Integrated network analysis reveals new genes suggesting COVID-19 chronic effects and treatment

The COVID-19 disease led to an unprecedented health emergency, still ongoing worldwide. Given the lack of a vaccine or a clear therapeutic strategy to counteract the infection as well as its secondary effects, there is currently a pressing need to generate new insights into the SARS-CoV-2 induced host response. Biomedical data can help to investigate new aspects of the COVID-19 pathogenesis, but source heterogeneity represents a major drawback and limitation. In this work, we applied data integration methods to develop a Unified Knowledge Space (UKS) and used it to identify a new set of genes associated with SARS-CoV-2 host response, both in vitro and in vivo. Functional analysis of these genes reveals possible long-term systemic effects of the infection, such as vascular remodelling and fibrosis. Finally, we identified a set of potentially relevant drugs targeting proteins involved in multiple steps of the host response to the virus.Peer reviewe

Comparison of gene expression profile in embryonic mesencephalon and neuronal primary cultures

Peer reviewe

Physiology, pathology and relatedness of human tissues from gene expression meta-analysis

Peer reviewe

The Responsiveness of TrkB to BDNF and Antidepressant Drugs Is Differentially Regulated during Mouse Development

Peer reviewe

Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation

The pharmacological arsenal against the COVID-19 pandemic is largely based on generic anti-inflammatory strategies or poorly scalable solutions. Moreover, as the ongoing vaccination campaign is rolling slower than wished, affordable and effective therapeutics are needed. To this end, there is increasing attention toward computational methods for drug repositioning and de novo drug design. Here, multiple data-driven computational approaches are systematically integrated to perform a virtual screening and prioritize candidate drugs for the treatment of COVID-19. From the list of prioritized drugs, a subset of representative candidates to test in human cells is selected. Two compounds, 7-hydroxystaurosporine and bafetinib, show synergistic antiviral effects in vitro and strongly inhibit viral-induced syncytia formation. Moreover, since existing drug repositioning methods provide limited usable information for de novo drug design, the relevant chemical substructures of the identified drugs are extracted to provide a chemical vocabulary that may help to design new effective drugs.Peer reviewe

Geophysical monitoring of Stromboli volcano: insight into recent volcanic activity

Stromboli is an open conduit strato-volcano of the Aeolian archipelago (Italy), characterized by typical Strom-bolian explosive activity, lasting for several centuries, and by the emission of huge amounts of gas. The normalactivity of Stromboli is characterized by some hundreds of moderate explosions per day. Major explosions, whichlaunch scoria up to hundreds of meters from the craters, lava flows and paroxysmal explosions, which producelarge ballistic blocks, sometimes take place. During the effusive eruption in 2002 - 2003, which caused a tsunamiwith waves of about 10 meters high along the coasts of the Island, the monitoring system was enhanced. In 2006INGV has added two Sacks-Evertson borehole volumetric dilatometers to the surveillance system, in order to mon-itor changes in the local strain field by measuring areal strain. Today we have a large amount of geophysical dataand observations that allow us to better understand how this volcano works. After a period of low explosive activitystarted in mid-2014, Stromboli has shown a more intense explosive activity in the last few months. During the re-cent phase of increased activity, the geophysical monitoring system detected four major explosions occurred on 26July, 23 October, 1 November and 1 December 2017, respectively. The current phase of reawakening of Strombolivolcano has led the Italian civil protection authorities to decree the "attention" alert level (yellow) on the Island.PublishedVienna, Austria1IT. Reti di monitoraggio e sorveglianz

Next Generation Molecular Diagnosis of Hereditary Spastic Paraplegias: An Italian Cross-Sectional Study

Hereditary spastic paraplegia (HSP) refers to a group of genetically heterogeneous neurodegenerative motor neuron disorders characterized by progressive age-dependent loss of corticospinal motor tract function, lower limb spasticity, and weakness. Recent clinical use of next generation sequencing (NGS) methodologies suggests that they facilitate the diagnostic approach to HSP, but the power of NGS as a first-tier diagnostic procedure is unclear. The larger-than-expected genetic heterogeneity-there are over 80 potential disease-associated genes-and frequent overlap with other clinical conditions affecting the motor system make a molecular diagnosis in HSP cumbersome and time consuming. In a single-center, cross-sectional study, spanning 4 years, 239 subjects with a clinical diagnosis of HSP underwent molecular screening of a large set of genes, using two different customized NGS panels. The latest version of our targeted sequencing panel (SpastiSure3.0) comprises 118 genes known to be associated with HSP. Using an in-house validated bioinformatics pipeline and several in silico tools to predict mutation pathogenicity, we obtained a positive diagnostic yield of 29% (70/239), whereas variants of unknown significance (VUS) were found in 86 patients (36%), and 83 cases remained unsolved. This study is among the largest screenings of consecutive HSP index cases enrolled in real-life clinical-diagnostic settings. Its results corroborate NGS as a modern, first-step procedure for molecular diagnosis of HSP. It also disclosed a significant number of new mutations in ultra-rare genes, expanding the clinical spectrum, and genetic landscape of HSP, at least in Italy

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

A state observer for the Virgo inverted pendulum

International audienceWe report an application of Kalman filtering to the inverted pendulum (IP) of the Virgo gravitational wave interferometer. Using subspace method system identification techniques, we calculated a linear mechanical model of Virgo IP from experimental transfer functions. We then developed a Kalman filter, based on the obtained state space representation, that estimates from open loop time domain data, the state variables of the system. This allows the observation (and eventually control) of every resonance mode of the IP mechanical structure independently