Miracle-dz/UniFAR-FTUs huggingface dataset:
Dietary Iron Promotes Azoxymethane-Induced Colon Tumors in Mice

Abstract: There is accumulating evidence that high levels of dietary iron may play a role in colon carcinogenesis. We used a mouse model to investigate the impact of elevated dietary iron on incidence of aberrant crypt foci (ACF; a preneoplastic lesion) on tumor formation and on induction of oxidative stress. A/J mice were injected intraperitoneally, once a week for 6 weeks, with the colonotropic carcinogen, azoxymethane (AOM) or saline (vehicle controls). Following AOM or saline treatments, mice were placed on diets of high (3,000 ppm) and low (30 ppm) iron. Mice in each treatment group were sacrificed at 6 and 10 weeks following the final injection with AOM or saline. Colons were removed for subsequent histopathological analysis, which revealed average increases of 4.6 ± 1.3 vs. 10.4 ± 2.5 total tumors at 6 weeks and 30.75 ± 2.7 vs. 41.5 ± 4.4 total tumors at 10 weeks per AOM-treated mouse on low- and high-iron diets, respectively. There were no significant differences in incidence of ACF attributable to iron, although there was a trend toward greater crypt multiplicity per focus in mice on high-iron diets. Notably, no tumors were observed in mice receiving vehicle control injections in place of carcinogen, regardless of the level of dietary iron. These data suggest that iron exerts its effect at the stage of tumor promotion, but is not sufficient to initiate tumor formation. To learn more about mechanisms by which iron promotes tumor growth, colons were assayed for several biomarkers of oxidative stress [BOS; total F2-isoprostanes (F2-IsoPs), 15-F2t-isoprostanes (8-IsoPGF2αs), Isofurans (IsoFs), and 8-hydroxyguanosines (8-OH[d]Gs)], as well as iron absorption, programmed cell death, and cellular proliferation. Elevated PCNA and TUNEL staining of the colon epithelium revealed hyperproliferative and apoptotic responses to iron, while no significant differences between iron groups were observed in each of the BOS that were assayed. Our results suggest that, following carcinogen exposure, elevated dietary iron promotes the growth of tumors with altered cellular homeostasis through a mechanism that is independent of oxidative stress.
Adhesion of Pseudomonas aeruginosa and Staphylococcus epidermidis to Silicone–Hydrogel Contact Lenses

Purpose. The purpose of this study is to compare the adhesion capabilities of the most important etiologic agents of microbial ocular infection to the recently available silicone–hydrogel lenses with those to a conventional hydrogel lens. Methods. In vitro static adhesion assays of Pseudomonas aeruginosa 10,145, Staphylococcus epidermidis 9142 (biofilm-positive), and 12,228 (biofilm-negative) to two extended-wear silicone–hydrogel lenses (balafilcon A and lotrafilcon A), a daily wear silicone–hydrogel lens (galyfilcon A) and a conventional hydrogel (etafilcon A) were performed. To interpret the adhesion results, lens surface relative hydrophobicity was assessed by water contact angle measurements. Results. P. aeruginosa and S. epidermidis 9142 exhibited greater adhesion capabilities to the extended wear silicone–hydrogel lenses than to the daily wear silicone– and conventional hydrogel lenses (p < 0.05). No statistical differences were found between the adhesion extent of these strains to galyfilcon A and etafilcon A. The biofilm negative strain of S. epidermidis adhered in larger extents to the silicone–hydrogel lenses than to the conventional hydrogel (p < 0.05), but in much lower amounts than the biofilm-positive strain. The water contact angle measurements revealed that the extended wear silicone–hydrogel lenses are hydrophobic, whereas the daily wear silicone– and conventional hydrogel lenses are hydrophilic. Conclusions. As a result of their hydrophobicity, the extended wear silicone–hydrogel lenses (lotrafilcon A and balafilcon A) may carry higher risk of microbial contamination than both the hydrophilic daily wear silicone–hydrogel lens, galyfilcon A and the conventional hydrogel lens, etafilcon A.
Rapid Delivery of Foreign Genes into Plants by Direct Rub-Inoculation with Intact Plasmid DNA of a Tomato Bushy Stunt Virus Gene Vector

ABSTRACT Tomato bushy stunt virus (TBSV) cDNA, positioned between a modified cauliflower mosaic virus 35S promoter and the hepatitis delta virus antigenomic ribozyme with a downstream nopaline synthase gene polyadenylation signal, established infections upon rub-inoculation of plants with intact plasmids. Application of this methodology produced a TBSV DNA-based gene vector which yielded readily detectable levels of localized foreign gene expression in inoculated leaves. This is the first demonstration of an infectious DNA from a member of theTombusviridae which permits rapid TBSV-mediated foreign-gene expression upon direct rub-inoculation of miniprep DNA onto a variety of plant species.
Egg production performance, egg yolk antioxidant profile and excreta concentration of corticosterone in golden pheasants (Chrysolophus pictus) fed diets containing different levels of green vegetables

In order to study the effect of feeding graded levels of green vegetables on egg production performance and egg yolk antioxidant status, 27 female golden pheasants (GP) were randomly distributed into three groups of nine each in an experiment based on completely randomized design. The diets of the birds in groups T1 , T2 and T3 contained 1.4%, 2.7% and 5.0% of green vegetables respectively. Feeding of experimental diets started on 12th February (day 1) and was continued till 30 June 2012. Average number of eggs laid and egg mass produced by the hens in group T3 was higher (p < 0.004) than those of T1 and T2 . Hen day egg production was lowest (p < 0.001) in group T1 . Roche yolk colour score was highest (p < 0.01) in T3 followed by T2 and was lowest in T1 . Other external and internal egg quality parameters were similar among the groups. Total antioxidant capacity (TAC) of egg yolk was higher (p < 0.04) in group T3 as compared to other two groups. Egg yolk concentration of total carotenoids, β-carotene, total sulfhydryl, protein-bound sulfhydryl and non-protein-bound sulfhydryl was higher (p < 0.05), whereas concentration of malondialdehyde was lower (p < 0.024) in group T3 as compared to other two groups. Excreta concentration of corticosterone was highest (p < 0.012) in T1 , followed by T2 , and was lowest in T3 . Egg yolk concentration of TAC and TSH was positively and that of malondialdehyde was negatively correlated with carotenoids intake. Excreta concentration of corticosterone was negatively correlated with carotenoids intake. It was concluded that incorporation of green vegetables in the diet at 5% on dry matter basis would improve egg production, egg yolk antioxidant status and the ability of the captive GP to combat stress.
Polyprotein processing in cis and in trans by hepatitis A virus 3C protease cloned and expressed in Escherichia coli

To determine the P3 region protein-processing sites cleaved by the hepatitis A virus 3C protease, a nested set of constructs containing a portion of 3A (3A* [the asterisk denotes an incomplete protein]), 3B and 3C and various amounts of 3D, fused in frame to Escherichia coli TrpE-coding sequences under control of the tryptophan promoter, was made. Additional plasmids that encoded a portion of 2C (2C*) and the P3 proteins, including complete or incomplete 3D sequences, were constructed. After induction, E. coli containing these recombinant plasmids produced high levels of fusion proteins as insoluble aggregates. 3C-mediated cleavage products were identified by comparison of expression with a matching set of plasmids, containing an engineered mutation in 3C. Cleavage products were detected by immunoblot analyses by using antisera against the TrpE protein, against 3D*, and against 3CD*. Scissile bonds were determined by N-terminal amino acid sequencing of the proteins formed by cleavage. The results showed that when a portion of 2C was present, the primary cleavage by the 3C protease was between 2C and 3A, and the cleavage site was QG, as predicted by J. I. Cohen, J. R. Ticehurst, R. H. Purcell, A. Buckler-White, and B. M. Baroudy, J. Virol. 61:50-59, 1987. Very little further cleavage of the released P3 protein was detected. When the fusion protein contained no 2C and included only 3A*-to-3D sequences, efficient cleavage occurred between 3B and 3C, at the QS pair, also as predicted by Cohen et al. (J. Virol. 61:50-59, 1987). The latter proteins were also cleaved between 3C and 3D, but less efficiently than between 3B and 3C. Extracts of bacteria expressing proteins from 3A* to 3D also cleaved a radiolabelled hepatitis A virus substrate containing VP1*2ABC* sequences in trans.
A Board Game to Assist Pharmacy Students in Learning Metabolic Pathways

Objectives. To develop and evaluate a board game designed to increase students’ enjoyment of learning metabolic pathways; their familiarity with pathway reactions, intermediates, and regulation; and, their understanding of how pathways relate to one another and to selected biological conditions. Design. The board game, entitled Race to Glucose, was created as a team activity for first-year pharmacy students in the biochemistry curriculum. Assessment. A majority of respondents agreed that the game was helpful for learning regulation, intermediates, and interpathway relationships but not for learning reactions, formation of energetic molecules, or relationships, to biological conditions. There was a significant increase in students’ scores on game-related examination questions (68.8% pretest vs. 81.3% posttest), but the improvement was no greater than that for examination questions not related to the game (12.5% vs. 10.9%). Conclusion. First-year pharmacy students considered Race to Glucose to be an enjoyable and helpful tool for learning intermediates, regulation, and interpathway relationships.
Bank Leverage, Capital Requirements and the Implied Cost of (Equity) Capital

Do heightened capital requirements impose private costs on banks by adversely affecting their cost of capital? And if so, does the effect differ across different groups of banks? Using an international sample of listed banks over the period from 1990 to 2017, I find that equity investors adjust their expected return weakly in accordance with the Modigliani and Miller (1958) Theorem when banks decrease their leverage. The adjustment is stronger for smaller banks, banks that rely more on deposit financing and when debt is reduced rather than deposits, which never triggers a statistically significant adjustment. In any cases, the adjustment is not strong enough to keep banks' cost of capital constant which is estimated to increase by 10 to 40bps, representing a relative increase of 2.8% to 12.6%, when shifting equity from 8% to 16%. When using the 2011 EBA capital exercise as a quasi-natural experiment to identify the impact of capital regulation on bank's cost of capital, results indicate a strong reduction in required returns for the treated banks. However, the reduction is mainly caused by shifts in asset risk, highlighting the importance of differentiating between short-run and long-run effects.
Determinants of bone mineral density in postmenopausal white Iowans.

BACKGROUND Osteoporosis is a major health problem for older individuals. For women, development of osteoporosis is a function of the accretion of "peak" bone mass in the third decade, age at menopause, and rate of bone loss with aging. Low bone mineral density (BMD) is a major risk factor for osteoporosis and fracture. The purpose of this study was to identify life style, nutritional, medical, and genetic predictors of low BMD in postmenopausal Iowa women. METHODS One hundred thirty-four postmenopausal White women ranging in age from 57 to 81 years were included in this case-control study. Bone mineral density was measured at the femoral neck, using dual photon X-ray absorptiometry (Hologic 2000 QDR). Sixty-six women with BMD measurements below 0.68 g/cm2 (the bottom quartile of the BMD distribution in the population from which participants were recruited), and 68 women with values at or above 0.83 g/cm2 (the top quartile of the BMD distribution in the same population) were included. Information about environmental, nutritional, medical, and life style modifiers of BMD was obtained by written questionnaire and telephone interview. To assess familial factors that might influence BMD, we obtained a detailed family history for each participant. In addition, we tested the hypothesis that allelic variation at the Vitamin D receptor (VDR), and the type I collagen gene (COL1A1 and COL1A2) loci influence BMD. RESULTS Weight, loss of height, age, and age at menopause were strong predictors of BMD in our population. After adjustment for these differences, we found no effect of genotype at the COL1A1, COL1A2, and VDR loci on BMD. CONCLUSIONS Bone mineral density is a complex trait that is influenced by several different modifiers; in the present study, weight was the best predictor of postmenopausal BMD. While several studies suggest that VDR genotype is an important determinant of BMD, we did not find this association in our population, nor did we identify an association between allelic variation at the type I collagen gene loci and BMD. Identification of genes that determine body mass index may provide additional insight into risk factors for low BMD, and osteoporotic fractures.
Diagnostic Capacity of 64-Slice Multidetector Computed Tomography for Acute Coronary Syndrome in Patients Presenting with Acute Chest Pain

Background/Aims: Early evaluations of patients presenting with acute chest pain remain difficult. We examined the diagnostic capacity of multidetector computed tomography (MDCT) for acute coronary syndrome (ACS) in patients presenting with acute chest pain. Methods/Results: We examined 36 consecutive patients presenting with acute chest pain with neither diagnostic ECG changes nor elevated biomarkers. 64-slice MDCT was performed, and we evaluated the presenceof significant coronaryartery stenosis (>50% reduction in lumen diameter). Significant stenosis was detected in 15 patients by MDCT. Among them, 11 patients were diagnosed as having ACS based on the findings of coronary angiography or myocardial perfusion single photon emission computed tomography (positive predictive value 73%). All 21 patients without significant stenosis by MDCT, except only one, were regarded as not having ACS (negative predictive value 95%). Sensitivity and specificity were 92 and 83%, respectively. In patients without a history of coronary artery disease (CAD), both the specificity and positive predictive value improved to 100% (sensitivity 90%; negative predictive value 95%). In patients with neither a history of CAD nor coronary calcification, the diagnostic accuracy of MDCT was 100%. Conclusions: MDCT has high diagnostic capacity for the early evaluation of ACS, especially in patients without a history of CAD or coronary calcification.
Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from Traditional Chinese Herbs

The three purified herbal compounds tetrahydropalmatine (Tet), neferine and berberine (Ber) were explored in vitro for basic inhibition mechanisms towards recombinant human CYP1A2, CYP2D6 and CYP3A4 metabolic activities. Phenacetin, dextromethorphan and testosterone, respectively, were used as CYP1A2, CYP2D6 and CYP3A4 substrates, and their metabolites were determined by validated HPLC methodologies. Positive inhibition controls were used. Mechanism‐based (irreversible) inhibition was assessed by time‐dependent and nicotinamide adenine dinucleotide phosphate‐dependent and reversible inhibition by Lineweaver–Burk plot assessments. Inhibition mechanisms were also assessed by computerized interaction prediction by using the Discovery Studio CDOCKER software (Accelrys, San Diego, CA, USA). Tetrahydropalmatine showed a mechanism‐based inhibition of both CYP1A2 and CYP2D6, and Ber of CYP2D6. Neferine and Ber both showed a nonmechanistic inhibition of CYP1A2. All compounds showed a similar and significant mechanism‐based inhibition of CYP3A4. Tetrahydropalmatine and Ber demonstrated both reversible and irreversible inhibition of CYP2D6 and CYP3A4. Tetrahydropalmatine and Ber displayed H‐bond and several Pi‐bond connections with specific amino acid residues of CYP1A2, CYP2D6 and CYP3A4, giving further knowledge to the identified reversible and irreversible herb–drug interactions. Tetrahydropalmatine and Ber should be considered for herb–drug interactions in clinical therapy until relevant clinical studies are available. Copyright © 2015 John Wiley & Sons, Ltd.
Therapeutic efficacy of anti‐dandruff shampoos: A randomized clinical trial comparing products based on potentiated zinc pyrithione and zinc pyrithione/climbazole

Dandruff is a chronic, relapsing scalp condition that negatively impacts the quality of life of sufferers. Regular use of anti‐fungal shampoos represents a proven therapeutic strategy to improve the most common symptoms of flakes and itch. Two recent approaches for enhancing the efficacy of anti‐fungal shampoos are maximizing bio‐availability of the active material or the addition of a second active material. Our aim is to compare the therapeutic efficacy of these two approaches – maximization of bio‐availability of the zinc pyrithione (ZPT) active material or the combination of ZPT with a secondary active material.
Relationship of physical activity vs body mass index with type 2 diabetes in women.

CONTEXT Physical inactivity and body mass index (BMI) are established independent risk factors in the development of type 2 diabetes; however, their comparative importance and joint relationship with diabetes are unclear. OBJECTIVE To examine the relative contributions and joint association of physical activity and BMI with diabetes. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 37 878 women free of cardiovascular disease, cancer, and diabetes with 6.9 years of mean follow-up. Weight, height, and recreational activities were reported at study entry. Normal weight was defined as a BMI of less than 25; overweight, 25 to less than 30; and obese, 30 or higher. Active was defined as expending more than 1000 kcal on recreational activities per week. MAIN OUTCOME MEASURE Incident type 2 diabetes, defined as a new self-reported diagnosis of diabetes. RESULTS During the follow-up, 1361 cases of incident diabetes occurred. Individually, BMI and physical activity were significant predictors of incident diabetes. Compared with normal-weight individuals, the multivariate-adjusted hazard ratio (HR) was 3.22 (95% confidence interval [CI], 2.69-3.87) for overweight individuals and 9.09 (95% CI, 7.62-10.8) for obese individuals. For overall activity (kilocalories expended per week), compared with the least active first quartile, the multivariate-adjusted HRs were 0.91 (95% CI, 0.79-1.06) for the second quartile, 0.86 (95% CI, 0.74-1.01) for the third, and 0.82 (95% CI, 0.70-0.97) for the fourth (P for trend =.01). In the combined analyses, overweight and obese participants, whether active or inactive, had significantly elevated risks, compared with normal-weight active individuals. The multivariate-adjusted HRs were 1.15 (95% CI, 0.83-1.59) for normal-weight inactive, 3.68 (95% CI, 2.63-5.15) for overweight active, 4.16 (95% CI, 3.05-5.66) for overweight inactive, 11.5 (95% CI, 8.34-15.9) for obese active, and 11.8 (95% CI, 8.75-16.0) for obese inactive participants. CONCLUSIONS Although BMI and physical inactivity are independent predictors of incident diabetes, the magnitude of the association with BMI was greater than with physical activity in combined analyses. These findings underscore the critical importance of adiposity as a determinant of diabetes.
How does bupropion work as a smoking cessation aid?

Bupropion exhibits reasonable efficacy as a smoking cessation aid, yet its precise mechanisms of action remain unclear. This review evaluates the mechanism of action of bupropion by considering the clinical evidence in combination with results from pre‐clinical experiments in vivo and in vitro. Bupropion is a weak inhibitor of dopamine and noradrenaline reuptake, and has also been shown to antagonise nicotinic acetylcholine receptor function. It is extensively metabolized in humans, its major metabolites reaching levels higher than those of bupropion itself. These metabolites share many of the pharmacological properties of bupropion, so they may play an important role in its clinical activity, yet they have been neglected in investigations into bupropion action. This review led to several conclusions: (1) the principal mode of bupropion action is upon the withdrawal symptoms following smoking cessation; (2) during withdrawal, bupropion may attenuate symptoms by mimicking nicotinic effects on dopamine and noradrenaline; (3) its ability to antagonize nicotinic receptors may prevent relapse by attenuating the reinforcing properties of nicotine, but probably cannot acutely reduce smoking; and (4) further exploration of bupropion metabolites and its role in withdrawal and relapse, within more appropriate animal models, could be crucial in the determination of the precise mechanisms by which bupropion exerts its activity in smoking cessation. Greater elucidation of the exact mechanisms of action of bupropion could lead to the development of new drugs even more beneficial in promoting smoking abstinence.
Indirect Network Effects in New Product Growth

Indirect network effects are of prime interest to marketers because they affect the growth and takeoff of software availability for and hardware sales of a new product. Although prior work on indirect network effects in the economics and marketing literature is valuable, there are two main shortcomings. First, empirical analysis of indirect network effects is rare. Second, in contrast to the importance prior literature credits to the “chicken-and-egg” paradox in these markets, the temporal pattern (i.e., Which leads to which? ) of indirect network effects remains unstudied. Based on empirical evidence of nine markets, this study shows that (1) indirect network effects, as commonly operationalized by prior literature, are weaker than expected from prior literature and (2) in most markets examined, hardware sales “lead” software availability, whereas the reverse almost never happens, contrary to existing beliefs. These findings are supported by multiple methods, such as takeoff and time-series analyses, and fit with the histories of the markets studied herein. For academia, the study identifies a need for new and more relevant conceptualizations of indirect network effects. For public policy, it questions the need for intervention in network markets. For management practice, it downplays the importance of the availability of a large library of software for hardware technology to be successful.
Financial Development, Rule of Law and Wealth Inequality: Bayesian Model Averaging Evidence

We examine the determinants of financial development using our global sample and employing a rich set of measures of financial development that assess the degree of depth, access, stability and efficiency of financial intermediaries. We use Bayesian model averaging to test competing theories within this unifying framework. Examining nearly 40 potential determinants of financial development, we find that the rule of law and the level of economic development are the most important. Wealth inequality is irrelevant for banking sector development but positively associated with stock market development. Finally, our results suggest that financial market regulations matter for stock market efficiency and financial stability.