MicroRNAs (miRNAs) form a large class of non-coding RNAs that function in repression of gene expression in eukaryotes. By recognizing short stretches of nucleotides within the untranslated regions of mRNAs, miRNAs recruit partner proteins to individual transcripts, leading to mRNA cleavage or hindering of translation. Bioinformatic predictions and a wealth of data from wet laboratory studies indicate that miRNAs control expression of a large proportion of protein-coding genes, implying involvement of miRNAs in regulation of most biologic processes. In this review we discuss the biology of miRNAs and present examples of how manipulation of miRNA expression or activity can be exploited to attain the desired phenotypic traits in cell engineering as well as achieve therapeutic outcomes in treatment of a diverse set of diseases.
F.21 Development of new health/diagnostic methods/procedures
COBISS.SI-ID: 3197041Ergoline derivative 9,10-Didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergoline bimaleinate (LEK-8829), possesses dopamine (DA) D1 agonistic and D2 antagonistic properties in the nigrostriatal and mesocorticolimbic DAergic pathways. These unique dual effects have suggested that LEK-8829 could effectively restore previously imbalanced functional linkage between D1 and D2receptors under schizophrenic conditions in which, LEK-8829 could improve both the negative and positive symptoms of schizophrenia. As dopamine D1 receptor agonist, LEK-8829 may also be beneficial in relieving the motor symptoms of parkinsonism, alone, or when co-administered with antiparkinsonic dopamine D2 agonists, such as ergoline derivative bromocriptine. Moreover, antiparkinsonic potential of LEK-8829 may be particularly useful when the treatment of parkinsonism with D2 agonist drugs is complicated by psychosis. Antiparkinsonic properties of LEK-8829 also suggest a lower propensity of the drug for the induction of extrapyramidal syndrome in the treatment of schizophrenia. Furthermore, by blocking dopamine D2 receptors, LEK-8829 could block the incentive for drug-seeking and drug-craving while by stimulating dopamine D1 receptors it could mediate drug reward and gratification. This implies that LEK-8829 could also attenuate the relapse of psychostimulant drug-addiction, while not being addictive by itself. We conclude that agents with LEK-8829-like dual actions toward dopamine receptors, may represent a newand potent drug class for the treatment parkinsonism, schizophrenia and drug-addiction.
F.21 Development of new health/diagnostic methods/procedures
COBISS.SI-ID: 27799513This work is aimed at correlating pre-mortem [18F]FDDNP positron emission tomography (PET) scan results in a patient with dementia with Lewy bodies (DLB), with cortical neuropathology distribution determined postmortem in three physical dimensions in whole brain coronal sections. Analysis of total amyloid- (A) distribution in frontal cortex and posterior cingulate gyrus confirmed its statistically significant correlation with cortical [18F]FDDNP PET binding values (distribution volume ratios, DVR) (p ( 0.001, R = 0.97, R2 = 0.94). Neurofibrillary tangle (NFT) distribution correlated significantly with cortical [18F]FDDNP PET DVR in the temporal lobe (p ( 0.001, R = 0.87, R2 = 0.76). Linear combination of A and NFT densities was highly predictive of [18F]FDDNP PET DVR through all analyzed regions of interest (p ( 0.0001, R = 0.92, R2 = 0.85), and both densities contributed significantly to the model. Lewy bodies were present at a much lower level than either A or NFTs and did not significantly contribute to the in vivo signal. [18F]FDG PET scan results in this patient were consistent with the distinctive DLB pattern of hypometabolism. This work offers a mapping brain model applicable to all imaging probes for verification of imaging results with A and/or tau neuropathology brain distribution using immunohistochemistry, fluorescence microscopy, and autoradiography.
F.22 Improvement to existing health/diagnostic methods/procedures
COBISS.SI-ID: 30574041W e developed a staining protocol that enables simultaneous visualization of myosin heavy chain (MHC) pure and hybrid muscle fiber types in rat skeletal muscle. Up to eight different muscle fiber types can be visualized in a single section of the rat extensor digitorum longus muscle, w hich contains all four adult MHC isoforms and show s plasticity during the denervationreinnervation process. Triple immunofluorescent staining of MHC1, MHC2a and MHC2b w ith primary antibodies BAD5 (isotype IgG2b), SC71 (isotype IgG1) and BFF3 (isotype IgM) and w ith three fluorophorelabeled isotypespecific secondary antibodies displays different muscle fiber types in a merged image of red, green and blue channels, each in its ow n color. Immunoperoxidase staining w ith primary antibody 6H1 directed against MHC2x can be additionally applied on the same tissue section to facilitate the identification of muscle fibers containing MHC2x. Triple staining can also be used in combination w ith other staining procedures to derive more information about the number of capillaries or the oxidative potential of muscle fiber types. Simultaneous visualization of multiple fiber types in a single merged image enables economical use of muscle samples and provides simple and rapid identification of all fiber types that are present in rat limb muscles.
F.21 Development of new health/diagnostic methods/procedures
COBISS.SI-ID: 30372825Using gold plated electrodes, inserted into the ratćs head above the dura of the left and right parietal cortex, we recorded EEG during deep and shallow anesthesia with either pentobarbital (PB) or ketamine-xylazine (KX). The fluctuations in time series were then analyzed using wavelet transforms and the spectral power was determined within 7 frequency intervals (slow wave 2, S2, 0.0067-0.0167 Hz; slow wave 1, S1, 0.02-0.19 Hz; delta, 0.2-3.9 Hz; theta,4-7.9 Hz; alpha, 8-12.9 Hz; beta, 13-24.9 Hz and gamma, 25-34.9 Hz). In addition, the coupling strengths between individual oscillatory components during deep and shallow anesthesia were evaluated for both anesthetics. We show specific changes for both anesthetics indicating that during deep anesthesia PB reduces high and low frequency activity (0.2-35 Hz) and enhancescoupling especially between delta, theta and alpha waves, while KX reduces low frequency activity (0.005 to 0.2 Hz) and enhances coupling betweenfrequency waves alpha, beta and gamma. Our results, using two anesthetics known to block different ion channels, provide an insight into brain dynamics and could have wide implications in creating biomarkers for detecting various neurophysiological modifications, such as in Alzheimer and Parkinson's disease or autism spectrum disorder, as well as in providing more realistic models of brain dynamics.
F.22 Improvement to existing health/diagnostic methods/procedures
COBISS.SI-ID: 29971417