20 research outputs found
A novel Bayesian approach to quantify clinical variables and to determine their spectroscopic counterparts in 1H NMR metabonomic data
<p>Abstract</p> <p>Background</p> <p>A key challenge in metabonomics is to uncover quantitative associations between multidimensional spectroscopic data and biochemical measures used for disease risk assessment and diagnostics. Here we focus on clinically relevant estimation of lipoprotein lipids by <sup>1</sup>H NMR spectroscopy of serum.</p> <p>Results</p> <p>A Bayesian methodology, with a biochemical motivation, is presented for a real <sup>1</sup>H NMR metabonomics data set of 75 serum samples. Lipoprotein lipid concentrations were independently obtained for these samples via ultracentrifugation and specific biochemical assays. The Bayesian models were constructed by Markov chain Monte Carlo (MCMC) and they showed remarkably good quantitative performance, the predictive R-values being 0.985 for the very low density lipoprotein triglycerides (VLDL-TG), 0.787 for the intermediate, 0.943 for the low, and 0.933 for the high density lipoprotein cholesterol (IDL-C, LDL-C and HDL-C, respectively). The modelling produced a kernel-based reformulation of the data, the parameters of which coincided with the well-known biochemical characteristics of the <sup>1</sup>H NMR spectra; particularly for VLDL-TG and HDL-C the Bayesian methodology was able to clearly identify the most characteristic resonances within the heavily overlapping information in the spectra. For IDL-C and LDL-C the resulting model kernels were more complex than those for VLDL-TG and HDL-C, probably reflecting the severe overlap of the IDL and LDL resonances in the <sup>1</sup>H NMR spectra.</p> <p>Conclusion</p> <p>The systematic use of Bayesian MCMC analysis is computationally demanding. Nevertheless, the combination of high-quality quantification and the biochemical rationale of the resulting models is expected to be useful in the field of metabonomics.</p
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
The Usefulness of Implicit Measures for the Screening, Assessment and Treatment of Problematic Alcohol Use in Individuals with Mild to Borderline Intellectual Disability
Systems biology approach on the elucidation of the response of Medicago truncatula plants towards salinity stress
Salt stress is one of the most important factors limiting plant productivity, with salinity affecting plant physiology and metabolism at multiple levels. The aim of this study was to explore, elucidate and decipher the role of antioxidant and salt tolerance mechanisms in the model legume Medicago truncatula. For this reason, three ecotypes of M. truncatula showing differential response to salinity were used: Jemalong A17 (moderate response), TN6.18 (sensitive to salinity) and TN1.11 (tolerant to salinity). Cellular damage levels were monitored in roots and leaves after 48 h of salt stress application with 200 mM NaCl by measuring lipid peroxidation levels, as well as nitric oxide and hydrogen peroxide content, further supported by leaf stomatal conductance and chlorophyll fluorescence readings. The salt-tolerant genotype TN1.11 displayed the lowest cellular damage and ROS/RNS content, while the salt-sensitive TN6.18 was affected the greatest. Transcriptional profiling using microarray analysis of salt-stressed M. truncatula displayed differential gene expression that was both genotype and tissue-dependent. A large number of regulatory genes (associated or not previously linked with salinity stress) from a variety of biochemical pathways showed a significant induction/suppression pattern. Furthermore, metabolite profiling of M. truncatula plants was employed to analyse the effect of salt stress in the accumulation of key metabolites and their interrelationships, leading to exclusive insights into the plants' metabolic networks which however appear to be genotype- and not tissue-dependent. This global approach (with the addition of currently performed proteomics analysis) will hopefully contribute in gaining new insights into the cellular response to salt stress in M. truncatula plants
A Heparin Purification Process Removes Spiked Transmissible Spongiform Encephalopathy Agent
High-frequency forecasting for grocery point-of-sales: intervention in practice and theoretical implications for operational design
Molecular insight into invasive group A streptococcal disease
Streptococcus pyogenes is also known as group A Streptococcus (GAS) and is an important human pathogen that causes considerable morbidity and mortality worldwide. The GAS serotype M1T1 clone is the most frequently isolated serotype from life-threatening invasive (at a sterile site) infections, such as streptococcal toxic shock-like syndrome and necrotizing fasciitis. Here, we describe the virulence factors and newly discovered molecular events that mediate the in vivo changes from non-invasive GAS serotype M1T1 to the invasive phenotype, and review the invasive-disease trigger for non-M1 GAS. Understanding the molecular basis and mechanism of initiation for streptococcal invasive disease may expedite the discovery of novel therapeutic targets for the treatment and control of severe invasive GAS diseases