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Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.

Introduction: Italy is one of the high-income countries hit hardest by Covid-19. During the first months of the pandemic, Italian healthcare workers were praised by media and the public for their efforts to face the emergency, although with limited knowledge and resources. However, healthcare workers soon had to face new challenges at a time when the national health system was working hard to recover. This study focuses on this difficult period to assess the impact of the COVID-19 pandemic on the mental health of Italian healthcare workers. Materials and Methods: Healthcare workers from all Italian regions [n = 5,502] completed an online questionnaire during the reopening phase after the first wave lockdown. We assessed a set of individual-level factors (e.g., stigma and violence against HCWs) and a set of workplace-level factors (e.g., trust in the workplace capacity to handle COVID-19) that were especially relevant in this context. The primary outcomes assessed were score ≥15 on the Patient Health Questionnaire-9 and score ≥4 on the General Health Questionnaire-12, indicators of clinically significant depressive symptoms and psychological distress, respectively. Logistic regression analyses were performed on depressive symptoms and psychological distress for each individual- and workplace-level factor adjusting for gender, age, and profession. Results: Clinically significant depressive symptoms were observed in 7.5% and psychological distress in 37.9% of HCWs. 30.5% of healthcare workers reported having felt stigmatized or discriminated, while 5.7% reported having experienced violence. Feeling stigmatized or discriminated and experiencing violence due to being a healthcare worker were strongly associated with clinically significant depressive symptoms [OR 2.98, 95%CI 2.36–3.77 and OR 4.72 95%CI 3.41–6.54] and psychological distress [OR 2.30, 95%CI 2.01–2.64 and OR 2.85 95%CI 2.16–3.75]. Numerous workplace-level factors, e.g., trust in the workplace capacity to han

The widespread cancelation of cultural events during the early 2020 stages of the COVID-19 pandemic led professional performing musicians across the world to experience an increasing economic fragility that threatened their health and wellbeing. Within this "new normal," developing countries have been at a higher risk due to their vulnerable health systems and cultural policies. Even in such difficult times, the music profession requires musicians to keep up their practicing routines, even if they have no professional commitments. This is because high level technical and expressive skills are crucial to sustaining a music career at a high performance level. However, it could be expected that not all musicians might have had the same engagement with music practice during lockdowns. In this study, we studied the experiences of 309 professional classical musicians based in European and Latin American countries with different levels of performing experience to examine their passionate (or lack thereof) engagement with music practice. Through the mixed methods combination of multigroup invariance and narrative analyses, we identified distinct profiles of musicians who displayed more harmonious or more obsessive passion orientations before and at the peak of the pandemic. We observed that musicians with higher levels of harmonious passion in particular were more capable of sustaining their practice at the peak of the pandemic and that these musicians were mostly located in Latin America-a paradox, considering that cultural politics supporting the careers of professional performing musicians and entrepreneurial education in Latin America are lacking to a great extent, especially in comparison with the European context. We explain this in terms of the "forced" self-management embraced by musicians in Latin American countries who want to engage with music practice both before and during the COVID-19 pandemic even if the music profession does not generate enough revenue for t

BACKGROUND: Among all psychoactive substances, alcohol consumption presents the most significant public health problem and is a leading risk factor for overall disease burden in Latin America. However, most people who meet criteria for a substance use disorder do not receive treatment in primary or secondary care sources. Community members can play a role in helping people to seek help as they are likely to encounter people experiencing problem drinking and recognize the signs. However, many do not have adequate mental health first aid knowledge or skills to provide help. We aimed to culturally adapt the existing English-language mental health first aid guidelines for helping someone with problem drinking for Argentina and Chile. METHODS: The Delphi consensus method was used to determine the importance of helping actions translated from the English-language guidelines and to add new actions suggested by expert panellists. The importance of each statement was rated by two expert panels. Panel one included people with lived experience (either their own or as a support person, n = 23) recruited in Argentina and panel two included health professionals (n = 31) recruited in Argentina and Chile. RESULTS: Overall, 165 helping actions were endorsed by panellists across two consecutive survey rounds. Endorsed items included 132 of the 182 items translated into Spanish from the English-language guidelines and 33 of the 61 new items generated from panellists' comments in the first survey round. CONCLUSIONS: While there were some similarities in recommended helping actions between English-speaking countries, and Argentina and Chile, key differences were seen in attitudes to low-risk drinking. While there was a relatively high level of agreement between health professionals and people with lived experience, some divergence of opinion was seen, particularly in the area of commitment to recovery as a condition for help. Future research should explore the implementation of the guid

Coastal aquatic ecosystems such as estuaries and coastal lagoons are important atmospheric methane sources that must be better constrained. This work presents a detailed characterization of the methane cycle in a tropical coastal lagoon (La Mancha, Veracruz, Mexico) and its tributary river over three distinct seasons, along a transect from the river to the sea connection. In addition to several physicochemical parameters, the dissolved methane, carbon dioxide, and oxygen concentrations were measured with high resolution in the sediments and the water column, combined with production/uptake rates. Methane and carbon dioxide cycles were further constrained by determining atmospheric flux over the entire river and lagoon sections. The results indicate that La Mancha is a highly contrasted ecosystem. The river section is characterized by a strong pycnocline, relatively high methane concentration, and active methanogenesis and methanotrophy, discharging into a relatively homogeneous lagoon section where the methane and carbon cycles are less active. Overall, both the river and the lagoon were a net source of methane and carbon dioxide, with an annual emission of 2.9 metric tons of methane and 2757 metric tons of carbon dioxide. The spatial structure of the main components of the methane, carbon dioxide, and oxygen cycles was established, and it was observed that depthwise heterogeneities predominated in the river section. In contrast, lengthwise heterogeneities dominated in the lagoon section.