Search results for "Toni"
showing 10 items of 8001 documents
miR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate myotonic dystrophy phenotypes in mammalian models
2018
Functional depletion of the alternative splicing factors Muscleblind-like (MBNL 1 and 2) is at the basis of the neuromuscular disease myotonic dystrophy type 1 (DM1). We previously showed the efficacy of miRNA downregulation in Drosophila DM1 model. Here, we screen for miRNAs that regulate MBNL1 and MBNL2 in HeLa cells. We thus identify miR-23b and miR-218, and confirm that they downregulate MBNL proteins in this cell line. Antagonists of miR-23b and miR-218 miRNAs enhance MBNL protein levels and rescue pathogenic missplicing events in DM1 myoblasts. Systemic delivery of these “antagomiRs” similarly boost MBNL expression and improve DM1-like phenotypes, including splicing alterations, histo…
Therapeutic Potential of AntagomiR-23b for Treating Myotonic Dystrophy
2020
Myotonic dystrophy type 1 (DM1) is a chronically debilitating, rare genetic disease that originates from an expansion of a noncoding CTG repeat in the dystrophia myotonica protein kinase (DMPK) gene. The expansion becomes pathogenic when DMPK transcripts contain 50 or more repetitions due to the sequestration of the muscleblind-like (MBNL) family of proteins. Depletion of MBNLs causes alterations in splicing patterns in transcripts that contribute to clinical symptoms such as myotonia and muscle weakness and wasting. We previously found that microRNA (miR)-23b directly regulates MBNL1 in DM1 myoblasts and mice and that antisense technology (“antagomiRs”) blocking this microRNA (miRNA) boost…
Gene variants of osteoprotegerin, estrogen-, calcitonin- and vitamin D-receptor genes and serum markers of bone metabolism in patients with Gaucher d…
2018
Anca Zimmermann,1 Radu A Popp,2 Heidi Rossmann,3 Simona Bucerzan,4 Ioana Nascu,4 Daniel Leucuta,5 Matthias M Weber,1 Paula Grigorescu-Sido41Department of Endocrinology and Metabolic Diseases, 1st Clinic and Polyclinic of Internal Medicine, University of Mainz, Mainz, Germany; 2Department of Medical Genetics, University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3Institute for Clinical Chemistry and Laboratory Medicine, University of Mainz, Mainz, Germany; 4Center of Genetic Diseases, 1st Pediatric Clinic, University of Medicine and Pharmacy, Cluj-Napoca, Romania; 5Department of Medical Informatics and Biostatistics, University of Medicine and Pharmacy, Cluj-Napoca, RomaniaPurpose: Oste…
Lateral Habenula 5-HT2C Receptor Function Is Altered by Acute and Chronic Nicotine Exposures
2021
Serotonin (5-HT) is important in some nicotine actions in the CNS. Among all the 5-HT receptors (5-HTRs), the 5-HT2CR has emerged as a promising drug target for smoking cessation. The 5-HT2CRs within the lateral habenula (LHb) may be crucial for nicotine addiction. Here we showed that after acute nicotine tartrate (2 mg/kg, i.p.) exposure, the 5-HT2CR agonist Ro 60-0175 (5–640 µg/kg, i.v.) increased the electrical activity of 42% of the LHb recorded neurons in vivo in rats. Conversely, after chronic nicotine treatment (6 mg/kg/day, i.p., for 14 days), Ro 60-0175 was incapable of affecting the LHb neuronal discharge. Moreover, acute nicotine exposure increased the 5-HT2CR-immunoreactive (IR)…
Ocular Clocks: Adapting Mechanisms for Eye Functions and Health
2018
Vision is a highly rhythmic function adapted to the extensive changes in light intensity occurring over the 24-hour day. This adaptation relies on rhythms in cellular and molecular processes, which are orchestrated by a network of circadian clocks located within the retina and in the eye, synchronized to the day/night cycle and which, together, fine-tune detection and processing of light information over the 24-hour period and ensure retinal homeostasis. Systematic or high throughput studies revealed a series of genes rhythmically expressed in the retina, pointing at specific functions or pathways under circadian control. Conversely, knockout studies demonstrated that the circadian clock re…
Modulation of Hippocampal Circuits by Muscarinic and Nicotinic Receptors
2017
This article provides a review of the effects of activation of muscarinic and nicotinic receptors on the physiological properties of circuits in the hippocampal formation. Previous articles have described detailed computational hypotheses about the role of cholinergic neuromodulation in enhancing the dynamics for encoding in cortical structures and the role of reduced cholinergic modulation in allowing consolidation of previously encoded information. This article will focus on addressing the broad scope of different modulatory effects observed within hippocampal circuits, highlighting the heterogeneity of cholinergic modulation in terms of the physiological effects of activation of muscarin…
Drift and evolutionary forces
2016
This arride analyzes the view of evolutionary theory as a theory of forces. The analogy with Newtonian mechanics has been challenged due to the alleged mismatch between drift and the other evolutionary forces. Since genetic drifr has no direction severa! authors tried to protect its status as a force: denying its lack of directionality, extending the notion of force and looking for a force in physics which also lacks of direction. I analyse these approaches, and although this strategy finally succeeds, this discussion overlooks the crucial point on the debate between causalists and statisticalists: the causal status of evolutionary theoty.; El presente artículo analiza la visión de la teorí…
Nonlinear femtosecond pulse propagation in an all-solid photonic bandgap fiber
2009
Nonlinear femtosecond pulse propagation in an all-solid photonic bandgap fiber is experimentally and numerically investigated. Guiding light in such fiber occurs via two mechanisms: photonic bandgap in the central silica core or total internal reflection in the germanium doped inclusions. By properly combining spectral filtering, dispersion tailoring and pump coupling into the fiber modes, we experimentally demonstrate efficient supercontinuum generation with controllable spectral bandwidth.
Perceived similarity between written Estonian and Finnish : Strings of letters or morphological units?
2017
The distance or similarity between two languages can be objective or actual, i.e. discoverable by the tools and methods of linguists, or perceived by users of the languages. In this article two methods, the Levenshtein Distance (LD), which purports to measure the objective distance, and the Index of Perceived Similarity (IPS), which quantifies language users’ perceptions, are compared. The data are the quantitative results of a test measuring conscious perceptions of similarity between Estonian and Finnish inflectional morphology by Finnish and Estonian native speakers (‘Finns’ and ‘Estonians’) with no knowledge of and exposure to the other (‘target’) language. The results show that Finns s…
Modeling Metaphysics: The Rise of Simulation and the Reversal of Platonism
2019
Philosophical reflection on and around Modeling and Simulation (M&S) is often focused on the ethical and epistemological implications of empirical findings or innovative methods within the field. In this paper I highlight some of the metaphysical implications of developments within M&S. I argue that the rise of simulation within and across scientific disciplines is accelerating the reversal of Platonism, whose emphasis on transcendence and reliance on hierarchical, static categories has dominated western philosophy for over two millennia. The success of M&S methodologies opens up new conceptual space for articulating a metaphysics of immanence that may provide a more adequate basis for unde…