Miracle-dz/UniFAR-FTUs huggingface dataset:
Positive and Negative Regulation of Type I Interferons by the Human T Cell Leukemia Virus Antisense Protein HBZ

ABSTRACT The pathogenesis of human T cell leukemia virus type 1 (HTLV-1) is strongly linked to the viral regulatory proteins Tax1 and HBZ, whose opposing functions contribute to the clinical outcome of infection. Type I interferons alpha and beta (IFN-α and IFN-β) are key cytokines involved in innate immunity, and IFN-α, in combination with other antivirals, is extensively used in the treatment of HTLV-1 infection. The relationship between HTLV-1 and IFN signaling is unclear, and to date the effect of HBZ on this pathway has not been examined. Here we report that HBZ significantly enhances interferon regulatory factor 7 (IRF7)-induced IFN-α- and IFN-stimulated response element (ISRE) promoter activities and IFN-α production and can counteract the inhibitory effect of Tax1. In contrast to this, we show that HBZ and Tax1 cooperate to inhibit the induction of IFN-β and ISRE promoters by IRF3 and IFN-β production. In addition, we reveal that HBZ enhances ISRE activation by IFN-α. We further show that HBZ enhances IRF7 and suppresses IRF3 activation by TBK1 and IKKε. We demonstrate that HBZ has no effect on virus-induced nuclear accumulation of IRF3, suggesting that it may inhibit IRF3 activity at a transcriptional level. We show that HBZ physically interacts with IRF7 and IKKε but not with IRF3 or TBK1. Overall, our findings suggest that both HBZ and Tax1 are negative regulators of immediate early IFN-β innate immune responses, while HBZ but not Tax1 positively regulates the induction of IFN-α and downstream IFN-α signaling. IMPORTANCE Type I interferons are powerful antiviral cytokines and are used extensively in the treatment of HTLV-1-induced adult T cell leukemia (ATL). To date, the relationship between HTLV-1 and the IFN pathway is poorly understood, and studies so far have focused on Tax1. Our study is unique in that it examined the effect of HBZ, alone or in combination with Tax1, on type I IFN signaling. This is important because HBZ is frequently the only viral protein expressed in infected cells, particularly at later stages of infection. A better understanding of the how HBZ regulates IFN signaling may lead to the development of therapeutics that can modify such responses and improve the clinical outcome for infected individuals.
Gene expression profiles of ion channels and receptors in mouse resistance arteries: Effects of cell type, vascular bed, and age

Receptors and ion channels of smooth muscle cells (SMCs) and endothelial cells (ECs) are integral to the regulation of vessel diameter and tissue blood flow. Physiological roles of ion channels and receptors in skeletal muscle and mesenteric arteries have been identified; however, their gene expression profiles are undefined. We tested the hypothesis that expression profiles for ion channels and receptors governing vascular reactivity vary with cell type, vascular bed, and age.
Integrating Language Knowledge Resources to Extend the English Inclusion Classifier to a New Language

This paper presents an unsupervised system that classifies English inclusions in written text. It will demonstrate that extending this English inclusion classifier, which was originally designed for German, requires minimal time and effort to adapt to a new language, in this case French. The analysis of several evaluation experiments carried out on French and German data shows that the system performs well for both languages and on unseen data from the same domain and language.
Therapeutic Potential of Date Palm Pollen for Testicular Dysfunction Induced by Thyroid Disorders in Male Rats

Hyper- or hypothyroidism can impair testicular function leading to infertility. The present study was designed to examine the protective effect of date palm pollen (DPP) extract on thyroid disorder-induced testicular dysfunction. Rats were divided into six groups. Group I was normal control. Group II received oral DPP extract (150 mg kg-1), group III (hyperthyroid group) received intraperitoneal injection of L-thyroxine (L-T4, 300μg kg-1; i.p.), group IV received L-T4 plus DPP extract, group V (hypothyroid group) received propylthiouracil (PTU, 10 mg kg-1; i.p.) and group VI received PTU plus DPP extract. All treatments were given every day for 56 days. L-T4 or PTU lowered genital sex organs weight, sperm count and motility, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone (T), testicular function markers and activities of testicular 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). Moreover, L-T4 or PTU increased estradiol (E2) serum level, testicular oxidative stress, DNA damage and apoptotic markers. Morphometric and histopathologic studies backed these observations. Treatment with DPP extract prevented LT4- or PTU induced changes. In addition, supplementation of DPP extract to normal rats augmented sperm count and motility, serum levels of LH, T and E2 paralleled with increased activities of 3β-HSD and 17β-HSD as well as testicular antioxidant status. These results provide evidence that DPP extract may have potential protective effects on testicular dysfunction induced by altered thyroid hormones.
Conserved Microsatellites in Ants Enable Population Genetic and Colony Pedigree Studies across a Wide Range of Species

Broadly applicable polymorphic genetic markers are essential tools for population genetics, and different types of markers have been developed for this purpose. Microsatellites have been employed as particularly polymorphic markers for over 20 years. However, PCR primers for microsatellite loci are often not useful outside the species for which they were designed. This implies that a new set of loci has to be identified and primers developed for every new study species. To overcome this constraint, we identified 45 conserved microsatellite loci based on the eight currently available ant genomes and designed primers for PCR amplification. Among these loci, we chose 24 for in-depth study in six species covering six different ant subfamilies. On average, 11.16 of these 24 loci were polymorphic and in Hardy-Weinberg equilibrium in any given species. The average number of alleles for these polymorphic loci within single populations of the different species was 4.59. This set of genetic markers will thus be useful for population genetic and colony pedigree studies across a wide range of ant species, supplementing the markers available for previously studied species and greatly facilitating the study of the many ant species lacking genetic markers. Our study shows that it is possible to develop microsatellite loci that are both conserved over a broad range of taxa, yet polymorphic within species. This should encourage researchers to develop similar tools for other large taxonomic groups.
Impact of different educational interventions on psychosocial well-being of women with a positive high-risk human papillomavirus and normal cervical cytology: a randomised trial

Abstract Introduction: The aim of this study was to compare the effect of two educational interventions on the psychosocial well-being of Hong Kong Chinese women who have a positive high-risk human papillomavirus (HPV) test and normal cervical cytology. Methods: Participants were randomised into either leaflet group, in which a written HPV factsheet was provided; or counselling group, in which a didactic HPV presentation in person in addition to the factsheet was provided. Women’s psychological conditions were assessed by self-administered questionnaires at pre, post (within one week) and 6 months after the educational interventions. Main outcome measures were psychosocial well-being (cervical cancer worry, anxiety and depression, screening-related anxieties, HPV-related shame) and knowledge of cervical screening and HPV. Results: Data from 121 women (52 in leaflet group; 69 in counselling group) were analysed. There was no significant difference in the psychosocial well-being between the two groups at alltime points. Irrespective of the two educational interventions, cervical cancer worry and anxiety decreased over time. The counselling group had a significantly higher score in knowledge of cervical screening and HPV compared with leaflet group (mean score 4.65 ± 0.19 versus 3.71 ± 0.23, p = 0.002) at post-educational intervention, but there was no significant difference (mean score 4.14 ± 0.22 versus 3.58 ± 0.24, p = 0.084) at 6 months. Discussion: Both educational interventions were comparable in relieving adverse HPV-related psychosocial effects. Combination of counselling and leaflet were more effective than leaflet only in improving women’s knowledge on cervical screening and HPV soon after educational interventions but the benefit was not apparent after 6 months.
Myofibroblast Differentiation and Enhanced Tgf-B Signaling in Cystic Fibrosis Lung Disease

Rationale TGF-β, a mediator of pulmonary fibrosis, is a genetic modifier of CF respiratory deterioration. The mechanistic relationship between TGF-β signaling and CF lung disease has not been determined. Objective To investigate myofibroblast differentiation in CF lung tissue as a novel pathway by which TGF-β signaling may contribute to pulmonary decline, airway remodeling and tissue fibrosis. Methods Lung samples from CF and non-CF subjects were analyzed morphometrically for total TGF-β1, TGF-β signaling (Smad2 phosphorylation), myofibroblast differentiation (α-smooth muscle actin), and collagen deposition (Masson trichrome stain). Results TGF-β signaling and fibrosis are markedly increased in CF (p<0.01), and the presence of myofibroblasts is four-fold higher in CF vs. normal lung tissue (p<0.005). In lung tissue with prominent TGF-β signaling, both myofibroblast differentiation and tissue fibrosis are significantly augmented (p<0.005). Conclusions These studies establish for the first time that a pathogenic mechanism described previously in pulmonary fibrosis is also prominent in cystic fibrosis lung disease. The presence of TGF-β dependent signaling in areas of prominent myofibroblast proliferation and fibrosis in CF suggests that strategies under development for other pro-fibrotic lung conditions may also be evaluated for use in CF.
Changes in Lipoprotein Particle Number With Ezetimibe/Simvastatin Coadministered With Extended‐Release Niacin in Hyperlipidemic Patients

Background Combination therapy with ezetimibe/simvastatin (E/S) and extended‐release niacin (N) has been reported to be safe and efficacious in concomitantly reducing low‐density lipoprotein cholesterol and increasing high‐density lipoprotein cholesterol in hyperlipidemic patients at high risk for atherosclerotic cardiovascular events. This analysis evaluated the effect of E/S coadministered with N on low‐density lipoprotein particle number (LDL‐P) and high‐density lipoprotein particle number (HDL‐P) as assessed by nuclear magnetic resonance (NMR) spectroscopy in patients with type IIa or IIb hyperlipidemia. Methods and Results This was an analysis of a previously reported 24‐week randomized, double‐blind study in type IIa/IIb hyperlipidemic patients randomized to treatment with E/S (10/20 mg/day)+N (titrated to 2 g/day) or N (titrated to 2 g/day) or E/S (10/20 mg/day). Samples from a subset of patients (577 of 1220) were available for post hoc analysis of LDL‐P and HDL‐P by NMR spectroscopy. Increases in HDL‐P (+16.2%) and decreases in LDL‐P (−47.7%) were significantly greater with E/S+N compared with N (+9.8% for HDL‐P and −21.5% for LDL‐P) and E/S (+12.8% for HDL‐P and −36.8% for LDL‐P). In tertile analyses, those with the lowest baseline HDL‐P had the greatest percent increase in HDL‐P (N, 18.4/7.9/2.1; E/S, 19.3/12.2/5.3; and E/S+N, 26.9/13.8/6.9; all P<0.001). Individuals in the highest tertile of LDL‐P had the greatest percent reduction in LDL‐P (N, 18.3/23.1/24.6; E/S, 29.7/38.3/41.8; and E/S+N, 44.3/49.0/50.5; all P<0.001). Conclusions These results suggest that E/S+N improves lipoprotein particle number, consistent with its lipid‐modifying benefits in type IIa or IIb hyperlipidemia patients and may exert the greatest effect in those with high LDL‐P and low HDL‐P at baseline. Clinical Trial Registration URL: Clinicaltrials.gov Identifier: NCT00271817
The effect of antipsychotic drugs and non-drug therapy on borderline and psychotic mentally ill patient ’ s quality-adjusted life-years ( QALY )

Quality of Life Research Center, Copenhagen, Denmark; Research Clinic for Holistic Medicine; Nordic School of Holistic Medicine, Copenhagen, Denmark; Scandinavian Foundation for Holistic Medicine, Sandvika, Norway; Interuniversity College, Graz, Austria; Faculty of Social Sciences, Department of Behavioral Sciences, Ariel University Center of Samaria, Ariel, Israel; National Institute of Child Health and Human Development; Office of the Medical Director, Division for Mental Retardation, Ministry of Social Affairs, Jerusalem, Israel Kentucky Children’s Hospital, University of Kentucky, Lexington, United States
miR-133b-5p contributes to hypoxic preconditioning-mediated cardioprotection by inhibiting the activation of caspase-8 and caspase-3 in cardiomyocytes

In a previous study using a microRNA (miRNA/miR) microarray assay, we demonstrated that miR-133b-5p was upregulated in response to hypoxic preconditioning (HPC). The present study was designed to investigate the role of the miR-133b-5p in HPC-induced cardioprotection and the underlying mechanisms involving caspase-8 and caspase-3 apoptotic signaling. Adult rats were subjected to myocardial ischemia/reperfusion (I/R) injury with or without ischemic preconditioning (IPC), and the level of miR-133b-5p in myocardium was measured. Neonatal rat cardiomyocytes were isolated and subjected to hypoxia/reoxygenation (H/R) injury, with or without HPC. miR-133b-5p antagomir was transfected into the cardiomyocytes to observe whether it could block HPC-induced cardioprotection. Cellular injury was evaluated by detecting cell viability, lactate dehydrogenase (LDH) activity and apoptotic rate. Reverse transcription-quantitative polymerase chain reaction was used to measure the level of miR-133b-5p. The activation of caspase-8 and caspase-3 were measured by western blot analysis to detect the cleaved fragments as well as a colorimetric assay. Following myocardial I/R injury, the expression of miR-133b-5p was decreased in myocardium, while this decrease was restored by IPC. HPC protected neonatal rat cardiomyocytes against H/R injury by increasing cell viability, while reducing LDH release and cell apoptosis. These protective effects were coupled with the upregulation of miR-133b-5p. However, the knockdown of miR-133b-5p in the cardiomyocytes blocked HPC-mediated cardioprotection as reflected by the aggravation of cell injury and apoptosis. HPC upregulated miR-133b-5p level was markedly suppressed by the antagomir. In addition, the cleavage and activities of caspase-8 and caspase-3 were inhibited by HPC while reversed by knockdown of miR-133b-5p. Upregulation of miR-133b-5p contributes to HPC-mediated cardioprotection in cardiomyocytes, and the mechanism may be associated with inhibition of caspase-8 and caspase-3 apoptotic signaling.
Do Domestic Dogs Understand Human Actions as Goal-Directed?

Understanding of other’s actions as goal-directed is considered a fundamental ability underlying cognitive and social development in human infants. A number of studies using the habituation-dishabituation paradigm have shown that the ability to discern intentional relations, in terms of goal-directedness of an action towards an object, appears around 5 months of age. The question of whether non-human species can perceive other’s actions as goal-directed has been more controversial, however there is mounting evidence that at least some primates species do. Recently domestic dogs have been shown to be particularly sensitive to human communicative cues and more so in cooperative and intentional contexts. Furthermore, they have been shown to imitate selectively. Taken together these results suggest that dogs may perceive others' actions as goal-directed, however no study has investigated this issue directly. In the current study, adopting an infant habituation-dishabituation paradigm, we investigated whether dogs attribute intentions to an animate (a human) but not an inanimate (a black box) agent interacting with an object. Following an habituation phase in which the agent interacted always with one of two objects, two sets of 3 trials were presented: new side trials (in which the agent interacted with the same object as in the habituation trial but placed in a novel location) and new goal trials (in which the agent interacted with the other object placed in the old location). Dogs showed a similar pattern of response to that shown in infants, looking longer in the new goal than new side trials when they saw the human agent interact with the object. No such difference emerging with the inanimate agent (the black box). Results provide the first evidence that a non-primate species can perceive another individual’s actions as goal-directed. We discuss results in terms of the prevailing mentalisitic and non-mentalistic hypotheses regarding goal-attribution.
Block models and personalized PageRank

Methods for ranking the importance of nodes in a network have a rich history in machine learning and across domains that analyze structured data. Recent work has evaluated these methods through the “seed set expansion problem”: given a subset S of nodes from a community of interest in an underlying graph, can we reliably identify the rest of the community? We start from the observation that the most widely used techniques for this problem, personalized PageRank and heat kernel methods, operate in the space of “landing probabilities” of a random walk rooted at the seed set, ranking nodes according to weighted sums of landing probabilities of different length walks. Both schemes, however, lack an a priori relationship to the seed set objective. In this work, we develop a principled framework for evaluating ranking methods by studying seed set expansion applied to the stochastic block model. We derive the optimal gradient for separating the landing probabilities of two classes in a stochastic block model and find, surprisingly, that under reasonable assumptions the gradient is asymptotically equivalent to personalized PageRank for a specific choice of the PageRank parameter α that depends on the block model parameters. This connection provides a formal motivation for the success of personalized PageRank in seed set expansion and node ranking generally. We use this connection to propose more advanced techniques incorporating higher moments of landing probabilities; our advanced methods exhibit greatly improved performance, despite being simple linear classification rules, and are even competitive with belief propagation.
A Novel Algorithm for Movement Artifact Removal in ECG Signals Acquired from Wearable Systems Applied to Horses

This study reports on a novel method to detect and reduce the contribution of movement artifact (MA) in electrocardiogram (ECG) recordings gathered from horses in free movement conditions. We propose a model that integrates cardiovascular and movement information to estimate the MA contribution. Specifically, ECG and physical activity are continuously acquired from seven horses through a wearable system. Such a system employs completely integrated textile electrodes to monitor ECG and is also equipped with a triaxial accelerometer for movement monitoring. In the literature, the most used technique to remove movement artifacts, when noise bandwidth overlaps the primary source bandwidth, is the adaptive filter. In this study we propose a new algorithm, hereinafter called Stationary Wavelet Movement Artifact Reduction (SWMAR), where the Stationary Wavelet Transform (SWT) decomposition algorithm is employed to identify and remove movement artifacts from ECG signals in horses. A comparative analysis with the Normalized Least Mean Square Adaptive Filter technique (NLMSAF) is performed as well. Results achieved on seven hours of recordings showed a reduction greater than 40% of MA percentage (between before- and after- the application of the proposed algorithm). Moreover, the comparative analysis with the NLMSAF, applied to the same ECG recordings, showed a greater reduction of MA percentage in favour of SWMAR with a statistical significant difference (p–value < 0.0.5).
Crystal structure of the Mus musculus cholesterol-regulated START protein 4 (StarD4) containing a StAR-related lipid transfer domain

The x-ray structure of the mouse cholesterol-regulated START protein 4 (StarD4) has been determined at 2.2-Å resolution, revealing a compact α/β structure related to the START domain present in the cytoplasmic C-terminal portion of human MLN64. The volume of the putative lipid-binding tunnel was estimated at 847 Å3, which is consistent with the binding of one cholesterol-size lipid molecule. Comparison of the tunnel-lining residues in StarD4 and MLN64-START permitted identification of possible lipid specificity determinants in both molecular tunnels. Homology modeling of related proteins, and comparison of the StarD4 and MLN64-START structures, showed that StarD4 is a member of a large START domain superfamily characterized by the helix-grip fold. Additional mechanistic and evolutionary studies should be facilitated by the availability of a second START domain structure from a distant relative of MLN64.
Knowledge expectations of recently diagnosed patients with knee osteoarthritis.

AIM The aim of this study was to assess the socio-demographic and disease-related symptoms and emotions and knowledge expectations of patients recently diagnosed with knee osteoarthritis. A further aim was to determine associations between selected demographic variables and patients' expected knowledge. BACKGROUND Patient counselling and information provision are recommended for all patients with knee osteoarthritis. In healthcare centres, there is a good possibility to establish the knowledge expectations of patients with knee osteoarthritis during counselling. Recent empirical evidence indicates a lack of research on knowledge expectations among recently diagnosed patients with knee osteoarthritis. DESIGN A quantitative, descriptive inquiry design was adopted. METHODS The data were collected from 252 recently diagnosed patients with knee osteoarthritis by a postal survey in 2013, using the Hospital Patient's Knowledge Expectations Scale as well as additional questions and statements. The data were analysed using multivariate linear regression. RESULTS Most of the respondents were female pensioners who also had other chronic diseases. Approximately half of the participants had had counselling on osteoarthritis. Knowledge expectations concerning pain management were emphasized. From the empowering knowledge perspective, the highest knowledge expectations concerned bio-physiological dimensions of knowledge, followed by ethical and financial dimensions. Age, employment status, pain and emotions of concern and hope among women and tiredness or fatigue and vocational/higher education among men were associated with knowledge expectations. CONCLUSION Patients with knee osteoarthritis have high knowledge expectations and there is a need to improve the counselling and care of pain and tiredness or fatigue symptoms. The development of the counselling of recently diagnosed patients with knee osteoarthritis also needs further research.