Miracle-dz/UniFAR-FTUs huggingface dataset:
The autophagy gene Atg16l1 differentially regulates Treg and TH2 cells to control intestinal inflammation

A polymorphism in the autophagy gene Atg16l1 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential for maintenance of balanced CD4+ T cell responses in the intestine. Selective deletion of Atg16l1 in T cells in mice resulted in spontaneous intestinal inflammation that was characterized by aberrant type 2 responses to dietary and microbiota antigens, and by a loss of Foxp3+ Treg cells. Specific ablation of Atg16l1 in Foxp3+ Treg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. Moreover, we also identify an unexpected role for autophagy in directly limiting mucosal TH2 cell expansion. These findings provide new insights into the reciprocal control of distinct intestinal TH cell responses by autophagy, with important implications for understanding and treatment of chronic inflammatory disorders. DOI: http://dx.doi. org/10.7554/eLife.12444. 001
Interaction between Single Nucleotide Polymorphism and Urinary Sodium, Potassium, and Sodium-Potassium Ratio on the Risk of Hypertension in Korean Adults

Hypertension is a complex disease explained with diverse factors including environmental factors and genetic factors. The objectives of this study were to determine the interaction effects between gene variants and 24 h estimated urinary sodium and potassium excretion and sodium-potassium excretion ratios on the risk of hypertension. A total of 8839 participants were included in the genome-wide association study (GWAS) to find genetic factors associated with hypertension. Tanaka and Kawasaki formulas were applied to estimate 24 h urinary sodium and potassium excretion. A total of 4414 participants were included in interaction analyses to identify the interaction effects of gene variants according to 24 h estimated urinary factors on the risk of hypertension. CSK rs1378942 and CSK-MIR4513 rs3784789 were significantly modified by urinary sodium-potassium excretion ratio. In addition, MKLN rs1643270 with urinary potassium excretion, LOC101929750 rs7554672 with urinary sodium and potassium excretion, and TENM4 rs10466739 with urinary sodium-potassium excretion ratio showed significant interaction effects. The present study results indicated that the mutant alleles of CSK rs1378942 and CSK-MIR4513 rs3784789 had the strongest protective effects against hypertension in the middle group of 24 h estimated urinary sodium-potassium excretion ratio. Further studies are needed to replicate these analyses in other populations.
Analytical strategies in human growth research

Human growth research requires knowledge of longitudinal statistical methods that can be analytically challenging. Even the assessment of growth between two ages is not as simple as subtracting the first measurement from the second, for example. This article provides an overview of the key analytical strategies available to human biologists in increasing order of complexity, starting with a review on how to express cross‐sectional measurements of size, before covering growth (conditional regression models, regression with conditional growth measures), growth curves (individual growth curves, mixed effects growth curves, latent growth curves), and patterns of growth (growth mixture modeling). The article is not a statistical treatise and has been written by a human biologist for human biologists; as such, it should be accessible to anyone with training in at least basic statistics. A summary table linking each analytical strategy to its applications is provided to help investigators match their hypotheses and measurement schedules to an analysis plan. In addition, worked examples using data on non‐Hispanic white participants in the Fels Longitudinal Study are used to illustrate how the analytical strategies might be applied to gain novel insight into human growth and its determinants and consequences. All too often, serial measurements are treated as cross‐sectional in analyses that do not harness the power of longitudinal data. The broad goal of this article is to encourage the rigorous application of longitudinal statistical methods to human growth research. Am. J. Hum. Biol. 27:69–83, 2015. © 2014 Wiley Periodicals, Inc.
The ability of primary auditory cortical ( A 1 ) neurons to detect amplitude modulation with 1 rate and temporal codes : neurometric analysis 2

12 Amplitude modulation (AM) is a common feature of natural sounds, and its detection is 13 biologically important. Even though most sounds are not fully modulated, the majority of 14 physiological studies have focused on fully modulated (100% modulation depth) sounds. We 15 presented AM noise at a range of modulation depths to awake macaque monkeys while recording 16 from neurons in primary auditory cortex (A1). The ability of neurons to detect partial AM with 17 rate and temporal codes was assessed using signal detection methods. On average, single cell 18 synchrony was as or more sensitive than spike count in modulation detection. Cells are less 19 sensitive to modulation depth if tested away from their best modulation frequency, particularly 20 for temporal measures. Mean neural modulation detection thresholds in A1 are not as sensitive 21 as behavioral thresholds, but using phase-locking the most sensitive neurons are more sensitive, 22 suggesting that for temporal measures the lower envelope principle cannot account for 23 thresholds. Three methods of pre-analysis pooling of spike trains (multi-unit, similar to 24 convergence from a cortical column; within-cell, similar to convergence of cells with matched 25 response properties; across-cell, similar to indiscriminate convergence of cells) all result in an 26 increase in neural sensitivity to modulation depth for both temporal and rate codes. For the 27 across-cell method, pooling of a few dozen cells can result in detection thresholds that 28 approximate those of the behaving animal. Using synchrony measures, indiscriminate pooling 29 results in sensitive detection of modulation frequencies between 20-60 Hz, suggesting that 30 differences in AM response phase are minor in A1. 31
Adjusting to the Receiving Country Outside the Sport Environment: A Composite Vignette of Canadian Immigrant Amateur Elite Athlete Acculturation

This qualitative project is focused on the challenges that newcomer athletes revealed when they considered their earliest encounters with a receiving culture during general daily life. Conversational interviews with 24 national and international amateur newcomer athletes were subjected to interpretive thematic analysis and developed into a composite vignette. This vignette unearths three themes revealing hope (theme: opportunities abound); uncertainty and fear (theme: weighing the risks for the journey ahead); and anger, humiliation, and hardening (theme: public stonings). Understanding the fluidities within the vignette will permit practitioners to explore the uncertainties of acculturation and find entry points to support athlete acculturation.
HYDROMETALLURGICAL PROCESS FOR EXTRACTION OF METALS FROM ELECTRONIC WASTE-PART II: DEVELOPMENT OF THE PROCESSES FOR THE RECOVERY OF COPPER FROM PRINTED CIRCUIT BOARDS (PCB)

Rapid technological development induces increase of generation of used electric and electronic equipment waste, causing a serious threat to the environment. Waste printed circuit boards (WPCBs), as the main component of the waste, are significant source of base and precious metals, especially copper and gold. In recent years, most of the activities on the recovery of base and precious metals from waste PCBs are focused on hydrometallurgical techniques as more exact, predictable and easily controlled compared to conventional pyrometallurgical processes. In this research essential aspects of the hydrometallurgical processing of waste of electronic and electrical equipment (WEEE) using sulfuric acid and thiourea leaching are presented. Based on the developed flow-sheet, both economic feasibility and return on investment for obtained processing conditions were analyzed. Furthermore, according to this analysis, SuperPro Designer software was used to develop a preliminary techno-economical assessment of presented hydrometallurgical process, suggested for application in small mobile plant addressed to small and medium sized enterprises (SMEs). Following of this paper, the described process is techno-economically feasible for amount of gold exceeding the limit value of 500ppm. Payback time is expected in time period from up to 7 years, depending on two deferent amounts of input waste material, 50kg and 100kg of WEEE per batch.
Mibefradil reduces blood glucose concentration in db/db mice

OBJECTIVE: Numerous recent studies suggest that abnormal intracellular calcium concentration ([Ca2+]i) is a common defect in diabetic animal models and patients. Abnormal calcium handling is an important mechanism in the defective pancreatic β-cell function in type 2 diabetes. T-type Ca2+ channel antagonists lower blood glucose in type 2 diabetes, but the mechanism remains unknown. METHODS: We examined the effect of the Ca2+ channel antagonist mibefradil on blood glucose in male db/db mice and phenotypically normal heterozygous mice by intraperitoneal injection. RESULTS: Mibefradil (15 mg/kg, i.p., b.i.d.) caused a profound reduction of fasting blood glucose from 430.92±20.46 mg/dl to 285.20±5.74 mg/dl in three days. The hypoglycemic effect of mibefradil was reproduced by NNC 55-0396, a compound structurally similar to mibefradil but more selective for T-type Ca2+ channels, but not by the specific L-type Ca2+ channel blocker nicardipine. Mibefradil did not show such hypoglycemic effects in heterozygous animals. In addition, triglycerides, basal insulin and food intake were significantly decreased by mibefradil treatment in the db/db mice but not in the controls. Western blot analysis, immunohistochemistry and immunofluorescence staining showed a significantly increased expression of T-type Ca2+ channel α-subunits Cav3.1 and Cav3.2 in liver and brain tissues from db/db mice compared to those from heterozygous animals. CONCLUSIONS: Collectively, these results suggest that T-type Ca2+ channels are potential therapeutic targets for antidiabetic drugs.
IL-4 and IL-13 Differentially Regulate TLR-Induced Eosinophil-Basophil Differentiation of Cord Blood CD34+ Progenitor Cells

Intrauterine environmental exposures have been shown to influence neonatal immunity and subsequent allergic disease development. We have previously shown that fewer lipopolysaccharide (LPS)-stimulated eosinophil-basophil (Eo/B) colonies grow from cord blood (CB) of high-atopic risk infants, compared to low-atopic risk infants. In the present study, we investigated whether a surrogate ex vivo TH2 milieu (i.e., either IL-4 or IL-13) could represent an underlying mechanism to explain our previous findings. CB CD34+ cells from healthy donors were cultured with IL-4 or IL-13 (in combination with LPS) and assessed for Eo/B differentiation using methylcellulose cultures and flow cytometry for related intracellular signalling pathways. Pharmacological inhibitors were added to the methylcellulose cultures to determine the effect of blocking intracellular signalling in CB CD34+ cells in relation to Eo/B colony forming unit (CFU) formation. Stimulation of CD34+ cells with IL-4, but not IL-13, reduced Eo/B CFU formation in the presence of LPS; this was found to be dependent on IL-4Rα and not IL-13Rα1. Additionally, IL-4 reduced the expression of ERK 1/2 after LPS stimulation, which was recovered by inhibition of IL-4Rα. While IL-13 did not have an inhibitory effect on ERK 1/2 expression, inhibition of ERK 1/2 significantly reduced Eo/B CFU formation. Thus, the responsiveness of CB CD34+ progenitor cells to LPS is differentially regulated by the TH2 cytokines, IL-4 and IL-13. This may have implications for in utero interactions between placental-derived pro-allergic cytokines and neonatal progenitor cells influencing Eo/B-mediated inflammatory responses in early life.
On some equivalence notions of synchronous systems

An important optimization tool in the design of synchronous systems is retiming, which in many cases allows a significant reduction in the length of the systems’ clock period. Even though the internal structure of systems changes upon retiming, their input-output behavior remains essentially the same. The original system and the one after the retiming can simulate each other in a suitable way. The equivalence notion arising from this kind of mutual simulation is called simulation equivalence, and the aim of this paper is to characterize simulation equivalence in an algebraic setting. It is shown that simulation equivalence is a congruence relation of the algebra of synchronous schemes, and that this congruence is the smallest one containing retiming equivalence and finitary strong equivalence. An axiomatization of these equivalences is presented in the general framework of strictly monoidal categories with feedback.
Erectile dysfunction, metabolic syndrome, and cardiovascular risks: facts and controversies

Erectile dysfunction (ED) is the most common male sexual dysfunction, and shares many risk factors with systemic conditions including cardiovascular disease (CVD) and the metabolic syndrome (MetS). ED is considered to be an independent risk factor for CVD and can be a harbinger of future cardiovascular events. Given this relationship, each encounter for ED should be viewed by healthcare providers as an opportunity to screen for CVD and other comorbid conditions, including the MetS, that can significantly affect a man’s overall health. While universally accepted screening guidelines are lacking, expert panels do recommend an approach to risk stratification in men with ED. In this review, we discuss the current state of understanding of the relationship between ED, the MetS, and CV risk, and how this impacts the approach to the patient presenting with ED.
Testosterone and cortisol in relationship to dietary nutrients and resistance exercise.

Manipulation of resistance exercise variables (i.e., intensity, volume, and rest periods) affects the endocrine response to exercise; however, the influence of dietary nutrients on basal and exercise-induced concentrations of hormones is less understood. The present study examined the relationship between dietary nutrients and resting and exercise-induced blood concentrations of testosterone (T) and cortisol (C). Twelve men performed a bench press exercise protocol (5 sets to failure using a 10-repetitions maximum load) and a jump squat protocol (5 sets of 10 repetitions using 30% of each subject's 1-repetition maximum squat) with 2 min of rest between all sets. A blood sample was obtained at preexercise and 5 min postexercise for determination of serum T and C. Subjects also completed detailed dietary food records for a total of 17 days. There was a significant (P < or = 0.05) increase in postexercise T compared with preexercise values for both the bench press (7.4%) and jump squat (15.1%) protocols; however, C was not significantly different from preexercise concentrations. Significant correlations were observed between preexercise T and percent energy protein (r = -0.71), percent energy fat (r = 0.72), saturated fatty acids (g.1,000 kcal-1.day-1; r = 0.77), monounsaturated fatty acids (g.1,000 kcal-1.day-1; r = 0.79, the polyunsaturated fat-to-saturated fat ratio (r = -0.63), and the protein-to-carbohydrate ratio (r = -0.59). There were no significant correlations observed between any nutritional variables and preexercise C or the absolute increase in T and C after exercise. These data confirm that high-intensity resistance exercise results in elevated postexercise T concentrations. A more impressive finding was that dietary nutrients may be capable of modulating resting concentrations of T.
Thrombocytopenia as a Predictor of Severe Acute Kidney Injury in Patients with Hantaan Virus Infections

Background Hematological abnormalities often occur several days before kidney injury in patients with hemorrhagic fever with renal syndrome (HFRS). We aimed to investigate the prevalence and prognostic value of the early hematological markers in patients with HFRS caused by Hantaan virus (HTNV) infection. Methods In a retrospective cohort study, we analyzed the case records of 112 patients with acute HTNV infection and evaluated the hematological markers for early prediction and risk stratification of HFRS patients with acute kidney injury (AKI). Results Of 112 patients analyzed, 66 (59%) developed severe AKI, defined as either receipt of acute dialysis or increased serum creatinine ≥354 µmol/L. The prognostic accuracy of hematological markers, as quantified by the area under the receiver-operating-characteristic curve (AUC), was highest with the nadir platelet count (AUC, 0.89; 95% CI, 0.83–0.95), as compared with the admission platelet count (AUC, 0.84; 95% CI, 0.77–0.92), and the admission and peak leukocyte counts. The nadir platelet count correlated moderately with the levels of peak blood urea nitrogen (r = –0.616) and serum creatinine (r = –0.589), the length of hospital stay (r = –0.599), and the number of dialysis sessions that each patient received during hospital stay (r = –0.625). By multivariate analysis, decreased nadir platelet count remained independently associated with the development of severe AKI (odds ratio, 27.57; 95% CI, 6.96–109.16; P<0.0001). Conclusions Thrombocytopenia, rather than leukocytosis, is independently associated with subsequent severe AKI among patients with acute HTNV infection.
CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE

Marrow cell suspensions of unprimed donor mice have been transplanted into X-irradiated syngeneic hosts. 5–46 days later, bone cavities and spleens contained regenerated cells of the immune system which required interaction with thymocytes (from intact donors) and antigen (SRBC) to form antigen-sensitive units (ASU) and to generate mature immunocytes. These cells were capable of differentiating either into direct or indirect hemolytic plaque-forming cells (PFC). The precursors of PFC regenerated earlier than the other cell type necessary for immunocompetence, the antigen-reactive cell (ARC). The latter was not found until 10 or more days after transplantation. Availability of ARC was inferred from PFC responses elicited by grafted mice challenged with SRBC at varying intervals. In a second series of experiments, graded numbers of marrow cells (ranging from 107 to 5 x 107) were transplanted with 5 x 107 or 108 thymocytes into irradiated mice, and SRBC were given 18 hr later. After 9–12 days the recipient spleens contained all or some of the following immunocytes: direct and indirect PFC, and hemagglutinating cluster-forming cells. The frequency of each immune response varied independently of the others, but in relation to the number of marrow cells grafted. This was interpreted to indicate that ASU formed in irradiated mice by interaction of marrow and thymus cells were similar to those of intact mice. In particular, they were specialized for the molecular class (IgM or IgG) and function (lysis or agglutination) of the antibody to be secreted by their descendent immunocytes. Hence, class-differentiation appeared to be conferred upon ASU by their marrow-derived components.
A reappraisal of success factors for Olympic cross-country skiing.

Cross-country (XC) skiing has been an Olympic event since the first Winter Games in Chamonix, France, in 1924. Due to more effective training and tremendous improvements in equipment and track preparation, the speed of Olympic XC-ski races has increased more than that of any other Olympic endurance sport. Moreover, pursuit, mass-start, and sprint races have been introduced. Indeed, 10 of the 12 current Olympic competitions in XC skiing involve mass starts, in which tactics play a major role and the outcome is often decided in the final sprint. Accordingly, reappraisal of the success factors for performance in this context is required. The very high aerobic capacity (VO2max) of many of today's world-class skiers is similar that of their predecessors. At the same time, the new events provide more opportunities to profit from anaerobic capacity, upper-body power, high-speed techniques, and "tactical flexibility. " The wide range of speeds and slopes involved in XC skiing requires skiers to continuously alternate between and adapt different subtechniques during a race. This technical complexity places a premium on efficiency. The relative amounts of endurance training performed at different levels of intensity have remained essentially constant during the past 4 decades. However, in preparation for the Sochi Olympics in 2014, XC skiers are performing more endurance training on roller skis on competition-specific terrain, placing greater focus on upper-body power and more systematically performing strength training and skiing at high speeds than previously.
Vasovagal reactions in blood donors during or immediately after blood donation

summary. The aim of the study was to estimate the type, incidence and causes of donor adverse reactions during and after blood donation in a Greek Blood Bank, where medical staff is responsible for donor selection. 12 173 blood donors were studied for adverse reactions. One‐hundred and seven (0·87%) donors had a vasovagal reaction during or after blood donation. Donors who gave blood occasionally had a significant greater incidence of reactions compared with volunteer donors (1·15 versus 0·53%) (P < 0·001). There was no significant difference between men and women (0·85 versus 0·95%). First‐time donors (1·7 versus 0·68%) and those under 30 years (1·15 versus 0·71%] had a significant greater possibility to have a reaction (P < 0·001). Twenty‐two of 107 (20·5%) donors had a syncopal reaction. There was not a causative correlation of haematocrit, haemoglobin, systolic and diastolic blood pressure, pulse rate and weight in women (except weight in men) in developing a reaction. The stressing experience of phlebotomy was the reason for the higher frequency of a reaction.
The Development of Sensitivity to Biological Motion in Noise

We investigated developmental changes in sensitivity to biological motion by asking 6-year-olds, 9-year-olds, and adults (twenty-four in each group) to discriminate point-light biological motion displays depicting one of a variety of human movements from scrambled versions of the same displays. When tested without noise dots, participants at all ages performed near ceiling levels and no differences in accuracy were found among the three age groups. Age differences emerged in the second task, in which we used a staircase procedure to determine threshold values of the number of noise dots that could be tolerated in producing a percentage correct value corresponding to a d' value of 1.4. Sensitivity to biological motion improved linearly with age (p < 0.01), with 6-year-olds performing significantly more poorly than adults. This immature performance contrasts with adult-like accuracy by 4 years of age for sensitivity to global motion (Parrish et al, 2005 Vision Research 45 827–837). The comparison implies an immaturity at 6 years of age in the neural networks involved specifically in the processing of biological motion, networks that may include the superior temporal sulcus (STS).