Biomedical subjects

U Pozzoli

Publications and source records attributed to U Pozzoli.

8 recordsLinked to original sources

PubMed2006

Effect of the catechol-O-methyltransferase val(158)met genotype on children's early phases of facial stimuli processing.

The ability to process and identify human faces matures early in life, is universal and is mediated by a distributed neural system. The temporal dynamics of this cognitive-emotional task can be studied by cerebral visual event-related potentials (ERPs) that are stable from midchildhood onwards. We hypothesized that part of individual variability in the parameters of the N170, a waveform that specifically marks the early, precategorical phases of human face processing, could be associated with genetic variation at the functional polymorphism of the catechol-O-methyltransferase (val(158)met) gene, which influences information processing, cognitive control tasks and patterns of brain activation during passive processing of human facial stimuli. Forty-nine third and fourth graders underwent a task of implicit processing of other children's facial expressions of emotions while ERPs were recorded. The N170 parameters (latency and amplitude) were insensitive to the type of expression, stimulus repetition, gender or school grade. Although limited by the absence of met- homozygotes among boys, data showed shorter N170 latency associated with the presence of 1-2 met158 alleles, and family-based association tests (as implemented in the PBAT version 2.6 software package) confirmed the association. These data were independent of the serotonin transporter promoter polymorphism and the N400 waveform investigated in the same group of children in a previous study. Some electrophysiological features of face processing may be stable from midchildhood onwards. Different waveforms generated by face processing may have at least partially independent genetic architectures and yield different implications toward the understanding of individual differences in cognition and emotions.

Catechol O-Methyltransferase↗

PubMed2005

Silencers regulate both constitutive and alternative splicing events in mammals.

Constitutive and alternative splicing events are regulated, in higher eukaryotes, by the action of multiple weak cis-acting elements and trans-acting factors. In particular, several evidences have suggested that silencers might have a fundamental role in preventing pseudoexon inclusion in mature transcripts and in defining constitutive exons by suppressing nearby decoy splice sites. Moreover, silencer elements allow the recruitment of regulatory factors to alternatively spliced exons, therefore participating in the modulation of alternative splicing pathways. Here we focus on splicing repression mechanisms in mammals, with particular concern to both exonic and intronic silencer elements, secondary structure formation and role in human genetic disease.Recently, in addition to the availability of a growing number of sequence elements deriving from the analysis of individual regulated exons, approaches have been developed that allowed the systematic identification of splicing silencers. These methods and are briefly described, as well as the motifs they retrieved, and summary of silenced exons is provided.

Alternative Splicing↗

PubMed2003

Trans-acting factors may cause dystrophin splicing misregulation in BMD skeletal muscles.

We analyzed dystrophin alternative splicing events in a large number of Becker muscular dystrophy (BMD) affected individuals presenting major hot-spot deletions. Evidence is shown that altered splicing patterns in these patients do not directly result from the gene defect but probably derive from modifications in trans- rather than cis-acting factors. Several potential CUG-binding protein 2 (CUG-BP2) binding sites were found to be located in the dystrophin gene region encompassing exons 43-60 and CUG-BP2 transcript analysis indicated that not only expression levels are increased in dystrophic muscles but also that different CUG-BP2 isoforms are expressed. The possibility that CUG-BP2 might have a role in dystrophin splicing regulation is discussed.

Alternative Splicing↗

PubMed2002

The dystrophin gene is alternatively spliced throughout its coding sequence.

We have analysed splicing patterns in the human dystrophin gene region encoding the rod and cysteine-rich domains in normal skeletal muscle, brain and heart tissues. Sixteen novel alternative transcripts were identified, the majority of them being present in all three tissues. Tissue-specific variants were also identified, suggesting a functional role of transcriptional diversity. Transcript analysis in dystrophinopathic autoptic and bioptic specimens revealed that pre-mRNAs secondary structure formation and relative strength of exon/exon association play little or no role in directing alternative splicing events. This analysis also showed that independent deletion events leading to the loss of the same exons may be associated with transcriptional variability.

Alternative Splicing↗

PubMed2002

Electrophysiological analysis of cognitive slowing in subjects with mitochondrial encephalomyopathy.

Mitochondrial encephalomyopathies (MEs) are multisystemic inherited disorders affecting tissues with high energy requirement such as the muscle, retina and central nervous system. Progressive external ophthalmoplegia and myopathy are the most common features in adults, and cognitive impairment is rare. In many neurodegenerative disorders, ERPs have been effectively performed to record cognitive slowing on tasks with different amount of information. To analyze the evidence for possible cognitive slowing, a standard auditory oddball paradigm with a button-press response was applied. Participants were 11 non-demented patients affected by mitochondrial encephalomyopathy and 14 age-matched normal controls. This hypothesis was tested using two tasks of different difficulty (pure tone vs. phonetic stimuli). Reaction time (RT), performance (P) and event-related potentials (ERPs) were measured. RT and P were not significantly different between the groups. Patients showed significantly increased N2 latency and reduced P3 amplitude on both tasks. No difference was found in pure tone and phonetic task conditions. Results were interpreted as electrophysiological signs of cognitive slowing--particularly in relation to stimulus evaluation--irrespective of sensory problems, response selection and cognitive load. These findings suggest that in ME patients, there may be a possible dysfunction of neural mechanisms underlying cognitive events and ERP generation.

Acoustic Stimulation↗

PubMed2001

Analysis of splicing parameters in the dystrophin gene: relevance for physiological and pathogenetic splicing mechanisms.

The molecular mechanisms that direct splice-site selection and assure orderly exon juxtaposition have not been fully clarified. The extraordinary nature of the dystrophin gene points to several hurdles in the processing of transcripts. In this study, dystrophin statistical and thermodynamic splicing parameters have been evaluated providing the first comprehensive description for a single human gene. We show that concomitant use of consensus values (CV) and DeltaDG degrees 37 values for U1snRNA annealing better discriminates between real donor sites and donor-like sequences. Evidence is also provided that, on average, out-of-frame dystrophin exons have significantly stronger CVs and more favorable DeltaDG degrees 37 values; this feature has never been reported and might reflect evolutionary-driven minimization of out-of-frame exon misplicing. Dystrophin splicing mutations have been reported to determine either Duchenne or Becker Muscular Dystrophy, but no comprehensive genotypic/phenotypic correlation has ever been investigated. We have analyzed splicing affecting single base-pair substitutions in the dystrophin gene with respect to their effect on splicing parameters; functional and clinical consequences are also reported. We have found 5'-splice-site mutation occurrence to be statistically related to mutability quotients and propose the use of DeltaDG degrees 37 values as a more effective tool than CV alone to describe donor site mutation consequences. Our analysis also indicates a nearly 100% correlation between clinical phenotype and the reading-frame rule determined at the RNA level. We consider that elucidation of the relative importance of splicing determinants might help to clarify the molecular mechanisms that direct correct splicing in complex genes and might be useful in the validation of predictive models.

Dystrophin↗

PubMed1999

Evolution of ocular clinical and electrophysiological findings in pediatric Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a hereditary autosomal-recessive disorder, characterized by mental retardation, obesity, pigmentary retinopathy, polydactyly and, only in males, hypogenitalism. Even though genetic studies have revealed five different forms of BBS correlated to distinct loci on different chromosomes, a diagnosis of BBS is still primarily based on clinical data. The present study discusses the evolution of clinical ophthalmological and electrophysiological characteristics of BBS patients in developmental age. The main results obtained on a sample of 13 pediatric patients are the following: * progressive loss of visual acuity arised early in the first decade of life * ophthalmoscopic signs of pigmentary retinopathy were present only in 46% of the children studied * striking anomalies in the electroretinogram were also detected in the cases without pigmentary retinopathy * the electroretinographic results, when detectable, suggested a greater involvement of the photopic system as against the scotopic system.

Bardet-Biedl Syndrome↗

PubMedDate not supplied

Effect of sodium pool changes on blood pressure in patients undergoing PFD: design of a prospective randomized multicenter trial.

Blood pressure control is important during dialysis and the interdialytic period because of the frequency and potential seriousness of hypotension and hypertension. Water and sodium removal play an important role in the genesis of intradialytic cardiovascular instability or hypertension. Changing dialysate sodium concentrations without the aid of a kinetic model can sometimes give good results but is only an empirical approach. Therefore, this clinical trial was designed to prospectively investigate the advantages of changes in the sodium pool on the blood pressure profile of patients undergoing paired filtration dialysis (PFD). The hypothesis to be tested is whether using a dialysate conductivity which, according to the conductivity kinetic model, ensures that the conductivity of the ultrafiltrate at the end of each dialysis session is 0.3 mS/cm more (B) or less (C) than the mean during the run-in period, improves blood pressure control either in patients prone to intradialytic hypotension or patients who are hypertensive or normotensive with antihypertensive treatment. Patients will be randomly allocated to one of two treatment sequences (where treatment A is standard PFD): AABB or ABAA for patients with intradialytic hypotension; AACC or ACAA for hypertensive patients. During the experimental phase arterial blood pressure will be measured and symptoms reported by the patients will be recorded.

Blood Pressure↗