1,721,022 research outputs found
Alcohol addiction: a molecular biology perspective.
Full text linkAlcohol misuse represents worldwide an important risk factor for death and disability. Excessive alcohol consumption is widely diffused in different ethnicities and alcohol use is part of the lifestyle of both young and old people. The genetic basis of alcohol dependence concerning ethanol metabolism and the pathways of reward circuits are well known. The role of genetic variants in the neurobiology of addiction as well as in response to medication in alcoholism therapy still represents an intriguing argument that needs to be deeply analyzed and explained. The molecular approach to the study of these aspects could be difficult because of the large number of genes and variations involved. Our work is intended to offer an overview of genes and variants involved in alcohol addiction and pharmacogenetics. Our aim is to delineate a molecular approach strategy to look at alcohol dependence from a genetic and applicative point of view. The indications provided in this work should be of help for those who wish to undertake a molecular study of this multifactorial disease
Demethylation and specific remethylation of the promoter-like region of the L family of mammalian transposable elements.
No full textTumor cells fail to trans-induce telomerase in human umbilical vein endothelial cell cultures
No full textThe shortening of the telomeres that occurs in most somatic cells and untransformed cell cultures is considered a hallmark of cellular senescence. Re-activation of telomerase, which is usually present in immortal cells, avoids telomere shortening and considerably extends the culture life span. Normal human endothelial cells are characterized by an accelerated rate of telomere shortening and reach replicative senescence after a limited number of cell divisions. It has recently been reported that human telomerase reverse transcriptase expression may be strongly up-regulated in human endothelial cells cocultivated with tumor cells. Due to the important implications of this finding on tumor progression, we have extensively analyzed for the presence of telomerase in primary human endothelial cells either cocultivated with tumor cells or grown with tumorconditioned medium. We found modest, but readily detectable, amounts of telomerase in all human endothelial cell cultures analyzed that disappeared as the cultures approached senescence. Quantitative reverse transcription-PCR also showed a direct correlation between human telomerase reverse transcriptase expression and the proliferative index of the cultures. Nevertheless, we did not find any evidence of induction of telomerase activity by tumor cells in any of the tested conditions. All data indicate that telomerase in human endothelial cells follows an activation program that is strictly associated to the culture growth rate
K+ at concentrations reached in the extracellular space during neuronal activity promotes a Ca2+-dependent glycogen hydrolysis in mouse cerebral cortex.
No full textThe effect of increasing [K+]0 on 3H-glycogen levels was examined in mouse cerebral cortical slices. K+ stimulates in a time- and concentration-dependent manner the hydrolysis of 3H-glycogen. Over 70% of the maximal effect is reached within 30 sec and the EC50 for the glycogenolytic action of K+ is 11 mM. Significant 3H-glycogen hydrolysis occurs at 5-12 mM [K+]0, concentrations reached by the ion in the extracellular space during neuronal activity. The K+-evoked glycogenolysis is Ca2+-dependent, and is inhibited by Ca2+-channel blockers such as Ni2+ and Mn2+, but not by Cd2+, nifedipine, and omega-conotoxin. Furthermore, the effect of K+ is not enhanced by the Ca2+-channel agonist Bay K 8644. This type of pharmacological profile suggests that the activation of voltage-sensitive Ca2+ channels of the T subtype mediates the glycogenolytic action of K+. This set of observations suggests that K+ released in the extracellular space by active neurons may promote the mobilization of energy substrates and therefore play a role in the coupling between neuronal activity and energy metabolism
AMPLIFICATION OF AN ANCESTRAL MAMMALIAN L1 FAMILY OF LONG INTERSPERSED REPEATED DNA OCCURRED JUST BEFORE THE MURINE RADIATION
No full textABSTRACT Each mammalian genus examined so far contains 50,000-100,000 members of an Li (LINE 1) family of long interspersed repeated DNA elements. Current knowledge on the evolution of LI families presents a paradox because, although Li families have been in mammalian genomes since before the mammalian radiation -80 million years ago, most members of the Li families are only a few million years old. Accordingly it has been suggested either that the extensive amplification that characterizes present-day Li families did not occur in the past or that old members were removed as new ones were generated. However, we show here that an ancestral rodent Li family was extensively amplified '10 million years ago and that the relics (""60,000 copies) of this amplification have persisted in modern murine genomes (Old World rats and mice). This amplification occurred just before the divergence of modern murine genera from their common ancestor and identifies the murine node in the lineage of modern muroid rodents. Our results suggest that repeated amplification of LI elements is a feature of the evolution of mammalian genomes and that ancestral amplification events could provide a useful tool for determining mammalian lineages
Effect of stress on hippocampal nociceptin expression in the rat
No full textNociceptin/orphanin FQ (N/OFQ) peptide and its receptor are not only ubiquitously expressed in mammalian brain and spinal cord but are also abundant in limbic structures, particularly in the hippocampus. The widespread distribution of N/OFQ reflects the broad spectrum of its biological actions such as nociception, food intake, spontaneous locomotor activity, and learning and memory processes. Since the hippocampus is involved in the control of adrenocortical activity, its role in stress-related phenomena is well characterized. In male Wistar rats, we first examined the effects of acute restraint stress (120 min) on the brain immunohistochemical localization of N/OFQ. The analysis carried out on sections obtained at the onset of stress revealed enhanced expression of N/OFQ in CA1, CA3, and the dentate gyrus as well as increased plasma corticosterone concentrations. Next, we examined whether endogenous glucocorticoid hormone plays a role in the modulation of hippocampal N/OFQ expression in response to stress. To this end, rats were injected with corticosterone (1 mg/kg) or subjected to restraint stress 1 week after adrenalectomy. Two hours after corticosterone administration, plasma glucocorticoid concentrations were comparable to those observed after restraint stress, while N/OFQ expression had significantly increased in all the hippocampal subfields examined. By contrast, in adrenalectomized rats, stress did not modify protein expression. These results confirm that stress can affect N/OFQ expression and that glucocorticoids may constitute hormonal mediators of this complex interplay
Reproducible DNA fingerprinting with the random amplified polymorphic DNA (RAPD) method.
No full textMuch interest has recently arisen in methods for DNA
fingerprinting based on the polymerase chain reaction (PCR).
Among these, the Random Amplified Polymorphic DNA (RAPD)
method, developed by Williams eta]. (1), is currently receiving
particular attention (2) because of its extreme simplicity and
requirement for minimal amounts of genomic DNA. The basic
strategy involves the PCR amplification of random fragments of
genomic DNA with single or multiple (3) primers of arbitrary
sequence. Polymorphism between individuals (or strains) is
detected as differences between the pattern of DNA fragments
amplified from the different DNAs using a given primer(s)
Metodo per determinare il deficit di attenzione con iperattività.
No full textLa presente invenzione fornisce strategie sia per la diagnosi e sia per il monitoraggio della efficacia dei trattamenti, per il disturbo da deficit di attenzione e iperattività (ADHD) in soggetti umani, mediante un semplice metodo di indagine epigenetica su campioni biologici. La presente invenzione è un indice composito che fa uso della valutazione dei livelli di metilazione del DNA in sei siti CpG a livello del promotore del gene che codifica per il Trasportatore della Dopamina (DAT), da usare in quanto tali o in combinazione con i livelli nel siero degli auto-anticorpi diretti verso il DAT (hDAT nAb). Gli inventori hanno anche scoperto che la presente invenzione può predire e/o monitorare l’efficacia delle terapie nella patologia ADHD, siano esse approcci cognitivo-comportamentali o comunque non farmacologici, sia con l’uso di quei farmaci psico-stimolanti analoghi al “Ritalin”: pertanto tali strategie terapeutiche, se combinate con i metodi prognostici oggetto della presente invenzione, possono essere messi in pratica con maggior efficacia.The present invention provides strategies for diagnosing and for monitoring of treatment efficacy, in case of ADHD (in human patients). The present invention is an index, composed on a first side by levels of methylation in six specific positions (CpG residues) within the promoter for the gene coding for Dopamine Transporter (DAT), to be used alone or in combination with levels (in serum) of auto-antibodies directed towards DAT (hDAT aAbs).
The inventors have also discovered that the present invention can predict and/or monitor the efficacy of therapeutic strategies, being them a cognitive-behavioral therapy or the alike, as well as the use of “Ritalin-like” psycho-stimulants: these therapeutic strategies, when combined with the prognostic methods of the present invention, can be practiced more effectively
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