Miracle-dz/UniFAR-FTUs huggingface dataset:
Fenretinide Induces Ubiquitin‐Dependent Proteasomal Degradation of Stearoyl‐CoA Desaturase in Human Retinal Pigment Epithelial Cells

Stearoyl‐CoA desaturase (SCD, SCD1), an endoplasmic reticulum (ER) resident protein and a rate‐limiting enzyme in monounsaturated fatty acid biosynthesis, regulates cellular functions by controlling the ratio of saturated to monounsaturated fatty acids. Increase in SCD expression is strongly implicated in the proliferation and survival of cancer cells, whereas its decrease is known to impair proliferation, induce apoptosis, and restore insulin sensitivity. We examined whether fenretinide, (N‐(4‐hydroxyphenyl)retinamide, 4HPR), which induces apoptosis in cancer cells and recently shown to improve insulin sensitivity, can modulate the expression of SCD. We observed that fenretinide decreased SCD protein and enzymatic activity in the ARPE‐19 human retinal pigment epithelial cell line. Increased expression of BiP/GRP78, ATF4, and GADD153 implicated ER stress. Tunicamycin and thapsigargin, compounds known to induce ER stress, also decreased the SCD protein. This decrease was completely blocked by the proteasome inhibitor MG132. In addition, PYR41, an inhibitor of ubiquitin activating enzyme E1, blocked the fenretinide‐mediated decrease in SCD. Immunoprecipitation analysis using anti‐ubiquitin and anti‐SCD antibodies and the blocking of SCD loss by PYR41 inhibition of ubiquitination further corroborate that fenretinide mediates the degradation of SCD in human RPE cells via the ubiquitin–proteasome dependent pathway. Therefore, the effect of fenretinide on SCD should be considered in its potential therapeutic role against cancer, type‐2 diabetes, and retinal diseases. J. Cell. Physiol. 229: 1028–1038, 2014. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
The actions of GR32191B, a thromboxane receptor antagonist, on the effects of inhaled PAF on human airways

We investigated acute bronchoconstriction and changes in airway responsiveness to methacholine following the inhalation of platelet activating factor (PAF) in an open study of 12 non‐asthmatic subjects. Ventilatory function was monitored using a flow rate at 30% of vital capacity (V̇30) and airway responsiveness was measured as PD40V̇30, i.e. the dose of metacholine causing a 40% fall in V̇30. PAF (3–422 μg) resulted in dose‐related acute bronchoconstriction in 10 of the 12 subjects. There was no association between the airway responsiveness to PAF and to methacholine. Ten subjects showed some increase in airway responsiveness to methacholine 1 or 3 days following PAF. Overall, these changes were statistically significant (P < 0·05) but were of small magnitude (geometric mean PD40V̇30 pre‐PAF=457 μg; 24 hr after PAF = 259 μg; 72 hr after PAF =258 μg) and variable: only seven subjects showing increased airway responsiveness on both day 1 and day 3 after PAF. Six subjects who appeared to show increases in airway responsiveness following PAF were re‐studied with the inhaled PAF pre‐medicated by either placebo or a specific thromboxane receptor antagonist (GR32191B) in a double‐blind fashion. GR32191B did not reduce the acute bronchoconstriction due to PAF. In this part of the study, these six subjects did not show significant increases in airway responsiveness following the placebo pre‐medicated PAF challenge and so no effect of the drug on airway responsiveness could be shown. We conclude that PAF‐induced bronchoconstriction in normal individuals is not mediated by thromboxane and that any increases in airway responsiveness following PAF are frequently poorly sustained, are poorly reproducible, and are not readily detectable.
Primary urothelial carcinoma of the upper tract: Important clinicopathological factors predicting bladder recurrence after surgical resection

The aim of the present study was to further characterize potential clinicopathological predictors for urinary bladder recurrence‐free survival (UBRFS) in patients with primary urothelial carcinoma of the upper urinary tract (UUT‐UC). The present series included 385 cases of surgically treated primary localized UUT‐UC without previous or concurrent urothelial carcinoma of the urinary bladder. Among the 374 patients with follow‐up information, clinicopathological features and therapeutic information including whether they received a laparoscopy‐assisted nephroureterectomy (LNU) and adjuvant chemotherapy were correlated with UBRFS. After a median follow up of 69 months, 86 patients (23%) developed urinary bladder recurrence. The median time to develop urinary bladder recurrence was 12 months. At the univariate level, an increment in histological grade (P= 0.0321), a prominent papillary configuration (P= 0.0004), LNU (P= 0.0397) and male gender (P= 0.0401) significantly predicted an inferior UBRFS. At the multivariate level, increase of histological grade (P < 0.0001, relative risk (RR) = 3.776), prominent papillary configuration (P < 0.0001, RR = 3.244), and male gender (P= 0.0463, RR = 1.444) independently predicted UBRFS. In conclusion, male patients and those with high‐grade and papillary UUT‐UC, and who received LNU had higher risks of urinary bladder recurrence. Accordingly, for these patients, more intensive follow up coupled with postoperative intravesical adjuvant therapy to prevent urinary bladder recurrence should also be considered.
CD25 Blockade protects T Cells from Activation‐induced Cell Death (AICD) via Maintenance of TOSO Expression

CD25 monoclonal antibody binding to the α‐chain of the Interleukin‐2 (IL‐2) receptor, blocks high‐affinity IL‐2 binding, thereby preventing complete T‐cell activation and being of ample importance in transplantation medicine and potentially the treatment of autoimmune disease. However, CD25 antibodies do not only block T‐cell activation but also prevent activation‐induced cell death (AICD) attributing a dual function to IL‐2. In this study, the modulation of the genomic expression profile of human peripheral blood mononuclear cells (PBMC) with therapeutic concentrations of humanized anti‐CD25 mAb was investigated. PBMC were stimulated with CD3 antibody OKT‐3 together with recombinant IL‐2 in the absence or presence of anti‐CD25 mAb. RNA was extracted and subjected to microarray analysis on U133A microarrays (Affymetrix). Anti‐CD25 treatment inhibited several genes typically expressed during T‐cell activation including granzyme B, signalling lymphocyte activation molecule, family member 1 (SLAMF1), CD40‐Ligand (CD40‐L), IL‐9 and interferon (IFN)‐γ. Interestingly, anti‐CD25 mAb also blocked the expression of several genes important for susceptibility to apoptosis, such as death receptor 6 (DR6) or reversed IL‐2‐mediated repression of anti‐apoptotic genes, such as Fas apoptotic inhibitory molecule 3 (FAIM3)/TOSO. Functional significance of DR6 and TOSO expression in IL‐2‐dependent T‐cell activation was subsequently evaluated by RNA interference in AICD: While siRNA specifically directed against DR6 did not modulate FAS‐L‐mediated apoptosis induction in primary T cells, down‐regulation of TOSO significantly increased susceptibility to apoptosis, emphasizing an important role for TOSO in IL‐2‐mediated AICD.
The influence of a standardized soybean extract (Glycine max) on the expression level of cytochrome P450 genes in vivo.

OBJECTIVE Soybean isoflavones are phytoestrogens that reduce menopausal symptoms and decrease the risk of certain chronic diseases, such as cancer and cardiovascular diseases. Despite the widespread use of soybean isoflavones as functional food and dietary supplements, data regarding the safety as well as herb-drug interactions, remain scarce. The aim of the study was to investigate the influence of soybean extract on the expression levels of cytochrome P450 (CYP) genes using real-time PCR (RT-PCR). MATERIALS AND METHODS Male Wistar rats were fed a standardized soybean extract containing 37% isoflavones (100 mg/kg) for 3 and 10 days. cDNA was synthesized from total RNA isolated from the liver using reverse transcription. The level of CYP genes expression was analyzed using RT-PCR method. RESULTS Soybean extract administration resulted in a significant increase of CYP1A1 expression level compared with the control group (1.5-fold; p < 0.05). An inductory effect was also observed for CYP2D1 by 32% (p < 0.01) after 10 days of treatment. No statistically significant differences were noted for CYPIA2, CYP2C6 and CYP3A2. In case of CYP3A1, the mRNA level of this gene was reduced by almost 35% (p < 0.05) both, after 3 and 10 days. CYP2D2 expression was also inhibited by the extract, but to a lesser degree when compared to CYP3A1. Moreover insignificant decrease of CYP2E1 expression level by 25% (p < 0.01) was observed after 3 days of treatment. CONCLUSIONS These findings suggest that soybean extract may change the expression of CYP enzymes involved in biotransformation of xenobiotics (drugs, procarcinogens).
A high-speed 2-D transform architecture with unique kernel for multi-standard video applications

In this paper, a high-speed two-dimensional (2-D) transform architecture with unique kernel for multi-standard video applications is proposed. On the basis of the new distributed arithmetic algorithm (NEDA), we utilize the recursive discrete cosine transform (DCT) algorithm to reduce the computational complexity of the NEDA and propose the unique kernel framework to unify the adder matrix design for different coefficient requirements. Owing to the proposed unique kernel framework, the adder matrices, which only have 13 adders, are independent to the coefficients of the 2-D transform. Therefore, many 2-D transform matrices can be easily realized via proposed unique kernel and the efficient routing network to accomplish multi-standard video coding requirement.
Videotape increases parental knowledge about pediatric pain management.

UNLABELLED Pediatric pain management often depends on parents recognition and assessment of their child's pain and their beliefs as to whether the pain should be treated. Parental misconceptions concerning pain assessment and pain management may therefore result in inadequate pain treatment, particularly in patients who are too young or too developmentally handicapped to self-report their pain. We hypothesized that viewing a concise, educational videotape would provide parents with instructive information that could correct misconceptions concerning pain and pain management in children. To do this, we evaluated the impact of an educational videotape on parental responses to a questionnaire about pediatric pain management. Parents of children scheduled for inpatient, postoperative hospital care were studied. After answering 30 questions, parents were randomly assigned to either view (Group 1) or not view (Group 2) a 19-min educational videotape. Immediately after viewing the videotape (Group 1), or 30 min after taking the first test (Group 2), parents were asked to answer the same questionnaire a second time. The effect of seeing the videotape was assessed by comparing post-pre test score differences using paired t-test. One-hundred parents were studied. Randomization was effective in assigning equitable groups. Initial scores of percent answers correct in each group were not different ([mean +/- SD] Group 1 [n = 50]: 68.7% +/- 18.8% vs Group 2 [n = 50]: 61.5% +/- 22.7%; P = 0.09). Viewing the videotape effectively increased test scores: paired t-test within groups demonstrated a significant difference in Group 1 (22.4% +/- 16.5%, P < 0.0001), whereas Group 2 scores changed to a much lesser degree (2.7% +/- 8.3%, P = 0.0271). All parents who viewed the videotape stated that it was informative regarding their understanding of their child's pain management. This study demonstrates the effectiveness of an educational videotape in changing parental knowledge concerning postoperative pediatric pain. This effective and efficient teaching medium may be useful in improving pain management in postoperative pediatric surgical patients. IMPLICATIONS Pediatric pain management often depends on parents recognition and assessment of their child's pain and their beliefs as to whether the pain should be treated. This prospective, randomized, controlled study demonstrated the effectiveness of an educational videotape in changing parental knowledge concerning postoperative pediatric pain. This effective and efficient teaching medium may be useful in preventing inadequate pain management in postoperative pediatric surgical patients.
High-intensity efforts in elite soccer matches and associated movement patterns, technical skills and tactical actions. Information for position-specific training drills

ABSTRACT This study aimed to translate movement patterns, technical skills and tactical actions associated with high-intensity efforts into metrics that could potentially be used to construct position-specific conditioning drills. A total of 20 individual English Premier League players’ high-intensity running profiles were observed multiple times (n = 100) using a computerised tracking system. Data were analysed using a novel high-intensity movement programme across five positions (centre back [CB], full-back [FB], central midfielder [CM], wide midfielder [WM] and centre forward [CF]). High-intensity efforts in contact with the ball and the average speed of efforts were greater in WMs than CBs, CMs and CFs (effect sizes [ES]: 0.9–2.1, P < 0.05). WMs produced more repeated efforts than CBs and CMs (ES: 0.6–1.3, P < 0.05). In possession, WMs executed more tricks post effort than CBs and CMs (ES: 1.2–1.3, P < 0.01). FBs and WMs performed more crosses post effort than other positions (ES: 1.1–2.0, P < 0.01). Out of possession, CFs completed more efforts closing down the opposition (ES: 1.4–5.0, P < 0.01) but less tracking opposition runners than other positions (ES: 1.5–1.8, P < 0.01). CFs performed more arc runs before efforts compared to CBs, FBs and WMs (ES: 0.9–1.4, P < 0.05), however, CBs completed more 0–90° turns compared to FBs, CMs and WMs (ES: 0.9–1.1, P < 0.01). The data demonstrate unique high-intensity trends in and out of possession that could assist practitioners when devising position-specific drills.
Special Education

SPEC ED 3318 Inclusive Classrooms: 3 semester hours Prerequisites: Completion of Level I courses. This class is an introductory overview of inclusive education, the characteristics of special populations in diverse classrooms, and issues related to compliance with state and federal law in serving students with varying needs. In addition, Individualized Education Plans (IEPs) and the eligibility process will be emphasized. Applicable strategies for the successful inclusion of all students that enhance collaboration among relevant stakeholders will be provided.
Enzyme‐Linked Immunosorbent Assay for Determination of Major Excrement Allergens of House Dust Mite Species D. pteronyssinus, D. farinae and D. microceras

Species‐specific enzyme‐linked immunosorbent assays (ELISA) for major excrement allergens (Dp42, Df6 and Dm6) of D. pteronyssinus, D. farinae and D. microceras in house dust were established, using immunoabsorbed, monospecific rabbit antibodies, coupled to horse radish peroxidase. The limit of detection was 13, 4 and 38 ng/ml, respectively. The coefficient of variation for the entire procedure, including dust sieving (212 μm) and extraction was 5–16% for allergen levels above 1000 ng/g dust. Allergen concentration by ELISA correlated well with the number of mite bodies identified and counted by microscopy in 31 dusts (r = 0.88, 0.86 and 0.82 for combined Dermatophagoides sp., D pteronyssinus and D farinae group, resp.) Dermatophagoides allergen was recorded in 21/22 mattress dusts (median: 26000 ng/g; maximum: 290,000 ng/g). D. pteronyssinus allergen occurred in largest amounts (median 7500 ng/g) followed by D. microceras (median 650 ng/g) and D. farinae (median 240 ng/g).
EVIDENCE-BASED PUBLIC HEALTH POLICY AND PRACTICE Healthy lifestyle choices: could sense of coherence aid health promotion?

Background: A research framework based on the personal characteristic defined by a sense of coherence (SOC) focuses on the effective use of resources to maintain good health. Objectives: To test the hypothesis that individual differences in SOC are associated with healthier lifestyle choices independently of social class and education. Design and setting: Cross sectional. Population based cohort study recruited through 35 general practice registers. Reported dietary intakes of alcohol, fruit and vegetables, fibre, saturated fat, non-discretionary salt (sodium), and total sugars were assessed by food frequency questionnaire. Current cigarette smoking, physical inactivity, and SOC were assessed through questionnaires. Participants: 7863 men and 10 424 women. Residents of Norfolk (UK). Results: Compared with participants with the weakest SOC, those with the strongest were 28% less likely to be current smokers (odds ratio 0.72 (95% confidence interval (CI), 0.58 to 0.89)), 36% less likely to be physically inactive (0.64 (0.55 to 0.75)), and reportedly consumed on average 63 g/day more fruit and vegetables (95% CI, 46 to 80), and 1.2 g/day more fibre (0.8 to 1.6). These associations were independent of age, sex, social class, and education. For physical inactivity and consumption of fruit, vegetables, and fibre, these differences exceeded those observed between the extremes of social class and education. Conclusions: Individual differences in SOC are associated with healthy lifestyle choices independently of social class and education, and may therefore aid the design of future health promotion interventions.
Regucalcin is an androgen‐target gene in the rat prostate modulating cell‐cycle and apoptotic pathways

Regucalcin (RGN) is a calcium (Ca2+)‐binding protein underexpressed in prostate adenocarcinoma comparatively to non‐neoplastic prostate or benign prostate hyperplasia cases. Moreover, RGN expression is negatively associated with the cellular differentiation of prostate adenocarcinoma, suggesting that loss of RGN may be associated with tumor onset and progression. However, the RGN actions over the control of prostate cell growth have not been investigated.
Isolation and characterisation of zona pellucida A (ZPA) cDNAs from two species of marsupial: regulated oocyte-specific expression of ZPA transcripts

The zona pellucida (ZP) is an extracellular glycoprotein coat that is deposited around the oocyte during folliculogenesis and performs several functions that relate to fertilisation and preimplantion development. In eutherian mammals it consists of three major glycoproteins – ZPA, ZPB, and ZPC – but little is known about its molecular constitution in marsupials. We have isolated the cDNA encoding the ZPA homologue in two distantly related marsupial series: the possum, Trichosurus vulpecula (a phalangerid) and the dunnart Sminthopsis crassicaudata (a dasyurid). The two cDNA sequences were 86% identical and showed extensive regions of homology to eutherian ZPA proteins, particularly in the central region of the molecule. Many other features of the ZPA protein, except the positioning of the N-linked glycosylation sites, were also conserved between marsupials and eutherians. ZPA expression was shown to occur maximally in the cytoplasm of the oocyte primary follicles with a little, but significant, expression in oocytes of both primordial follicles and in the cytoplasm of the oocyte in follicles with an antral cavity. No expression was seen in surrounding follicle or granulosa cells
Bone mineral density in mature, premenopausal ultramarathon runners.

We measured bone mineral density (BMD) in 25 premenopausal ultramarathon (56 km) runners aged 29-39 yr and related risk factors for decreased BMD with actual BMD. Fifteen runners who had never had oligo/amenorrhea (R) were compared with 10 runners (OA): 4 oligomenorrheic, 2 amenorrheic, and 4 with prior oligo/amenorrhea. Menstrual, dietary and training data were obtained. BMD of the lumbar spine (LS) and proximal femur (F) were measured by dual energy x-ray densitometry. Both groups had similar body mass (58 +/- 8 vs 57 +/- 8 kg), running and dietary histories. F BMD was not different (P = 0.07) and correlated only with BMI (P < 0.05; r = 0.43). LS BMD was lower in OA (0.946 +/- 0.098 g.cm-2) than R (1.088 +/- 0.069 g.cm-2; P < 0.001). Menstrual History Index (MHI), (estimated periods.yr-1 since age 13), was higher in R (11.6 +/- 0.6) than OA (9.4 +/- 2.1; P < 0.01). LS BMD correlated with MHI (P < 0.0005; r = 0.67) and years oligomenorrheic (P < 0.01; r = -0.58) but not years amenorrheic, parity, breastfeeding, diet, or training. In conclusion, in mature women distance runners low LS BMD is related to a history of oligo/amenorrhea regardless of resumption of regular menstrual cycles in some subjects. Not only amenorrhea, but also prolonged oligomenorrhea may negatively influence peak adult bone mass.
Fibrillar type I collagens enhance platelet-dependent thrombin generation via glycoprotein VI with direct support of α2β1 but not αIIbβ3 integrin

Summary The role of collagens and collagen receptors was investigated in stimulating platelet-dependent thrombin generation. Fibrillar type-I collagens, including collagen from human heart, were most potent in enhancing thrombin generation, in a way dependent on exposure of phosphatidylserine (PS) at the platelet surface. Soluble, non-fibrillar type-I collagen required pre-activation of integrin α2β1 with Mn2+ for enhancement of thrombin generation. With all preparations, blocking of glycoprotein VI (GPVI) with 9O12 antibody abrogated the collagen-enhanced thrombin generation, regardless of the α2β1 activation state. Blockade of α2β1 alone or antagonism of autocrine thromboxane A2 and ADP were less effective. Blockade of αIIbβ3 with abciximab suppressed thrombin generation in platelet-rich plasma, but this did not abolish the enhancing effect of collagens. The high activity of type-I fibrillar collagens in stimulating GPVI-dependent procoagulant activity was confirmed in whole-blood flow studies, showing that these collagens induced relatively high expression of PS. Together, these results indicate that: i) fibrillar type-I collagen greatly enhances thrombin generation, ii) GPVI-induced platelet activation is principally responsible for the procoagulant activity of fibrillar and non-fibrillar collagens, iii) α2β1 and signaling via autocrine mediators facilitate and amplify this GPVI activity, and iv) αIIbβ3 is not directly involved in the collagen effect.