Miracle-dz/UniFAR-FTUs huggingface dataset:
Retrieval of conditioned fear activates the basolateral and intercalated nucleus of amygdala

The amygdala is one of the crucial brain structures for conditioned fear, in which conditioned stimuli are received by the basolateral nucleus of the amygdala (BLA), inducing a fear reaction via the central nucleus of the amygdala (CeA). Whereas BLA sends glutamatergic projections into CeA, the intercalated nucleus of the amygdala (ITC) sends GABAergic projections into CeA, which is doubly regulated by BLA and ITC. In the present study, we investigated the characteristics of the neural cells activated by retrieval of conditioned fear in BLA and ITC using immunohistochemistry, in situ hybridization, and Western blot analysis of transcription factors and neural cell markers. Because most conditioned fear‐induced c‐Fos‐positive cells in BLA were glutaminase positive and 67‐kDa isomer of glutamic acid decarboxylase (GAD67) negative, these cells are speculated to be glutamatergic. Seventy‐eight percent of the phosphorylated CREB (pCREB)‐positive cells were glutaminase double positive and 13% of the pCREB‐positive cells were GAD67 double positive, indicating that many of the conditioned fear‐induced pCREB‐positive cells in BLA were glutamatergic, but at least some of the pCREB‐positive cells were GABAergic. These results suggested that CREB phosphorylation was increased both in glutamatergic and in GABAergic neurons, but c‐Fos expression was increased mainly in glutamatergic neurons in BLA. CREB phosphorylation but not c‐Fos expression in ITC was specifically increased by retrieval of conditioned fear. It is therefore speculated that ITC GABAergic neurons were activated by retrieval of conditioned fear and that transcription factors other than c‐Fos were relevant to the activation. © 2011 Wiley‐Liss, Inc.
Subcellular localization of Pfs16, a Plasmodium falciparum gametocyte antigen

SUMMARY We have used immunoelectron microscopy to investigate the subcellular location of Pfs16 in Plasmodium falciparum. It was detected in the outer membrane region of gametocytes and more specifically on the parasitophorous vacuole membrane (pvm), since, during gametogenesis when the pvm disintegrates, the majority of the antigen was detected on the remains of this membrane in multilaminated whorls and not on the gamete plasma membrane. The antigen was also present on other gametocyte cellular structures, including those which we believe to be Garnham bodies, present in the host cell cytoplasm of some gametocytes. The antigen was present too on the membrane surrounding cytostomes and the resulting food vacuoles in the parasite cytoplasm.
Alkyl Hydroperoxide Reductase Is the Primary Scavenger of Endogenous Hydrogen Peroxide in Escherichia coli

ABSTRACT Hydrogen peroxide is generated during aerobic metabolism and is capable of damaging critical biomolecules. However, mutants ofEscherichia coli that are devoid of catalase typically exhibit no adverse phenotypes during growth in aerobic media. We discovered that catalase mutants retain the ability to rapidly scavenge H2O2 whether it is formed internally or provided exogenously. Analysis of candidate genes revealed that the residual activity is due to alkyl hydroperoxide reductase (Ahp). Mutants that lack both Ahp and catalase could not scavenge H2O2. These mutants excreted substantial amounts of H2O2, and they grew poorly in air. Ahp is kinetically a more efficient scavenger of trace H2O2 than is catalase and therefore is likely to be the primary scavenger of endogenous H2O2. Accordingly, mutants that lack Ahp accumulated sufficient hydrogen peroxide to induce the OxyR regulon, whereas the OxyR regulon remained off in catalase mutants. Catalase still has an important role in wild-type cells, because the activity of Ahp is saturated at a low (10−5 M) concentration of H2O2. In contrast, catalase has a high Km, and it therefore becomes the predominant scavenger when H2O2 concentrations are high. This arrangement is reasonable because the cell cannot provide enough NADH for Ahp to rapidly degrade large amounts of H2O2. In sum,E. coli does indeed generate substantial H2O2, but damage is averted by the scavenging activity of Ahp.
Simple Acts for a Better World: A Gameful System for Prosocial Behavior: Preliminary Design and Research Plan

Games and gameful systems designed to support social change most often seek to persuade by inducing empathy and outrage through the depiction of the direness of social issues and thus motivating people to take action. However, motivation is only one possible angle from which to approach behavior change. When capability or opportunity for meaningful impact are not given, people may refrain from taking action even when motivated. This work-in-progress outlines the theoretical background and design plan for a pervasive gameful system. Based on the behavior change wheel this system is designed to propose simple actions tailored to the player's given capabilities and opportunities, thereby encouraging prosocial behavior. We conclude with a discussion of the research plan for the evaluation of the prototype and the prosocial actions by means of two rounds of mixed-method diary studies.
High Throughput Measurement of Ca++ Dynamics in Human Stem Cell-Derived Cardiomyocytes by Kinetic Image Cytometery: A Cardiac Risk Assessment Characterization Using a Large Panel of Cardioactive and Inactive Compounds.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as a powerful in vitro model for cardiac safety assessment which may allow for better identification of compounds with poor arrhythmogenic liability profiles early in the drug discovery process. Here, we describe our examination of the Kinetic Image Cytometer (KIC) system's ability to predict adverse compound effects using hiPS-CMs and a library of 53 compounds, the majority of which are known to be cardioactive compounds, and several negative controls. The KIC provides a high throughput method for analyzing intracellular calcium transients. In the cardiomyocyte, intracellular calcium transients integrate the electrochemical signals of the action potential (AP) with the molecular signaling pathways regulating contraction. Drug-induced alterations in the shape and duration of AP result in changes to the shape and duration of the intracellular calcium transient. By examining calcium transient dynamics in hiPS-CMs, KIC can be used as a phenotypic screen to assess compound effects across multiple ion channel types (MITs), detecting MITs, calcium handling and signaling effects. The results of this blinded study indicate that using hiPS-CMs, KIC is able to accurately detect drug-induced changes in Ca(2+) transient dynamics (ie, duration and beat rate) and therefore, may be useful in predicting drug-induced arrhythmogenic liabilities in early de-risking within the drug discovery phase.
Hyperpolarization-activated inward leakage currents caused by deletion or mutation of carboxy-terminal tyrosines of the Na+/K+-ATPase α subunit

The Na+/K+-ATPase mediates electrogenic transport by exporting three Na+ ions in exchange for two K+ ions across the cell membrane per adenosine triphosphate molecule. The location of two Rb+ ions in the crystal structures of the Na+/K+-ATPase has defined two “common” cation binding sites, I and II, which accommodate Na+ or K+ ions during transport. The configuration of site III is still unknown, but the crystal structure has suggested a critical role of the carboxy-terminal KETYY motif for the formation of this “unique” Na+ binding site. Our two-electrode voltage clamp experiments on Xenopus oocytes show that deletion of two tyrosines at the carboxy terminus of the human Na+/K+-ATPase α2 subunit decreases the affinity for extracellular and intracellular Na+, in agreement with previous biochemical studies. Apparently, the ΔYY deletion changes Na+ affinity at site III but leaves the common sites unaffected, whereas the more extensive ΔKETYY deletion affects the unique site and the common sites as well. In the absence of extracellular K+, the ΔYY construct mediated ouabain-sensitive, hyperpolarization-activated inward currents, which were Na+ dependent and increased with acidification. Furthermore, the voltage dependence of rate constants from transient currents under Na+/Na+ exchange conditions was reversed, and the amounts of charge transported upon voltage pulses from a certain holding potential to hyperpolarizing potentials and back were unequal. These findings are incompatible with a reversible and exclusively extracellular Na+ release/binding mechanism. In analogy to the mechanism proposed for the H+ leak currents of the wild-type Na+/K+-ATPase, we suggest that the ΔYY deletion lowers the energy barrier for the intracellular Na+ occlusion reaction, thus destabilizing the Na+-occluded state and enabling inward leak currents. The leakage currents are prevented by aromatic amino acids at the carboxy terminus. Thus, the carboxy terminus of the Na+/K+-ATPase α subunit represents a structural and functional relay between Na+ binding site III and the intracellular cation occlusion gate.
Antifibrillatory effects of clofilium in the rabbit isolated heart

1 This study was designed to determine whether clofilium exhibits antifibrillatory activity in a pinacidil + hypoxia‐induced model of ventricular fibrillation (VF) in Langendorff‐perfused hearts. 2 Ten minutes after exposure to vehicle or clofilium (0.1, 1.0 and 10.0 μm), hearts were exposed to pinacidil (1.25 μm), then subjected to 12 min of hypoxia and reoxygenated. Onset to VF was recorded. Additional groups of hearts were pretreated with UK‐68,798 (1.0, 3.0 and 10.0 μm), a delayed rectifier channel blocker, and 5‐hydroxydecanoate (10 μm), a known ATP‐dependent K+ channel blocker, and subjected to an identical protocol. 3 Clofilium decreased the incidence of VF in a concentration‐dependent manner; 7/9 control hearts developed VF vs 1/9 hearts (P = 0.007, Fisher's Exact) treated with 10.0 μm clofilium. In addition, 5‐hydroxydecanoate protected hearts from VF, while UK‐68,798 pretreatment did not. 4 In a separate group of hearts, electrically‐induced VF was converted to sinus rhythm in 10/11 hearts after clofilium was introduced as a bolus. 5 Clofilium is capable of preventing VF in the rabbit isolated heart in a concentration‐dependent manner. We have data to suggest that the ability of clofilium to attenuate the effects of pinacidil + hypoxia in our model may include blockade of metabolically active K+ channels, i.e., KATP (glibenclamide‐sensitive) channel.
On Predicting Sociodemographic Traits and Emotions from Communications in Social Networks and Their Implications to Online Self-Disclosure

Social media services such as Twitter and Facebook are virtual environments where people express their thoughts, emotions, and opinions and where they reveal themselves to their peers. We analyze a sample of 123,000 Twitter users and 25 million of their tweets to investigate the relation between the opinions and emotions that users express and their predicted psychodemographic traits. We show that the emotions that we express on online social networks reveal deep insights about ourselves. Our methodology is based on building machine learning models for inferring coarse-grained emotions and psychodemographic profiles from user-generated content. We examine several user attributes, including gender, income, political views, age, education, optimism, and life satisfaction. We correlate these predicted demographics with the emotional profiles emanating from user tweets, as captured by Ekman's emotion classification. We find that some users tend to express significantly more joy and significantly less sadness in their tweets, such as those predicted to be in a relationship, with children, or with a higher than average annual income or educational level. Users predicted to be women tend to be more opinionated, whereas those predicted to be men tend to be more neutral. Finally, users predicted to be younger and liberal tend to project more negative opinions and emotions. We discuss the implications of our findings to online privacy concerns and self-disclosure behavior.
Optimal Multi-model Ensemble Method in Seasonal Climate Prediction

Given a large number of dynamical model predictions, this study endeavors to improve seasonal climate prediction through optimizing multi-model ensemble (MME) method. We have developed a new MME method and evaluated it using 15 dynamical models’ retrospective forecasts for the period 1981-2001 in comparison with other MME methods. The strengths of the new method lie in a statistical error correction procedure for predictions of individual model and a discreet selection procedure of reliable predictors among all possible candidates. The conspicuous improvement of the new method is achieved against other MME methods over the regions in which the average of individual models’ skill is very poor, such as land area and extratropical oceans. It is demonstrated that the selection procedure for the reliable predictors allows the present method to get more effective as the number of model predictions being used increases.
Dual Functions of Nbs1 in the Repair of DNA Breaks and Proliferation Ensure Proper V(D)J Recombination and T-Cell Development

ABSTRACT Immunodeficiency and lymphoid malignancy are hallmarks of the human disease Nijmegen breakage syndrome (NBS; OMIM 251260), which is caused by NBS1 mutations. Although NBS1 has been shown to bind to the T-cell receptor alpha (TCRα) locus, its role in TCRβ rearrangement is unclear. Hypomorphic mutations of Nbs1 in mice and patients result in relatively mild T-cell deficiencies, raising the question of whether the truncated Nbs1 protein might have clouded a certain function of NBS1 in T-cell development. Here we show that the deletion of the entire Nbs1 protein in T-cell precursors (Nbs1T-del) results in severe lymphopenia and a hindrance to the double-negative 3 (DN3)-to-DN4 transition in early T-cell development, due to abnormal TCRβ coding and signal joints as well as the functions of Nbs1 in T-cell expansion. Chromatin immunoprecipitation (ChIP) analysis of the TCR loci reveals that Nbs1 depletion compromises the loading of Mre11/Rad50 to V(D)J-generated DNA double-strand breaks (DSBs) and thereby affects resection of DNA termini and chromatin conformation of the postcleavage complex. Although a p53 deficiency relieves the DN3→DN4 transition block, neither a p53 deficiency nor ectopic expression of TCRαβ rescues the major T-cell loss in Nbs1T-del mice. All together, these results demonstrate that Nbs1's functions in both repair of V(D)J-generated DSBs and proliferation are essential for T-cell development.
Gender and Animacy Knowledge Discovery from Web-Scale N-Grams for Unsupervised Person Mention Detection

In this paper we present a simple approach to discover gender and animacy knowledge for person mention detection. We learn noun-gender and noun-animacy pair counts from web-scale n-grams using specific lexical patterns, and then apply confidence estimation metrics to filter noise. The selected informative pairs are then used to detect person mentions from raw texts in an unsupervised learning framework. Experiments showed that this approach can achieve high performance comparable to state-of-the-art supervised learning methods which require manually annotated corpora and gazetteers.
Circulating Rather Than Cardiac Angiotensin-(1-7) Stimulates Cardioprotection After Myocardial Infarction

Background—Angiotensin (Ang)-(1-7) attenuates the development of heart failure. In addition to its local effects on cardiovascular tissue, Ang-(1-7) also stimulates bone marrow, which harbors cells that might complement the therapeutic effect of Ang-(1-7). We studied the effects of Ang-(1-7) either produced locally in the heart or subcutaneously injected during the development of heart failure induced by myocardial infarction (MI) and explored the role of cardiovascular progenitor cells in promoting the effects of this heptapeptide. Methods and Results—Effects of Ang-(1-7) on bone marrow–derived mononuclear cells in rodents, particularly endothelial progenitor cells, were investigated in vitro and in vivo in rats, in mice deficient for the putative Ang-(1-7) receptor Mas, and in mice overexpressing Ang-(1-7) exclusively in the heart. Three weeks after MI induction through permanent coronary artery occlusion, effects of Ang-(1-7) either produced locally in the heart or injected into the subcutaneous space were investigated. Ang-(1-7) stimulated proliferation of endothelial progenitor cells isolated from sham or infarcted rodents. The stimulation was blunted by A779, a Mas receptor blocker, or by Mas deficiency. Infusion of Ang-(1-7) after MI increased the number of c-kit– and vascular endothelial growth factor–positive cells in infarcted hearts, inhibited cardiac hypertrophy, and improved cardiac function 3 weeks after MI, whereas cardiomyocyte-derived Ang-(1-7) had no effect. Conclusions—Our data suggest circulating rather than cardiac Ang-(1-7) to be beneficial after MI. This beneficial effect correlates with a stimulation of cardiac progenitor cells in vitro and in vivo. This characterizes the heptapeptide as a promising new tool in stimulating cardiovascular regeneration under pathophysiological conditions.
Changing spectrum and outcome of 705 fetal congenital heart disease cases: 12 years, experience in a third-level center

Introduction Congenital heart diseases are the most common prenatal and postnatal malformations. Nowadays, fetal echocardiography is a widely practiced technique; however, the impact of prenatal diagnosis on prognosis of the newborns affected by congenital heart disease remains uncertain. Objective To assess the outcome and the changes in the spectrum of prenatally detected congenital heart disease in our tertiary care centre in 12 years of activity (1995–2006). Methods and results We detected 705 congenital heart diseases: 32% (223) were associated with extracardiac or chromosomal anomalies or both, and 68% (482) were isolated. Termination of pregnancy was chosen in 81% for associated anomalies and 37% for isolated anomalies (P < 0.001). Of these, more than one-third occurred in hypoplasic left heart cases. The general survival rate was 72%; it was significantly lower in the group with associated heart diseases (46 vs. 80%, P < 0.001). Over 12 years we noticed a reduction in the number of multimalformed fetuses and of the hypoplasic left heart cases, and a higher number of aortic arch anomalies detected. During the past 6 years of activity the survival rate obtained has significantly increased (55 to 84%, P < 0.05), the termination rate has significantly decreased (35 to 14%, P < 0.001) and the number of neonatal deaths has significantly decreased (39 to 10%, P < 0.001). Conclusion The survival and the voluntary termination of fetuses with prenatally detected congenital heart diseases are strongly influenced by disease severity and by associated extracardiac or chromosomal anomalies, or both. Over 12 years, the spectrum of fetal congenital heart disease has changed and their outcome has significantly improved.
Dual microcatheter coil embolization of acutely ruptured wide-necked intracranial aneurysms

The dual microcatheter technique is an alternative treatment for stent-assisted coiling in acutely ruptured wide-necked aneurysms because of no antiplatelet therapy. We assessed the safety and efficacy of this technique in ruptured wide-necked aneurysms. Between March 2008 and March 2016, 56 acutely ruptured aneurysms were treated with the dual microcatheter technique. The angiographic results, treatment-related complications, and clinical outcome were documented. Angiographic follow-up was available in 37 patients at a mean of 20.6 months (6 to 81 months). On the postembolization angiograms, 27 (48.2%) aneurysms showed complete occlusion (Raymond 1), 15 (26.8%) showed neck remnant (Raymond 2), and 14 (25.0%) showed body remnant (Raymond 3). Treatment-related complications occurred in seven patients (12.5%) and six patients remained asymptomatic. The permanent complication rate was 1.8% (1/56). A good outcome (modified Rankin Scale (mRS) score, 0–2) was observed in 64.3% of patients at the time of discharge. Five patients had died, all of the sequelae of subarachnoid hemorrhage. The overall mortality rate was 8.9% (5/56); however, the treatment-related mortality rate was 0%. Of the 37 aneurysms for which angiographic follow-up was available, 21 (56.8%) aneurysms demonstrated recanalization. Five aneurysms with recanalization were retreated endovascularly. There was one aneurysm re-rupture on follow-up and it rebled 21 months after the initial procedure. The dual microcatheter technique is a safe and effective treatment for acutely ruptured wide-necked aneurysms due to low treatment-related complication and mortality rate. However, the high rate of postembolization incomplete occlusion and recanalization remains as the main challenge.
Family interventions in traumatized immigrants and refugees: A systematic review

The importance of the family as a unit in the aftermath of trauma necessitates the use of family interventions among immigrants and refugees. While abundant clinical material suggests that family-based trauma interventions are applicable across cultures, very little is known about the extent to which family treatment modalities are effective for immigrants and refugees. We conducted a systematic review of intervention studies that have been designed or modified specifically for traumatized immigrant and refugee families. The terms “trauma,” “family,” and “immigrants/refugees/culture” were used along with different terms for “intervention. ” Studies with no research methodology were excluded. Only 6 experimental studies met our inclusion criteria; 4 of them describe school-based interventions and 2 present multifamily support groups. The shortage of research in this area does not allow clear conclusions about the effectiveness of family interventions for traumatized immigrants or refugees. The complexity of employing methodologically rigorous research in small communities is discussed. Future trials should go beyond the individualistic approach and focus on posttraumatic stress disorder to address family-level processes, such as family relationship, communication, and resilience.
On the Performance of OpenDPI in Identifying P2P Truncated Flows

This paper aims to show the impact on classification accuracy and the level of computational gain that could be obtained in applying deep packet inspection on truncated peer to peer traffic flows instead of complete ones. Using one of the latest open source classifiers, experiments were conducted to evaluate classification performance on full and truncated network flows for different protocols, focusing on the detection of peer to peer. Despite minor exceptions, all the results show that with the latest deep packet inspection classifiers, which may incorporate different helper technologies, inspecting the first packets at the beginning of each flow, may still provide concrete computational gain while an acceptable level of classification accuracy is maintained. The present paper discusses this tradeoff and provides some recommendations on the number of packets to be inspected for the detection of peer to peer flows and some other common application protocols. As such, a new sampling approach is proposed, which accommodates samples to the stateful , taking into consideration the characteristics of the protocols being classified. Keywords-IP traffic classification; p2p; peer to peer; deep packet inspection; DPI optimization