Miracle-dz/UniFAR-FTUs huggingface dataset:
Mesenchymal Cell Precursors of Peritubular Smooth Muscle Cells of the Mouse Testis Can Be Identified by the Presence of the p75 Neurotrophin Receptor1

Abstract In the mouse embryo, at approximately 11.5 days postcoitum (dpc), cells migrate from the mesonephros into the developing testis to contribute to the somatic population of the interstitial compartment (i.e., peritubular myoid cells, Leydig cells, and endothelial cells). Studies from this laboratory have shown that the interstitial population of mesenchymal cells in fetal and newborn mouse testis express the p75 neurotrophin receptor (p75NTR, formerly known as the low-affinity nerve growth factor receptor); part of the cell population progressively congregates around testis cords, later to be replaced by contractile peritubular myoid cells, which express smooth muscle cell markers. In the present study, we show that the migrating cells and the p75NTR-expressing cells are the same population. We also show that the neurotrophin receptor is a useful endogenous marker to follow cell migration within the urogenital ridge and to identify and isolate mesenchymal precursors of myoid cells. A time-course immunolocalization study of the location of p75NTR-bearing cells within the urogenital ridge of mouse embryos between 10.5 and 12.5 dpc showed that the interstitium of the fetal testis was progressively occupied by p75NTR(+) cells. The progressive increase of p75NTR expression within the developing testis was confirmed by immunoblot analysis of proteins isolated from the fetal gonads. Organ cultures of isolated testes or testis-mesonephros grafts confirmed that p75NTR(+) cells do not appear in the testis unless a mesonephros is attached to it. Cells bearing the p75NTR receptor, purified from 12.5-dpc male mouse mesonephroi by immunomagnetic sorting, were able to differentiate in vitro into myoid cells. Immunofluorescence analysis of postnatal testis sections confirmed the presence around the tubules of cells coexpressing p75NTR and α-smooth muscle actin. The ability to identify and purify precursors of myoid cells may be of considerable help for studying the mechanisms regulating their differentiation.
Determinants of asthma control among children in Saudi Arabia

Abstract Objective: Asthma is the most common chronic disease among children. Uncontrolled asthma may considerably decrease the quality of life for patients and their families. Our objective was to identify possible risk factors for poor asthma control in children. Methods: A cross-sectional study was conducted among children with asthma aged 4–11 years who attended a pediatric clinic for follow-up visits at one of the major teaching hospitals in Riyadh, Saudi Arabia. Asthma control status was measured by the childhood asthma control test. Multiple logistic regression analysis was performed to explore the relationships between the outcome and exposure variables. Results: Uncontrolled asthma was present in 89 out of 158 children (59.3%). Asthma control improved with the number of siblings. Control improved by 69% with two or three siblings (OR = 0.31, 95% CI = 0.10–0.96) and by 87% with four or more siblings (OR = 0.13, 95% CI = 0.04–0.48). Similarly, asthma control improved with an increased asthma knowledge of the caregiver (OR = 0.87, 95% CI = 0.81–0.93). Household incomes less than SAR 15 000 and sharing a bedroom increased the odds of having uncontrolled asthma by 2.30 (95% CI = 1.02–5.21) and 3.33 (95% CI = 1.33–8.35), respectively. Conclusions: In addition to knowledge, socioeconomic factors, such as family income, household crowding, and the number of siblings are associated with asthma control among children in Saudi Arabia. Further research is needed to investigate the role of these factors.
Crystal Structure of Lipoate-Protein Ligase A Bound with the Activated Intermediate

Lipoic acid is the covalently attached cofactor of several multi-component enzyme complexes that catalyze key metabolic reactions. Attachment of lipoic acid to the lipoyl-dependent enzymes is catalyzed by lipoate-protein ligases (LPLs). In Escherichia coli, two distinct enzymes lipoate-protein ligase A (LplA) and lipB-encoded lipoyltransferase (LipB) catalyze independent pathways for lipoylation of the target proteins. The reaction catalyzed by LplA occurs in two steps. First, LplA activates exogenously supplied lipoic acid at the expense of ATP to lipoyl-AMP. Next, it transfers the enzyme-bound lipoyl-AMP to the ϵ-amino group of a specific lysine residue of the lipoyl domain to give an amide linkage. To gain insight into the mechanism of action by LplA, we have determined the crystal structure of Thermoplasma acidophilum LplA in three forms: (i) the apo form; (ii) the ATP complex; and (iii) the lipoyl-AMP complex. The overall fold of LplA bears some resemblance to that of the biotinyl protein ligase module of the E. coli biotin holoenzyme synthetase/bio repressor (BirA). Lipoyl-AMP is bound deeply in the bifurcated pocket of LplA and adopts a U-shaped conformation. Only the phosphate group and part of the ribose sugar of lipoyl-AMP are accessible from the bulk solvent through a tunnel-like passage, whereas the rest of the activated intermediate is completely buried inside the active site pocket. This first view of the activated intermediate bound to LplA allowed us to propose a model of the complexes between Ta LplA and lipoyl domains, thus shedding light on the target protein/lysine residue specificity of LplA.
NT-proBNP predicts mortality in patients with rheumatoid arthritis: results from 10-year follow-up of the EURIDISS study

Objectives Patients with rheumatoid arthritis (RA) have a higher mortality than the general population, and this increased mortality is related to demographic and disease variables. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor of mortality both in general and patient populations, but has not been shown to predict mortality in patients with RA. This study examines whether NT-proBNP can further improve the prediction of mortality in RA. Methods 182 patients with RA of 5–9 years disease duration were comprehensively examined in 1997. Serum samples were frozen and later batch analysed for NT-proBNP levels and other biomarkers. Adjusted univariate and logistic regression analyses were performed with death within the 10-year follow-up period as the dependent variable. Significant predictors were also examined as dichotomised variables. Results Mortality was predicted in univariate analyses by the following variables: age, sex, homozygosity for HLA-DRB1 shared epitope alleles, Health Assessment Questionnaire, 28-joint Disease Activity Score (DAS28) and NT-proBNP. A multivariate model with age, sex, DAS28 and NT-proBNP as independent variables showed the greatest discrimination. Conclusion NT-proBNP provided incremental information in the prediction of mortality in this cohort of patients with RA.
EFFECTS OF SPRINT AND PLYOMETRIC TRAINING ON MUSCLE FUNCTION AND ATHLETIC PERFORMANCE

The purpose of this study was to evaluate the effects of sprint training on muscle function and dynamic athletic performance and to compare them with the training effects induced by standard plyometric training. Male physical education students were assigned randomly to 1 of 3 groups: sprint group (SG; n = 30), plyometric group (PG; n = 30), or control group (CG; n = 33). Maximal isometric squat strength, squat-and counter-movement jump (SJ and CMJ) height and power, drop jump performance from 30-cm height, and 3 athletic performance tests (standing long jump, 20-m sprint, and 20-yard shuttle run) were measured prior to and after 10 weeks of training. Both experimental groups trained 3 days a week; SG performed maximal sprints over distances of 10–50 m, whereas PG performed bounce-type hurdle jumps and drop jumps. Participants in the CG group maintained their daily physical activities for the duration of the study. Both SG and PG significantly improved drop jump performance (15.6 and 14.2%), SJ and CMJ height (∼10 and 6%), and standing long jump distance (3.2 and 2.8%), whereas the respective effect sizes (ES) were moderate to high and ranged between 0.4 and 1.1. In addition, SG also improved isometric squat strength (10%; ES = 0.4) and SJ and CMJ power (4%; ES = 0.4, and 7%; ES = 0.4), as well as sprint (3.1%; ES = 0.9) and agility (4.3%; ES = 1.1) performance. We conclude that short-term sprint training produces similar or even greater training effects in muscle function and athletic performance than does conventional plyometric training. This study provides support for the use of sprint training as an applicable training method of improving explosive performance of athletes in general.
Chronic administration of lipopolysaccharide and proteases induces periodontal inflammation and hepatic steatosis in rats.

BACKGROUND Epidemiologic studies suggest a relationship between periodontitis and liver diseases. A rat periodontitis model was used to investigate whether a causal relationship exists between periodontitis and liver diseases. METHODS Fourteen male Wistar rats (8 weeks old) were divided into two groups: a periodontitis group in which Escherichia coli lipopolysaccharide (LPS) and Streptomyces griseus proteases were applied into the gingival sulcus for 8 weeks, and a control group using pyrogen-free water instead. After blood samples were collected, periodontal tissues and liver specimens were analyzed. RESULTS Chronic administration of LPS and proteases to the gingival sulcus induced periodontitis and liver injury, including steatosis with inflammation and sinusoidal fibrosis. Apoptosis, enhanced concentration of 8-hydroxydeoxyguanosine, and activated production of tumor necrosis factor-alpha in liver were observed in the periodontitis group, with increased gingival inflammation, serum LPS, and reactive oxygen species. CONCLUSION Periodontal inflammation in a rat model induced fatty liver disease through increased serum LPS.
Phylogeny and biogeography of Allium (Amaryllidaceae: Allieae) based on nuclear ribosomal internal transcribed spacer and chloroplast rps16 sequences, focusing on the inclusion of species endemic to China.

BACKGROUND AND AIMS The genus Allium comprises more than 800 species, placing it among the largest monocotyledonous genera. It is a variable group that is spread widely across the Holarctic region. Previous studies of Allium have been useful in identifying and assessing its evolutionary lineages. However, there are still many gaps in our knowledge of infrageneric taxonomy and evolution of Allium. Further understanding of its phylogeny and biogeography will be achieved only through continued phylogenetic studies, especially of those species endemic to China that have often been excluded from previous analyses. Earlier molecular studies have shown that Chinese Allium is not monophyletic, so the goal of the present study was to infer the phylogeny and biogeography of Allium and to provide a classification of Chinese Allium by placement of Chinese species in the context of the entire phylogeny. METHODS Phylogenetic studies were based on sequence data of the nuclear ribosomal internal transcribed spacer (ITS) and chloroplast rps16 intron, analysed using parsimony and Bayesian approaches. Biogeographical patterns were conducted using statistical dispersal-vicariance analysis (S-DIVA). KEY RESULTS Phylogenetic analyses indicate that Allium is monophyletic and consists of three major clades. Optimal reconstructions have favoured the ancestors of Amerallium, Anguinum, Vvedenskya, Porphyroprason and Melanocrommyum as originating in eastern Asia. CONCLUSIONS Phylogenetic analyses reveal that Allium is monophyletic but that some subgenera are not. The large genetic distances imply that Allium is of ancient origin. Molecular data suggest that its evolution proceeded along three separate evolutionary lines. S-DIVA indicates that the ancestor of Amerallium, Anguinum, Vvedenskya, Porphyroprason and Melanocrommyum originated from eastern Asia and underwent different biogeographical pathways. A taxonomic synopsis of Chinese Allium at sectional level is given, which divides Chinese Allium into 13 subgenera and 34 sections.
Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Purpose: TP53 mutations in early-stage non–small cell lung cancer (NSCLC) may be associated with worse survival but their prognostic role in advanced NSCLC is controversial. In addition, it remains unclear whether mutated patients represent a clinically homogeneous group. Experimental Design: We retrospectively examined TP53 mutations and outcome in a training cohort of 318 patients with stage IIIB–IV NSCLC: 125 epidermal growth factor receptor (EGFR) wild-type (wt) and 193 EGFR mutated (mut). An independent validation cohort of 64 EGFR-mut patients was subsequently analyzed. Mutations were classified as “disruptive” and “nondisruptive” according to their predicted degree of disturbance of the p53 protein structure and function. Results: In the training cohort, TP53 mutations were found in 43 of the 125 EGFR-wt patients (34.4%). Of these, 28 had nondisruptive TP53 mutations and a median overall survival (OS) of 8.5 months, compared with 15.6 months for the remaining 97 patients (P = 0.003). In the EGFR-mut group, TP53 mutations were found in 50 of the 193 patients (25.9%). The OS for the 26 patients with TP53 nondisruptive mutations was 17.8 months versus 28.4 months for the remaining 167 patients (P = 0.04). In the validation cohort, the 11 patients with nondisruptive TP53 mutations had a median OS of 18.1 months compared with 37.8 months for the 53 remaining patients (P = 0.006). In multivariate analyses, nondisruptive TP53 mutations had an independent, significant association with a shorter OS. Conclusions: Nondisruptive mutations in the TP53 gene are an independent prognostic factor of shorter survival in advanced NSCLC. Clin Cancer Res; 20(17); 4647–59. ©2014 AACR.
Mediation by 5‐hydroxytryptamine of the femoral vasoconstriction induced by acid challenge of the rat gastric mucosa

1 Gastric mucosal barrier disruption in the presence of luminal acid causes femoral vasoconstriction via a pathway that appears to be stimulated by messengers generated in the injured gastric mucosa. This study was undertaken to analyse the gastric factors that are responsible for the femoral vasoconstrictor response. 2 Gastric mucosal barrier disruption in the presence of luminal acid was induced by perfusing the stomach of urethane‐anaesthetized rats with ethanol (15 %) in 0.01‐0.15 M HCl. Blood flow in the left gastric and right femoral artery was estimated by the ultrasonic transit time shift technique. 3 Gastric perfusion of ethanol in HCl caused loss of H+ ions from the gastric lumen, decreased the HCO3− concentration in hepatic portal vein blood, induced macroscopic histological damage to the gastric mucosa, dilated the left gastric artery and constricted the femoral artery. These responses were related to the HCl concentration in the ethanol‐containing perfusion medium. 4 The femoral vasoconstriction was also seen when, instead of ethanol, taurocholate (20 mM) was used to disrupt the gastric mucosal barrier in the presence of 0.15 M HCl. 5 The femoral vasoconstriction evoked by gastric perfusion of ethanol in HCl was left unaltered by pharmacological blockade of gastrin and histamine receptors. In contrast, the 5‐hydroxytryptamine 5‐HT1/2 receptor antagonist methiothepin, but not the 5‐HT2A receptor antagonist ketanserin or the 5‐HT3 receptor antagonist granisetron, inhibited the ability of both 5‐hydroxytryptamine and gastric acid back‐diffusion to constrict the femoral artery. 6 Gastric acid back‐diffusion caused release of 5‐hydroxytryptamine into the gastric lumen, which was related to the HCl concentration in the ethanol‐containing perfusion medium. 7 These data show that femoral vasoconstriction evoked by gastric mucosal barrier disruption depends on back‐diffusion of acid into the mucosa. The acid‐induced damage results in release of 5‐hydroxytryptamine from the gastric mucosa, and the pathway leading to constriction of the femoral artery involves 5‐hydroxytryptamine acting via 5‐HT1/2 receptors as a messenger molecule.
BMP-7 Blocks the Cyclosporine-A-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells

Aims: The nephrotoxic side effects of cyclosporine A (CsA) are partly due to induction of the epithelial-to-mesenchymal transition (EMT), possibly through upregulation of connective tissue growth factor (CTGF). Bone morphogenetic protein (BMP-7) has been reported to protect against and reverse renal injury via its renotropic and antifibrotic effects. We therefore designed a method to investigate the mechanism by which BMP-7 inhibits CSA-induced EMT in cultured human renal proximal tubular epithelial (HK-2) cells and whether BMP-7 can antagonize CsA-induced profibrogenic effects. Methods: Cultured HK-2 cells were treated with CsA or a combination of CsA and BMP-7 for 72 h. Morphological changes were assessed by phase-contrast microscopy. The expression of α-smooth muscle actin (α-SMA), E-cadherin, collagen type I and CTGF was analyzed by immunofluorescence, RT-PCR, and Western blot. Additionally, the effect of CTGF silencing on CsA-mediated gene expression was assessed. Results: CsA-induced EMT was associated with decreased expression of E-cadherin, increased expression of α-SMA, collagen type I and CTGF, and loss of epithelial morphology. BMP-7 inhibited these effects in a dose-dependent manner. Using siRNA, CTGF knock-down also attenuated EMT-associated phenotypic changes induced by CsA. Conclusion: These data suggest that BMP-7 can block CsA-induced EMT by downregulating the expression of CTGF, a downstream mediator of EMT.
Trends in initiation of alcohol use in the United States 1975 to 2003.

INTRODUCTION Alcohol is the drug of choice for youth in the United States. By 8th grade, more than 40% of youth have used alcohol; by 12th grade, almost 80% have done so (MTF, 2003). And many of these young people begin drinking at relatively early ages. On average, boys start drinking earlier than girls, and whites and Native Americans start drinking earlier than youth of other race/ethnicities. As alcohol consumption is such a high prevalence behavior among young people, it is crucial to understand the initiation of drinking as well as possible, so as to facilitate and inform interventions to delay this behavior. One facet of this involves investigating trends in the initiation of drinking. METHODS Multiple years of data from 3 national surveys, Monitoring the Future (MTF)-1975 to 2003 for 12th graders, 1993 to 2003 for 8th and 10th graders; the National Household Survey on Drug Abuse (NHSDA) [now called the National Survey on Drug Use and Health (NSDUH)]-1991 to 1998; and the Youth Risk Behavior Surveillance System (YRBSS)-1991 to 2003, were analyzed using joinpoint analysis to further understanding of trends in the initiation of drinking by youth. The present analysis examines whether the age of drinking initiation has changed over time and evaluates trends in the percentages of youth who start drinking by various grades. RESULTS Simultaneous examination of data from the 3 surveys indicates that 7th and 8th grades (when most youth are 13-14) are peak years for the initiation of drinking. Further, the present analysis shows that although the percentage of youth who start drinking early (before age 13) has declined (YRBSS, MTF), the average age of initiation of drinking for these "very early starters" did not change over the period 1991 to 1998 (NHSDA/NSDUH). At the same time, an upward shift in the "normative" age of initiation has occurred (NHSDA/NSDUH, MTF). Results of analyses by gender and race/ethnicity indicate similar trends over time. CONCLUSION A more nuanced understanding of the initiation of drinking can have important implications for prevention.
Clinical and Demographic Characteristics of Erosion-free and Erosion-present Status in Psoriatic Arthritis in a Cohort Study

Objective. Psoriatic arthritis (PsA) has been recognized as a severe erosive disease. However, some patients do not develop erosions. We aimed to determine the prevalence, characteristics, and predictors of erosion-free patients (EFP) as compared with erosion-present patients (EPP) among patients with PsA followed prospectively. Methods. This is a retrospective analysis conducted on patients from the Toronto PsA cohort. Patients with at least 10 years of followup and radiographs were analyzed. Radiographs were scored with the modified Steinbrocker method. Baseline (first visit to clinic) characteristics were used to predict the development of erosions with logistic regression models. To examine the effect of time-varying covariates, Cox regression models were fit for the time to development of erosions from baseline. Results. Among 290 patients, 12.4% were EFP and 87.6% were EPP over the study period. The mean time to development of erosion in the EPP over the course of followup was 6.8 ± 6.1 years. EFP were diagnosed with psoriasis at a younger age compared with EPP. In both models, actively inflamed joints and clinically damaged joints were predictive of the development of erosion, whereas a longer duration of psoriasis at baseline decreased the odds of developing erosion. EPP had a higher percentage of unemployment as compared with EFP at baseline and followup visits. Conclusion. Among patients with PsA followed for at least 10 years, 12.4% never develop erosions. The clinical and radiographic findings can ultimately assist in the stratification of a patient’s prognosis regarding the development of erosions.
Herpes simplex‐specific IgG subclass response in herpetic keratitis

The measurement of the local IgG response in ocular Herpes simplex virus infection presents particular problems due to the difficulty in obtaining sufficient tear samples and the possible transudation of IgG from the serum to the inflamed eye. Using specific monoclonal antibodies to Human IgG subclasses in an enzyme‐linked immunoabsorbant assay (ELISA) the local IgG antibody response in Herpes simplex keratitis was analysed. All serum samples from patients and controls contained quantifiable levels of HSV specific IgG1 and IgG4 antibody. Comparison of serum antibody levels with tear levels for patients showed that HSV specific IgG1 serum concentrations were 16.1 fold or more higher than in tears, whereas IgG4 concentrations were only 6.5 fold higher in serum than in tears. This difference was not apparent in the control group. Radioimmunoprecipitation assay of 35S‐methionine labelled HSV antigens revealed only minor differences in the protein profiles produced by immunoprecipitation using serum or tear antibody. These results suggest a role for IgG4 antibodies in mucosal immunity in the eye as has been suggested for the mucosal surface of the lung.