Miracle-dz/UniFAR-FTUs huggingface dataset:
A Bromodomain-Containing Host Protein Mediates the Nuclear Importation of a Satellite RNA of Cucumber Mosaic Virus

ABSTRACT Replication of the satellite RNA (satRNA) of Cucumber Mosaic Virus is dependent on replicase proteins of helper virus (HV). However, we recently demonstrated that like with Potato spindle tuber viroid (PSTVd), a satRNA associated with Cucumber Mosaic Virus strain Q (Q-satRNA) has the propensity to localize in the nucleus and generate multimers that subsequently serve as templates for HV-dependent replication. But the mechanism regulating the nuclear importation of Q-satRNA is unknown. Here we show that the nuclear importation of Q-satRNA is mediated by a bromodomain-containing host protein (BRP1), which is also apparently involved in the nuclear localization of PSTVd. A comparative analysis of nuclear and cytoplasmic fractions from Nicotiana benthamiana plants coinfected with Q-satRNA and its HV confirmed the association of Q-satRNA but not HV with the nuclear compartment. A combination of the MS2-capsid protein-based RNA tagging assay and confocal microscopy demonstrated that the nuclear localization of Q-satRNA was completely blocked in transgenic lines of Nicotiana benthamiana (ph5.2nb) that are defective in BRP1 expression. This defect, however, was restored when the ph5.2nb lines of N. benthamiana were trans-complemented by ectopically expressed BRP1. The binding specificity of BRP1 with Q-satRNA was confirmed in vivo and in vitro by coimmunoprecipitation and electrophoretic mobility shift assays, respectively. Finally, infectivity assays involving coexpression of Q-satRNA and its HV in wild-type and ph5.2nb lines of N. benthamiana accentuated a biological role for BRP1 in the Q-satRNA infection cycle. The significance of these results in relation to a possible evolutionary relationship to viroids is discussed.
Ontogeny of Synovial Macrophages and the Roles of Synovial Macrophages From Different Origins in Arthritis

The ontogeny of macrophages in most organ/tissues in human body has been proven. Due to the limited number and inaccessibility of synovial macrophages (SM), the origin of SM has not been fully illuminated. The objective of this study was designed to investigate the ontogeny of SM and to evaluate the role of SM from different origins in arthritis. Two origins of SM, embryonic SM (ESM) and bone marrow SM (BMSM) were identified in Cx3cr1-EGFP mice, CCR2−/− mice and bone marrow (BM) chimera model by using a stringent sorting strategy. The cellular features, including dynamic total cell number, in situ proliferation, phagocytosis and expressions of pro-inflammatory and anti-inflammatory genes, of ESM and BMSM were compared. In addition, ESM and BMSM showed different expression patterns in Rheumatoid Arthritis (RA) patients' synovium and during the developmental process of collagen-induced arthritis (CIA) mice. Taken together, these results demonstrated that the SM at least has two origins, ESM and BMSM. The different cellular property and dynamic expression patterns in RA patients/CIA mice highlight the notion that ESM and BMSM might play different role in arthritis.
Efficient nonparametric belief propagation for pose estimation and manipulation of articulated objects

A “pull” message passing algorithm is an efficient nonparametric belief propagation for pose estimation of articulated objects. Robots working in human environments often encounter a wide range of articulated objects, such as tools, cabinets, and other jointed objects. Such articulated objects can take an infinite number of possible poses, as a point in a potentially high-dimensional continuous space. A robot must perceive this continuous pose to manipulate the object to a desired pose. This problem of perception and manipulation of articulated objects remains a challenge due to its high dimensionality and multimodal uncertainty. Here, we describe a factored approach to estimate the poses of articulated objects using an efficient approach to nonparametric belief propagation. We consider inputs as geometrical models with articulation constraints and observed RGBD (red, green, blue, and depth) sensor data. The described framework produces object-part pose beliefs iteratively. The problem is formulated as a pairwise Markov random field (MRF), where each hidden node (continuous pose variable) is an observed object-part’s pose and the edges denote the articulation constraints between the parts. We describe articulated pose estimation by a “pull” message passing algorithm for nonparametric belief propagation (PMPNBP) and evaluate its convergence properties over scenes with articulated objects. Robot experiments are provided to demonstrate the necessity of maintaining beliefs to perform goal-driven manipulation tasks.
Monitoring Marine Habitats With Photogrammetry: A Cost-Effective, Accurate, Precise and High-Resolution Reconstruction Method

Underwater photogrammetry has been increasingly used to study and monitor the three-dimensional characteristics of marine habitats, despite a lack of knowledge on the quality and reliability of the reconstructions. More particularly, little attention has been paid to exploring and estimating the relative contribution of multiple acquisition parameters on the model resolution (distance between neighbor vertices), accuracy (closeness to true positions/measures) and precision (variability of positions/measures). On the other hand, some studies used expensive or cumbersome camera systems that can restrict the number of users of this technology for the monitoring of marine habitats. This study aimed at developing a simple and cost-effective protocol able to produce accurate and reproducible high-resolution models. Precisely, the effect of the camera system, flying elevation, camera orientation and number of images on the resolution and accuracy of marine habitat reconstructions was tested through two experiments. A first experiment allowed for testing all combinations of acquisition parameters through the building of 192 models of the same 36 m(2) study site. The flying elevation and camera system strongly affected the model resolution, while the photo density mostly affected bundle adjustment accuracy and total processing time. The camera orientation, in turn, mostly affected the reprojection error. The best combination of parameters was used in a second experiment to assess the accuracy and precision of the resulting reconstructions. The average model resolution was 3.4 mm, and despite a decreasing precision in the positioning of markers with distance to the model center (0.33, 0.27, and 1.2 mm/m Standard Deviation (SD) in X, Y, Z, respectively), the measures were very accurate and precise: 0.08% error +/- 0.06 SD for bar lengths, 0.36% +/- 0.51 SD for a rock model area and 0.92% +/- 0.54 SD for its volume. The 3D geometry of the rock only differed by 1.2 mm +/- 0.8 SD from the ultra-high resolution in-air reference. These results suggest that this simple and cost-effective protocol produces accurate and reproducible models that are suitable for the study and monitoring of marine habitats at a small reef scale.
The Role of Attachment Style in Predicting Repetition of Adolescent Self‐Harm: A Longitudinal Study

This study investigated whether insecure attachment is associated with poorer outcomes at 6‐month follow‐up in adolescents who self‐harm. At baseline the Child Attachment Interview was administered to 52 adolescents (13‐17 years) referred to specialist child and adolescent mental health services and with a recent history of self‐harm. Participants also completed self‐report measures of self‐harm, peer attachment, anxiety, and depression and were administered the means end problem‐solving task. Self‐harm behavior and problem‐solving skills were assessed again at 6‐month follow‐up. At baseline, 14 (27%) were securely attached to their mothers. In the 49 (94%) adolescents followed‐up, those with insecure maternal attachment and insecure peer attachment were more likely to have repeated self‐harm. In addition, securely attached adolescents showed greater improvement in problem‐solving skills. These findings indicate that secure maternal and peer attachments may help recovery from self‐harm, possibly by supporting the acquisition of problem‐solving skills, and highlights the importance of social connections and attachments for youth with a history of self‐harm.
FDTD and SPICE Simulations for Lossy and Dispersive Nonlinear Transmission Lines Used for Pulse Compression : a Comparison

For the first time, we demonstrate the simulation of lossy and dispersive non linear transmission lines (NLTLs) used for pulse compression, by two different time-domain approaches: SPICE and a full wave 3D FDTD. Results show a good agreement between the two approaches. Output pulse risetime is very affected by DC and skin-effect losses.
Structuring baseball live games based on speech recognition using task dependent knowledge and emotion state recognition

It is a difficult problem to recognize baseball live speech because the speech is rather fast, noisy, emotional and disfluent due to rephrasing, repetition, mistakes and grammatical deviation caused by the spontaneous speaking style. To solve these problems, we propose a speech recognition method incorporating emotion state as well as baseball game knowledge, such as counting of inning, out, strike and ball. Due to this emotion state and task dependent knowledge, the proposed method can effectively prevent speech recognition errors. This method is formalized in the framework of probability theory and implemented in the conventional speech decoding (Viterbi) algorithm. Experimental results show that the proposed approach improves the structuring and segmentation accuracy as well as keywords accuracy.
Porcine enteric spirochete infections in the UK: surveillance data and preliminary investigation of atypical isolates

Abstract Investigations into the possible causes of colitis and typhlocolitis were carried out on 98 pig units in the United Kingdom between 1997 and 1999. Brachyspira pilosicoliwas identified most commonly, occurring as the suggested primary agent in 18% of the outbreaks but forming part of mixed infections in another 24% of outbreaks. The equivalent figures for other bacterial pathogens were: B. hyodysenteriae, 13% and 16%; Lawsonia intracellularis, 10% and 15%; Salmonella species, 6% and 12%; and Yersinia species, 4% and 10%. Unclassified Brachyspira species of unknown pathogenicity were identified in 12% of outbreaks. The 24 unclassified isolates divided into three groups on the basis of their phenotypic characteristics. In addition, there were 50 atypical Brachyspira species isolates that showed differences between their phenotypic characteristics and genetic identity based on sequence analysis of a section of the 23S rDNA gene. Four representative atypical isolates were found to be pathogenic as a result of an experimental oral challenge study in pigs.
Meta-analysis on the efficacy of psychological treatments for anorexia nervosa.

OBJECTIVE This meta-analysis examines the efficacy of recently developed psychological treatments for anorexia nervosa, compared with control condition. Outcome criteria are weight gain, eating disorder pathology, and quality of life. METHOD Twelve thousand nine hundred ninety-seven abstracts, published between 1980 and 2017, were retrieved. End-of-treatment data from 1,279 participants, from 15 of 17 eligible studies, were used to calculate pooled-effect sizes (Hedges' g) for outcome using random-effects model. Subgroup analyses were used to explore the influence of various patient and study characteristics. RESULTS No significant differences between psychological treatment and controls were found on weight gain, g = 0.07, 95% CI [-0.09, 0.23], eating disorder pathology, g = 0.06, 95% CI [-0.10, 0.21], and quality of life, g = -0.11, 95% CI [-0.36, 0.15]. Studies including only patients over 18 years of age were more effective on weight gain than studies including adolescents as well. High-quality studies and studies with reported therapist training had larger effects on weight gain and quality of life compared with low-quality studies and studies without reported training. CONCLUSIONS Despite progress in the development of specialized treatments, the efficacy of psychological treatment over an active control condition could not be established. Outcomes, however, are obscured by low-quality and heterogeneous studies.
The E3 ligase VHL promotes follicular helper T cell differentiation via glycolytic-epigenetic control

Follicular helper T (Tfh) cells are essential for germinal center formation and effective humoral immunity, which undergo different stages of development to become fully polarized. However, the detailed mechanisms of their regulation remain unsolved. Here we found that the E3 ubiquitin ligase VHL was required for Tfh cell development and function upon acute virus infection or antigen immunization. VHL acted through the hypoxia-inducible factor 1α (HIF-1α)-dependent glycolysis pathway to positively regulate early Tfh cell initiation. The enhanced glycolytic activity due to VHL deficiency was involved in the epigenetic regulation of ICOS expression, a critical molecule for Tfh development. By using an RNA interference screen, we identified the glycolytic enzyme GAPDH as the key target for the reduced ICOS expression via m6A modification. Our results thus demonstrated that the VHL-HIF-1α axis played an important role during the initiation of Tfh cell development through glycolytic-epigenetic reprogramming.
A canonical promoter organization of the transcription machinery and its regulators in the Saccharomyces genome

The Pol II transcription machinery assembles and operates in the context of nucleosomes, which have well‐defined canonical positions at the beginning and end of protein‐coding genes. However, the predominant organizational theme by which the transcription machinery and chromatin regulators are positioned within promoter regions or throughout genes in a genome is largely unknown. We have mapped the genomic location of diverse representative components of the gene regulatory machinery in Saccharomyces cerevisiae to an experimental resolution of <40 bp using ChIP‐chip. Defining how these factors are arranged with respect to each other and to promoter nucleosome positions should provide insight into how the organization of the transcription machinery at promoters regulates gene expression. We find that the ‐1 nucleosome, which establishes the upstream border of the promoter region, is a likely target of substantial regulation (assuming that occupancy is linked to function) since nearly all tested chromatin remodeling complexes selectively occupy the ‐1 nucleosomal region compared to the +1 region. Furthermore, we find that the ‐1 nucleosome is depleted rather than laterally displaced when Pol II is present, but not when only TBP and TFIIB are recruited. This suggests that the ‐1 nucleosome is removed during PIC assembly, after TBP and TFIIB have been recruited, but before or concurrent with Pol II recruitment, which might explain the prevalence of remodeling complexes in the vicinity of the ‐1 nucleosome.
Investigating the stratified efficacy and safety of pharmacological blood pressure-lowering: an overall protocol for individual patient-level data meta-analyses of over 300 000 randomised participants in the new phase of the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC)

Introduction Previous research from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) and others has shown that pharmacological blood pressure (BP)- lowering substantially reduces the risk of major cardiovascular events, including ischaemic heart disease, heart failure and stroke. In this new phase, the aim is to conduct individual patient-level data (IPD) meta-analyses involving eligible BP-lowering randomised controlled trials (RCTs) to address uncertainties relating to efficacy and safety of BP-lowering treatment. Methods and analysis RCTs investigating the effect of pharmacological BP-lowering, with a minimum of 1000 patient-years of follow-up in each trial arm, are eligible. Our systematic review identified 100 potentially eligible trials. We requested their investigators/sponsors to contribute baseline, follow-up and outcomes data. As of June 2018, the collaboration has obtained data from 49 trials (n=315 046 participants), with additional data currently in the process of being transferred from four RCTs (n=34 642 participants). In addition, data harmonisation has commenced. Scientific activities of the collaboration are overseen by the Steering Committee with input from all collaborators. Detailed protocols for individual meta-analyses will be developed and registered on public platforms. Ethics and dissemination Ethics approval has been obtained for this new and extended phase of the BPLTTC, the largest collaboration of de-identified IPD from RCTs. It offers an efficient and ethical manner of re-purposing existing data to answer clinically important questions relating to BP treatment as well as methodological questions relating to IPD meta-analyses. Among the immediate impacts will include reliable quantification of effects of treatment modifiers, such as baseline BP, age and prior disease, on both vascular and non-vascular outcomes. Analyses will further assess the impact of BP-lowering on important, but less well understood, outcomes, such as new-onset diabetes and renal disease. Findings will be published in peer-reviewed medical journals on behalf of the collaboration.
Database analysis of the risk factors of bisphosphonate-related osteonecrosis of the jaw in Hungarian patients

Objective Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but serious side effect of bisphosphonates (BPs). Since this disease has no independent code in either of the diseases’ or in the medical procedures’ classifications, it is hard to estimate how many BP patients are affected. Design A retrospective observational epidemiological registry-based study was carried out, using the data of the national service of Hungary on the incidence of BRONJ and related factors. Setting A data analysis was performed, which is relevant for the whole Hungarian population from 2010 to 2014. The socioeconomic and medication data of 236 207 BP patients were analysed, and a method was worked out to define BRONJ patients from the Hungarian BP population. Primary and secondary outcome measures The incidences of BRONJ were analysed according to genders and the types of the BP drugs administered. The marginal interdependence between the types of BP drugs, modes of administration and main indication was calculated. Results 340 BP patients (0.1%) developed BRONJ. The incidence of BRONJ in Hungary in the malignant indication of BPs is 0.9%, and 0.1% in the non-malignant indication, and the OR to develop BRONJ was OR=9.7 (95% CI 7.8 to 12.1) between them. Although more women developed BRONJ, the proportion of men was significantly higher than that of women. Steroids increase the risk of jaw osteonecrosis, and differences were also found between the BP drugs. Conclusions Oncology indicated, intravenously administered and steroid comedicated BP therapies pose a high risk of developing BRONJ in the Hungarian population.
68Ga-Galmydar: A PET imaging tracer for noninvasive detection of Doxorubicin-induced cardiotoxicity

Background Cancer patients undergoing Doxorubicin (DOX) treatment are susceptible to acute and chronic cardiac anomalies, including aberrant arrhythmias, ventricular dysfunction, and heart failure. To stratify patients at high risk for DOX -related heart failure (CHF), diagnostic techniques have been sought. While echocardiography is used for monitoring LVEF and LV volumes due to its wide-availability and cost-efficiency, it may not identify early stages of the initiation of DOX-induced systolic heart failure. To address these limitations, PET tracers could also provide noninvasive assessment of early and reversible metabolic changes of the myocardium. Objective Herein, we report a preliminary investigation of 68Ga-Galmydar potential to monitor Dox-induced cardiomyopathy in vivo, ex vivo, and in cellulo employing both nuclear- and optical imaging. Methods and results To assess 68Ga-Galmydar ability for monitoring DOX-induced cardiomyopathy, microPET imaging was performed 5 d post treatment of rats either with a single dose of DOX (15 mg/kg) or vehicle as a control (saline) and images were co-registered for anatomical reference using CT. Following tail-vein injection of the radiotracer in rats at 60 min, micro-PET/CT static scan (10 min acquisition), 68Ga-Galmydar demonstrated 1.91-fold lower uptake in hearts of DOX-treated (standard uptake value; SUV: 0.92, n = 3) rats compared with their vehicle treated (SUV: 1.76, n = 3) control counterparts. For correlation of PET imaging data, post-imaging quantitative biodistribution studies were also performed, wherein excised organs were counted for γ activity, and normalized to injected dose. The post imaging pharmacokinetic data also demonstrated heart uptake values of 2.0 fold lower for DOX treated rats(%ID/g; DOX: 0.44 ± 0.1, n = 3) compared to their vehicle-treated controls (%ID/g; Control: 0.89 ± 0.03, n = 3, p = 0.04). Employing the fluorescent traits of Galmydar, live cell fluorescence imaging indicated a gradual decrease in uptake and retention of Galmydar within mitochondria of H9c2 cells following DOX-treatment, while indicating dose-dependent and time-dependent uptake profiles. Following depolarization of electronegative transmembrane gradients at the mitochondrial membrane, the uptake of the probe was decreased in H9c2 cells, and the uptake profiles were found to be identical, using both fluorescence and radiotracer bioassays. Finally, the decreased uptake of the metalloprobe in H9c2 cells also correlated with caspase-3 expression resulting from DOX-induced cardiotoxicity and cell death. Conclusions 68Ga-Galmydar could provide a noninvasive assessment of DOX-related and likely reversible metabolic changes at earliest stages. Further studies with other chemotherapeutics (potentially capable of inducing cardiomyopathy) are underway.
Induction of COX‐2 by LPS in macrophages is regulated by Tpl2‐dependent CREB activation signals

Macrophage activation by bacterial lipopolysaccharide (LPS) promotes the secretion of pro‐inflammatory cytokines, such as tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β), and of secondary mediators, such as leukotrienes and prostaglandins (PGs). Mice lacking the gene encoding the serine/threonine protein kinase Tpl2/Cot produce low levels of TNF‐α in response to LPS because of an ERK‐dependent post‐transcriptional defect, and they are resistant to LPS/D‐galactosamine‐induced endotoxin shock. In this study we demonstrate that prostaglandin E2 and its regulatory enzyme, COX‐2, are also targets of Tpl2‐transduced LPS signals in bone marrow‐derived mouse macrophages. Thus, LPS‐stimulated Tpl2−/− macrophages express low levels of COX‐2 and PGE2, compared with wild‐type Tpl2+/+ cells. The ability of Tpl2 to regulate COX‐2 expression depends on ERK signals that activate p90Rsk and Msk1, which in turn phosphorylate CREB, a key regulator of COX‐2 transcription. These data identify physiological targets of Tpl2 signaling downstream of ERK and further implicate Tpl2 in the pathophysiology of inflammation.