Functional and in silico Characterization of Neutralizing Interactions Between Antibodies and the Foot-and-Mouth Disease Virus Immunodominant Antigenic Site

Molecular knowledge of virus–antibody interactions is essential for the development of better vaccines and for a timely assessment of the spread and severity of epidemics. For foot-and-mouth disease virus (FMDV) research, in particular, computational methods for antigen–antibody (Ag–Ab) interaction, and cross-antigenicity characterization and prediction are critical to design engineered vaccines with robust, long-lasting, and wider response against different strains. We integrated existing structural modeling and prediction algorithms to study the surface properties of FMDV Ags and Abs and their interaction. First, we explored four modeling and two Ag–Ab docking methods and implemented a computational pipeline based on a reference Ag–Ab structure for FMDV of serotype C, to be used as a source protocol for the study of unknown interaction pairs of Ag–Ab. Next, we obtained the variable region sequence of two monoclonal IgM and IgG antibodies that recognize and neutralize antigenic site A (AgSA) epitopes from South America serotype A FMDV and developed two peptide ELISAs for their fine epitope mapping. Then, we applied the previous Ag–Ab molecular structure modeling and docking protocol further scored by functional peptide ELISA data. This work highlights a possible different behavior in the immune response of IgG and IgM Ab isotypes. The present method yielded reliable Ab models with differential paratopes and Ag interaction topologies in concordance with their isotype classes. Moreover, it demonstrates the applicability of computational prediction techniques to the interaction phenomena between the FMDV immunodominant AgSA and Abs, and points out their potential utility as a metric for virus-related, massive Ab repertoire analysis or as a starting point for recombinant vaccine design.Fil: Marrero Diaz de Villegas, Ruben. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Seki, Cristina. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Animal; ArgentinaFil: Mattion, Nora Marta. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Animal; ArgentinaFil: König, Guido Alberto. Instituto Nacional de Tecnología Agropecuaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

COVID-19 pandemic and student reading achievement: findings from a school panel study

Since 2020, the COVID-19 pandemic had an impact on education worldwide. There is increased discussion of possible negative effects on students’ learning outcomes and the need for targeted support. We examined fourth graders’ reading achievement based on a school panel study, representative on the student level, with N = 111 elementary schools in Germany (total: N = 4,290 students, age: 9–10 years). The students were tested with the Progress in International Reading Literacy Study instruments in 2016 and 2021. The analysis focused on (1) total average differences in reading achievement between 2016 and 2021, (2) average differences controlling for student composition, and (3) changes in achievement gaps between student subgroups (i.e., immigration background, socio-cultural capital, and gender). The methodological approach met international standards for the analysis of large-scale assessments (i.e., multiple multi-level imputation, plausible values, and clustered mixed-effect regression). The results showed a substantial decline in mean reading achievement. The decline corresponds to one-third of a year of learning, even after controlling for changes in student composition. We found no statistically significant changes of achievement gaps between student subgroups, despite numerical tendencies toward a widening of achievement gaps between students with and without immigration background. It is likely that this sharp achievement decline was related to the COVID-19 pandemic. The findings are discussed in terms of further research needs, practical implications for educating current student cohorts, and educational policy decisions regarding actions in crises such as the COVID-19 pandemic

Engagiert, engagierter... Fernstudent! Die Bedeutung von Ressourcen und Engagement im Fernstudium

Das Fernstudium stellt besondere Anforderungen an die Studierenden. Es fordert eine selbstregulierte Lernstruktur sowie ein Zeitmanagement, die es erlauben, Studium, Familie und Berufstätigkeit miteinander zu vereinen. Zudem sind meist mehrere Jahre zwischen Schule und Studium vergangen. So liegt die Vermutung nahe, dass gerade bei Studierenden an einer Fernuniversität das Engagement (Bakker, Schaufeli, Leiter & Taris, 2008) besonders bedeutsam ist. Für die Betrachtung dieses Sachverhaltes wurde die Utrecht Work Engagement Scale für Studierende (UWES-S) (Schaufeli, Martinez, Pinto, Salanova & Bakker, 2002) herangezogen. Mit deren Übersetzung ins Deutsche wurde das Studienengagement Fernunistudierenden untersucht. Ferner wurde die Grundannahme des Job-Demands-Resources-Modells (JD-R) (Schaufeli & Bakker, 2004; Bakker & Demerouti, 2007), dass Ressourcen einen durch Engagement vermittelten Einfluss auf den Studienerfolg besitzen (Hakanen, Schaufeli & Ahola, 2008), von uns auf den Studienkontext übertragen. Gerade für Fernstudierende interessante und relevante Ressourcen könnten z.B. die wahrgenommene allgemeine und studienkontextbezogene soziale Unterstützung, die Selbstwirksamkeitserwartung und die erlebte Autonomie bei der Einteilung des Studiums sein. In dieser Studie wurden von uns die folgenden Fragestellungen untersucht: Kann die Übersetzung und Anpassung der UWES-S für unseren Kontext als valide bezeichnet werden? Unterscheiden sich Fernstudierende von Studierenden an Präsenzuniversitäten im Engagement (unabhängig vom Alter)? Gibt es zwischen im Fernstudium relevanten Ressourcen und dem Studienerfolg einen Zusammenhang, der durch das Studienengagement vermittelt wird

Exploring the identification, validation, and categorization of costs and benefits of education in mental health: the PECUNIA project

BackgroundMental health problems can lead to costs and benefits in other sectors (e.g. in the education sector) in addition to the healthcare sector. These related costs and benefits are known as intersectoral costs and benefits (ICBs). Although some ICBs within the education sector have been identified previously, little is known about their extensiveness and transferability, which is crucial for their inclusion in health economics research.ObjectivesThe aim of this study was to identify ICBs in the education sector, to validate the list of ICBs in a broader European context, and to categorize the ICBs using mental health as a case study.MethodsPreviously identified ICBs in the education sector were used as a basis for this study. Additional ICBs were extracted from peer-reviewed literature in PubMed and grey literature from six European countries. A comprehensive list of unique items was developed based on the identified ICBs. The list was validated by surveying an international group of educational experts. The survey results were used to finalize the list, which was categorized according to the care atom.ResultsAdditional ICBs in the education sector were retrieved from ninety-six sources. Fourteen experts from six European countries assessed the list for completeness, clarity, and relevance. The final list contained twenty-four ICBs categorized into input, throughput, and output.ConclusionBy providing a comprehensive list of ICBs in the education sector, this study laid further foundations for the inclusion of important societal costs in health economics research in the broader European context

Exploring the identification, validation, and categorization of the cost and benefits of criminal justice in mental health: the PECUNIA project

Background Mental health disorders and their treatments produce significant costs and benefits in both healthcare and non-healthcare sectors. The latter are often referred to as intersectoral costs and benefits (ICBs). Little is known about healthcare-related ICBs in the criminal justice sector and how to include these in health economics research. Objectives The triple aim of this study is (i) to identify healthcare-related ICBs in the criminal justice sector, (ii) to validate the list of healthcare-related ICBs in the criminal justice sector on a European level by sector-specific experts, and (iii) to classify the identified ICBs. Methods A scientific literature search in PubMed and an additional grey literature search, carried out in six European countries, were used to retrieve ICBs. In order to validate the international applicability of the ICBs, a survey was conducted with an international group of experts from the criminal justice sector. The list of criminal justice ICBs was categorized according to the PECUNIA conceptual framework. Results The full-text analysis of forty-five peer-reviewed journal articles and eleven grey literature sources resulted in a draft list of items. Input from the expert survey resulted in a final list of fourteen unique criminal justice ICBs, categorized according to the care atom. Conclusion This study laid further foundations for the inclusion of important societal costs of mental health-related interventions within the criminal justice sector. More research is needed to facilitate the further and increased inclusion of ICBs in health economics research

Bidirectional silencing of RNA polymerase I transcription by a strand switch region in Trypanosoma brucei

The procyclin genes in Trypanosoma brucei are transcribed by RNA polymerase I as part of 5–10 kb long polycistronic transcription units on chromosomes VI and X. Each procyclin locus begins with two procyclin genes followed by at least one procyclin-associated gene (PAG). In procyclic (insect midgut) form trypanosomes, PAG mRNA levels are about 100-fold lower than those of procyclins. We show that deletion of PAG1, PAG2 or PAG3 results in increased mRNA levels from downstream genes in the same transcription unit. Nascent RNA analysis revealed that most of the effects are due to increased transcription elongation in the knockouts. Furthermore, transient and stable transfections showed that sequence elements on both strands of PAG1 can inhibit Pol I transcription. Finally, by database mining we identified 30 additional PAG-related sequences that are located almost exclusively at strand switch regions and/or at sites where a change of RNA polymerase type is likely to occur

The identification of economically relevant health and social care services for mental disorders in the PECUNIA project

Background: Health economic research is still facing significant problems regarding the standardization and international comparability of health care services. As a result, comparative effectiveness studies and cost-effectiveness analyses are often not comparable. This study is part of the PECUNIA project, which aimed to improve the comparability of economic evaluations by developing instruments for the internationally standardized measurement and valuation of health care services for mental disorders. The aim of this study was to identify internationally relevant services in the health and social care sectors relevant for health economic studies for mental disorders. Methods: A systematic literature review on cost-of-illness studies and economic evaluations was conducted to identify relevant services, complemented by an additional grey literature search and a search of resource use measurement (RUM) questionnaires. A preliminary long-list of identified services was explored and reduced to a short-list by multiple consolidation rounds within the international research team and an external international expert survey in six European countries. Results: After duplicate removal, the systematic search yielded 15,218 hits. From these 295 potential services could be identified. The grey literature search led to 368 and the RUM search to 36 additional potential services. The consolidation process resulted in a preliminary list of 186 health and social care services which underwent an external expert survey. A final consolidation step led to a basic list of 56 services grouped into residential care, daycare, outpatient care, information for care, accessibility to care, and self-help and voluntary care. Conclusions: The initial literature searches led to an extensive number of potential service items for health and social care. Many of these items turned out to be procedures, interventions or providing professionals rather than services and were removed from further analysis. The resulting list was used as a basis for typological coding, the development of RUM questionnaires and corresponding unit costs for international mental health economic studies in the PECUNIA project.</p

A unified approach for a posteriori high-order curved mesh generation using solid mechanics

The paper presents a unified approach for the a posteriori generation of arbitrary high-order curvilinear meshes via a solid mechanics analogy. The approach encompasses a variety of methodologies, ranging from the popular incremental linear elastic approach to very sophisticated non-linear elasticity. In addition, an intermediate consistent incrementally linearised approach is also presented and applied for the first time in this context. Utilising a consistent derivation from energy principles, a theoretical comparison of the various approaches is presented which enables a detailed discussion regarding the material characterisation (calibration) employed for the different solid mechanics formulations. Five independent quality measures are proposed and their relations with existing quality indicators, used in the context of a posteriori mesh generation, are discussed. Finally, a comprehensive range of numerical examples, both in two and three dimensions, including challenging geometries of interest to the solids, fluids and electromagnetics communities, are shown in order to illustrate and thoroughly compare the performance of the different methodologies. This comparison considers the influence of material parameters and number of load increments on the quality of the generated high-order mesh, overall computational cost and, crucially, the approximation properties of the resulting mesh when considering an isoparametric finite element formulation

Genome-Wide Association Study Identifies Single Nucleotide Polymorphism in DYRK1A Associated with Replication of HIV-1 in Monocyte-Derived Macrophages

Background: HIV-1 infected macrophages play an important role in rendering resting T cells permissive for infection, in spreading HIV-1 to T cells, and in the pathogenesis of AIDS dementia. During highly active anti-retroviral treatment (HAART), macrophages keep producing virus because tissue penetration of antiretrovirals is suboptimal and the efficacy of some is reduced. Thus, to cure HIV-1 infection with antiretrovirals we will also need to efficiently inhibit viral replication in macrophages. The majority of the current drugs block the action of viral enzymes, whereas there is an abundance of yet unidentified host factors that could be targeted. We here present results from a genome-wide association study identifying novel genetic polymorphisms that affect in vitro HIV-1 replication in macrophages. Methodology/Principal Findings: Monocyte-derived macrophages from 393 blood donors were infected with HIV-1 and viral replication was determined using Gag p24 antigen levels. Genomic DNA from individuals with macrophages that had relatively low (n = 96) or high (n = 96) p24 production was used for SNP genotyping with the Illumina 610 Quad beadchip. A total of 494,656 SNPs that passed quality control were tested for association with HIV-1 replication in macrophages, using linear regression. We found a strong association between in vitro HIV-1 replication in monocyte-derived macrophages and SNP rs12483205 in DYRK1A (p = 2.16×10-5). While the association was not genome-wide significant (p<1×10-7), we could replicate this association using monocyte-derived macrophages from an independent group of 31 individuals (p = 0.0034). Combined analysis of the initial and replication cohort increased the strength of the association (p = 4.84×10-6). In addition, we found this SNP to be associated with HIV-1 disease progression in vivo in two independent cohort studies (p = 0.035 and p = 0.0048). Conclusions/Significance: These findings suggest that the kinase DYRK1A is involved in the replication of HIV-1, in vitro in macrophages as well as in vivo. © 2011 Bol et al

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives