Yield of array-CGH analysis in Tunisian children with autism spectrum disorder

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic underpinnings. Microarray-based comparative genomic hybridization (aCGH) technology has been proposed as a first-level test in the genetic diagnosis of ASD and of neurodevelopmental disorders in general. Methods: We performed aCGH on 98 Tunisian children (83 boys and 15 girls) diagnosed with ASD according to DSM-IV criteria. Results: “Pathogenic” or “likely pathogenic” copy number variants (CNVs) were detected in 11 (11.2%) patients, CNVs of “uncertain clinical significance” in 26 (26.5%), “likely benign” or “benign” CNVs were found in 37 (37.8%) and 24 (24.5%) patients, respectively. Gene set enrichment analysis involving genes spanning rare “pathogenic,” “likely pathogenic,” or “uncertain clinical significance” CNVs, as well as SFARI database “autism genes” in common CNVs, detected eight neuronal Gene Ontology classes among the top 10 most significant, including synapse, neuron differentiation, synaptic signaling, neurogenesis, and others. Similar results were obtained performing g: Profiler analysis. Neither transcriptional regulation nor immune pathways reached significance. Conclusions: aCGH confirms its sizable diagnostic yield in a novel sample of autistic children from North Africa. Recruitment of additional families is under way, to verify whether genetic contributions to ASD in the Tunisian population, differently from other ethnic groups, may involve primarily neuronal genes, more than transcriptional regulation and immune-related pathways

Medicinal plants and their bacterial microbiota: A review on antimicrobial compounds production for plant and human health

Medicinal plants (MPs) have been used since antiquity in traditional and popular medicine, and they represent a very important source of bioactive molecules, including antibiotic, antiviral, and antifungal molecules. Such compounds are often of plant origin, but in some cases, an origin or a modification from plant microbiota has been shown. Actually, the research continues to report the production of bioactive molecules by plants, but the role of plant–endophytic interaction is emerging. Classic examples are mainly concerned with fungal endophytes; however, it has been recently shown that bacterial endophytes can also play an important role in influencing the plant metabolism related to the synthesis of bioactive compounds. In spite of this, a deep investigation on the power of MP bacterial endophytes is lacking. Here, an overview of the studies on MP bacterial microbiota and its role in the production of plant antimicrobial compounds contributing to prime host defense system and representing a huge resource for biotech and therapeutic applications is provided

Medicinal Plants and Their Bacterial Microbiota: A Review on Antimicrobial Compounds Production for Plant and Human Health

Medicinal plants (MPs) have been used since antiquity in traditional and popular medicine, and they represent a very important source of bioactive molecules, including antibiotic, antiviral, and antifungal molecules. Such compounds are often of plant origin, but in some cases, an origin or a modification from plant microbiota has been shown. Actually, the research continues to report the production of bioactive molecules by plants, but the role of plant–endophytic interaction is emerging. Classic examples are mainly concerned with fungal endophytes; however, it has been recently shown that bacterial endophytes can also play an important role in influencing the plant metabolism related to the synthesis of bioactive compounds. In spite of this, a deep investigation on the power of MP bacterial endophytes is lacking. Here, an overview of the studies on MP bacterial microbiota and its role in the production of plant antimicrobial compounds contributing to prime host defense system and representing a huge resource for biotech and therapeutic applications is provided

Phenotypic spectrum of NRXN1 mono- and bi-allelic deficiency: A systematic review

Neurexins are presynaptic cell adhesion molecules critically involved in synaptogenesis and vesicular neurotransmitter release. They are encoded by three genes (NRXN1-3), each yielding a longer alpha (α) and a shorter beta (β) transcript. Deletions spanning the promoter and the initial exons of the NRXN1 gene, located in chromosome 2p16.3, are associated with a variety of neurodevelopmental, psychiatric, neurological and neuropsychological phenotypes. We have performed a systematic review to define (a) the clinical phenotypes most associated with mono-allelic exonic NRXN1 deletions, and (b) the phenotypic features of NRXN1 bi-allelic deficiency due to compound heterozygous deletions/mutations. Clinically, three major conclusions can be drawn: (a) incomplete penetrance and pleiotropy do not allow reliable predictions of clinical outcome following prenatal detection of mono-allelic exonic NRXN1 deletions. Newborn carriers should undergo periodic neuro-behavioral observations for the timely detection of warning signs and the prescription of early behavioral intervention; (b) the presence of additional independent genetic risk factors should always be sought, as they may influence prognosis; (c) children with exonic NRXN1 deletions displaying early-onset, severe psychomotor delay in the context of a Pitt-Hopkins-like syndrome 2 phenotype, should undergo DNA sequencing of the spared NRXN1 allele in search for mutations or very small insertions/deletions

Diagnostic yield and clinical impact of chromosomal microarray analysis in autism spectrum disorder

Background: Autism spectrum disorder (ASD) is characterized by high heritability estimates and recurrence rates; its genetic underpinnings are very heterogeneous and include variable combinations of common and rare variants. Array-comparative genomic hybridization (aCGH) offers significant sensitivity for the identification of copy number variants (CNVs), which can act as susceptibility or causal factors for ASD. Methods: The aim of this study was to evaluate both diagnostic yield and clinical impact of aCGH in 329 ASD patients of Italian descent. Results: Pathogenic/likely pathogenic CNVs were identified in 50/329 (15.2%) patients, whereas 89/329 (27.1%) carry variants of uncertain significance. The 10 most enriched gene sets identified by Gene Ontology Enrichment Analysis are primarily involved in neuronal function and synaptic connectivity. In 13/50 (26.0%) patients with pathogenic/likely pathogenic CNVs, the outcome of array-CGH led to the request of 25 additional medical exams which would not have otherwise been prescribed, mainly including brain MRI, EEG, EKG, and/or cardiac ultrasound. A positive outcome was obtained in 12/25 (48.0%) of these additional tests. Conclusions: This study confirms the satisfactory diagnostic yield of aCGH, underscoring its potential for better, more in-depth care of children with autism when genetic results are analyzed also with a focus on patient management

9q34.3 microduplications lead to neurodevelopmental disorders through EHMT1 overexpression

Both copy number losses and gains occur within subtelomeric 9q34 region without common breakpoints. The microdeletions cause Kleefstra syndrome (KS), whose responsible gene is EHMT1. A 9q34 duplication syndrome (9q34 DS) had been reported in literature, but it has never been characterized by a detailed molecular analysis of the gene content and endpoints. To the best of our knowledge, we report on the first patient carrying the smallest 9q34.3 duplication containing EHMT1 as the only relevant gene. We compared him with 21 reported patients described here as carrying 9q34.3 duplications encompassing the entire gene and extending within ~\u20093 Mb. By surveying the available clinical and molecular cytogenetic data, we were able to discover that similar neurodevelopmental disorders (NDDs) were shared by patient carriers of even very differently sized duplications. Moreover, some facial features of the 9q34 DS were more represented than those of KS. However, an accurate in silico analysis of the genes mapped in all the duplications allowed us to support EHMT1 as being sufficient to cause a NDD phenotype. Wider patient cohorts are needed to ascertain whether the rearrangements have full causative role or simply confer the susceptibility to NDDs and possibly to identify the cognitive and behavioral profile associated with the increased dosage of EHMT1

Assessing the impact of a construction virtual reality game on design review skills of construction student

Being able to perform an effective design review is a fundamental skill that every design or construction student should possess. Performing a design review requires critical thinking, analysis, and communication skills. To support the acquisition of these skills, this study investigated the impact of a virtual reality game, the design review simulator (DRS), in a classroom environment. To assess the impact of the game, the authors performed a crossover experiment with 120 students. The students were split into groups and were asked to perform design reviews in two treatment conditions, 2D drawings or the DRS. A knowledge test was administered at the end of different treatments to collect quantitative data on the students’ performance. Results from this research indicate that the DRS supported students in identifying a higher number of design mistakes. Furthermore, students that played with the DRS after performing 2D drawings reviews scored significantly higher in the knowledge test. The research results contribute to the growing knowledge base on the implementation of VR in the classroom and in supporting students in meeting learning objectives related to design review skills. In particular, the research illustrated that the benefits of VR found in the construction industry in terms of improved communication, user involvement, and feedback collection could be translated into the classroom environment

A novel nonsense ATP7A pathogenic variant in a family exhibiting a variable occipital horn syndrome phenotype

We report on a family with occipital horn syndrome (OHS) diagnosed in the proband's late fifties. A novel ATP7A pathogenic variant (c.4222A > T, p.(Lys1408*)), representing the first nonsense variant and the second late truncation causing OHS rather than classic Menkes disease, was found to segregate in the family. The predicted maintenance of transmembrane domains is consistent with a residual protein activity, which may explain the mild clinical presentation

The cultivable bacterial microbiota associated to the medicinal plant Origanum vulgare L.: from antibiotic resistance to growth-inhibitory properties

The insurgence of antibiotic resistance and emergence of multidrug-resistant (MDR) pathogens prioritize research to discover new antimicrobials. In this context, medicinal plants produce bioactive compounds of pharmacological interest: some extracts have antimicrobial properties that can contrast different pathogens. For such a purpose, Origanum vulgare L. (Lamiaceae family) is a medicinal aromatic plant, whose essential oil (EO) is recognized for its antiseptic, antimicrobial and antiviral activities. The cultivable bacteria from different compartments (i.e., flower, leaf, stem and soil) were isolated in order to: (i) characterize the bacterial microbiota associated to the plant, determining the forces responsible for the structuring of its composition (by evaluation of cross inhibition); (ii) investigate if bacterial endophytes demonstrate antimicrobial activities against human pathogens. A pool of plants belonging to O. vulgare species was collected and the specimen chemotype was defined by hydrodistillation of its essential oil. The isolation of plant associated bacteria was performed from the four compartments. Microbiota was further characterized through a culture-independent approach and next-generation sequencing analysis, as well. Isolates were molecularly typed by Random Amplified Polymorphic DNA (RAPD) profiling and taxonomically assigned by 16S rRNA gene sequencing. Antibiotic resistance profiles of isolates and pairwise cross-inhibition of isolates on agar plates (i.e., antagonistic interactions) were also assessed. High level of diversity of bacterial isolates was detected at both genus and strain level in all different compartments. Most strains were tolerant against common antibiotics; moreover, they produced antagonistic patterns of interactions mainly with strains from different compartments with respect to that of original isolation. Strains that exhibited high inhibitory properties were further tested against human pathogens, revealing a strong capacity to inhibit the growth of strains resistant to several antibiotics. In conclusion, this study regarded the characterization of O. vulgare L. chemotype and of the bacterial communities associated to this medicinal plant, also allowing the evaluation of antibiotic resistance and antagonistic interactions. This study provided the bases for further analyses on the possible involvement of endophytic bacteria in the production of antimicrobial molecules that could have an important role in clinical and therapeutic applications

Tunability experiments at the FERMI@Elettra free-electron laser

FERMI@Elettra is a free electron-laser (FEL)-based user facility that, after two years of commissioning, started preliminary users' dedicated runs in 2011. At variance with other FEL user facilities, FERMI@Elettra has been designed to deliver improved spectral stability and longitudinal coherence. The adopted scheme, which uses an external laser to initiate the FEL process, has been demonstrated to be capable of generating FEL pulses close to the Fourier transform limit. We report on the first instance of FEL wavelength tuning, both in a narrow and in a large spectral range (fine- and coarse-tuning). We also report on two different experiments that have been performed exploiting such FEL tuning. We used fine-tuning to scan across the 1s–4p resonance in He atoms, at ≈23.74 eV (52.2 nm), detecting both UV–visible fluorescence (4p–2s, 400 nm) and EUV fluorescence (4p–1s, 52.2 nm). We used coarse-tuning to scan the M4,5 absorption edge of Ge (∼29.5 eV) in the wavelength region 30–60 nm, measured in transmission geometry with a thermopile positioned on the rear side of a Ge thin foil