What Can Mental Models do for Inter- and Transdisciplinary Research in Agri-Food Systems?

Agrarsysteme zeichnen sich zunehmend durch Komplexität aus, was die Schaffung eines gemeinsamen Verständnisses des Systems zunehmend erschwert. Systemisches Denken sowie Inter- und Transdisziplinarität werden als Mittel zur Verbesserung unseres Verständnisses von Agrarsystemen befürwortet. Mentale Modelle können ein Instrument sein, um unterschiedliche Sichtweisen auf Agrarsysteme aufzudecken. Durch die Externalisierung interner Wahrnehmungen können mentale Modelle zur Vermittlung von Systemwissen, Förderung von Systemdenken und zu einem gemeinsamen Verständnis beitragen. Gemeinsam mit Forschenden und Praktiker*innen aus inter- und transdisziplinären Agrarsystemprojekten habe ich zehn mentale Modelle erstellt, um zu beurteilen, wie die Teilnehmenden Systemdenkfähigkeiten demonstrieren und wo sie in ihrem Verständnis von Agrarsystemen übereinstimmen. Durch die Analyse der Unterschiede, Systeme, Beziehungen und Perspektiven innerhalb der mentalen Modelle bewerte ich die Systemdenkfähigkeiten der Teilnehmenden. Die Ergebnisse zeigen, dass die mentalen Modelle unterschiedliche Grade an Systemdenken-Fähigkeiten aufweisen. Während es eine Konvergenz im Verständnis der Probleme zu geben scheint, mit denen Agrarsysteme konfrontiert sind, gibt es eine Divergenz hinsichtlich der Frage, wie Nachhaltigkeit erreicht werden kann. Die Ergebnisse legen nahe, dass mentale Modelle ein nützliches Instrument zur Förderung des systemischen Denkens sein können. Darüber hinaus diskutiere ich ihren Einsatz in inter- und transdisziplinären Projekten, die Vorteile von erfahrenen Moderatoren für den Erhebungsprozess und die Einbeziehung in die Projektplanungsphasen. Da inter- und transdisziplinäre Forschung in hohem Maße auf einem gemeinsamen Verständnis des jeweiligen Themas beruht, deuten die Ergebnisse darauf hin, dass mentale Modelle dazu beitragen können, die Kluft zwischen unterschiedlichen Standpunkten zu überbrücken, indem sie das Wissen über das Agrarsystem erfassen und vermitteln.Agri-food systems have been increasingly characterized by complexity, which increasingly obstructs the creation of shared understandings of the system. Systems thinking and inter- and transdisciplinarity have been advocated for as ways of improving our understanding of agri-food systems. Mental models can be a tool for revealing different views of agri-food systems. By externalizing internal perceptions, eliciting mental models can function as a means of communicating systems knowledge, fostering systems thinking skills, and creating shared understandings. I co-created ten mental models with researchers and practitioners from inter- and transdisciplinary agri-food projects to assess how participants demonstrate systems thinking skills and where they converge and diverge in their understandings of agri-food systems. By analyzing the distinctions, systems, relationships, and perspectives within the mental models, I assess participants’ systems thinking skills. The findings show that participants’ mental models demonstrate varying degrees of systems thinking skills. While there seems to be convergence in understanding what problems agri-food systems face, there is a divergence in how to progress towards sustainability. The results suggest that mental models can be a useful tool to foster systems thinking. Moreover, I discuss their use in inter- and transdisciplinary projects, the benefits of skilled facilitators for the elicitation process, and the inclusion in project planning phases. As inter- and transdisciplinary research relies heavily shared understandings of the topic at hand, the findings indicate that mental models can help bridge the gap between different viewpoints by capturing and communicating knowledge of the agri-food system

A Digital Twin of the Angiotensin II Receptor Blocker Losartan: Physiologically Based Modeling of Blood Pressure Regulation

Background/Objectives: Losartan, an angiotensin II receptor blocker (ARB) used to treat hypertension and heart failure, shows significant variability in pharmacokinetics (PK) and pharmacodynamics (PD) among individuals. Methods: In this study, we developed a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model of losartan and its active metabolite, E3174, using curated data from 25 clinical trials. The model mechanistically describes the processes of absorption, hepatic metabolism, renal and fecal excretion, and pharmacodynamic blood pressure regulation. Simulation studies examined the effects of dose, hepatic and renal impairment, and genetic polymorphisms in cytochrome p450 2C9 (CYP2C9) and P-glycoprotein 1, also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1), on the model. Results: The model successfully reproduced key PK/PD observations, including dose-dependent receptor blockade, attenuated responses with hepatic impairment, modest enhancement with renal impairment, and substantial variability in E3174 formation dependent on CYP2C9; the effects of ABCB1 were minimal. Specifically, dose dependency simulations confirmed the saturable nature of CYP2C9 metabolism, predicting a decreasing E3174-to-losartan ratio and a stronger, sustained suppression of blood pressure and aldosterone at higher doses. Hepatic impairment was predicted to lead to elevated losartan plasma concentrations (increased AUC) and attenuated metabolite formation, confirming the clinical need for dose reduction. Renal impairment simulations predicted stable losartan AUC but showed an overestimation of E3174 accumulation compared to observed data, where E3174 exposure remained stable. Genetic variability (CYP2C9) was the major determinant of response, with simulations confirming that reduced-function alleles lead to a 1.6- to 3-fold increase in losartan AUC and diminished blood pressure reduction. ABCB1 variability resulted in only minor modulation of systemic exposure and blood pressure effects. Conclusions: This mechanistic digital twin framework provides a quantitative basis for understanding variability in losartan therapy and supports its application in individualized dosing strategies.M.K. was supported by the BMBF grant number 031L0304B and by the DFG grant number 436883643 and 465194077. M.M. was supported by the Federal Ministry of Research, Technology and Space (BMFTR, Germany) within ATLAS by grant number 031L0304B and by the German Research Foundation (DFG) within the Priority Programme SPP 2311, Subproject SimLivA by grant number 465194077.BMBFFederal Ministry of Research, Technology and Space (BMFTR, Germany) within ATLASDFGGerman Research Foundation (DFG) within the Priority Programme SPP 2311, Subproject SimLivAPeer Reviewe

Climate change reshapes freshwater fish distributions in a semi-arid basin of the middle East

Climate change alters habitat conditions, reshapes species distributions, and intensifies extinction risks across terrestrial, marine, and freshwater ecosystems. Freshwater systems in arid and semi-arid regions are particularly vulnerable to climate change due to their sensitivity to hydrological variability and the limited dispersal abilities of aquatic species. However, assessing these impacts is often challenged by data scarcity, particularly regarding species occurrences. We investigated how climate change will affect habitat suitability for endemic, native, and alien fishes in the Karun River basin, a critically important river system in the Middle East. We applied ensemble Species Distribution Models (SDMs) that combine Random Forest and MaxEnt algorithms with high-resolution environmental predictors. We then projected current and future habitat suitability under three general circulation models (IPSL-CM6A-LR, GFDL-ESM4, MPI-ESM1-2-HR) and two climate scenarios (SSP1-2.6 and SSP5-8.5). Ensemble models performed well across all fish groups, with mean AUC values of 0.96, 0.94, and 0.93 and mean TSS values of 0.88, 0.85, and 0.84 for endemic, native, and alien species, respectively. Sensitivity averaged 97%, 99%, and 93%, specificity 94%, 96%, and 88%, and overall accuracy 95%, 96%, and 88% across the three groups. Compound Topographic Index, temperature, and precipitation were the most important predictors of current habitat suitability. Climate change is projected to result in net habitat changes ranging from + 21% to + 13% for endemic species, + 57% to + 46% for native species, and + 5% to + 99% for alien species. These results suggest that alien fish may benefit from climate change, highlighting the need for local conservation and management strategies to protect vulnerable endemic species and control the potentially expanding ranges of alien species.Open Access funding enabled and organized by Projekt DEAL.Leibniz-Institut für Gewässerökologie und Binnenfischerei (IGB) im Forschungsverbund Berlin e.V. (3473)Peer Reviewe

Characterisation of MuRF1 Expression and Interaction Using Multi-Omics in Glucocorticoid Skeletal Muscle Atrophy

Muskelatrophie ist gekennzeichnet durch eine Reduktion des Durchmessers von Muskelfasern als Reaktion auf eine lang anhaltende körperliche Inaktivität, Erkrankung (z.B. Krebs, Diabetes, Sepsis usw.) oder durch Alterung. Muskelatrophie wird ausgelöst durch den Abbau der kleinsten kontraktilen Einheit – dem Sarkomer – was die betroffenen Muskelgewebe schwächt und die Lebensqualität der Patienten einschränkt. Während die schrittweisen Mechanismen, die zum Abbau des Sarkomers führen, noch nicht vollständig verstanden sind, wurden trotzdem bereits wichtige Marker identifiziert, die mit Atrophie in Zusammenhang stehen. Ein solcher robuster Marker ist die Ubiquitin-E3-Ligase MuRF1, die durch das Gen Trim63 kodiert wird. Trotz intensiver Bemühungen, die genaue Funktion dieses Enzyms zu verstehen, ist seine Rolle bei der Atrophie bisher unklar. Um diese E3-Ligase Funktion besser zu verstehen, habe ich das globale Transkriptom und Proteom in einem C2C12-Muskelzellkulturmodell bestimmt. Zusätzlich habe ich interagierende Faktoren von MuRF1 und seine Expressionsumgebung während der Differenzierung und der Dexamethason-induzierten Atrophie weiter charakterisiert. Transkriptomische und proteomische Profile zeigten eine globale Herunterregulierung von zytoplasmatischen Ribosomen in der Atrophie, während die Häufigkeit mitochondrialer Komponenten erhöht war. Darüber hinaus wurde ein akuter Anstieg alternativer RNA Spleißereignisse beobachtet. Hierzu zählten auch Gene, die zuvor mit Atrophie in Verbindung gebracht wurden. Eine erhöhte MuRF1-Expression wurde als Reaktion auf die Dexamethason-Behandlung festgestellt, obwohl kein unmittelbarer Abbau von Sarkomerkomponenten sichtbar war. Durch Proximity-Labeling mit TurboID wurde festgestellt, dass MuRF1 sich in unmittelbarer räumlicher Nähe zu MuRF2 und MuRF3 sowie dem deubiquitinierenden Enzym USP28 und einer weiteren Ubiquitin-E3-Ligase TRIM25 befindet.Skeletal muscle atrophy is a debilitating condition characterised by loss in muscle mass in response to prolonged physical inactivity, disease or aging. This involves reduction in muscle fibre diameter as well as the disassembly and degradation of the sarcomere, which renders the affected muscle tissue weaker to compromise the patients’ quality of life. While much remains to be investigated regarding the stepwise mechanisms of sarcomere breakdown, key markers associated with atrophy have been identified. One such robust marker is the ubiquitin E3 ligase MuRF1 encoded by the Trim63 gene. Despite intensive efforts to understand the precise function of this enzyme, its role in atrophy remains unclear. In this project, I employed global transcriptomic, proteomic and interactomic screening to further characterise MuRF1 behaviour and its expression environment in the C2C12 muscle cell culture model during differentiation and dexamethasone-induced atrophy. Transcriptomic and proteomic profiles showed global downregulation of cytoplasmic ribosomes during atrophy, while abundance of mitochondrial machinery was increased. Furthermore, an acute spike in alternative splicing events was observed, also among genes previously associated with atrophy progression. Increased MuRF1 expression was detected in response to dexamethasone treatment, despite no immediate sarcomere component degradation. Through proximity labelling using TurboID, MuRF1 was found to be in close spatial proximity to MuRF2 and MuRF3, as well as the deubiquitinating enzyme USP28 and another ubiquitin E3 ligase TRIM25

Psychosoziale Herausforderungen und Ressourcen von trans, nichtbinären und genderqueeren jungen Erwachsenen

Trans, nicht-binäre und genderqueere Identitäten werden gesellschaftlich stigmatisiert. Personen, die diesen Identitäten angehören, sind dadurch besonders häufig von mentalen Gesundheitsproblemen betroffen. In der vorliegenden Untersuchung wurden psychosoziale Herausforderungen und Ressourcen von trans, nicht-binären und genderqueeren jungen Erwachsenen auf Grundlage des Minderheitenstress-Modells (Meyer, 2003) erforscht. Die Belastungs-, sowie Resilienzfaktoren der Stichprobe (n = 121) wurden mittels des auf Deutsch übersetzten Gender Minority Stress and Resilience Measure (Testa et al., 2015) erfasst und statistisch analysiert. Ergänzend wurden mit vier Teilnehmenden Leitfaden-gestützte Interviews zu den von ihnen erfahrenen Belastungen und genutzten Umgangsstrategien geführt und inhaltsanalytisch ausgewertet. Es zeigten sich höhere Werte in spezifischen Aspekten von Minderheitenstress für Personen mit niedrigem monatlichen Einkommen, sowie für nicht-binäre Personen und Menschen, die nicht geoutet sind. Es konnten als relevante neue Stressoren Geschlechtsdysphorie und Grübeln ermittelt werden. In Bezug auf die Ressourcen, konnte das Minderheitenstress-Modell um die Kategorien Bestätigung und Repräsentation, sowie medizinische und institutionelle Unterstützung erweitert werden. Zusätzlich ließen sich verschiedene Coping-Mechanismen ausmachen. Heteronormativität wurde als Bezugsrahmen und Einflussgröße für die Ausformung der Identität, erlebte Belastung und genutzte Umgangsstrategien identifiziert.Trans, non-binary, and genderqueer identities are socially stigmatized. This leads to a higher number of mental health conditions in individuals who belong to these identity groups. This study examined the psychosocial challenges and resources of trans, non-binary, and genderqueer young adults based on the minority stress model (Meyer, 2003). The stress and resilience factors of the sample (n = 121) were assessed using a German translation of the Gender Minority Stress and Resilience Measure (Testa et al., 2015) and statistically analyzed. In addition, guided interviews were conducted with four participants regarding their experiences with stress and coping strategies. The interviews were evaluated using content analysis. Higher scores were found in specific aspects of minority stress for individuals with low monthly income, as well as for non-binary individuals and closeted individuals. Gender dysphoria and Rumination were identified as relevant new stressors. With regard to resources, the minority stress model was expanded to include the categories of Affirmation and Representation, as well as Medical and Institutional Support. Additionally, various coping mechanisms were identified. Heteronormativity was identified as a reference framework and influencing factor for the formation of identity, experienced stress, and coping strategies used

Pooled single-cell screen in colorectal cancer defines transcriptional modules linked to oncogenes

Oncogenic mutations shape colorectal cancer (CRC) biology, yet their impact on transcriptional phenotypes remains incompletely understood, and their individual prognostic value is limited. Here, we perform a pooled single-cell transcriptomic screen of over 100,000 CRC cells with a comprehensive barcoded library of oncogenic variants across genetically diverse CRC lines. Using a variational autoencoder-based interpretable factor model, we identify ten conserved oncogene-driven transcriptional modules (TMOs) representing core cancer phenotypes such as cellular plasticity, inflammatory response, replicative stress, and epithelial-to-mesenchymal transition. Engagement of these modules can be context-dependent, reflecting interactions between oncogene-induced driver pathways and background genetics. TMO activity in patient tumors stratifies CRC cohorts into high- and low-risk groups, improving relapse-free survival prediction beyond existing classification systems. Our study systematically links oncogenic signaling to transcriptional states and clinical outcomes, establishing a functional framework for module-based patient stratification in precision oncology.Synopsis: Single-cell screening with a comprehensive barcoded library of oncogenic variants in a panel of CRC lines identifies conserved transcriptional modules representing cancer phenotypes. Several modules can stratify patient cohorts into high and low-risk groups. An interpretable factor model identifies module signatures for core cancer traits. High activity of the Inflammatory Response, Plasticity/Drug Resistance, and EMT modules are associated with a worse prognosis in CRC patient cohorts. High Replicative Stress module activity is associated with a better prognosis in CRC patient cohorts. Transcriptional modules can improve CRC classification systems such as CMS.Deutsche Forschungsgemeinschaft (DFG)http://dx.doi.org/10.13039/501100001659Bundesministerium für Forschung, Technologie und RaumfahrtDeutschen Konsortium für Translationale Krebsforschung (DKTK)http://dx.doi.org/10.13039/501100012353Federal Ministry of Research, Technology and Space (BMFTR)Peer Reviewe

Elephant Trunks: A Comprehensive Investigation From Behavior To Brain

Elefanten sind charismatische Tiere, und ihre kräftigen, geschickten Rüssel zählen zu den faszinierendsten Anpassungen der Natur. Alle drei Arten – Asiatische Elefanten (Elephas maximus), Afrikanische Savannen- (Loxodonta africana) und Waldelefanten (Loxodonta cyclotis) – sind vom Aussterben bedroht oder stark gefährdet. Diese Arbeit konzentriert sich auf Asiatische und Afrikanische Savannenelefanten, die sich trotz äußerlicher Ähnlichkeit in Verhalten, Morphologie und Anatomie unterscheiden. Die Sinneswelt der Elefanten wird von Hören und Riechen geprägt, doch der Tastsinn über den Rüssel spielt eine zentrale, bisher unterschätzte Rolle. Der Rüssel ist ein multifunktionales Werkzeug für Nahrungsaufnahme, Trinken, Riechen, Tasten, Vokalisationen, soziale Interaktion, Objektmanipulation und zahlreiche kognitive Leistungen. Entsprechend zeigen ihre Gehirne Spezialisierungen im Zusammenhang mit Rüsselkontrolle und rüsselbezogener Wahrnehmung. Die ersten beiden Kapitel befassen sich mit Verhalten und Kognition Asiatischer Elefanten und Rüsselverhaltensweisen. Ein Fall beschreibt zielgerichteten Werkzeuggebrauch, bei dem eine Elefantin einen Wasserschlauch zum Duschen nutzte. Ein weiteres Kapitel schildert, wie eine Elefantin Bananen mithilfe feinmotorischer Rüsselbewegungen schälte und dieses Verhalten sozial anpasste. Das dritte Kapitel untersucht die Rüsselmorphologie, beschreibt artspezifische Faltenmuster und deren Ontogenese. Das vierte Kapitel präsentiert die erste Studie zur motorischen Kontrolle der Gesichtsmuskulatur beider Arten und berichtet über rüsselspezifische neuronale Spezialisierungen. Diese Dissertation betont die zentrale Bedeutung des Rüssels für Wahrnehmung und Verhalten, hebt wichtige artspezifische Unterschiede hervor und unterstreicht die Notwendigkeit vergleichender Forschung. Zudem werden Herausforderungen der Arbeit mit Elefanten sowie die Verantwortung von Forschenden für den Schutz dieser beeindruckenden Tiere dargestellt.Elephants are charismatic animals, and their powerful, dexterous trunks are among nature’s most remarkable adaptations. Today, three elephant species remain – Asian elephants (Elephas maximus), African savanna elephants (Loxodonta africana), and African forest elephants (Loxodonta cyclotis) – all endangered or critically endangered. This thesis focuses on Asian and African savanna elephants, which show distinct behavioral, morphological, and anatomical traits. Elephants rely heavily on auditory and olfactory perception, yet touch – especially via the trunk – plays a central, previously underestimated role. Their trunks are multifunctional tools essential for feeding, drinking, olfaction, somatosensation, vocalization, social interaction, object manipulation, and many cognitive abilities. Correspondingly, their brains show specializations linked to trunk control and perception. The first chapters address Asian elephant behavior and cognition, highlighting trunk use. One case describes goal-directed tool use in which a female used a hose to shower herself, while a younger female appeared to interfere with the water flow. Chapter two details how an elephant peeled bananas using fine motor trunk skills and adapted this behavior socially. The third chapter examines trunk morphology, reporting species differences in trunk wrinkles and their ontogeny. The fourth chapter presents the first study of facial motor control in both species, revealing trunk-related specializations and species differences in facial motor nuclei, including correlates of the African elephant’s two trunk-tip fingers. Overall, this thesis underscores the trunk’s central role in elephant behavior and cognition, highlights key species differences, and stresses the importance and challenges of comparative research. It concludes by emphasizing researchers’ responsibility to support the conservation and welfare of these remarkable animals

Benchmarking variational quantum algorithms for combinatorial optimization in practice

Variational quantum algorithms, and in particular variants of the variational quantum eigensolver, have been proposed as approaches to combinatorial optimization (CO) problems. With only shallow ansatz circuits, these methods are considered suitable for current noisy intermediate-scale quantum hardware. Yet, the resources required to train variational circuits often scale superpolynomially with problem size. In this study, we numerically investigate the practical implications of this scaling for CO problems, using Max-Cut and random QUBO instances as benchmarks. For a fixed computational budget, we compare the average performance of training shallow variational circuits, sampling with replacement, and greedy local search. We identify the minimum problem size at which the quantum algorithms consistently outperform random sampling, and for each size, we characterize their separation from greedy local search. Beyond average-case performance, we analyze correlations between algorithms across individual problem instances. These results strengthen the case for intuitive yet meaningful benchmarks of variational quantum algorithms for CO problems under realistic resource constraints.Open Access funding enabled and organized by Projekt DEAL.Deutsches Elektronen-Synchrotron (DESY) (4201)Peer Reviewe

Placental Histiocyte Phenotypes in Chronic Histiocytic Intervillositis: A Comprehensive Immunophenotypic and Morphologic Atlas

Chronic histiocytic intervillositis (CHI) is a placental lesion characterized by an inflammatory response, significantly influencing maternal and fetal outcomes. This study aims to develop a comprehensive morphologic atlas detailing the localization of fetal and maternal macrophages within the context of CHI. We employed immunohistochemical and multiplexing techniques to analyze placental samples, identifying expression patterns and spatial distribution of key macrophage markers, including CD68, CD163, CD14, and HLA-DR. The results revealed a marked accumulation of activated macrophages in both the intervillous space and villous stroma, with distinct differences in morphology and immunophenotype of fetal Hofbauer cells versus maternal macrophages. Our findings contribute to a better understanding of the immune landscape in CHI and provide a valuable resource for further research into placental immune dynamics. By establishing this morphologic atlas, we aim to enhance diagnostic and therapeutic strategies for affected pregnancies, thereby improving the diagnostic approach and making it more straightforward to recognize CHI histologically.This research received no external funding.Peer Reviewe