Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the NF-E2-related Factor-2-dependent Genes Conferring Protection against Oxidative Stress in Primary Cortical Astrocytes Using Oligonucleotide Microarray Analysis*

The antioxidant responsive element (ARE) mediates transcriptional regulation of phase II detoxification enzymes and antioxidant proteins such as NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferases, and glutamate-cysteine ligase. In this study, we demonstrate that NF-E2-related factor-2 (Nrf2) plays a major role in transcriptional activation of ARE-driven genes and identify Nrf2-dependent genes by oligonucleotide microarray analysis using primary cortical astrocytes from Nrf2+/+ and Nrf2−/− mice. Nrf2−/−astrocytes had decreased basal NQO1 activity and no induction bytert-butylhydroquinone compared with Nrf2+/+ astrocytes. Similarly, both basal and induced levels of human NQO1-ARE-luciferase expression in Nrf2−/− astrocytes were significantly lower than in Nrf2+/+ astrocytes. Furthermore, human NQO1-ARE-luciferase expression in Nrf2−/−astrocytes was restored by overexpression of Nrf2, whereas ARE activation in Nrf2+/+ astrocytes was completely blocked by dominant-negative Nrf2. In addition, we observed that Nrf2-dependent genes protected primary astrocytes from H2O2- or platelet-activating factor-induced apoptosis. In support of these observations, we identified Nrf2-dependent genes encoding detoxification enzymes, glutathione-related proteins, antioxidant proteins, NADPH-producing enzymes, and anti-inflammatory genes using oligonucleotide microarrays. Proteins within these functional categories are vital to the maintenance and responsiveness of a cell defense system, suggesting that an orchestrated change in gene expression via Nrf2 and the ARE gives a synergistic protective effect against oxidative stress.
Three distinct kinetic groupings of the synaptotagmin family: candidate sensors for rapid and delayed exocytosis.

Synaptotagmins (syts) are a family of membrane proteins present on a variety of intracellular organelles. In vertebrates, 16 isoforms of syt have been identified. The most abundant isoform, syt I, appears to function as a Ca2+ sensor that triggers the rapid exocytosis of synaptic vesicles from neurons. The functions of the remaining syt isoforms are less well understood. The cytoplasmic domain of syt I binds membranes in response to Ca2+, and this interaction has been proposed to play a key role in secretion. Here, we tested the Ca(2+)-triggered membrane-binding activity of the cytoplasmic domains of syts I-XII; eight isoforms tightly bound to liposomes that contained phosphatidylserine as a function of the concentration of Ca2+. We then compared the disassembly kinetics of Ca2+. syt.membrane complexes upon rapid mixing with excess Ca2+ chelator and found that syts can be classified into three distinct kinetic groups. syts I, II, and III constitute the fast group; syts V, VI, IX, and X make up the medium group; and syt VII exhibits the slowest kinetics of disassembly. Thus, isoforms of syt, which have much slower disassembly kinetics than does syt I, might function as Ca2+ sensors for asynchronous release, which occurs after Ca2+ domains have collapsed. We also compared the temperature dependence of Ca2+. syt.membrane assembly and disassembly reactions by using squid and rat syt I. These results indicate that syts have diverged to release Ca2+ and membranes with distinct kinetics.
Central fatigue after cycling evaluated using peripheral magnetic stimulation.

UNLABELLED Central and peripheral mechanisms contribute to fatigue during exercise. Electrical and transcranial magnetic stimulation have been used to assess these fatigue mechanisms. Peripheral magnetic stimulation (PMS) of the femoral nerve is associated with very little subject discomfort and has been shown to elicit quadriceps contractions of >70% maximal voluntary contraction (MVC). PURPOSE To examine peripheral versus central mechanisms of fatigue in men during prolonged cycling using a peripheral nerve magnetic stimulation-based technique. METHODS Eleven men (aged 41 +/- 3 yr) cycled for 2 h at approximately 66% of VO2peak (55 +/- 2 mL x kg(-1) x min(-1)) with five 1-min sprints interspersed, followed by a 3-km time trial. Oxygen consumption was measured every 20 min to verify a constant workload. RPE were measured simultaneously and during each sprint using a Borg scale. Quadriceps isometric strength testing was performed in a seated position before and after cycling: 1) MVC, 2) MVC with superimposed magnetic stimulation to measure central activation ratio (CAR), 3) femoral nerve stimulation alone. One-minute recoveries were allowed between contractions. Changes in metabolic measurements over time were analyzed with repeated-measures ANOVA, and strength changes before to after with Student's paired t-tests. RESULTS HR (P = 0.03) and RPE (P < 0.001) increased over time during the 2 h, and MVC declined by 22% (P = 0.001) indicating fatigue. Force elicited by PMS alone decreased 17% (P < 0.001). CAR decreased from 83% before exercise to 71% (P = 0.005) after exercise indicating a loss of central drive. PMS-induced force was > or =90% of MVC. CONCLUSIONS Results clearly demonstrate that trained cyclists experience significant central fatigue during prolonged cycling. PMS may be a better technique for identifying central fatigue than the traditionally used interpolated twitch technique.
The contribution of educational class in improving accuracy of cardiovascular risk prediction across European regions: The MORGAM Project Cohort Component

Objective To assess whether educational class, an index of socioeconomic position, improves the accuracy of the SCORE cardiovascular disease (CVD) risk prediction equation. Methods In a pooled analysis of 68 455 40–64-year-old men and women, free from coronary heart disease at baseline, from 47 prospective population-based cohorts from Nordic countries (Finland, Denmark, Sweden), the UK (Northern Ireland, Scotland), Central Europe (France, Germany, Italy) and Eastern Europe (Lithuania, Poland) and Russia, we assessed improvements in discrimination and in risk classification (net reclassification improvement (NRI)) when education was added to models including the SCORE risk equation. Results The lowest educational class was associated with higher CVD mortality in men (pooled age-adjusted HR=1.64, 95% CI 1.42 to 1.90) and women (HR=1.31, 1.02 to 1.68). In men, the HRs ranged from 1.3 (Central Europe) to 2.1 (Eastern Europe and Russia). After adjustment for the SCORE risk, the association remained statistically significant overall, in the UK and Eastern Europe and Russia. Education significantly improved discrimination in all European regions and classification in Nordic countries (clinical NRI=5.3%) and in Eastern Europe and Russia (NRI=24.7%). In women, after SCORE risk adjustment, the association was not statistically significant, but the reduced number of deaths plays a major role, and the addition of education led to improvements in discrimination and classification in the Nordic countries only. Conclusions We recommend the inclusion of education in SCORE CVD risk equation in men, particularly in Nordic and East European countries, to improve social equity in primary prevention. Weaker evidence for women warrants the need for further investigations.
Norwegian export of farmed salmon − trade costs and market concentration

ABSTRACT While variation in unit value most commonly has been associated with quality in the trade literature, observed differences in prices between markets might also be explained by variation in market concentration and the degree of competition. Using transaction data on Norwegian exports of salmon, we introduce a Herfindahl index as a measure of competition in a standard gravity model. We find that competition typically is weaker in small and distant markets that due to high trade costs are served by relatively few firms. We argue that the anti-competitive impact of trade costs may explain price differentiation between markets even for homogeneous products.
Association of MEGSIN 2093C-2180T haplotype at the 3' untranslated region with disease severity and progression of IgA nephropathy.

BACKGROUND MEGSIN is a gene predominantly expressed in the renal mesangium, and is upregulated in IgA nephropathy (IgAN). Our previous study has shown that the 2093C and 2180T alleles at the 3' untranslated region (3'UTR) of the gene are associated with susceptibility to IgAN, but the relationships of these genetic variants with the clinical manifestations and renal histological lesions of IgAN have not been examined previously. METHODS 302 IgAN patients followed up for 52.8+/-22.5 months were investigated. Haplotypes at the 3'UTR were constructed using the 2093C/T and 2180C/T alleles. The genotype-phenotype relationship was studied by correlations of haplotypes and the clinical data and renal histopathological changes. RESULTS The 2093C-2180T haplotype was present more often in patients with disease that progressed more rapidly (chi2((C-T/others)) = 8.429, P = 0.004), and was also correlated with hypertension (chi2((C-T/others)) = 6.459, P = 0.012), severe proteinuria (>or=2 g/d) (chi2((C-T/others)) = 6.332, P = 0.013), and Lee's class IV and V histological changes (chi2((C-T/others)) = 9.640, P = 0.008). CONCLUSION In this Chinese population, the 2093C-2180T haplotype at the 3'UTR of MEGSIN gene is associated with more severe forms of IgAN, and more rapid disease progression. This provides further evidence for the involvement of genetic variations of MEGSIN in the pathogenesis of IgAN.
Comparative effect of an essential oil mouthrinse on plaque, gingivitis and salivary Streptococcus mutans levels: a double blind randomized study

An open, randomized, controlled study with two parallel treatment groups was done to evaluate the efficacy of a Lippia sidoides essential oil (EO) 1% mouthrinse compared with chlorhexidine 0.12% mouthrinse, applied two times daily for 1 week, in the treatment of dental plaque and gingivitis. Fifty‐five patients were included in the study. The efficacy variables were the colony count of Streptococcus mutans from the stimulated saliva and periodontal indices on days 0, 7 and 30 after commencement of therapy. Twenty eight patients received chlorhexidine mouthrinse (Periogard®) and 27 Lippia sidoides essential oil mouthrinse (Cepakill®). The clinical and microbiological parameters were significantly reduced by both mouthrinses. No significant difference was seen between the two groups (p > 0.05). There was a significant reduction in the colony count of S. mutans in both groups (p < 0.05). Chlorhexidine treatment reduced more efficiently than L. sidoides, however, no statistical difference was seen, the efficacy of both groups was similar (p = 0.3). The results indicate that Chlorhexidine mouthrinse reduced plaque index, gingival bleeding and the number of CFU (colonies forming units) more efficiently than L. sidoides but did not reach statistical significance. This study demonstrated that Lippia sidoides EO mouthrinse is effective in reducing microbial plaque and gingival inflammation. Copyright © 2009 John Wiley & Sons, Ltd.
Avatar-Assisted Case Studies

Engaging students in active techniques that promote learning and socialization in nursing may be achieved using Voki technology. The authors discuss a project, and its outcomes, that used avatar-assisted case studies. Instructors looking for a new teaching technology that can be integrated into case studies are encouraged to explore this venue as an active learning technology.
Telemonitoring of Type 2 Diabetes Mellitus in Italy.

BACKGROUND Type 2 diabetes mellitus (DM) affects 382 million people worldwide. INTRODUCTION This study aimed at assessing whether telemonitoring (TM) of DM patients improves health-related quality of life (HRQoL). MATERIALS AND METHODS As part of the RENEWING HEALTH project, 299 DM patients with HbA1c >7.0% were enrolled in a randomized controlled trial, with 208 patients in the TM group and 91 patients in the usual-care group. TM electronically transmitted glucose measurements to physicians during a 12-month follow-up. The SF-36v2 questionnaire was used to assess HRQoL. RESULTS In a total of 243 patients analyzed, the study did not identify any clinically important improvement in HRQoL, our primary endpoint. There was no statistically significant difference in HbA1c between the two groups; however, outpatient visits and planned hospitalizations were significantly reduced in the TM group (p < 0.0001 and p = 0.02). DISCUSSION The results regarding HRQoL might be, at least in part, an artifact stemming from the criteria used to select patients. TM reduced ambulatory visits and planned hospital admissions, an important result that plausibly reflects the fact that clinicians can strictly monitor their patients' health status without face-to-face contacts. CONCLUSIONS Enhancement of HRQoL should represent the most critical goal of DM healthcare delivery. Effects of TM on HRQoL of diabetic patients should be studied further.
Business cycles and earnings management strategies: a study in Brazilian public firms,

ABSTRACT This study contributes to the literature dealing with the influence of macroeconomic factors on accounting information quality, since it analyzes the earnings management strategies of firms, specifically identifying different discretionary behaviors among economic cycles: 1) different levels of earnings management through accruals between phases of the business cycle, and 2) the trade-off between earnings management through accruals and real earnings management. The results indicate that the accounting information reported should be analyzed with greater caution by its users, especially in periods of great economic oscillations, when managers can increase or reduce opportunistic behavior. The research population comprised non-financial companies with shares traded on the São Paulo Stock, Commodities, and Futures Exchange (BM&FBovespa) and the sample was composed of 247 firms per year, covering the period from 2000 to 2015 and totaling 2,501 observations. The phases of business cycles were used as a proxy for the economic environment and were based on Schumpeter's (1939) study, which divides an business cycle into four distinct phases: expansion, recession, contraction, and recovery. Discretionary accruals were estimated according to the Pae (2005) and Paulo (2007) models. Real earnings management was estimated as described by Roychowdhury (2006), using only the abnormal behavior of production costs and operational decisions. The results of this research show that earnings management strategies, using either accruals or real manipulation, as well as the choice between these strategies, are impacted by the economic environment. The evidence suggests that managers have different opportunistic behavior in each phase of the business cycle. Specifically, they increase the level of discretionary accruals in contractionary phases and reduce it during recoveries, while they manage earnings downwards via real manipulation in recessions and contractions.
Tobacco Reduces Membrane HLA Class I That Is Restored by Transfection with Transporter Associated with Antigen Processing 1 cDNA1

HLA class I molecules are recognized by CTL that eliminate virally infected and malignantly transformed cells presenting foreign peptide—a process termed immunosurveillance. Many tumors have reduced levels of membrane HLA class I. Tumor cells with mutations that reduce HLA class I avoid immunosurveillance and continue to proliferate. As tobacco use can induce tumors, we examined the effect of tobacco extracts on membrane HLA class I. These studies show that culture of cells in media containing tobacco extracts reduces membrane HLA class I, but not other proteins, on primary keratinocytes and other cell types. Culture in tobacco extracts, but not extracts of other substances, reduces TAP1 protein, but does not reduce expression of HLA class I H chain, L chain, or the housekeeping protein β-actin. The reduction of TAP1 protein occurs within 4 h and is dose-dependent. Culture in tobacco extracts reduces TAP1 protein abundance, but not steady-state mRNA abundance. Tobacco-treated cells show defects in HLA class I biosynthesis similar to those found in TAP1-deficient cell lines. Transfection with TAP1 cDNA restores TAP1 protein abundance, HLA class I biosynthesis, and cell surface expression. Combined, these data show that culture in tobacco extracts reduces TAP1 protein abundance and membrane HLA class I levels. Reduction in membrane HLA class I could permit subsequent malignant transformation of cells to be undetected by the immune system.
Tourism and economic growth: a meta-analysis of panel data studies

Although for decades it has been acknowledged that tourism likely contributes to economic growth, theoretical models that consider a causal relationship between both are a recent phenomenon. From a sample of 11 studies based on panel data techniques published through to 2011, and for a total of 87 heterogeneous estimations, a metaanalysis is performed by applying models for both fixed and random effects, with the main objective being to calculate a summary measure of the effects of tourism on economic growth. While the results obtained point to a positive elasticity between economic growth and tourism, the magnitude of the effect was found to vary according to the methodological procedure employed in the original studies for empirical
DNA in the Criminal Justice System: The DNA Success Story in Perspective ,

Current figures on the efficiency of DNA as an investigative tool in criminal investigations only tell part of the story. To get the DNA success story in the right perspective, we examined all forensic reports from serious (N = 116) and high‐volume crime cases (N = 2791) over the year 2011 from one police region in the Netherlands. These data show that 38% of analyzed serious crime traces (N = 384) and 17% of analyzed high‐volume crime traces (N = 386) did not result in a DNA profile. Turnaround times (from crime scene to DNA report) were 66 days for traces from serious crimes and 44 days for traces from high‐volume crimes. Suspects were truly identified through a match with the Offender DNA database of the Netherlands in 3% of the serious crime cases and in 1% of the high‐volume crime cases. These data are important for both the forensic laboratory and the professionals in the criminal justice system to further optimize forensic DNA testing as an investigative tool.
Rectal Application of a Highly Osmolar Personal Lubricant in a Macaque Model Induces Acute Cytotoxicity but Does Not Increase Risk of SHIV Infection

Background Personal lubricant use is common during anal intercourse. Some water-based products with high osmolality and low pH can damage genital and rectal tissues, and the polymer polyquaternium 15 (PQ15) can enhance HIV replication in vitro. This has raised concerns that lubricants with such properties may increase STD/HIV infection risk, although in vivo evidence is scarce. We use a macaque model to evaluate rectal cytotoxicity and SHIV infection risk after use of a highly osmolar (>8,000 mOsm/kg) water-based lubricant with pH of 4.4, and containing PQ15. Methods Cytotoxicity was documented by measuring inflammatory cytokines and epithelial tissue sloughing during six weeks of repeated, non-traumatic lubricant or control buffer applications to rectum and anus. We measured susceptibility to SHIVSF162P3 infection by comparing virus doses needed for rectal infection in twenty-one macaques treated with lubricant or control buffer 30 minutes prior to virus exposure. Results Lubricant increased pro-inflammatory cytokines and tissue sloughing while control buffer (phosphate buffered saline; PBS) did not. However, the estimated AID50 (50% animal infectious dose) was not different in lubricant- and control buffer-treated macaques (p = 0.4467; logistic regression models). Conclusions Although the test lubricant caused acute cytotoxicity in rectal tissues, it did not increase susceptibility to infection in this macaque model. Thus neither the lubricant-induced type/extent of inflammation nor the presence of PQ15 affected infection risk. This study constitutes a first step in the in vivo evaluation of lubricants with regards to HIV transmission.
Managerial Incentives, Operational Decisions, and Firm Outcomes: Evidence From a Quasi-Experiment at a Retail Chain

Using a novel data set from 75 stores of a department store retail chain that changed its incentive plan for store managers to spur greater cooperation among them and with the corporate office, we examine how incentives impact operational decisions and, consequently, store outcomes. We measure store performance using sales growth, accuracy in labor scheduling, and labor productivity. We find that emphasizing corporate goals in managers’ incentives has resulted in worsening of performance at the store level. This effect is mainly the product of store managers exerting less effort in response to the change in their pay schemes. We also document deterioration in three underlying operational decisions involved in labor scheduling, i.e., sales forecasting, labor planning, and labor execution (defined as the adjustments to labor plan in response to new demand information since the labor plan was generated) as a result of the incentive change.
In vitro and in vivo effects of clinically important camptothecin analogues on multidrug-resistant cells.

The cytotoxic alkaloid camptothecin (CPT) and several of its analogues, including the clinically relevant topotecan (TPT), irinotecan (CPT-11), and 9-aminocamptothecin, were evaluated for differential cytotoxic effect and DNA damage induction in multidrug-sensitive (AuxB1) and multidrug-resistant (MDR) (CHRC5) Chinese hamster ovary cells. CPT, 10-hydroxycamptothecin, and 10,11-methylenedioxycamptothecin produced equivalent amounts of cell growth inhibition and/or DNA single-strand breakage in the two cell lines. TPT, SN-38 (the active metabolite of CPT-11), and 9-aminocamptothecin were 12-, 9-, and 10-fold, respectively, less toxic to the MDR than to the wild-type cells. These findings are consistent with differences in yields of DNA single-strand breaks produced in AuxB1 and CHRC5 cells by 2-hr incubations with the various compounds. In both assays, the resistance ratios of the topoisomerase I inhibitors were approximately one-tenth those of known MDR drugs such as vinblastine or amsacrine. Thus, cultured cells that overexpress P-glycoprotein have the potential to develop some level of cross-resistance to all three topoisomerase I inhibitors currently in the clinic. The chemical basis for cross-resistance of cultured MDR cell lines to certain CPT analogues is not yet understood, but is likely more complex than positive charge alone. TPT had a reasonable therapeutic effect on B6D2F1 female mice implanted with MDR sublines of P388 leukemia, compared with its effect on mice implanted with wild-type P388 cells. (ABSTRACT TRUNCATED AT 250 WORDS)