Alcohol addiction: a molecular biology perspective.

Alcohol 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

The janus face of oxidative stress in health and disease: The cause or the cure?

Reactive oxygen species (ROS), reactive nitrogen species (RNS) and diffusible reactive species (DRS), under certain concentrations, play an important role at the physiological level. The role of antioxidant molecules, endogenous and exogenous, is to maintain adequate amounts of ROS and RNS. The increase in ROS and RNS due to an overproduction of these species or a decrease in antioxidant molecules leads to the phenomenon called oxidative stress. Oxidative stress is involved in the physiological process of aging but is implicated in pathologies such as some types of tumors, neurodegenerative and autoimmune disorders, male infertility, cardiovascular disorders such as atrial fibrillation, and lung disorders such as chronic obstructive pulmonary disorders and pulmonary hypertension. This involvement has aroused widespread interest, especially because many studies try to exploit it at a therapeutic level. The purpose of this review is to discuss pathologies in which oxidative stress has an important role and for this reason, it can be targeted for a therapeutic intervention to improve or cure the pathology; sometimes modulation of oxidative stress can be used to improve the effect of the therapy

Infinite forme bellissime. Anatomia comparata degli spermatozoi

Le forme con le quali si manifestano gli spermatozoi nel regno animale sono infinite, praticamente una per ogni specie, a dispetto della diffusa rappresentazione degli spermatozoi come cellule semplici con una testa rotonda e una coda a frusta. Le regole generali sono poche: l’uniforme struttura del motore della coda ‒ quando presente ‒ detto axonema, e la presenza di un modello “primitivo” di spermatozoo almeno in alcune specie in quasi tutti i phyla. Ogni gruppo sistematico, poi, si è “inventato” proprie modalità per migliorare l’efficienza di fecondazione, e ciò è stato accompagnato da modificazioni dello spermatozoo, rendendone diagnostica la morfologia: accanto all’evoluzione delle specie, dunque, esiste un’evoluzione dello spermatozoo, e queste non sempre vanno di pari passo. Ciò permette di identificare l’appartenenza sistematica di una specie a partire dalla semplice osservazione di una sezione al microscopio, aiutando la collocazione sistematica di gruppi incertae sedis. Le ragioni della straordinaria variabilità di forma degli spermatozoi sono ancora in parte misteriose, e certamente, almeno in parte, sono da ricercarsi nelle complesse relazioni con gli apparati genitali femminili

Fossilized spermatozoa preserved in a 50-Myr-old annelid cocoon from Antarctica

The origin and evolution of clitellate annelids-earthworms, leeches and their relatives-is poorly understood, partly because body fossils of these delicate organisms are exceedingly rare. The distinctive egg cases (cocoons) of Clitellata, however, are relatively common in the fossil record, although their potential for phylogenetic studies has remained largely unexplored. Here, we report the remarkable discovery of fossilized spermatozoa preserved within the secreted wall layers of a 50-Myr-old clitellate cocoon from Antarctica, representing the oldest fossil animal sperm yet known. Sperm characters are highly informative for the classification of extant Annelida. The Antarctic fossil spermatozoa have several features that point to affinities with the peculiar, leech-like 'crayfish worms' (Branchiobdellida). We anticipate that systematic surveys of cocoon fossils coupled with advances in non-destructive analytical methods may open a new window into the evolution of minute, soft-bodied life forms that are otherwise only rarely observed in the fossil record.Facultad de Ciencias Naturales y Muse

A Genotypic-oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macro-categories of Cystic Fibrosis.

Cystic Fibrosis (CF) is a monogenic disease caused by mutations of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. The genotype-phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, 125 different mutated alleles (11 of which with novel mutations and 10 of which complex) and 225 genotypes were found. A strong correlation between mutational patterns at the genotypic level and phenotypic macro-categories emerged. This specificity appears to be largely dependent on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macro-categories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype - phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype - phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway

walk through programming for industrial applications

Abstract Collaboration between humans and robots is increasingly desired in several application domains, including the manufacturing domain. The paper describes a software control architecture for industrial robotic applications allowing human-robot cooperation during the programming phase of a robotic task. The control architecture is based on admittance control and tool dynamics compensation for implementing walk-through programming and manual guidance. Further steps to integrate this system on a real set-up include the robot kinematics and a socket communication that sends a binary file to the robot

Perinatal S-Adenosylmethionine Supplementation Represses PSEN1 Expression by the Cellular Epigenetic Memory of CpG and Non-CpG Methylation in Adult TgCRD8 Mice

DNA methylation, the main epigenetic modification regulating gene expression, plays a role in the pathophysiology of neurodegeneration. Previous evidence indicates that 50 -flanking hypomethylation of PSEN1, a gene involved in the amyloidogenic pathway in Alzheimer’s dis- ease (AD), boosts the AD-like phenotype in transgenic TgCRND8 mice. Supplementation with S-adenosylmethionine (SAM), the methyl donor in the DNA methylation reactions, reverts the patho- logical phenotype. Several studies indicate that epigenetic signatures, driving the shift between normal and diseased aging, can be acquired during the first stages of life, even in utero, and manifest phenotypically later on in life. Therefore, we decided to test whether SAM supplementation during the perinatal period (i.e., supplementing the mothers from mating to weaning) could exert a protec- tive role towards AD-like symptom manifestation. We therefore compared the effect of post-weaning vs. perinatal SAM treatment in TgCRND8 mice by assessing PSEN1 methylation and expression and the development of amyloid plaques. We found that short-term perinatal supplementation was as effective as the longer post-weaning supplementation in repressing PSEN1 expression and amyloid deposition in adult mice. These results highlight the importance of epigenetic memory and methyl donor availability during early life to promote healthy aging and stress the functional role of non-CpG methylation