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During the extended activity of Mount Etna volcano in February–April 2021, three distinct paroxysmal events took place from February 21 to 26, which were associated with a very uncommon transport of the injected upper‐tropospheric plumes toward the north. Using a synergy of observations and modeling, we characterized the emissions and three‐dimensional dispersion for these three plumes, monitored their downwind distribution and optical properties, and estimated their radiative impacts at selected locations. With a satellite‐based source inversion, we estimate the emitted sulfur dioxide (SO2) mass at an integrated value of 55 kt and plumes injections at up to 12 km altitudes, which qualifies this series as an extreme event for Mount Etna. Then, we combine Lagrangian dispersion modeling, initialized with measured temporally resolved SO2 emission fluxes and altitudes, with satellite observations to track the dispersion of the three individual plumes. The transport toward the north allowed the height‐resolved downwind monitoring of the plumes at selected observatories in France, Italy, and Israel, using LiDARs and photometric aerosol observations. Volcanic‐specific aerosol optical depths (AODs) in the visible spectral range ranging from about 0.004 to 0.03 and local daily average shortwave radiative forcing (RF) ranging from about −0.2 to −1.2 W m−2 (at the top of atmosphere) and from about −0.2 to −3.0 W m−2 (at the surface) are found. The composition (possible presence of ash), AOD, and RF of the plume have a large inter‐plume and intra‐plume variability and thus depend strongly on the position of the sampled section of the plumes. Plain Language Summary: The volcanic plumes from Mount Etna's eruptions disperse usually toward the east, to the Central‐Eastern Mediterranean, where ground stations are not available to monitor and characterize them. During the extended intense volcanic activity of Mount Etna in February–April 2021, some of the plumes dispersed toward the north, in an area where many and well‐equipped ground observatories are available. This was a unique opportunity to study the emissions, dispersion dynamics, shape/composition, and impacts of Mount Etna's aerosol plumes. We analyzed these rare events using many information layers: satellite observations, numerical simulation of the plume's dispersion, and downwind ground‐based observatories. By coupling these information pieces, we could reconstruct these events and untangle their impacts from those of a major Saharan dust outbreak that occurred simultaneously. These events were found quite extreme for Mount Etna (extreme emissions and high altitude—around 12 km). We found that this type of extreme Etna's eruptions has a relevant (and not yet studied) impact on the atmospheric composition and regional climate in the Mediterranean area. The plumes, after continental dispersion, exhibit a complex filamentary shape and a complex aerosol composition and properties, due to the presence of both sulfur‐containing particles and ash. Key Points: Three distinct paroxysmal events took place at Mount Etna from February 21 to 26, 2021 and the plumes were transported toward the northPlumes dispersion is characterized with Lagrangian modeling initialized with measured SO2 emissions and with satellite observationsA series of LiDARs detected and characterized the plumes downwind and their observations are used to estimate the plumes radiative forcing [ABSTRACT FROM AUTHOR]

Water vapour measurements from a ground-based Raman lidar and an airborne differential absorption lidar, complemented by high-resolution numerical simulations from two mesoscale models (AROME-WMED and Meso-NH), are considered to investigate three transition events from Mistral/Tramontane to southerly marine flow taking place in the Montpellier region (southern France) in the time frame September-October 2012, during the Hydrological Cycle in the Mediterranean Experiment Special Observation Period 1. Low-level wind reversals associated with these transitions are found to have a strong impact on water vapour transport, leading to a large variability of the water vapour vertical and horizontal distributions. Water vapour mixing ratio within the boundary layer is found to vary from typical values in the range 4-8 g kg−1 during the Mistral/Tramontane flows to values in the range 8-15 g kg−1 during the southerly marine flows. The increase/decrease in water vapour mixing ratio within the boundary layer may be abrupt and marked during these transition periods, with values increasing/decreasing by a factor of 2-4 within 1 h. The high spatial and temporal resolutions of the lidar data allow monitoring the time evolution of the water vapour field during these transitions from predominantly northerly Mistral/Tramontane flow to a predominantly southerly flow, permitting identification of the quite sharp separation between these flows, which is also satisfactorily well captured by the mesoscale models. Water vapour measurements from the ground-based lidar are complemented by particle backscatter measurements from the same system, which reveal the significant variability in the aerosol and cloud fields associated with these transition events. [ABSTRACT FROM AUTHOR]

The planetary boundary layer (PBL) includes the portion of the atmosphere which is directly influenced by the presence of the earth's surface. Aerosol particles trapped within the PBL can be used as tracers to study the boundarylayer vertical structure and time variability. As a result of this, elastic backscatter signals collected by lidar systems can be used to determine the height and the internal structure of the PBL. The present analysis considers three different methods to estimate the PBL height. The first method is based on the determination of the first-order derivative of the logarithm of the range-corrected elastic lidar signals. Estimates of the PBL height for specific case studies obtained through this approach are compared with simultaneous estimates from the potential temperature profiles measured by radiosondes launched simultaneously to lidar operation. Additional estimates of the boundary layer height are based on the determination of the first-order derivative of the range-corrected rotational Raman lidar signals. This latter approach results to be successfully applicable also in the afternoon-evening decaying phase of the PBL, when the effectiveness of the approach based on the elastic lidar signals may be compromised or altered by the presence of the residual layer. Results from these different approaches are compared and discussed in the paper, with a specific focus on selected case studies collected by the University of Basilicata Raman lidar system BASIL during the Convective and Orographically-induced Precipitation Study (COPS). [ABSTRACT FROM AUTHOR]

Accurate measurements of the vertical profiles of water vapour are of paramount importance for most key areas of atmospheric sciences. A comprehensive inter-comparison between different remote sensing and in-situ sensors has been carried out in the frame work of the first Special Observing Period of the Hydrological cycle in the Mediterranean Experiment for the purpose of obtaining accurate error estimates for these sensors. The inter-comparison involves a ground-based Raman lidar (BASIL), an airborne DIAL (LEANDRE2), a microwave radiometer, radiosondes and aircraft in-situ sensors.

Accurate measurements of the vertical profiles of atmospheric temperature are necessary to advance the knowledge of dynamics-thermodynamicsradiative interaction mechanisms triggering convection, and ultimately improve weather forecasting capabilities. Comprehensive intercomparisons between different remote sensing and in-situ sensors have to be carried for the purpose of obtaining accurate error estimates for these sensors. This paper reports results obtained in the frame of the Hydrological Cycle in the Mediterranean Experiment – Special Observation Period (HyMeX-SOP1).

Measurements carried out by the Raman lidar system BASIL are reported to demonstrate the capability of this instrument to characterize turbulent processes within the Convective Boundary Layer (CBL). In order to resolve the vertical profiles of turbulent variables, high resolution water vapour and temperature measurements, with a temporal resolution of 10 sec and a vertical resolution of 90 and 210 m, respectively, are considered. Measurements of higher-order moments of the turbulent fluctuations of water vapour mixing ratio and temperature are obtained based on the application of spectral and auto-covariance analyses to the water vapour mixing ratio and temperature time series. The algorithms are applied to a case study (IOP 5, 20 April 2013) from the HD(CP)2 Observational Prototype Experiment (HOPE), held in Central Germany in the spring 2013. The noise errors are demonstrated to be small enough to allow the derivation of up to fourth-order moments for both water vapour mixing ratio and temperature fluctuations with sufficient accuracy.

Water vapour measurements from a ground-based Raman lidar and an airborne differential absorption lidar, complemented by high resolution numerical simulations from two mesoscale models (Arome-WMED and MESO-NH), are considered to investigate transition events from Mistral/Tramontane to southerly marine flow taking place over the Gulf of Lion in Southern France in the time frame September-October 2012, during the Hydrological Cycle in the Mediterranean Experiment (HyMeX) Special Observation Period 1 (SOP1). Low-level wind reversals associated with these transitions are found to have a strong impact on water vapour transport, leading to a large variability of the water vapour vertical and horizontal distribution. The high spatial and temporal resolution of the lidar data allow to monitor the time evolution of the three-dimensional water vapour field during these transitions from predominantly northerly Mistral/Tramontane flow to a predominantly southerly flow, allowing to identify the quite sharp separation between these flows, which is also quite well captured by the mesoscale models.

Measurements carried out by the Raman lidar system BASIL and the University of Cologne wind lidar are reported to demonstrate the capability of these instruments to characterize water vapour fluxes within the Convective Boundary Layer (CBL). In order to determine the water vapour flux vertical profiles, high resolution water vapour and vertical wind speed measurements, with a temporal resolution of 1 sec and a vertical resolution of 15-90, are considered. Measurements of water vapour flux profiles are based on the application of covariance approach to the water vapour mixing ratio and vertical wind speed time series. The algorithms are applied to a case study (IOP 11, 04 May 2013) from the HD(CP)2 Observational Prototype Experiment (HOPE), held in Central Germany in the spring 2013. For this case study, the water vapour flux profile is characterized by increasing values throughout the CBL with lager values (around 0.1 g/kg m/s) in the entrainment region. The noise errors are demonstrated to be small enough to allow the derivation of water vapour flux profiles with sufficient accuracy.

In November 2012 the University of BASILicata Raman Lidar system (BASIL) was approved to enter the International Network for the Detection of Atmospheric Composition Change (NDACC). This network includes more than 70 high-quality, remote-sensing research stations for observing and understanding the physical and chemical state of the upper troposphere and stratosphere and for assessing the impact of stratosphere changes on the underlying troposphere and on global climate. As part of this network, more than thirty groundbased Lidars deployed worldwide are routinely operated to monitor atmospheric ozone, temperature, aerosols, water vapour, and polar stratospheric clouds. In the frame of NDACC, BASIL performs measurements on a routine basis each Thursday, typically from local noon to midnight, covering a large portion of the daily cycle. Measurements from BASIL are included in the NDACC database both in terms of water vapour mixing ratio and temperature. This paper illustrates some measurement examples from BASIL, with a specific focus on water vapour measurements, with the goal to try and characterize the system performances.

Positive-sense single-stranded RNA viruses significantly reshape intracellular membranes to generate viral replication organelles that form a controlled niche in which nucleic acids, enzymes, and cofactors accumulate to assure an efficient replication of the viral genome. In recent years, advancements in electron microscopy (EM) techniques have enabled imaging of these viral factories in a near-native state providing significantly higher molecular details that have led to progress in our general understanding of virus biology. In this review, we describe the contribution of the cutting-edge EM approaches to the current knowledge of replication organelles biogenesis, structure, and functions., (© 2023 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

The measles virus (MeV) and canine distemper virus (CDV) belong to the genus Morbillivirus of the Paramyxoviridae family. They are enveloped viruses harboring a non-segmented negative-sense RNA. Morbilliviruses are extremely contagious and transmitted through infectious aerosol droplets. Both MeV and CDV may cause respiratory infections and fatal encephalitis, although a high incidence of brain infections is unique to CDV. Despite the availability of a safe and effective vaccine against these viruses, in recent years we are witnessing a strong resurgence of Morbillivirus infection. Measles still kills more than 100,000 people each year, and CDV causes widespread outbreaks, especially among wild animals, including non-human primates. No drugs are currently approved for MeV and CDV. Therefore, the identification of effective antiviral agents represents an unmet medical need. Here, we have investigated the potential antiviral properties of nitazoxanide (NTZ) against MeV and CDV. Antiviral activity was explored with live virus and cell-based assays. NTZ is a thiazolide that is approved by the FDA as an antiprotozoal agent for the treatment of Giardia intestinalis and Cryptosporidium parvum . Further, nitazoxanide and its metabolite tizoxanide have recently emerged as broad-spectrum antiviral agents. We found that NTZ blocks the MeV and CDV replication, acting at the post-entry level. Moreover, we showed that NTZ affects the function of the viral fusion protein (F), impairing viral spread. Our results indicate that NTZ should be further explored as a therapeutic option in measles and canine distemper virus treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Multiple Sclerosis (MS) is a chronic disease with a high prevalence of neuropsychiatric symptoms. Mindfulness is a practice that encourages individuals to cultivate a present-focused, acceptance-based approach for managing psychological distress. Its positive effect on MS has been demonstrated, but learning such technique is expensive and time-consuming. In this study, we investigated the feasibility and efficacy of an 8-week, at-home, smart-device aided mindfulness program in a cohort of MS patients. Specifically, we explored the role of a brain-sensing headband providing real-time auditory feedback as supportive tool for meditation exercises., Methods: The study included two visits, one at baseline and another after the mindfulness program. We measured adherence to the proposed mindfulness treatment and its effect on questionnaires investigating different psychological domains, cognition, fatigue, quality of life and quantitative EEG parameters. All participants received a smart biofeedback device to be used during the therapeutic program consisting of daily meditative exercises., Results: Twenty-nine patients were recruited for the present study. Among them, 27 (93%) completed the entire program and 17 (63%) completed more than 80% of the scheduled sessions. We observed a statistically significant reduction of the Ruminative Response Scale score and a significant increase of the Digit Span Backward. Regarding neurophysiological data, we found a significant reduction of the whole-scalp beta and parieto-occipital theta power post intervention., Conclusion: Our results show that an at-home, smart-device aided mindfulness program is feasible for people with MS. The efficacy in terms of reappraisals of stress, cognitive and emotional coping responses is also supported by our neurophysiological data. Further studies are warranted to better explore the role of such approaches in managing the psychological impact of MS diagnosis., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FC has received travel grants and/or speaking honoraria from Biogen, Merck, Sanofi-Genzyme, and Roche and research grants from Merck. The other authors have no conflicting interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is ongoing and has shown the community that flexible methods for rapidly identifying and screening candidate antivirals are needed. Assessing virus-neutralizing activity of human serum to monitor population immunity and response to infection and vaccination is key to pandemic control. We developed a virus neutralization platform strategy that relies only on bioinformatic and genetic information of the virus of interest. The platform uses viral envelope glycoprotein cDNAs to set up an assay that mimics multicycle infection but is safe and, therefore, amenable to biosafety level 2 (BSL2) conditions for viruses that require BSL3 facilities (e.g., SARS-CoV-1 and SARS-CoV-2). As a complement to this platform, we present a new cell-based immunofluorescent (CBI) assay that uses SARS-CoV-2 spike protein (S)-expressing cells to accurately measure the neutralization potential of human sera and is readily adaptable to variants of concern. These methods should be useful additions to the tools for assessing antiviral immunity, whether acquired via natural infection or vaccines. IMPORTANCE Assays for rapid biosafety level 2 (BSL2) evaluation of neutralizing properties of antibodies acquired via natural infection or through vaccination is urgently needed. Here, we propose a combinatorial approach in which sera are screened for SARS-CoV-2 spike protein (S) binding using a cell-based immunofluorescent (CBI) assay, and positive samples are further evaluated in a pseudotyped viral multicycle infection-mimicking protocol under BSL2 conditions.

According to the World Cancer Report, cancer rates have been increased by 50% with 15 million new cases in the year 2020. Hepatocellular carcinoma (HCC) is the only one of the most common tumors to cause a huge increase in mortality with a survival rate between 40% and 70% at 5 years, due to the high relapse and limitations associated with current therapies. Despite great progress in medicine, oncological research is always looking for new therapies: different technologies have been evaluated in clinical trials and others have been already used in clinics. Among them, oncolytic virotherapy represents a therapeutic option with a widespread possibility of approaches and applications. Oncolytic viruses are naturally occurring, or are engineered, viruses characterized by the unique features of preferentially infecting, replicating, and lysing malignant tumor cells, as well as activating the immune response. The combination of oncolytic virotherapy and chemical drugs are arousing great interest in the tumor treatment. In this scenario, novel and promising anticancer therapies comprise combinations of oncolytic viruses and epigenetic modulators or inhibitors of the signalling pathways. Combination treatments are required to improve the immune response and allow viral entry, replication, and diffusion between proximal cells. In this review, we summarize all combination therapies associated with virotherapy, including co-administered inhibitors of chromatin modifiers (combination strategies) and inserted target sites for miRNAs (recombination or arming strategies).

The purpose of the current study was to determine the phenolic composition, antioxidant, and antimicrobial activities in grape cane extracts from typical cultivars of Southern Italy. Aqueous extracts at different pHs (1-13) were prepared from "Aglianico", "Fiano", and "Greco" grape canes. The results demonstrated that an alkaline pH (13.00) produced the best polyphenol-rich extracts, as the total phenolic content was more than double when compared to the respective extracts prepared at pH 1.00. "Greco" grape canes gave the highest quantity of phenolic compounds at each pH, ranging from 42.7 ± 0.4 to 104.3 ± 3.0 mg Gallic Acid Equivalents (GAE)/g Dry Extract (DE) from pH 1.00 to 13.00. The Radical Scavenging Activity (RSA) and the Ferric Reducing Antioxidant Power (FRAP) were measured. The highest antioxidant activity was showed by "Greco" extract at pH 7.00. Seventy-five compounds were identified in the extracts by HPLC-MS with six of them described for the first time in grape canes. Procyanidins were highly abundant in extracts at pH 7.00, whereas stilbenoids were the most represented compounds at pH 13.00. Very strong antiviral activity against herpes simplex viruses was recorded for the extracts at pH 7.00 and 13.00 that were active in the early stages of infection by acting directly against the viral particles. The overall results suggest that grape canes, currently underutilized, can be usefully valorised by providing active extracts to use as antioxidant and antiviral agents.

Despite advances in medical knowledge, parasitic diseases remain a significant global health burden and their pharmacological treatment is often hampered by drug toxicity. Therefore, drug delivery systems may provide useful advantages when used in combination with conventional therapeutic compounds. Dendrimers are three-dimensional polymeric structures, characterized by a central core, branches and terminal functional groups. These nanostructures are known for their defined structure, great water solubility, biocompatibility and high encapsulation ability against a wide range of molecules. Furthermore, the high ratio between terminal groups and molecular volume render them a hopeful vector for drug delivery. These nanostructures offer several advantages compared to conventional drugs for the treatment of parasitic infection. Dendrimers deliver drugs to target sites with reduced dosage, solving side effects that occur with accepted marketed drugs. In recent years, extensive progress has been made towards the use of dendrimers for therapeutic, prophylactic and diagnostic purposes for the management of parasitic infections. The present review highlights the potential of several dendrimers in the management of parasitic diseases.

Clinical manifestations of COVID-19 caused by the new coronavirus SARS-CoV-2 are associated with age 1,2 . Adults develop respiratory symptoms, which can progress to acute respiratory distress syndrome (ARDS) in the most severe form, while children are largely spared from respiratory illness but can develop a life-threatening multisystem inflammatory syndrome (MIS-C) 3-5 . Here, we show distinct antibody responses in children and adults after SARS-CoV-2 infection. Adult COVID-19 cohorts had anti-spike (S) IgG, IgM and IgA antibodies, as well as anti-nucleocapsid (N) IgG antibody, while children with and without MIS-C had reduced breadth of anti-SARS-CoV-2-specific antibodies, predominantly generating IgG antibodies specific for the S protein but not the N protein. Moreover, children with and without MIS-C had reduced neutralizing activity as compared to both adult COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children independent of whether they develop MIS-C, with implications for developing age-targeted strategies for testing and protecting the population.

Objective: The coronavirus disease 2019 (COVID-19) has radically changed the world in a few weeks. Italy has been one of the first and most affected countries with more than 30,000 deaths up to now. Public health measures as quarantine or national lockdown are necessary to limit the spread of infectious diseases, but it is unsurprising that depriving people of their liberty has negative psychological effects. This is especially the case for people with chronic diseases, including neurological conditions like multiple sclerosis (MS). People with MS (PwMS) have a higher burden of neuropsychiatric comorbidities and are known to undertake maladaptive coping strategies in stress conditions. The aim of the present study is to investigate the impact of COVID-19 pandemic lockdown on mental health of an Italian cohort of PwMS in comparison with healthy controls (HCs). Methods: A total of 60 PwMS and 50 HCs (chosen among patients' cohabitants) were asked to answer a Web-based survey. This survey inquired about the impact of COVID-19 on patient's quality of life, job, and daily routine. Mood, fatigue, and sleep quality were evaluated using the Beck Depression Inventory II (BDI-II), the Generalized Anxiety Disease 7 (GAD-7), the Fatigue Severity Scale (FSS), and the Pittsburgh Sleep Quality Index (PSQI). Results: Overall, patients had higher scores of BDI, FSS, and PSQI, and these differences were statistically significant ( p < 0.05). When we looked at the subscores of the BDI, we detected a statistically significant difference for the neurovegetative part-that concerns with sleep, appetite, sex, and quality of sleep ( p < 0.05). One out of five patients reported new symptoms or worsening of known symptom, in particular, sensory disturbances, and fatigue. However, no symptoms were severe enough to require hospitalization. When we looked for correlations among variables, we found that there was a significant relationship between unemployment and BDI total score, GAD-7, and PSQI in MS group. The presence of new symptoms or the worsening of symptoms positively related to FSS and to PSQI. Discussion: We identified that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had a significant impact on the psychological status of patients with MS. Compared with the general population, PwMS presented a higher burden of depressive symptoms, a worse sleep quality and perceived an increase in fatigue level, one of the most disabling symptoms of MS. The COVID-19 epidemic poses a challenge to psychological resilience. More studies are warranted to better understand the long-term consequences of the pandemic on mental health of vulnerable people during the disease outbreaks., (Copyright © 2020 Motolese, Rossi, Albergo, Stelitano, Villanova, Di Lazzaro and Capone.)

Crimean-Congo Haemorrhagic Fever (CCHF) is an increasingly relevant viral zoonosis caused by the negative-sense single-stranded (ss) RNA Crimean-Congo Haemorrhagic Fever Orthonairovirus (CCHFV) (Nairoviridae family, Bunyavirales order). The viral genome is divided into three segments (L-M-S) of distinct size and functions. The infection is generally mediated by a tick vector, in particular belonging to the Hyalomma genus, and the transmission follows a tick-vertebrate-tick ecologic cycle, with asymptomatic infected animals functioning as reservoirs and amplifiers for CCHFV. Human hosts could be infected primarily through infected ticks or by contact with infected hosts or their body fluids and tissues, also in a nosocomial way and in occupational contexts. Infected symptomatic patients generally manifest a nonspecific illness, which progresses across four stages, with possibly lethal outcomes. Disease outbreaks show a widespread geographic diffusion and a highly variable mortality rate, dramatically peaking in untreated patients. The lack of an adequate animal model and the elevated virus biological risk (only manageable under biosafety level 4 conditions) represent strongly limiting factors for a better characterization of the disease and for the development of specific therapies and vaccines. The present review discusses updated information on CCHFV-related disease, including details about the virus (taxonomy, structure, life cycle, transmission modalities) and considering CCHF pathogenesis, epidemiology and current strategies (diagnostic, therapeutic and preventive)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Partial replacement of α-amino acid residues with β-amino acid residues has been established as a strategy for preserving target-engagement by helix-forming polypeptides while altering other properties. The impact of β-residue incorporation within polypeptides that adopt less regular conformations, however, has received less attention. The C-terminal heptad repeat (HRC) domains of fusion glycoproteins from pathogenic paramyxoviruses contain a segment that must adopt an extended conformation in order to coassemble with the N-terminal heptad repeat (HRN) domain in the postfusion state and drive a merger of the viral envelope with a target cell membrane. Here, we examine the impact of single α-to-β substitutions within this extended N-terminal segment of an engineered HRC peptide designated VIQKI. Stabilities of hexameric coassemblies formed with the native human parainfluenza virus 3 (HPIV3) HRN have been evaluated, the structures of five coassemblies have been determined, and antiviral efficacies have been measured. Many sites within the extended segment show functional tolerance of α-to-β substitution. These results offer a basis for future development of paramyxovirus infection inhibitors with novel biological activity profiles, possibly including resistance to proteolysis.

A clinical isolate of measles virus (MeV) bearing a single amino acid alteration in the viral fusion protein (F; L454W) was previously identified in two patients with lethal sequelae of MeV central nervous system (CNS) infection. The mutation dysregulated the viral fusion machinery so that the mutated F protein mediated cell fusion in the absence of known MeV cellular receptors. While this virus could feasibly have arisen via intrahost evolution of the wild-type (wt) virus, it was recently shown that the same mutation emerged under the selective pressure of small-molecule antiviral treatment. Under these conditions, a potentially neuropathogenic variant emerged outside the CNS. While CNS adaptation of MeV was thought to generate viruses that are less fit for interhost spread, we show that two animal models can be readily infected with CNS-adapted MeV via the respiratory route. Despite bearing a fusion protein that is less stable at 37°C than the wt MeV F, this virus infects and replicates in cotton rat lung tissue more efficiently than the wt virus and is lethal in a suckling mouse model of MeV encephalitis even with a lower inoculum. Thus, either during lethal MeV CNS infection or during antiviral treatment in vitro , neuropathogenic MeV can emerge, can infect new hosts via the respiratory route, and is more pathogenic (at least in these animal models) than wt MeV. IMPORTANCE Measles virus (MeV) infection can be severe in immunocompromised individuals and lead to complications, including measles inclusion body encephalitis (MIBE). In some cases, MeV persistence and subacute sclerosing panencephalitis (SSPE) occur even in the face of an intact immune response. While they are relatively rare complications of MeV infection, MIBE and SSPE are lethal. This work addresses the hypothesis that despite a dysregulated viral fusion complex, central nervous system (CNS)-adapted measles virus can spread outside the CNS within an infected host., (Copyright © 2019 American Society for Microbiology.)

During a measles virus (MeV) epidemic in 2009 in South Africa, measles inclusion body encephalitis (MIBE) was identified in several HIV-infected patients. Years later, children are presenting with subacute sclerosing panencephalitis (SSPE). To investigate the features of established MeV neuronal infections, viral sequences were analyzed from brain tissue samples of a single SSPE case and compared with MIBE sequences previously obtained from patients infected during the same epidemic. Both the SSPE and the MIBE viruses had amino acid substitutions in the ectodomain of the F protein that confer enhanced fusion properties. Functional analysis of the fusion complexes confirmed that both MIBE and SSPE F protein mutations promoted fusion with less dependence on interaction by the viral receptor-binding protein with known MeV receptors. While the SSPE F required the presence of a homotypic attachment protein, MeV H, in order to fuse, MIBE F did not. Both F proteins had decreased thermal stability compared to that of the corresponding wild-type F protein. Finally, recombinant viruses expressing MIBE or SSPE fusion complexes spread in the absence of known MeV receptors, with MIBE F-bearing viruses causing large syncytia in these cells. Our results suggest that alterations to the MeV fusion complex that promote fusion and cell-to-cell spread in the absence of known MeV receptors is a key property for infection of the brain. IMPORTANCE Measles virus can invade the central nervous system (CNS) and cause severe neurological complications, such as MIBE and SSPE. However, mechanisms by which MeV enters the CNS and triggers the disease remain unclear. We analyzed viruses from brain tissue of individuals with MIBE or SSPE, infected during the same epidemic, after the onset of neurological disease. Our findings indicate that the emergence of hyperfusogenic MeV F proteins is associated with infection of the brain. We also demonstrate that hyperfusogenic F proteins permit MeV to enter cells and spread without the need to engage nectin-4 or CD150, known receptors for MeV that are not present on neural cells., (Copyright © 2019 American Society for Microbiology.)

The impact of influenza virus infection is felt each year on a global scale when approximately 5-10% of adults and 20-30% of children globally are infected. While vaccination is the primary strategy for influenza prevention, there are a number of likely scenarios for which vaccination is inadequate, making the development of effective antiviral agents of utmost importance. Anti-influenza treatments with innovative mechanisms of action are critical in the face of emerging viral resistance to the existing drugs. These new antiviral agents are urgently needed to address future epidemic (or pandemic) influenza and are critical for the immune-compromised cohort who cannot be vaccinated. We have previously shown that lipid tagged peptides derived from the C-terminal region of influenza hemagglutinin (HA) were effective influenza fusion inhibitors. In this study, we modified the influenza fusion inhibitors by adding a cell penetrating peptide sequence to promote intracellular targeting. These fusion-inhibiting peptides self-assemble into ∼15-30 nm nanoparticles (NPs), target relevant infectious tissues in vivo, and reduce viral infectivity upon interaction with the cell membrane. Overall, our data show that the CPP and the lipid moiety are both required for efficient biodistribution, fusion inhibition, and efficacy in vivo.

GTSE1 over-expression has been reported as a potential marker for metastasis in various types of malignancies, including breast cancer. Despite this, the transcriptional regulation of this protein and the causes of its misregulation in tumors remain largely unknown. The aims of this work were to elucidate how GTSE1 is regulated at the transcriptional level and to clarify the mechanism underlying GTSE1-dependent cell functions in triple-negative breast cancer (TNBC). Here, we identified GTSE1 as a novel target gene of the TEAD4 transcription factor, highlighting a role for the YAP and TAZ coactivators in the transcriptional regulation of GTSE1. Moreover, we found that TEAD4 controls the formation of cell protrusions required for cell migration through GTSE1, unveiling a relevant effector role for this protein in the TEAD-dependent cellular functions and confirming TEAD4 role in promoting invasion and metastasis in breast cancer. Finally, we highlighted a role for the pRb-E2F1 pathway in the control of GTSE1 transcription and observed that treatment with drugs targeting the pRb-E2F1 or YAP/TAZ-TEAD pathways dramatically downregulated the expression levels of GTSE1 and of other genes involved in the formation of metastasis, suggesting their potential use in the treatment of TNBC., Competing Interests: CONFLICTS OF INTEREST The authors have not conflicts of interest to declare.

We study the dynamics of elastic interfaces-membranes-immersed in thermally excited fluids. The work contains three components: the development of a numerical method, a purely theoretical approach, and numerical simulation. In developing a numerical method, we first discuss the dynamical coupling between the interface and the surrounding fluids. An argument is then presented that generalizes the single-relaxation-time lattice-Boltzmann method for the simulation of hydrodynamic interfaces to include the elastic properties of the boundary. The implementation of this method is outlined and it is tested by simulating the static behavior of spherical bubbles and the dynamics of bending waves. By means of the fluctuation-dissipation theorem we recover analytically the equilibrium frequency power spectrum of thermally fluctuating membranes and the correlation function of the excitations. Also, the nonequilibrium scaling properties of the membrane roughening are deduced, leading us to formulate a scaling law describing the interface growth, W2(L,t)=L(3) g(t/L(5/2)), where W, L, and t are the width of the interface, the linear size of the system, and the time, respectively, and g is a scaling function. Finally, the phenomenology of thermally fluctuating membranes is simulated and the frequency power spectrum is recovered, confirming the decay of the correlation function of the fluctuations. As a further numerical study of fluctuating elastic interfaces, the nonequilibrium regime is reproduced by initializing the system as an interface immersed in thermally preexcited fluids.