bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel p75NTR Signaling Pathway Promotes Survival, Not Death, of Immunopurified Neocortical Subplate Neurons
Authors: DeFreitas Michael F. , McQuillen Patrick S. , Shatz Carla J. 
Published: April 2018

Subplate neurons of mammalian neocortex undergo pronounced cell death postnatally, long after they have matured and become incorporated into functional cortical circuits. They express the p75 neurotrophin receptor (p75NTR), which is known to signal cell death in some types of neurons via the activation of sphingomyelinase and the concomitant increase in the sphingolipid ceramide. To evaluate the role of p75NTR in subplate neurons, they were immunopurified and culturedin vitro. Contrary to its known function as a death receptor, ligand binding to p75NTR promotes subplate neuron survival. Moreover, p75NTR-dependent survival is blocked by inhibition of ceramide synthesis and rescued by addition of its precursor sphingomyelin. Inhibition of Trk signaling does not block survival, nor is Trk signaling alone sufficient to promote survival. Thus, ligand-dependent p75NTR regulation of the ceramide pathway mediates survival in certain neurons and may represent an important target for neuroprotective drugs in degenerative diseases involving p75NTR-expressing neurons, such as Alzheimer's disease.
Activity of Thalamic Reticular Neurons during Spontaneous Genetically Determined Spike and Wave Discharges
Authors: Slaght Seán J. , Leresche Nathalie , Deniau Jean-Michel , Crunelli Vincenzo , Charpier Stéphane 
Published: April 2018

This study reports the first intracellular recordings obtained during spontaneous, genetically determined spike and wave discharges (SWDs) in nucleus reticularis thalami (NRT) neurons from the genetic absence epilepsy rats from Strasbourg (GAERS), a model that closely reproduces the typical features of childhood absence seizures.A SWD started with a large hyperpolarization, which was independent of the preceding firing, and decreased in amplitude but did not reverse in polarity up to potentials ≥ −90 mV. This hyperpolarization and the slowly decaying depolarization that terminated a SWD were unaffected by recording with KCl-filled electrodes. The prolonged (up to 15 action potentials), high-frequency bursts present during SWDs were tightly synchronized between adjacent neurons, correlated with the EEG spike component, and generated by a low-threshold Ca2+potential, which, in turn, was brought about by the summation of high-frequency, small-amplitude depolarizing potentials.Fast hyperpolarizing IPSPs were not detected either during or in the absence of SWDs. Recordings with KCl-filled electrodes, however, showed a more depolarized resting membrane potential and a higher background firing, whereas the SWD-associated bursts had a longer latency to the EEG spike and a lower intraburst frequency. This novel finding demonstrates that spontaneous genetically determined SWDs occur in the presence of intra-NRT lateral inhibition.The unmasking of these properties in the GAERS NRT confirms their unique association with spontaneous genetically determined SWDs and thus their likely involvement in the pathophysiological processes of the human condition.
Corollary Discharge Inhibition of Ascending Auditory Neurons in the Stridulating Cricket
Authors: Poulet James F. A. , Hedwig Berthold 
Published: April 2018

Acoustically communicating animals are able to process external acoustic stimuli despite generating intense sounds during vocalization. We have examined how the crickets' ascending auditory pathway copes with self-generated, intense auditory signals (chirps) during singing (stridulation). We made intracellular recordings from two identified ascending auditory interneurons, ascending neuron 1 (AN1) and ascending neuron 2 (AN2), during pharmacologically elicited sonorous (two-winged), silent (one-winged), and fictive (isolated CNS) stridulation.During sonorous chirps, AN1 responded with bursts of spikes, whereas AN2 was inhibited and rarely spiked. Low-amplitude hyperpolarizing potentials were recorded in AN1 and AN2 during silent chirps. The potentials were also present during fictive chirps. Therefore, they were the result of a centrally generated corollary discharge from the stridulatory motor network. The spiking response of AN1 and AN2 to acoustic stimuli was inhibited during silent and fictive chirps. The maximum period of inhibition occurred in phase with the maximum spiking response to self-generated sound in a sonorously stridulating cricket. In some experiments (30%) depolarizing potentials were recorded during silent chirps. Reafferent feedback elicited by wing movement was probably responsible for the depolarizing potentials.In addition, two other sources of inhibition were present in AN1: (1) IPSPs were elicited by stimulation with 12.5 kHz stimuli and (2) a long-lasting hyperpolarization followed spiking responses to 4.5 kHz stimuli. The hyperpolarization desensitized the response of AN1 to subsequent quieter stimuli. Therefore, the corollary discharge will reduce desensitization by suppressing the response of AN1 to self-generated sounds.
Post-Traumatic Hyperexcitability Is Not Caused by Impaired Buffering of Extracellular Potassium
Authors: Santhakumar Vijayalakshmi , Voipio Juha , Kaila Kai , Soltesz Ivan 
Published: April 2018

Impaired extracellular potassium buffering has been proposed as one of the major mechanisms underlying the increased risk for temporal lobe epilepsy after brain injury (D'Ambrosio et al., 1999). The present study systematically tested this hypothesis by measuring the resting [K+]oand recovery of the stimulation-evoked [K+]oincreases in the dentate gyrus after experimental head trauma, using a combination of whole-cell recordings and ion-selective microelectrode recordings in rat hippocampal slices. Despite the presence of hyperexcitability, the resting [K+]owas not increased after injury. The faster rate of increase and larger amplitude of the orthodromically evoked [K+]oelevation after head trauma occurred in association with a greater population spike with shorter response latency. Contrary to the assumption in previous studies that the evoked activity in control and injured neuronal circuits is the same during antidromic activation, stimulation of granule cell axons in glutamate receptor antagonists evoked a greater [K+]oincrease and a larger population spike. Although perforant path stimulation resulted in a larger [K+]oelevation after injury, the rate of clearance of the [K+]otransients evoked either by neuronal activity or by external application of potassium was not compromised. The [K+]oincrease evoked by activation of the presynaptic afferents in isolation was not increased. In addition, the postsynaptic neuronal depolarization and firing evoked by exogenous potassium application was decreased after trauma.These results show that the regulation of [K+]ois not impaired after injury and indicate that the larger [K+]oincrease evoked by neuronal activity is a consequence, rather than the primary mechanism underlying post-traumatic hyperexcitability.
Individual Cerebellar Purkinje Cells Express Different cGMP Phosphodiesterases (PDEs):In VivoPhosphorylation of cGMP-Specific PDE (PDE5) as an Indicator of cGMP-dependent protein kinase (PKG) Activation
Authors: Shimizu-Albergine Masami , Rybalkin Sergei D. , Rybalkina Irina G. , Feil Robert , Wolfsgruber Wiebke , Hofmann Franz , Beavo Joseph A. 
Published: April 2018

The nitric oxide (NO)-cGMP pathway has been implicated as playing a crucial role in the induction of cerebellar long-term depression (LTD). The amplitude and duration of the cGMP signal is controlled by cyclic nucleotide phosphodiesterases (PDEs). Here we identify PDE5 and PDE1B as the two major cGMP-hydrolyzing PDEs specifically and differentially expressed in the Purkinje neurons of mouse cerebellum. PDE5 was found in all Purkinje neurons, whereas PDE1B was detected only in a subset of these cells, suggesting that individual Purkinje cells may differentially regulate cGMP, depending on the PDE isozymes expressed.Although expression of guanylate cyclase and/or cGMP-dependent protein kinase (PKG) in Purkinje cells have been reported, neither cGMP accumulation nor PKG activation in these cellsin vivohas been demonstrated. To determine if changes in PKG activation and PDE5 regulation occurin vivowe have examined the phosphorylation of PDE5 in mouse cerebellar Purkinje cells by immunocytochemistry and Western blot analyses using a phosphospecific PDE5 antibody. Injection of sodium nitroprusside or selective PKG activators into the lateral ventricle of mouse brain induced PDE5 phosphorylationin vivo, but was completely missing in Purkinje cell-specific PKG I knock-out mice. In cerebellar slices, treatment with sildenafil or IBMX led to different levels of phospho-PDE5 accumulation and activation of PDE5. These results suggest that phosphorylation of PDE5 in Purkinje neurons after cGMP-PKG activation performs a critical role in the termination of the cGMP signal during LTD progression; moreover, PDE5 phosphorylation may be used as anin vivoindicator for PKG activation.
Rapid Critical Period Induction by Tonic Inhibition in Visual Cortex
Authors: Iwai Youichi , Fagiolini Michela , Obata Kunihiko , Hensch Takao K. 
Published: April 2018

Mice lacking a synaptic isoform of glutamic acid decarboxylase (GAD65) do not exhibit ocular dominance plasticity unless an appropriate level of GABAergic transmission is restored by direct infusion of benzodiazepines into the brain. To better understand how intracortical inhibition triggers experience-dependent changes, we dissected the precise timing requirement for GABA function in the monocular deprivation (MD) paradigm.Diazepam (DZ) or vehicle solution was infused daily before and/or during 4 d of MD in GAD65 knock-out mice. Extracellular single-unit recordings from the binocular zone of visual cortex were performed at the end of deprivation. We found that a minimum treatment of 2 d near the beginning of MD was sufficient to fully activate plasticity but did not need to overlap the deprivation per se. Extended delay after DZ infusion eventually led to loss of plasticity accompanied by improved intrinsic inhibitory circuit function. Two day DZ treatment just after eye opening similarly closed the critical period prematurely in wild-type mice.Raising wild-type mice in complete darkness from birth delayed the peak sensitivity to MD as in other mammals. Interestingly, 2 d DZ infusion in the dark also closed the critical period, whereas equally brief light exposure during dark-rearing had no such effect. Thus, enhanced tonic signaling through GABAAreceptors rapidly creates a milieu for plasticity within neocortex capable of triggering a critical period for ocular dominance independent of visual experience itself.
Dissociable Contributions of the Human Amygdala and Orbitofrontal Cortex to Incentive Motivation and Goal Selection
Authors: Arana F. Sergio , Parkinson John A. , Hinton Elanor , Holland Anthony J. , Owen Adrian M. , Roberts Angela C. 
Published: April 2018

Theories of incentive motivation attempt to capture the way in which objects and events in the world can acquire high motivational value and drive behavior, even in the absence of a clear biological need. In addition, for an individual to select the most appropriate goal, the incentive values of competing desirable objects need to be defined and compared. The present study examined the neural substrates by which appetitive incentive value influences prospective goal selection, using positron emission tomographic neuroimaging in humans. Sated subjects were shown a series of restaurant menus that varied in incentive value, specifically tailored for each individual, and in half the trials, were asked to make a selection from the menu.The amygdala was activated by high-incentive menus regardless of whether a choice was required. Indeed, activity in this region varied as a function of individual subjective ratings of incentive value. In contrast, distinct regions of the orbitofrontal cortex were recruited both during incentive judgments and goal selection. Activity in the medial orbital cortex showed a greater response to high-incentive menus and when making a choice, with the latter activity also correlating with subjective ratings of difficulty. Lateral orbitofrontal activity was observed selectively when participants had to suppress responses to alternative desirable items to select their most preferred. Taken together, these data highlight the differential contribution of the amygdala and regions within the orbitofrontal cortex in a neural system underlying the selection of goals based on the prospective incentive value of stimuli, over and above homeostatic influences.
Single-Unit Activity Patterns in Nuclei That Control the Electromotor Command Nucleus during Spontaneous Electric Signal Production in the MormyridBrienomyrus brachyistius
Authors: Carlson Bruce A. 
Published: April 2018

Mormyrid fish generate weak electric organ discharges (EODs) used for communication and navigation. EODs are initiated in the medullary command nucleus (CN), which receives dense projections from the mesencephalic precommand nucleus (PCN) and the adjacent thalamic dorsal posterior nucleus (DP), plus a minor projection from the ventral edge of the toral ventroposterior nucleus (VPv). The dorsal region of the ventroposterior nucleus (VPd) projects to DP-PCN and receives input from the electric organ corollary discharge pathway. I recorded extracellularly from single units within DP-PCN and VPd and correlated their activity patterns with electromotor output to generate hypotheses on electromotor control mechanisms.DP-PCN neurons show an oscillatory pattern of activity, firing within a window of 10-200 msec before each EOD, while remaining silent for 50-150 msec after each EOD. VPd neurons only fire during the silent period of DP-PCN neurons, suggesting that they provide recurrent inhibition to DP-PCN. During “scallops”, only DP-PCN neurons with high baseline firing rates increase their activity, whereas during “accelerations”, only neurons with low baseline firing rates show a strong increase in activity. Thus, the generation of different displays likely results from the activation of different groups of neurons projecting to CN. The activity of VPd neurons decreases during both displays, suggesting that disinhibition plays an important role in their generation. The mormyrid electromotor network shares many functional properties with central pattern generators (CPGs) found in relatively simple motor systems, indicating that it may be an excellent model system for studying CPG function in vertebrate communication.
Processing of the Arousal of Subliminal and Supraliminal Emotional Stimuli by the Human Amygdala
Authors: Gläscher Jan , Adolphs Ralph 
Published: April 2018

The amygdala is known to play an important role in conscious and unconscious processing of emotional and highly arousing stimuli. Neuroanatomical evidence suggests that the amygdala participates in the control of autonomic responses, such as skin conductance responses (SCRs), elicited by emotionally salient stimuli, but little is known regarding its functional role in such control.We investigated this issue by showing emotional visual stimuli of varying arousal to patients with left (n= 12), right (n= 8), and bilateral (n= 3) amygdala damage and compared their results with those from 38 normal controls. Stimuli were presented both subliminally (using backward masking) and supraliminally under lateralized presentation to one visual hemifield. We collected SCRs as a physiological index of emotional responses. Subjects subsequently rated each stimulus on valence and arousal under free viewing conditions.There were two key findings: (1) impaired overall SCR after right amygdala damage; and (2) impaired correlation of SCR with the rated arousal of the stimuli after left amygdala damage. The second finding was strengthened further by finding a positive correlation between the evoked SCR magnitude and postsurgery amygdala volume, indicating impaired autonomic responses with larger tissue damage. Bilateral amygdala damage resulted in severe impairments on both of the above measures.Our results provide support for the hypothesis that the left and right amygdalae subserve different functions in emotion processing: the left may decode the arousal signaled by the specific stimulus, whereas the right may provide a global level of autonomic activation triggered automatically by any arousing stimulus.
Genomic Instability Promoted by Overexpression of Mismatch Repair Factors in Yeast: A Model for Understanding Cancer Progression
Authors: Chakraborty Ujani , Dinh Timothy A , Alani Eric 
Published: April 2018

AbstractIncreased expression of mismatch repair proteins often correlates with tumor aggressiveness. Chakraborty, Dinh, and Alani report that co-overexpression of Msh2 and Msh6 in yeast results in genome instability phenotypes that are dependent on interaction with...Mismatch repair (MMR) proteins act in spellchecker roles to excise misincorporation errors that occur during DNA replication. Curiously, large-scale analyses of a variety of cancers showed that increased expression of MMR proteins often correlated with tumor aggressiveness, metastasis, and early recurrence. To better understand these observations, we used The Cancer Genome Atlas and Gene Expression across Normal and Tumor tissue databases to analyze MMR protein expression in cancers. We found that the MMR genes MSH2 and MSH6 are overexpressed more frequently than MSH3, and that MSH2 and MSH6 are often cooverexpressed as a result of copy number amplifications of these genes. These observations encouraged us to test the effects of upregulating MMR protein levels in baker’s yeast, where we can sensitively monitor genome instability phenotypes associated with cancer initiation and progression. Msh6 overexpression (two- to fourfold) almost completely disrupted mechanisms that prevent recombination between divergent DNA sequences by interacting with the DNA polymerase processivity clamp PCNA and by sequestering the Sgs1 helicase. Importantly, cooverexpression of Msh2 and Msh6 (∼eightfold) conferred, in a PCNA interaction-dependent manner, several genome instability phenotypes including increased mutation rate, increased sensitivity to the DNA replication inhibitor HU and the DNA-damaging agents MMS and 4-nitroquinoline N-oxide, and elevated loss-of-heterozygosity. Msh2 and Msh6 cooverexpression also altered the cell cycle distribution of exponentially growing cells, resulting in an increased fraction of unbudded cells, consistent with a larger percentage of cells in G1. These novel observations suggested that overexpression of MSH factors affected the integrity of the DNA replication fork, causing genome instability phenotypes that could be important for promoting cancer progression.
Influence Organization Cultural, Work Condition to Job Satisfaction and Employee Performance Denpasar's Republic of Indonesia Radio
Authors: Kasih Ni Nyoman , Putu Agung Anak Agung , Sudja I Nengah 
Published: April 2018

In this time era of emulation business world very tight, to generate the consequence in company emulation. This emulation claim the company to reorganize the its business strategy every day, very tight emulation lay in how a implementation company can process the product creation or its service better and more with quality compared to a other business competitor. This Research target to analysis the cultural influence organization, environmental work to satisfaction work and employees performance Republic Of Indonesia Radio ( RRI ) Denpasar. Sum up the sample in this research as much 60 responder, with the method of data collecting primary by using appliance closed. Technique analysis that is descriptive analysis technique, path analysis by Partial is Least Square PLS.
Result of research that is organizational culture have an effect on positive to performance of employees of RRI Denpasar. Environmental work to have an effect on positive to performance of employees of RRI Denpasar. Organizational Cultural have an effect on positive to satisfaction work the employees of RRI Denpasar. Environmental work to have an effect on positive to satisfaction work the employees of RRI Denpasar. Satisfaction work to have an effect on positive performance of employees of RRI Denpasar
Challenges and Trends in Business Ethics Education: Mindmapping University Curriculunm for the Promotion of Justice and Sustainability for the Whole Society
Authors: Seran Alexander , Suhartoko YB 
Published: April 2018

The challenge of business ethics today is the problem of justice and sustainability. In the same time justice and sustainability have become the global trends in economic fora when people get together in academic seminars and other public discussions try to seek resolution about doing the right thing on the right place in the right time regarding economic crisis that we as society face in day to day experience. Increasing income inequality expands in size and scale that to some extent calls for the government intervention into markets on behalf of conditioning well-being of the whole society. On the one hand, there are challenges brought in societies by business that orient to price equilibrium when markets operate in the absence of external coercions such as reallocations, tax, and market operations. In order to be considered efficient market, business in the marketplace set aside the economic policy that favors the government intervention. On the other hand, there are trends in responding to the self-interest market by arguing ethically on values and principles of justice and sustainability in which economic policy that favors the government intervention is considered necessary. The aim of this paper is to shed lights to business ethics education in the school of economics and business to encapsulate the theory of economic welfare in its curriculum management and types of teaching through which young people are well-prepared to have good reasons in decision-making processes in dealing business in the marketplace. The requirement of good reasons is reflected in decision-making both as integrity and social responsibility. Decision-making that reflects integrity and social responsibility characterize the quality of ethical conducts. Therefore, business ethics education requires a theory that grounds economic welfare on the insight that economy is for the greater good of all human beings. This theory of economic welfare needs a reconstructive method to uncover the insight of justice and sustainability.