mGlu5-mediated signalling in developing astrocyte and the pathogenesis of autism spectrum disorders.

Astrocytes, the largest glial population in human and murine brains, are crucial to the regulation of synaptic connectivity. During the first three weeks of postnatal development, immature astrocytes express mGlu5 and expands several fold while undergoing a transition towards their mature phase. Although mGlu5-mediated signalling in astrocyte functions has been extensively studied in the last decades, whether this signalling is implicated in the mechanisms governing their development, as well as the effects of dysregulated astrocytic development on neurodevelopmental disorders, are still unclear. The aim of this review is to examine what is known about the mGlu5-mediated signalling in the developing astrocytes and its possible contribution to the pathophysiology of autism spectrum disorders

Arms down cone beam CT hepatic angiography: are we focusing on the wrong target?

We read with great interest the recent article by Dr. Gonzalez-Aguirre and colleagues entitled ‘‘Arms Down Cone Beam CT Hepatic Angiography Performance Assessment: Vascular Imaging Quality and Imaging Artefacts’’ [1]. One of the most important advantages of cone beam CT (CBCT) is the possibility to evaluate the lesion’s feeders assisting their identification and catheterization [2]. In this set, the patient’s arms positioning is crucial in order not to impair CBCT imaging. Dr. Gonzalez-Aguirre et al. had elegantly demonstrated that vessels’ visualization is independent from the patient’s arms position, allowing to perform the entire procedure without patient’s movements. This minimizes the risk of contamination and reduces procedural time. However, literature shows that the major pivotal strength of CBCT, either mono-phasic or possibly bi-phasic, is the ability to depict in intra-procedurally ‘‘occult lesions’’, not visible at pre-procedural second-line non-invasive imaging (MRI, MDCT) [3]. This ability is not just for show, but yield to some major clinical implications: the visualization of an occult nodule identifies a subset of population experiencing fast tumour growth, having consequences on the number of adjunctive treatments controlling tumour growth (adjunctive RFA, or TACE procedures) and prioritization for transplantation [4]. Moreover, bi-phasic CBCT, with its unique ability to intra-procedural permit nodule characterization, could help in patients’ reclassification and real-time TACE strategy modification [5]. In this light would be a crucial interest for the audience to know whether the CBCT acquisition with arms down does not alter the diagnostic performance of the modality and ability of lesion’s characterization, especially for those lesion localized peripherally, where the beam hardening artefacts have been shown to be significant. Finally, patient’s positioning is fundamental for CBCT imaging. By acquiring the scan with patient’s arm down, liver volume would not be located within the rotation isocentre. This could be a substantial limitation for lesion located within the left liver lobe, eventually hypertrophied, and for high BMI patients

Astrocytes and Microglia and Their Potential Link with Autism Spectrum Disorders.

The cellular mechanism(s) underlying autism spectrum disorders (ASDs) are not fully understood although it has been shown that various genetic and environmental factors contribute to their etiology. As increasing evidence indicates that astrocytes and microglial cells play a major role in synapse maturation and function, and there is evidence of deficits in glial cell functions in ASDs, one current hypothesis is that glial dysfunctions directly contribute to their pathophysiology. The aim of this review is to summarize microglia and astrocyte functions in synapse development and their contributions to ASDs

Analysis of synaptic-like microvesicle exocytosis of B-cells using a live imaging technique.

Pancreatic β-cells play central roles in blood glucose homeostasis. Beside insulin, these cells release neurotransmitters and other signaling molecules stored in synaptic-like microvesicles (SLMVs). We monitored SLMV exocytosis by transfecting a synaptophysin-pHluorin construct and by visualizing the cells by Total Internal Reflection Fluorescence (TIRF) microscopy. SLMV fusion was elicited by 20 mM glucose and by depolarizing K(+) concentrations with kinetics comparable to insulin secretion. SLMV exocytosis was prevented by Tetanus and Botulinum-C neurotoxins indicating that the fusion machinery of these organelles includes VAMP-2/-3 and Syntaxin-1, respectively. Sequential visualization of SLMVs by TIRF and epifluorescence microscopy showed that after fusion the vesicle components are rapidly internalized and the organelles re-acidified. Analysis of single fusion episodes revealed the existence of two categories of events. While under basal conditions transient fusion events prevailed, long-lasting episodes were more frequent upon secretagogue exposure. Our observations unveiled similarities between the mechanism of exocytosis of insulin granules and SLMVs. Thus, diabetic conditions characterized by defective insulin secretion are most probably associated also with inappropriate release of molecules stored in SLMVs. The assessment of the contribution of SLMV exocytosis to the manifestation of the disease will be facilitated by the use of the imaging approach described in this study

Spatio-temporal overview of neuroinflammation in an experimental mouse stroke model.

After ischemic stroke, in the lesion core as well as in the ischemic penumbra, evolution of tissue damage and repair is strongly affected by neuroinflammatory events that involve activation of local specialized glial cells, release of inflammatory mediators, recruiting of systemic cells and vascular remodelling. To take advantage of this intricate response in the quest to devise new protective therapeutic strategies we need a better understanding of the territorial and temporal interplay between stroke-triggered inflammatory and cell death-inducing processes in both parenchymal and vascular brain cells. Our goal is to describe structural rearrangements and functional modifications occurring in glial and vascular cells early after an acute ischemic stroke. Low and high scale mapping of the glial activation on brain sections of mice subjected to 30 minutes middle cerebral artery occlusion (MCAO) was correlated with that of the neuronal cell death, with markers for microvascular changes and with markers for pro-inflammatory (IL-1β) and reparative (TGFβ1) cytokines. Our results illustrate a time-course of the neuroinflammatory response starting at early time-points (1 h) and up to one week after MCAO injury in mice, with an accurate spatial distribution of the observed phenomena

Circular Bedforms Due to Pit Foraging of Greater Flamingo Phoenicopterus roseus in a Back-barrier Intertidal Habitat

The Greater Flamingo Phoenicopterus roseus is known as an ecosystem engineer, rearranging sediment in peculiar bedforms as a consequence of its filter-feeding behaviour. In recent decades, the populations of the Greater Flamingo have notably increased, and now the species is one of the most abundant waterbirds in Mediterranean wetlands. Owing to its range expansion, it inhabits and exploits new and suitable foraging sites detectable by foraging structures left on the sediment. There are few images of the foraging morphologies in the literature, possibly due to their ephemeral nature and difficulty in detecting them. In this manuscript, we present a very detailed UAV (Unmanned Aerial Vehicle) image of an aggregate of pit foraging structures of Greater Flamingo discovered on a back-barrier washover fan in the Marano and Grado Lagoon (Northern Adriatic, Italy)

Alteration of beta-cell constitutive NO synthase activity is involved in the abnormal insulin response to arginine in a new rat model of type 2 diabetes.

We have previously obtained a new type 2 diabetic syndrome in adult rats given streptozotocin and nicotinamide, characterized by reduced beta-cell mass, partially preserved insulin response to glucose and tolbutamide and excessive responsiveness to arginine. We have also established that the neuronal isoform of constitutive NO synthase (nNOS) is expressed in beta-cells and modulates insulin secretion. In this study, we explored the kinetics of glucose- and arginine-stimulated insulin release in perifused isolated islets as well as the effect of N-omega-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, to get insight into the possible mechanisms responsible for the arginine hypersensitivity observed in vitro in this and other models of type 2 diabetes. A reduced first phase and a blunted second phase of insulin secretion were observed upon glucose stimulation of diabetic islets, confirming previous data in the isolated perfused rat pancreas. Exposure of diabetic islets to 10 mM arginine, in the presence of 2.8 mM glucose, elicited a remarkable monophasic increment in insulin release, which peaked at 639 +/- 31 pg/islet/min as compared to 49 +/- 18 pg/islet/min in control islets (P << 0.01). The addition of L-NAME to control islets markedly enhanced the insulin response to arginine, as expected from the documented inhibitory effect exerted by nNOS activity in normal beta-cells, whereas it did not further modify the insulin secretion in diabetic islets, thus implying the occurrence of a defective nNOS activity in these islets. A reduced expression of nNOS mRNA was found in the majority but not in all diabetic islet preparations and therefore cannot totally account for the absence of L-NAME effect, that might also be ascribed to post-transcriptional mechanisms impairing nNOS catalytic activity. In conclusion, our results provide for the first time evidence that functional abnormalities of type 2 experimental diabetes, such as the insulin hyper-responsiveness to arginine, could be due to an impairment of nNOS expression and/or activity in beta-cell

Management of post-intubation tracheal stenoses using the endoscopic approach

Background and Aim. Tracheal stenosis is a common complication of intubation with or without subsequent tracheotomy whose management remains poorly defined. Over 600 post-intubation tracheal stenoses have been treated in our centre since 1982: the aim of this study was to determine the safety and efficacy of our endoscopic approach. Methods. This retrospective study includes 113 new cases treated between 1998 and 2001. We chose this period to have a standardised technique and a significant number of cases with a sufficiently long follow up (28-78 months). Forty patients who did not meet the criteria for “true stenosis” (granulomas, pseudoglottic stenosis, etc.) were excluded from the study. Results. 73 patients (50±21 years) entered the study: 13 (18%) web-like and 60 (82%) complex stenoses. Most web-like stenoses were successfully treated with Laser Assisted Mechanical Dilation (LAMD) alone; among complex stenoses LAMD was sufficient to treat 13 patients (22%), whereas 47 patients (78%) required stent placement: 22 had their stent removed after one year and did not require any further therapy, 13 inoperable patients required permanent stent and 12 were referred to surgery after failure of multiple endoscopic treatments. No permanent complications secondary to endoscopic treatment were observed. 48 patients (66%) obtained a stable, good result with the endoscopic procedure, 13 (18%) required a permanent stent while 12 patients (16%) were referred to surgery. Conclusions. Our results indicate that the endoscopic treatment of post-intubation tracheal stenoses performed in an expert setting can be considered a safe first-line therapy, leaving some selected cases and the relapsing stenoses, for surgical resection

A model of hyphal tip growth involving microtubule-based transport

We propose a simple model for mass transport within a fungal hypha and its subsequent growth. Inspired by the role of microtubule-transported vesicles, we embody the internal dynamics of mass inside a hypha with mutually excluding particles progressing stochastically along a growing one-dimensional lattice. The connection between long range transport of materials for growth, and the resulting extension of the hyphal tip has not previously been addressed in the modelling literature. We derive and analyse mean-field equations for the model and present a phase diagram of its steady state behaviour, which we compare to simulations. We discuss our results in the context of the filamentous fungus, Neurospora crassa.Comment: 5 pages, 5 figure

Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes.

Adult neurogenesis is regulated by the neurogenic niche, through mechanisms that remain poorly defined. Here, we investigated whether niche-constituting astrocytes influence the maturation of adult-born hippocampal neurons using two independent transgenic approaches to block vesicular release from astrocytes. In these models, adult-born neurons but not mature neurons showed reduced glutamatergic synaptic input and dendritic spine density that was accompanied with lower functional integration and cell survival. By taking advantage of the mosaic expression of transgenes in astrocytes, we found that spine density was reduced exclusively in segments intersecting blocked astrocytes, revealing an extrinsic, local control of spine formation. Defects in NMDA receptor (NMDAR)-mediated synaptic transmission and dendrite maturation were partially restored by exogenous D-serine, whose extracellular level was decreased in transgenic models. Together, these results reveal a critical role for adult astrocytes in local dendritic spine maturation, which is necessary for the NMDAR-dependent functional integration of newborn neurons