Epidemiology of Noble Pen Shell (Pinna nobilis L. 1758) Mass Mortality Events in Adriatic Sea Is Characterised with Rapid Spreading and Acute Disease Progression

From May to October 2019, multiple mass mortality events (MMEs) of Pinna nobilis were observed along Croatian coastline starting from the south-east and rapidly progressing in north-western direction. Time dynamics of the MMEs closely followed general speed and direction patterns of surface sea-currents, advancing approximately 350 km in less than 3 months. Surveillance, clinical evaluation, and sample collection were performed on multiple sites with various degrees of mortality rates. Moribund P. nobilis individuals were collected and subjected to pathological, molecular, and microscopical investigation. Affected animals were positive for Mycobacterium in 70% of the individuals, and Haplosporidium pinnae was present in 58% of the cases. Observed pathological lesions were most severe where concurrent presence of both pathogens was confirmed (in 45.8% of moribund individuals). Moderate to strong lesions were observed in animals positive for Mycobacterium only (25% of cases), and lesions were absent or minor to moderate when only H. pinnae was confirmed (16% of cases). Considering the rapid and severe spread of the MMEs, the areas less exposed to major sea currents appeared to be at lower risk of pathogen transmission. Surveillance activities along the Croatian coastline identified several P. nobilis populations in such “lower risk” areas without apparent mortality or clinical symptoms. Such areas are of particular interest as source of potentially healthy individuals to support active recovery actions

Nanosecond-Level Resilient GNSS-Based Time Synchronization in Telecommunication Networks Through WR-PTP HA

In recent years, the push for accurate and reliable time synchronization has gained momentum in critical infrastructures, especially in telecommunication networks, driven by the demands of 5G new radio and next-generation technologies that rely on submicrosecond timing accuracy for radio access network (RAN) nodes. Traditionally, atomic clocks paired with global navigation satellite systems (GNSS) timing receivers have served as grand master clocks, supported by dedicated network timing protocols. However, this approach struggles to scale with the increasing numbers of RAN intermediate nodes. To address scalability and high-accuracy synchronization, a more cost-effective and capillary solution is needed. Standalone GNSS timing receivers leverage ubiquitous satellite signals to offer stable timing signals but can expose networks to radio-frequency attacks due to the consequent proliferation of GNSS antennas. Our research introduces a solution by combining the white rabbit precise time protocol with a backup timing source logic acting in case of timing disruptive attacks against GNSS for resilient GNSS-based network synchronization. It has been rigorously tested against common jamming, meaconing, and spoofing attacks, consistently maintaining 2 ns relative synchronization accuracy between nodes, all without the need for an atomic clock

Relative Frequencies of Blue Stragglers in Galactic Globular Clusters: Constraints for the Formation Mechanisms

We discuss the main properties of the Galactic globular cluster (GC) blue straggler stars (BSS), as inferred from our new catalog containing nearly 3000 BSS. The catalog has been extracted from the photometrically homogeneous V vs. (B-V) color-magnitude diagrams (CMD) of 56 GCs, based on WFPC2 images of their central cores. In our analysis we used consistent relative distances based on the same photometry and calibration. The number of BSS has been normalized to obtain relative frequencies (F_{BSS}) and specific densities (N_S) using different stellar populations extracted from the CMD. The cluster F_{BSS} is significantly smaller than the relative frequency of field BSS. We find a significant anti-correlation between the BSS relative frequency in a cluster and its total absolute luminosity (mass). There is no statistically significant trend between the BSS frequency and the expected collision rate. F_{BSS} does not depend on other cluster parameters, apart from a mild dependence on the central density. PCC clusters act like normal clusters as far as the BSS frequency is concerned. We also show that the BSS luminosity function for the most luminous clusters is significantly different, with a brighter peak and extending to brighter luminosities than in the less luminous clusters. These results imply that the efficiency of BSS production mechanisms and their relative importance vary with the cluster mass.Comment: 12 pages, 3 figures. accepted for publication in ApJ

Absence of Rac1 and Rac3 GTPases in the nervous system hinders thymic, splenic and immune-competence development

The nervous system influences organ development by direct innervation and the action of hormones. We recently showed that the specific absence of Rac1 in neurons (Rac1N) in a Rac3-deficient (Rac3KO) background causes motor behavioural defects, epilepsy, and premature mouse death around postnatal day 13. We report here that Rac1N/Rac3KO mice display a progressive loss of immune-competence. Comparative longitudinal analysis of lymphoid organs from control, single Rac1N or Rac3KO, and double Rac1N/Rac3KO mutant animals showed that thymus development is preserved up to postnatal day 9 in all animals, but is impaired in Rac1N/Rac3KO mice at later times. This is evidenced by a drastic reduction in thymic cell numbers. Cell numbers were also reduced in the spleen, leading to splenic tissue disarray. Organ involution occurs in spite of unaltered thymocyte and lymphocyte subset composition, and proper mature T-cell responses to polyclonal stimuli in vitro. Suboptimal thymus innervation by tau-positive neuronal terminals possibly explains the suboptimal thymic output and arrested thymic development, which is accompanied by higher apoptotic rates. Our results support a role for neuronal Rac1 and Rac3 in dictating proper lymphoid organ development, and suggest the existence of lymphoid-extrinsic mechanisms linking neural defects to the loss of immune-competence

Modeling SARS-CoV-2 spike/ACE2 protein–protein interactions for predicting the binding affinity of new spike variants for ACE2, and novel ACE2 structurally related human protein targets, for COVID-19 handling in the 3PM context

Aims The rapid spread of new SARS-CoV-2 variants has highlighted the crucial role played in the infection by mutations occurring at the SARS-CoV-2 spike receptor binding domain (RBD) in the interactions with the human ACE2 receptor. In this context, it urgently needs to develop new rapid tools for quickly predicting the affinity of ACE2 for the SARS-CoV-2 spike RBD protein variants to be used with the ongoing SARS-CoV-2 genomic sequencing activities in the clinics, aiming to gain clues about the transmissibility and virulence of new variants, to prevent new outbreaks and to quickly estimate the severity of the disease in the context of the 3PM. Methods In our study, we used a computational pipeline for calculating the interaction energies at the SARS-CoV-2 spike RBD/ACE2 protein–protein interface for a selected group of characterized infectious variants of concern/interest (VoC/ VoI). By using our pipeline, we built 3D comparative models of the SARS-CoV-2 spike RBD/ACE2 protein complexes for the VoC B.1.1.7-United Kingdom (carrying the mutations of concern/interest N501Y, S494P, E484K at the RBD), P.1- Japan/Brazil (RBD mutations: K417T, E484K, N501Y), B.1.351-South Africa (RBD mutations: K417N, E484K, N501Y), B.1.427/B.1.429-California (RBD mutations: L452R), the B.1.141 (RBD mutations: N439K), and the recent B.1.617.1- India (RBD mutations: L452R; E484Q) and the B.1.620 (RBD mutations: S477N; E484K). Then, we used the obtained 3D comparative models of the SARS-CoV-2 spike RBD/ACE2 protein complexes for predicting the interaction energies at the protein–protein interface. Results Along SARS-CoV-2 mutation database screening and mutation localization analysis, it was ascertained that the most dangerous mutations at VoC/VoI spike proteins are located mainly at three regions of the SARS-CoV-2 spike “boat-shaped” receptor binding motif, on the RBD domain. Notably, the P.1 Japan/Brazil variant present three mutations, K417T, E484K, N501Y, located along the entire receptor binding motif, which apparently determines the highest interaction energy at the SARS-CoV-2 spike RBD/ACE2 protein–protein interface, among those calculated. Conversely, it was also observed that the replacement of a single acidic/hydrophilic residue with a basic residue (E484K or N439K) at the “stern” or “bow” regions, of the boat-shaped receptor binding motif on the RBD, appears to determine an interaction energy with ACE2 receptor higher than that observed with single mutations occurring at the “hull” region or with other multiple mutants. In addition, our pipeline allowed searching for ACE2 structurally related proteins, i.e., THOP1 and NLN, which deserve to be investigated for their possible involvement in interactions with the SARS-CoV-2 spike protein, in those tissues showing a low expression of ACE2, or as a novel receptor for future spike variants. A freely available web-tool for the in silico calculation of the interaction energy at the SARS-CoV-2 spike RBD/ACE2 protein–protein interface, starting from the sequences of the investigated spike and/or ACE2 variants, was made available for the scientific community at: https:// www. mitoa irm. it/ covid 19aff​initi es. Conclusion In the context of the PPPM/3PM, the employment of the described pipeline through the provided webservice, together with the ongoing SARS-CoV-2 genomic sequencing, would help to predict the transmissibility of new variants sequenced from future patients, depending on SARS-CoV-2 genomic sequencing activities and on the specific amino acid replacement and/or on its location on the SARS-CoV-2 spike RBD, to put in play all the possible counteractions for preventing the most deleterious scenarios of new outbreaks, taking into consideration that a greater transmissibility has not to be necessarily related to a more severe manifestation of the disease

Satellite-derived Time for Enhanced Telecom Networks Synchronization: the ROOT Project

Satellite-derived timing information plays a determinant role in the provisioning of an absolute time reference to telecommunications networks, as well as in a growing set of other critical infrastructures. In light of the stringent requirements in terms of time, frequency, and phase synchronization foreseen in upcoming access network architectures (i.e., 5G), Global Navigation Satellite System (GNSS) receivers are expected to ensure enhanced accuracy and reliability not only in positioning but also in timing. High-end GNSS timing receivers combined with terrestrial cesium clocks and specific transport protocols can indeed satisfy such synchronization requirements by granting sub-nanosecond accuracy. As a drawback, the network infrastructure can be exposed to accidental interferences and intentional cyber-attacks. Within this framework, the ROOT project investigates the effectiveness and robustness of innovative countermeasures to GNSS and cybersecurity threats within a reference network architecture

NGC 5746:Formation history of a massive disc-dominated galaxy

The existence of massive galaxies lacking a classical bulge has often been proposed as a challenge to ΛCDM. However, recent simulations propose that a fraction of massive disc galaxies might have had very quiescent merger histories, and also that mergers do not necessarily build classical bulges. We test these ideas with deep MUSE observations of NGC 5746, a massive (~1011 M⊙) edge-on disc galaxy with no classical bulge. We analyse its stellar kinematics and stellar populations, and infer that a massive and extended disc formed very early: 80 per cent of the galaxy's stellar mass formed more than 10 Gyr ago. Most of the thick disc and the bar formed during that early phase. The bar drove gas towards the centre and triggered the formation of the nuclear disc followed by the growth of a boxy/peanut-shaped bulge. Around ~8 Gyr ago, a ~1:10 merger happened, possibly on a low-inclination orbit. The satellite did not cause significant vertical heating, did not contribute to the growth of a classical bulge, and did not destroy the bar and the nuclear disc. It was however an important event for the galaxy: by depositing its stars throughout the whole galaxy it contributed ~30 per cent of accreted stars to the thick disc. NGC 5746 thus did not completely escape mergers, but the only relatively recent significant merger did not damage the galaxy and did not create a classical bulge. Future observations will reveal if this is representative of the formation histories of massive disc galaxies

Type III interferons disrupt the lung epithelial barrier upon viral recognition

Viral infections of the lower respiratory tract are a leading cause of mortality. Mounting evidence indicates that most severe cases are characterized by aberrant immune responses and do not depend on viral burden. In this study, we assessed how type III interferons (IFN-λ) contribute to the pathogenesis induced by RNA viruses. We report that IFN-λ is present in the lower, but not upper, airways of patients with coronavirus disease 2019 (COVID-19). In mice, we demonstrate that IFN-λ produced by lung dendritic cells in response to a synthetic viral RNA induces barrier damage, causing susceptibility to lethal bacterial superinfections. These findings provide a strong rationale for rethinking the pathophysiological role of IFN-λ and its possible use in clinical practice against endemic viruses, such as influenza virus as well as the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection