Search results for " Regulation"
showing 10 items of 3187 documents
Poly-ADP-Ribose (PAR) as an epigenetic flag
2009
Epigenetics is the study of hereditable chromatin modifications, such as DNA methylation, histone modifications, and nucleosome-remodelling, which occur without alterations to the DNA sequence. The establishment of different epigenetic states in eukaryotes depends on regulatory mechanisms that induce structural changes in chromatin in response to environmental and cellular cues. Two classes of enzymes modulate chromatin accessibility: chromatin-covalent modifiers and ATP-dependent chromatin remodelling complexes. The first class of enzymes catalyzes covalent modifications of DNA as well as the amino- and carboxy-terminal tails of histones, while the second uses the energy of ATP hydrolysis …
Darwinism and pharmacogenomics: from 'one treatment fits all' to 'selection of the richest'?
2004
Pharmacogenomics and pharmacogenetics are relatively new fields, and have arisen from recent advances in genetic research. They offer new perspectives on the development of pharmaceuticals, allowing drug design to be targeted specifically to the genotype of selected populations. The discussion of who will be considered for the development of these tailored drugs and who will be excluded, in a situation in which both research resources and public expenditure are limited, is provoking and has led to several, still unanswered ethical questions and concerns about fairness and the potential discrimination of fringe groups. Based on the statistical analyses of population averages, patient groups …
Fitness Trade-Offs Determine the Role of the Molecular Chaperonin GroEL in Buffering Mutations
2015
Molecular chaperones fold many proteins and their mutated versions in a cell and can sometimes buffer the phenotypic effect of mutations that affect protein folding. Unanswered questions about this buffering include the nature of its mechanism, its influence on the genetic variation of a population, the fitness trade-offs constraining this mechanism, and its role in expediting evolution. Answering these questions is fundamental to understand the contribution of buffering to increase genetic variation and ecological diversification. Here, we performed experimental evolution, genome resequencing, and computational analyses to determine the trade-offs and evolutionary trajectories of Escherich…
TRESK channel contributes to depolarization-induced shunting inhibition and modulates epileptic seizures.
2020
Glutamatergic and GABAergic synaptic transmission controls excitation and inhibition of postsynaptic neurons, whereas activity of ion channels modulates neuronal intrinsic excitability. However, it is unclear how excessive neuronal excitation affects intrinsic inhibition to regain homeostatic stability under physiological or pathophysiological conditions. Here, we report that a seizure-like sustained depolarization can induce short-term inhibition of hippocampal CA3 neurons via a mechanism of membrane shunting. This depolarization-induced shunting inhibition (DShI) mediates a non-synaptic, but neuronal intrinsic, short-term plasticity that is able to suppress action potential generation and…
The Regulatory State vs. the Networked Polity: confronting narratives of change
2014
The aim of the article is to summarize and reassess the innovations brought about by governance theory. It is argued that the notion of governance is a conceptual device that could help rationalise and articulate the changes undertaken by liberal democracies since the late 1970s. The article suggests the need to distinguish between two distinct research programmes composing governance studies, which are influenced by alternative epistemic traditions—political economy and economic sociology. Rationalizations of change influenced by political economy support the idea that the outcome of recent political change is a market-oriented “Regulatory State”, while those influence by economic sociolog…
Demonstration of an endocrine signaling circuit for insulin in the sponge Geodia cydonium.
1989
Abstract The existence of an insulin-mediated cell-to-cell signaling in the sponge Geodia cydonium is demonstrated in this study by molecular biological and immunological techniques. The sequence of a sponge cDNA clone encoding preproinsulin was analyzed for the first time and determined to comprise a high homology to human preproinsulin (60-80% homology). The predicted polypeptide of preproinsulin from sponge contains two disulfide bridges which link the A- to the B-chain. The intra-A chain disulfide bridge is absent. Applying immunological and electron microscopical techniques it is shown that insulin is produced in specialized cells (spherulous cells). Experimental evidence is presented …
Compromised central tolerance of ICA69 induces multiple organ autoimmunity
2014
For reasons not fully understood, patients with an organ-specific autoimmune disease have increased risks of developing autoimmune responses against other organs/tissues. We identified ICA69, a known β-cell autoantigen in Type 1 diabetes, as a potential common target in multi-organ autoimmunity. NOD mice immunized with ICA69 polypeptides exhibited exacerbated inflammation not only in the islets, but also in the salivary glands. To further investigate ICA69 autoimmunity, two genetically modified mouse lines were generated to modulate thymic ICA69 expression: the heterozygous ICA69(del/wt) line and the thymic medullary epithelial cell-specific deletion Aire-ΔICA69 line. Suboptimal central neg…
5' tRNA halves are highly expressed in the primate hippocampus and might sequence-specifically regulate gene expression
2020
Fragments of mature tRNAs have long been considered as mere degradation products without physiological function. However, recent reports show that tRNA-derived small RNAs (tsRNAs) play prominent roles in diverse cellular processes across a wide spectrum of species. Contrasting the situation in other small RNA pathways the mechanisms behind these effects appear more diverse, more complex, and are generally less well understood. In addition, surprisingly little is known about the expression profiles of tsRNAs across different tissues and species. Here, we provide an initial overview of tsRNA expression in different species and tissues, revealing very high levels of 5′ tRNA halves (5′ tRHs) pa…
Effect of flupirtine on Bcl-2 and glutathione level in neuronal cells treated in vitro with the prion protein fragment (PrP106-126).
1997
Flupirtine, trade name Katadolon, is a centrally acting nonopioid analgesic that has recently been found to display cytoprotective activity in vitro and in vivo on neurons induced to undergo apoptosis. This report shows that the PrP106-126 fragment of the prion protein, which is the likely etiological agent for a series of encephalopathies, is toxic to cortical neurons in vitro. Simultaneously, PrP106-126 influences the molecular GSH content and the bcl-2 expression in neurons. Significant toxicity (32% reduction in cell viability) was observed at a concentration of 50 microM of the peptide after 9 days of incubation, while at higher concentrations toxicity increased to 70%. Neurotoxicity w…
Diritto alla privacy e accesso agli atti del fascicolo telematico processuale da parte di terzi-giornalisti: “quo vadis” Italia?
2023
In this work, we want to try to examine what might be – today – the consequences of a contrast between the national legislation, artt. 51 and 52 of 30 June 2003, n. 196 (so-called Privacy Code) and art. 17 of the d.P.C.M. of 16 February 2016, n. 40, and the European legislation, art. 55 of the Privacy Regulation of 25 May 2016, n. 679, regarding the relationship between the protection of personal data, the right of access to the deeds of the electronic file of the administrative process by third parties (here of interest to journalists) and the right to information.