Pharmacological rescue of adult hippocampal neurogenesis in a mouse model of X-linked intellectual disability

Oligophrenin-1 (OPHN1) is a Rho GTPase activating protein whose mutations cause X-linked intellectual disability (XLID). How loss of function of Ophnl affects neuronal development is only partly understood. Here we have exploited adult hippocampal neurogenesis to dissect the steps of neuronal differentiation that are affected by Ophn1 deletion. We found that mice lacking Ophnl display a reduction in the number of newborn neurons in the dentate gyrus. A significant fraction of the Ophn1-deficient newly generated neurons failed to extend an axon towards CM, and showed an altered density of dendritic protrusions. Since Ophnl-deficient mice display overactivation of Rho-associated protein kinase (ROCK) and protein kinase A (PICA) signaling, we administered a clinically approved ROCK/PICA inhibitor (fasudil) to correct the neurogenesis defects. While administration of fasudil was not effective in rescuing axon formation, the same treatment completely restored spine density to control levels, and enhanced the long-term survival of adult-born neurons in mice lacking Ophn1. These results identify specific neurodevelopmental steps that are impacted by Ophn1 deletion, and indicate that they may be at least partially corrected by pharmacological treatment. (C) 2017 The Authors. Published by Elsevier Inc

Phenolic composition of hydrophilic extract of manna from sicilian Fraxinus angustifolia vahl and its reducing, antioxidant and anti-inflammatory activity in vitro

Manna, a very singular vegetable product derived from the spontaneous solidification of the sap of some Fraxinus species, has long been known for its mild laxative and emollient properties. In this work, a hydro-alcoholic extract of manna (HME) from Sicilian Fraxinus angustifolia Vahl was investigated using HPLC-DAD to find phenol components and using chemical and biological in vitro assays to determine its reducing, antioxidant and anti-inflammatory capacity. We identified elenolic acid, tyrosol, hydroxytyrosol, catechin, fraxetin, verbascoside, gallic acid, procyanidin-B1, and luteolin 3,7 glucoside, in order of abundance. Measurements of total antioxidant activity by Folin-Ciocalteu reaction and ferric reducing ability (FRAP), as well as of scavenger activity towards ABTS•+, DPPH•, and perferryl-myoglobin radicals, showed that the phytocomplex effectively reduced oxidants with different standard potentials. When compared with vitamin E, HME also behaved as an efficient chain-breaking antioxidant against lipoperoxyl radicals from methyl linoleate. In cellular models for oxidative stress, HME counteracted membrane lipid oxidation of human erythrocytes stimulated by tert-butyl hydroperoxide and prevented the generation of reactive oxygen species, as well as the GSH decay in IL-1β–activated intestinal normal-like cells. Moreover, in this in vitro intestinal bowel disease model, HME reduced the release of the pro-inflammatory cytokines IL-6 and IL-8. These findings may suggest that manna acts as an antioxidant and anti-inflammatory natural product in humans, beyond its well-known effects against constipation

Topology and energy transport in networks of interacting photosynthetic complexes

We address the role of topology in the energy transport process that occurs in networks of photosynthetic complexes. We take inspiration from light harvesting networks present in purple bacteria and simulate an incoherent dissipative energy transport process on more general and abstract networks, considering both regular structures (Cayley trees and hyperbranched fractals) and randomly-generated ones. We focus on the the two primary light harvesting complexes of purple bacteria, i.e., the LH1 and LH2, and we use network-theoretical centrality measures in order to select different LH1 arrangements. We show that different choices cause significant differences in the transport efficiencies, and that for regular networks centrality measures allow to identify arrangements that ensure transport efficiencies which are better than those obtained with a random disposition of the complexes. The optimal arrangements strongly depend on the dissipative nature of the dynamics and on the topological properties of the networks considered, and depending on the latter they are achieved by using global vs. local centrality measures. For randomly-generated networks a random arrangement of the complexes already provides efficient transport, and this suggests the process is strong with respect to limited amount of control in the structure design and to the disorder inherent in the construction of randomly-assembled structures. Finally, we compare the networks considered with the real biological networks and find that the latter have in general better performances, due to their higher connectivity, but the former with optimal arrangements can mimic the real networks' behaviour for a specific range of transport parameters. These results show that the use of network-theoretical concepts can be crucial for the characterization and design of efficient artificial energy transport networks.Comment: 14 pages, 16 figures, revised versio

Antioxidant Betalains from Cactus Pear (Opuntia Ficus Indica) inhibit endothelial ICAM-1 expression

It has been suggested that some pigments would have antioxidant properties and that their presence in dietary constituents would contribute to reduce the risk of oxidative stress\u2013correlated diseases. Among others, inflammatory response depends on redox status and may implicate oxidative stress. Vascular endothelial cells are a direct target of oxidative stress in inflammation. We have tested the impact of the free radical scavenger and antioxidant properties of betalains from the prickle pear in an in vitro model of endothelial cells. Here we show the capacity of betalains to protect endothelium from cytokine- induced redox state alteration, through ICAM-1 inhibition. KEYWORDS: endothelial cells; ICAM-1; betalains; antiinflammatory drug

Monitoraggio delle deformazioni della cupola del Teatro Massimo di Palermo con l\u2019impiego di tecniche topografiche e fotogrammetriche integrate.

L\u2019articolo riporta i primi risultati di uno studio finalizzato al monitoraggio delle deformazioni della cupola del Teatro Massimo di Palermo provocate dalle dilatazioni termiche, con l\u2019impiego di tecniche topografiche e fotogrammetriche integrate. In particolare, sono state utilizzate due stazioni totali robotizzate e sistemi di fotogrammetria digitale di elevata precisione. Per correlare gli spostamenti dei carrelli sui quali poggia la struttura in acciaio della cupola con i gradienti termici, sono state acquisite immagini termiche diversificate. L\u2019obiettivo principale del lavoro consisteva nel confronto delle due tecniche di rilievo in relazione a misure di deformazione di entit\ue0 molto ridotta (submillimetrica). I risultati ottenuti dimostrano che i carrelli funzionano ancora correttamente. Infatti, per un gradiente termico di 6\ub0 C misurato dalla termo camera, entrambe le tecniche topografiche e fotogrammetriche hanno evidenziato spostamenti dell\u2019ordine di 0.8 mm, in accordo con le previsioni del modello teorico.This paper shows the first results of a study aimed at monitoring the deformations of the dome of the Massimo Theatre in Palermo caused by thermal dilatations, with the use of topographic and photogrammetric integrated techniques. Particularly, two robotic total stations and high precision digital photogrammetric systems were employed. In order to correlate the displacements of the rollers on which the steel structure of the dome rest with the thermal gradients, different thermal images were acquired. The main goal of the work was to compare the two techniques with reference to very small (sub-millimeter) deformation measurements. The obtained results show that the rollers are still working correctly. In fact, for a thermal gradient of 6 \ub0C surveyed by thermographic camera, both topographic and photogrammetric techniques determined displacements of the order of 0.8 mm, according with the expected deformations of the theoretic model

Focused ultrasound-enabled brain tumor liquid biopsy

Abstract Although blood-based liquid biopsies have emerged as a promising non-invasive method to detect biomarkers in various cancers, limited progress has been made for brain tumors. One major obstacle is the blood-brain barrier (BBB), which hinders efficient passage of tumor biomarkers into the peripheral circulation. The objective of this study was to determine whether FUS in combination with microbubbles can enhance the release of biomarkers from the brain tumor to the blood circulation. Two glioblastoma tumor models (U87 and GL261), developed by intracranial injection of respective enhanced green fluorescent protein (eGFP)-transduced glioblastoma cells, were treated by FUS in the presence of systemically injected microbubbles. Effect of FUS on plasma eGFP mRNA levels was determined using quantitative polymerase chain reaction. eGFP mRNA were only detectable in the FUS-treated U87 mice and undetectable in the untreated U87 mice (maximum cycle number set to 40). This finding was replicated in GL261 mice across three different acoustic pressures. The circulating levels of eGFP mRNA were 1,500–4,800 fold higher in the FUS-treated GL261 mice than that of the untreated mice for the three acoustic pressures. This study demonstrated the feasibility of FUS-enabled brain tumor liquid biopsies in two different murine glioma models across different acoustic pressures