PH-Controlled Assembly of DNA Tiles

We demonstrate a strategy to trigger and finely control the assembly of supramolecular DNA nanostructures with pH. Control is achieved via a rationally designed strand displacement circuit that responds to pH and activates a downstream DNA tile self-assembly process. We observe that the DNA structures form under neutral/basic conditions, while the self-assembly process is suppressed under acidic conditions. The strategy presented here demonstrates a modular approach toward building systems capable of processing biochemical inputs and finely controlling the assembly of DNA-based nanostructures under isothermal conditions. In particular, the presented architecture is relevant for the development of complex DNA devices able to sense and respond to molecular markers associated with abnormal metabolism

Folding-upon-binding and signal-on electrochemical DNA sensor with high affinity and specificity

Here we investigate a novel signal-on electrochemical DNA sensor based on the use of a clamp-like DNA probe that binds a complementary target sequence through two distinct and sequential events, which lead to the formation of a triplex DNA structure. We demonstrate that this target-binding mechanism can improve both the affinity and specificity of recognition as opposed to classic probes solely based on Watson-Crick recognition. By using electrochemical signaling to report the conformational change, we demonstrate a signal-on E-DNA sensor with up to 400% signal gain upon target binding. Moreover, we were able to detect with nanomolar affinity a perfectly matched target as short as 10 bases (K(D) = 0.39 nM). Finally, thanks to the molecular "double-check" provided by the concomitant Watson-Crick and Hoogsteen base pairings involved in target recognition, our sensor provides excellent discrimination efficiency toward a single-base mismatched target

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

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

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

Bridging pro-inflammatory signals, synaptic transmission and protection in spinal explants in vitro

Multiple sclerosis is characterized by tissue atrophy involving the brain and the spinal cord, where reactive inflammation contributes to the neurodegenerative processes. Recently, the presence of synapse alterations induced by the inflammatory responses was suggested by experimental and clinical observations, in experimental autoimmune encephalomyelitis mouse model and in patients, respectively. Further knowledge on the interplay between pro-inflammatory agents, neuroglia and synaptic dysfunction is crucial to the design of unconventional protective molecules. Here we report the effects, on spinal cord circuits, of a cytokine cocktail that partly mimics the signature of T lymphocytes sub population Th1. In embryonic mouse spinal organ-cultures, containing neuronal cells and neuroglia, cytokines induced inflammatory responses accompanied by a significant increase in spontaneous synaptic activity. We suggest that cytokines specifically altered signal integration in spinal networks by speeding the decay of GABAA responses. This hypothesis is supported by the finding that synapse protection by a non-peptidic NGF mimetic molecule prevented both the changes in the time course of GABA events and in network activity that were left unchanged by the cytokine production from astrocytes and microglia present in the cultured tissue. In conclusion, we developed an important tool for the study of synaptic alterations induced by inflammation, that takes into account the role of neuronal and not neuronal resident cells

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

Numbers in the Blind's “Eye”

Background: Although lacking visual experience with numerosities, recent evidence shows that the blind perform similarly to sighted persons on numerical comparison or parity judgement tasks. In particular, on tasks presented in the auditory modality, the blind surprisingly show the same effect that appears in sighted persons, demonstrating that numbers are represented through a spatial code, i.e. the Spatial-Numerical Association of Response Codes (SNARC) effect. But, if this is the case, how is this numerical spatial representation processed in the brain of the blind? Principal Findings: Here we report that, although blind and sighted people have similarly organized numerical representations, the attentional shifts generated by numbers have different electrophysiological correlates (sensorial N100 in the sighted and cognitive P300 in the blind). Conclusions: These results highlight possible differences in the use of spatial representations acquired through modalities other than vision in the blind population