiological demands, a pool of ∼5% of all vesicles provides sufficient vesicles for release. During intense stimulation, such as occurs in the presence of high extracellular K+, the synapse resorts to bulk endocytosis, a very slow mode of recycling.
Restoring Tip60 HAT/HDAC2 Balance in the Neurodegenerative Brain Relieves Epigenetic Transcriptional Repression and Reinstates Cognition
Authors: Panikker Priyalakshmi , Xu Song-Jun , Zhang Haolin , Sarthi Jessica , Beaver Mariah , Sheth Avni , Akhter Sunya , Elefant Felice 
Published: April 2018

Cognitive decline is a debilitating hallmark during preclinical stages of Alzheimer's disease (AD), yet the causes remain unclear. Because histone acetylation homeostasis is critical for mediating epigenetic gene control throughout neuronal development, we postulated that its misregulation contributes to cognitive impairment preceding AD pathology. Here, we show that disruption of Tip60 histone acetlytransferase (HAT)/histone deacetylase 2 (HDAC2) homeostasis occurs early in the brain of an AD-associated amyloid precursor protein (APP)Drosophilamodel and triggers epigenetic repression of neuroplasticity genes well before Aβ plaques form in male and female larvae. Repressed genes display enhanced HDAC2 binding and reduced Tip60 and histone acetylation enrichment. Increasing Tip60 in the AD-associated APP brain restores Tip60 HAT/HDAC2 balance by decreasing HDAC2 levels, reverses neuroepigenetic alterations to activate synaptic plasticity genes, and reinstates brain morphology and cognition. SuchDrosophilaneuroplasticity gene epigenetic signatures are conserved in male and female mouse hippocampus and their expression and Tip60 function is compromised in hippocampus from AD patients. We suggest that Tip60 HAT/HDAC2-mediated epigenetic gene disruption is a critical initial step in AD that is reversed by restoring Tip60 in the brain.SIGNIFICANCE STATEMENTMild cognitive impairment is a debilitating hallmark during preclinical stages of Alzheimer's disease (AD), yet its causes remain unclear. Although recent findings support elevated histone deacetylase 2 (HDAC2) as a cause for epigenetic repression of synaptic genes that contribute to cognitive deficits, whether alterations in histone acetlytransferase (HAT) levels that counterbalance HDAC2 repressor action occur and the identity of these HATs remain unknown. We demonstrate that disruption of Tip60 HAT/HDAC2 homeostasis occurs early in the ADDrosophilabrain and triggers epigenetic repression of neuroplasticity genes before Aβ plaques form. Increasing Tip60 in the AD brain restores Tip60 HAT/HDAC2 balance, reverses neuroepigenetic alterations to activate synaptic genes, and reinstates brain morphology and cognition. Our data suggest that disruption of the Tip60 HAT/HDAC2 balance is a critical initial step in AD.
Risk factors for Clostridium difficile infections in Baranya County, Southern Hungary
Authors: Vigvári Szabolcs , Sipos Dávid , Kappéter Ágnes , Feiszt Zsófia , Kovács Beáta , Péterfi Zoltán 
Published: April 2018

In the past decade, Clostridium difficile infections (CDIs) have become a major public health challenge. Their epidemiology has radically changed with a significant rise in the number of cases and an increase in severe episodes. Recurrence and failure of conventional treatments are very common. Furthermore, a spread of CDI has emerged in general population without the usual risk factors (unexposed to antibiotic treatment, young people, etc.). The conventional treatments (metronidazole and vancomycin) are still effective and are the first-line antibiotics with new recommendations. New therapeutic strategies are now available. Recent studies show a better efficacy of vancomycin compared with metronidazole for severe episodes. Fidaxomicin is a novel antibiotic drug with an efficacy similar to vancomycin and a lower risk of recurrence. Finally, for relapsing forms, fecal microbiota transplantation (FMT) seems to be the best option. We determined risk factors for CDI among patients treated at the infectious diseases ward of our hospital in Pécs. The study included 886 patients with CDI from 2009 to 2014. The average number of recurrent episodes was 2.16 and the proportion of severe cases was 66%. Among our patients, 726 (82%) had taken antibiotics and 769 (86.8%) had been hospitalized in the prior 3 months before developing CDI. We have found that prior statin use could be a significant risk factor of CDI (OR: 1.7765, 95% CI: 1.3966–2.2597, p < 0.0001). Finally, we present the comparative efficacy of different types of treatment (metronidazole, vancomycin, fidaxomicin, and FMT).
EFFECT OF PRE-TREATMENT ON QUALITATIVE INDICES OF WHITE ROOTS
Authors: Bilenka I. , Golinskaya Ya. , Dzyuba N. , Martirosian H. 
Published: April 2018

In the work, various technological methods are presented of preliminary processing of celery and parsnip roots to prevent their darkening during cooking in restaurants. These methods are: immersing in a citric acid solution (c = 0.05 %, 0.1 %, 0.15 %), in solution NaCl (c = 0. 5%, 1 %, 2 %), and microwave processing in various modes. The activity of peroxidase, polyphenol oxidase, and ascorbate oxidase enzymes of root crops in the varietal section is also determined. Fresh white roots were selected as research objects: celery of the varieties Yablucnyy and Diamant, and parsnip of the varieties Student and Kruhlyy. It was revealed that polyphenol oxidase shows the highest activity. In order to inactivate the above-stated oxidoreductase, different methods of treating white roots were compared, too. The lowest oxidative enzymes activity was characteristic of the roots of the Diamant varieties and the parsnip roots of the Student variety, which were selected for further work. Studies have been carried out on changes in the mass fraction of L-ascorbic acid during steam blasting and microwave processing in different modes. It is proved that the treatment of white roots with ultra high frequency irradiation at 650 W for 1 minute is optimal. Such treatment allowes preventing the darkening of the raw material after its peeling due to the action of oxidation-reducing enzymes. It also allows preserving L-ascorbic acid by 64.6 % and 65.0 % in the roots of celery and parsnip, respectively. The distribution of polyphenol oxidase activity in the celery and parsnip root crop is analyzed. The results of the work can be used in preparation of dishes with the use of white roots in restaurants in order to improve technological techniques during processing of raw materials into finished products, improve its quality, and preserve L-ascorbic acid, as well as expand the range of culinary products based on spicy aromatic raw materials.
MIST Borsalarında Rassal Yürüyüş Hipotezi
Authors: GEMİCİ Eray , POLAT Müslüm 
Published: April 2018

Borsalarda
hisse senetlerinin fiyatı arz ve talebe göre belirlenmektedir. Eğer borsada
rassal yürüyüş hipotezi geçerli ise geçmiş verilerden hareketle fiyat
tahmininde bulunmak mümkün olmamaktadır. Aksi takdirde bu bilgileri kullanan
kişiler fiyat tahmininde bulunabilmekte ve normalüstü kazanç elde
edebilmektedirler. Bu makalenin amacı MIST ülkelerinde (Meksika, Endonezya,
Güney Kore ve Türkiye) Ocak 1998 – Temmuz 2017 döneminde borsa endekslerinin
zayıf formda etkin olup olmadığını ortaya koymaktır. Bu amaçla MIST borsalarının rassal yürüyüş
süreci 2016 yılında Furuoka tarafından literatüre kazandırılan birim
kök testi ile incelenmiştir. Elde edilen bulgular, incelenen piyasaların zayıf
formda etkin olmadığına işaret etmektedir.