31325 research outputs found
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Trifunctional sphingomyelin derivatives enable nanoscale resolution of sphingomyelin turnover in physiological and infection processes via expansion microscopy
No full textSphingomyelin is a key molecule of sphingolipid metabolism, and its enzymatic breakdown is associated with various infectious diseases. Here, we introduce trifunctional sphingomyelin derivatives that enable the visualization of sphingomyelin distribution and sphingomyelinase activity in infection processes. We demonstrate this by determining the activity of a bacterial sphingomyelinase on the plasma membrane of host cells using a combination of Förster resonance energy transfer and expansion microscopy. We further use our trifunctional sphingomyelin probes to visualize their metabolic state during infections with Chlamydia trachomatis and thereby show that chlamydial inclusions primarily contain the cleaved forms of the molecules. Using expansion microscopy, we observe that the proportion of metabolized molecules increases during maturation from reticulate to elementary bodies, indicating different membrane compositions between the two chlamydial developmental forms. Expansion microscopy of trifunctional sphingomyelins thus provides a powerful microscopy tool to analyze sphingomyelin metabolism in cells at nanoscale resolution.Deutsche Forschungsgemeinschaft (German Research Foundation)https://doi.org/10.13039/501100001659Peer Reviewe
Existence of similarity profiles for diffusion equations and systems
No full textWe study the existence of similarity profiles for diffusion equations and reaction diffusion systems on the real line, where the different nontrivial limits are imposed for x→-∞and x→+∞. These similarity profiles solve a coupled system of nonlinear ODEs that can be treated by monotone operator theory.Peer Reviewe
Developing countries can adapt to climate change effectively using nature-based solutions
No full textEvidence on the effectiveness of climate change adaptation interventions in low- and middle-income countries has been rapidly growing in recent years, particularly in the agricultural and coastal sectors. Here we address the question of whether results are consistent across intervention types, and risk reduction versus development-related outcomes using a systematic review of 363 empirical observations published in the scientific literature. Generally, we found more evidence of risk reduction outcomes in the coastal sector than in the agricultural sector, and more evidence of development-related outcomes in the agricultural sector. Further, results indicate that nature-based solutions have the strongest positive effects for both the coastal and agricultural sectors. Social/behavioural interventions in the coastal sector show negative effects on development-related outcomes that will need to be further tested. Taken together, our results highlight the opportunity for development and climate adaptation practitioners to promote adaptation interventions with co-benefits beyond risk reduction, particularly in the case of nature-based solutions.Peer Reviewe
Multimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88
No full textProline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis by binding to the polypeptide exit tunnel (PET) near the peptidyl transferase center. Api137, an optimized derivative of honeybee PrAMP apidaecin, inhibits protein expression by trapping release factors (RFs), which interact with stop codons on ribosomes to terminate translation. This study uses cryo-EM, functional assays and molecular dynamic (MD) simulations to show that Api137 additionally occupies a second binding site near the exit of the PET and can repress translation independently of RF-trapping. Api88, a C-terminally amidated (-CONH2) analog of Api137 (-COOH), binds to the same sites, occupies a third binding pocket and interferes with the translation process presumably without RF-trapping. In conclusion, apidaecin-derived PrAMPs inhibit bacterial ribosomes by multimodal mechanisms caused by minor structural changes and thus represent a promising pool for drug development efforts.Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)https://doi.org/10.13039/501100002347German Federal Ministry for Education and ResearchPeer Reviewe
DIVERGesTOOL—development of a toolbox for the assessment of sex/gender diversity
No full textIn der epidemiologischen Gesundheitsforschung besteht ein großer Bedarf an umfassenden Erhebungsinstrumenten, die der Multidimensionalität und Variabilität von Geschlecht gerecht werden. Das Forschungsprojekt DIVERGesTOOL griff diesen in den letzten Jahren immer deutlicher werdenden Bedarf auf. Es verfolgte das Ziel, eine anwendungsorientierte Toolbox zur Erfassung geschlechtlicher Vielfalt für die quantitative Gesundheitsforschung in Deutschland zu entwickeln. Der Entwicklungsprozess war partizipativ angelegt, Vertreter*innen großer epidemiologischer Studien in Deutschland wurden direkt einbezogen. Im Rahmen von vier gemeinsamen Workshops wurde eine Toolbox entwickelt, die sich aus mehreren Bestandteilen zusammensetzt: Die Basis-Items sind ein grundlegendes, allgemein nutzbares Set aus drei Fragen, die sich am Two-Step-Approach orientieren. Sie werden anstelle der bisher routinemäßig in den Gesundheitswissenschaften angewendeten binären Geschlechtsvariable empfohlen. Zudem enthält die Toolbox Zusatz-Items mit beispielhaften Fragebogen-Items für spezifische Fragestellungen oder Studienpopulationen. Ergänzt wurden die Items um ausführliche Anwendungshinweise und Hintergrundinformationen. Die Toolbox steht Interessierten online kostenlos über die Website des Projektes zur Verfügung ( https://www.uni-bremen.de/divergestool-projekt/divergestool-toolbox ). Langfristig soll die DIVERGesTOOL-Toolbox Forschende dabei unterstützen, geschlechtliche Vielfalt in die eigene Forschung zu integrieren, und somit zu mehr Geschlechtersensibilität in der Gesundheitsforschung und validen Forschungsergebnissen beitragen.In health research, there is a need for comprehensive survey instruments capable of assessing the multidimensionality and variability of sex/gender. The research project DIVERGesTOOL was conducted in response to this need, which has become increasingly evident in recent years. The aim was to develop an application-oriented toolbox for the assessment of sex/gender diversity in quantitative health-related research in Germany. The development process followed a participatory design, as representatives of large epidemiological studies in Germany were directly involved. During four collaborative workshops, a toolbox was developed that contains several different elements. The basic items are a generally usable set of three different questionnaire items based on the two-step approach. They are recommended as a replacement for the binary sex or gender item that are currently routinely used in health-related research. In addition, the toolbox contains further exemplary questionnaire items for specific research questions or study populations. The developed items were supplemented with detailed instructions for their application and additional information. The toolbox is an open online resource accessible to any user ( https://www.uni-bremen.de/divergestool-projekt/divergestool-toolbox ). In the long term, the DIVERGesTOOL is intended to support researchers in integrating sex/gender diversity into their own research and thus to contribute to more sex/gender sensitivity in health-related research and valid findings.Peer Reviewe
Egalitarian gender role attitudes give girls the edge: Exploring the role of students’ gender role attitudes in reading and math
No full textGender differences in reading and math have been reported for many years. Girls outperform boys in reading (representing a school domain stereotyped as female); boys often perform slightly better in math (a stereotypical male domain). Research has so far investigated the contribution of domain-specific academic self-concepts and interests as well as gender stereotypes to these gender differences. Students’ gender role attitudes (GRAs) and their relation with gender disparities in school performance, however, have been studied little. This study examines if students’ GRAs contribute to explaining boys’ higher math achievement and girls’ higher reading achievement. Using PISA-2009 data from Germany, the sample included 9,460 grade nine students (49.70% girls; Mage = 15.61 years). Regression analyses revealed that egalitarian GRAs are beneficial for all students. Still more so for girls, egalitarian GRAs help girls perform particularly well in reading and compensate for possible disadvantages in math. In reading, girls with egalitarian GRAs reached higher performance scores than boys with egalitarian GRAs. In math, girls with egalitarian GRAs scored nearly as high as boys with egalitarian GRAs. Boys also benefited from egalitarian GRAs, although not as much as girls. Although gender disparities in reading and math achievement were explained only partly by students’ GRAs, supporting boys and girls in endorsing egalitarian GRAs is worthwhile as they may help to increase societal gender equality more broadly.Open Access funding enabled and organized by Projekt DEAL.Humboldt-Universität zu Berlin (1034)Peer Reviewe
A Hidden Convexity of Nonlinear Elasticity
No full textA technique for developing convex dual variational principles for the governing PDE of nonlinear elastostatics and elastodynamics is presented. This allows the definition of notions of a variational dual solution and a dual solution corresponding to the PDEs of nonlinear elasticity, even when the latter arise as formal Euler–Lagrange equations corresponding to non-quasiconvex elastic energy functionals whose energy minimizers do not exist. This is demonstrated rigorously in the case of elastostatics for the Saint-Venant Kirchhoff material (in all dimensions), where the existence of variational dual solutions is also proven. The existence of a variational dual solution for the incompressible neo-Hookean material in 2-d is also shown. Stressed and unstressed elastostatic and elastodynamic solutions in 1 space dimension corresponding to a non-convex, double-well energy are computed using the dual methodology. In particular, we show the stability of a dual elastodynamic equilibrium solution for which there are regions of non-vanishing length with negative elastic stiffness, i.e. non-hyperbolic regions, for which the corresponding primal problem is ill-posed and demonstrates an explosive ‘Hadamard instability;’ this appears to have implications for the modeling of physically observed softening behavior in macroscopic mechanical response.Open Access funding provided by Carnegie Mellon UniversityArmy Research Laboratoryhttp://dx.doi.org/10.13039/100006754Simons Foundationhttp://dx.doi.org/10.13039/100000893Carnegie Mellon UniversityPeer Reviewe
Modeling brain network flexibility in networks of coupled oscillators: a feasibility study
No full textModeling the functionality of the human brain is a major goal in neuroscience for which many powerful methodologies have been developed over the last decade. The impact of working memory and the associated brain regions on the brain dynamics is of particular interest due to their connection with many functions and malfunctions in the brain. In this context, the concept of brain flexibility has been developed for the characterization of brain functionality. We discuss emergence of brain flexibility that is commonly measured by the identification of changes in the cluster structure of co-active brain regions. We provide evidence that brain flexibility can be modeled by a system of coupled FitzHugh-Nagumo oscillators where the network structure is obtained from human brain Diffusion Tensor Imaging (DTI). Additionally, we propose a straightforward and computationally efficient alternative macroscopic measure, which is derived from the Pearson distance of functional brain matrices. This metric exhibits similarities to the established patterns of brain template flexibility that have been observed in prior investigations. Furthermore, we explore the significance of the brain’s network structure and the strength of connections between network nodes or brain regions associated with working memory in the observation of patterns in networks flexibility. This work enriches our understanding of the interplay between the structure and function of dynamic brain networks and proposes a modeling strategy to study brain flexibility.Open Access funding enabled and organized by Projekt DEAL.Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659Technische Universität Berlinhttp://dx.doi.org/10.13039/501100006764Berlin International Graduate School in Model and Simulation based researchTechnische Universität Berlin (3136)Peer Reviewe
Large-scale agricultural investments and local food security – Evidence from a mixed-method case study in Benin
No full textLarge-scale agricultural investments (LSAIs) and their impacts on local communities in host countries have been controversially discussed in recent years. As scholars increasingly call for more structured and comprehensive analyses, we develop a mixed-method approach using an expanded version of the “Right to Food” (RtF) framework to systematically investigate the local food security impacts of a recently established tomato-producing LSAI in Central Benin, West Africa. We find that the LSAI keeps natural resources as accessible as possible for the local community and provides employment opportunities, leading to higher dietary diversity of employees and multiplier effects in the local economy. At the same time, we find inequalities regarding the compensation of former land users as well as high job insecurity for temporary laborers who face high transportation costs to reach the LSAI. We argue that fair and inclusive compensation, improved access to markets and machinery, access to natural resources for often overlooked groups (pastoralists, hunters, fishermen) and social infrastructure are crucial factors in promoting positive outcomes of LSAIs on communities and that strong local institutions play a key role for achieving this. We conclude that the specific characteristics of our case (relatively small size, labor-intensive crop, focus on regional markets) provide favorable conditions for positive impacts on local food security. We encourage further, structured mixed-method studies, ideally including longitudinal and comparative research designs, to investigate the multidimensional effects related to the establishment of LSAIs. The extended RtF framework can thereby serve as a structural lens to systematically analyze the findings.Open Access funding enabled and organized by Projekt DEAL.Stiftung fiat panishttp://dx.doi.org/10.13039/501100011087Johann Heinrich von Thünen-Institut, Bundesforschungsinstitut für Ländliche Räume, Wald und Fischerei (4249)Peer Reviewe
What does the current health care legislation mean for research with healthcare-related data?
No full textHintergrund:Am 14.12.2023 verabschiedete der Deutsche Bundestag zwei Gesetze, die für die Gesundheitsforschung und -versorgung der kommenden Jahre erhebliche Bedeutung haben: erstens das Gesetz zur verbesserten Nutzung von Gesundheitsdaten (Gesundheitsdatennutzungsgesetz [GDNG]) und zweitens das Gesetz zur Beschleunigung der Digitalisierung des Gesundheitswesens (Digital-Gesetz [DigiG]). Die Gesetze traten mit Wirkung zum 26.03.2024 in Kraft. Laut Mitteilung des zuständigen Bundesgesundheitsministeriums sollen die Gesetze unter anderem Gesundheitsdaten für die Forschung erschließen (GDNG) sowie Austausch und Nutzung von Gesundheitsdaten vorantreiben (DigiG). Methodik: In diesem Beitrag wollen wir die beiden Gesetze hinsichtlich ihrer Bedeutung für die Forschung mit versorgungsnahen Daten untersuchen. Die Gesetze werden im Lichte bestehender Regelungen zur Zulässigkeit der Datenspeicherung und -verarbeitung analysiert und mit anderen Modellen der Datennutzung der Versorgungsforschung ins Verhältnis gesetzt. Ergebnisse: Im Ergebnis haben die Gesetze erhebliches Potenzial für die Forschung. Dies betrifft insbesondere die Möglichkeit zum Linkage von Krebsregister- und GKV-Abrechnungsdaten (GKV – gesetzliche Krankenversicherung) sowie die Eigenforschung von Gesundheitseinrichtungen im Verbund. Schlussfolgerung: Nun kommt es auf die konkrete Umsetzung, den Aufbau erforderlicher Strukturen und das Verhalten der Datenschutzaufsichtsbehörden an, ob diese Potenziale ausgeschöpft werden.Introduction: On 14 December 2023, the German Bundestag passed two bills that will be of considerable importance for health care as well as research on health care in the upcoming years: the Act for the Improved Use of Health Data (Health Data Usage Act—GDNG) and the Act on Accelerating the Digitalization of the Healthcare System (Digital Law—DigiG). The laws came into effect on 26 March 2024. According to a statement from the responsible Federal Ministry of Health, the laws are intended, among other things, to make health data for research (GDNG) available and promote the exchange and use of health data (DigiG). Methods: In this article, we want to examine the two laws with regard to their importance for research with routine practice data. The laws are analyzed in light of existing regulations on the admissibility of data storage and processing and compared with other models of data use in health services research. Results: The laws will have considerable potential for research. This applies in particular to the possibility of linking cancer registry and claims data as well as research of health facilities with their own data in a network. Conclusion: Whether the potential of the new legislation is exploited, now depends on its implementation, on the establishment of the necessary structures and on the data protection authorities’ conduct.Peer Reviewe