Miracle-dz/UniFAR-FTUs huggingface dataset:
RNAseq Analysis of the Parasitic Nematode Strongyloides stercoralis Reveals Divergent Regulation of Canonical Dauer Pathways

The infectious form of many parasitic nematodes, which afflict over one billion people globally, is a developmentally arrested third-stage larva (L3i). The parasitic nematode Strongyloides stercoralis differs from other nematode species that infect humans, in that its life cycle includes both parasitic and free-living forms, which can be leveraged to investigate the mechanisms of L3i arrest and activation. The free-living nematode Caenorhabditis elegans has a similar developmentally arrested larval form, the dauer, whose formation is controlled by four pathways: cyclic GMP (cGMP) signaling, insulin/IGF-1-like signaling (IIS), transforming growth factor β (TGFβ) signaling, and biosynthesis of dafachronic acid (DA) ligands that regulate a nuclear hormone receptor. We hypothesized that homologous pathways are present in S. stercoralis, have similar developmental regulation, and are involved in L3i arrest and activation. To test this, we undertook a deep-sequencing study of the polyadenylated transcriptome, generating over 2.3 billion paired-end reads from seven developmental stages. We constructed developmental expression profiles for S. stercoralis homologs of C. elegans dauer genes identified by BLAST searches of the S. stercoralis genome as well as de novo assembled transcripts. Intriguingly, genes encoding cGMP pathway components were coordinately up-regulated in L3i. In comparison to C. elegans, S. stercoralis has a paucity of genes encoding IIS ligands, several of which have abundance profiles suggesting involvement in L3i development. We also identified seven S. stercoralis genes encoding homologs of the single C. elegans dauer regulatory TGFβ ligand, three of which are only expressed in L3i. Putative DA biosynthetic genes did not appear to be coordinately regulated in L3i development. Our data suggest that while dauer pathway genes are present in S. stercoralis and may play a role in L3i development, there are significant differences between the two species. Understanding the mechanisms governing L3i development may lead to novel treatment and control strategies.
Ventilatory and heart rate responses to exercise : better predictors of heart failure mortality than peak oxygen consumption.

BACKGROUND An abnormally low chronotropic response and an abnormally high ventilatory response (V(E)/V(CO2)) to exercise are common in patients with severe heart failure, but their relative prognostic impacts have not been well explored. METHODS AND RESULTS Consecutive patients with heart failure referred for metabolic stress testing who were not taking beta-blockers or intravenous inotropes (n=470) were followed for 1.5 years. The chronotropic index was calculated while peak V(O2) and V(E)/V(CO2) were directly measured. Chronotropic index and peak V(O2) were considered abnormal if in the lowest 25th percentiles of the patient cohort, whereas V(E)/V(CO2) was considered abnormal if in the highest 25th percentile. For comparative purposes, a group of 17 healthy controls underwent metabolic testing as well. Compared with controls, heart failure patients had markedly abnormal ventilatory and chronotropic responses to exercise. In the heart failure cohort, there were 71 deaths. In univariate analyses, predictors of death included high V(E)/V(CO2) low chronotropic index, low V(O2), low resting systolic blood pressure, and older age. Nonparametric Kaplan-Meier plots demonstrated that by dividing the population according to peak V(E)/V(CO2) and peak V(O2), it is possible to identify low, intermediate, and very high risk groups. In multivariate analyses, the only independent predictors of death were high V(E)/V(CO2) (adjusted relative risk [RR] 3.20, 95% CI 1.95 to 5.26, P<0.0001) and low chronotropic index (adjusted RR 1.94, 95% CI 1.18 to 3.19, P=0.0009). CONCLUSIONS The ventilatory and chronotropic responses to exercise are powerful and independent predictors of heart failure mortality.
Fluid and kinetic structure of magnetic merging in the Swarthmore Spheromak Experiment

Measurement of the in‐plane Lorentz force and the out‐of‐plane magnetic field associated with the Hall electric field near the reconnection zone in the Swarthmore Spheromak Experiment (SSX) confirms expectations, based on simulation, theory and spacecraft data, that the quadrupolar out‐of‐plane magnetic field is a signature of collisionless effects in magnetic reconnection with a weak guide field.
High levels of B-type natriuretic peptide predict weaning failure from mechanical ventilation in adult patients after cardiac surgery

OBJECTIVE: The failure to wean from mechanical ventilation is related to worse outcomes after cardiac surgery. The aim of this study was to evaluate whether the serum level of B-type natriuretic peptide is a predictor of weaning failure from mechanical ventilation after cardiac surgery. METHODS: We conducted a prospective, observational cohort study of 101 patients who underwent on-pump coronary artery bypass grafting. B-type natriuretic peptide was measured postoperatively after intensive care unit admission and at the end of a 60-min spontaneous breathing test. The demographic data, hemodynamic and respiratory parameters, fluid balance, need for vasopressor or inotropic support, and length of the intensive care unit and hospital stays were recorded. Weaning failure was considered as either the inability to sustain spontaneous breathing after 60 min or the need for reintubation within 48 h. RESULTS: Of the 101 patients studied, 12 patients failed the weaning trial. There were no differences between the groups in the baseline or intraoperative characteristics, including left ventricular function, EuroSCORE and lengths of the cardiac procedure and cardiopulmonary bypass. The B-type natriuretic peptide levels were significantly higher at intensive care unit admission and at the end of the breathing test in the patients with weaning failure compared with the patients who were successfully weaned. In a multivariate model, a high B-type natriuretic peptide level at the end of a spontaneous breathing trial was the only independent predictor of weaning failure from mechanical ventilation. CONCLUSIONS: A high B-type natriuretic peptide level is a predictive factor for the failure to wean from mechanical ventilation after cardiac surgery. These findings suggest that optimizing ventricular function should be a goal during the perioperative period.
Prevalence of Hepatitis C Virus Genotypes in Mashhad, Northeast Iran

Background: Hepatitis C is a disease with significant global impact. The distribution of hepatitis C virus (HCV) genotypes in Mashhad (the Northeast and the biggest city after the capital of Iran) is unknown. The purpose of this study was to determine the prevalence of HCV genotypes among HCV seropositive patients, and to study the relationship between types, virologic and demographic features of patients in Mashhad. Methods: Three hundred and eighty-two clinical specimens obtained from HCV-infected patients referred to Ghaem Hospital in Mashhad during a period of 2009 to 2010 were selected. HCV genotype was determined by Nested PCR amplification of HCV core gene using genotype specific primers. Results: Totally, 299 patients were male (79.9%). The most common HCV genotype was genotype 3a, with 150 (40%) of subjects. Genotype 1a was the other frequent genotype, with 147(39.2%) subjects. Frequency of genotypes for 1b, 5 and 2 was 41(10.9%), 13(3.4%) and 9(2.4%), respectively. Mix genotype including 1a+1b in 4 (1.04%), 1a+3a in 3 (0.8%) was found in 7 patients. Four percent out of these samples had an undetermined genotype. Among the hemophilia patient, there were 13(48.1%) genotypes as 1a, 3(11.1%) 1b and 10(37%) 3a, respectively. Conclusion: The dominant HCV genotype among patients living in Mashhad was 3a. This study gives added evidence of the predominant HCV genotypes in Iran.
Annonacin, a Natural Mitochondrial Complex I Inhibitor, Causes Tau Pathology in Cultured Neurons

A neurodegenerative tauopathy endemic to the Caribbean island of Guadeloupe has been associated with the consumption of anonaceous plants that contain acetogenins, potent lipophilic inhibitors of complex I of the mitochondrial respiratory chain. To test the hypothesis that annonacin, a prototypical acetogenin, contributes to the etiology of the disease, we investigated whether annonacin affects the cellular distribution of the protein tau. In primary cultures of rat striatal neurons treated for 48 h with annonacin, there was a concentration-dependent decrease in ATP levels, a redistribution of tau from the axons to the cell body, and cell death. Annonacin induced the retrograde transport of mitochondria, some of which had tau attached to their outer membrane. Taxol, a drug that displaces tau from microtubules, prevented the somatic redistribution of both mitochondria and tau but not cell death. Antioxidants, which scavenged the reactive oxygen species produced by complex I inhibition, did not affect either the redistribution of tau or cell death. Both were prevented, however, by forced expression of the NDI1 nicotinamide adenine dinucleotide (NADH)-quinone-oxidoreductase of Saccharomyces cerevisiae, which can restore NADH oxidation in complex I-deficient mammalian cells and stimulation of energy production via anaerobic glycolysis. Consistently, other ATP-depleting neurotoxins (1-methyl-4-phenylpyridinium, 3-nitropropionic, and carbonyl cyanide m-chlorophenylhydrazone) reproduced the somatic redistribution of tau, whereas toxins that did not decrease ATP levels did not cause the redistribution of tau. Therefore, the annonacin-induced ATP depletion causes the retrograde transport of mitochondria to the cell soma and induces changes in the intracellular distribution of tau in a way that shares characteristics with some neurodegenerative diseases.
Conflict in married couples: personality predictors of anger and upset.

This research had two central goals: to examine the role of personality in (a) performing actions that anger spouses, and (b) eliciting anger-provoking actions from spouses. Personality data on a sample of married persons (N = 214) were obtained from three sources--self-report, spouse-observer report, and independent interviewers' reports. In a separate session, subjects recorded which of 147 upsetting actions their spouses had performed in the past year. A series of hierarchical multiple regressions revealed the effects of Surgency, Agreeableness, Conscientiousness, Emotional Stability, and Intellect on evoking upset in spouses through condescension (e.g., treating spouse as stupid or inferior), possessiveness (demanding too much time and attention), abuse (slapping spouse), unfaithfulness (having sex with others), inconsiderateness (leaving toilet seat up), moodiness (crying a lot), alcohol abuse (drinking too much alcohol), emotional constriction (hiding emotions to act tough), and self-centeredness (acting selfishly). Discussion of this research focuses on the implications of personality for conflict in marital relationships.
Global or local? Predicting secondary structure and accessibility in mRNAs

Determining the structural properties of mRNA is key to understanding vital post-transcriptional processes. As experimental data on mRNA structure are scarce, accurate structure prediction is required to characterize RNA regulatory mechanisms. Although various structure prediction approaches are available, it is often unclear which to choose and how to set their parameters. Furthermore, no standard measure to compare predictions of local structure exists. We assessed the performance of different methods using two types of data: transcriptome-wide enzymatic probing information and a large, curated set of cis-regulatory elements. To compare the approaches, we introduced structure accuracy, a measure that is applicable to both global and local methods. Our results showed that local folding was more accurate than the classic global approach. We investigated how the locality parameters, maximum base pair span and window size, influenced the prediction performance. A span of 150 provided a reasonable balance between maximizing the number of accurately predicted base pairs, while minimizing effects of incorrect long-range predictions. We characterized the error at artificial sequence ends, which we reduced by setting the window size sufficiently greater than the maximum span. Our method, LocalFold, diminished all border effects and produced the most robust performance.
Construction and properties of an intracellular serine protease mutant of Bacillus subtilis

An intracellular serine protease (ISP-1) mutant of Bacillus subtilis was created by introducing a frameshift into the coding region of the cloned gene. Intracellular protease activity in the mutant was very low, yet sporulation in both nutrient broth and minimal medium was normal. The rate of bulk protein turnover in the mutant was slightly slower than that in the wild-type strain. These results suggest that the gene for ISP-1 is not essential and that ISP-1 is not the major enzyme involved in protein turnover during sporulation.
A sensorimotor driver model for steering control

The work described in this paper is part of a larger research program named Partage whose goal is to appropriately share lateral control between the driver and an electronic copilot or assistance. The present study is looking for a cybernetic model of a driver steering road vehicle, which makes the sensorimotor dynamics explicit. The proposed model takes into account both visual and kinesthetic perception, and includes compensatory and anticipatory processes. As such, it extends previous works. Starting from simulated car trajectories, the unknown parameters of the model are identified using the grey box identification concept. The driver-vehicle system is then analyzed with respect to the parameter sensitivity.
The Evolution of Mathematical Modeling of Glioma Proliferation and Invasion

Gliomas are well known for their potential for aggressive proliferation as well as their diffuse invasion of the normal-appearing parenchyma peripheral to the bulk lesion. This review presents a history of the use of mathematical modeling in the study of the proliferative-invasive growth of gliomas, illustrating the progress made in understanding the in vivo dynamics of invasion and proliferation of tumor cells. Mathematical modeling is based on a sequence of observation, speculation, development of hypotheses to be tested, and comparisons between theory and reality. These mathematical investigations, iteratively compared with experimental and clinical work, demonstrate the essential relationship between experimental and theoretical approaches. Together, these efforts have extended our knowledge and insight into in vivo brain tumor growth dynamics that should enhance current diagnoses and treatments.
The First Nucleotide Binding Fold of the Cystic Fibrosis Transmembrane Conductance Regulator Can Function as an Active ATPase (*)

Cystic fibrosis is caused by mutations in the cell membrane protein called CFTR (cystic fibrosis transmembrane conductance regulator) which functions as a regulated Cl channel. Although it is known that CFTR contains two nucleotide domains, both of which exhibit the capacity to bind ATP, it has not been demonstrated directly whether one or both domains can function as an active ATPase. To address this question, we have studied the first CFTR nucleotide binding fold (NBF1) in fusion with the maltose-binding protein (MBP), which both stabilizes NBF1 and enhances its solubility. Three different ATPase assays conducted on MBP-NBF1 clearly demonstrate its capacity to catalyze the hydrolysis of ATP. Significantly, the mutations K464H and K464L in the Walker A consensus motif of NBF1 markedly impair its catalytic capacity. MBP alone exhibits no ATPase activity and MBP-NBF1 fails to catalyze the release of phosphate from AMP or ADP. The Vmax of ATP hydrolysis (30 nmol/min/mg of protein) is significant and is markedly inhibited by azide and by the ATP analogs 2′-(3′)-O-(2,4,6-trinitrophenyl)-adenosine-5′-triphosphate and adenosine 5′-(β,-imido)triphosphate. As inherited mutations within NBF1 account for most cases of cystic fibrosis, results reported here are fundamental to our understanding of the molecular basis of the disease.
Direct chemical evidence for eumelanin pigment from the Jurassic period

Melanin is a ubiquitous biological pigment found in bacteria, fungi, plants, and animals. It has a diverse range of ecological and biochemical functions, including display, evasion, photoprotection, detoxification, and metal scavenging. To date, evidence of melanin in fossil organisms has relied entirely on indirect morphological and chemical analyses. Here, we apply direct chemical techniques to categorically demonstrate the preservation of eumelanin in two > 160 Ma Jurassic cephalopod ink sacs and to confirm its chemical similarity to the ink of the modern cephalopod, Sepia officinalis. Identification and characterization of degradation-resistant melanin may provide insights into its diverse roles in ancient organisms.
USENIX Association Proceedings of HotOS IX : The 9 th Workshop on Hot Topics in Operating Systems

Peer-to-peer storage aims to build large-scale, reliable and available storage from many small-scale unreliable, low-availability distributed hosts. Data redundancy is the key to any data guarantees. However, preserving redundancy in the face of highly dynamic membership is costly. We use a simple resource usage model to measured behavior from the Gnutella file-sharing network to argue that large-scale cooperative storage is limited by likely dynamics and cross-system bandwidth — not by local disk space. We examine some bandwidth optimization strategies like delayed response to failures, admission control, and load-shifting and find that they do not alter the basic problem. We conclude that when redundancy, data scale, and dynamics are all high, the needed cross-system bandwidth is unreasonable.
Cell surface expression of receptor protein tyrosine phosphatase RPTP mu is regulated by cell-cell contact

RPTP mu is a transmembrane protein tyrosine phosphatase with an adhesion molecule-like ectodomain. It has recently been shown that RPTP mu mediates homophilic interactions when expressed in insect cells. In this study, we have examined how RPTP mu may function as a cell contact receptor in mink lung epithelial cells, which express RPTPmu endogenously, as well as in transfected 3T3 cells. We find that RPTP mu has a relatively short half-life (3-4 hours) and undergoes posttranslational cleavage into two noncovalently associated subunits, with both cleaved and uncleaved molecules being present on the cell surface (roughly at a 1:1 ratio); shedding of the ectodomain subunit is observed in exponentially growing cells. Immunofluorescence analysis reveals that surface expression of RPTPmu is restricted to regions of tight cell-cell contact. RPTPmu surface expression increases significantly with increasing cell density. This density-induced upregulation of RPTP mu is independent of its catalytic activity and is also observed when transcription is driven by a constitutive promoter, indicating that modulation of RPTPmu surface expression occurs posttranscriptionally. Based on our results, we propose the following model of RPTP mu function: In the absence of cell-cell contact, newly synthesized RPTP mu molecules are rapidly cleared from the cell surface. Cell-cell contact causes RPTPmu to be trapped at the surface through homophilic binding, resulting in accumulation of RPTP mu at intercellular contact regions. This contact-induced clustering of RPTPmu may then lead to tyrosine dephosphorylation of intracellular substrates at cell-cell contacts.
Personalized prediction of first-cycle in vitro fertilization success

Choi B, Bosch E, Lannon BM, et al. Fertil Steril 2013; 20 March. pii: S0015-0282(13)00273-2. doi: 10.1016/j.fertnstert. 2013.02. 016 This paper provides the background research that resulted in an online predictor for in vitro fertilisation (IVF) success. It is based on the outcomes of >13 000 treatments from three centres in the USA, Spain and Canada. Intuitively it attempts to provide an answer for the question that all couples ask when considering IVF: Will it work? The National Institute for Health and Clinical Excellence (NICE) recommends that treatment should be provided for those with a predicted live birth rate of …
A vertebrate crossveinless 2 homologue modulates BMP activity and neural crest cell migration

Previous work has revealed that proteins that bind to bone morphogenetic proteins (BMPs) and inhibit their signalling have a crucial role in the spatial and temporal regulation of cell differentiation and cell migration by BMPs. We have identified a chick homologue of crossveinless 2, a Drosophila gene that was identified in genetic studies as a promoter of BMP-like signalling. Chick Cv-2 has a conserved structure of five cysteine-rich repeats similar to those found in several BMP antagonists, and a C-terminal Von Willebrand type D domain. Cv-2 is expressed in the chick embryo in a number of tissues at sites at which elevated BMP signalling is required. One such site of expression is premigratory neural crest, in which at trunk levels threshold levels of BMP activity are required to initiate cell migration. We show that, when overexpressed, Cv-2 can weakly antagonise BMP4 activity in Xenopus embryos, but that in other in vitro assays Cv-2 can increase the activity of co-expressed BMP4. Furthermore, we find that increased expression of Cv-2 causes premature onset of trunk neural crest cell migration in the chick embryo, indicative of Cv-2 acting to promote BMP activity at an endogenous site of expression. We therefore propose that BMP signalling is modulated both by antagonists and by Cv-2 that acts to elevate BMP activity.
Early Term Deliveries and the Risk of Pediatric Obstructive Sleep Apnoea in the Offspring

BACKGROUND Preterm delivery may affect the development of the upper airways resulting in a higher risk of obstructive sleep apnoea (OSA). We investigated whether children born at early term (37-38 6/7 weeks' gestation) are at an increased risk for childhood OSA as compared with those born later. METHODS In this population-based cohort analysis all singleton deliveries occurring between 1991-2013 at a single regional tertiary medical centre were included. Gestational age upon delivery was sub-divided into: early preterm (<33 6/7 weeks' gestation), late preterm (34-36 6/7), early term, full term (39-40 6/7), late term (41-41 6/7), and post term (>42 0/7). Incidence of OSA related hospitalizations of the offspring, up to the age of 18 years, was evaluated. A survival curve and a Cox model were used to assess the association. RESULTS During the study period 240 953 deliveries met the inclusion criteria. OSA hospitalization (n = 1320) rates decreased as gestational age increased from 1.1% in the early preterm group, 0.8% in late preterm, 0.7% at early term, 0.5% in full term, 0.4% in late term, to 0.3% in post term born children. In the Cox regression, early term delivery exhibited an increased risk for paediatric OSA (adjusted hazard ratio (HR) 1.3 95% Confidence interval (CI) 1.2, 1.5) while late and post term deliveries were associated with significantly lower OSA risk when compared with full term (HR 0.8 95% CI 0.6, 0.9 and HR 0.6 95% CI 0.4, 0.8, respectively). CONCLUSIONS Early term deliveries are associated with higher rates of paediatric OSA, which decrease gradually as gestational age advances.