Miracle-dz/UniFAR-FTUs huggingface dataset:
Title Inactivation Of Atm / atr Dna Damage Checkpoint Promotes Androgen Induced Chromosomal Instability In Prostate Epithelial Cells

The ATM/ATR DNA damage checkpoint functions in the maintenance of genetic stability and some missense variants of the ATM gene have been shown to confer a moderate increased risk of prostate cancer. However, whether inactivation of this checkpoint contributes directly to prostate specific cancer predisposition is still unknown. Here, we show that exposure of non-malignant prostate epithelial cells (HPr-1AR) to androgen led to activation of the ATM/ATR DNA damage response and induction of cellular senescence. Notably, knockdown of the ATM gene expression in HPr-1AR cells can promote androgeninduced TMPRSS2: ERG rearrangement, a prostate-specific chromosome translocation frequently found in prostate cancer cells. Intriguingly, unlike the non-malignant prostate epithelial cells, the ATM/ATR DNA damage checkpoint appears to be defective in prostate cancer cells, since androgen treatment only induced a partial activation of the DNA damage response. This mechanism appears to preserve androgen induced autophosphorylation of ATM and phosphorylation of H2AX, lesion processing and repair pathway yet restrain ATM/CHK1/CHK2 and p53 signaling pathway. Our findings demonstrate that ATM/ATR inactivation is a crucial step in promoting androgen-induced genomic instability and prostate carcinogenesis. Citation: Chiu Y-T, Liu J, Tang K, Wong Y-C, Khanna KK, et al. (2012) Inactivation of ATM/ATR DNA Damage Checkpoint Promotes Androgen Induced Chromosomal Instability in Prostate Epithelial Cells. PLoS ONE 7(12): e51108. doi:10.1371/journal.pone. 0051108 Editor: Fazlul H. Sarkar, Wayne State University School of Medicine, United States of America Received July 11, 2012; Accepted October 29, 2012; Published December 18, 2012 Copyright: 2012 Chiu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the National Health and Medical Research Council grants (APP1031221 and APP1031228). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: MTL currently serves as an academic editor for PLOS ONE and this does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. * E-mail: mingtat.ling@qut.edu. au
Relaxivity‐iron calibration in hepatic iron overload: Probing underlying biophysical mechanisms using a Monte Carlo model

Iron overload is a serious condition for patients with β‐thalassemia, transfusion‐dependent sickle cell anemia, and inherited disorders of iron metabolism. MRI is becoming increasingly important in noninvasive quantification of tissue iron, overcoming the drawbacks of traditional techniques (liver biopsy). Effective transverse relaxation rate (1/effective transverse relaxation time) rises linearly with iron while transverse relaxation rate (1/T2) has a curvilinear relationship in human liver. Although recent work has demonstrated clinically valid estimates of human liver iron, the calibration varies with MRI sequence, field strength, iron chelation therapy, and organ imaged, forcing recalibration in patients. To understand and correct these limitations, a thorough understanding of the underlying biophysics is of critical importance. Toward this end, a Monte Carlo‐based approach, using human liver as a “model” tissue system, was used to determine the contribution of particle size and distribution on MRI signal relaxation. Relaxivities were determined for hepatic iron concentrations ranging from 0.5 to 40 mg iron per gram dry tissue weight. Model predictions captured the linear and curvilinear relationship of effective transverse relaxation rate and transverse relaxation rate with hepatic iron concentrations, respectively, and were within in vivo confidence bounds; contact or chemical exchange mechanisms were not necessary. A validated and optimized model will aid understanding and quantification of iron‐mediated relaxivity in tissues where biopsy is not feasible (heart and spleen). Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.
A CYTOLOGICAL STUDY OF NOCARDIA CORALLINA AND OTHER ACTINOMYCETES

The cytology and life cycles of the Actinomycetes recently have received critical study. The presence of an apparent life cycle has been shown in Streptomyces (Kijeneberger-Nobel, 1947) and Actinomyces (Morris, 1951). McClung (1950) stained nuclear-like bodies and studied the proes of fragmentation in several species of Nocadia. The investigation, however, omitted a careful examination of germination, cytology, and division of the coccoidal forms. These recent cytological studies have relied primarily on the acid-Giemsa nuclear stain and various cell wall stains, some of which will not stain cross septa. This investigation was undertaken to determine the cytology of the genus Nocadia and other Actinomyetes by using the Chance crystal-violet nuclear stain, cell wall stains, and phase microscopy. The crystal-violet nuclear stain does not involve acid hydrolysis or other harsh treatment and should prove of value in clarifying the nuclear cytology of the Actinomycetes.
In Vitro Efficacy of the Combination of Ciprofloxacin and Cefotaxime against Vibrio vulnificus

ABSTRACT We performed time-kill studies of antimicrobial combinations that included minocycline, cefotaxime, and ciprofloxacin with Vibrio vulnificus ATCC 27562. Cefotaxime-plus-ciprofloxacin combinations acted synergistically against V. vulnificus in vitro, and this combination regimen can be a good choice as the empirical treatment for suspected necrotizing fasciitis due to V. vulnificus.
Gene-environment processes linking peer victimization and physical health problems: a longitudinal twin study.

OBJECTIVE This study examined whether (a) a genetic disposition for physical health problems increases the risk of peer victimization and (b) peer victimization interacts with genetic vulnerability in explaining physical health problems. METHODS Participants were 167 monozygotic and 119 dizyogtic twin pairs. Physical symptoms were assessed in early childhood and early adolescence. Peer victimization was assessed in middle childhood. RESULTS Genetic vulnerability for physical health problems in early childhood was unrelated to later peer victimization, but genetic vulnerability for physical health problems during early adolescence increased the risk of victimization. Victimization did not interact with genetic factors in predicting physical symptoms. Environmental, not genetic, factors had the greatest influence on the development of physical symptoms in victims. CONCLUSION Genetic vulnerability for physical health problems in early adolescence increases the risk of peer victimization. Whether victims suffer a further increase in physical symptoms depends on the presence of protective environmental factors.
A case of severe hyperaldosteronism caused by a de novo mutation affecting a critical salt bridge Kir3.4 residue.

CONTEXT Familial hyperaldosteronism type III (FH-III) is a rare and clinically heterogeneous condition, that can display mild as well as severe phenotypes. Point mutations in the KCNJ5 gene, affecting the ion selectivity of the inward rectifier K(+) channel 4 (Kir3.4), underlie the molecular basis of FH-III. OBJECTIVE The objective of the study was to investigate the effects of a de novo germline KCNJ5 mutation. PATIENTS AND METHODS We describe the case of a girl who came to medical attention at the age of 2 years because of polydipsia, polyuria, and failure to thrive. The patient, affected by hypertension and hypokalemia, was diagnosed with primary aldosteronism on the basis of extremely high aldosterone levels and suppressed plasma renin activity. Genomic DNA was isolated and KCNJ5 sequenced. Human adrenocortical cells were used as an in vitro model for the functional characterization of the mutant channel. RESULTS KCNJ5 sequencing in the index case and her parents revealed a de novo p.Glu145Gln germline mutation. The substitution resulted in Na(+)-dependent depolarization of adrenal cells and increased intracellular calcium concentration, which activated the transcription of NR4A2 and, in turn, CYP11B2. Pharmacological studies revealed that the mutant channel was insensitive to tertiapin-Q and calcium-channel blocker verapamil. CONCLUSIONS Herein we report the identification of a novel KCNJ5 germline mutation responsible for severe hyperaldosteronism that presented in infancy with symptoms of diabetes insipidus. The findings of this study further elucidate the etiology of FH-III and expand our knowledge of this rare condition.
The Feasibility of a Web-Based Surveillance System to Collect Health Risk Behavior Data from College Students

This study examined the feasibility of collecting health risk behavior data from undergraduate students using a Web-based survey. Undergraduates were randomly selected and assigned randomly to a mail survey group and a Web survey group. There were no statistically significant differences between the two groups for demographics, response rates, item completion, and item completion errors. Yet differences were found for response time and sensitive item completion. This is the first study to demonstrate the feasibility of collecting health risk behavior data from undergraduates using the Web. Undergraduates are just as likely to respond to a Web survey compared with a mail survey and more likely to answer socially threatening items using this method. Also, the Web format and protocol required less time to administer. Researchers and practitioners conducting health survey research with college students or other homogeneous populations who have access to e-mail and the Web should consider using a Web-based survey design as an alternative to a mail, self-administered survey. In such a population, a Web-based survey should not discourage participation, particularly if participants are interested in the questionnaire content.
[Does maternal obesity increase the risk of fetal abnormalities? Analysis of 20,248 newborn infants of the Mainz Birth Register for detecting congenital abnormalities].

AIM To investigate the risk of congenital malformations for newborn of obese women (BMI > or = 30) compared with women of average prepregnancy weight. METHODS We performed a prospective, population-based case-control study of 20,248 newborn born in the city of Mainz. A total of 1,451 infants (cases) with and 8,088 without congenital malformations (controls) were analysed. The relative risks of associations between obesity and malformations were calculated as odds ratios (OR) with 95% confidence intervals (CI). RESULTS The prevalence of malformations in children of obese mothers is 11.1% and thus approximately 4% higher than those of the total study population. There is a significant odds ratio for major malformations (OR 1.3; KI 1.0-1.7). Statistically significant associations were calculated for malformations of the internal urogenital system (OR 1.7; 1.1-2.8), the eyes (OR 5.0; 1.3-20.0) and for orofacial clefts (OR 1.7; 1.1-2.8). Among the specific malformations the highest associations occurred for encephalocele (OR 7.3; 1.1-50.6), common truncus arteriosus (OR 6.3; 1.6-24.8) and Potter sequence (OR 6.3; 1.6-24.8). Adjustment for confounding factors (e.g. maternal diabetes mellitus and age) did not change the odds ratios. CONCLUSIONS Our data demonstrate that newborn of obese mothers are at an increased risk for malformations. An adequate prenatal examination of these pregnancies should include ultrasound screening by specially trained ultrasonographers in tertiary units (DEGUM II/DEGUM III) and serum alpha-fetoprotein measurements. Public health campaigns for prevention are advised.
Prompted awareness and use of Eating Well with Canada's Food Guide: a population-based study.

BACKGROUND Little is known about the awareness of Canada's Food Guide (CFG). The present study aimed to report the general and specific awareness of CFG recommendations among adults in Alberta, Canada. METHODS For this cross-sectional study, respondents (aged >18 years) from randomly selected households completed a telephone survey. Questions pertaining to CFG, physical activity, and vegetable and fruit consumption were included. Logistic regression determined associations between demographic characteristics and awareness of CFG. RESULTS Thousand two hundred and ten Albertans (50% female, mean age 50.5 years) responded. Most [86.5%; 95% confidence interval (CI) = 84.6-88.4] indicated being generally aware of CFG when prompted and 82.5% were aware of specific CFG recommendations. There were no differences in age between those generally aware and unaware of CFG. Female sex [odds ratio (OR) = 3.6; 95%CI = 24-5.4], Caucasian ethnicity (OR = 3.7; 95% CI = 2.3-5.8), income ≥ Canadian $100 000 per annum (OR = 1.6; 95% CI = 1.1-2.3), reporting ≥5 vegetables and fruit per day (OR = 2.1; 95% CI = 1.4-3.2), exceeding recommended levels for physical activity (OR = 2.0; 95% CI = 1.3-2.9) and perception of current weight as healthy (OR = 1.8; 95% CI = 1.2-2.8) were associated with an awareness of CFG. CONCLUSIONS Sex, ethnicity and income were associated with general awareness of CFG. Future studies could explore the relationship between awareness and other health-related behaviours.
Oral findings of Down syndrome children in Chennai city, India.

PURPOSE To assess the common oral findings and anomalies of Down syndrome (DS) children in Chennai city, India. MATERIALS AND METHODS Among the 130 DS children examined, 102 children aged 15 years and below were included in the study. There were 57 male children and 45 female children in the total study sample. A specially prepared case record was used to record the following findings in each child: a brief family and personal history; anomalies of soft tissues, teeth, occlusion, and temporomandibular joint. Age wise and sex wise comparisons of the findings were done. RESULTS About 97 children (95%) had the habit of regular tooth brushing. Everted lower lip (66%), retained primary teeth (31%), and midface deficiency (76%) were the most commonly seen soft tissue, dental, and occlusion anomalies, respectively. CONCLUSIONS Midface deficiency was the most common orofacial anomaly seen in these children, followed by everted lower lip and retained primary teeth. Almost all the children had a regular tooth brushing habit. All the children examined were offered free dental treatment in our dental college.
Paralympic sport: an emerging area for research and consultancy in sports biomechanics

The Paralympic Games are the pinnacle of sport for many athletes with a disability. The overall purpose of this paper is to highlight the role that the field of sports biomechanics specifically (and sports science in general) may play in improving performance in various summer Paralympic sports through research and consultancy. To achieve this broad aim, this review provides some history and background on the Summer Paralympic Games, discusses the eligibility and classification rules, describes the potential for the constraints-led approach of dynamical systems theory to inform practice and research in this area, and reviews selected studies examining the biomechanics of the primary forms of Paralympic locomotion. Some recommendations on how sports biomechanics can help facilitate improvements in Paralympic athletic performance through applied research and consultancy are provided, along with commentary on what may be some of the most important issues addressing Paralympic sport.
Prognostic factors for intensive care unit admission, intensive care outcome, and post-intensive care survival in patients with de novo acute myeloid leukemia: a single center experience

Background Acute myeloid leukemia is a life-threatening disease associated with high mortality rates. A substantial number of patients require intensive care. This investigation analyzes risk factors predicting admission to the intensive care unit in patients with acute myeloid leukemia eligible for induction chemotherapy, the outcome of these patients, and prognostic factors predicting their survival. Design and Methods A total of 406 consecutive patients with de novo acute myeloid leukemia (15–89 years) were analyzed retrospectively. Markers recorded at the time of diagnosis included karyotype, fibrinogen, C-reactive protein, and Charlson comorbidity index. In patients requiring critical care, the value of the Simplified Acute Physiology Score II, the need for mechanical ventilation, and vasopressor support were recorded at the time of intensive care unit admission. The independent prognostic relevance of the parameters was tested by multivariate analysis. Results Sixty-two patients (15.3%) required intensive care, primarily due to respiratory failure (50.0%) or life-threatening bleeding (22.6%). Independent risk factors predicting intensive care unit admission were lower fibrinogen concentration, the presence of an infection, and comorbidity. The survival rate was 45%, with the Simplified Acute Physiology Score II being the only independent prognostic parameter (P<0.05). Survival was inferior in intensive care patients compared to patients not admitted to an intensive care unit. However, no difference between intensive care and non-intensive care patients was found concerning continuous complete remission at 6 years or survival at 6 years in patients who survived the first 30 days after diagnosis (non-intensive care patients: 28%; intensive care patients: 20%, P>0.05). Conclusions Ongoing infections, low fibrinogen and comorbidity are predictive for intensive care unit admission in acute myeloid leukemia. Although admission was a risk factor for survival, continuous complete remission and survival of patients alive at day 30 were similar in patients who were admitted or not admitted to an intensive care unit.
The effects of dietary intake and dietary concentration of organic and inorganic copper supplements on egg and plasma cholesterol levels.

Summary To evaluate the effect of source and dosage of supplemental copper on cholesterol contents of the egg, blood plasma, liver and excreta, and to determine the levels of copper residue in the liver, egg yolk, whole egg and excreta of laying hens. One hundred and eight 35-week old Black Harco laying hens were randomly assigned to 6 dietary treatments in a 2 X 3 factorial arrangement of treatments. The copper sources were copper proteinate (CuP) and copper sulphate pentahydrate (CuSO4.5H2O) fed at three dosages (0, 125 and 250 mgCu kg -1 ) respectively for a 10 weeks periods. Whole egg and egg yolk cholesterol concentrations of CuP supplemented diets were significantly (P 0.05) in Cu residues values of the excreta, whole egg and egg yolk in both Cu sources. Cu residue levels in the liver, whole egg, egg yolk and the excreta increased in a Cu dosage dependent manner. Cu residue levels were significantly influenced by the interaction of Cu source and dosage.
Lymphocyte P‐glycoprotein expression and activity before and after rifampicin in man

Abstract— It has recently been shown that P‐glycoprotein (P‐gp) is inducible by rifampicin in the human gut as shown in intestinal biopsies. The present study was performed in order to test the hypothesis that human peripheral lymphocytes can be used to assess such an inducibility. We also assessed inter‐ and intra‐individual variability of P‐gp expression and activity in peripheral lymphocytes. Blood samples from 13 healthy volunteers were collected 1.7, 14 and 19 days after inclusion. Rifampicin treatment (600 mg/day) was administered from clay 15 to day 18. Lymphocyte P‐gp expression was measured at the messenger RNA level by semi‐quantitative RT‐PCR and at the protein level by immunostaining flow cytometry. P‐gp activity was determined by flow cytometry with rhodamine 123 efflux. Cytochrome P4503A4 (CYP3A4) inducibility was measured by comparing the urinary metabolic ratio of 6β‐hydroxycortisol/cortisol on day 14 and 19. Lymphocyte P‐gp expression and activity was not induced by rifampicin, while it increased CYP3A4 activity from 5.0 ± 4.0 to 22.9 ± 16.6 (P < 0.001). There was a 3–4‐fold inter‐individual variability and a 3–44% intra‐individual variability of lymphocyte P‐gp expression and activity. Peripheral lymphocytes are not an appropriate material to assess P‐gp inducibility in humans. P‐gp shows significant inter‐ and intra‐individual variability in human lymphocytes.
Prenatal and Postnatal Contents of Amino Acid Neurotransmitters in Mouse Parietal Cortex

This study documents the variation in the amino acid neurotransmitter contents during mouse parietal cortex development, from embryonic day 13 (E13) until young adulthood, between postnatal day 21 (P21) and P30. Taurine, an inhibitory neurotransmitter and neuromodulator, is the most abundant neurotransmitter in the developing neocortex, whereas, at the adult stage, glutamate is the more prominent neurotransmitter playing an excitatory role, and GABA is the major inhibitory neurotransmitter. During the proliferative stage of neurogenesis in the mouse cerebral cortex, between E13 and E17, relatively high levels of glutamate, aspartate, taurine and glycine were detected, consistent with a possible trophic influence of these neurotransmitters during cortical development prior to synaptogenesis. Between E17 and E19, a significant decline in the contents of these neurotransmitters was observed, consistent with earlier reports of cell death in the ventricular and subventricular zones during this stage of development. During the perinatal period, a progressive increment in glutamate level was seen between E21 and P5, and then the values remained constant until the second postnatal week. Glutamate also decreased by about 25% between P11 and P15, on the other hand, aspartate diminished by about 20% between P7 and P9. These results were consistent with previous reports of histogenetic cell death during the first 2 postnatal weeks in mouse neocortex. GABA increased from the embryonic period until young adulthood, in contrast, the glycine content decreased; thus, in the adult parietal cortex, the GABA content was about 2.6-fold higher than that of glycine. During the first postnatal week, the concentrations of glutamate and GABA showed significant increments between P0 and P5, while those of aspartate and glycine remained constant. During this period, amino acids are predominantly excitatory and the cerebral cortex is vulnerable to epileptiform activity; the significant increment in taurine content between P0 and P3 suggests a neuroprotective action of taurine against excitotoxicity. At P15, coinciding with the period of maximum cortical synaptogenesis, significant increments in GABA and glycine contents were observed which could be related to the maturation of inhibitory synaptic transmission. At the young adult stage, there was a rise in the levels of both excitatory neurotransmitters, glutamate and aspartate, and a significant reduction in the contents of all three inhibitory neurotransmitters, GABA, glycine and taurine.