Genomic and epigenetic evidence for oxytocin receptor deficiency in autism

<p>Abstract</p> <p>Background</p> <p>Autism comprises a spectrum of behavioral and cognitive disturbances of childhood development and is known to be highly heritable. Although numerous approaches have been used to identify genes implicated in the development of autism, less than 10% of autism cases have been attributed to single gene disorders.</p> <p>Methods</p> <p>We describe the use of high-resolution genome-wide tilepath microarrays and comparative genomic hybridization to identify copy number variants within 119 probands from multiplex autism families. We next carried out DNA methylation analysis by bisulfite sequencing in a proband and his family, expanding this analysis to methylation analysis of peripheral blood and temporal cortex DNA of autism cases and matched controls from independent datasets. We also assessed oxytocin receptor (OXTR) gene expression within the temporal cortex tissue by quantitative real-time polymerase chain reaction (PCR).</p> <p>Results</p> <p>Our analysis revealed a genomic deletion containing the oxytocin receptor gene, <it>OXTR </it>(MIM accession no.: 167055), previously implicated in autism, was present in an autism proband and his mother who exhibits symptoms of obsessive-compulsive disorder. The proband's affected sibling did not harbor this deletion but instead may exhibit epigenetic misregulation of this gene through aberrant gene silencing by DNA methylation. Further DNA methylation analysis of the CpG island known to regulate <it>OXTR </it>expression identified several CpG dinucleotides that show independent statistically significant increases in the DNA methylation status in the peripheral blood cells and temporal cortex in independent datasets of individuals with autism as compared to control samples. Associated with the increase in methylation of these CpG dinucleotides is our finding that <it>OXTR </it>mRNA showed decreased expression in the temporal cortex tissue of autism cases matched for age and sex compared to controls.</p> <p>Conclusion</p> <p>Together, these data provide further evidence for the role of OXTR and the oxytocin signaling pathway in the etiology of autism and, for the first time, implicate the epigenetic regulation of <it>OXTR </it>in the development of the disorder.</p> <p>See the related commentary by Gurrieri and Neri: <url>http://www.biomedcentral.com/1741-7015/7/63</url></p

A multifrequency and multisensor approach for the study and the restoration of monuments: the case of the Cathedral of Matera

In this paper we propose an integrated approach to diagnostic prospecting applied to the cathedral of Matera, in Southern Italy. In particular, we have performed both an ultrasonic tomography and a high frequency GPR prospecting on some pillars of the Church to investigate about possible structural yielding and a GPR prospecting at lower frequencies on the floor, where also a linear inversion algorithm has been applied to the data

Recurrent intussusception caused by submucosal, heterotopic gastric mucosa in the terminal ileum

Isolated, heterotopic gastric mucosa (HGM) can be a rare, pathologic leading point for intestinal intussusception in pediatric age. Affected children often experience recurrent episodes of intussusception, sometimes with delay in diagnosis and more than one surgery, because of difficulty in clear diagnosis and identification of HGM. Intraoperative findings of isolated HGM, as reported in literature, are visible or palpable lesions, protruding into the intestinal lumen. We describe the case of a 4 years old boy with recurrent intussusception, caused by a very small islet of ileal, isolated HGM, entirely developing in the submucosal layer and with a normal overlying mucosa. The difficulties in its diagnosis and treatment are described and the role of 99mTc pertechnetate scan and ultrasound are discussed. Keywords: Heterotopic gastric mucosa, Intussusception, 99mTc pertechnetate sca

Integrated Techniques for Analysis and Monitoring of Historical Monuments: the case of S.Giovanni al Sepolcro in Brindisi (Southern Italy)

In this paper, an integrated prospecting performed in the atypical Romanesque church of San Giovanni al Sepolcro in Brindisi, southern Italy is presented. Ground-penetrating radar (GPR) and ultrasonic data have been gathered on the circular load-bearing colonnade of the monument. Here the results achieved on two of the columns are shown. The GPR data have been processed and have allowed to identify and focus the medieval internal metallic hinges joining the stone trunks in one of the columns and some reinforcement rebars in the other (and probably also the residual track of a restored fracture). The ultrasonic data have allowed to monitor the state of compactness and to assess the effectiveness of reinforcement interventions on the columns

Prenatal and postnatal urinary tract dilation: advantages of a standardized ultrasound definition and classification

Urinary tract dilatation is identified sonographically in 1-2% of fetuses and reflects a spectrum of possible nephro-uropathies. There is significant variability in the clinical management of individuals with prenatal urinary tract dilatation to postnatal urinary pathologies, because of a lack of consensus and uniformity in defining and classifying urinary tract dilation. Ultrasonography is the first step to screen and diagnose kidneys and the urinary tract diseases of the children. The need for a correct ultrasound approach led to the realization of algorithms aimed at standardizing the procedures, the parameters and the classifications. Our objective was to highlight the strengths of the Classification of Urinary Tract Dilation (UTD) suggested by the Consensus Conference which took place in 2014 with the participation of eight Scientific Societies and was subsequently published on the Journal of Pediatric Urology. Before its spread out, the definition of UTD was not uniform and the ultrasonographic measurements were not clearly defined, leading to misunderstandings between physicians. The Classification by the Consensus Conference of 2014 represents a revolutionary tool for the diagnosis and management of UTD. Furthermore, the parameters suggested by the classification proposed are applicable for both prenatal and postnatal classification, ensuring a correct follow-up in children with UTD whose diagnosis had been already made during pregnancy

Headache and Comorbidity in Children and Adolescents

Headache is one of the most common neurological symptom reported in childhood and adolescence, leading to high levels of school absences and being associated with several comorbid conditions, particularly in neurological, psychiatric and cardiovascular systems. Neurological and psychiatric disorders, that are associated with migraine, are mainly depression, anxiety disorders, epilepsy and sleep disorders, ADHD and Tourette syndrome. It also has been shown an association with atopic disease and cardiovascular disease, especially ischemic stroke and patent foramen ovale (PFO)

Benzodiazepine scaffold as drug-like molecular simplification of FR235222: A chemical tool for exploring HDAC inhibition

Synthesis, computational study and biological evaluation of peptidomimetic analogues of FR235222 (3), a natural immunosuppressant and HDAC inhibitor, have been reported. These new compounds, bearing α-hydroxyketone moiety, as more stable zinc binding group (ZBG), were evaluated in vitro as HDAC inhibitors against the human HDACs isoforms 1-9 and in cellular antiproliferative assays on U937 human leukemia cell line. The 1,4-benzodiazepin-2,5- dione (BDZ), capping group and the natural ZBG, (S,R)-2-amino-9-hydroxy-8- oxodecanoic acid (Ahoda), were evaluated in order to probe HDAC inhibition and/or paralogue selectivity. Some of the new derivatives showed an interesting activity against a number of HDAC isozymes. The observed activity profile was rationalized by a computational assisted SAR study, in order to understand how the BDZ classes interact with the enzyme into the catalytic pocket. Despite its poor solubility, compound 17b showed significant antiproliferative profile and HDAC inhibition activity. In order to assess how the solubility issue could have affected the biological outcome, bioassay conditions were reproduced and quantification of precipitated particulate material was evaluated by turbidimetric and NMR studies together with physicochemical descriptors prediction. Thus, BDZ 17b has been chosen to be promising lead compounds for further optimization, in order to elucidate molecule-enzyme surface recognition