Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression and Function of SNAP-25 as a Universal SNARE Component in GABAergic Neurons

Intracellular vesicular trafficking and membrane fusion are important processes for nervous system development and for the function of neural circuits. Synaptosomal-associated protein 25 kDa (SNAP-25) is a component of neural soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) core complexes that mediate the exocytotic release of neurotransmitters at chemical synapses. Previous results from mouse mutant models and pharmacological/neurotoxin blockades have demonstrated a critical role for SNAP-25-containing SNARE complexes in action potential (AP)-dependent release at cholinergic and glutamatergic synapses and for calcium-triggered catecholamine release from chromaffin cells. To examine whether SNAP-25 participates in the evoked release of other neurotransmitters, we investigated the expression and function of SNAP-25 in GABAergic terminals. Patch-clamp recordings in fetal Snap25-null mutant cortex demonstrated that ablation of SNAP-25 eliminated evoked GABAA receptor-mediated postsynaptic responses while leaving a low level of spontaneous AP-independent events intact, supporting the involvement of SNAP-25 in the regulated synaptic transmission of early developing GABAergic neurons. In hippocampal cell cultures of wild-type mice, punctate staining of SNAP-25 colocalized with both GABAergic and glutamatergic synaptic markers, whereas stimulus-evoked vesicular recycling was abolished at terminals of both transmitter phenotypes in Snap25−/− neurons. Moreover, immunohistochemistry and fluorescence in situ hybridization revealed coexpression of SNAP-25, VGAT (vesicular GABA transporter), and GAD65/67 (glutamic acid decarboxylase 65/67) in interneurons within several regions of the adult brain. Our results thus provide evidence that SNAP-25 is critical for evoked GABA release during development and is expressed in the presynaptic terminals of mature GABAergic neurons, consistent with its function as a component of a fundamental core SNARE complex required for stimulus-driven neurotransmission.
Labour Market Developments and Social Welfare

Summary Employment and activity rates in the new EU Member States (NMS) declined significantly up to the early 2000s and started to increase along with strong GDP growth thereafter. Job losses following the outbreak of the economic and financial crisis varied substantially across countries and have not been offset yet. Overall, the low-educated and the young people are very disadvantaged on the NMS labour markets. With the exception of Poland and Slovenia, non-standard types of employment are uncommon in the NMS, following the pattern of Southern EU countries. Employment protection legislation has been adjusted to ‘European standards’ in the entire region. Union density and consequently the impact of trade unions on wage setting and employment in the NMS fell dramatically. In all NMS unemployment insurance schemes as well as minimum wage regulations were introduced at the beginning of the 1990s, but are less generous than in the EU-15.
Indifferents as an interface between Contra and Pro

In most sociophysical simulations on public opinion, only two opinions are allowed: Pro and Contra. However, in all political elections many people do not vote. Here we analyse two models of dynamics of public opinion, taking into account Indifferent voters: {\it i)} the Sznajd model with symmetry Pro-Contra, {\it ii)} the outflow one move voter model, where Contra's are converted to Indifferent by their Pro neighbours. Our results on the Sznajd model are in an overall agreement with the results of the mean field approach and with those known from the initial model formulation. The simulation on the voter model shows that an amount of Contra's who remain after convertion depends on the network topology.
Lung function decline in COPD trials: bias from regression to the mean

The decline in lung function over time is a fundamental measure of disease progression among patients with chronic obstructive pulmonary disease (COPD). As a result, forced expiratory volume in one second (FEV1) decline has been used as a central outcome measure for many randomised controlled trials evaluating whether pharmacological treatments could modify the natural history of COPD. These trials, mostly focussed on assessing the benefit of inhaled corticosteroids, and their meta-analyses highlighted the complexities of analysing data from repeated FEV1 measurements over time, particularly in the context of studying COPD patients who discontinue follow-up early and in large numbers. This has lead to contradictory results and divergent conclusions 1–3. At present, the recent paper from the Towards a Revolution in COPD Health (TORCH) trial reports that the yearly decline in FEV1 was significantly slower with fluticasone, salmeterol or both compared with placebo 4. A common misconception in the interpretation of these studies is that the effect of the study drug on FEV1 decline is likely to be greater than the data suggest. The rationale is that more patients receiving placebo were discontinuing the study drugs and the patients who dropped out early had a steeper decline in lung function than those who remained. Consequently, it has generally been believed that the resulting analysis “actually minimises the differences observed in the rate of FEV1 decline” 4. To clarify this misconception, a fundamental aspect of the design and statistical analysis of these trials is addressed, namely bias from regression to the mean resulting from the absence of an authentic intent-to-treat approach. It is described based on the TORCH trial and illustrated using data from the Canadian Optimal randomised trial. Most of the trials to date are not designed for a full intent-to-treat …
The Ubiquitin E3 Ligase NOSIP Modulates Protein Phosphatase 2A Activity in Craniofacial Development

Holoprosencephaly is a common developmental disorder in humans characterised by incomplete brain hemisphere separation and midface anomalies. The etiology of holoprosencephaly is heterogeneous with environmental and genetic causes, but for a majority of holoprosencephaly cases the genes associated with the pathogenesis could not be identified so far. Here we report the generation of knockout mice for the ubiquitin E3 ligase NOSIP. The loss of NOSIP in mice causes holoprosencephaly and facial anomalies including cleft lip/palate, cyclopia and facial midline clefting. By a mass spectrometry based protein interaction screen we identified NOSIP as a novel interaction partner of protein phosphatase PP2A. NOSIP mediates the monoubiquitination of the PP2A catalytic subunit and the loss of NOSIP results in an increase in PP2A activity in craniofacial tissue in NOSIP knockout mice. We conclude, that NOSIP is a critical modulator of brain and craniofacial development in mice and a candidate gene for holoprosencephaly in humans.
Peer Interaction Does Not Always Improve Children’s Mental State Talk Production in Oral Narratives. A Study in 6- to 10-Year-Old Italian Children

Joint narratives are a mean through which children develop and practice their Theory of Mind (ToM), thus they represent an ideal means to explore children’s use and development of mental state talk. However, creating a learning environment for storytelling based on peer interaction, does not necessarily mean that students will automatically exploit it by engaging in productive collaboration, thus it is important to explore under what conditions peer interaction promotes children’s ToM. This study extends our understanding of social aspects of ToM, focusing on the effect of joint narratives on school-age children’s mental state talk. Fifty-six Italian primary school children participated in the study (19 females and 37 males). Children created a story in two different experimental conditions (individually and with a partner randomly assigned). Each story told by the children, as well as their dialogs were recorded and transcribed. Transcriptions of narratives were coded in terms of text quality and mental state talk, whereas transcriptions of dialogs were coded in terms of quality of interaction. The results from this study confirmed that peer interaction does not always improve children’s mental state talk performances in oral narratives, but certain conditions need to be satisfied. Peer interaction was more effective on mental state talk with lower individual levels and productive interactions, particularly in terms of capacity to regulate the interactions. When children were able to focus on the interaction, as well as the product, they were also exposed to each other’s reasoning behind their viewpoint. This level of intersubjectivity, in turn, allowed them to take more in consideration the contribution of mental states to the narrative.
Synaptic and Temporal Ensemble Interpretation of Spike-Timing-Dependent Plasticity

We postulate that a simple, three-state synaptic switch governs changes in synaptic strength at individual synapses. Under this switch rule, we show that a variety of experimental results on timing-dependent plasticity can emerge from temporal and spatial averaging over multiple synapses and multiple spike pairings. In particular, we show that a critical window for the interaction of pre- and postsynaptic spikes emerges as an ensemble property of the collective system, with individual synapses exhibiting only a minimal form of spike coincidence detection. In addition, we show that a Bienenstock-Cooper-Munrolike, rate-based plasticity rule emerges directly from such a model. This demonstrates that two apparently separate forms of neuronal plasticity can emerge from a much simpler rule governing the plasticity of individual synapses.
OKUN’S LAW IN MALAYSIA: AN AUTOREGRESSIVE DISTRIBUTED LAG (ARDL) APPROACH WITH HODRICK-PRESCOTT (HP) FILTER

Okun’s Law has present in most of the European countries. It explained the negative relationship between output growth and unemployment rate. It has been a norm for the existence of the negative relationship between output growth and unemployment. The impact of high unemployment rate is direct, right after the recession or the decrease of output growth. It is therefore important to discover the effect of the relationship because from there, we will be able to effectively determine the suitable policy. This paper tends to examine the existence of Okun’s relationship in terms of Malaysia context using a rather new econometric approach. The relationship is measured by applying the first difference and gap model with Hodrick-Prescott filter (HP filter), furthered with Autogressive Distributed Lag (ARDL) to determine the co-integration between the variables and their causality. The main reason of applying ARDL is because of the small sample of data and it’s applicability on the order of integration, which is regardless even if the regressors are stationary. Additional to that, the method enables us to find the relationship between unemployment and output without determining the natural rate of output nor natural rate of unemployment
Evaluation of Na+ enrichment and expression of some carbohydrate related genes in indica rice seedlings under salt stress.

Salt-affected soil is one of the most important abiotic stresses, leading to reduce rice productivity in many regions of the world. The objective of this investigation was to determine the Na + , soluble sugar and starch contents and expression of some starch-related genes in two genotypes, Pokkali (salt tolerant) and IR29 (salt sensitive), grown under 200 mM NaCl. Three-week-old rice seedlings cvs. Pokkali and IR29 were treated with 0 or 200 mM NaCl subsequently Na + , starch content, soluble sugar and growth characters were evaluated. The Na + concentration in salt-stressed seedlings cv. IR29 was reached following leaf sheath>leaf blade>root tissues. Na + accumulation in leaf blade and leaf sheath was positively related to soluble sugar enrichment (r 2 >0.68). In starch biosynthesis, OsAGPS2b mRNA expression in leaf blade of rice seedlings cv. Pokkali was up-regulated for 66%, when exposed to 200 mM NaCl for 48h, leading to starch accumulation. Soluble starch content in salt-stressed seedlings was peaked to 68.84 g g -1 FW in the leaf blade of cv. Pokkali and 165.83 g g -1 FW in leaf sheath of cv. IR29 which was confirmed by iodine dye staining. In cv. Pokkali, soluble starch in the leaf blade of salt-stressed seedlings was enhanced and correlated with Na + gathering CoroNa green emission. Growth performances of indica rice cv. IR29 seedlings were significantly declined when subjected to salt stress for 4 d. Na + absorption by root tissue was greater in IR29 than that in Pokkali. The starch concentration in salt-stressed seedlings of cv. Pokkali was the maximum to 68.8 g g -1 FW in the leaf blade, and it related to up-regulated levels of OsAGPS2b mRNA and OsGPL1. The study concludes that the regulation of carbohydrate metabolism in salt tolerant cultivar of rice may play a key role as a major salt defense mechanism when seedlings subjected to 200 mM NaCl.
The widening scope of inter‐organizational networking:

Strategic alliances and networks have become an integral part of contemporary strategic organizational thinking. Their spread seems to correspond with the increasing rate of joint venture formations and outsourcing endeavours that have dominated the business arena in the past decade or so. Examines the widening scope of networking in the light of the underlying economic, sectoral and social dimensions. Argues that outsourcing remains a fundamental economic ingredient in network formation, and shows that networking, as a novel form of organization, is far‐reaching and gaining unprecedented expansion throughout a wide range of economic sectors, as well as on a global scale. Examines and discusses the role of informal (social) networking and the important issue of trust. Outlines and discusses issues relating to the success of future networks.
A Further Study of the Luminosity-dependent Cyclotron Resonance Energies of the Binary X-Ray Pulsar 4U 0115+63 with the Rossi X-Ray Timing Explorer

We report on the RXTE observations of the binary X-ray pulsar 4U 0115+63, covering an outburst in 1999 March-April with 44 pointings. The 3-30 keV PCA spectra and the 15-50 keV HEXTE spectra were analyzed jointly for cyclotron resonance features. When the 3-50 keV luminosity at an assumed distance of 7 kpc was in the range (5-13) × 1037 ergs s-1, harmonic double cyclotron features were observed in absorption at ~11 and ~22 keV, as was measured previously during typical outbursts. As the luminosity decreased below ~5 × 1037 ergs s-1, the second resonance disappeared, and the fundamental resonance energy gradually increased, up to ~16 keV at 0.16 × 1037 ergs s-1. These results reconfirm the report by Mihara et al. using Ginga, who observed a single absorption at ~16 keV in a minor (~1037 ergs s-1) outburst of this object. The luminosity-dependent cyclotron resonance energy might possibly be understood as a result of a decrease in the accretion column height, in response to a decrease in the mass accretion rate.
The pathophysiological significance of PPM1D and therapeutic targeting of PPM1D-mediated signaling by GSK2830371 in mantle cell lymphoma

PPM1D is a serine/threonine phosphatase that negatively regulates key DNA damage response proteins, such as p53, p38 MAPK, histone H2A.X, and ATM. We investigated the pathophysiological significance of PPM1D and its therapeutic targeting by the novel PPM1D inhibitor GSK2830371 in mantle cell lymphoma (MCL). Oncomine-based analyses indicated increased PPM1D mRNA levels in MCL cells compared with their normal counterpart cells. Higher PPM1D expression was associated with higher expression of the proliferation gene signature and poorer prognosis in patients. Eight MCL (three p53 wild-type and five mutant) cell lines were exposed to GSK2830371. GSK2830371 inhibited the cell growth, being prominent in p53 wild-type cells. GSK2830371 induced apoptosis in sensitive cells, as evidenced by induction of phosphatidylserine externalization and loss of mitochondrial membrane potential. p53 knockdown de-sensitized cell sensitivity. GSK2830371 increased the levels of total and Ser15-phosphorylated p53, and p53 targets p21 and PUMA. GSK2830371 and the MDM2 inhibitor Nutlin-3a acted synergistically in p53 wild-type cells. Interestingly, GSK2830371 sensitized MCL cells to bortezomib and doxorubicin in p53 wild-type and mutant cells; p38 signaling appeared to be involved in the GSK2830371/bortezomib lethality. PPM1D inhibition may represent a novel therapeutic strategy for MCL, which can be exploited in combination therapeutic strategies for MCL.
Reply to 'Comments on the examples in ''Dynamic output feedback compensation for linear systems with independent amplitude and rate saturations'''

Hui (1998) discussed the steady state error occurring in the examples given in Tyan and Bernstein (1997). As was pointed out in Hui (1998), the steady state error was due to the under capacity of control amplitude due to the saturation nonlinearity. In this responding letter, we increase the saturation level and demonstrate that even though the requirement of saturation capacity is satisfied, the given LQG controller still gives totally unsatisfactory response compared to that of the controller derived in Tyan and Bernstein (1997).
Simultaneous Effects of Slip Conditions and Wall Properties on MHD Peristaltic Flow of a Maxwell Fluid with Heat Transfer

The effects of both wall slip conditions and heat transfer on the magnetohydrodynamics (MHD) peristaltic flow of a Maxwell fluid in a porous planar channel with elastic wall properties have been studied. Mathematical formulation is based upon the modified Darcy’s law. The analytical solution has been derived for the stream function and temperature under the assumptions of small wave number.The results obtained in the analysis have been discussed numerically and explained graphically.
Variations of emotional display rules within and across cultures: A comparison between Canada, USA, and Japan.

This study investigates emotional display rules for seven basic emotions. The main goal was to compare emotional display rules of Canadians, US Americans, and Japanese across as well as within cultures regarding the specific emotion, the type of interaction partner, and gender. A total of 835 university students participated in the study. The results indicate that Japanese display rules permit the expression of powerful (anger, contempt, and disgust) significantly less than those of the two North American samples. Japanese also think that they should express positive emotions (happiness, surprise) significantly less than the Canadian sample. Furthermore, Japanese varied the display rules for different interaction partners more than the two North American samples did only for powerful emotions. Gender differences were similar across all three cultural groups. Men expressed powerful emotions more than women and women expressed powerless emotions (sadness, fear) and happiness more than men. Depending on the type of emotion and interaction partner some shared display rules occurred across culture and gender. The implications of these findings are discussed in relation to cultural dimensions and other cultural characteristics.
Spontaneously hypertensive rats: further evaluation of age-related memory performance and cholinergic marker expression.

OBJECTIVE The spontaneously hypertensive rat (SHR), often used to study cardiovascular disease processes, may also be utilized to model certain central nervous system changes associated with memory disorders. Previous work in our laboratory indicated that central nicotinic acetylcholine receptors are markedly diminished and that memory-related task performance is impaired in this rodent phenotype. Due to the well-documented importance of the central cholinergic system to memory processes and its vulnerability to the effects of aging, it was of interest to measure other cholinergic markers and to further evaluate memory function in older SHRs. METHOD Radial arm maze performance was used to assess working memory, quantitative receptor autoradiography with [3H]-pirenzipine, [3H]-AFDX-384 and [3H]-epibatidine (combined with cytisine) was used to determine the densities of muscarinic-M1 and -M2 and nicotinic cholinergic alpha3 receptors, respectively. Immunoblotting experiments were also used to determine the expression of the presynaptic cholinergic markers, choline acetyltransferase and the vesicular acetylcholine transporter. RESULTS Radial arm maze performance was impaired in hypertensive (compared with normotensive Wistar and Wistar-Kyoto) rats, regardless of age. M1 binding was increased in frontal and prefrontal cortical areas in SHR (p < 0.05), whereas M2 densities were higher in the hypertensive phenotype in the caudate putamen. A lower expression of alpha3-containing nicotinic receptors was observed in the superior colliculus in SHRs. Age-related differences in the expression of the vesicular acetylcholine transporter were noted in the hippocampus. CONCLUSION The SHR may be useful to model some aspects (particularly hypertension-related) of memory disorders, especially those in which cholinergic function is altered.
Football and corporate social responsibility

Surprisingly few academic articles have been written about football and Corporate Social Responsibility (CSR). A number of themes emerged from a literature review of CSR and sport. For this research, it was decided to concentrate on four key issues: to consider the relevance of institutional isomorphism to football clubs‟ CSR policies; to understand the motivations behind the decisions of football clubs to implement CSR policies; to describe the policies and programmes in detail and define their scope, and to examine how outcomes of schemes are measured. The research would also consider recommendations for improving practice across the areas of investigation. The research was undertaken with the assistance of four professional football clubs: three of the clubs in the Premier League and one in the Championship in season 2011/2012. Face to face interviews were carried out with representatives from the clubs or their community arms. Interviews were also undertaken with the representative of a football club trust with an extensive community programme and a Director of a research organisation with experience in this field to obtain an overview of the issues. The research findings are presented by setting out the backgrounds to the four case study football clubs and then the key issues are developed in the results and discussion sections with relevant quotations. The findings from the research reveal a broadening conception of CSR within football, but with motivations that are not always coherently expressed. The broad conception includes diverse community programmes measured increasingly sophisticatedly, but poorly evaluated wider policies. Many of these findings can be seen as related to institutional isomorphism. The key issues are taken forward into the study's conclusion, which considers the future direction of the CSR programmes of football clubs, limitations of the research and recommendations for further research.