The role of myristoylation in the membrane association of the Lassa virus matrix protein Z

The Z protein is the matrix protein of arenaviruses and has been identified as the main driving force for budding. Both LCMV and Lassa virus Z proteins bud from cells in the absence of other viral proteins as enveloped virus-like particles. Z accumulates near the inner surface of the plasma membrane where budding takes place. Furthermore, biochemical data have shown that Z is strongly membrane associated. The primary sequence of Z lacks a typical transmembrane domain and until now it is not understood by which mechanism Z is able to interact with cellular membranes. In this report, we analyzed the role of N-terminal myristoylation for the membrane binding of Lassa virus Z. We show that disruption of the N-terminal myristoylation signal by substituting the N-terminal glycine with alanine (Z-G2A mutant) resulted in a significant reduction of Z protein association with cellular membranes. Furthermore, removal of the myristoylation site resulted in a relocalization of Z from a punctuate distribution to a more diffuse cellular distribution pattern. Finally, treatment of Lassa virus-infected cells with various myristoylation inhibitors drastically reduced efficient Lassa virus replication. Our data indicate that myristoylation of Z is critical for its binding ability to lipid membranes and thus, for effective virus budding

Pedagogical observation in telecollaborative learning contexts

This article aims at proposing an observation grid for teachers who work in telecollaborative learning contexts. In order to do that, a theoretical framework about telecollaborative learning environments, mediation and observation is presented. We develop a case study about observation practices performed by mediators related to the project ‘Teletandem Brazil: foreign languages for all’, which can be defined as a telecollaborative context for language learning The research data consist of eight open-ended questionnaires about mediators observation performances. The analysis affiliates a qualitative interpretation approach guided by Grounded Theory constructs. Finally, based on the literature, on the case study results discussed herein and on our experiences as researchers in tandem learning projects, we present a reflexive framework about pedagogical observation practices in telecollaborative and multimodal learning contexts. Keywords: pedagogical observation, telecollaboration, teletandem.</p

Observação pedagógica em contexto de aprendizagem telecolaborativa

This article aims at proposing an observation grid for teachers who work in telecollaborative learning contexts. In order to do that, a theoretical framework about telecollaborative learning environments, mediation and observation is presented. We develop a case study about observation practices performed by mediators related to the project ‘Teletandem Brazil: foreign languages for all’, which can be defined as a telecollaborative context for language learning The research data consist of eight open-ended questionnaires about mediators observation performances. The analysis affiliates a qualitative interpretation approach guided by Grounded Theory constructs. Finally, based on the literature, on the case study results discussed herein and on our experiences as researchers in tandem learning projects, we present a reflexive framework about pedagogical observation practices in telecollaborative and multimodal learning contexts. Keywords: pedagogical observation, telecollaboration, teletandem.O presente artigo tem como objetivo propor uma grade de observação para professores que atuam em contextos telecolaborativos de aprendizagem. Para isso, apresentamos um quadro teórico sobre ambientes telecolaborativos de aprendizagem, mediação e observação, e propomos um estudo de caso sobre as práticas de observação desempenhadas por mediadores vinculados a um contexto telecolaborativo de aprendizagem de línguas, o projeto Teletandem Brasil: línguas estrangeiras para todos. Os dados são constituídos por oito questionários abertos sobre as práticas de observação desses mediadores e a análise se enquadra em uma abordagem qualitativa de interpretação orientada pelos construtos da Teoria Fundamentada em Dados, ou Grounded Theory. Assim, com base na literatura, nos resultados do estudo de caso aqui analisado e em nossa experiência como pesquisadoras de projetos de aprendizagem em tandem, apresentamos, ao final do artigo, um quadro reflexivo e embasado em pesquisa sobre práticas de observação pedagógica em contextos telecolaborativos e multimodais de aprendizagem.Palavras-chave: observação pedagógica, telecolaboração, teletandem

Increasing Number of Individuals Receiving Hepatitis B nucleos(t)ide Analogs Therapy in Germany, 2008–2019

Background: Germany is a low prevalence country for hepatitis B virus (HBV) infection with higher prevalence in vulnerable groups. The number of treated chronic hepatitis B (CHB) patients is unknown. We aimed to determine the number of CHB patients treated with nucleos(t)ide analogs (NUCs), the treatment costs within the statutory health insurance (SHI) in Germany and per patient per month. Methods: Data on pharmacy bills of NUCs to patients with SHI between 2008 and 2019 were purchased from Insight Health™ and described. Negative binomial regression was used for trend analysis. Results: Number of patients increased between 2008 and 2019 (4.9% per year) with little changes in treatment options. Overall prescription costs were increasing (6.7% per year on average) until the introduction of tenofovir and entecavir generics in 2017 after which costs decreased by 31% in 2019. Average therapy costs peaked at 498 Euro per patient per month in 2016 and decreased to 214 Euro in 2019. Prescriptions changed from 30 to 90 pills per pack over time. HBV therapy was prescribed to 97% by three medical specialist groups, mainly specialists in internal medicine (63%), followed by hospital-based outpatient clinics (20%) and general practitioners (15%). Contrary to guideline recommendation, adefovir was still prescribed after 2011 for 1–5% of patients albeit with decreasing tendency. Prescriptions per 100,000 inhabitants were highest in Berlin and Hamburg. Conclusion: Our data shows, that the number of treated CHB patients increased steadily, while NUC therapy costs decreased. We recommend continued testing and treatment for those eligible to prevent advanced liver disease and possibly decrease further transmission of HBV.Peer Reviewe

Synchronizing the timing of anoxia, volcanism and the pacing of the Earth’s orbit in the Early Cretaceous

Recurrent acceleration of the hydrolysing cycle, so-called Episodes of Environmental Changes, occur in the Early Cretaceous. As the geologic time scale show large uncertainties, the pacing and the chronological relationship of these events remain obscure. We present here new radio-astrochronologic data from the Neuquén Basin (Argentina) anchored to the Tethyan realm. The new time sale of the Valanginian-Hauterivian provides ages of ammonite zones with an uncertainty of ± 0.2 myr and provides much precise age of the start of the Weissert Event. The age of the start of the Weissert Event is at 134.5 ± 0.2 myr, which is exactly synchronous with the main phase of the Paraná-Etendeka large igneous province activity. Most recent duration and age estimates from the Berriasian to the Barremian are reviewed and differ from the Geologic Time Scale 2016 by several million of years. Thanks to this new time scale, belemnite δ13C are reviewed and show a strong pacing with a period of 2.4 myr, which correspond to the long-eccentricity cycle. Higher amplitudes of the 2.4-myr cycle are observed at time of large igneous province emplacement, which may be due to accelerated hydrolysis cycle following CO2 input to the atmosphere from the volcanic activity.Fil: Martinez, Mathieu. Universite de Rennes I; FranciaFil: Aguirre Urreta, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Lescano, Marina Aurora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Omarini, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Tunik, Maisa Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Frederichs, Thomas. Universitat Bremen; AlemaniaFil: Nickl, Anna-Leah. Universitat Bremen; AlemaniaFil: Pälike, Heiko. Universitat Bremen; AlemaniaEGU General Assembly 2019VienaAustriaEuropean Geosciences Unio

Role of Fas and Treg Cells in Fracture Healing as Characterized in the Fas-Deficient (lpr) Mouse Model of Lupus

Previous studies showed that loss of tumor necrosis factor α (TNFα) signaling delayed fracture healing by delaying chondrocyte apoptosis and cartilage resorption. Mechanistic studies showed that TNFα induced Fas expression within chondrocytes; however, the degree to which chondrocyte apoptosis is mediated by TNFα alone or dependent on the induction of Fas is unclear. This question was addressed by assessing fracture healing in Fas-deficient B6.MRL/Faslpr/J mice. Loss of Fas delayed cartilage resorption but also lowered bone fraction in the calluses. The reduced bone fraction was related to elevated rates of coupled bone turnover in the B6.MRL/Faslpr/J calluses, as evidenced by higher osteoclast numbers and increased osteogenesis. Analysis of the apoptotic marker caspase 3 showed fewer positive chondrocytes and osteoclasts in calluses of B6.MRL/Faslpr/J mice. To determine if an active autoimmune state contributed to increased bone turnover, the levels of activated T cells and Treg cells were assessed. B6.MRL/Faslpr/J mice had elevated Treg cells in both spleens and bones of B6.MRL/Faslpr/J but decreased percentage of activated T cells in bone tissues. Fracture led to ∼30% to 60% systemic increase in Treg cells in both wild-type and B6.MRL/Faslpr/J bone tissues during the period of cartilage formation and resorption but either decreased (wild type) or left unchanged (B6.MRL/Faslpr/J) the numbers of activated T cells in bone. These results show that an active autoimmune state is inhibited during the period of cartilage resorption and suggest that iTreg cells play a functional role in this process. These data show that loss of Fas activity specifically in chondrocytes prolonged the life span of chondrocytes and that Fas synergized with TNFα signaling to mediate chondrocyte apoptosis. Conversely, loss of Fas systemically led to increased osteoclast numbers during later periods of fracture healing and increased osteogenesis. These findings suggest that retention of viable chondrocytes locally inhibits osteoclast activity or matrix proteolysis during cartilage resorption

Exploring factors influencing patient mortality and loss to follow-up in two paediatric hospital wards in Zamfara, North-West Nigeria, 2016-2018

Introduction Child mortality has been linked to infectious diseases, malnutrition and lack of access to essential health services. We investigated possible predictors for death and patients lost to follow up (LTFU) for paediatric patients at the inpatient department (IPD) and inpatient therapeutic feeding centre (ITFC) of the Anka General Hospital (AGH), Zamfara State, Nigeria, to inform best practices at the hospital. Methods We conducted a retrospective cohort review study using routinely collected data of all patient admissions to the IPD and ITFC with known hospital exit status between 2016 and 2018. Unadjusted and adjusted rate ratios (aRR) and respective 95% confidence intervals (95% CI) were calculated using Poisson regression to estimate the association between the exposure variables and mortality as well as LTFU. Results The mortality rate in IPD was 22% lower in 2018 compared to 2016 (aRR 0.78; 95% CI 0.66–0.93) and 70% lower for patients coming from lead-affected villages compared to patients from other villages (aRR 0.30; 95% CI 0.19–0.48). The mortality rate for ITFC patients was 41% higher during rainy season (aRR 1.41; 95% CI 1.2–1.6). LTFU rates in ITFC increased in 2017 and 2018 when compared to 2016 (aRR 1.6; 95% CI 1.2–2.0 and aRR 1.4; 95% CI 1.1–1.8) and patients in ITFC had 2.5 times higher LTFU rates when coming from a lead-affected village. Conclusions Our data contributes clearer understanding of the situation in the paediatric wards in AGH in Nigeria, but identifying specific predictors for the multifaceted nature of mortality and LTFU is challenging. Mortality in paediatric patients in IPD of AGH improved during the study period, which is likely linked to better awareness of the hospital, but still remains high. Access to healthcare due to seasonal restrictions contributes to mortalities due to late presentation. Increased awareness of and easier access to healthcare, such as for patients living in lead-affected villages, which are still benefiting from an MSF lead poisoning intervention, decreases mortalities, but increases LTFU. We recommend targeted case audits and qualitative studies to better understand the role of health-seeking behaviour, and social and traditional factors in the use of formal healthcare in this part of Nigeria and potentially similar settings in other countries

Sustainable environmental geotechnics practices for a green economy

The revitalisation of the global economy after the Covid-19 era presents environmental geotechnics with the opportunity to reinforce the need for a change in paradigm towards a green, circular economy and to promote aggressively the use and development of sustainable technologies and management practices. This paper aims to assist in this effort by concentrating on several thematic areas where sustainability solutions and future improvements are sought. These include the re-entry of construction and demolition of wastes, excavated materials, industrial wastes and marine sediments into the production cycle and the reuse of existing foundations. Despite the recent trend in advanced countries towards recycling and waste-to-energy thermal treatment, landfills still constitute the most common municipal solid waste management practice, especially in low-and-middle-income countries, and technological solutions to improve their environmental footprint are hereby presented. At the same time, remediation solutions are required to address the multitude of contaminated sites worldwide. Advanced developments that incorporate environmental, economic and social dimensions are expounded by the authors, together with sustainable ground improvement solutions for infrastructure projects conducted in soft and weak soils. The topic of thermo-active geostructures concludes this paper, where, apart from their infrastructure utility, these structures have the potential to contribute to the renewable energy source.Published versionThe second author would like to acknowledge the support of the Office of the Associate Provost for Research and Academic Development at Abu Dhabi University, UAE through grant19300540

The Global Jukebox: A public database of performing arts and culture

Standardized cross-cultural databases of the arts are critical to a balanced scientific under- standing of the performing arts, and their role in other domains of human society. This paper introduces the Global Jukebox as a resource for comparative and cross-cultural study of the performing arts and culture. The Global Jukebox adds an extensive and detailed global database of the performing arts that enlarges our understanding of human cultural diversity. Initially prototyped by Alan Lomax in the 1980s, its core is the Cantometric s dataset, encompassing standardized codings on 37 aspects of musical style for 5,776 traditional songs from 1,026 societies. The Cantometrics dataset has been cleaned and checked for reliability and accuracy, and includes a full coding guide with audio training examples ( https:// theglobaljukebox. org/?songsofearth ). Also being released are seven additional datasets coding and describing instrumentation, conversation, popular music, vowel and consonant placement, breath management , social factors, and societies. For the first time, all digitized Global Jukebox data are being made available in open-access, downloadable format ( https://github.com/theglobaljukebox ), linked with streaming audio recordings (theglobaljukebox.org) to the maximum extent allowed while respecting copyright and the wishes of cul- ture-bearers. The data are cross-indexed with the Database of Peoples, Languages, and Cultures (D-PLACE) to allow researchers to test hypotheses about worldwide coevolution of aesthetic patterns and traditions. As an example, we analyze the global relationship between song style and societal complexity, showing that they are robustly related, in contrast to previous critiques claiming that these proposed relationships were an artifact of autocorrelation (though causal mechanisms remain unresolved