FUS Alters circRNA Metabolism in Human Motor Neurons Carrying the ALS-Linked P525L Mutation.

Deregulation of RNA metabolism has emerged as one of the key events leading to the degeneration of motor neurons (MNs) in Amyotrophic Lateral Sclerosis (ALS) disease. Indeed, mutations on RNA-binding proteins (RBPs) or on proteins involved in aspects of RNA metabolism account for the majority of familiar forms of ALS. In particular, the impact of the ALS-linked mutations of the RBP FUS on many aspects of RNA-related processes has been vastly investigated. FUS plays a pivotal role in splicing regulation and its mutations severely alter the exon composition of transcripts coding for proteins involved in neurogenesis, axon guidance, and synaptic activity. In this study, by using in vitro-derived human MNs, we investigate the effect of the P525L FUS mutation on non-canonical splicing events that leads to the formation of circular RNAs (circRNAs). We observed altered levels of circRNAs in FUSP525L MNs and a preferential binding of the mutant protein to introns flanking downregulated circRNAs and containing inverted Alu repeats. For a subset of circRNAs, FUSP525L also impacts their nuclear/cytoplasmic partitioning, confirming its involvement in different processes of RNA metabolism. Finally, we assess the potential of cytoplasmic circRNAs to act as miRNA sponges, with possible implications in ALS pathogenesis.

Fear itself. Is fear a determinant of the efficacy oflockdowns?

Among non-pharmaceutical measures for fighting the COVID-19 pandemic, one of the most important is the implementation of lockdowns. The cost and effectiveness of this policy remains a much-debated topic in economics. In this study we investigate whether a 'fear effect' is at work in influencing the effectiveness of lockdowns. According to previous contributions on the topic, fear can increase protective habits, and for this reason we may imagine that a high number of COVID-19-caused deaths creates fear among the population, which may make people more likely to follow government prescriptions and observe lockdowns strictly. By means of a qualitative-quantitative analysis, we find that among the 46 countries that reported coronavirus-caused deaths before the implementation of a lockdown, the top quartile for per capita deaths has better results in terms of reducing new COVID-19 cases after a lockdown, compared to the worst quartile. This suggests that the number of reported deaths, as well as its communication to the population, are important determinants of the effectiveness of a lockdown.

In COVID We Trust: The Impact of The Pandemic on Religiousness-Evidence from Italian Regions.

By changing many aspects of everyday life, the COVID-19 pandemic and the social distance policies implemented to face it have affected the behaviour of people all over the world. Has the pandemic also affected people's approach towards the divine? Previous evidence suggests that prayer searches on the Internet rose during the pandemic and that people tend to rely mainly on intrinsic rather than extrinsic religiousness to cope with adversity. In the present contribution, using a set of panel random effect estimators, we compare the change in religious attendance in Italian regions before and during the pandemic. Our results suggest that there has been an increase in religiousness during the COVID-19 pandemic. Our findings are robust to several specifications of the model and to different estimators. This suggests that people derive more comfort from religious activities during hard times that are characterized by uncertainty.

Back to school or back to lockdown? The effects of opening schools on the diffusion of COVID-19 in Italian regions.

The opening of schools that coincided with the beginning of fall 2020 and the arrival of the second wave of COVID-19 in continental Europe has fostered significant debate in several countries. Some contributions have suggested that youngsters play a minor role in the spread of the virus, given the specific characteristics of this infection; other scholars have raised concerns about the necessary movement that involves keeping schools open, and the consequent potential spread of the virus. In this study, we focus on the Italian case, an interesting setting in which to test the impact of opening schools on the spread of COVID-19, because of the different dates at which schools have opened in the various Italian provinces, and because of the different rates at which the virus has spread across Italy. Our results suggest that open schools have a positive impact on COVID-19 cases, whose spread occurs between 10 and 14 days after opening. While closing schools or using distance learning have other social and economic consequences, making it necessary for policymakers to adopt a holistic evaluation, it should be taken into account that open schools have an impact on the spread of the pandemic.

Fighting the COVID pandemic: National policy choices in non-pharmaceutical interventions.

The COVID-19 pandemic pushed countries to adopt various non-pharmaceutical interventions (NPIs). Due to the features of the pandemic, which spread over time and space, governments could decide whether or not to follow policy choices made by leaders of countries affected by the virus before them. In this study, we aim to empirically model the adoption of NPIs during the first wave of COVID-19 in the 14 European countries with more than 10 million inhabitants, in order to detect whether a policy diffusion mechanism occurred. By means of a multivariate approach based on Principal Component Analysis and Cluster Analysis, we manage to derive three clusters representing different behaviour models to which the different European countries belong in the different periods of the first wave: pre-pandemic, summer relaxation and deep-lockdown scenarios. These results bring a two-fold contribution: on the one hand, they may help us to understand differences and similarities among European countries during the first wave of the COVID-19 outbreak and guide future quantitative or qualitative studies; on the other, our findings suggest that with minor exceptions (such as Sweden and Poland), different countries adopted very similar policy strategies, which are likely to be due more to the unfolding of the pandemic than to specific governmental strategies.

Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription.

OBJECTIVE: The HBV HBx regulatory protein is required for transcription from the covalently closed circular DNA (cccDNA) minichromosome and affects the epigenetic control of both viral and host cellular chromatin. DESIGN: We explored, in relevant cellular models of HBV replication, the functional consequences of HBx interaction with DLEU2, a long non-coding RNA (lncRNA) expressed in the liver and increased in human hepatocellular carcinoma (HCC), in the regulation of host target genes and the HBV cccDNA. RESULTS: We show that HBx binds the promoter region, enhances the transcription and induces the accumulation of DLEU2 in infected hepatocytes. We found that nuclear DLEU2 directly binds HBx and the histone methyltransferase enhancer of zeste homolog 2 (EZH2), the catalytic active subunit of the polycomb repressor complex 2 (PRC2) complex. Computational modelling and biochemical evidence suggest that HBx and EZH2 share two preferential binding sites in DLEU2 intron 1. HBx and DLEU2 co-recruitment on the cccDNA displaces EZH2 from the viral chromatin to boost transcription and viral replication. DLEU2-HBx association with target host promoters relieves EZH2 repression and leads to the transcriptional activation of a subset of EZH2/PRC2 target genes in HBV-infected cells and HBV-related HCCs. CONCLUSIONS: Our results highlight the ability of HBx to bind RNA to impact on the epigenetic control of both viral cccDNA and host genes and provide a new key to understand the role of DLEU2 and EZH2 overexpression in HBV-related HCCs and HBx contribution to hepatocytes transformation.

Multimodal neuroimaging in anorexia nervosa.

Anorexia nervosa (AN) is a severe and complex psychiatric disorder characterized by intense fear about weight gain and finalized to food-related control behaviors. Growing interest has been demonstrated about neurobiological processes subtend to AN physiopathology. The present review aimed to collect neurostructural and neurofunctional available data from 2010 to 2019. Results have been organized according to the neuroimaging technique employed, also including a specific section on electroencephalographic results, mostly neglected in previous reviews. Diffuse cerebral vulnerability has been demonstrated and the contribution of several structures has been identified. Insula, cingulate cortex, parietal and frontal areas are primarily involved both by structural and functional perspectives. Moreover, consistent alterations in white matter integrity and brain electrical activity have been reported. Neuroimaging findings give a substantial contribution to AN pathophysiological description, also in order to understand altered but reversible processes in the passage from acute illness phase to disorder's remission, useful also for defining therapy.

Unlocking the importance of perceived governance: The impact on COVID-19 in NUTS-2 European regions.

In the immediate aftermath of the pandemic, governments implemented non-pharmaceutical interventions (NPIs). Previous literature suggests that NPI effectiveness is influenced by governance quality. The acceptance and perceived necessity of these measures by the public are crucial to their success, as NPIs cannot be easily enforced without public support. Does regional governance also play a role? This study examines the correlation between the quality of governance in European NUTS-2 regions and the spread of COVID-19. The findings indicate that overall perceived governance, and its perceived quality and corruption pillars, significantly impact the effectiveness of these interventions. This effect was pronounced during the first wave and then diminished in importance, disappearing before vaccines were available, suggesting that regional governance matters especially in the immediate aftermath of an exogenous shock.

The fear of COVID-19 contagion: an exploratory EEG-fMRI study.

Pandemics have the potential to change how people behave and feel. The COVID-19 pandemic is no exception; thus, it may serve as a "challenging context" for understanding how pandemics affect people's minds. In this study, we used high-density electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to examine the neural correlates of fear of contagion during the most critical moments of COVID-19 in Italy (i.e., October 2020-May 2021). To do that, we stimulated participants (N = 17; nine females) with artificial-intelligence-generated faces of people presented as healthy, recovered from COVID-19, or infected by SARS-CoV-2. The fMRI results documented a modulation of large bilateral fronto-temporo-parietal functional brain networks. Critically, we found selective recruitment of cortical (e.g., frontal lobes) and subcortical fear-related structures (e.g., amygdala and putamen) of the so-called social brain network when participants observed COVID-19-related faces. Consistently, EEG results showed distinct patterns of brain activity selectively associated with infected and recovered faces (e.g., delta and gamma rhythm). Together, these results highlight how pandemic contexts may reverberate in the human brain, thus influencing most basic social and cognitive functioning. This may explain the emergence of a cluster of psychopathologies during and after the COVID-19 pandemic. Therefore, this study underscores the need for prompt interventions to address pandemics' short- and long-term consequences on mental health.

The Relationship between Executive Functions and Body Weight: Sex as a Moderating Variable.

This study explores the interplay between executive functions and body weight, examining both the influence of biological factors, specifically sex, and methodological issues, such as the choice between Body Mass Index (BMI) and waist circumference (WC) as the primary anthropometric measure. A total of 386 participants (222 females, mean age = 45.98 years, SD = 17.70) were enrolled, from whom sociodemographic (sex, age, years of formal education) and anthropometric (BMI and WC) data were collected. Executive functions were evaluated using the Frontal Assessment Battery-15 (FAB15). The results showed the increased effectiveness of WC over BMI in examining the relationships between executive functions, sex differences, and body weight. In particular, this study revealed that there was a significant moderating effect of sex at comparable levels of executive functioning. Specifically, women with higher executive performance had lower WCs than their male counterparts, suggesting that executive function has a greater impact on WC in women than in men. Our findings highlight the importance of conducting more in-depth investigations of the complex relationship between cognitive deficits and weight gain, considering confounding variables of behavioral, psychobiological, and neurophysiological origin.

The effect of self-esteem on the spread of a pandemic. A cross-country analysis of the role played by self-esteem in the spread of the COVID-19 pandemic.

Extant research on COVID-19 suggests that many socio-economic determinants, by affecting personal behavior, have influenced the evolution of the pandemic. In this paper we study the role played in this regard by average levels of self-esteem in the public. There are reasons to believe that both low and very levels of self-esteem may have an effect on the spread of COVID-19, for opposite reasons. On the one hand, people with low self-esteem may not worry enough to behave in the way recommended (and prescribed, through non-pharmaceutical interventions) by the authorities; people with very high self-esteem, on the other hand, may be over-confident and fail to follow the prescriptions, believing that they do not need them. In this study we test this hypothesis by means of a quantitative cross-country analysis, using a hybrid model and the Rosenberg self-esteem scale. Our results suggest the existence of a U-shaped relationship between the trend of COVID-19 and average levels of self-esteem in a country.

Assessing the effectiveness of mandatory outdoor mask policy: The natural experiment of Campania.

Face masks are possibly the main symbol of the COVID-19 pandemic. Once rarely used in Western countries, in the last two years they have become an object it is impossible to leave one's home without. Italy made their use a legal requirement, even outdoors, from late 2020 to early 2022. The effectiveness of this policy in reducing COVID-19 cases has been widely debated. The recent cancellation of their mandatory use in Italy offers an interesting setting in which to test its impact, since one Italian region (Campania) extended the restriction for a further three weeks. We aim to shed some light on the real-world impact of mandatory use of face masks outdoors, identifying the effect of this policy on the spread of COVID-19. By means of a quantitative analysis, employing a synthetic control method approach, we find that Campania had statistically the same number of cases as its synthetic counterfactual, built from a donor pool formed from the other Italian provinces. Hence, results suggest that while it imposes a burden on the public, the use of face masks outdoors is not correlated with a decrease in the number of COVID-19 cases.

On the determinants of anti-COVID restriction and anti-vaccine movements: the case of IoApro in Italy.

Following restrictions to control the spread of COVID-19, and subsequent vaccination campaigns, sentiments against such policies were quick to arise. While individual-level determinants that led to such attitudes have drawn much attention, there are also reasons to believe that the macro context in which these movements arose may contribute to their evolution. In this study, exploiting data on business activities which supported a major Italian anti-restriction and anti-vaccine movement, IoApro, using quantitative analysis that employs both a fractional response probit and logit model and a beta regression model, we investigate the relationship between socio-economic characteristics, institutional quality, and the flourishing of this movement. Our results suggest a U-shaped relationship between income and the proliferation of the movement, meaning that support for these movements increases the greater the degree of economic decline. Our results further indicate that the share of the population between 40 and 60 years old is positively related to support for such movements, as is institutional corruption.

Sex differences in functional brain networks involved in interoception: An fMRI study.

Interoception can be described as the ability to perceive inner body sensations and it is different between biological sex. However, no previous research correlated this ability with brain functional connectivity (FC) between males and females. In this study, we used resting-state functional magnetic resonance imaging to investigate FC of networks involved in interoception among males and females in a sample of healthy volunteers matched for age. In total, 67 participants (34 females, mean age 44.2; 33 males, mean age 37.2) underwent a functional MRI session and completed the Self-Awareness Questionnaire (SAQ) that tests the interoceptive awareness. To assess the effect of sex on scores obtained on the SAQ we performed a multivariate analysis of variance. A whole-brain seed-to-seed FC analysis was conducted to investigate the correlation between SAQ score and FC, and then to test differences in FC between males and females with SAQ score as a covariate. MANOVA revealed a significant difference in SAQ scores between males and females with higher values for the second ones. Also, significant correlations among interoception scores and FC in Salience network and fronto-temporo-parietal brain areas have been detected, with a sharp prevalence for the female. These results support the idea of a female advantage in the attention toward interoceptive sensations, suggesting common inter-network areas that concur to create the sense of self.

Simultaneous real-time EEG-fMRI neurofeedback: A systematic review.

Neurofeedback (NF) is a biofeedback technique that teaches individuals self-control of brain functions by measuring brain activations and providing an online feedback signal to modify emotional, cognitive, and behavioral functions. NF approaches typically rely on a single modality, such as electroencephalography (EEG-NF) or a brain imaging technique, such as functional magnetic resonance imaging (fMRI-NF). The introduction of simultaneous EEG-fMRI tools has opened up the possibility of combining the high temporal resolution of EEG with the high spatial resolution of fMRI, thereby increasing the accuracy of NF. However, only a few studies have actively combined both techniques. In this study, we conducted a systematic review of EEG-fMRI-NF studies (N = 17) to identify the potential and effectiveness of this non-invasive treatment for neurological conditions. The systematic review revealed a lack of homogeneity among the studies, including sample sizes, acquisition methods in terms of simultaneity of the two procedures (unimodal EEG-NF and fMRI-NF), therapeutic targets field, and the number of sessions. Indeed, because most studies are based on a single session of NF, it is difficult to draw any conclusions regarding the therapeutic efficacy of NF. Therefore, further research is needed to fully understand non-clinical and clinical potential of EEG-fMRI-NF.

ß-arrestin1-E2F1-ac axis regulates physiological apoptosis and cell cycle exit in cellular models of early postnatal cerebellum.

Development of the cerebellum is characterized by rapid proliferation of cerebellar granule cell precursors (GCPs) induced by paracrine stimulation of Sonic hedgehog (Shh) signaling from Purkinje cells, in the external granular layer (EGL). Then, granule cell precursors differentiate and migrate into the inner granular layer (IGL) of the cerebellum to form a terminally differentiated cell compartment. Aberrant activation of Sonic hedgehog signaling leads to granule cell precursors hyperproliferation and the onset of Sonic hedgehog medulloblastoma (MB), the most common embryonal brain tumor. ß-arrestin1 (ARRB1) protein plays an important role downstream of Smoothened, a component of the Sonic hedgehog pathway. In the medulloblastoma context, ß-arrestin1 is involved in a regulatory axis in association with the acetyltransferase P300, leading to the acetylated form of the transcription factor E2F1 (E2F1-ac) and redirecting its activity toward pro-apoptotic gene targets. This axis in the granule cell precursors physiological context has not been investigated yet. In this study, we demonstrate that ß-arrestin1 has antiproliferative and pro-apoptotic functions in cerebellar development. ß-arrestin1 silencing increases proliferation of Sonic hedgehog treated-cerebellar precursor cells while decreases the transcription of E2F1-ac pro-apoptotic targets genes, thus impairing apoptosis. Indeed, chromatin immunoprecipitation experiments show a direct interaction between ß-arrestin1 and the promoter regions of the pro-apoptotic E2F1 target gene and P27, indicating the double role of ß-arrestin1 in controlling apoptosis and cell cycle exit in a physiological context. Our data elucidate the role of ß-arrestin1 in the early postnatal stages of cerebellar development, in those cell compartments that give rise to medulloblastoma. This series of experiments suggests that the physiological function of ß-arrestin1 in neuronal progenitors is to directly control, cooperating with E2F1 acetylated form, transcription of pro-apoptotic genes.

On the functional brain networks involved in tool-related action understanding.

Tool-use skills represent a significant cognitive leap in human evolution, playing a crucial role in the emergence of complex technologies. Yet, the neural mechanisms underlying such capabilities are still debated. Here we explore with fMRI the functional brain networks involved in tool-related action understanding. Participants viewed images depicting action-consistent (e.g., nail-hammer) and action-inconsistent (e.g., scarf-hammer) object-tool pairs, under three conditions: semantic (recognizing the tools previously seen in the pairs), mechanical (assessing the usability of the pairs), and control (looking at the pairs without explicit tasks). During the observation of the pairs, task-based left-brain functional connectivity differed within conditions. Compared to the control, both the semantic and mechanical conditions exhibited co-activations in dorsal (precuneus) and ventro-dorsal (inferior frontal gyrus) regions. However, the semantic condition recruited medial and posterior temporal areas, whereas the mechanical condition engaged inferior parietal and posterior temporal regions. Also, when distinguishing action-consistent from action-inconsistent pairs, an extensive frontotemporal neural circuit was activated. These findings support recent accounts that view tool-related action understanding as the combined product of semantic and mechanical knowledge. Furthermore, they emphasize how the left inferior parietal and anterior temporal lobes might be considered as hubs for the cross-modal integration of physical and conceptual knowledge, respectively.

COVID-19 Diffusion Before Awareness: The Role of Football Match Attendance in Italy.

Anecdotal evidence suggests that football matches may have played a role in the spread of COVID-19 all over Europe. Nevertheless, from a scientific point of view, the impact of football matches on the spread of COVID-19 remains unclear. In this paper we study, via a quantitative analysis, the case of Italy, a country badly affected by COVID, and one where attending football matches is very popular. We consider the impact of matches played in January and February 2020 on the dynamic of the pandemic in March and April the same year. Our results, which consider all levels of Italian professional football, and the highest level of amateur football, show that matches played in January and February had an impact on the evolution of the pandemic in March and April. These results suggest that great care must be taken before considering re-opening stadia.

COVID-19 in Central Asia: exploring the relationship between governance and non-pharmaceutical intervention.

To fight coronavirus disease 2019, non-pharmaceutical interventions were adopted all over the world. Non-pharmaceutical intervention (NPI) effectiveness also depends on governments' capacity to implement sound policies. Stay-at-home orders are binding measures that can raise serious concerns among the population. The perceived quality and effective need for these measures are therefore crucial for the willingness of the citizens to accept NPIs. This study investigates the relationship between the efficacy of NPIs and governance quality in Central Asia. Results suggest that overall governance quality matters and that in this relationship regulatory quality is more important than rule of law, which matters more than government effectiveness.

Does social capital enforce social distancing? The role of bridging and bonding social capital in the evolution of the pandemic.

By shaping the way people look at members of their networks as well as strangers, social capital affects the behavior of a population during a pandemic. Over the course of 2020, various countries implemented non-pharmaceutical interventions (NPI), imposing restrictions that were difficult to enforce (due to the scale of the policies) in order to protect the public from the threat of COVID-19. This is an interesting quasi-experimental setting in which to test the compliance of populations with different levels of social capital with government suggestions and prescriptions. With the help of European Social Survey data, and the John Hopkins University dataset on the spread of COVID-19 around the world, the present work aims to test the impact within a sample of European countries with different social capital stocks on the spread of coronavirus. The results show that countries with higher social capital have fewer COVID-19 cases, ceteris paribus for NPI. This is especially true if this capital is of the bonding kind.