Gut mobilization improves behavioral symptoms and modulates urinary p-cresol in chronically constipated autistic children: A prospective study

Chronic constipation is common among children with ASD and is associated with more severe hyperactivity, anxiety, irritability, and repetitive behaviors. Young autistic children with chronic constipation display higher urinary, and foecal concentrations of p-cresol, an aromatic compound produced by gut bacteria, known to negatively affect brain function. Acute p-cresol administration to BTBR mice enhances anxiety, hyperactivity and stereotypic behaviors, while blunting social interaction. This study was undertaken to prospectively assess the behavioral effects of gut mobilization in young autistic children with chronic constipation, and to verify their possible correlation with urinary p-cresol. To this aim, 21 chronically constipated autistic children 2–8 years old were evaluated before (T0), 1 month (T1), and 6 months (T2) after intestinal mobilization, recording Bristol stool scale scores, urinary p-cresol concentrations, and behavioral scores for social interaction deficits, stereotypic behaviors, anxiety, and hyperactivity. Gut mobilization yielded a progressive and highly significant decrease in all behavioral symptoms over the 6-month study period. Urinary p-cresol levels displayed variable trends not significantly correlated with changes in behavioral parameters, mainly increasing at T1 and decreasing at T2. These results support gut mobilization as a simple strategy to ameliorate ASD symptoms, as well as comorbid anxiety and hyperactivity, in chronically constipated children. Variation in p-cresol absorption seemingly provides limited contributions, if any, to these behavioral changes. Further research will be needed to address the relative role of reduced abdominal discomfort following mobilization, as compared to specific modifications in microbiome composition and in gut bacteria-derived neuroactive compounds

Hypermethioninemia in Campania: Results from 10 years of newborn screening

In the last years tandem mass spectrometry (MS/MS) has become a leading technology used for neonatal screening purposes. Newborn screening by MS/MS on dried blood spot samples (DBS) has one of its items in methionine levels: the knowledge of this parameter allows the identification of infant affected by homocystinuria (cystathionine β-synthase, CBS, deficiency) but can also lead, as side effect, to identify cases of methionine adenosyltransferase (MAT) type I/III deficiency. We started an expanded newborn screening for inborn errors of metabolism in Campania region in 2007. Here we report our ten years experience on expanded newborn screening in identifying patients affected by hypermethioninemia. During this period we screened approximately 77,000 infants and identified two cases: one case of classical homocystinuria and one patient affected by defect of MAT I/III. In this paper we describe these patients and their biochemical follow-up and review the literature concerning worldwide newborn screening reports on incidence of CBS and MAT deficiency

Virus-resistant transgenic plants : benefits, risks and biosafety

Virus-resistant transgenic plants (VRTPs) were first reported two decades ago. However, since the early 1990s, concerns have been raised regarding the potential environmental impact of VRTPs, in particular those which express viral genes. One hypothetical risk is that viral sequences expressed from the transgene could recombine with the genome of a non-target virus, and thus lead to emergence of a novel virus. Recombination between viral RNA and transgene mRNA has already been shown to occur for several viruses under conditions of high selection pressure: when the inoculated virus has been disabled by a genomic deletion. Recent work carried out by the Virology Group at Ca\u2019Tron has focused specifically on cucumoviruses (family Bromoviridae), a genus where viral recombinants have been detected both in the field and laboratory. A sensitive and robust RT-PCR method has been optimized to detect viral recombinants both under conditions of high and low selection pressure, where the virus inoculated is either disabled or wild-type, respectively. Results, under conditions of low selection pressure, showed that those recombinants found in tobacco plants infected with two different cucumoviruses were comparable to those found in tobacco transgenic for part of one cucumovirus genome infected with another cucumovirus. It was therefore concluded that in this specific case novel viral recombinants are not expected to appear. Conditions of high selection pressure for the analysis of recombinants were produced by engineering mutants with six nucleotide deletions at various points along the 3\u2019 non-coding region of Cucumber mosaic virus (CMV) strain I17F. Results so far show an increase in the number of observed recombination sites compared to the low selection pressure study. Detailed studies on and around one of the principal recombination hotspots found (nt 1902) have shown it to be directly involved in the production of a short subgenomic RNA known as RNA5. The RNA structure around hotspot nt 1902 has been determined both in vitro and in silico, with phylogenetic and recombinant analyses identifying its putative role in cucumovirus evolution. It is intended that this study should eventually provide a model for assisting researchers in designing safer viral transgenes, while improving our understanding of the mechanism(s) involved virus RNA recombination, and therefore evolution

Evaluation of the risks that recombination in transgenic plants expressing a viral coat protein gene would lead to the emergence of novel viruses

The development of virus-resistant transgenic plants was one of the early success stories of plant biotechnology. In nearly all cases, resistance has been obtained by expression by the transgenic plant of part of the genome of the target virus, most often a gene coding for the viral coat protein. However, since the early 1990s, there has been concern that these plants could be the source of new viruses. This is because it is well known that viruses exchange genetic information by the means of recombination, and that recombination is an important element contributing to virus evolution and the emergence of viral diseases. But in addition, recombination has also been described in virus-resistant transgenic plants, which in this case occurs between the mRNA of the viral transgene and the RNA of the genome of a virus related to the target virus. For this reason, our recent research has focused on the potential epidemiological impact of recombination in transgenic plants

Evaluation of the risks that recombination in transgenic plants expressing a viral coat protein gene would lead to the emergence of novel viruses

The development of virus-resistant transgenic plants was one of the early success stories of plant biotechnology. In nearly all cases, resistance has been obtained by expression by the transgenic plant of part of the genome of the target virus, most often a gene coding for the viral coat protein. However, since the early 1990s, there has been concern that these plants could be the source of new viruses. This is because it is well known that viruses exchange genetic information by the means of recombination, and that recombination is an important element contributing to virus evolution and the emergence of viral diseases. But in addition, recombination has also been described in virus-resistant transgenic plants, which in this case occurs between the mRNA of the viral transgene and the RNA of the genome of a virus related to the target virus. For this reason, our recent research has focused on the potential epidemiological impact of recombination in transgenic plants

A dual role for Tbx1 in cardiac lymphangiogenesis through genetic interaction with Vegfr3

The transcription factor TBX1 is the major gene implicated in 22q11.2 deletion syndrome (22q11.2DS). The complex clinical phenotype includes vascular anomalies and a recent report presented new cases of primary lymphedema in 22q11.2DS patients. We have previously shown that TBX1 is required for systemic lymphatic vessel development in prenatal mice and it is critical for their survival postnatally. Using loss-of-function genetics and transgenesis in the mouse, we show here a strong genetic interaction between Tbx1 and Vegfr3 in cardiac lymphangiogenesis. Intriguingly, we found that different aspects of the cardiac lymphatic phenotype in Tbx1-Vegfr3 compound heterozygotes were regulated independently by the two genes, with Tbx1 primarily regulating vessel numbers and Vegfr3 vessel morphology. Consistent with this observation, Tbx1Cre-activated expression of a Vegfr3 transgene rescued partially the cardiac lymphatic abnormalities in compound heterozygotes. Through time-controlled genetic experiments, we show that Tbx1 is activated and required in cardiac lymphatic endothelial cell (LEC) progenitors between E10.5 and E11.5. Furthermore, we found that it is also required later in development for the growth of the cardiac lymphatics. Finally, our study revealed a differential sensitivity between ventral and dorsal cardiac lymphatics to the effects of altered Tbx1 and Vegfr3 gene dosage, and we show that this likely results from an earlier requirement for Tbx1 in ventral cardiac LEC progenitors