Comparative analysis of HTLV-1 and HTLV-2 post-translational modifications of Tax proteins in relation to their intracellular localization and activation of gene expression

Poster presentatio

Influenza vaccination landscape in Italy: A comprehensive study through the OBVIOUS project lens

Influenza annually claims an estimated 8,000 lives in Italy. Despite no-cost vaccinations for high-risk groups, hesitancy persists. This study aims to pinpoint social and behavioral vaccination determinants, forming strategies to bolster vaccine uptake. From April 11 to May 29, 2022, we surveyed a demographic-stratified sample of 10,000 Italian adults, employing the WHO's Behavioral and Social Drivers of Vaccination (BesD) framework. Of those, 4,613 (46.1%) were eligible for the influenza vaccine and included in the analysis. Roughly a third remained unvaccinated and unwilling. Central Italy showed the highest resistance, with significant percentages of seniors and professionals like teachers, law enforcement, and healthcare workers expressing noncompliance. A lack of awareness of being in a target group correlated significantly with vaccine refusal or delayed acceptance. Other refusal factors included female gender, being aged 45-54, rural residency, absence of higher education, perceived vaccine unsafety, and having vaccine-opposed acquaintances. Thus, addressing these perceptions and enhancing awareness can potentially increase vaccination rates and lessen disease impact

Loss of Ambra1 promotes melanoma growth and invasion

Melanoma is the deadliest skin cancer. Despite improvements in the understanding of the molecular mechanisms underlying melanoma biology and in defining new curative strategies, the therapeutic needs for this disease have not yet been fulfilled. Herein, we provide evidence that the Activating Molecule in Beclin-1-Regulated Autophagy (Ambra1) contributes to melanoma development. Indeed, we show that Ambra1 deficiency confers accelerated tumor growth and decreased overall survival in Braf/Pten-mutated mouse models of melanoma. Also, we demonstrate that Ambra1 deletion promotes melanoma aggressiveness and metastasis by increasing cell motility/invasion and activating an EMT-like process. Moreover, we show that Ambra1 deficiency in melanoma impacts extracellular matrix remodeling and induces hyperactivation of the focal adhesion kinase 1 (FAK1) signaling, whose inhibition is able to reduce cell invasion and melanoma growth. Overall, our findings identify a function for AMBRA1 as tumor suppressor in melanoma, proposing FAK1 inhibition as a therapeutic strategy for AMBRA1 low-expressing melanoma. The absence of scaffold protein Ambra1 leads to hyperproliferation and growth in mouse models. Here the authors show that Ambra1 deficiency accelerates melanoma growth and increases metastasis in mouse models of melanoma through FAK1 hyperactivation

DNA damage contributes to neurotoxic inflammation in Aicardi-Goutières Syndrome astrocytes

Aberrant induction of type I IFN is a hallmark of the inherited encephalopathy Aicardi-Goutières syndrome (AGS), but the mechanisms triggering disease in the human central nervous system (CNS) remain elusive. Here, we generated human models of AGS using genetically modified and patient-derived pluripotent stem cells harboring TREX1 or RNASEH2B loss-of-function alleles. Genome-wide transcriptomic analysis reveals that spontaneous proinflammatory activation in AGS astrocytes initiates signaling cascades impacting multiple CNS cell subsets analyzed at the single-cell level. We identify accumulating DNA damage, with elevated R-loop and micronuclei formation, as a driver of STING- and NLRP3-related inflammatory responses leading to the secretion of neurotoxic mediators. Importantly, pharmacological inhibition of proapoptotic or inflammatory cascades in AGS astrocytes prevents neurotoxicity without apparent impact on their increased type I IFN responses. Together, our work identifies DNA damage as a major driver of neurotoxic inflammation in AGS astrocytes, suggests a role for AGS gene products in R-loop homeostasis, and identifies common denominators of disease that can be targeted to prevent astrocyte-mediated neurotoxicity in AGS

PRENOLIN project. Results of the validation phase at sendai site

One of the objectives of the PRENOLIN project is the assessment of uncertainties associated with non-linear simulation of 1D site effects. An international benchmark is underway to test several numerical codes, including various non-linear soil constitutive models, to compute the non-linear seismic site response. The preliminary verification phase (i.e. comparison between numerical codes on simple, idealistic cases) is now followed by the validation phase, which compares predictions of such numerical estimations with actual strong motion data recorded from well-known sites. The benchmark presently involves 21 teams and 21 different non-linear computations. Extensive site characterization was performed at three sites of the Japanese KiK-net and PARI networks. This paper focuses on SENDAI site. The first results indicate that a careful analysis of the data for the lab measurement is required. The linear site response is overestimated while the non-linear effects are underestimated in the first iteration. According to these observations, a first set of recommendations for defining the non-linear soil parameters from lab measurements is proposed. PRENOLIN is part of two larger projects: SINAPS@, funded by the ANR (French National Research Agency) and SIGMA, funded by a consortium of nuclear operators (EDF, CEA, AREVA, ENL)

Global Control of Motor Neuron Topography Mediated by the Repressive Actions of a Single Hox Gene

In the developing spinal cord, regional and combinatorial activities of Hox transcription factors are critical in controlling motor neuron fates along the rostrocaudal axis, exemplified by the precise pattern of limb innervation by more than fifty Hox-dependent motor pools. The mechanisms by which motor neuron diversity is constrained to limb levels are, however, not well understood. We show that a single Hox gene, Hoxc9, has an essential role in organizing the motor system through global repressive activities. Hoxc9 is required for the generation of thoracic motor columns, and in its absence, neurons acquire the fates of limb-innervating populations. Unexpectedly, multiple Hox genes are derepressed in Hoxc9 mutants, leading to motor pool disorganization and alterations in the connections by thoracic and forelimb-level subtypes. Genome-wide analysis of Hoxc9 binding suggests that this mode of repression is mediated by direct interactions with Hox regulatory elements, independent of chromatin marks typically associated with repressed Hox genes.National Institutes of Health (U.S.) (P01NS055923

Analysis of the P. lividus sea urchin genome highlights contrasting trends of genomic and regulatory evolution in deuterostomes

Sea urchins are emblematic models in developmental biology and display several characteristics that set them apart from other deuterostomes. To uncover the genomic cues that may underlie these specificities, we generated a chromosome-scale genome assembly for the sea urchin Paracentrotus lividus and an extensive gene expression and epigenetic profiles of its embryonic development. We found that, unlike vertebrates, sea urchins retained ancestral chromosomal linkages but underwent very fast intrachromosomal gene order mixing. We identified a burst of gene duplication in the echinoid lineage and showed that some of these expanded genes have been recruited in novel structures (water vascular system, Aristotle's lantern, and skeletogenic micromere lineage). Finally, we identified gene-regulatory modules conserved between sea urchins and chordates. Our results suggest that gene-regulatory networks controlling development can be conserved despite extensive gene order rearrangement

COVID-19 Vaccine Refusal and Delay among Adults in Italy: Evidence from the OBVIOUS Project, a National Survey in Italy

BACKGROUND: Vaccine hesitancy was defined by the World Health Organization (WHO) in 2019 as a major threat to global health. In Italy, reluctance to receive vaccines is a widespread phenomenon that was amplified during the COVID-19 pandemic by fear and mistrust in government. This study aims to depict different profiles and characteristics of people reluctant to vaccinate, focusing on the drivers of those who are in favor of and those who are opposed to receiving the COVID-19 vaccine. METHODS: A sample of 10,000 Italian residents was collected. A survey on COVID-19 vaccination behavior and possible determinants of vaccine uptake, delay, and refusal was administered to participants through a computer-assisted web interviewing method. RESULTS: In our sample, 83.2% stated that they were vaccinated as soon as possible ("vaccinators"), 8.0% delayed vaccination ("delayers"), and 6.7% refused to be vaccinated ("no-vaccinators"). In general, the results show that being female, aged between 25 and 64, with an education level less than a high school diploma or above a master's degree, and coming from a rural area were characteristics significantly associated with delaying or refusing COVID-19 vaccination. In addition, it was found that having minimal trust in science and/or government (i.e., 1 or 2 points on a scale from 1 to 10), using alternative medicine as the main source of treatment, and intention to vote for certain parties were characteristics associated with profiles of "delayers" or "no-vaccinators". Finally, the main reported motivation for delaying or not accepting vaccination was fear of vaccine side effects (55.0% among delayers, 55.6% among no-vaccinators). CONCLUSION: In this study, three main profiles of those who chose to be vaccinated are described. Since those who are in favor of vaccines and those who are not usually cluster in similar sociodemographic categories, we argue that findings from this study might be useful to policy makers when shaping vaccine strategies and choosing policy instruments

RENEB intercomparisons applying the conventional Dicentric Chromosome Assay (DCA)

Purpose: Two quality controlled inter-laboratory exercises were organized within the EU project ‘Realizing the European Network of Biodosimetry (RENEB)’ to further optimize the dicentric chromosome assay (DCA) and to identify needs for training and harmonization activities within the RENEB network. Materials and methods: The general study design included blood shipment, sample processing, analysis of chromosome aberrations and radiation dose assessment. After manual scoring of dicentric chromosomes in different cell numbers dose estimations and corresponding 95% confidence intervals were submitted by the participants. Results: The shipment of blood samples to the partners in the European Community (EU) were performed successfully. Outside the EU unacceptable delays occurred. The results of the dose estimation demonstrate a very successful classification of the blood samples in medically relevant groups. In comparison to the 1st exercise the 2nd intercomparison showed an improvement in the accuracy of dose estimations especially for the high dose point. Conclusions: In case of a large-scale radiological incident, the pooling of ressources by networks can enhance the rapid classification of individuals in medically relevant treatment groups based on the DCA. The performance of the RENEB network as a whole has clearly benefited from harmonization processes and specific training activities for the network partners

Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms

In a preregistered, cross-sectional study we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC=0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4<10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable