ESONET LIDO Demonstration Mission: the Iberian Margin node.

The Gulf of Cadiz is one of two the test sites chosen for the demonstration of the ESONET - LIDO Demonstration Mission (DM) [1], which will establish a first nucleus of regional network of multidisciplinary sea floor observatories. The Gulf of Cadiz is a highly populated area, characterized by tsunamigenic sources, which caused the devastating earthquake and tsunamis that struck Lisbon in 1755. The seismic activity is concentrated along a belt going from this region to the Azores and the main tsunamigenic tectonic sources are located near the coastline. In the framework of the EU - NEAREST project [2] the GEOSTAR deep ocean bottom multi-parametric observatory was deployed for a one year mission off cape Saint Vincent at about 3200 m depth. GEOSTAR was equipped with a set of oceanographic, seismic and geophysical sensors and with a new tsunami detector prototype. In November 2009 the GEOSTAR abyssal station equipped with the tsunami prototype was redeployed at the same site on behalf of NEAREST and ESONET - LIDO DM. The system is able to communicate from the ocean bottom to the land station via an acoustic and satellite link. The abyssal station is designed both for long term geophysical and oceanographic observation and for tsunami early warning purpose. The tsunami detection is performed by two different algorithms: a new real time dedicated tsunami detection algorithm which analyses the water pressure data, and a seismic algorithm which triggers on strong events. Examples of geophysical and oceanographic data acquired by the abyssal station during the one year mission will be shown. The development of a new acoustic antenna equipped with a stand alone and autonomous acquisition system will allow the recording of marine mammals and the evaluation of environmental noise. ReferencesEGUPublishedVienna1.8. Osservazioni di geofisica ambientaleope

FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation

FUsed in Sarcoma (FUS) is a multifunctional RNA binding protein (RBP). FUS mutations lead to its cytoplasmic mislocalization and cause the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Here, we use mouse and human models with endogenous ALS-associated mutations to study the early consequences of increased cytoplasmic FUS. We show that in axons, mutant FUS condensates sequester and promote the phase separation of fragile X mental retardation protein (FMRP), another RBP associated with neurodegeneration. This leads to repression of translation in mouse and human FUS-ALS motor neurons and is corroborated in vitro, where FUS and FMRP copartition and repress translation. Last, we show that translation of FMRP-bound RNAs is reduced in vivo in FUS-ALS motor neurons. Our results unravel new pathomechanisms of FUS-ALS and identify a novel paradigm by which mutations in one RBP favor the formation of condensates sequestering other RBPs, affecting crucial biological functions, such as protein translation

ESONET LIDO Demonstration Mission: the East Sicily node

Off East Sicily (at 2100 m depth, 25 km off the harbour of Catania) a prototype of a cabled deep-sea observatory (NEMO-SN1) was set up and has been operational in real-time since 2005 (the cabled deep-sea multi-parameter station SN1, equipped with geophysical and environmental sensors and the cabled NEMO-OνDE, equipped with 4 broadband hydrophones). The Western Ionian Sea is one of the node sites for the upcoming European permanent underwater network (EMSO). Within the activities of the EC project ESONET-NoE some demonstration missions have been funded. The LIDO-DM (Listening to the Deep Ocean-Demonstration Mission) is one of these and is re- lated to two sites, East Sicily and Iberian Margin (Gulf of Cadiz), the main aims being geo-hazards monitoring and warning (seismic, tsunami, and volcanic) and bio-acoustics. The LIDO-DM East Sicily installation represents a fur- ther major step within ESONET-NoE, resulting in a fully integrated system for multidisciplinary deep-sea science, capable to transmit and distribute data in real time to the scientific community and to the general public. LIDO-DM East Sicily hosts a large number of sensors aimed at monitoring and studying oceanographic and environmental parameters (by means of CTD, ADCP, 3-C single point current meter, turbidity meter), geophysical phenomena (low frequency hydrophones, accelerometer, gravity meter, vector and scalar magnetometers, seismometer, abso- lute and differential pressure gauges), ocean noise monitoring and identification and tracking of biological acoustic sources in deep sea. The latter will be performed using two tetrahedral arrays of 4 hydrophones, located at a relative distance of about 5 km, and at about 25 km from the shore. The whole system will be connected and powered from shore, by means of the electro-optical cable net installed at the East Sicily Site Infrastructure, and synchronised with GPS. Sensors data sampling is performed underwater and transmitted via optical fibre link, with optimal S/N ratio for all signals. This will also permit real-time data acquisition, analysis and distribution on-shore. Innova- tive electronics for the off-shore data acquisition and transmission systems has been designed, built and tested. A dedicated computing and networking infrastructure for data acquisition, storage and distribution through the internet has been also created. The deployment and connection of the deep sea structures will be performed using the dedicated ROV and Deep Sea Shuttle handling facilities (PEGASO, owned by INGV and INFN). LIDO-DM constitutes the enhancement of the Western Ionian site in view of the EMSO Research Infrastructure.PublishedVienna1.8. Osservazioni di geofisica ambientaleope

ESONET LIDO Demonstration Mission: the Iberian Margin node.

The Gulf of Cadiz is one of two the test sites chosen for the demonstration of the ESONET - LIDO Demonstration Mission (DM) [1], which will establish a first nucleus of regional network of multidisciplinary sea floor observatories. The Gulf of Cadiz is a highly populated area, characterized by tsunamigenic sources, which caused the devastating earthquake and tsunamis that struck Lisbon in 1755. The seismic activity is concentrated along a belt going from this region to the Azores and the main tsunamigenic tectonic sources are located near the coastline. In the framework of the EU - NEAREST project [2] the GEOSTAR deep ocean bottom multi-parametric observatory was deployed for a one year mission off cape Saint Vincent at about 3200 m depth. GEOSTAR was equipped with a set of oceanographic, seismic and geophysical sensors and with a new tsunami detector prototype. In November 2009 the GEOSTAR abyssal station equipped with the tsunami prototype was redeployed at the same site on behalf of NEAREST and ESONET - LIDO DM. The system is able to communicate from the ocean bottom to the land station via an acoustic and satellite link. The abyssal station is designed both for long term geophysical and oceanographic observation and for tsunami early warning purpose. The tsunami detection is performed by two different algorithms: a new real time dedicated tsunami detection algorithm which analyses the water pressure data, and a seismic algorithm which triggers on strong events. Examples of geophysical and oceanographic data acquired by the abyssal station during the one year mission will be shown. The development of a new acoustic antenna equipped with a stand alone and autonomous acquisition system will allow the recording of marine mammals and the evaluation of environmental noise. Reference

ESONET LIDO Demonstration Mission: the East Sicily node

Off East Sicily (at 2100 m depth, 25 km off the harbour of Catania) a prototype of a cabled deep-sea observatory (NEMO-SN1) was set up and has been operational in real-time since 2005 (the cabled deep-sea multi-parameter station SN1, equipped with geophysical and environmental sensors and the cabled NEMO-OνDE, equipped with 4 broadband hydrophones). The Western Ionian Sea is one of the node sites for the upcoming European permanent underwater network (EMSO). Within the activities of the EC project ESONET-NoE some demonstration missions have been funded. The LIDO-DM (Listening to the Deep Ocean-Demonstration Mission) is one of these and is re- lated to two sites, East Sicily and Iberian Margin (Gulf of Cadiz), the main aims being geo-hazards monitoring and warning (seismic, tsunami, and volcanic) and bio-acoustics. The LIDO-DM East Sicily installation represents a fur- ther major step within ESONET-NoE, resulting in a fully integrated system for multidisciplinary deep-sea science, capable to transmit and distribute data in real time to the scientific community and to the general public. LIDO-DM East Sicily hosts a large number of sensors aimed at monitoring and studying oceanographic and environmental parameters (by means of CTD, ADCP, 3-C single point current meter, turbidity meter), geophysical phenomena (low frequency hydrophones, accelerometer, gravity meter, vector and scalar magnetometers, seismometer, abso- lute and differential pressure gauges), ocean noise monitoring and identification and tracking of biological acoustic sources in deep sea. The latter will be performed using two tetrahedral arrays of 4 hydrophones, located at a relative distance of about 5 km, and at about 25 km from the shore. The whole system will be connected and powered from shore, by means of the electro-optical cable net installed at the East Sicily Site Infrastructure, and synchronised with GPS. Sensors data sampling is performed underwater and transmitted via optical fibre link, with optimal S/N ratio for all signals. This will also permit real-time data acquisition, analysis and distribution on-shore. Innova- tive electronics for the off-shore data acquisition and transmission systems has been designed, built and tested. A dedicated computing and networking infrastructure for data acquisition, storage and distribution through the internet has been also created. The deployment and connection of the deep sea structures will be performed using the dedicated ROV and Deep Sea Shuttle handling facilities (PEGASO, owned by INGV and INFN). LIDO-DM constitutes the enhancement of the Western Ionian site in view of the EMSO Research Infrastructure

C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons.

Intronic hexanucleotide expansions in C9ORF72 are common in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but it is unknown whether loss of function, toxicity by the expanded RNA or dipeptides from non-ATG-initiated translation are responsible for the pathophysiology. We determined the interactome of C9ORF72 in motor neurons and found that C9ORF72 was present in a complex with cofilin and other actin binding proteins. Phosphorylation of cofilin was enhanced in C9ORF72-depleted motor neurons, in patient-derived lymphoblastoid cells, induced pluripotent stem cell-derived motor neurons and post-mortem brain samples from ALS patients. C9ORF72 modulates the activity of the small GTPases Arf6 and Rac1, resulting in enhanced activity of LIM-kinases 1 and 2 (LIMK1/2). This results in reduced axonal actin dynamics in C9ORF72-depleted motor neurons. Dominant negative Arf6 rescues this defect, suggesting that C9ORF72 acts as a modulator of small GTPases in a pathway that regulates axonal actin dynamics

Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis

Objective To identify shared polygenic risk and causal associations in amyotrophic lateral sclerosis (ALS). Methods Linkage disequilibrium score regression and Mendelian randomization were applied in a large-scale, data-driven manner to explore genetic correlations and causal relationships between >700 phenotypic traits and ALS. Exposures consisted of publicly available genome-wide association studies (GWASes) summary statistics from MR Base and LD-hub. The outcome data came from the recently published ALS GWAS involving 20,806 cases and 59,804 controls. Multivariate analyses, genetic risk profiling, and Bayesian colocalization analyses were also performed. Results We have shown, by linkage disequilibrium score regression, that ALS shares polygenic risk genetic factors with a number of traits and conditions, including positive correlations with smoking status and moderate levels of physical activity, and negative correlations with higher cognitive performance, higher educational attainment, and light levels of physical activity. Using Mendelian randomization, we found evidence that hyperlipidemia is a causal risk factor for ALS and localized putative functional signals within loci of interest. Interpretation Here, we have developed a public resource () which we hope will become a valuable tool for the ALS community, and that will be expanded and updated as new data become available. Shared polygenic risk exists between ALS and educational attainment, physical activity, smoking, and tenseness/restlessness. We also found evidence that elevated low-desnity lipoprotein cholesterol is a causal risk factor for ALS. Future randomized controlled trials should be considered as a proof of causality. Ann Neurol 2019;85:470-481Peer reviewe

Detection potential of the KM3NeT detector for high-energy neutrinos from the Fermi bubbles

A recent analysis of the Fermi Large Area Telescope data provided evidence for a high-intensity emission of high-energy gamma rays with a E 2 spectrum from two large areas, spanning 50 above and below the Galactic centre (the ‘‘Fermi bubbles’’). A hadronic mechanism was proposed for this gamma-ray emission making the Fermi bubbles promising source candidates of high-energy neutrino emission. In this work Monte Carlo simulations regarding the detectability of high-energy neutrinos from the Fermi bubbles with the future multi-km3 neutrino telescope KM3NeT in the Mediterranean Sea are presented. Under the hypothesis that the gamma-ray emission is completely due to hadronic processes, the results indicate that neutrinos from the bubbles could be discovered in about one year of operation, for a neutrino spectrum with a cutoff at 100 TeV and a detector with about 6 km3 of instrumented volume. The effect of a possible lower cutoff is also considered.Published7–141.8. Osservazioni di geofisica ambientaleJCR Journalrestricte

Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered

Expansion cone for the 3-inch PMTs of the KM3NeT optical modules

[EN] Detection of high-energy neutrinos from distant astrophysical sources will open a new window on the Universe. The detection principle exploits the measurement of Cherenkov light emitted by charged particles resulting from neutrino interactions in the matter containing the telescope. A novel multi-PMT digital optical module (DOM) was developed to contain 31 3-inch photomultiplier tubes (PMTs). In order to maximize the detector sensitivity, each PMT will be surrounded by an expansion cone which collects photons that would otherwise miss the photocathode. Results for various angles of incidence with respect to the PMT surface indicate an increase in collection efficiency by 30% on average for angles up to 45 degrees with respect to the perpendicular. Ray-tracing calculations could reproduce the measurements, allowing to estimate an increase in the overall photocathode sensitivity, integrated over all angles of incidence, by 27% (for a single PMT). Prototype DOMs, being built by the KM3NeT consortium, will be equipped with these expansion cones.This work is supported through the EU, FP6 Contract no. 011937, FP7 grant agreement no. 212252, and the Dutch Ministry of Education, Culture and Science.Adrián Martínez, S.; Ageron, M.; Aguilar, JA.; Aharonian, F.; Aiello, S.; Albert, A.; Alexandri, M.... (2013). Expansion cone for the 3-inch PMTs of the KM3NeT optical modules. Journal of Instrumentation. 8(3):1-19. https://doi.org/10.1088/1748-0221/8/03/T03006S1198