Neural cell adhesion molecule-mediated fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex

GABAergic basket interneurons form perisomatic synapses, which are essential for regulating neural networks, and their alterations are linked to various cognitive dysfunction. Maturation of basket synapses in postnatal cortex is activity dependent. In particular, activity-dependent downregulation of polysialiac acid carried by the neural cell adhesion molecule (NCAM) regulates the timing of their maturation. Whether and how NCAM per se affects GABAergic synapse development is unknown. Using single-cell genetics to knock out NCAM in individual basket interneurons in mouse cortical slice cultures, at specific developmental time periods, we found that NCAM loss during perisomatic synapse formation impairs the process of basket cell axonal branching and bouton formation. However, loss of NCAM once the synapses are already formed did not show any effect. We further show that NCAM120 and NCAM140, but not the NCAM180 isoform, rescue the phenotype. Finally, we demonstrate that a dominant-negative form of Fyn kinase mimics, whereas a constitutively active form of Fyn kinase rescues, the effects of NCAM knockdown. Altogether, our data suggest that NCAM120/NCAM140-mediated Fyn activation promotes GABAergic synapse maturation in postnatal cortex

Potentialities of Complex Network Theory Tools for Urban Drainage Networks Analysis

Urban drainage networks (UDNs) represent important infrastructures to protect and maintain community health and safety. For these reasons, technicians and researcher are focusing more and more on topics related to vulnerability, resilience and monitoring for controlling illicit intrusions, contaminant and pathogenic spread. In the last years the complex network theory (CNT) is attracting attention as a new, useful and structured approach to analyze urban systems. The aim of this work is to evaluate potentialities of CNT approaches for UDNs vulnerability assessment and monitoring system planning. Limits and potentialities of applicability of CNT tools to UDNs are first provided evaluating the performances of standard centrality metrics. Then, it is proposed the use of tailored metrics embedding prior information, as intrinsic relevance of each node and pipe flow direction, which derive from the Horton's hierarchy and geometric data (pipe slope), respectively, without performing hydraulic simulations. The analysis is applied on two schematic literature networks of different complexity and to a real case-study. The results suggest that vulnerability/resilience, monitoring design, contaminant and pathogenic spreads can be effectively analyzed using tailored metrics. Therefore, the proposed approach represents a complementary tool respect the more complex and computationally expensive methodologies and it is particular useful for large complex networks

Tubulin nitration in human gliomas

Immunohistochem. and biochem. investigations showed that significant protein nitration occurs in human gliomas, esp. in grade IV glioblastomas at the level of astrocytes and oligodendrocytes and neurons. Enhanced alpha-tubulin immunoreactivity was co-present in the same elements in the glioblastomas. Proteomic methodologies were employed to identify a nitrated protein band at 55 kDa as alpha-tubulin. Peptide mass fingerprinting procedures demonstrated that tubulin is nitrated at Tyr224 in grade IV tumor samples but is unmodified in grade I samples and in non-cancerous brain tissue. These results provide the first characterization of endogenously nitrated tubulin from human tumor samples

Exponential instability in the fractional Calder\'on problem

In this note we prove the exponential instability of the fractional Calder\'on problem and thus prove the optimality of the logarithmic stability estimate from \cite{RS17}. In order to infer this result, we follow the strategy introduced by Mandache in \cite{M01} for the standard Calder\'on problem. Here we exploit a close relation between the fractional Calder\'on problem and the classical Poisson operator. Moreover, using the construction of a suitable orthonormal basis, we also prove (almost) optimality of the Runge approximation result for the fractional Laplacian, which was derived in \cite{RS17}. Finally, in one dimension, we show a close relation between the fractional Calder\'on problem and the truncated Hilbert transform.Comment: 17 page

Computing Volume Bounds of Inclusions by EIT Measurements

The size estimates approach for Electrical Impedance Tomography (EIT) allows for estimating the size (area or volume) of an unknown inclusion in an electrical conductor by means of one pair of boundary measurements of voltage and current. In this paper we show by numerical simulations how to obtain such bounds for practical application of the method. The computations are carried out both in a 2D and a 3D setting.Comment: 20 pages with figure

Identificazione mediante DNA barcoding del mitilide alloctono <i>Xenostrobus securis</i> e nuove segnalazioni in Mediterraneo occidentale = DNA barcoding identification of the exotic mussel <i>Xenostrobus securis</i> and new records in Western Mediterranean

The present study reports species' identification by means of DNA barcoding and new records of the invasive pygmy mussel Xenostrobus securis (Lam. 1819) (Mollusca, Bivalvia), native to South Oceania, in some Western Mediterranean brackish-water biotopes. Monitoring of this species is recommended, given its ecological effects on native biological communities and as fouling agent

Grouping of orally ingested silica nanomaterials via use of an integrated approach to testing and assessment to streamline risk assessment

Background: Nanomaterials can exist in different nanoforms (NFs). Their grouping may be supported by the formulation of hypotheses which can be interrogated via integrated approaches to testing and assessment (IATA). IATAs are decision trees that guide the user through tiered testing strategies (TTS) to collect the required evidence needed to accept or reject a grouping hypothesis. In the present paper, we investigated the applicability of IATAs for ingested NFs using a case study that includes different silicon dioxide, SiO2 NFs. Two oral grouping hypotheses addressing local and systemic toxicity were identified relevant for the grouping of these NFs and verified through the application of oral IATAs. Following different Tier 1 and/or Tier 2 in vitro methods of the TTS (i.e., in vitro dissolution, barrier integrity and inflammation assays), we generated the NF datasets. Furthermore, similarity algorithms (e.g., Bayesian method and Cluster analysis) were utilized to identify similarities among the NFs and establish a provisional group(s). The grouping based on Tier 1 and/or Tier 2 testing was analyzed in relation to available Tier 3 in vivo data in order to verify if the read-across was possible and therefore support a grouping decision. Results: The measurement of the dissolution rate of the silica NFs in the oro-gastrointestinal tract and in the lysosome identified them as gradually dissolving and biopersistent NFs. For the local toxicity to intestinal epithelium (e.g. cytotoxicity, membrane integrity and inflammation), the biological results of the gastrointestinal tract models indicate that all of the silica NFs were similar with respect to the lack of local toxicity and, therefore, belong to the same group; in vivo data (although limited) confirmed the lack of local toxicity of NFs. For systemic toxicity, Tier 1 data did not identify similarity across the NFs, with results across different decision nodes being inconsistent in providing homogeneous group(s). Moreover, the available Tier 3 in vivo data were also insufficient to support decisions based upon the obtained in vitro results and relating to the toxicity of the tested NFs. Conclusions: The information generated by the tested oral IATAs can be effectively used for similarity assessment to support a grouping decision upon the application of a hypothesis related to toxicity in the gastrointestinal tract. The IATAs facilitated a structured data analysis and, by means of the expert’s interpretation, supported read-across with the available in vivo data. The IATAs also supported the users in decision making, for example, reducing the testing when the grouping was well supported by the evidence and/or moving forward to advanced testing (e.g., the use of more suitable cellular models or chronic exposure) to improve the confidence level of the data and obtain more focused information

Sensory Experience Differentially Modulates the mRNA Expression of the Polysialyltransferases ST8SiaII and ST8SiaIV in Postnatal Mouse Visual Cortex

Polysialic acid (PSA) is a unique carbohydrate composed of a linear homopolymer of α-2,8 linked sialic acid, and is mainly attached to the fifth immunoglobulin-like domain of the neural cell adhesion molecule (NCAM) in vertebrate neural system. In the brain, PSA is exclusively synthesized by the two polysialyltransferases ST8SiaII (also known as STX) and ST8SiaIV (also known as PST). By modulating adhesive property of NCAM, PSA plays a critical role in several neural development processes such as cell migration, neurite outgrowth, axon pathfinding, synaptogenesis and activity-dependent plasticity. The expression of PSA is temporally and spatially regulated during neural development and a tight regulation of PSA expression is essential to its biological function. In mouse visual cortex, PSA is downregulated following eye opening and its decrease allows the maturation of GABAergic synapses and the opening of the critical period for ocular dominance plasticity. Relatively little is known about how PSA levels are regulated by sensory experience and neuronal activity. Here, we demonstrate that while both ST8SiaII and ST8SiaIV mRNA levels decrease around the time of eye opening in mouse visual cortex, only ST8SiaII mRNA level reduction is regulated by sensory experience. Using an organotypic culture system from mouse visual cortex, we further show that ST8SiaII gene expression is regulated by spiking activity and NMDA-mediated excitation. Further, we show that both ST8SiaII and ST8SiaIV mRNA levels are positively regulated by PKC-mediated signaling. Therefore, sensory experience-dependent ST8SiaII gene expression regulates PSA levels in postnatal visual cortex, thus acting as molecular link between visual activity and PSA expression