Miracle-dz/UniFAR-FTUs huggingface dataset:
New Family of Regulators in the Environmental Signaling Pathway Which Activates the General Stress Transcription Factor ςB of Bacillus subtilis

ABSTRACT Expression of the general stress regulon of Bacillus subtilis is controlled by the alternative transcription factor ςB, which is activated when cells encounter growth-limiting energy or environmental stresses. The RsbT serine-threonine kinase is required to convey environmental stress signals to ςB, and this kinase activity is magnified in vitro by the RsbR protein, a positive regulator important for full in vivo response to salt or heat stress. Previous genetic analysis suggested that RsbR function is redundant with other unidentified regulators. A search of the translated B. subtilis genome found six paralogous proteins with significant similarity to RsbR: YetI, YezB, YkoB, YojH, YqhA, and YtvA. Their possible regulatory roles were investigated using three different approaches. First, genetic analysis found that null mutations in four of the six paralogous genes have marked effects on the ςB environmental signaling pathway, either singly or in combination. The two exceptions wereyetI and yezB, adjacent genes which appear to encode a split paralog. Second, biochemical analysis found that YkoB, YojH, and YqhA are specifically phosphorylated in vitro by the RsbT environmental signaling kinase, as had been previously shown for RsbR, which is phosphorylated on two threonine residues in its C-terminal region. Both residues are conserved in the three phosphorylated paralogs but are absent in the ones that were not substrates of RsbT: YetI and YezB, each of which bears only one of the conserved residues; and YtvA, which lacks both residues and instead possesses an N-terminal PAS domain. Third, analysis in the yeast two-hybrid system suggested that all six paralogs interact with each other and with the RsbR and RsbS environmental regulators. Our data indicate that (i) RsbR, YkoB, YojH, YqhA, and YtvA function in the environmental stress signaling pathway; (ii) YtvA acts as a positive regulator; and (iii) RsbR, YkoB, YojH, and YqhA collectively act as potent negative regulators whose loss increases ςB activity more than 400-fold in unstressed cells.
Liver and kidney disease in ciliopathies

Hepatorenal fibrocystic diseases (HRFCDs) are among the most common inherited human disorders. The discovery that proteins defective in the autosomal dominant and recessive polycystic kidney diseases (ADPKD and ARPKD) localize to the primary cilia and the recognition of the role these organelles play in the pathogenesis of HRFCDs led to the term “ciliopathies. ” While ADPKD and ARPKD are the most common ciliopathies associated with both liver and kidney disease, variable degrees of renal and/or hepatic involvement occur in many other ciliopathies, including Joubert, Bardet–Biedl, Meckel–Gruber, and oral–facial–digital syndromes. The ductal plate malformation (DPM), a developmental abnormality of the portobiliary system, is the basis of the liver disease in ciliopathies that manifest congenital hepatic fibrosis (CHF), Caroli syndrome (CS), and polycystic liver disease (PLD). Hepatocellular function remains relatively preserved in ciliopathy‐associated liver diseases. The major morbidity associated with CHF is portal hypertension (PH), often leading to esophageal varices and hypersplenism. In addition, CD predisposes to recurrent cholangitis. PLD is not typically associated with PH, but may result in complications due to mass effects. The kidney pathology in ciliopathies ranges from non‐functional cystic dysplastic kidneys to an isolated urinary concentration defect; the disorders contributing to this pathology, in addition to ADPKD and ARPKD, include nephronophithisis (NPHP), glomerulocystic kidney disease and medullary sponge kidneys. Decreased urinary concentration ability, resulting in polyuria and polydypsia, is the first and most common renal symptom in ciliopathies. While the majority of ADPKD, ARPKD, and NPHP patients require renal transplantation, the frequency and rate of progression to renal failure varies considerably in other ciliopathies. This review focuses on the kidney and liver disease found in the different ciliopathies. Published 2009 Wiley‐Liss, Inc.
Probabilistic Submodular Maximization in Sub-Linear Time

In this paper, we consider optimizing submodular functions that are drawn from some unknown distribution. This setting arises, e.g., in recommender systems, where the utility of a subset of items may depend on a user-specific submodular utility function. In modern applications, the ground set of items is often so large that even the widely used (lazy) greedy algorithm is not efficient enough. As a remedy, we introduce the problem of sublinear time probabilistic submodular maximization: Given training examples of functions (e.g., via user feature vectors), we seek to reduce the ground set so that optimizing new functions drawn from the same distribution will provide almost as much value when restricted to the reduced ground set as when using the full set. We cast this problem as a two-stage submodular maximization and develop a novel efficient algorithm for this problem which offers a 1 2 (1− 1 e2 ) approximation ratio for general monotone submodular functions and general matroid constraints. We demonstrate the effectiveness of our approach on several real-world applications where running the maximization problem on the reduced ground set leads to two orders of magnitude speed-up while incurring almost no loss.
Social support and psychological distress in rheumatoid arthritis: a 4-year prospective study

Introduction: The objective of the study was to investigate the course of psychological distress in early rheumatoid arthritis patients and to explore the strength of its associations with disease-related variables over time. A further aim focused specifically on the associations between social support and psychological distress. Methods: The study had a longitudinal design, with four annual measurements over consecutive years. The course and stability of psychological distress on the individual level were investigated via test–retest correlation coefficients and changes over time were studied using the Friedman test for repeated measurements. Hierarchical regression analysis was performed to analyze the multilinear associations of disease activity, functional disability, joint tenderness, pain and social support with psychological distress. Results: Significant cross-sectional associations were found among functional disability, joint tenderness, pain, emotional support, instrumental support and psychological distress. However, after controlling for the erratic pattern of the disease and the relevant variables, only initial psychological distress and emotional support retained a significant relationship with psychological distress. The final regression model, in which functional disability, pain, emotional support and initial psychological distress were significant variables, explained 36% of the variance in psychological distress. Conclusion: The study stresses the importance of initial psychological distress, which was found to have the highest correlation with psychological distress experienced 4 years later. In addition, higher emotional support and lower pain were found to be the only variables independently associated with lower levels of psychological distress after controlling for the relevant variables. Implications for Rehabilitation Psychological distress is a relevant problem in rheumatoid arthritis patients and should be recognized early in the disease as it might reflect a lack of social resources which can be crucial in the further course of the disease. Special attention should be paid to different types of social support in relation to psychological distress, which might improve targeting psychosocial interventions.
Sliding window recursive DFT with dyadic downsampling — A new strategy for time-varying power harmonic decomposition

The main objective of this paper is to present a time-varying harmonic decomposition using the sliding-window Discrete Fourier Transform including a dyadic downsampling. The method has been conceived to decompose and to visualize time-varying harmonics up to 15th order, with a low computational effort. The downsampling must be done carefully in order to impose no aliasing error to the lower order harmonics. The algorithm has been very efficient and helpful when tracking time-varying power harmonic and it has been applied to track harmonic distortion and understand time-dependent power quality events. The method presents potential for other applications such as control and protection.
When Available Resources Become Negative Resources

This study uses signal detection measures and secondary task reaction times (STRTs) to examine the effects of structural complexity and information density on processing television messages. Of particular interest are results pertaining to cognitive overload experienced while processing structurally complex and informationally dense messages. When required resources exceed available resources—that is, when a state of cognitive overload is reached—both memory sensitivity and criterion bias drop dramatically while STRTs get faster. The results provide support for the contention that secondary task reaction times are often very fast during highly complex messages because the system is overloaded and therefore resources are shifted from the primary task to the secondary task. Also of interest, the liberal shift in criterion bias starts before overload has occurred, suggesting that criterion bias may be tracking available resources.
Interleukin‐1β and microRNA‐146a in an immature rat model and children with mesial temporal lobe epilepsy

Purpose: Increasing evidence indicates that neuroinflammation plays a critical role in the pathogenesis of mesial temporal lobe epilepsy (MTLE). The aim of this study was to investigate the dynamic expression of interleukin (IL)–1β as a proinflammatory cytokine and microRNA (miR)‐146a as a posttranscriptional inflammation‐associated microRNA (miRNA) in the hippocampi of an immature rat model and children with MTLE.
Social benefit payments and acute injury among low-income mothers

Background Human error due to risky behaviour is a common and important contributor to acute injury related to poverty. We studied whether social benefit payments mitigate or exacerbate risky behaviours that lead to emergency visits for acute injury among low-income mothers with dependent children. Methods We analyzed total emergency department visits throughout Ontario to identify women between 15 and 55 years of age who were mothers of children younger than 18 years, who were living in the lowest socio-economic quintile and who presented with acute injury. We used universal health care databases to evaluate emergency department visits during specific days on which social benefit payments were made (child benefit distribution) relative to visits on control days over a 7-year interval (1 April 2003 to 31 March 2010). Results A total of 153 377 emergency department visits met the inclusion criteria. We observed fewer emergencies per day on child benefit payment days than on control days (56.4 v. 60.1, p = 0.008). The difference was primarily explained by lower values among mothers age 35 years or younger (relative reduction 7.29%, 95% confidence interval [CI] 1.69% to 12.88%), those living in urban areas (relative reduction 7.07%, 95% CI 3.05% to 11.10%) and those treated at community hospitals (relative reduction 6.83%, 95% CI 2.46% to 11.19%). No significant differences were observed for the 7 days immediately before or the 7 days immediately after the child benefit payment. Interpretation Contrary to political commentary, we found that small reductions in relative poverty mitigated, rather than exacerbated, risky behaviours that contribute to acute injury among low-income mothers with dependent children.
A Chemical and Enzymatic Approach to Study Site-Specific Sumoylation

A variety of cellular pathways are regulated by protein modifications with ubiquitin-family proteins. SUMO, the Small Ubiquitin-like MOdifier, is covalently attached to lysine on target proteins via a cascade reaction catalyzed by E1, E2, and E3 enzymes. A major barrier to understanding the diverse regulatory roles of SUMO has been a lack of suitable methods to identify protein sumoylation sites. Here we developed a mass-spectrometry (MS) based approach combining chemical and enzymatic modifications to identify sumoylation sites. We applied this method to analyze the auto-sumoylation of the E1 enzyme in vitro and compared it to the GG-remnant method using Smt3-I96R as a substrate. We further examined the effect of smt3-I96R mutation in vivo and performed a proteome-wide analysis of protein sumoylation sites in Saccharomyces cerevisiae. To validate these findings, we confirmed several sumoylation sites of Aos1 and Uba2 in vivo. Together, these results demonstrate that our chemical and enzymatic method for identifying protein sumoylation sites provides a useful tool and that a combination of methods allows a detailed analysis of protein sumoylation sites.
Technological review on endoscopic submucosal dissection: available equipment, recent developments and emerging techniques

Abstract Endoscopic submucosal dissection (ESD) is widely practiced in Japan and the Eastern World and is rapidly expanding in western countries for the management of early malignancies of the upper and lower gastrointestinal tube. In addition, novel therapeutic applications deriving from ESD have emerged including the treatment of achalasia, of submucosal tumors, of diverticula, of strictures and of reflux disease. An ESD procedure necessitates not only skills and specific training, but also familiarization with a vast spectrum of devices (endoscopes, high-frequency generators and their settings, endoknives, hoods, irrigation devices) and techniques (such as countertraction, artificial ulcer closure), that render the procedure faster, more efficient and safer. This technological article gives an overview on current and novel equipment for an ESD and associated techniques.
Granulocyte‐derived elastase and gelatinase B are required for dermal–epidermal separation induced by autoantibodies from patients with epidermolysis bullosa acquisita and bullous pemphigoid

Epidermolysis bullosa acquisita (EBA) and bullous pemphigoid (BP) are two clinically and immunologically distinct autoimmune subepidermal blistering skin diseases associated with IgG autoantibodies against the dermal–epidermal junction. BP antibodies are directed against the hemidesmosomal antigens BP180 and BP230, and those in patients with EBA target type VII collagen, a major component of anchoring fibrils. While the pathogenetic mechanisms of subepidermal blistering in BP have been previously studied using a passive transfer mouse model, the effector pathways of blister formation in EBA are largely unknown. Autoantibodies to type VII collagen and BP180 have recently been shown to induce leucocyte‐mediated subepidermal cleavage in cryosections of human skin. The aim of the present study was to identify human leucocyte protease(s) instrumental in dermal–epidermal separation induced by autoantibodies to type VII collagen and BP180. When incubated with cryosections of human skin pretreated with IgG from patients with EBA or BP but not from patients with anti‐laminin 5 mucous membrane pemphigoid or healthy controls, granulocytes were recruited to the dermal–epidermal junction and induced subepidermal splits. A combination of broad‐range protease inhibitors as well as inhibitors of serine and matrix metalloproteases completely abolished dermal–epidermal separation induced by EBA or BP autoantibodies. When characterizing the proteases involved more specifically, selective inhibition of human leucocyte elastase or gelatinase B/MMP‐9 was also found to result in suppression of blistering. These findings strongly suggest that elastase and gelatinase B are essential for granulocyte‐mediated proteolysis resulting in dermal–epidermal separation in EBA and BP patients' skin. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cerebroretinal Microangiopathy With Calcifications and Cysts Associated With CTC1 and NDP Mutations

Mutations in the conserved telomere maintenance component 1 (CTC1) gene were recently described in Coats plus syndrome and in cerebroretinal microangiopathy with calcifications and cysts. Norrie disease protein (NDP) gene was found mutated in Norrie disease, in Familial Exudative Vitreoretinopathy, and in Coats syndrome. Here we describe a boy affected by Norrie disease who developed typical features of cerebroretinal microangiopathy with calcifications and cysts. Direct sequencing of the CTC1 and NDP genes in this patient shows the presence of compound heterozygosity for 2 mutations in CTC1 (c.775G>A, pV259M and a novel microdeletion c.1213delG) and a missense mutation in the NDP gene (c.182T>C, p.L61P). Based on these genetic findings and on the expression of both genes in endothelial cells, we postulate that microangiopathy might be a primary underlying pathologic abnormality in cerebroretinal microangiopathy with calcifications and cysts. This hypothesis is further supported by magnetic resonance imaging (MRI) data showing multiple minute calcifications in the deep gray nuclei and in terminal arteriolar zones.
Adherence and Persistence to Long-Acting Anticholinergics Treatment Episodes in Patients With Chronic Obstructive Pulmonary Disease

Background:No studies have examined adherence or persistence to long-acting anticholinergics (LAAC) treatment episodes in patients with chronic obstructive pulmonary disease (COPD). Objective: To estimate 1-year adherence and 5-year persistence to LAAC during treatment episodes, and the likelihood of initiating a subsequent treatment episode. Methods: A retrospective cohort of LAAC-treated COPD patients was reconstructed from Quebec databases. A treatment episode was initiated at cohort entry, defined as the first LAAC prescription date on/after the first COPD diagnosis date recorded between October 1, 2003, and March 31, 2014. We identified a subsequent treatment episode up to 5 years after the end of the episode initiated at cohort entry. We measured adherence as the proportion of days covered over 1 year. Persistence was defined as prescription renewal within 90 days of the previous prescription and was plotted using Kaplan-Meier curves over 5 years. The 5-year hazard and cumulative incidence of initiating a subsequent episode were estimated with survival analyses. We compared adherence and persistence between the treatment episodes using t and log-rank tests. Results: The cohort included 113 435 COPD patients. Adherence and persistence to LAAC were significantly lower in the subsequent treatment episode (55% vs 63%; P < 0.0001). The likelihood of initiating a subsequent episode was greatest immediately after the cessation of the initial episode, with 59% of patients starting a subsequent episode within 1 year. Conclusion: Adherence and persistence to LAAC were lower in the subsequent treatment episode. Interventions should be offered quickly after LAAC cessation.
Putative Calcium Channels CchA and MidA Play the Important Roles in Conidiation, Hyphal Polarity and Cell Wall Components in Aspergillus nidulans

Although the high affinity Ca2+ channel, Cch1, and its subunit Mid1 have been investigated and evaluated in yeast and some of filamentous fungi, little is known about the function of their homologs in the Aspergilli. Here, we have functionally characterized the yeast homologs, CchA and MidA, in Aspergillus nidulans using conditional and null deletion mutants. CchA and MidA not only have functional benefits of fast growth, which is consistent with Cch1 and Mid1 in yeast, but also have unique and complex roles in regulating conidiation, hyphal polarity and cell wall components in low-calcium environments. The defect of CchA or MidA resulted in a sharp reduction in the number of conidiospores, accompanied by abnormal metulae, and undeveloped-phialides at a higher density of inoculum. Most interestingly, these conidiation defects in mutants can, remarkably, be rescued either by extra-cellular Ca2+ in a calcineurin-dependent way or by osmotic stress in a calcineurin-independent way. Moreover, the fact that the phenotypic defects are not exacerbated by the presence of the double deletion, together with the Y2H assay, indicates that CchA and MidA may form a complex to function together. Our findings suggest that the high-affinity Ca2+ channel may represent a viable and completely unexplored avenue to reduce conidiation in the Aspergilli.
Genetic and phenotypic diversity in selected genotypes of tef (Eragrostis tef (Zucc.) Trotter

Tef [Eragrostis tef (Zucc.) Trotter] is an important staple food crop, especially in Ethiopia where it is annually grown on 2.8 million hectares of land. It is important for food security in the region, in spite of having a low yield, mainly due to lodging. In this study, 15 representative landraces as well as three improved varieties have been selected for in-depth characterization of many parameters, especially those implicated in yield. The genotypes were clustered into six groups, mainly based on agronomic traits and about 80% of the diversity in the genotypes could be explained on the basis of four principal components. In general, all traits investigated showed substantial diversity among genotypes, offering high chances for improving tef through direct selection or intra-specific hybridization. Moreover, in view of climatic changes, breeding with early maturing landraces such as Red dabi or Karadebi would be advantageous to cope with moisture scarcity during the later stage of crop maturity.
Clinical Differences between Younger and Older Adults with HIV/AIDS Starting Antiretroviral Therapy in Uganda and Zimbabwe: A Secondary Analysis of the DART Trial

Objective Clinical and immunological data about HIV in older adults from low and middle income countries is scarce. We aimed to describe differences between younger and older adults with HIV starting antiretroviral therapy in two low–income African countries. Methods Setting: HIV clinics in Uganda and Zimbabwe. Design: Secondary exploratory cross-sectional analysis of the DART randomized controlled trial. Outcome Measures: Clinical and laboratory characteristics were compared between adults aged 18-49 years (younger) and ≥ 50 years (older), using two exploratory multivariable logistic regression models, one with HIV viral load (measured in a subset pre-ART) and one without. Results A total of 3316 eligible participants enrolled in DART were available for analysis; 219 (7%) were ≥ 50 years and 1160 (35%) were male. Across the two adjusted regression models, older adults had significantly higher systolic blood pressure, lower creatinine clearance and were consistently less likely to be females compared to younger adults with HIV. Paradoxically, the models separately suggested that older adults had statistically significant (but not clinically important) higher CD4+ cell counts and higher plasma HIV–1 viral copies at initiation. Crude associations between older age and higher baseline hemoglobin, body mass index, diastolic blood pressure and lower WHO clinical stage were not sustained in the adjusted analysis. Conclusions Our study found clinical and immunological differences between younger and older adults, in a cohort of Africans starting antiretroviral therapy. Further investigations should explore how these differences could be used to ensure equity in service delivery and affect outcomes of antiretroviral therapy.