Miracle-dz/UniFAR-FTUs huggingface dataset:
An evaluation of the criteria and procedures used for selection of occupational therapy students at South African universities.

The existing selection criteria and procedures applied at universities training occupational therapists in South Africa are not meeting the country's need for selecting students who adequately fulfill the demographic mix which represents the South African population. The aims of this research were: to investigate the existing criteria and procedures used for the selection of occupational therapy students; to establish recommendations with regard to how these criteria and procedures can be adapted to allow for more appropriate and equitable selection of students, and to obtain opinions from qualified therapists about those characteristics deemed most important for them to possess in the current South African Health System. A combination of quantitative and qualitative methodology was adopted. A survey was undertaken to obtain basic information and statistics about the numbers of applicants selected, and the existing selection criteria and procedures currently used to select occupational therapy students in South African universities. A series of two focus groups for each of the eight existing universities were carried out i.e. one incorporating the views of lecturers and clinicians and the other the views of students. The purpose of these groups was to obtain existing and emerging views of qualified therapists and students on current selection processes, what could be recommended to make selection fairer for disadvantaged applicants and what specific characteristics of qualified therapists would be most desirable in the current health system. The results indicate that the proportion of African students admitted into occupational therapy degrees is still far below numbers of other race groups, particularly white South Africans. That existing selection criteria and procedures are still dominated by eurocentric influence, particularly in the historically white universities, although there are definite attempts on the part of all occupational therapy training centres to overcome this, and that there are serious problems related to recruitment of African applicants which are partly the cause of the low numbers of African applicants. Characteristics deemed most desirable in qualified occupational therapists included many, most significant were: flexibility, particularly a special ability to be able to adjust to all types of people and cultures which included good communication and interpersonal skills; the ability to be assertive where appropriate; a "life-Iong-Ieamer" attitude including a visionary mentality/attitude; creativity and inriovative thinking; perseverance, determination and good management skills.
Ribophorin I regulates substrate delivery to the oligosaccharyltransferase core

Protein N-glycosylation is widespread among biological systems, and the fundamental process of transferring a lipid-linked glycan to suitable asparagine residues of newly synthesized proteins occurs in both prokaryotes and eukaryotes. The core reaction is mediated by Stt3p family members, and in many organisms this component alone is sufficient to constitute the so called oligosaccharyltransferase (OST). However, eukaryotes typically have a more elaborate OST with several additional subunits of poorly defined function. In the mammalian OST complex one such subunit, ribophorin I, is proposed to facilitate the N-glycosylation of certain precursors during their biogenesis at the endoplasmic reticulum. Here, we use cell culture models to show that ribophorin I depletion results in substrate-specific defects in N-glycosylation, clearly establishing a defined physiological role for ribophorin I. To address the molecular mechanism of ribophorin I function, a cross-linking approach was used to explore the environment of nascent glycoproteins during the N-glycosylation reaction. We show for the first time that ribophorin I can regulate the delivery of precursor proteins to the OST complex by capturing substrates and presenting them to the catalytic core.
Synergistic control of T cell development and tumor suppression by diacylglycerol kinase α and ζ

Diacylglycerol (DAG) kinases (DGKs) are a family of enzymes that convert DAG to phosphatidic acid (PA), the physiologic functions of which have been poorly defined. We report here that DGK α and ζ synergistically promote T cell maturation in the thymus. Absence of both DGKα and ζ (DGKα−/−ζ−/−) results in a severe decrease in the number of CD4+CD8− and CD4−CD8+ single-positive thymocytes correlating with increased DAG-mediated signaling. Positive selection, but not negative selection, is impaired in DGKα−/−ζ−/− mice. The developmental blockage in DGKα−/−ζ−/− mice can be partially overcome by treatment with PA. Furthermore, decreased DGK activity also promotes thymic lymphomagenesis accompanying elevated Ras and Erk1/2 activation. Our data demonstrate a synergistic and critical role of DGK isoforms in T cell development and tumor suppression, and indicate that DGKs not only terminate DAG signaling but also initiate PA signaling in thymocytes to promote positive selection.
PPARδ regulates multiple proinflammatory pathways to suppress atherosclerosis

Lipid homeostasis and inflammation are key determinants in atherogenesis, exemplified by the requirement of lipid-laden, foam cell macrophages for atherosclerotic lesion formation. Although the nuclear receptor PPARδ has been implicated in both systemic lipid metabolism and macrophage inflammation, its role as a therapeutic target in vascular disease is unclear. We show here that orally active PPARδ agonists significantly reduce atherosclerosis in apoE−/− mice. Metabolic and gene expression studies reveal that PPARδ attenuates lesion progression through its HDL-raising effect and anti-inflammatory activity within the vessel wall, where it suppresses chemoattractant signaling by down-regulation of chemokines. Activation of PPARδ also induces the expression of regulator of G protein signaling (RGS) genes, which are implicated in blocking the signal transduction of chemokine receptors. Consistent with this, PPARδ ligands repress monocyte transmigration and macrophage inflammatory responses elicited by atherogenic cytokines. These results reveal that PPARδ antagonizes multiple proinflammatory pathways and suggest PPARδ-selective drugs as candidate therapeutics for atherosclerosis.
Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus

The mortality of human infection by influenza A/H5N1 virus can exceed 80%. The high mortality and its poor response to the neuraminidase inhibitor oseltamivir have been attributed to uncontrolled virus-induced cytokine storm. We challenged BALB/c mice with 1,000 LD50 of influenza A/Vietnam/1194/04. Survival, body weight, histopathology, inflammatory markers, viral loads, T lymphocyte counts, and neutralizing antibody response were documented in infected mice treated individually or in combination with zanamvir, celecoxib, gemfibrozil, and mesalazine. To imitate the real-life scenario, treatment was initiated at 48 h after viral challenge. There were significant improvements in survival rate (P = 0.02), survival time (P < 0.02), and inflammatory markers (P < 0.01) in the group treated with a triple combination of zanamivir, celecoxib, and mesalazine when compared with zanamivir alone. Zanamivir with or without immunomodulators reduced viral load to a similar extent. Insignificant prolongation of survival was observed when individual agents were used alone. Significantly higher levels of CD4+ and CD8+ T lymphocytes and less pulmonary inflammation were also found in the group receiving triple therapy. Zanamivir alone reduced viral load but not inflammation and mortality. The survival benefits of adding celecoxib and mesalazine to zanamivir could be caused by their synergistic effects in reducing cytokine dysfunction and preventing apoptosis. Combinations of a neuraminidase inhibitor with these immunomodulators should be considered in randomized controlled treatment trials of patients suffering from H5N1 infection.
Metamaterials on Paper as a Sensing Platform

There is increasing interest in the development of cost-effective, practical, portable, and disposable diagnostic devices suited to on-site detection and analysis applications, which hold great promise for global health care,[1,2] environmental monitoring,[3] water and food safety,[4] as well as medical and threat reductions. [5] Lab-on-a-chip (LOC) devices, which scale single or multiple lab processes down to chip format (millimeters to a few square centimeters in size), facilitated by micro- and nanoscale technologies have attracted significant attention because of their small sample volume requirements and excellent portability. [6] Various LOC devices have been designed and fabricated in the past two decades, most of which involve a lithography-based patterning process on a solid or elastomeric substrate, such as glass or plastic, for a variety of functionalities that include sample preparation,[7] microfluidic mixing,[8] biochemical reactions,[9] and analysis. [10]
Alcohol, suppressed anger and violence.

AIMS Is alcohol related causally to violence, and if so, is the effect of drinking contingent on suppressed anger such that it is strongest among individuals who are highly inclined to withhold angry feelings? We addressed these questions by analysing panel data using a method that diminishes the effects of confounding factors. DESIGN We analysed data on heavy episodic drinking and violent behaviour from the second (1994) and third (1999) waves of the Young in Norway Longitudinal Study (n = 2697; response rate: 67%). The first difference method was applied to estimate the association between these behaviours, implying that changes in the frequency of violence were regressed on changes in the frequency of drinking. Hence, the effects of time-invariant confounders were eliminated. Analyses were conducted for the whole sample, and for groups scoring low, medium and high on a short version of the STAXI anger suppression scale. FINDINGS Changes in drinking were related positively and significantly to changes in violent behaviour, but the alcohol effect varied with the level of suppressed anger: it was strongest in the high-anger group (elasticity estimate = 0.053, P = 0.011) and weakest (and insignificant) in the low-anger group (elasticity estimate = 0.004, P = 0.806). CONCLUSIONS Alcohol use may be related causally to violence, but the effect of drinking is confined to individuals who are inclined to suppress their angry feelings.
Field evidence that ecosystem service projects support biodiversity and diversify options

Ecosystem service approaches to conservation are being championed as a new strategy for conservation, under the hypothesis that they will broaden and deepen support for biodiversity protection. Where traditional approaches focus on setting aside land by purchasing property rights, ecosystem service approaches aim to engage a much wider range of places, people, policies, and financial resources in conservation. This is particularly important given projected intensification of human impacts, with rapid growth in population size and individual aspirations. Here we use field research on 34 ecosystem service (ES) projects and 26 traditional biodiversity (BD) projects from the Western Hemisphere to test whether ecosystem service approaches show signs of realizing their putative potential. We find that the ES projects attract on average more than four times as much funding through greater corporate sponsorship and use of a wider variety of finance tools than BD projects. ES projects are also more likely to encompass working landscapes and the people in them. We also show that, despite previous concern, ES projects not only expand opportunities for conservation, but they are no less likely than BD projects to include or create protected areas. Moreover, they do not draw down limited financial resources for conservation but rather engage a more diverse set of funders. We also found, however, that monitoring of conservation outcomes in both cases is so infrequent that it is impossible to assess the effectiveness of either ES or BD approaches.
Cyclic adenosine monophosphate differentiated β-endorphin neurons promote immune function and prevent prostate cancer growth

Pituitary adenylate cyclase-activating peptide (PACAP), a cAMP-activating agent, is highly expressed in the hypothalamus during the period when many neuroendocrine cells become differentiated from the neural stem cells (NSCs). Activation of the cAMP system in rat hypothalamic NSCs differentiated these cells into β-endorphin (BEP)-producing neurons in culture. When these in vitro differentiated neurons were transplanted into the paraventricular nucleus (PVN) of the hypothalamus of an adult rat, they integrated well with the surrounding cells and produced BEP and its precursor gene product, proopiomelanocortin (POMC). Animals with BEP cell transplants demonstrated remarkable protection against carcinogen induction of prostate cancer. Unlike carcinogen-treated animals with control cell transplants, rats with BEP cell transplants showed rare development of glandular hyperplasia, prostatic intraepithelial neoplasia (PIN), or well differentiated adenocarcinoma with invasion after N-methyl-N-nitrosourea (MNU) and testosterone treatments. Rats with the BEP neuron transplants showed increased natural killer (NK) cell cytolytic function in the spleens and peripheral blood mononuclear cells (PBMCs), elevated levels of antiinflammatory cytokine IFN-γ, and decreased levels of inflammatory cytokine tumor necrosis factor-α (TNF-α) in plasma. These results identified a critical role for cAMP in the differentiation of BEP neurons and revealed a previously undescribed role of these neurons in combating the growth and progression of neoplastic conditions like prostate cancer, possibly by increasing the innate immune function and reducing the inflammatory milieu.
Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33

We performed a three-phase genome-wide association study (GWAS) using cases and controls from a genetically isolated population, Ashkenazi Jews (AJ), to identify loci associated with breast cancer risk. In the first phase, we compared allele frequencies of 150,080 SNPs in 249 high-risk, BRCA1/2 mutation-negative AJ familial cases and 299 cancer-free AJ controls using χ2 and the Cochran–Armitage trend tests. In the second phase, we genotyped 343 SNPs from 123 regions most significantly associated from stage 1, including 4 SNPs from the FGFR2 region, in 950 consecutive AJ breast cancer cases and 979 age-matched AJ controls. We replicated major associations in a third independent set of 243 AJ cases and 187 controls. We obtained a significant allele P value of association with AJ breast cancer in the FGFR2 region (P = 1.5 × 10−5, odds ratio (OR) 1.26, 95% confidence interval (CI) 1.13–1.40 at rs1078806 for all phases combined). In addition, we found a risk locus in a region of chromosome 6q22.33 (P = 2.9 × 10−8, OR 1.41, 95% CI 1.25–1.59 at rs2180341). Using several SNPs at each implicated locus, we were able to verify associations and impute haplotypes. The major haplotype at the 6q22.33 locus conferred protection from disease, whereas the minor haplotype conferred risk. Candidate genes in the 6q22.33 region include ECHDC1, which encodes a protein involved in mitochondrial fatty acid oxidation, and also RNF146, which encodes a ubiquitin protein ligase, both known pathways in breast cancer pathogenesis.
Chemically Driven Nanoscopic Magnetic Phase Separation at the SrTiO3(001)/La1‐xSrxCoO3 Interface

The degradation in magnetic properties in very thin film complex oxides is studied using SrTiO(3)(001)/La(1-x)Sr(x)CoO(3), providing unequivocal evidence for nanoscopic interfacial magnetic phase separation. Electron microscopy and spectroscopy reveal that this occurs due to inhomogeneity in local hole doping, driven by subtle, depthwise variations in the Sr and O stoichiometry. Simple thermodynamic and structural arguments for the origin of these variations are provided.
Paternal incarceration and trajectories of marijuana and other illegal drug use from adolescence into young adulthood: evidence from longitudinal panels of males and females in the United States.

AIMS One-eighth of young adults in the United States report that their biological father has ever been incarcerated (FEI). This study is the first to examine associations between FEI and trajectories of substance use during the transition from adolescence into young adulthood for the US population. DESIGN Using multi-level modeling techniques, trajectories of marijuana and other illegal drug use are examined, with FEI as the primary independent variable. SETTING Data are from the first three waves of the National Longitudinal Study of Adolescent Health, a nationally representative sample of US adolescents beginning in 1995. PARTICIPANTS Panels of 7157 males and 7997 females followed from adolescence (7th-12th grades) into early adulthood (ages 18-27 years). MEASUREMENTS Dependent variables included an ordinal measure of marijuana frequency of use in last thirty days, and a dichotomous measure for whether respondent had any use in the last thirty days of illegal drugs such crystal meth, cocaine, heroin, hallucinogens, PCP, LSD, speed, and ecstasy. FINDINGS Among males and females, respectively, FEI is associated with an increased frequency of marijuana use, and increased odds of any other illegal drug use. Interactions between FEI and age further reveal that FEI is associated with an accentuated trajectory (i.e. a steeper slope) of marijuana use, and an elevated risk (i.e. higher mean level) of other illegal drug use. CONCLUSIONS Analysis provides some of the first evidence that paternal incarceration is significantly associated with drug use among U.S. males and females, even after controlling for a number of family background, parental, and individual characteristics.
MKP-1 inhibits high NaCl-induced activation of p38 but does not inhibit the activation of TonEBP/OREBP: Opposite roles of p38α and p38δ

High NaCl rapidly activates p38 MAPK by phosphorylating it, the phosphorylation presumably being regulated by a balance of kinases and phosphatases. Kinases are known, but the phosphatases are uncertain. Our initial purpose was to identify the phosphatases. We find that in HEK293 cells transient overexpression of MAPK phosphatase-1 (MKP-1), a dual-specificity phosphatase, inhibits high NaCl-induced phosphorylation of p38, and that overexpression of a dominant negative mutant of MKP-1 does the opposite. High NaCl lowers MKP-1 activity by increasing reactive oxygen species, which directly inhibit MKP-1, and by reducing binding of MKP-1 to p38. Because inhibition of p38 is reported to reduce hypertonicity-induced activation of the osmoprotective transcription factor, TonEBP/OREBP, we anticipated that MKP-1 expression might also. However, overexpression of MKP-1 has no significant effect on Ton EBP/OREBP activity. This paradox is explained by opposing effects of p38α and p38δ, both of which are activated by high NaCl and inhibited by MKP-1. Thus, we find that overexpression of p38α increases high NaCl-induced TonEBP/OREBP activity, but overexpression of p38δ reduces it. Also, siRNA-mediated knockdown of p38δ enhances the activation of TonEBP/OREBP. We conclude that high NaCl inhibits MKP-1, which contributes to the activation of p38. However, opposing actions of p38α and p38δ negate any effect on TonEBP/OREBP activity. Thus, activation of p38 isoforms by hypertonicity does not contribute to activation of TonEBP/OREBP because of opposing effects of p38α and p38δ, and effects of inhibitors of p38 depend on which isoform is affected, which can be misleading.
High-resolution x-ray structure of human aquaporin 5

Human aquaporin 5 (HsAQP5) facilitates the transport of water across plasma membranes and has been identified within cells of the stomach, duodenum, pancreas, airways, lungs, salivary glands, sweat glands, eyes, lacrimal glands, and the inner ear. AQP5, like AQP2, is subject to posttranslational regulation by phosphorylation, at which point it is trafficked between intracellular storage compartments and the plasma membrane. Details concerning the molecular mechanism of membrane trafficking are unknown. Here we report the x-ray structure of HsAQP5 to 2.0-Å resolution and highlight structural similarities and differences relative to other eukaryotic aquaporins. A lipid occludes the putative central pore, preventing the passage of gas or ions through the center of the tetramer. Multiple consensus phosphorylation sites are observed in the structure and their potential regulatory role is discussed. We postulate that a change in the conformation of the C terminus may arise from the phosphorylation of AQP5 and thereby signal trafficking.
Neural correlates of verbal learning in adolescent alcohol and marijuana users.

AIMS Alcohol and marijuana are the most widely used intoxicants among adolescents, yet their potential unique and interactive influences on the developing brain are not well established. Brain regions subserving learning and memory undergo continued maturation during adolescence, and may be particularly susceptible to substance-related neurotoxic damage. In this study, we characterize brain response during verbal learning among adolescent users of alcohol and marijuana. DESIGN Participants performed a verbal paired associates encoding task during functional magnetic resonance imaging (fMRI) scanning. SETTING Adolescent subjects were recruited from local public schools and imaged at a university-based fMRI center. PARTICIPANTS Participants were 74 16-18-year-olds, divided into four groups: (i) 22 controls with limited alcohol and marijuana experience, (ii) 16 binge drinkers, (iii) eight marijuana users and (iv) 28 binge drinking marijuana users. MEASUREMENTS Diagnostic interview ensured that all teens were free from neurological or psychiatric disorders; urine toxicology and breathalyzer verified abstinence for 22-28 days before scanning; a verbal paired associates task was administered during fMRI. FINDINGS Groups demonstrated no differences in performance on the verbal encoding task, yet exhibited different brain response patterns. A main effect of drinking pointed to decreased inferior frontal but increased dorsal frontal and parietal fMRI response among binge drinkers (corrected P < 0.05). There was no main effect of marijuana use. Binge drinking × marijuana interactions were found in bilateral frontal regions (corrected P < 0.05), where users of either alcohol or marijuana showed greater response than non-users, but users of both substances resembled non-users. CONCLUSIONS Adolescent substance users demonstrated altered fMRI response relative to non-using controls, yet binge drinking appeared to be associated with more differences in activation than marijuana use. Alcohol and marijuana may have interactive effects that alter these differences, particularly in prefrontal brain regions.