Miracle-dz/UniFAR-FTUs huggingface dataset:
An Early HIV Mutation within an HLA-B*57-Restricted T Cell Epitope Abrogates Binding to the Killer Inhibitory Receptor 3DL1

ABSTRACT Mutations within MHC class I-restricted epitopes have been studied in relation to T cell-mediated immune escape, but their impact on NK cells via interaction with killer Ig-like receptors (KIRs) during early HIV infection is poorly understood. In two patients acutely infected with HIV-1, we observed the appearance of a mutation within the B*57-restricted TW10 epitope (G9E) that did not facilitate strong escape from T cell recognition. The NK cell receptor KIR3DL1, carried by these patients, is known to recognize HLA-B*5703 and is associated with good control of HIV-1. Therefore, we tested whether the G9E mutation influenced the binding of HLA-B*5703 to soluble KIR3DL1 protein by surface plasmon resonance, and while the wild-type sequence and a second (T3N) variant were recognized, the G9E variant abrogated KIR3DL1 binding. We extended the study to determine the peptide sensitivity of KIR3DL1 interaction with epitopes carrying mutations near the C termini of TW10 and a second HLA-B*57-restricted epitope, IW9. Several amino acid changes interfered with KIR3DL1 binding, the most extreme of which included the G9E mutation commonly selected by HLA-B*57. Our results imply that during HIV-1 infection, some early-emerging variants could affect KIR-HLA interaction, with possible implications for immune recognition.
Being your own boss: the many faces of self-employment

The number of individuals registered as self-employed in the UK has grown considerablyover the past decade. The economics literature generally agrees that the self-employedwork longer hours than their counterparts who are in paid employment and earn less.However, most of the literature considers the self-employed as a homogeneous group ofindividuals, whereas in reality, the term now encompasses a variety of very differententrepreneurs, such as businesses or partnerships, sole traders, freelance workers andsub-contractors. Using UK panel data, this paper examines the differences in thecharacteristics of self-employed individuals by self-employment type to highlight thedifference between these groups and their employed counterparts. Random effect probitestimations that model the determinants of being in different self-employment groupshighlight the heterogeneous nature of self-employment and their different determinants.Wage estimations reveal different returns to separate classifications of self-employment.
Effect of prepartum administration of monensin in a controlled-release capsule on milk production and milk components in early lactation.

Dry cows and pregnant heifers from 25 farms near Guelph, Ontario, Canada were enrolled in a large double-blind, randomized clinical trial that was designed to evaluate the impact of monensin on energy metabolism, health, and production. A total of 503 cows was given monensin in controlled-release capsules, and 507 were administered placebo capsules 3 wk prior to the expected calving date. The effects of treatment on milk production and milk components at the first three Dairy Herd Improvement (DHI) tests were evaluated using repeated measures analysis of variance. Treatment with monensin increased milk production, but this effect was dependent on body condition score prior to calving. Cows that were classified as thin (score of < or = 3.0) did not have increased production in response to monensin treatment. Cows with fair body condition (score of 3.25 to 3.75) produced significantly more milk at the second DHI test (+0.85 kg), but cows that were fat (score of > or = 4.0) produced significantly more milk than did controls for all three DHI tests (+1.25 kg) in early lactation. Monensin significantly increased projected 305-d milk production in cows from herds at increased risk of ketosis. Treatment with monensin had no significant effect on either milk fat percentage or milk protein percentage.
Regulatory T cell subsets in peripheral blood of celiac disease patients and TLR2 expression: correlation with oxidative stress

The study was carried out to study expression of Toll like receptors 2 (TLR2), natural/inducible Treg and Interferon‐γ alongside oxidative stress and understand their significance in pediatric samples. Influence of oxidative stress on Celiac Disease was analysed by evaluating lipid peroxidation, reduced glutathione, Glutathione peroxidase, etc. A comparison was performed among CD patients, CD patients on gluten free diet (GFD), and healthy controls. Peripheral nTregs exhibited a similar pattern of reduced numbers in CD and GFD cases when compared to healthy controls. On the other hand, inducible Tregs were much lower in GFD patients as compared to CD patients. Expression of TLR2 on iTregs was elevated in CD and GFD, however, expression on nTregs was unaltered in all the three groups. The inflammatory cytokine IFN‐γ positive Treg cells were found to be elevated in CD as compared to control group. Oxidative stress was elevated in CD as compared to healthy controls while that in GFD samples was lower in comparison to CD. The levels of LPO, activities of enzymes SOD and Catalase were higher in CD and GFD samples when compared to controls. However, enzyme Glutathione peroxidase and reduced glutathione levels declined in both CD and GFD groups as compared to controls. This report highlights the effect of elevated oxidative stress in CD on reduced traffic of iTregs toward periphery. A strong correlation was observed between the cytokine IFN‐γ and TLR2 expression in movement of iTregs in CD patients.
Ubiquitin‐specific protease 2‐69 in macrophages potentially modulates metainflammation

Macrophages play a critical role in chronic inflammation and metabolic diseases. We identified a longer splice variant of ubiquitin specific protease (USP) 2‐69 as a novel molecule that modulates pathways implicated in metabolic disorders. Expression levels of aP2/FABP4 and PAI‐1/SERPINE1 genes were increased by 4‐and 1.8‐fold, respectively, after short hairpin RNA‐mediated knockdown (KD) of the USP2 gene, and such expression was alleviated by overexpression of USP2‐69 in human myeloid cell lines. Supernatants derived from USP2‐KD cells induced IL6 (~ 6‐fold) and SAA3 (~ 15‐fold) in 3T3‐L1 adipocytes to suggest the anti‐inflammatory properties of USP2. In addition, we observed a 30% decrease in the number of macrophages in mesenteric adipose tissue derived from USP2‐69 transgenic mice fed a high‐fat diet for 14 wk compared with that in their C57BL/6 littermates (P<0.01), which was consistent with a ~40% decrease in transcription of aP2 and PAI‐1. The aP2 locus exhibited elevated chromatin accessibility (>2.1‐fold), methylation of histone H3 lysine 4 (>4.5‐fold), and acetylation of histone H4 (>2.5‐fold) in USP2‐KD cells. Transfection of isopeptidase‐mutated USP2‐69 did not alter chromatin conformation on the aP2 locus in USP2‐KD cells. Our results suggest that USP2‐69 suppresses meta‐inflammatory molecules involved in the development of type‐2 diabetes. —Kitamura, H. , Kimura, S. , Shimamoto, Y. , Okabe, J., Ito, M. , Miyamoto, T. , Naoe, Y. , Kikuguchi, C. , Meek, B. , Toda, C. , Okamoto, S. , Kanehira, K. , Hase, K. , Watarai, H. , Ishizuka, M. , El‐Osta, A. , Ohara, O. , Miyoshi, I. , Ubiquitin‐specific protease 2–69 in macrophages potentially modulates metainflammation. FASEB J. 27, 4940–4953 (2013). www.fasebj. org
Darkness at Noon: Sunscreens and Vitamin D3

We are assured by responsible scientific and governmental organizations that sunscreens should be routinely worn to reduce skin cancer risk. We are also advised that wearing sunscreens will not hinder our ability to produce sufficient previtamin D3 (preD3) from casual sunlight exposure. We report the examination of a series of 166 solar spectra, obtained on different days throughout a year, evaluated for erythemic and preD3 effectiveness and the relative effects of recommended Sun protection factor (SPF) 15 sunscreen. The results show that the sunscreen is much more effective in blocking the formation of preD3, than its labeled SPF for preventing sunburn. In fact with sunscreen applied only miniscule amounts of preD3 are predicted to be made outdoors even with extensive exposure. This raises important questions regarding the safest way to use sunlight exposure to promote healthy vitamin D3 levels and suggests the need to modify the public safety “Safe Sun” messages.
Predictors of Response in Emergency Department Patients Receiving Intravenous Opioids for Severe Pain

The primary objective of this study was to identify significant environmental and patient characteristics of emergency department (ED) patients who responded to intravenous (IV) hydromorphone and IV morphine for severe pain. Secondary objectives were to investigate the individual effect of the significant environmental and patient characteristics of responders, and to assess the nature and strength of the correlation of initial dose and change in pain score from arrival to pre‐administration. A retrospective chart review was performed in patients who received IV hydromorphone or morphine in the ED for severe pain. Key evaluated patient characteristics included patient demographics, recent opioid use, history of drug or alcohol abuse, and pain location, among others. Key evaluated environmental characteristics included initial opioid administered, time to first dose, initial pain score, and initial dose of opioid administered, among others. Environmental and patient characteristics associated with response to pain management were first identified using bivariate analyses and then entered into a multiple stepwise logistic regression mode. Patients were excluded if they were younger than 18 years, did not have a follow‐up pain score within 2 hours of drug administration, or if they were discharged from the ED within 1 hour of administration. Patients meeting the inclusion criteria were grouped into two cohorts based on response and lack of response to treatment. A total of 200 patients were included. A decrease in pain score from arrival until pre‐administration pain score and an inactive tobacco history had a positive association with response (odds ratio [OR] 1.488, 95% confidence interval [CI] 1.088–2.036, p=0.013, and OR 1.835, 95% CI 0.801–4.200, overall p=0.022, respectively). A higher initial dose and an active tobacco history had a negative association with response (OR 0.715, 95% CI 0.580–0.881, p=0.002, and OR 0.582, 95% CI 0.296–1.144, overall p=0.022, respectively). Two characteristics were associated with response to IV opioid pain management in the ED, inactive tobacco history and an increase in pain score from arrival until pre‐administration, and two characteristics were associated with nonresponse to IV opioid pain management in the ED, active tobacco history and a higher initial dose. Previous literature supports both characteristics identified as risk factors but does not support either characteristic identified as protective factors, prompting the need for further research.
Factors that influence teacher attrition in secondary schools in the Omusati education region, Namibia

High teacher turnover is a common problem in the Ministry of Education in all schools around Namibia, specifically in the Omusati Education Region. This research sought to highlight factors that influence teacher attrition in secondary schools in the Omusati Education Region. The research revealed that though hundreds of teachers were graduating from universities and colleges around the country each year, schools have never had enough qualified teachers. A high teacher turnover is also very costly to the government in terms of recruitment and selection costs, which have to be met in continuously filling vacant posts. A high turnover of teachers creates instability in the school system and thereby affecting the performance of learners. The study revealed different factors, which influenced the level of teacher attrition, such as the lack of administrative support for teachers, poor remuneration, death and illness-induced attrition. The review of literature also revealed different strategies that have been used elsewhere in dealing with the problem of high turnover in schools. The strategies included strengthening administrative structures in schools, reviewing the remuneration of teachers, improving the recruitment of teachers and improving the general working conditions of teachers. The study used the triangulated research methodology in the data-gathering process, which involved questionnaires that were given out to teachers and interviews held with Circuit Inspectors. Sixty-four questionnaires were recovered and four interviews were held with Circuit Inspectors. The field and theoretical research findings revealed that interpersonal relations had a limited influence on teacher attrition. Advancement factors were found to have significant influence on the rate of attrition, as teachers left the profession because of limited career advancement opportunities within the teaching profession. One of the major causes of teacher attrition was also found to be unfavourable working conditions such as heavy teaching loads, inadequate resources, and inadequate preparation time. Teachers’
Contrasting Role of Temperature in Structuring Regional Patterns of Invasive and Native Pestilential Stink Bugs

Objectives Assessment and identification of spatial structures in the distribution and abundance of invasive species is important for unraveling the underlying ecological processes. The invasive agricultural insect pest Halyomorpha halys that causes severe economic losses in the United States is currently expanding both within United States and across Europe. We examined the drivers of H. halys invasion by characterizing the distribution and abundance patterns of H. halys and native stink bugs (Chinavia hilaris and Euschistus servus) across eight different spatial scales. We then quantified the interactive and individual influences of temperature, and measures of resource availability and distance from source populations, and their relevant spatial scales. We used Moran’s Eigenvector Maps based on Gabriel graph framework to quantify spatial relationships among the soybean fields in mid-Atlantic Unites States surveyed for stink bugs. Findings Results from the multi-spatial scale, multivariate analyses showed that temperature and its interaction with resource availability and distance from source populations structures the patterns in H. halys at very broad spatial scale. H. halys abundance decreased with increasing average June temperature and distance from source population. H. halys were not recorded at fields with average June temperature higher than 23.5°C. In parts with suitable climate, high H. halys abundance was positively associated with percentage developed open area and percentage deciduous forests at 250m scale. Broad scale patterns in native stink bugs were positively associated with increasing forest cover and, in contrast to the invasive H. halys, increasing mean July temperature. Our results identify the contrasting role of temperature in structuring regional patterns in H. halys and native stink bugs, while demonstrating its interaction with resource availability and distance from source populations for structuring H. halys patterns. Conclusion These results help predicting the pest potential of H. halys and vulnerability of agricultural systems at various regions, given the climatic conditions, and its interaction with resource availability and distance from source populations. Monitoring and control efforts within parts of the United States and Europe with more suitable climate could focus in areas of peri-urban developments with deciduous forests and other host plants, along with efforts to reduce propagule pressure.
The relationship between acute stress disorder and posttraumatic stress disorder in the neonatal intensive care unit.

BACKGROUND Having an infant hospitalized in the neonatal intensive care unit (NICU) is a highly stressful event for parents. Researchers have proposed posttraumatic stress disorder (PTSD) as a model to explain the psychological reaction of parents to their NICU experience. OBJECTIVE The authors sought to examine the prevalence of PTSD in parents 4 months after the birth of their premature or sick infants and the relationship of PTSD and symptoms of acute stress disorder (ASD) immediately after their infant's birth. METHOD Eighteen parents completed a self-report measure of ASD at baseline in addition to self-report measures of PTSD and depression at a 4-month follow-up assessment. RESULTS In the sample, 33% of fathers and 9% of mothers met criteria for PTSD. ASD symptoms were significantly correlated with both PTSD and depression. Fathers showed a more delayed onset in their PTSD symptoms, but, by 4 months, were at even greater risk than mothers. DISCUSSION The relatively high levels of psychological distress experienced by parents coupled with the potential negative outcomes on the parent and infant suggest that it is important to try to prepare parents for the expected psychological reactions that may occur in the event of a NICU hospitalization and also to support parents during the transition to home care.
Short sleep duration in middle childhood: risk factors and consequences.

STUDY OBJECTIVES To measure sleep duration in 7-year-old children; identify the determinants of sleep duration; and assess the association between short sleep duration and obesity, cognitive functioning, and behaviour. DESIGN Longitudinal study with disproportionate sampling of the participants. SETTING Community. PARTICIPANTS 591 seven-year-old children, of whom 519 had complete sleep data. INTERVENTIONS Not applicable. MEASUREMENTS Sleep duration was assessed by actigraphy. Other measurements included height, weight, BMI, percentage body fat as assessed by bioimpedance assay, intelligence (WISC-III) and behaviour (Strengths & Difficulties questionnaire, parent and teachers Conners Rating Scales). RESULTS Mean time in bed according to parental report was 10.9 hours (SD 0.8). Mean sleep duration by actigraphy was 10.1 (SD 0.8) hours. In multivariable analysis, sleep duration was longer on weekdays vs. weekend nights (31.5 min, P = 0.002), in winter (40.5 min), autumn (31.1 min), and spring (14.8 min) compared with summer (P <0.0001), and in those with younger siblings (11.7 min, P = 0.03). Sleep duration was shorter when bedtime was after 21:00 (-41.1 min, P <0.0001). In multivariable analysis, sleep duration <9 hours was associated with being overweight/ obese (BMI: OR = 3.32; 95% CI = 1.40, 7.87) with an increase of 3.34% body fat (P = 0.03), and this was not explained by physical activity or television watching. Short sleep duration was also associated with higher emotional lability scores (Conners Rating Scale Parent Form; P = 0.03). IQ (WISC-III) and attention deficit / hyperactivity disorder scores (both parent and teachers Conners Rating Scales) did not differ with sleep duration. CONCLUSIONS Sleep duration in 7-year-old children varies considerably among individuals. The duration is affected by weekday, season, and having younger siblings. Importantly, short sleep duration was shown to be an independent risk factor for obesity/overweight.
Human immunodeficiency virus glycoprotein (gp120) infused into rat brain induces interleukin 1 to elevate pituitary-adrenal activity and decrease peripheral cellular immune responses.

Intracerebroventricular (i.c.v.) infusion of glycosylated recombinant gp120, the envelope protein of human immunodeficiency virus, in various doses (100 ng to 4 micrograms) resulted in detection of interleukin 1 (IL-1) activity in a high percentage (61%; 33 of 54) of rat brains, whereas IL-1 was very rarely detected in brains of animals infused with several control substances (4%; 1 of 28). To detect IL-1, clarified glial lysate of diencephalon plus brainstem was subjected to gel exclusion chromatography and fractions were assessed for thymocyte stimulation. IL-1 was seen 2, 6, and 24 hr postinfusion. i.c. v. gp120 also produced known effects of IL-1 in brain, elevating steroid concentration in plasma and decreasing cellular immune responses [natural killer (NK) cell activity and mitogenic response to Con A] of blood and splenic lymphocytes. When gp120 was infused together with alpha-melanocyte-stimulating hormone (20 ng), which blocks many biological actions of IL-1, gp120 no longer elevated steroids or decreased NK cell activity. After intravenous gp120, IL-1 was not found in brain or plasma, indicating that stimulation of IL-1 in brain by i.c. v. gp120 was not due to gp120 affecting infiltrating cells from blood or to elevated circulating IL-1. That induction of IL-1 in brain might have resulted from lipopolysaccharide (LPS) in the gp120 solution was ruled out by studies showing that (i) heating of the infusion solution, which does not affect the capacity of LPS to induce IL-1, eliminated the ability of gp120 infusion to induce brain IL-1, and (ii) gp120 induced IL-1 in brains of LPS-resistant C3H/HeJ mice. Injection of gp120 directly into the hippocampus stimulated IL-1 more readily than i.c. v. infusion. Thymocyte stimulation produced by active fractions of gp120-infused brains was blocked by monoclonal antibody to IL-1 receptors. These findings indicate that elevation of IL-1 in brain can result from infection with human immunodeficiency virus and may be responsible for certain abnormalities (e.g., elevated activity of pituitary-adrenal axis) seen in AIDS patients.
A subcortical network of dysfunction in TLE measured by magnetic resonance spectroscopy

Objective: The goal of this work was to evaluate the relationship between neuronal injury/loss in the hippocampus, thalamus, and putamen in temporal lobe epilepsy (TLE) patients using 1H magnetic resonance spectroscopic imaging. Methods: 1H spectroscopic images from the hippocampus and thalamus of controls and patients with TLE were acquired at 4 T. The spectroscopic imaging data were reconstructed using an automated voxel-shifting method based on anatomic landmarks providing four, six, and three loci for the hippocampus, thalamus, and putamen, respectively. For correlation analysis, the hippocampal and striatal loci were averaged to provide single estimates of the entire structure, whereas the thalamus was divided into two regions, an anterior and posterior measure, using the average of three loci each. Results: The ratio of N-acetyl aspartate to creatine (NAA/Cr), a measure of neuronal injury/loss, was significantly reduced in both the ipsilateral and contralateral hippocampi and thalami. NAA/Cr in the ipsilateral hippocampus was significantly correlated with the ipsilateral and contralateral anterior and posterior thalami, putamen, and contralateral hippocampus. In control subjects, the hippocampi were only correlated with each other. Conclusions: The data demonstrate that there is significant neuronal injury/loss in both the ipsilateral and contralateral thalami in temporal lobe epilepsy patients, with greater impairment in the anterior portions of the ipsilateral thalamus. The degree of injury/loss in the ipsilateral and contralateral thalamus and putamen is directly correlated with that of the ipsilateral hippocampus. This is consistent with the hypothesis that the impairment and damage associated with recurrent seizures as measured by N-acetyl aspartate originating in the hippocampus results in injury and impairment in other subcortical structures.