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Institute of Physiology ASCR, v.v.i.
Videnska 1083
CZ-14220 Prague 4
Czech Republic

Phone:     +420 24106 1111
                  +420 24447 2270
Fax:          +420 24106 2488

E-mail: fgubiomed.cas.cz

Achievements



Review articles in prestige journal Nature Genetics

Identification of osteoglycin (Ogn) as a genetic determinant predisposing to left ventricular hypertrophy in rats, mice, and humans

Left ventricular mass (LVM) and cardiac gene expression are complex phenotypes that are regulated by factors both intrinsic and extrinsic to the heart. To dissect experimentally the major determinants of LVM indexed to body mass (LVMI), we used a panel of recombinant inbred (RI) rat strains in a novel approach that integrates genetic linkage and gene expression studies with quantitative trait transcript (QTT) analysis. Using comprehensive telemetric haemodynamic data, we controlled for the key extrinsic factors expected to influence LVMI. We generated genome-wide expression profiles across the RI panel and show that cardiac gene expression and LVMI are controlled predominantly by genetic factors as opposed to extra-cardiac stimuli. Genetic linkage analysis was used to map the cis and trans determinants of gene expression for thousands of genes across the rat genome. Genomewide QTT analysis for LVMI revealed two significant QTT clusters of cis regulated genes, one of which colocalised to a previously mapped LVMI QTL. We refined this QTL and identified functional sequence variants in Ogn, the major candidate at this locus. In translational studies, out of a possible 22,000 transcripts OGN was the most highly correlated gene with human LVMI. As observed in the rat, neither LMVI nor OGN expression correlated with haemodynamic measures in humans. Finally, we tested the functional effects of Ogn and showed that LVMI was significantly attenuated the Ogn knockout mouse. This is the first study to integrate eQTL, and QTT analyses and demonstrates the power of systems approaches for the study of complex traits.
E. Petretto, R. Sarwar, I. Grieve, H. Lu, M. K. Kumaran, P. J. Muckett, J. Mangion, B. Schroen, M. Benson, P. P. Punjabi, S. K. Prasad, D. J.P ennell, C. Kiesewetter, E. S. Tasheva, L. M. Corpuz, M. D. Webb, G. W. Conrad, T. W. Kurtz, V. Kren, J. Fischer, N. Hubner, Y. M. Pinto, M. Pravenec, T. J. Aitman, S. A. Cook: Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass, Nature Genetics 40:546-552, 2008, Nature Genetics 40:538-545, 2008, IF=25.556
 


Author: pravenecbiomed.cas.cz
 




Journal article: Journal of Hypertension
Role of nifedipine-sensitive sympathetic vasoconstriction in maintenance of high blood pressure in spontaneously hypertensive rats: effect of Gi-protein inactivation by pertussis toxin

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Journal article: Neurochemistry International
The interactions of the C-terminal region of the TRPC6 channel with calmodulin

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Journal article: Journal of Comparative Neurology
Expression and light sensitivity of clock genes Per1 and Per2 and immediate-early gene c-fos within the retina of early postnatal Wistar rats.

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Journal article: Epilepsia
Metabotropic glutamate receptors as a target for anticonvulsant and anxiolytic action in immature rats.

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) Journal article: Analytical and Bioanalytical Chemistry
Determination of insoluble avian eggshell matrix proteins.

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Journal article: Journal of Biological Rhythms
Exposure of Pregnant Rats to Restricted Feeding Schedule Synchronizes the SCN Clocks of Their Fetuses under Constant Light but Not under a Light-Dark Regime

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Journal article: Journal of Neuroinflammation
Tumor necrosis factor α sensitizes spinal cord TRPV1 receptors to the endogenous agonist N-oleoyldopamine

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Journal article: Biochimica Et Biophysica Acta-Molecular Cell Research
Essential role for the putative S6 inner pore region in the activation gating of the human TRPA1 channel.

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Journal article: Journal of Structural Biology
A new epigenetic marker: The replication-coupled, cell cycle-dependent, dual modification of the histone H4 tail.

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Journal article: International Journal of Biochemistry and Cell Biology
Mitochondrial reticulum network dynamics in relation to oxidative stress, redox regulation, and hypoxia.

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Journal article: American Journal of Physiology-Heart and Circulatory Physiology
Pathways to embryonic heart failure.

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Journal article: Neuroscience
Temperature dependence of N-methyl-d-aspartate receptor channels and N-methyl-d-aspartate receptor excitatory postsynaptic currents.

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Journal article: Epilepsia
Vigabatrin but not valproate prevents development of age-specific flexion seizures induced by N-methyl-d-aspartate (NMDA) in immature rats.

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Journal article: Neuroscience
Modulation of AMPA excitatory postsynaptic currents in the spinal cord dorsal horn neurons by insulin.

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Journal article: Endocrinology
Chronic Intermittent Hypoxia Induces 11Beta-Hydroxysteroid Dehydrogenase in Rat Heart.

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Journal article: Epilepsia
Antagonists of group I metabotropic glutamate receptors and cortical afterdischarges in immature rats.

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Journal article: International Journal of Biochemistry and Cell Biology
Pro-oxidant mitochondrial matrix-targeted ubiquinone MitoQ10 acts as anti-oxidant at retarded electron transport or proton pumping within Complex I.

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Journal article: Chronobiology International
Temporal Gradient in the Clock Gene and Cell-Cycle Checkpoint Kinase Wee1 Expression along the Gut.

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Journal article: Journal of Neurophysiology
The Role of The TRPV1 Endogenous Agonist N-Oleoyldopamine in Modulation of Nociceptive Signaling at the Spinal Cord Level.

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Journal article: Proceedings of the National Academy of Sciences of the USA
Spatial decisions and cognitive strategies of monkeys and humans based on abstract spatial stimuli in rotation test.

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Review articles in prestige journal Nature Genetics
Identification of distribution and functional impact of DNA copy number variation in the rat

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Review articles in prestige journal Nature Genetics
Identification of single nucleotide polymorphisms and haplotype mapping in the rat

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Review articles in prestige journal Nature Genetics
Identification of renal Cd36 as a genetic determinant of blood pressure and risk for hypertension

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Journal article: Nature Genetics
Molecular-genetic basis of severe inherited mitochondrial disease – neonatal encephalo-cardiomyopathy.

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Article: Obesity
Chemical derivatives of docosahexaenoic acid (DHA) in the prevention and reversal of obesity in mice fed a high-fat diet

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Article: Diabetologia
n-3 fatty acids and rosiglitazone exerts additive effects on muscle glycogen synthesis in mice fed a high-fat diet

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Journal article: Proceedings of National Academy of Sciences of the USA
Risperidone and ritanserin but not haloperidol block effect of dizocilpine on the active allothetic place avoidance task

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Journal article: FASEB
In vivo content of mitochondrial ATP synthase is controlled by expression of the gene encoding hydrophobic subunit c.

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Review article: Oncogene
Current informations about the FOXO subgroup of forkhead transcription factors and mechanism of regulation

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Journal article: PLoS Computational Biology
Efficient coding principle confirmed for the sense of smell

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Journal article: Neurobiology of Aging
Evidence of impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mouse model of Alzheimer´s disease.

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Journal article: American Journal of Physiology Endocrinology and Metabolism
Induction of muscle thermogenesis by high-fat diet in mice: association with obesity-resistance

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Journal article: Journal of Pineal Research
The role of proline residues in the structure and function of human MT2 receptor.

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