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The Tsunami Alert Centre of the National Institute of Geophysics and Volcanology (CAT-INGV) has been promoting, since 2018, the study of tsunami risk perception in Italy. Between 2018 and 2021 a semi-structured questionnaire on the perception of tsunami risk was administered to a sample of 5842 citizens residing in 450 Italian coastal municipalities, representative of more than 12 million people. The survey was conducted with the computer-assisted telephone interviewing (CATI) methodology, described in Cerase et al. (2019), who published the results of the first pilot survey (about 1000 interviews). The large sample and the socio-demographic stratification give an excellent representation of the resident population in the surveyed Italian coastal municipalities. Moreover, in 2021 an optimized version of the questionnaire was also administered via Telepanel (a tool for collecting proportional and representative opinions of citizens) that was representative of the Italian population and included 1500 people distributed throughout the country. In this work we present the main results of the three survey phases, with a comparison among the eight surveyed regions and between the coastal regions and some coastal metropolitan cities involved in the investigations (Rome, Naples, Bari, Reggio Calabria, and Catania). Data analysis reveals heterogeneous and generally low tsunami risk perception. Some seaside populations, in fact, show a good perception of tsunami risk, while others, such as in Apulia and Molise, reveal a lower perception, most likely due to the long time elapsed since the last event and lack of memory. We do not find relevant differences related to the socio-demographic characteristics (age, gender) of the sample, whereas the education degree appears to affect people's perception. The survey shows that the respondents' predominant source of information on tsunamis is the television and other media sources (such as newspapers, books, films, internet), while the official sources (e.g., civil protection, local authorities, universities and research institutes) do not contribute significantly. Also, we find an interesting difference in people's understanding of the words tsunami and maremoto, the local term commonly used in Italy until the 2004 Sumatra–Andaman event, which should be taken into account in scientific and risk communication. The Telepanel survey, based on a nationwide sample, highlights a lower level of tsunami risk perception in comparison to average risk perception levels found in the coastal-municipality sample. Our results are being used to drive our communication strategy aimed at reducing tsunami risk in Italy, to activate dissemination and educational programs (data driven), to fill the data gap on tsunami risk perception in the North-Eastern Atlantic, Mediterranean and connected seas (NEAM) area, and to implement multilevel civil protection actions (national and local, top-down and bottom-up). Not least, outputs can address a better development of the UNESCO Tsunami Ready program in Italy.

X chromosome inactivation (XCI) is the process of silencing one of the X chromosomes in cells of the female mammal which ensures dosage compensation between the sexes. Although theoretically random in somatic tissues, the choice of which X chromosome is chosen to be inactivated can be biased in mice by genetic element(s) associated with the so-called X-controlling element ( Xce ). Although the Xce was first described and genetically localized nearly 40 y ago, its mode of action remains elusive. In the approach presented here, we identify a single long noncoding RNA (lncRNA) within the Xce locus, Lppnx, which may be the driving factor in the choice of which X chromosome will be inactivated in the developing female mouse embryo. Comparing weak and strong Xce alleles we show that Lppnx modulates the expression of Xist lncRNA , one of the key factors in XCI, by controlling the occupancy of pluripotency factors at Intron1 of Xist . This effect is counteracted by enhanced binding of Rex1 in DxPas34 , another key element in XCI regulating the activity of Tsix lncRNA, the main antagonist of Xist, in the strong but not in the weak Xce allele. These results suggest that the different susceptibility for XCI observed in weak and strong Xce alleles results from differential transcription factor binding of Xist Intron 1 and DxPas34 , and that Lppnx represents a decisive factor in explaining the action of the Xce .

The genomes of metazoans are organized at multiple spatial scales, ranging from the double helix of DNA to whole chromosomes. The intermediate genomic scale of kilobases to megabases, which corresponds to the 50–300 nm spatial scale, is particularly interesting, as the 3D arrangement of chromatin is implicated in multiple regulatory mechanisms. In this context, polycomb group (PcG) proteins stand as major epigenetic modulators of chromatin function, acting prevalently as repressors of gene transcription by combining chemical modifications of target histones with physical crosslinking of distal genomic regions and phase separation. The recent development of super-resolution microscopy (SRM) has strongly contributed to improving our comprehension of several aspects of nano-/mesoscale (10–200 nm) chromatin domains. Here, we review the current state-of-the-art SRM applied to PcG proteins, showing that the application of SRM to PcG activity and organization is still quite limited and mainly focused on the 3D assembly of PcG-controlled genomic loci. In this context, SRM approaches have mostly been applied to multilabel fluorescence in situ hybridization (FISH). However, SRM data have complemented the maps obtained from chromosome capture experiments and have opened a new window to observe how 3D chromatin topology is modulated by PcGs.

Genomic repeats have been intensely studied as regulatory elements controlling gene transcription, splicing and genome architecture. Our understanding of the role of the repetitive RNA such as the RNA coming from genomic repeats, or repetitive sequences embedded in mRNA/lncRNAs, in nuclear and cellular functions is instead still limited. In this review we discuss evidence supporting the multifaceted roles of repetitive RNA and RNA binding proteins in nuclear organization, gene regulation, and in the formation of dynamic membrane-less aggregates. We hope that our review will further stimulate research in the consolidating field of repetitive RNA biology.

Neurological and neuropsychiatric disorders affect men and women differently. Multiple sclerosis, Alzheimer's disease, anxiety disorders, depression, meningiomas and late-onset schizophrenia affect women more frequently than men. By contrast, Parkinson's disease, autism spectrum condition, attention-deficit hyperactivity disorder, Tourette's syndrome, amyotrophic lateral sclerosis and early-onset schizophrenia are more prevalent in men. Women have been historically under-recruited or excluded from clinical trials, and most basic research uses male rodent cells or animals as disease models, rarely studying both sexes and factoring sex as a potential source of variation, resulting in a poor understanding of the underlying biological reasons for sex and gender differences in the development of such diseases. Putative pathophysiological contributors include hormones and epigenetics regulators but additional biological and non-biological influences may be at play. We review here the evidence for the underpinning role of the sex chromosome complement, X chromosome inactivation, and environmental and epigenetic regulators in sex differences in the vulnerability to brain disease. We conclude that there is a pressing need for a better understanding of the genetic, epigenetic and environmental mechanisms sustaining sex differences in such diseases, which is critical for developing a precision medicine approach based on sex-tailored prevention and treatment.

The long non-coding RNA Xist induces heterochromatinization of the X chromosome by recruiting repressive protein complexes to chromatin. Here we gather evidence, from the literature and from computational analyses, showing that Xist assemblies are similar in size, shape and composition to phase-separated condensates, such as paraspeckles and stress granules. Given the progressive sequestration of Xist’s binding partners during X-chromosome inactivation, we formulate the hypothesis that Xist uses phase separation to perform its function.

The onset of random X inactivation in mouse requires the switch from a symmetric to an asymmetric state, where the identities of the future inactive and active X chromosomes are assigned. Here we show that RIF1 and KAP1 are two fundamental factors for the definition of the asymmetry. Our data show that at the onset of mESC differentiation, upregulation of the long non-coding RNA Tsix weakens the symmetric RIF1 association with the Xist promoter, and opens a window of opportunity for a more stable association of KAP1. KAP1 is required to sustain high levels of Tsix, thus reinforcing and propagating the asymmetry, and, as a result, marking the future active X chromosome. Furthermore, we show that RIF1 association with the future inactive X chromosome is essential for Xist upregulation. This double-bookmarking system, based on the mutually exclusive relationships of Tsix and RIF1, and RIF1 and KAP1, thus coordinates the identification of the inactive and active X chromosomes and initiates a self-sustaining loop that transforms an initially stochastic event into a stably inherited asymmetric X chromosome state.

We present the results of an ongoing research for assessing tsunami risk perception in southern Italy. The study is motivated by the need of addressing a sound communication strategy for tsunami risk reduction, related to the activities of the Tsunami Alert Centre (CAT) of INGV, operating within the framework of the Italian civil protection system. The area of the second step of this study includes five regions of Italy (Basilicata, Calabria, Molise, Puglia, Sicily), facing on Adriatic, Ionian and Tyrrhenian seas, located in one of the most hazardous areas of the Mediterranean. In all the area the memory of relevant tsunamis is loose, since the last destructive event dates back to 1908 (due to the Messina-Reggio Calabria M~7 earthquake). The main goal of this study is to verify how people’s perception of tsunami risk compares with the hazard assessed by scientific data, and which are the main factors controlling people’s knowledge and awareness. We analysed a sample of more than 1,600 interviewees representing about 4 million people living in the coastal municipalities of the five considered regions. Results show that risk perception appears to be generally low, with significant differences among different areas, likely due to the the time elapsed since the last events. The survey results for the first two investigated regions (Calabria and Puglia, see Cerase et al., NHESS, 2019) showed that people’s perception and understanding of tsunamis are affected by media accounts of the mega-tsunamis of Sumatra 2004 and Japan 2011. At the same time, the risk posed by small tsunamis is basically underrated or neglected, posing some critical questions for risk mitigation strategies, particularly in touristic areas. Furthermore, the survey’s results show that for lay people the word ‘tsunami’ has a different meaning with respect to the Italian traditional word ‘maremoto’, implying that the same physical phenomenon would be understood in two different ways by younger, educated people and elders with low education level. In addition, people have high expectations from authorities, CPAs, research institutions about warnings. Moreover, living in different coastal areas appears to have a significant influence on the way tsunami hazard is perceived: Interviewees of Tyrrhenian Calabria are more likely to associate tsunami risk to volcanoes with respect to those living in the Ionian coastal areas, coherently with the presence of Aeolian volcanic islands and feared submarine volcanoes in the Tyrrhenian. A somehow unexpected result is that TV emerges as the most relevant source of knowledge for 90% of the sample. Some categories declared to prefer getting early warnings through broadcast media and sirens rather than receiving by SMS or apps, suggesting the need for redundancy and modulation of EW messages. We will present an update of the survey which is presently ongoing, related to the five regions. These results could help in addressing risk communication and mitigation policies.

Polycomb steps to inactivate X XX females silence one of their X chromosomes. This involves a process whereby a noncoding RNA known as Xist coats one of the X chromosomes and recruits chromatin silencing factors. The Polycomb complexes PRC1 and PRC2 are also known to be involved in X chromosome inactivation. Almeida et al. elucidate a key role of a specific complex, PCGF3/5-PRC1, in initiating Polycomb recruitment by Xist RNA. They further demonstrate that Polycomb recruitment is critical for Xist-mediated chromosome silencing and female embryogenesis. Science , this issue p. 1081

Mice carrying single chromosome substitutions (consomic mice) provide a unique platform for investigating complex phenotypes. A proportion of such phenotypes fall into the category of transgressive phenotypes, i.e. heritable extreme phenotypes lying outside the range of either parent. We hypothesized that analysis of transgressive phenotype in consomic mice potentially reveals unique cellular and molecular signatures associated with extreme phenotypic variations. We used a system-biology approach to build a reference set of 571 transgressive phenotypes in consomic mice using phenome metadata and additional 13 B-cell specific transgressive phenotypes using experimental data. As a proof of concept, we investigated clinically-relevant hyper-IgM phenotype. A combination of flow-cytometry, RNA-Sequencing and in-vitro validation confirmed that the hyper-IgM is associated with defective B-cell lymphopoiesis at the cellular and the down-regulation of the CCR7 gene at the molecular level. Our approach provides a complete pipeline to discover and validate transgressive phenotypes relevant to health and disease conditions.

Development is a complex process regulated both by genetic and epigenetic and environmental clues. Recently, long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression in several tissues including the brain. Altered expression of lncRNAs has been linked to several neurodegenerative, neurodevelopmental and mental disorders. The identification and characterization of lncRNAs that are deregulated or mutated in neurodevelopmental and mental health diseases are fundamental to understanding the complex transcriptional processes in brain function. Crucially, lncRNAs can be exploited as a novel target for treating neurological disorders. In our review, we first summarize the recent advances in our understanding of lncRNA functions in the context of cell biology and then discussing their association with selected neuronal development and neurological disorders.

The rise of racism in Europe In recent years online racism has seen a quick and serious growth in many European and non-European countries, till to become a worrying global phenomenon. One of the most striking examples of such process is the rise of White Supremacist Movements online. Their strategy mainly consists in disguising their hidden political agenda and attempting to subvert and destroy civil rights by presenting their standpoints through an overturn of the rhetoric of the civil rights movement. Undoubtedly, the increasing racism which is rotten in hidden racist expressions, is exploiting “favorable” conditions as the financial crisis, the increase of social conflicts and the rise of populist issues in politics. In Italy, as an example, UNAR, the Italian national anti-discrimination Office, documented that complaints for online racism weighed for 30.9% of the overall cases involving the media (UNAR, 2013). Similar situations also occurred in other European countries such as Slovenia, Finland, Hungary and United Kingdom, as it emerged by part of the research carried out within the framework of the European project LIGHT ON. Nowadays, racist claims are often hidden under a subtle and sophisticated rethoric. In fact, a huge amount of disguised racist contents is currently published on the Internet in form of occasional bigotry or individuals’ outburst, whereas they are, as a matter of fact, intended to foster racist attitudes among people and to support the “normalization” of racism. Some scholars defined as “common sense racism” or “rational racism” talking against immigrants, refugees, minority members (as well as homosexuals and disabled) as undesirable and avoiding to be labeled as “racist”.

The word media hype is often used as rhetorical argument to dismiss waves of media attention as overblown, disproportional and exaggerated. But these explosive news waves, as well as - nowadays - the twitter storms, are object of scientific research, because they are an important phenomenon in the public area. Sometimes it is indeed 'much ado about nothing' but in many cases these media storms have play an important role in political issues, scandals and crises. Twitter storms sometimes ruin reputations within hours. Although different concepts are used, such as media hypes, news waves, media storms, information cascades or risk amplification, all the studies in this book refer to the same process in which key events trigger a chain of reactions and interactions, building up huge news waves in the media or rapidly spreading social epidemics in the social media. This book offers the first comprehensive overview of this important topic. It is not only interesting for scholars and students in media and journalism, but also for professionals in PR and communication, crisis communication and reputation management.

Recent experimental evidence indicates that lncRNAs can act as regulatory molecules in the context of development and disease. Xist, the master regulator of X chromosome inactivation, is a classic example of how lncRNAs can exert multi-layered and fine-tuned regulatory functions, by acting as a molecular scaffold for recruitment of distinct protein factors. In this review, we discuss the methodologies employed to define Xist RNA structures and the tight interplay between structural clues and functionality of lncRNAs. This model of modular function dictated by structure, can be also generalized to other lncRNAs, beyond the field of X chromosome inactivation, to explain common features of similarly folded RNAs.

The compensation of the different level of transcripts of X-linked genes in male and female mammals is achieved through X chromosome inactivation, a complex process that differentially regulates the sex chromosomes of female cells. This mechanism has been dissected at evolutionary, genetic and molecular levels: here, we discuss some of the latest examples that illustrate better these intricate connections, focusing particularly on the emerging role of spatial and three-dimensional chromatin arrangements in the building of this special chromosome, the inactive X chromosome.

In female m ammals, one of the two X chromosomes in each cell is transcriptionally silenced in order to achieve dosage compensation between the genders in a process called X chromosome inactivation. The master regulator of this process is the long non-coding RNA Xist. During X-inactivation, Xist accumulates in cis on the future inactive X chromosome, triggering a cascade of events that provoke the stable silencing of the entire chromosome, with relatively few genes remaining active. How Xist spreads, what are its binding sites, how it recruits silencing factors and how it induces a specific topological and nuclear organization of the chromatin all remain largely unanswered questions. Recent studies have improved our understanding of Xist localization and the proteins with which it interacts, allowing a reappraisal of ideas about Xist function. We discuss recent advances in our knowledge of Xist-mediated silencing, focusing on Xist spreading, the nuclear organization of the inactive X chromosome, recruitment of the polycomb complex and the role of the nuclear matrix in the process of X chromosome inactivation.

Maintenance of X-inactivation is achieved through a combination of different repressive mechanisms, thus perpetuating the silencing message through many cell generations. The second human X-Y pseudoautosomal region 2 (PAR2) is a useful model to explore the features and internal relationships of the epigenetic circuits involved in this phenomenon. Recently, we demonstrated that DNA methylation plays an essential role for the maintenance of X- and Y-inactivation of the PAR2 gene SYBL1; here we report that the silencing of the second repressed PAR2 gene, SPRY3, appears to be independent of DNA methylation. In contrast to SYBL1, the inactive X and Y alleles of SPRY3 are not reactivated in cells treated with a DNA methylation inhibitor and in cells from ICF (immunodeficiency, centromeric instability, facial anomalies) syndrome patients, which have mutations in the DNA methyltransferase gene DNMT3B. SPRY3 X- and Y-inactivation is associated with a differential enrichment of repressive histone modifications and the recruitment of Polycomb 2 group proteins compared to the active X allele. Another major factor in SPRY3 repression is late replication; the inactive X and Y alleles of SPRY3 have delayed replication relative to the active X allele, even in ICF syndrome cells where the closely linked SYBL1 gene is reactivated and advanced in replication. The relatively stable maintenance of SPRY3 silencing compared with SYBL1 suggests that genes without CpG islands may be less prone to reactivation than previously thought and that genes with CpG islands require promoter methylation as an additional layer of repression.

In female mammals, one of the two X chromosomes is transcriptionally silenced to equalize X-linked gene dosage relative to XY males, a process termed X chromosome inactivation. Mechanistically, this is thought to occur via directed recruitment of chromatin modifying factors by the master regulator, X-inactive specific transcript (Xist) RNA, which localizes in cis along the entire length of the chromosome. A well-studied example is the recruitment of polycomb repressive complex 2 (PRC2), for which there is evidence of a direct interaction involving the PRC2 proteins Enhancer of zeste 2 (Ezh2) and Supressor of zeste 12 (Suz12) and the A-repeat region located at the 5' end of Xist RNA. In this study, we have analyzed Xist-mediated recruitment of PRC2 using two approaches, microarray-based epigenomic mapping and superresolution 3D structured illumination microscopy. Making use of an ES cell line carrying an inducible Xist transgene located on mouse chromosome 17, we show that 24 h after synchronous induction of Xist expression, acquired PRC2 binding sites map predominantly to gene-rich regions, notably within gene bodies. Paradoxically, these new sites of PRC2 deposition do not correlate with Xist-mediated gene silencing. The 3D structured illumination microscopy was performed to assess the relative localization of PRC2 proteins and Xist RNA. Unexpectedly, we observed significant spatial separation and absence of colocalization both in the inducible Xist transgene ES cell line and in normal XX somatic cells. Our observations argue against direct interaction between Xist RNA and PRC2 proteins and, as such, prompt a reappraisal of the mechanism for PRC2 recruitment in X chromosome inactivation.

Polycomb group (PcG) proteins play an important role in the control of developmental gene expression in higher organisms. In mammalian systems, PcG proteins participate in the control of pluripotency, cell fate, cell cycle regulation, X chromosome inactivation and parental imprinting. In this study we have analysed the function of the mouse PcG protein polycomblike 2 (Pcl2), one of three homologues of the Drosophila Polycomblike (Pcl) protein. We show that Pcl2 is expressed at high levels during early embryogenesis and in embryonic stem (ES) cells. At the biochemical level, Pcl2 interacts with core components of the histone H3K27 methyltransferase complex Polycomb repressive complex 2 (PRC2), to form a distinct substoichiometric biochemical complex, Pcl2-PRC2. Functional analysis using RNAi knockdown demonstrates that Pcl2-PRC2 facilitates both PRC2 recruitment to the inactive X chromosome in differentiating XX ES cells and PRC2 recruitment to target genes in undifferentiated ES cells. The role of Pcl2 in PRC2 targeting in ES cells is critically dependent on a conserved PHD finger domain, suggesting that Pcl2 might function through the recognition of a specific chromatin configuration.

The compensation of the different level of transcripts of X-linked genes in male and female mammals is achieved through X chromosome inactivation, a complex process that differentially regulates the sex chromosomes of female cells. This mechanism has been dissected at evolutionary, genetic and molecular levels: here, we discuss some of the latest examples that illustrate better these intricate connections, focusing particularly on the emerging role of spatial and three-dimensional chromatin arrangements in the building of this special chromosome, the inactive X chromosome.

Epigenetic regulation is involved in the maintenance of long-term silencing phenomena, such as X-inactivation and genomic imprinting in mammals. Gene repression is mediated by several mechanisms, such as histone modifications, DNA methylation, and recruitment of Polycomb proteins. To understand the mechanistic relationships between these mechanisms for stable gene silencing, we analyzed the mechanisms of X- and Y-inactivation of the PAR2 gene SYBL1, previously showed to be regulated by concerted epigenetic mechanisms. Maintenance of stable repression occurs via the recruitment of both MBDPs and PRC2 complexes to SYBL1 promoter. Their binding is equally sensitive to defective DNA methylation seen in cells derived from ICF syndrome patients. Multiple occupancy is a feature shared within long-term repressed genes, such as the X-inactivated PGK1 and the imprinted IGF2. MBD2, MBD3, and MeCP2 occupy SYBL1 promoter simultaneously, as revealed by sequential ChIP. We did not find this co-occurring binding when looked for members of PRC2 complex together with any of the methyl-binding proteins. Furthermore, in co-transfection assays, MECP2 can silence methylated SYBL1 promoter, whereas the mutated protein fails. However, RNA interference of endogenous MECP2 does not induce the expression of the inactive SYBL1 alleles, suggesting that its silencing activity can be replaced by the other methyl-binding proteins. Our data suggest that maintenance of long-term silencing involves multiple layers of epigenetic control functionally redundant. PRC2 and MBD proteins could collaborate to different phases of this process, the former possibly recruiting DNMTs to the silenced promoters, the latter dictating the lock of the transcription. J. Cell. Physiol. 210: 711-719, 2007. (c) 2006 Wiley-Liss, Inc

BACKGROUND Microsatellite instability (MSI) has been reported in endometrial carcinoma (EC) and in colorectal carcinoma (CRC), primarily as a result of defective DNA mismatch repair (MMR). The MMR gene hMLH1 commonly is inactivated in both EC and CRC. In the current study, epigenetic mechanisms involved in hMLH1 inactivation have been investigated to further elucidate the role of these mechanisms in the pathogenesis of EC and CRC. METHODS Polymerase chain reaction (PCR)-based microsatellite analysis performed on paraffin-embedded tissues was used to select 42 sporadic carcinomas (21 ECs and 21 CRCs) with MSI. Immunohistochemistry (IHC), using the anti-hMLH1 antibody, and mutation analysis, using denaturing high-performance liquid chromatography and automated sequencing, were performed on unstable carcinoma samples. Methylation analysis, using modified protocols for bisulfite treatment and methylation-specific PCR (MSP), was performed on DNA from archival tissue samples. RESULTS No MSI-positive tumor samples with normal hMLH1 immunostaining (n = 7) exhibited hMLH1 promoter methylation, whereas 8 of 35 unstable cases with loss of hMLH1 expression (23%) exhibited MSP amplification. Among analyzed cases, germ-line mutations of hMLH1 were found in 4 of 20 unmethylated samples (20%) and in 0 of 8 methylated samples. Bisulfite sequencing of amplification products from methylated samples demonstrated that almost all CpG dinucleotides within the hMLH1 promoter elements underwent methylation. CONCLUSIONS Although an MMR gene other than hMLH1 may be responsible for genetic instability in MSI-positive/IHC-positive tumors, the presence of MSP amplification and allelic deletions within the hMLH1 locus in subsets of MSI-positive/IHC-negative cases strongly suggests that hMLH1 promoter methylation may contribute to the inactivation of both hMLH1 alleles. Bisulfite analysis suggests that the mechanisms of hMLH1 silencing may depend on CpG density rather than site-specific methylation. Cancer 2003;98:1540–6. © 2003 American Cancer Society. DOI 10.1002/cncr.11651