VisIVO - Integrated Tools and Services for Large-Scale Astrophysical Visualization

VisIVO is an integrated suite of tools and services specifically designed for the Virtual Observatory. This suite constitutes a software framework for effective visual discovery in currently available (and next-generation) very large-scale astrophysical datasets. VisIVO consists of VisiVO Desktop - a stand alone application for interactive visualization on standard PCs, VisIVO Server - a grid-enabled platform for high performance visualization and VisIVO Web - a custom designed web portal supporting services based on the VisIVO Server functionality. The main characteristic of VisIVO is support for high-performance, multidimensional visualization of very large-scale astrophysical datasets. Users can obtain meaningful visualizations rapidly while preserving full and intuitive control of the relevant visualization parameters. This paper focuses on newly developed integrated tools in VisIVO Server allowing intuitive visual discovery with 3D views being created from data tables. VisIVO Server can be installed easily on any web server with a database repository. We discuss briefly aspects of our implementation of VisiVO Server on a computational grid and also outline the functionality of the services offered by VisIVO Web. Finally we conclude with a summary of our work and pointers to future developments

VisIVOWeb: A WWW Environment for Large-Scale Astrophysical Visualization

This article presents a newly developed Web portal called VisIVOWeb that aims to provide the astrophysical community with powerful visualization tools for large-scale data sets in the context of Web 2.0. VisIVOWeb can effectively handle modern numerical simulations and real-world observations. Our open-source software is based on established visualization toolkits offering high-quality rendering algorithms. The underlying data management is discussed with the supported visualization interfaces and movie-making functionality. We introduce VisIVOWeb Network, a robust network of customized Web portals for visual discovery, and VisIVOWeb Connect, a lightweight and efficient solution for seamlessly connecting to existing astrophysical archives. A significant effort has been devoted for ensuring interoperability with existing tools by adhering to IVOA standards. We conclude with a summary of our work and a discussion on future developments

Microglia in prion diseases: Angels or demons?

Prion diseases are rare transmissible neurodegenerative disorders caused by the accumulation of a misfolded isoform (PrPSc) of the cellular prion protein (PrPC) in the central nervous system (CNS). Neuropathological hallmarks of prion diseases are neuronal loss, astrogliosis, and enhanced microglial proliferation and activation. As immune cells of the CNS, microglia participate both in the maintenance of the normal brain physiology and in driving the neuroinflammatory response to acute or chronic (e.g., neurodegenerative disorders) insults. Microglia involvement in prion diseases, however, is far from being clearly understood. During this review, we summarize and discuss controversial findings, both in patient and animal models, suggesting a neuroprotective role of microglia in prion disease pathogenesis and progression, or\u2014conversely\u2014a microglia-mediated exacerbation of neurotoxicity in later stages of disease. We also will consider the active participation of PrPC in microglial functions, by discussing previous reports, but also by presenting unpublished results that support a role for PrPC in cytokine secretion by activated primary microglia

Celiac disease and headache in children: A narrative state of the art

Celiac disease (CD) is one of the most important entity of the wide spectrum of gluten-related disorders (GRDs). It is well known that neurological manifestation can be present either at the onset of CD, or appear during the development of the pathology, and different can be the neurologic findings. Clinical features are very variable, ranging from typical manifestations of gastrointestinal involvement to neurologic symptom. The most frequent neurologic signs reported were headache, epileptic seizure, migraine, mental retardation, ataxia and attention deficit and hyperactive disorder. Headache either in form of migraine, or in non-specific form represents one of the main clinical presentation in CD. The aim of this work is to provide a narrative review of the pediatric literature focused on the cephalalgic features of children with CD evaluating the potential benefits of a gluten free diet (GFD). Papers were identified by searching for related literature in Medline (PubMed) and Embase using the words “Celiac Disease” and “Headache” or “Migraine” by specifying “children”/“paediatric age” for reports published since 1972 till 31th October 2018. According to our inclusion criteria, a total of 25 papers has been evaluated. Although it is still controversial if headache is prevalent in CD children a correct compliance to a GFD seems to improve the neurological symptoms even if the underlying pathogenic relationship between CD and neurologic system involvement is still not fully understood. (www.actabiomedica.it)

BCR-ABL residues interacting with ponatinib are critical to preserve the tumorigenic potential of the oncoprotein

Patients with chronic myeloid leukemia in whom tyrosine kinase inhibitors (TKIs) fail often present mutations in the BCR-ABL catalytic domain. We noticed a lack of substitutions involving 4 amino acids (E286, M318, I360, and D381) that form hydrogen bonds with ponatinib. We therefore introduced mutations in each of these residues, either preserving or altering their physicochemical properties. We found that E286, M318, I360, and D381 are dispensable for ABL and BCR-ABL protein stability but are critical for preserving catalytic activity. Indeed, only a "conservative" I360T substitution retained kinase proficiency and transforming potential. Molecular dynamics simulations of BCR-ABLI360T revealed differences in both helix αC dynamics and protein-correlated motions, consistent with a modified ATP-binding pocket. Nevertheless, this mutant remained sensitive to ponatinib, imatinib, and dasatinib. These results suggest that changes in the 4 BCR-ABL residues described here would be selected against by a lack of kinase activity or by maintained responsiveness to TKIs. Notably, amino acids equivalent to those identified in BCR-ABL are conserved in 51% of human tyrosine kinases. Hence, these residues may represent an appealing target for the design of pharmacological compounds that would inhibit additional oncogenic tyrosine kinases while avoiding the emergence of resistance due to point mutations.This work was supported by an investigator grant to P.V. from Associazione Italiana per la Ricerca sul Cancro (AIRC) and by funding from the Biotechnology and Biological Sciences Research Council (BB/I023291/1 and BB/H018409/1 to AP and FF). P.B. is the recipient of an AIRC - Marie Curie fellowship

Incidental ameloblastoma diagnosed after treatment for childhood tumor

Abstract Ameloblastoma is a rare odontogenic neoplasm accounting for 1% of all tumors of the jaws. It is rarely diagnosed in pediatric and adolescent age. Cancer treatment is a well-known risk factor for the onset of secondary malignancies among childhood cancer survivors, but any link between ameloblastoma and prior cancer treatments has yet to be explored. Here we report on two cases of ameloblastoma diagnosed in patients previously treated for tumors in pediatric age

A counterfactual approach to measure the impact of wet grassland conservation on UK breeding bird populations

Wet grassland wader populations in the United Kingdom have experienced severe declines over the last three decades. To help mitigate these declines, the Royal Society for the Protection of Birds (RSPB) has restored and managed lowland wet grassland nature reserves to benefit these and other species. However, the impact that these reserves have on bird population trends has not been experimentally evaluated, as appropriate control populations do not readily exist. In this study, we compare population trends from 1994 ‐ 2018 for five bird species of conservation concern that breed on these nature reserves with counterfactual trends using matched breeding bird survey observations. Our results showed positive effects of conservation interventions for all four wader species that these reserves aim to benefit: Lapwing (Vanellus vanellus), Redshank (Tringa totanus), Curlew (Numenius arquata) and Snipe (Gallinago gallinago). There was no positive effect of conservation interventions on reserves for the passerine, Yellow Wagtail (Motacilla flava). We compared reserve trends with three different counterfactuals, based on different scenarios of how reserve populations could have developed in the absence of conservation, and found that reserve trends performed better regardless of the counterfactual used. Our approach using monitoring data to produce valid counterfactual controls is a broadly applicable method allowing large‐scale evaluation of conservation impact

The Link of the Prion Protein with Ca2+ Metabolism and ROS Production, and the Possible Implication in A\u3b2 Toxicity

The cellular prion protein (PrPC) is an ubiquitous cell surface protein mostly expressed in neurons, where it localizes to both pre- and post-synaptic membranes. PrPC aberrant conformers are the major components of mammalian prions, the infectious agents responsible for incurable neurodegenerative disorders. PrPC was also proposed to bind aggregated misfolded proteins/peptides, and to mediate their neurotoxic signal. In spite of long-lasting research, a general consensus on the precise pathophysiologic mechanisms of PrPC has not yet been reached. Here we review our recent data, obtained by comparing primary neurons from PrP-expressing and PrP-knockout mice, indicating a central role of PrPC in synaptic transmission and Ca2+ homeostasis. Indeed, by controlling gene expression and signaling cascades, PrPC is able to optimize glutamate secretion and regulate Ca2+ entry via store-operated channels and ionotropic glutamate receptors, thereby protecting neurons from threatening Ca2+ overloads and excitotoxicity. We will also illustrate and discuss past and unpublished results demonstrating that A\u3b2 oligomers perturb Ca2+ homeostasis and cause abnormal mitochondrial accumulation of reactive oxygen species by possibly affecting the PrP-dependent downregulation of Fyn kinase activity

Als‐associated sod1(G93a) decreases serca pump levels and increases store‐operated ca2+ entry in primary spinal cord astrocytes from a transgenic mouse model

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective death of motor neurons (MNs), probably by a combination of cell- and non-cell-autonomous processes. The past decades have brought many important insights into the role of astrocytes in nervous system function and disease, including the implication in ALS pathogenesis possibly through the impairment of Ca2+-dependent astrocyte-MN cross-talk. In this respect, it has been recently proposed that altered astrocytic store-operated Ca2+ entry (SOCE) may underlie aberrant gliotransmitter release and astrocyte-mediated neurotoxicity in ALS. These observations prompted us to a thorough investigation of SOCE in primary astrocytes from the spinal cord of the SOD1(G93A) ALS mouse model in comparison with the SOD1(WT)-expressing controls. To this purpose, we employed, for the first time in the field, genetically-encoded Ca2+ indicators, allowing the direct assessment of Ca2+ fluctuations in different cell domains. We found increased SOCE, associated with decreased expression of the sarco-endoplasmic reticulum Ca2+-ATPase and lower ER resting Ca2+ concentration in SOD1(G93A) astrocytes compared to control cells. Such findings add novel insights into the involvement of astrocytes in ALS MN damage