P. Piccinelli - Academia.edu (original) (raw)
Papers by P. Piccinelli
Developmental Medicine & Child Neurology, 2008
Nucleic Acids Research - NAR, 2005
RNA, 2007
An RNA hairpin structure referred to as the iron-responsive element (IRE) and iron regulatory pro... more An RNA hairpin structure referred to as the iron-responsive element (IRE) and iron regulatory proteins (IRPs) are key players in the control of iron metabolism in animal cells. They regulate translation initiation or mRNA stability, and the IRE is found in a variety of mRNAs, such as those encoding ferritin, transferrin receptor (Tfr), erythroid aminolevulinic acid synthase (eALAS), mitochondrial aconitase (mACO), ferroportin, and divalent metal transporter 1 (DMT1). We have studied the evolution of the IRE by considering all mRNAs previously known to be associated with this structure and by computationally examining its occurrence in a large variety of eukaryotic organisms. More than 100 novel sequences together with ;50 IREs that were previously reported resulted in a comprehensive view of the phylogenetic distribution of this element. A comparison of the different mRNAs shows that the IREs of eALAS and mACO are found in chordates, those of ferroportin and Tfr1 are found in vertebrates, and the IRE of DMT1 is confined to mammals. In contrast, the IRE of ferritin occurs in a majority of metazoa including lower metazoa such as sponges and Nematostella (sea anemone). These findings suggest that the ferritin IRE represents the ancestral version of this type of translational control and that during the evolution of higher animals the IRE structure was adopted by other genes. On the basis of primary sequence comparison between different organisms, we suggest that some of these IREs developed by ''convergent evolution'' through stepwise changes in sequence, rather than by recombination events. 08.
Nucleic Acids Research, 2006
The RNases P and MRP are involved in tRNA and rRNA processing, respectively. Both enzymes in euka... more The RNases P and MRP are involved in tRNA and rRNA processing, respectively. Both enzymes in eukaryotes are composed of an RNA molecule and 9-12 protein subunits. Most of the protein subunits are shared between RNases P and MRP. We have here performed a computational analysis of the protein subunits in a broad range of eukaryotic organisms using profile-based searches and phylogenetic methods. A number of novel homologues were identified, giving rise to a more complete inventory of RNase P/MRP proteins. We present evidence of a relationship between fungal Pop8 and the protein subunit families Rpp14/Pop5 as well as between fungal Pop6 and metazoan Rpp25. These relationships further emphasize a structural and functional similarity between the yeast and human P/MRP complexes. We have also identified novel P and MRP RNAs and analysis of all available sequences revealed a K-turn motif in a large number of these RNAs. We suggest that this motif is a binding site for the Pop3/Rpp38 proteins and we discuss other structural features of the RNA subunit and possible relationships to the protein subunit repertoire.
Nucleic Acids Research, 2005
RNases P and MRP are ribonucleoprotein complexes involved in tRNA and rRNA processing, respective... more RNases P and MRP are ribonucleoprotein complexes involved in tRNA and rRNA processing, respectively. The RNA subunits of these two enzymes are structurally related to each other and play an essential role in the enzymatic reaction. Both of the RNAs have a highly conserved helical region, P4, which is important in the catalytic reaction. We have used a bioinformatics approach based on conserved elements to computationally analyze available genomic sequences of eukaryotic organisms and have identified a large number of novel nuclear RNase P and MRP RNA genes. For MRP RNA for instance, this investigation increases the number of known sequences by a factor of three. We present secondary structure models of many of the predicted RNAs. Although all sequences are able to fold into the consensus secondary structure of P and MRP RNAs, a striking variation in size is observed, ranging from a Nosema locustae MRP RNA of 160 nt to much larger RNAs, e.g. a Plasmodium knowlesi P RNA of 696 nt. The P and MRP RNA genes appear in tandem in some protists, further emphasizing the close evolutionary relationship of these RNAs.
Neurology, 1999
A family is described in which bilateral perisylvian polymicrogyria was present in 6 members of 3... more A family is described in which bilateral perisylvian polymicrogyria was present in 6 members of 3 consecutive generations. Typical anatomic and clinical findings of the syndrome, with a mild phenotype, were present in the 5 affected women from all 3 generations. More severe impairment was observed in the only affected male individual, a boy, in the third generation. Analysis of the pedigree and severity of the phenotype in the affected boy are consistent with transmission of an X-linked dominant trait, although other patterns of inheritance cannot be ruled out with certainty.
Journal of Child Neurology, 2000
A 17-year-old boy with polymorphic simple and complex partial seizures is described. Magnetic res... more A 17-year-old boy with polymorphic simple and complex partial seizures is described. Magnetic resonance imaging revealed a unilateral periventricular nodular heterotopia near the occipital ventricular right horn. Interictal and ictal electroencephalographic recordings showed bilateral specific epileptiform anomalies in the occipital region and asynchronous slow waves in frontal areas. Single photon emission computed tomography documented a reduction in regional cerebral blood flow in an area of the left occipital cortex and a symmetric increase in tracer uptake in the frontal lobes. The neuropsychologic assessment revealed a dysfunction of the frontal associative areas. Data collected led the authors to suspect a more diffuse cortical dysfunction than the nodular heterotopia revealed on magnetic resonance imaging.
Geomicrobiology Journal, 2012
Over the last decade or so, several studies have investigated the formation, mineralogy and micro... more Over the last decade or so, several studies have investigated the formation, mineralogy and microbial composition of iron oxyhydroxides. Here, we focus on the exploration of the microbial community structure of iron oxyhydroxide minerals that often occur in tight association with microbial life, which are referred to as Biogenic Iron Oxyhydroxides (BIOS). BIOS deposits host a wide range of microbial taxa usually found living in the oxic, suboxic and anaerobic interfaces of the biogeosphere. These organisms are responsible for the global cycling of Fe, N, C and S. Near the surface of BIOS mats, O 2 at ambient atmospheric levels rapidly reacts with dissolved Fe(II) to form insoluble Fe(III) minerals. Due to the activity of highly efficient heterotrophic O 2 respirers, BIOS biofilms usually transit from the top to the bottom (within a mm range) into a suboxic zone where microaerophilic iron-oxidizing bacteria thrive, transforming Fe(II) to Fe(III), while generating organic carbon. The bulk of the Fe(III), produced by both biotic and abiotic processes, is precipitated and fixed into a variety of cellular matrices. The resulting iron oxyhydroxides provide highly reactive surfaces responsible for the secondary sequestration of a vast range of trace elements. Given the fact that the mineralogical composition of BIOS is fairly well known, we focus here on the diversity of the microorganisms associated with BIOS deposited over wide geographical scales. This manuscript also presents condensed information that demonstrates that the biogeochemistry of BIOS appears to provide niche-specific conditions that select for similar microbial taxa across different spatial scales. We suggest that globally, these lineages play an important and similar role in BIOS development in the aerobic biogeosphere regardless of the location.
BMC Genomics, 2011
Background: Gene regulation through cis-regulatory elements plays a crucial role in development a... more Background: Gene regulation through cis-regulatory elements plays a crucial role in development and disease. A major aim of the post-genomic era is to be able to read the function of cis-regulatory elements through scrutiny of their DNA sequence. Whilst comparative genomics approaches have identified thousands of putative regulatory elements, our knowledge of their mechanism of action is poor and very little progress has been made in systematically de-coding them. Results: Here, we identify ancient functional signatures within vertebrate conserved non-coding elements (CNEs) through a combination of phylogenetic footprinting and functional assay, using genomic sequence from the sea lamprey as a reference. We uncover a striking enrichment within vertebrate CNEs for conserved binding-site motifs of the Pbx-Hox hetero-dimer. We further show that these predict reporter gene expression in a segment specific manner in the hindbrain and pharyngeal arches during zebrafish development.
Minerva pediatrica, 1998
In this article, the interrelations between biological and emotional factors in learning disabili... more In this article, the interrelations between biological and emotional factors in learning disabilities in Turner's syndrome are studied. This is a transversal study with a 18 months neuropsychiatric follow-up. Five girls with the syndrome, aged between 12 and 22 years have been studied using Wechsler scales (WISC-R and WAIS), individual interviews and psychodiagnostic tests, to describe both their cognitive profile and psychological traits. The intelligence tests show selective impairments in visuo-spatial area, with lower score on performance IQ, especially in the sub-tests "Block Design" and "Object Assembly"; individual interviews and psychodiagnostic tests show signs of psychological disease, often consequences of this syndrome, and only in one girl with an associated diagnosis of psychosis. Psychological and environmental factors, as well as the genetics, may play an important role in the impairment of cognitive abilities, and the neuropsychological aspec...
Pediatrics, 1996
This report presents the case of a previously healthy 6-year-old girl who had an ischemic injury ... more This report presents the case of a previously healthy 6-year-old girl who had an ischemic injury corresponding to the territory perfused by the lateral branches of the lenticulostriate arteries of the middle cerebral artery. Stroke in childhood is rare, and the specific causes are identified in only half the cases. Our patient was carefully studied for any hereditary or acquired risk factors for stroke, but we found only one, an endoscopic injection of Teflon performed 1 year before to correct vesicoureteral reflux. This suggests the risk of potential migration of Teflon particles to the brain, where they can block the microcirculation.
ISSLS 88., International Symposium on Subscriber Loops and Services, 1988
This paper describes the tranceiver developed in Italy for the ISDN pilot project and concentrate... more This paper describes the tranceiver developed in Italy for the ISDN pilot project and concentrate on the reasons why this system has been chosen. Moreover laboratory and field trial results are reported.
Seizure, 2010
To study neuropsychological functions in children with idiopathic epilepsy at onset of treatment ... more To study neuropsychological functions in children with idiopathic epilepsy at onset of treatment and after 1 year of therapy and to identify factors associated with cognitive impairment. 43 Subjects aged 5.2-16.9 years with newly diagnosed idiopathic epilepsy were enrolled and started treatment with valproate or carbamazepine. At admission and after 12 months, all patients underwent clinical examinations, the Child Behavioural Checklist, EEG and a neuropsychological test battery. The results of each test were correlated to demographic, clinical, electrophysiological and therapeutic variables. Except for attention, all neuropsychological functions were normal at admission and after 12 months. An improvement with time was noted for memory (p<0.05) and logical-executive functions (p<0.01). Attentive deficit was worse at 12 months (53.5% vs. 32.6%). Low socio-economic level and emotional and behavioural disturbances were the only factors negatively correlated to intelligence, memory and attention. Compared to valproate, carbamazepine was most commonly implicated. Idiopathic epilepsy can affect attention, even before starting treatment. Emotional and behavioural difficulties and a low socio-economical status are associated with cognitive impairment.
Pediatric Neurology, 2001
Neurogenetics, 2005
Benign familial neonatal convulsion (BFNC) is a rare autosomal dominant disorder caused by mutati... more Benign familial neonatal convulsion (BFNC) is a rare autosomal dominant disorder caused by mutations in KCNQ2 and KCNQ3, two genes encoding for potassium channel subunits. A large family with nine members affected by BFNC is described in the present study. All affected members of this family carry a novel deletion/insertion mutation in the KCNQ2 gene (c.761_770del10insA), which determines a premature truncation of the protein. In addition, in the family of the proposita's father, a novel sequence variant (c.2687A> G) in KCNQ3 leading to the p.N821S amino acid change was detected. When heterologously expressed in Chinese hamster ovary cells, KCNQ2 subunits carrying the mutation failed to form functional potassium channels in homomeric configuration and did not affect channels formed by KCNQ2 and/or KCNQ3 subunits. On the other hand, homomeric and heteromeric potassium channels formed by KCNQ3 subunits carrying the p.N821S variant were indistinguishable from those formed by wild-type KCNQ3 subunits. Finally, the current density of the cells mimicking the double heterozygotic condition for both KCNQ2 and KCNQ3 alleles of the proband was decreased by approximately 25% when compared to cells expressing only wild-type alleles. Collectively, these results suggest that, in the family investigated, the KCNQ2 mutation is responsible for the BFNC phenotype, possibly because of haplo-insufficiency, whereas the KCNQ3 variant is functionally silent, a result compatible with its lack of segregation with the BFNC phenotype.
Nature Genetics, 2013
Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ~500 mil... more Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ~500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms.
Journal of Child Neurology, 2003
It has recently been demonstrated that patients with Angelman&amp... more It has recently been demonstrated that patients with Angelman's syndrome who exhibited a deletion on cytogenetic tests show more severe clinical pictures with drug-resistant epilepsy than patients with Angelman's syndrome not carrying the deletion. To verify if this difference in clinical severity can be attributed to genes for the three γ-aminobutyric acid (GABA)A receptor subunits (GABRB3, GABRA5, GABRG3) located in
Journal of Child Neurology, 2004
Before starting antiepilepsy therapy (T1) and after 1 year (T2), 19 children (7 female) affected ... more Before starting antiepilepsy therapy (T1) and after 1 year (T2), 19 children (7 female) affected by focal or generalized idiopathic epilepsy were considered with the aim of studying attention performance. All of the children received a neurological examination and clinical interview, electroencephalography (EEG) in wakefulness or sleep, and a standardized computerized measure of attention (Conners' Continuous Performance Test). At T1, 21% of the patients showed a specific attention disorder, and their percentage rose to 42% after 1 year, despite complete control of seizures. The prognosis was strongly correlated with (1) the presence of active seizures for a period of over 6 months, (2) the persistence of specific interictal abnormalities on an electroencephalogram at T2, and (3) the presence of emotional and behavioral disorders at the diagnosis of epilepsy. Our results confirm that attention disorders are frequent in children with idiopathic epilepsy. The Conners' Continuous Performance Test has proven useful both for diagnosis and follow-up over time.
Journal of Child Neurology, 2001
Pervasive developmental disorders are characterized by severe, pervasive impairment in several ar... more Pervasive developmental disorders are characterized by severe, pervasive impairment in several areas of development, with distorted communication skills and stereotypical behavior. Pervasive developmental disorders have a heterogeneous etiology related to brain damage, familial affective psychopathology, chromosomal abnormalities, or dysfunction of neuromodulators. Recently, it has been suggested that the GABRB3 gene, located within chromosome 15q11-13, is a candidate for pervasive developmental disorder. In inverted duplicated chromosome 15 syndrome, in which there is a small marker chromosome derived from inversion and duplication of the chromosome 15q11-q13 region, all patients present with pervasive developmental disorder. To further investigate a possible involvement of the gamma-aminobutyric acid (GABA)ergic system in the inverted duplicated chromosome 15 syndrome, we evaluated plasma levels of GABA and diazepam binding inhibitor in 6 patients with inverted duplicated chromosome 15 and in 8 subjects not affected by neurologic disease. Our findings do not seem to support this hypothesis as no significant differences were found in the GABA and diazepam binding inhibitor plasma levels between patients with inverted duplicated chromosome 15 and controls, but we must consider the possibility that a genetic abnormality of the GABA(A) receptor could be present in patients with inverted duplicated chromosome 15 and still not be reflected in an alteration in either GABA or diazepam binding inhibitor levels in plasma.
Developmental Medicine & Child Neurology, 2008
Nucleic Acids Research - NAR, 2005
RNA, 2007
An RNA hairpin structure referred to as the iron-responsive element (IRE) and iron regulatory pro... more An RNA hairpin structure referred to as the iron-responsive element (IRE) and iron regulatory proteins (IRPs) are key players in the control of iron metabolism in animal cells. They regulate translation initiation or mRNA stability, and the IRE is found in a variety of mRNAs, such as those encoding ferritin, transferrin receptor (Tfr), erythroid aminolevulinic acid synthase (eALAS), mitochondrial aconitase (mACO), ferroportin, and divalent metal transporter 1 (DMT1). We have studied the evolution of the IRE by considering all mRNAs previously known to be associated with this structure and by computationally examining its occurrence in a large variety of eukaryotic organisms. More than 100 novel sequences together with ;50 IREs that were previously reported resulted in a comprehensive view of the phylogenetic distribution of this element. A comparison of the different mRNAs shows that the IREs of eALAS and mACO are found in chordates, those of ferroportin and Tfr1 are found in vertebrates, and the IRE of DMT1 is confined to mammals. In contrast, the IRE of ferritin occurs in a majority of metazoa including lower metazoa such as sponges and Nematostella (sea anemone). These findings suggest that the ferritin IRE represents the ancestral version of this type of translational control and that during the evolution of higher animals the IRE structure was adopted by other genes. On the basis of primary sequence comparison between different organisms, we suggest that some of these IREs developed by ''convergent evolution'' through stepwise changes in sequence, rather than by recombination events. 08.
Nucleic Acids Research, 2006
The RNases P and MRP are involved in tRNA and rRNA processing, respectively. Both enzymes in euka... more The RNases P and MRP are involved in tRNA and rRNA processing, respectively. Both enzymes in eukaryotes are composed of an RNA molecule and 9-12 protein subunits. Most of the protein subunits are shared between RNases P and MRP. We have here performed a computational analysis of the protein subunits in a broad range of eukaryotic organisms using profile-based searches and phylogenetic methods. A number of novel homologues were identified, giving rise to a more complete inventory of RNase P/MRP proteins. We present evidence of a relationship between fungal Pop8 and the protein subunit families Rpp14/Pop5 as well as between fungal Pop6 and metazoan Rpp25. These relationships further emphasize a structural and functional similarity between the yeast and human P/MRP complexes. We have also identified novel P and MRP RNAs and analysis of all available sequences revealed a K-turn motif in a large number of these RNAs. We suggest that this motif is a binding site for the Pop3/Rpp38 proteins and we discuss other structural features of the RNA subunit and possible relationships to the protein subunit repertoire.
Nucleic Acids Research, 2005
RNases P and MRP are ribonucleoprotein complexes involved in tRNA and rRNA processing, respective... more RNases P and MRP are ribonucleoprotein complexes involved in tRNA and rRNA processing, respectively. The RNA subunits of these two enzymes are structurally related to each other and play an essential role in the enzymatic reaction. Both of the RNAs have a highly conserved helical region, P4, which is important in the catalytic reaction. We have used a bioinformatics approach based on conserved elements to computationally analyze available genomic sequences of eukaryotic organisms and have identified a large number of novel nuclear RNase P and MRP RNA genes. For MRP RNA for instance, this investigation increases the number of known sequences by a factor of three. We present secondary structure models of many of the predicted RNAs. Although all sequences are able to fold into the consensus secondary structure of P and MRP RNAs, a striking variation in size is observed, ranging from a Nosema locustae MRP RNA of 160 nt to much larger RNAs, e.g. a Plasmodium knowlesi P RNA of 696 nt. The P and MRP RNA genes appear in tandem in some protists, further emphasizing the close evolutionary relationship of these RNAs.
Neurology, 1999
A family is described in which bilateral perisylvian polymicrogyria was present in 6 members of 3... more A family is described in which bilateral perisylvian polymicrogyria was present in 6 members of 3 consecutive generations. Typical anatomic and clinical findings of the syndrome, with a mild phenotype, were present in the 5 affected women from all 3 generations. More severe impairment was observed in the only affected male individual, a boy, in the third generation. Analysis of the pedigree and severity of the phenotype in the affected boy are consistent with transmission of an X-linked dominant trait, although other patterns of inheritance cannot be ruled out with certainty.
Journal of Child Neurology, 2000
A 17-year-old boy with polymorphic simple and complex partial seizures is described. Magnetic res... more A 17-year-old boy with polymorphic simple and complex partial seizures is described. Magnetic resonance imaging revealed a unilateral periventricular nodular heterotopia near the occipital ventricular right horn. Interictal and ictal electroencephalographic recordings showed bilateral specific epileptiform anomalies in the occipital region and asynchronous slow waves in frontal areas. Single photon emission computed tomography documented a reduction in regional cerebral blood flow in an area of the left occipital cortex and a symmetric increase in tracer uptake in the frontal lobes. The neuropsychologic assessment revealed a dysfunction of the frontal associative areas. Data collected led the authors to suspect a more diffuse cortical dysfunction than the nodular heterotopia revealed on magnetic resonance imaging.
Geomicrobiology Journal, 2012
Over the last decade or so, several studies have investigated the formation, mineralogy and micro... more Over the last decade or so, several studies have investigated the formation, mineralogy and microbial composition of iron oxyhydroxides. Here, we focus on the exploration of the microbial community structure of iron oxyhydroxide minerals that often occur in tight association with microbial life, which are referred to as Biogenic Iron Oxyhydroxides (BIOS). BIOS deposits host a wide range of microbial taxa usually found living in the oxic, suboxic and anaerobic interfaces of the biogeosphere. These organisms are responsible for the global cycling of Fe, N, C and S. Near the surface of BIOS mats, O 2 at ambient atmospheric levels rapidly reacts with dissolved Fe(II) to form insoluble Fe(III) minerals. Due to the activity of highly efficient heterotrophic O 2 respirers, BIOS biofilms usually transit from the top to the bottom (within a mm range) into a suboxic zone where microaerophilic iron-oxidizing bacteria thrive, transforming Fe(II) to Fe(III), while generating organic carbon. The bulk of the Fe(III), produced by both biotic and abiotic processes, is precipitated and fixed into a variety of cellular matrices. The resulting iron oxyhydroxides provide highly reactive surfaces responsible for the secondary sequestration of a vast range of trace elements. Given the fact that the mineralogical composition of BIOS is fairly well known, we focus here on the diversity of the microorganisms associated with BIOS deposited over wide geographical scales. This manuscript also presents condensed information that demonstrates that the biogeochemistry of BIOS appears to provide niche-specific conditions that select for similar microbial taxa across different spatial scales. We suggest that globally, these lineages play an important and similar role in BIOS development in the aerobic biogeosphere regardless of the location.
BMC Genomics, 2011
Background: Gene regulation through cis-regulatory elements plays a crucial role in development a... more Background: Gene regulation through cis-regulatory elements plays a crucial role in development and disease. A major aim of the post-genomic era is to be able to read the function of cis-regulatory elements through scrutiny of their DNA sequence. Whilst comparative genomics approaches have identified thousands of putative regulatory elements, our knowledge of their mechanism of action is poor and very little progress has been made in systematically de-coding them. Results: Here, we identify ancient functional signatures within vertebrate conserved non-coding elements (CNEs) through a combination of phylogenetic footprinting and functional assay, using genomic sequence from the sea lamprey as a reference. We uncover a striking enrichment within vertebrate CNEs for conserved binding-site motifs of the Pbx-Hox hetero-dimer. We further show that these predict reporter gene expression in a segment specific manner in the hindbrain and pharyngeal arches during zebrafish development.
Minerva pediatrica, 1998
In this article, the interrelations between biological and emotional factors in learning disabili... more In this article, the interrelations between biological and emotional factors in learning disabilities in Turner's syndrome are studied. This is a transversal study with a 18 months neuropsychiatric follow-up. Five girls with the syndrome, aged between 12 and 22 years have been studied using Wechsler scales (WISC-R and WAIS), individual interviews and psychodiagnostic tests, to describe both their cognitive profile and psychological traits. The intelligence tests show selective impairments in visuo-spatial area, with lower score on performance IQ, especially in the sub-tests "Block Design" and "Object Assembly"; individual interviews and psychodiagnostic tests show signs of psychological disease, often consequences of this syndrome, and only in one girl with an associated diagnosis of psychosis. Psychological and environmental factors, as well as the genetics, may play an important role in the impairment of cognitive abilities, and the neuropsychological aspec...
Pediatrics, 1996
This report presents the case of a previously healthy 6-year-old girl who had an ischemic injury ... more This report presents the case of a previously healthy 6-year-old girl who had an ischemic injury corresponding to the territory perfused by the lateral branches of the lenticulostriate arteries of the middle cerebral artery. Stroke in childhood is rare, and the specific causes are identified in only half the cases. Our patient was carefully studied for any hereditary or acquired risk factors for stroke, but we found only one, an endoscopic injection of Teflon performed 1 year before to correct vesicoureteral reflux. This suggests the risk of potential migration of Teflon particles to the brain, where they can block the microcirculation.
ISSLS 88., International Symposium on Subscriber Loops and Services, 1988
This paper describes the tranceiver developed in Italy for the ISDN pilot project and concentrate... more This paper describes the tranceiver developed in Italy for the ISDN pilot project and concentrate on the reasons why this system has been chosen. Moreover laboratory and field trial results are reported.
Seizure, 2010
To study neuropsychological functions in children with idiopathic epilepsy at onset of treatment ... more To study neuropsychological functions in children with idiopathic epilepsy at onset of treatment and after 1 year of therapy and to identify factors associated with cognitive impairment. 43 Subjects aged 5.2-16.9 years with newly diagnosed idiopathic epilepsy were enrolled and started treatment with valproate or carbamazepine. At admission and after 12 months, all patients underwent clinical examinations, the Child Behavioural Checklist, EEG and a neuropsychological test battery. The results of each test were correlated to demographic, clinical, electrophysiological and therapeutic variables. Except for attention, all neuropsychological functions were normal at admission and after 12 months. An improvement with time was noted for memory (p<0.05) and logical-executive functions (p<0.01). Attentive deficit was worse at 12 months (53.5% vs. 32.6%). Low socio-economic level and emotional and behavioural disturbances were the only factors negatively correlated to intelligence, memory and attention. Compared to valproate, carbamazepine was most commonly implicated. Idiopathic epilepsy can affect attention, even before starting treatment. Emotional and behavioural difficulties and a low socio-economical status are associated with cognitive impairment.
Pediatric Neurology, 2001
Neurogenetics, 2005
Benign familial neonatal convulsion (BFNC) is a rare autosomal dominant disorder caused by mutati... more Benign familial neonatal convulsion (BFNC) is a rare autosomal dominant disorder caused by mutations in KCNQ2 and KCNQ3, two genes encoding for potassium channel subunits. A large family with nine members affected by BFNC is described in the present study. All affected members of this family carry a novel deletion/insertion mutation in the KCNQ2 gene (c.761_770del10insA), which determines a premature truncation of the protein. In addition, in the family of the proposita's father, a novel sequence variant (c.2687A> G) in KCNQ3 leading to the p.N821S amino acid change was detected. When heterologously expressed in Chinese hamster ovary cells, KCNQ2 subunits carrying the mutation failed to form functional potassium channels in homomeric configuration and did not affect channels formed by KCNQ2 and/or KCNQ3 subunits. On the other hand, homomeric and heteromeric potassium channels formed by KCNQ3 subunits carrying the p.N821S variant were indistinguishable from those formed by wild-type KCNQ3 subunits. Finally, the current density of the cells mimicking the double heterozygotic condition for both KCNQ2 and KCNQ3 alleles of the proband was decreased by approximately 25% when compared to cells expressing only wild-type alleles. Collectively, these results suggest that, in the family investigated, the KCNQ2 mutation is responsible for the BFNC phenotype, possibly because of haplo-insufficiency, whereas the KCNQ3 variant is functionally silent, a result compatible with its lack of segregation with the BFNC phenotype.
Nature Genetics, 2013
Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ~500 mil... more Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ~500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms.
Journal of Child Neurology, 2003
It has recently been demonstrated that patients with Angelman&amp... more It has recently been demonstrated that patients with Angelman's syndrome who exhibited a deletion on cytogenetic tests show more severe clinical pictures with drug-resistant epilepsy than patients with Angelman's syndrome not carrying the deletion. To verify if this difference in clinical severity can be attributed to genes for the three γ-aminobutyric acid (GABA)A receptor subunits (GABRB3, GABRA5, GABRG3) located in
Journal of Child Neurology, 2004
Before starting antiepilepsy therapy (T1) and after 1 year (T2), 19 children (7 female) affected ... more Before starting antiepilepsy therapy (T1) and after 1 year (T2), 19 children (7 female) affected by focal or generalized idiopathic epilepsy were considered with the aim of studying attention performance. All of the children received a neurological examination and clinical interview, electroencephalography (EEG) in wakefulness or sleep, and a standardized computerized measure of attention (Conners' Continuous Performance Test). At T1, 21% of the patients showed a specific attention disorder, and their percentage rose to 42% after 1 year, despite complete control of seizures. The prognosis was strongly correlated with (1) the presence of active seizures for a period of over 6 months, (2) the persistence of specific interictal abnormalities on an electroencephalogram at T2, and (3) the presence of emotional and behavioral disorders at the diagnosis of epilepsy. Our results confirm that attention disorders are frequent in children with idiopathic epilepsy. The Conners' Continuous Performance Test has proven useful both for diagnosis and follow-up over time.
Journal of Child Neurology, 2001
Pervasive developmental disorders are characterized by severe, pervasive impairment in several ar... more Pervasive developmental disorders are characterized by severe, pervasive impairment in several areas of development, with distorted communication skills and stereotypical behavior. Pervasive developmental disorders have a heterogeneous etiology related to brain damage, familial affective psychopathology, chromosomal abnormalities, or dysfunction of neuromodulators. Recently, it has been suggested that the GABRB3 gene, located within chromosome 15q11-13, is a candidate for pervasive developmental disorder. In inverted duplicated chromosome 15 syndrome, in which there is a small marker chromosome derived from inversion and duplication of the chromosome 15q11-q13 region, all patients present with pervasive developmental disorder. To further investigate a possible involvement of the gamma-aminobutyric acid (GABA)ergic system in the inverted duplicated chromosome 15 syndrome, we evaluated plasma levels of GABA and diazepam binding inhibitor in 6 patients with inverted duplicated chromosome 15 and in 8 subjects not affected by neurologic disease. Our findings do not seem to support this hypothesis as no significant differences were found in the GABA and diazepam binding inhibitor plasma levels between patients with inverted duplicated chromosome 15 and controls, but we must consider the possibility that a genetic abnormality of the GABA(A) receptor could be present in patients with inverted duplicated chromosome 15 and still not be reflected in an alteration in either GABA or diazepam binding inhibitor levels in plasma.