Evidence of recent interkingdom horizontal gene transfer between bacteria and Candida parapsilosis

<p>Abstract</p> <p>Background</p> <p>To date very few incidences of interdomain gene transfer into fungi have been identified. Here, we used the emerging genome sequences of <it>Candida albicans </it>WO-1, <it>Candida tropicalis, Candida parapsilosis, Clavispora lusitaniae, Pichia guilliermondii</it>, and <it>Lodderomyces elongisporus </it>to identify recent interdomain HGT events. We refer to these as CTG species because they translate the CTG codon as serine rather than leucine, and share a recent common ancestor.</p> <p>Results</p> <p>Phylogenetic and syntenic information infer that two <it>C. parapsilosis </it>genes originate from bacterial sources. One encodes a putative proline racemase (PR). Phylogenetic analysis also infers that there were independent transfers of bacterial PR enzymes into members of the Pezizomycotina, and protists. The second HGT gene in <it>C. parapsilosis </it>belongs to the phenazine F (PhzF) superfamily. Most CTG species also contain a fungal PhzF homolog. Our phylogeny suggests that the CTG homolog originated from an ancient HGT event, from a member of the proteobacteria. An analysis of synteny suggests that <it>C. parapsilosis </it>has lost the endogenous fungal form of PhzF, and subsequently reacquired it from a proteobacterial source. There is evidence that <it>Schizosaccharomyces pombe </it>and Basidiomycotina also obtained a PhzF homolog through HGT.</p> <p>Conclusion</p> <p>Our search revealed two instances of well-supported HGT from bacteria into the CTG clade, both specific to <it>C. parapsilosis</it>. Therefore, while recent interkingdom gene transfer has taken place in the CTG lineage, its occurrence is rare. However, our analysis will not detect ancient gene transfers, and we may have underestimated the global extent of HGT into CTG species.</p

Organ-distribution of the Metabolite 2-Aminothiazoline-4-Carboxylic Acid in a Rat Model following Cyanide Exposure

The reaction of cyanide (CN−) with cystine to produce 2-aminothiazoline-4-carboxylic acid (ATCA) is one of the independent detoxification pathways of cyanide in biological systems. In this report, in vivo production of ATCA and its distributions in plasma and organs were studied after a subcutaneous sublethal dose of 4 mg/kg body weight potassium cyanide (KCN) administration to rats. At this sublethal dose of KCN, ATCA concentration was not significantly increased in the plasma samples, however, it was found significantly increased in liver samples. These results suggested that ATCA might not be a good diagnostic biomarker in plasma for sublethal cyanide exposure; however, liver could serve as the right organ for the detection of ATCA in post-mortem examinations involving cyanide exposure in military, firefighting, industrial and forensic settings

Spectrophotometric Analysis of the Cyanide Metabolite 2-Aminothiazoline-4-Carboxylic Acid (ATCA)

Methods of directly evaluating cyanide levels are limited by the volatility of cyanide and by the difficulty of establishing steady-state cyanide levels with time. We investigated the measurement of a stable, toxic metabolite, 2-aminothiazoline-4-carboxylic acid (ATCA), in an attempt to circumvent the challenge of directly determining cyanide concentrations in aqueous media. This study was focused on the spectrophotometric ATCA determination in the presence of cyanide, thiocyanate (SCN−), cysteine, rhodanese, thiosulfate, and other sulfur donors. The method involves a thiazolidine ring opening in the presence of p-(hydroxy-mercuri)-benzoate, followed by the reaction with diphenylthiocarbazone (dithizone). The product is spectrophotometrically analyzed at 625 nm in carbon tetrachloride. The calibration curve was linear with a regression line of Y = 0.0022x (R2 = 0.9971). Interference of cyanide antidotes with the method was determined. Cyanide, thiosulfate, butanethiosulfonate (BTS), and rhodanese did not appreciably interfere with the analysis, but SCN− and cysteine significantly shifted the standard curve. This sensitive spectrophotometric method has shown promise as a substitute for the measurement of the less stable cyanide

Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix

The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High VEGF expression was associated with a poor prognosis. A univariate log rank analysis found a significant relationship with overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not local control (P = 0.23). There was no correlation between VEGF expression and disease stage, tumour differentiation, patient age, or tumour radiosensitivity (SF2). In a Cox multivariate analysis of survival VEGF expression was the most significant independent prognostic factor (P = 0.001). After allowing for VEGF only SF2 was a significant prognostic factor (P = 0.003). In conclusion, immunohistochemical analysis of VEGF expression is a highly significant and independent prognostic indicator of overall and metastasis-free survival for patients treated with radiotherapy for advanced carcinoma of the cervix. It is also a rapid and easy method that could be used in the clinical setting, to identify patients at high risk of failure with conventional radiotherapy who may benefit from novel approaches or chemoradiotherapy. © 2000 Cancer Research Campaig

The role of the General Practitioner in weight management in primary care – a cross sectional study in General Practice

BACKGROUND: Obesity has become a global pandemic, considered the sixth leading cause of mortality by the WHO. As gatekeepers to the health system, General Practitioners are placed in an ideal position to manage obesity. Yet, very few consultations address weight management. This study aims to explore reasons why patients attending General Practice appointments are not engaging with their General Practitioner (GP) for weight management and their perception of the role of the GP in managing their weight. METHODS: In February 2006, 367 participants aged between 17 and 64 were recruited from three General Practices in Melbourne to complete a waiting room self - administered questionnaire. Questions included basic demographics, the role of the GP in weight management, the likelihood of bringing up weight management with their GP and reasons why they would not, and their nominated ideal person to consult for weight management. Physical measurements to determine weight status were then completed. The statistical methods included means and standard deviations to summarise continuous variables such as weight and height. Sub groups of weight and questionnaire answers were analysed using the chi2 test of significant differences taking p as < 0.05. RESULTS: The population sample had similar obesity co-morbidity rates to the National Heart Foundation data. 74% of patients were not likely to bring up weight management when they visit their GP. Negative reasons were time limitation on both the patient's and doctor's part and the doctor lacking experience. The GP was the least likely person to tell a patient to lose weight after partner, family and friends. Of the 14% that had been told by their GP to lose weight, 90% had cardiovascular obesity related co-morbidities. GPs (15%) were 4th in the list of ideal persons to manage weight after personal trainer CONCLUSION: Patients do not have confidence in their GPs for weight management, preferring other health professionals who may lack evidence based training. Concurrently, GPs target only those with obesity related co-morbidities. Further studies evaluating GPs' opinions about weight management, effective strategies that can be implemented in primary care and the co-ordination of the team approach need to be done

Simultaneous Determination of 3-mercaptopyruvate and Cobinamide in Plasma by Liquid Chromatography–tandem Mass Spectrometry

The current suite of Food and Drug Administration (FDA) approved antidotes (i.e., sodium nitrite, sodium thiosulfate, and hydroxocobalamin) are effective for treating cyanide poisoning, but individually, each antidote has major limitations (e.g., large effective dosage or delayed onset of action). To mitigate these limitations, next-generation cyanide antidotes are being investigated, including 3-mercaptopyruvate (3-MP) and cobinamide (Cbi). Analytical methods capable of detecting these therapeutics individually and simultaneously (for combination therapy) are essential for the development of 3-MP and Cbi as potential cyanide antidotes. Therefore, a liquid chromatography–tandem mass-spectrometry method for the simultaneous analysis of 3-MP and Cbi was developed. Sample preparation of 3-MP consisted of spiking plasma with an internal standard (13C3-3-MP), precipitation of plasma proteins, and derivatizing 3-MP with monobromobimane to produce 3-mercaptopyruvate-bimane. Preparation of Cbi involved denaturing plasma proteins with simultaneous addition of excess cyanide to convert each Cbi species to dicyanocobinamide (Cbi(CN)2). The limits of detection for 3-MP and Cbi were 0.5 μM and 0.2 μM, respectively. The linear ranges were 2–500 μM for 3-MP and 0.5–50 μM for Cbi. The accuracy and precision for 3-MP were 100 ± 9% and \u3c8.3% relative standard deviation (RSD), respectively. For Cbi(CN)2, the accuracy was 100 ± 13% and the precision was \u3c9.5% RSD. The method presented here was used to determine 3-MP and Cbi from treated animals and may ultimately facilitate FDA approval of these antidotes for treatment of cyanide poisoning

Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background: Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15. Methods and Findings: Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL-and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15. Conclusion: Changes in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight

Cyanide Toxicokinetics: The Behavior of Cyanide, Thiocyanate and 2-Amino-2-Thiazoline-4-Carboxylic Acid in Multiple Animal Models

Cyanide causes toxic effects by inhibiting cytochrome c oxidase, resulting in cellular hypoxia and cytotoxic anoxia, and can eventually lead to death. Cyanide exposure can be verified by direct analysis of cyanide concentrations or analyzing its metabolites, including thiocyanate (SCN−) and 2-amino-2-thiazoline-4-carboxylic acid (ATCA) in blood. To determine the behavior of these markers following cyanide exposure, a toxicokinetics study was performed in three animal models: (i) rats (250–300 g), (ii) rabbits (3.5–4.2 kg) and (iii) swine (47–54 kg). Cyanide reached a maximum in blood and declined rapidly in each animal model as it was absorbed, distributed, metabolized and eliminated. Thiocyanate concentrations rose more slowly as cyanide was enzymatically converted to SCN−. Concentrations of ATCA did not rise significantly above the baseline in the rat model, but rose quickly in rabbits (up to a 40-fold increase) and swine (up to a 3-fold increase) and then fell rapidly, generally following the relative behavior of cyanide. Rats were administered cyanide subcutaneously and the apparent half-life (t1/2) was determined to be 1,510 min. Rabbits were administered cyanide intravenously and the t1/2 was determined to be 177 min. Swine were administered cyanide intravenously and the t1/2 was determined to be 26.9 min. The SCN−t1/2 in rats was 3,010 min, but was not calculated in rabbits and swine because SCN−concentrations did not reach a maximum. The t1/2 of ATCA was 40.7 and 13.9 min in rabbits and swine, respectively, while it could not be determined in rats with confidence. The current study suggests that cyanide exposure may be verified shortly after exposure by determining significantly elevated cyanide and SCN− in each animal model and ATCA may be used when the ATCA detoxification pathway is significant

Inferring Core-Collapse Supernova Physics with Gravitational Waves

Stellar collapse and the subsequent development of a core-collapse supernova explosion emit bursts of gravitational waves (GWs) that might be detected by the advanced generation of laser interferometer gravitational-wave observatories such as Advanced LIGO, Advanced Virgo, and LCGT. GW bursts from core-collapse supernovae encode information on the intricate multi-dimensional dynamics at work at the core of a dying massive star and may provide direct evidence for the yet uncertain mechanism driving supernovae in massive stars. Recent multi-dimensional simulations of core-collapse supernovae exploding via the neutrino, magnetorotational, and acoustic explosion mechanisms have predicted GW signals which have distinct structure in both the time and frequency domains. Motivated by this, we describe a promising method for determining the most likely explosion mechanism underlying a hypothetical GW signal, based on Principal Component Analysis and Bayesian model selection. Using simulated Advanced LIGO noise and assuming a single detector and linear waveform polarization for simplicity, we demonstrate that our method can distinguish magnetorotational explosions throughout the Milky Way (D <~ 10kpc) and explosions driven by the neutrino and acoustic mechanisms to D <~ 2kpc. Furthermore, we show that we can differentiate between models for rotating accretion-induced collapse of massive white dwarfs and models of rotating iron core collapse with high reliability out to several kpc.Comment: 22 pages, 9 figure