Miracle-dz/UniFAR-FTUs huggingface dataset:
Niacin Deficiency Alters p53 Expression and Impairs Etoposide-Induced Cell Cycle Arrest and Apoptosis in Rat Bone Marrow Cells

Abstract One focus of chemoprevention research is the interaction of nutrients with specific molecular targets associated with the maintenance of genomic stability. This study tested the impact of dietary niacin status on bone marrow NAD+ and poly(ADP-ribose) (pADPr) levels, p53 expression, and etoposide (ETO)-induced apoptosis and cell cycle arrest. After 3 wk on niacin-deficient (ND), pair-fed niacin-replete (PF), or nicotinic acid–supplemented (4 g/kg diet) (NA) diets, Long-Evans rats were gavaged with ETO (25 mg/kg) or vehicle. ND and NA diets caused a 72% decrease and a 240% increase in bone marrow NAD+, respectively. Basal and ETO-induced pADPr levels differed dramatically among ND, PF, and NA diets (undetectable, 42 and 216 fmol/million cells, respectively; basal and undetectable, 119 and 484 fmol/million cells, respectively, following ETO). ND diet alone caused overexpression of two distinct isoforms of p53. Levels of p53 in PF and NA marrow increased in response to ETO treatment, but this did not occur in ND bone marrow. Quantitative polymerase chain reaction of regular and alternative spliced variants of p53 mRNA revealed that niacin deficiency actually decreased both forms of p53 message, implicating protein stability in the accumulation of p53 in ND marrow. ETO-induced apoptosis (TUNEL) was suppressed during niacin deficiency and enhanced by supplementation. G1 arrest was also impaired in ND bone marrow relative to PF and NA. Despite a poor G1 arrest, p21 waf1 was overexpressed in the ND bone marrow and dramatically induced following ETO treatment. In conclusion, dietary niacin deficiency causes changes in NAD+ and pADPr metabolism, alters p53 expression, and impairs cellular responses to DNA damage.
Skeletal muscle channelopathies: new insights into the periodic paralyses and nondystrophic myotonias

Purpose of reviewTo summarize advances in our understanding of the clinical phenotypes, genetics, and molecular pathophysiology of the periodic paralyses, the nondystrophic myotonias, and other muscle channelopathies. Recent findingsThe number of pathogenic mutations causing periodic paralysis, nondystrophic myotonias, and ryanodinopathies continues to grow with the advent of exon hierarchy analysis strategies for genetic screening and better understanding and recognition of disease phenotypes. Recent studies have expanded and clarified the role of gating pore current in channelopathy pathogenesis. It has been shown that the gating pore current can account for the molecular and phenotypic diseases observed in the muscle sodium channelopathies, and, given that homologous residues are affected in mutations of calcium channels, it is possible that pore leak represents a pathomechanism applicable to many channel diseases. Improvements in treatment of the muscle channelopathies are on the horizon. A randomized controlled trial has been initiated for the study of mexiletine in nondystrophic myotonias. The class IC antiarrhythmia drug flecainide has been shown to depress ventricular ectopy and improve exercise capacity in patients with Andersen–Tawil syndrome. SummaryRecent studies have expanded our understanding of gating pore current as a disease-causing mechanism in the muscle channelopathies and have allowed new correlations to be drawn between disease genotype and phenotype.
Single‐step unimolecular non‐first‐order enzyme deactivation kinetics

A two‐parameter deactivation model is proposed to describe the kinetics of activity stabilization for some enzymes. The single‐step unimolecular mechanism exhibits non‐first‐order deactivation kinetics since the final enzyme state, E1 is not completely inactivated. The usefulness of the model is demonstrated by applying it to the inactivation of different enzymes. The influence of the concentration of active ester, ionic strength, and pH on the model parameters is examined during the inactivation of electric eel acetylcholinesterase.25 In general, inactivators would decrease the level of activity stabilization, α1, and increase the first‐order inactivation rate constant, k1. The effect of protecting agents would be to increase α1 and to decrease k1.
Predicting pregnancy and spermatogenesis by survival analysis during gonadotrophin treatment of gonadotrophin-deficient infertile men.

BACKGROUND Predictors of fertility or spermatogenesis during gonadotrophin therapy of gonadotrophin-deficient men remain poorly defined. METHODS AND RESULTS In order to evaluate potential predictors, this study evaluated 29 consecutive gonadotrophin-deficient men all desiring paternity who received 43 courses of therapy in one centre between 1982 and 1998. The Kaplan-Meier survival analysis estimates of median (SE) time to a sperm concentration of >0, >5 and >20 x 10(6)/ml were 5.5 (1.1), 12.4 (2.3) and 29.1 (1.9) months respectively. Conception occurred in 22/43 cycles (with eight men achieving two pregnancies) with a median (SE) Kaplan-Meier estimate of 20.5 (4.7) months. The median sperm concentration at conception was 5.0 (SE 2.0; range 0.0-59.5) x 10(6)/ml. Multivariate correlated Cox proportional hazards models predicting these same sperm thresholds and conception were developed by forward stepwise variable selection with verification of the model by backward stepping. Larger testicular volume, prior gonadotrophin therapy, completion of puberty, older age, the absence of adverse fertility factors and the absence of multiple pituitary hormone deficiency predicted a favourable response. Multivariate modelling suggests that the two most important predictors of sperm output are testicular volume and pubertal status. The most important potentially modifiable predictor was prior gonadotrophin therapy. The efficacy of recombinant and urinary FSH were similar. Prior androgen therapy and partner's age did not appear to be significant. CONCLUSIONS Since prolonged treatment may be required to induce spermatogenesis, attention to these predictors may allow appropriate early use of advanced reproductive technologies.
Relationship between Provider Stigma and Predictors of Staff Turnover among Addiction Treatment Providers

ABSTRACT To further our knowledge about feasible targets for improving quality of addiction treatment services, the current study provides preliminary assessment of the relationship between provider stigma and indicators of staff turnover. As predicted, results suggest that higher provider stigma was significantly related to lower ratings of job satisfaction and workplace climate. However, provider stigma was not significantly related to burnout. Our preliminary findings, if replicated, suggest the importance of considering provider stigma as a risk factor for future staff turnover and job dissatisfaction. Promising provider stigma interventions do exist and offer viable opportunity for improving quality of addiction treatment.
Juvenile polyps of the colon and rectum

ISCI'SSIONS ON POLYPS OF THE COLON AND D rectum in children have been coniplicated in the past by failure to distinguish between relatively rare neoplastic adenomatous polyps and the much more common juvenile polyps.1R Some authors,*, 14 not performing pathological examinations of all specimens, have probably included siich polyp-producing lesions as in yomas and lipomas in their reports. Others have even included adenocarcinomas among polyps of the colon and rectum.37 Since a inalignant potential of polyps of the large intestine of children123 18338 and of
CHANGES IN DNA, RNA, AND PROTEIN SYNTHESIS IN THE DEVELOPING LENS.

Lens cell DNA, RNA, and protein synthesis in the developing mouse eye were studied with the use of tritium-labeled thymidine, uridine, and l-leucine and autoradiographic techniques. In the mouse embryonic lens, epithelial cells undergoing DNA synthesis were found over the entire anterior lens surface. From birth and until the eyes opened the percentage of epithelial cells undergoing DNA synthesis rapidly decreased. Later the percentage of epithelial cells undergoing DNA synthesis teas nearly constant as the germinative zone became localized in the lens equator region. RNA synthesis occurred in all nucleated cells of the developing lens from the embryonic stage until the eyelids opened. With lens maturity the H uridine was incorporated into the RNA of only the more superficial cells. A similar pattern of tritium incorporation was seen with H l-leucine.
Influence of Ozone Stress on Soybean Response to Carbon Dioxide Enrichment: I. Foliar Properties

Tropospheric O₃ can cause foliar injury, decreased growth, and decreased yield, whereas CO₂ enrichment generally causes opposite effects. Little is known about plant response to mixtures of O₃ and CO₂. Open-top field chambers were used to determine if foliar responses of soybean [Glycine max (L.) Merr. ] to CO₂ enrichment are affected by O₃ stress and vice versa. Plants were grown in 14-L pots and exposed to four CO₂ and three O₃ concentrations in 12 combinations. The CO₂ treatments were ambient (366 μL⁻) and three treatments with CO₂ added for 24 h d 1 at approximately 1.3, 1.6, and 2.0 times ambient. The O₃ treatments were charcoal-filtered air (CF), nonfiltered air (NF), and NF with O₃ added for 12 h⁻¹ (NF+), resulting in seasonal concentrations of approximately 20, 46, and 75 μL L⁻¹. Foliar effects of CO₂ enrichment were dependent on the amount of stress caused by O₃. In the CF treatment, plants were not stressed by O₃, and CO₂ enrichment caused chlorosis and decreased chlorophyll. In the NF and NF+ treatments, plants were stressed by 03, and CO₂ enrichment suppressed chlorosis and increased chlorophyll. Ozone decreased specific leaf weight, increased foliar N and C, and decreased C/N ratios, whereas CO₂ caused opposite responses for these measures. Ozone increased foliar S and B but did not affect P or K concentrations. Conversely, CO₂ enrichment suppressed foliar S, B, P, and K concentrations. These interactions between O₃ and CO₂ emphasize a need to consider the amount of plant stress caused by O₃ in studies to measure effects of CO₂ enrichment. Cooperative investigations of the USDA-ARS Air Quality Research Unit and the North Carolina State University. Funded in part by the North Carolina Agricultural Research Service.
Formation and Biological Targets of Quinones: Cytotoxic versus Cytoprotective Effects

Quinones represent a class of toxicological intermediates, which can create a variety of hazardous effects in vivo including, acute cytotoxicity, immunotoxicity, and carcinogenesis. In contrast, quinones can induce cytoprotection through the induction of detoxification enzymes, anti-inflammatory activities, and modification of redox status. The mechanisms by which quinones cause these effects can be quite complex. The various biological targets of quinones depend on their rate and site of formation and their reactivity. Quinones are formed through a variety of mechanisms from simple oxidation of catechols/hydroquinones catalyzed by a variety of oxidative enzymes and metal ions to more complex mechanisms involving initial P450-catalyzed hydroxylation reactions followed by two-electron oxidation. Quinones are Michael acceptors, and modification of cellular processes could occur through alkylation of crucial cellular proteins and/or DNA. Alternatively, quinones are highly redox active molecules which can redox cycle with their semiquinone radical anions leading to the formation of reactive oxygen species (ROS) including superoxide, hydrogen peroxide, and ultimately the hydroxyl radical. Production of ROS can alter redox balance within cells through the formation of oxidized cellular macromolecules including lipids, proteins, and DNA. This perspective explores the varied biological targets of quinones including GSH, NADPH, protein sulfhydryls [heat shock proteins, P450s, cyclooxygenase-2 (COX-2), glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase 1, (NQO1), kelch-like ECH-associated protein 1 (Keap1), IκB kinase (IKK), and arylhydrocarbon receptor (AhR)], and DNA. The evidence strongly suggests that the numerous mechanisms of quinone modulations (i.e., alkylation versus oxidative stress) can be correlated with the known pathology/cytoprotection of the parent compound(s) that is best described by an inverse U-shaped dose–response curve.
Cellular and clinical perspectives on skeletal insulin‐like growth factor I

Insulin‐like growth factor (IGF) I, a polypeptide synthesized by skeletal cells, is presumed to act as an autocrine regulator of bone formation. IGF I stimulates bone replication of preosteoblastic cells and enhances the differentiated function of the osteoblast. The synthesis of skeletal IGF I is regulated by systemic hormones, most notably parathyroid hormone and glucocorticoids, as well as by locally produced factors, such as prostaglandins and other skeletal growth factors. Whereas hormones and growth factors regulate IGF I synthesis, the exact level of regulation has not been established and may involve both transcriptional and posttranscriptional mechanisms. The IGF I gene contains six exons, and both exon 1 and 2 contain transcription initiation sites. Extrahepatic tissues, including bone, express exon 1 transcripts, and regulation of the exon 1 promoter activity in osteoblasts is currently under study. It is apparent that the regulation of IGF I gene transcription as well as the regulation of mRNA stability is complex and tissue specific. It is possible that abnormalities in skeletal IGF I synthesis or activity play a role in the pathogenesis of bone disorders. In view of its important anabolic actions in bone, it is tempting to postulate the use of IGF I for the treatment of disorders characterized by decreased bone mass. An alternative could be the stimulation of the local production of IGF I in bone. © 1994 Wiley‐Liss, Inc.
Agrobacterium-mediated Genetic Transformation of Two Varieties of Jute (Corchorus capsularis L.)

Transformation experiments were carried out using different explants of two varieties of white jute ( Corchorus capsularis L.), namely, CVL-1 and CVE-3 with Agrobacterium tumefaciens strain (LBA4404/pBI121) containing the GUS and npt II genes. Maximum transformation ability was obtained from petiole-attached cotyledons and mature embryo explants. Kanamycin at a concentration of 200 mg/l was found optimum for selection of transformed shoots developed from mature embryos. Histochemical assay revealed the stable expression of the GUS gene within the various tissues of transformed plantlets. Stable integration of GUS and npt II genes were confirmed by PCR analysis of genomic DNA isolated from these transformed shoots. Key words: Jute, Transformation, GUS expression, PCR analysis D.O. I. 10.3329/ptcb.v18i1. 3245 Plant Tissue Cult. & Biotech. 18 (1): 7-16, 2008 (June)
Practice Association of Pharmaceutical Teachers of India A Study on Prescribing Pattern and Potential Drug-drug Interactions in Type 2 Diabetes Mellitus Inpatients

Over the last decade, diabetes mellitus has emerged as an important clinical and public health problem throughout the world. The aim of the study is to evaluate prescribing pattern and potential drug-drug interactions in hospitalized patients with type 2 diabetes mellitus. The prospective study was conducted over a period of six months in the department of Medicine, Bharati Hospital. The prevalence of type2 diabetes was high in male 57.14 % than female 42.86%. Majority of the patients 51 (48.57%) belonged to age group of 41–60 years. Average drugs per prescription were 12.2. 99.0% of the drugs were prescribed by their brand names. 73.77% of the drugs prescribed were from the WHO list of essential drugs. Totally, 58.10 % of patients were on monotherapy and human insulin (50.48%) was commonly prescribed. In combination therapy, Glimepride and Metformin with insulin (10.48 %) were mostly consumed followed by Glimepiride and Metformin (4.76%) fixed dose therapy. 60 drug -drug interactions were encountered in the study, comprising of 18 (17.14%) actual and 42 (40.00%) were potential drug -drug interactions. As per severity, 16.67% were major, 72.22% were moderate and 11.11% were minor. The potential drug-drug interactions are frequent in type 2 diabetes mellitus and hence, deserve clinical attention. In our study, the generic drug prescription is low and the essential drug prescription is high, hence the prescription by generics should be promoted more for cost effective treatment.
Testosterone and ageing: what have we learned since the Institute of Medicine report and what lies ahead?

A 2003 report by the Institute of Medicine (IOM) surveyed the literature on the benefits and risks of testosterone replacement therapy in older men and identified knowledge gaps and research needs. This review summarises some key studies published since the IOM report. The possible relationship of testosterone to risk of prostate cancer remains a concern; however, no new evidence has emerged to suggest that testosterone replacement therapy increases the risk. Recent studies have demonstrated that hypogonadism in men may be more prevalent than previously thought, is strongly associated with metabolic syndrome, and may be a risk factor for type 2 diabetes and cardiovascular disease. Clinical studies have shown that testosterone replacement therapy in hypogonadal men improves metabolic syndrome indicators and cardiovascular risk factors. Maintaining testosterone concentrations in the normal range has been shown to contribute to bone health, lean muscle mass, and physical and sexual function, suggesting that testosterone replacement therapy may help to prevent frailty in older men. Based on current knowledge, testosterone replacement therapy is unlikely to pose major health risks in patients without prostate cancer and may offer substantial health benefits. Larger, longer‐term randomised studies are needed to fully establish the effects of testosterone replacement therapy.
Elastic-net based beamforming in medical ultrasound imaging

This paper presents a new way of addressing beamforming in ultrasound imaging, by formulating it, for each image depth, as an inverse problem solved using elastic-net regularization. This approach was evaluated on both simulated and in vivo data showing a gain in contrast, while maintaining an increased value of the signal-to-noise ratio compared to two standard ultrasound beamforming methods.
Sit to stand transfer: performance in rising power, transfer time and sway by age and sex in senior athletes

Objective: To observe the differences in performance variables of the sit to stand transfer (as measured on the NeuroCom Balance Master) in a population of senior athletes. Method: A convenience sample of 173 subjects aged 50 years and older. Data were obtained from voluntary participation in a health fair offered at the annual Huntsman World Senior Games in St George, Utah, USA. All sit to stand tests were performed on the NeuroCom Balance Master. The measured parameters were weight transfer time (WTT), rising power (force exerted to rise), and centre of gravity sway (COG sway) during the rising phase. Results: A significant difference was found between stratified age groups (50–64 and 65+ years) on rising power. There was also a sex difference in rising power. No significant differences were found in weight transfer time or COG sway. Conclusion: While rising power decreases with increasing age in senior athletes, WTT and COG sway remain similar regardless of age or sex. The maintenance of these other two variables (WTT and COG sway) may be attributable to physical activity and/or participation in sport.
Comparative elite sport development : systems, structures and public policy

Chapter 1: Introduction by Barrie Houlihan and Mick Green Chapter 2: China by Fan Hong Chapter 3: Japan by Mayumi Ya-Ya Yamamoto Chapter 4: Singapore by Lionel Teo Chapter 5: Germany by Karen Petry, Dirk Steinbach and Verena Burk Chapter 6: France by Emmanuel Bayle, Christophe Durand and Luc Nikonoff Chapter 7: Poland by Jolanta Yyuko Chapter 8: Norway by Pal Augestad and Nils Asle Bergsgard Chapter 9: New Zealand by Shane Collins Chapter 10: United States by Emily Sparvero, Laurence Chalip, and B. Christine Green Chapter 11: Conclusions by Mick Green and Barrie Houlihan
Entry of a Novel Marine DNA Virus, Singapore Grouper Iridovirus, into Host Cells Occurs via Clathrin-Mediated Endocytosis and Macropinocytosis in a pH-Dependent Manner

ABSTRACT Iridoviruses are nucleocytoplasmic DNA viruses which cause great economic losses in the aquaculture industry but also show significant threat to global biodiversity. However, a lack of host cells has resulted in poor progress in clarifying iridovirus behavior. We investigated the crucial events during virus entry using a combination of single-virus tracking and biochemical assays, based on the established virus-cell infection model for Singapore grouper iridovirus (SGIV). SGIV infection in host cells was strongly inhibited when cells were pretreated with drugs blocking clathrin-mediated endocytosis, including sucrose and chlorpromazine. Inhibition of key regulators of macropinocytosis, including Na+/H+ exchanger, Rac1 GTPase, p21-activated kinase 1 (PAK1), protein kinase C (PKC), and myosin II, significantly reduced SGIV uptake. Cy5-labeled SGIV particles were observed to colocalize with clathrin and macropinosomes. In contrast, disruption of cellular cholesterol by methyl-β-cyclodextrin and nystatin had no effect on virus infection, suggesting that SGIV entered grouper cells via the clathrin-mediated endocytic pathway and macropinocytosis but not via caveola-dependent endocytosis. Furthermore, inhibitors of endosome acidification such as chloroquine and bafilomycin A1 blocked virus infection, indicating that SGIV entered cells in a pH-dependent manner. In addition, SGIV particles were observed to be transported along both microtubules and actin filaments, and intracellular SGIV motility was remarkably impaired by depolymerization of microtubules or actin filaments. The results of this study for the first time demonstrate that not only the clathrin-dependent pathway but also macropinocytosis are involved in fish DNA enveloped virus entry, thus providing a convenient tactic for exploring the life cycle of DNA viruses. IMPORTANCE Virus entry into host cells is critically important for initiating infections and is usually recognized as an ideal target for the design of antiviral strategies. Iridoviruses are large DNA viruses which cause serious threats to ecological diversity and the aquaculture industry worldwide. However, the current understanding of iridovirus entry is limited and controversial. Singapore grouper iridovirus (SGIV) is a novel marine fish DNA virus which belongs to genus Ranavirus, family Iridoviridae. Here, using single-virus tracking technology in combination with biochemical assays, we investigated the crucial events during SGIV entry and demonstrated that SGIV entered grouper cells via the clathrin-mediated endocytic pathway in a pH-dependent manner but not via caveola-dependent endocytosis. Furthermore, we propose for the first time that macropinocytosis is involved in iridovirus entry. Together, this work not only contributes greatly to understating iridovirus pathogenesis but also provides an ideal model for exploring the behavior of DNA viruses in living cells.