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Izhevskaya V.L.,Research Center for Medical Genetics
Vestnik Rossiiskoi Akademii Meditsinskikh Nauk | Year: 2011

Selected ethical problems arising in the studies of mutagenic effects and genetic testing at the workplace (genetic monitoring and genetic screening) are discussed.

Birerdinc A.,George Mason University | Jarrar M.,George Mason University | Jarrar M.,United Arab Emirates University | Stotish T.,George Mason University | And 3 more authors.
Progress in Lipid Research | Year: 2013

Brown adipocytes constitute a metabolically active tissue responsible for non-shivering thermogenesis and the depletion of excess calories. Differentiation of brown fat adipocytes de novo or stimulation of pre-existing brown adipocytes within white adipose depots could provide a novel method for reducing the obesity and alleviating the consequences of type II diabetes worldwide. In this review, we addressed several molecular mechanisms involved in the control of brown fat activity, namely, the β3-adrenergic stimulation of thermogenesis during exposure to cold or by catecholamines; the augmentation of thyroid function; the modulation of peroxisome proliferator-activated receptor gamma (PPARγ), transcription factors of the C/EBP family, and the PPARγ co-activator PRDM16; the COX-2-driven expression of UCP1; the stimulation of the vanilloid subfamily receptor TRPV1 by capsaicin and monoacylglycerols; the effects of BMP7 or its analogs; the cannabinoid receptor antagonists and melanogenesis modulating agents. Manipulating one or more of these pathways may provide a solution to the problem of harnessing brown fat's thermogenic potential. However, a better understanding of their interplay and other homeostatic mechanisms is required for the development of novel therapies for millions of obese and/or diabetic individuals.© 2012 Elsevier Ltd. All rights reserved.

Sikaroodi M.,George Mason University | Galachiantz Y.,Biomedical Center | Baranova A.,George Mason University | Baranova A.,Research Center for Medical Genetics
Current Molecular Medicine | Year: 2010

Tumor markers are the molecules that indicate the presence or prognosis of malignancy. Most often, tumor markers are produced by the cancer tissue itself. Many of them could be secreted into the body fluids in small quantities. Thus, tumor markers could be useful for early diagnostics of primary tumors and relapsed disease, as well as for determining tumor prognosis and predicting likely response of the tumor to therapy. Tumor markers are part of the clinical routine. Nevertheless, lack of sensitivity and specificity precludes routine usage of single tumor markers in population-based screening. Shortcomings of single tumor markers could be solved by parallel evaluation of multiple tumor markers that can perform with required certainty. Genome and proteome-wide approaches currently lead to identification and initial characterization of hundreds new tumor marker candidates. Most prominent of such methods are serological analyses of recombinant cDNA expression libraries (SEREX), 2-dimensional polyacrylamide gel electrophoresis, mass spectrometry, as well as protein and DNA microarrays. Last but not the least is a computational approach allowing high-throughput detection of tumor marker candidate genes in publicly available datasets. Listed approaches are critically discussed in this review as well as the most crucial tumor-related findings. Finally, a perspective on the future of tumor markers in the tailored medicine is given. © 2010 Bentham Science Publishers Ltd.

Mayburd A.,George Mason University | Baranova A.,George Mason University | Baranova A.,Research Center for Medical Genetics
BMC Systems Biology | Year: 2013

Background: High-throughput profiling of human tissues typically yield as results the gene lists comprised of a mix of relevant molecular entities with multiple false positives that obstruct the translation of such results into mechanistic hypotheses. From general probabilistic considerations, gene lists distilled for the mechanistically relevant components can be far more useful for subsequent experimental design or data interpretation.Results: The input candidate gene lists were processed into different tiers of evidence consistency established by enrichment analysis across subsets of the same experiments and across different experiments and platforms. The cut-offs were established empirically through ontological and semantic enrichment; resultant shortened gene list was re-expanded by Ingenuity Pathway Assistant tool. The resulting sub-networks provided the basis for generating mechanistic hypotheses that were partially validated by literature search. This approach differs from previous consistency-based studies in that the cut-off on the Receiver Operating Characteristic of the true-false separation process is optimized by flexible selection of the consistency building procedure. The gene list distilled by this analytic technique and its network representation were termed Compact Disease Model (CDM). Here we present the CDM signature for the study of early-stage Alzheimer's disease. The integrated analysis of this gene signature allowed us to identify the protein traffic vesicles as prominent players in the pathogenesis of Alzheimer's. Considering the distances and complexity of protein trafficking in neurons, it is plausible that spontaneous protein misfolding along with a shortage of growth stimulation result in neurodegeneration. Several potentially overlapping scenarios of early-stage Alzheimer pathogenesis have been discussed, with an emphasis on the protective effects of AT-1 mediated antihypertensive response on cytoskeleton remodeling, along with neuronal activation of oncogenes, luteinizing hormone signaling and insulin-related growth regulation, forming a pleiotropic model of its early stages. Alignment with emerging literature confirmed many predictions derived from early-stage Alzheimer's disease' CDM.Conclusions: A flexible approach for high-throughput data analysis, the Compact Disease Model generation, allows extraction of meaningful, mechanism-centered gene sets compatible with instant translation of the results into testable hypotheses. © 2013 Mayburd and Baranova; licensee BioMed Central Ltd.

Smyth A.R.,University of Nottingham | Bell S.C.,The Prince Charles Hospital | Bell S.C.,Queensland Childrens Medical Research Institute | Bryon M.,Cystic Fibrosis Unit | And 13 more authors.
Journal of Cystic Fibrosis | Year: 2014

Specialised CF care has led to a dramatic improvement in survival in CF: in the last four decades, well above what was seen in the general population over the same period. With the implementation of newborn screening in many European countries, centres are increasingly caring for a cohort of patients who have minimal lung disease at diagnosis and therefore have the potential to enjoy an excellent quality of life and an even greater life expectancy than was seen previously. To allow high quality care to be delivered throughout Europe, a landmark document was published in 2005 that sets standards of care. Our current document builds on this work, setting standards for best practice in key aspects of CF care. The objective of our document is to give a broad overview of the standards expected for screening, diagnosis, pre-emptive treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support. For comprehensive details of clinical care of CF, references to the most up to date European Consensus Statements, Guidelines or Position Papers are provided in Table 1. We hope that this best practice document will be useful to clinical teams both in countries where CF care is developing and those with established CF centres. © 2014 European Cystic Fibrosis Society.

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