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Realizing quantitative quasiparticle modeling of skyrmion dynamics in arbitrary potentials
Full text linkWe demonstrate fully quantitative Thiele model simulations of magnetic skyrmion dynamics on previously unattainable experimentally relevant large length and time scales by ascertaining the key missing parameters needed to calibrate the experimental and simulation timescales and current-induced forces. Our work allows us to determine complete spatial pinning energy landscapes that enable quantification of experimental studies of diffusion in arbitrary potentials within the Lifson-Jackson framework. Our method enables us to ascertain the timescales, and by isolating the effect of ultralow current density (order 10^{6} A/m^{2}) generated torques we directly infer the total force acting on the skyrmion for a quantitative modeling
A subcellular sampling instrument allows spatial resolution of amyloid deposit-derived organelle-specific effects in microglia
Full text linkMethodological developments in biomedical research are currently moving towards single-cell approaches. This allows for a much better spatial and functional characterization of, for example, the deterioration of cells within a tissue in response to noxae. However, subcellular resolution is also essential to elucidate whether observed impairments are driven by an explicit organelle. Here, we use the Single Cellome™ System SS2000 (Yokogawa) to investigate the local effects of Aβ plaque-like deposits (characteristic for Alzheimer’s disease) on mitochondria in the mouse microglial cell line SIM-A9. First, the specificity of subcellular extraction is demonstrated by detecting subcellular staining and RT-qPCR concerning marker genes by comparing nuclear and mitochondrial samples. Oxygen consumption and gene expression is then assessed in cells near and far from peptide deposits. Mostly, all analyses confirm the high specificity and integrity of the sampled material. In addition, impact of the peptide deposits occur concerning spatial distribution of the cells: e.g., oxygen consumption is only reduced in cells close to Aβ deposits but not in proximity to deposits of biologically inactive Aβ (scrambled) or in far distance. Moreover, a distance-related gene expression pattern occurs, demonstrating the local initiation of mitochondrial changes of microglia when approaching toxic peptide deposits
Exploring determinants of mediterranean lifestyle adherence : findings from the multinational MEDIET4ALL e-survey across ten mediterranean and neighboring countries
Full text linkBackground/Objectives: Despite its well-established health benefits, adherence to the Mediterranean lifestyle (MedLife) has declined globally, including in its region of origin, alongside a significant shift toward ultra-processed food consumption. Understanding the factors associated with MedLife adherence is essential for developing targeted interventions and tailored policy recommendations. As part of the MEDIET4ALL PRIMA project, this cross-sectional study aimed to comprehensively examine geo-demographic, socio-economic, psychological, behavioral, and barrier-related factors associated with and potentially contributing to MedLife adherence. Methods: Data were collected from 4010 participants aged 18 years and above across ten Mediterranean and neighboring countries using the multinational MEDIET4ALL e-survey, which included the validated MedLife index, along with various other questionnaires. Results: Results indicate that only 22% of respondents demonstrated high adherence to the Mediterranean lifestyle (MedLife), with significant variability observed across countries, age groups, education levels, and health statuses. Spain had the highest proportion of participants with high adherence (38%). Factors associated with significantly higher adherence rates include older age, living in the Mediterranean region, higher education levels, a greater awareness of MedLife principles, lower perceived barriers, normal BMI, better health status, and stable economic and marital conditions (p-values ranging from 0.04 to <0.001). Additionally, individuals with high MedLife adherence exhibited more socially and physically active lifestyles and experienced less psychological strain (p < 0.001). Regression analyses identified MedLife awareness as the strongest positive predictor of adherence (β = 0.206), followed by social participation (β = 0.194) and physical activity (β = 0.096). Additional positive contributors include life satisfaction, sleep quality, living in the Mediterranean region, age, and education (β ranging from 0.049 to 0.093). Conversely, factors that are negatively associated with adherence include sedentary behavior, living environment, and barriers such as low motivation, taste dislike, price unaffordability, limited availability, and the time-consuming nature of preparing Mediterranean food (MedFood; β ranging from −0.036 to −0.067). Conclusions: These findings indicate that fewer than one in four adults across Mediterranean and neighboring countries demonstrate high adherence to MedLife, supporting prior evidence of suboptimal adherence even within Mediterranean regions. This study identified a range of behavioral, socio-demographic, and environmental factors—both positive and negative predictors—that can help guide the design of targeted, culturally adapted interventions to promote MedLife behavior. Future research should incorporate objective measurements and longitudinal monitoring to better understand underlying mechanisms, establish causality, and develop sustainable strategies for enhancing MedLife adherence in diverse populations
Molekulare Konsequenzen der Methionin-Restriktion
Full text link130 Seiten ; Illustrationen, Diagramm
Chemical and structural variations of bivalve shells at the micrometer scale – taking sclerochronology to the next level
Full text linkxxiii, 159 Seiten ; Illustrationen, Diagramm
ACC1 is a dual metabolic-epigenetic regulator of Treg stability and immune tolerance
Full text linkObjective:
Regulatory T cells (Tregs) are essential in maintaining immune tolerance and controlling inflammation. Treg stability relies on transcriptional and post-translational mechanisms, including histone acetylation at the Foxp3 locus and FoxP3 protein acetylation. Additionally, Tregs depend on specific metabolic programs for differentiation, yet the underlying molecular mechanisms remain elusive. We aimed to investigate the role of acetyl-CoA carboxylase 1 (ACC1) in the differentiation, stability, and function of regulatory T cells (Tregs).
Methods:
We used either T cell-specific ACC1 knockout mice or ACC1 inhibition via a pharmacological agent to examine the effects on Treg differentiation and stability. The impact of ACC1 inhibition on Treg function was assessed in vivo through adoptive transfer models of Th1/Th17-driven inflammatory diseases.
Results:
Inhibition or genetic deletion of ACC1 led to an increase in acetyl-CoA availability, promoting enhanced histone and protein acetylation, and sustained FoxP3 transcription even under inflammatory conditions. Mice with T cell-specific ACC1 deletion exhibited an enrichment of double positive RORγt+FoxP3+ cells. Moreover, Tregs treated with an ACC1 inhibitor demonstrated superior long-term stability and an enhanced capacity to suppress Th1/Th17-driven inflammatory diseases in adoptive transfer models.
Conclusions:
We identified ACC1 as a metabolic checkpoint in Treg biology. Our data demonstrate that ACC1 inhibition promotes Treg differentiation and long-term stability in vitro and in vivo. Thus, ACC1 serves as a dual metabolic and epigenetic hub, regulating immune tolerance and inflammation by balancing de novo lipid synthesis and protein acetylation
The psychological dynamics of hybrid work - exploring the role of work location, basic need satisfaction, and contextual aspects of telework in daily employee well-being
Full text linkThe COVID-19 pandemic has significantly accelerated the adoption of hybrid-work models, where employees regularly alternate between working from home and the office. This shift has transformed telework from an exception to a norm, fundamentally changing the modern work landscape and raising critical questions regarding its psychological implications. Existing research on telework presents mixed findings regarding its impact on employee well-being, highlighting the need to explore the mediating and moderating factors. Given the widespread adoption of hybrid-work models with frequent transitions between work locations, it is also crucial to shift the focus from between-person to within-person effects.
To address these research gaps, this dissertation investigates the within-person effects of hybrid work on employee well-being through three empirical daily diary studies. Drawing on the job demands-resources theory, challenge-hindrance stressor framework, and self-determination theory, this dissertation is guided by three research objectives. First, the direct effects of hybrid work on daily employee outcomes are examined, focusing on within-person variability. Second, the mediating role of basic psychological need satisfaction (autonomy, competence, and relatedness) is explored to explain the relationship between work location and employee well-being. Third, the moderating role of key telework aspects in the hybrid-work context is investigated. These include the time spent teleworking (telework intensity), the prevalence and acceptance of telework within organizations (telework normativeness), and the perceived voluntariness of daily work location choice (daily telework voluntariness), as well as the moderating role of work location in stressor-outcome relationships.
Study 1 examined the direct effect of work location on emotional exhaustion and its indirect effect on perceived performance, using daily diary data from 151 employees (N = 876 observations). Multilevel structural equation modeling (MSEM) revealed that employees experienced lower emotional exhaustion and, in turn, higher perceived performance on days when they worked from home compared to days when they worked in the office. Furthermore, telework intensity, telework normativeness, and daily telework voluntariness were examined as potential moderators, reflecting key characteristics of the evolving hybrid work. Conditional indirect effects indicate that these effects were more pronounced when employees rarely worked from home (low telework intensity), belonged to organizations where telework was uncommon (low telework normativeness), or had limited choice over their work location (low daily telework voluntariness).
Study 2 investigated the mediating mechanisms through which work location affects work engagement and cognitive stress, focusing on the role of basic need satisfaction. Based on daily data from 114 employees (N = 744 observations), multilevel mediation models revealed that working from home was associated with higher autonomy- and competence-need satisfaction, which positively affected work engagement and reduced cognitive stress. Conversely, working from home was associated with lower relatedness-need satisfaction, which contributed to increased work engagement and reduced cognitive stress. Multilevel moderated mediation models further indicated that telework normativeness weakened the indirect effects of autonomy- and relatedness-need satisfaction.
Study 3 shifted the focus to the moderating effect of work location on the relationship between time pressure (a challenge stressor), professional isolation (a hindrance stressor), and work engagement and emotional exhaustion. MSEM analysis of daily data from 124 employees (N = 609 observations) revealed a significant two-way interaction effect only of work location and professional isolation on emotional exhaustion. As in Studies 1 and 2, this study also explored the moderating role of telework normativeness, revealing significant three-way interactions among work location, telework normativeness, and stressors. These interactions influenced the relationships between time pressure and work engagement and emotional exhaustion, and professional isolation and work engagement, with mixed interaction patterns.
Overall, these studies comprehensively examined the psychological dynamics inherent in hybrid work. The findings underscore the importance of within-person effects and the need to consider both mediating factors, such as basic need satisfaction, and moderating factors, such as telework intensity, normativeness, and voluntariness, in shaping employee outcomes. The practical implications of these findings are significant for organizations navigating the future of work, offering valuable insights into the promotion and design of hybrid-work arrangements. This dissertation highlights the importance of encouraging flexible work arrangements that enhance employees’ autonomy and competence while actively mitigating negative effects such as isolation. It is crucial to consider the prevalence of telework within organizations and strike a balance between the advantages of home-based and office-based work to ensure a supportive and productive hybrid-work environment.Die COVID-19-Pandemie hat die Einführung hybrider Arbeitsmodelle, bei denen Mitarbeitende regelmäßig zwischen Homeoffice und Büro wechseln, erheblich beschleunigt. Dieser Wandel hat die Verbreitung des Arbeitens von zuhause erheblich gesteigert, was die moderne Arbeitswelt grundlegend verändert und kritische Fragen zu den psychologischen Implikationen aufwirft. Die bisherige Homeoffice-Forschung kommt zu gemischten Ergebnissen hinsichtlich der Auswirkungen auf das Wohlbefinden von Mitarbeitenden, was die Notwendigkeit unterstreicht, mediierende und moderierende Faktoren zu untersuchen. Angesichts der zunehmenden Verbreitung hybrider Arbeitsmodelle mit häufigen Wechseln zwischen den Arbeitsorten, ist es zudem wichtig, den Fokus von between-person- auf within-person-Effekte zu verlagern.
Um diese Forschungslücken zu schließen, untersucht diese Dissertation die within-person Effekte hybrider Arbeit auf das Wohlbefinden von Mitarbeitenden anhand von drei empirischen Tagebuch-Studien. Basierend auf der Job-Demands-Resources-Theorie, dem Challenge-Hindrance-Stressor-Framework und der Selbstbestimmungstheorie wird die Dissertation von drei Forschungszielen geleitet. Erstens werden die direkten Effekte hybrider Arbeit auf die täglichen Arbeitsergebnisse und das Wohlbefinden der Mitarbeitenden untersucht, wobei der Fokus auf der within-person-Variabilität liegt. Zweitens wird die Befriedigung der psychologischen Grundbedürfnisse nach Autonomie, Kompetenz und sozialer Eingebundenheit als Mediator-Variable analysiert, um den Zusammenhang zwischen dem Arbeitsort und dem Wohlbefinden von Mitarbeitenden zu erklären. Drittens werden relevante Moderatoren im hybriden Arbeitskontext untersucht. Der Schwerpunkt liegt dabei auf zentralen Homeofficeaspekten: Die Zeit, die im Homeoffice verbracht wird (Homeoffice-Intensität), die Verbreitung und Akzeptanz von Homeoffice im Unternehmen (Homeoffice-Normativität) und die wahrgenommene Freiwilligkeit bei der täglichen Wahl des Arbeitsortes (tägliche Homeoffice-Freiwilligkeit), sowie die moderierende Rolle des Arbeitsortes in der Beziehung zwischen Stressoren und dem Wohlbefinden.
Studie 1 untersuchte den direkten Effekt des Arbeitsortes auf die emotionale Erschöpfung sowie den daraus resultierenden indirekten Einfluss auf die wahrgenommene Leistung anhand von Tagebuchdaten von 151 Mitarbeitenden (N = 876 Beobachtungen). Die Ergebnisse von Multilevel-Strukturgleichungsmodellen (MSEM) zeigten, dass Mitarbeitende an Homeofficetagen weniger emotionale Erschöpfung und dementsprechend eine höhere Leistung wahrgenommen haben als an Bürotagen. Darüber hinaus wurden die moderierenden Rollen von Homeoffice-Intensität, Homeoffice-Normativität und die täglicher Homeoffice-Freiwilligkeit untersucht, die relevante Merkmale der sich verändernden hybriden Arbeitswelt widerspiegeln. Die bedingten indirekte Effekte zeigten, dass die Effekte stärker ausgeprägt waren, wenn Mitarbeitende seltener von zu Hause arbeiteten (geringe Homeoffice-Intensität), in Organisationen arbeiteten, in denen Homeoffice weniger verbreitet war (geringe Homeoffice-Normativität), oder weniger Wahlmöglichkeiten hinsichtlich ihres Arbeitsortes hatten (geringe tägliche Homeoffice-Freiwilligkeit).
In Studie 2 wurden die mediierenden Mechanismen für den Einfluss des Arbeitsortes auf das Arbeitsengagement und die kognitive Beanspruchung untersucht. Der Fokus lag dabei auf der Rolle der Befriedigung der psychologischen Grundbedürfnisse. Basierend auf Tagebuchdaten von 114 Mitarbeitenden (N = 744 Beobachtungen) zeigten Multilevel-Mediationsmodelle, dass die Arbeit im Homeoffice mit einer höheren Befriedigung der Bedürfnisse nach Autonomie und Kompetenz verbunden war. Dies wirkte sich positiv auf das Arbeitsengagement aus und reduzierte die kognitive Beanspruchung. Demgegenüber war die Arbeit im Homeoffice mit einer geringeren Befriedigung des Bedürfnisses nach sozialer Eingebundenheit verbunden. Dies erhöhte ebenfalls das Arbeitsengagement und reduzierte die kognitive Beanspruchung. Multilevel-moderierte Mediationsmodelle zeigten zudem, dass Homeoffice-Normativität die indirekten Effekte der Befriedigung der Bedürfnisse nach Autonomie und sozialer Eingebundenheit abschwächte.
Studie 3 richtete den Fokus auf die moderierende Wirkung des Arbeitsortes auf die Beziehung zwischen Zeitdruck (einem Challenge-Stressor), beruflicher Isolation (einem Hindrance-Stressor) und Arbeitsengagement sowie emotionaler Erschöpfung. Die MSEM-Analyse der Tagebuchdaten von 124 Mitarbeitenden (N = 609 Beobachtungen) ergab eine signifikante Zweifachinteraktion zwischen Arbeitsort und beruflicher Isolation in Bezug auf emotionale Erschöpfung. Wie in den Studien 1 und 2 wurde auch in dieser Studie die moderierende Rolle der Homeoffice-Normativität untersucht. Hier zeigten sich signifikante Dreifachinteraktionen von Arbeitsort, Homeoffice-Normativität und den Stressoren, die sowohl den Zusammenhang zwischen Zeitdruck und Arbeitsengagement bzw. emotionaler Erschöpfung als auch zwischen beruflicher Isolation und emotionaler Erschöpfung beeinflusste, wobei gemischte Interaktionsmuster auftraten.
Insgesamt untersuchten diese Studien umfassend die psychologischen Dynamiken hybrider Arbeit. Die Ergebnisse unterstreichen die Bedeutung von within-person-Effekten und die Notwendigkeit, sowohl mediierende Faktoren wie die Befriedigung grundlegender Bedürfnisse als auch moderierende Faktoren wie die Intensität, Normativität und Freiwilligkeit von Homeoffice in die Betrachtung der Mitarbeitendenergebnisse einzubeziehen.
Die praktischen Implikationen dieser Ergebnisse sind für Unternehmen, die sich mit der Zukunft der Arbeit befassen, von großer Bedeutung. Sie bieten wertvolle Hinweise zur Förderung und Gestaltung hybrider Arbeitsformen. Die Dissertation unterstreicht, wie wichtig es ist, flexible Arbeitsregelungen zu fördern, die die Autonomie und Kompetenz von Mitarbeitenden stärken und gleichzeitig negative Auswirkungen wie Isolation aktiv mindern. Dabei ist außerdem entscheidend, die Verbreitung von Homeoffice innerhalb einer Organisation zu berücksichtigen und die Vorteile von Homeoffice- und Büroarbeit gleichermaßen in Betracht zu ziehen, um eine unterstützendes und produktives hybrides Arbeitsumfeld zu gewährleisten.X, 137 Seiten ; Diagramm
Anti-coronaviral activities of natural products and their derivatives
Full text linkThe COVID-19 pandemic, caused by SARS-CoV-2, has had a profound impact on global
health and economies, highlighting the urgent need for novel, effective antiviral agents.
Following its first report in Wuhan, China in 2019, it quickly spread around the world with
more than 7 million fatalities and over 777 million reported cases as of February 2025. While
vaccines have played a crucial role in decreasing disease severity, the continuous emergence
of new mutant strains, particularly the Omicron subvariants, poses a significant challenge.
These variants have demonstrated an increased ability to evade immune detection, reducing the
efficacy of existing vaccines and antibody therapies. Moreover, the period between disease
outbreaks has become shorter, and there is a possibility that more viral epidemics will occur
soon. Thus, the identification of pan-coronaviral inhibitors, capable of targeting viral structures
essential for replication and host entry, is crucial for pandemic preparedness and long-term
antiviral strategies. The present PhD thesis demonstrates that natural product derivatives can
serve as pan-coronaviral inhibitors.
The main protease (Mpro or 3CLpro) in coronaviruses represents a promising specific drug target
as it is essential for the cleavage of the virus polypeptide and has a unique cleavage site that
does not exist in human host proteases. Here we explored potential natural pan-coronavirus
drugs using in vitro and in silico approaches and three coronavirus main proteases as treatment
targets. Hypericin, rosmarinic acid, isorhamnetin, and luteolin inhibited Mpro of SARS-CoV-2,
while hypericin and isorhamnetin inhibited Mpro of SARS-CoV-1; hypericin showed inhibitory
effects toward Mpro of MERS-CoV. Microscale thermophoresis confirmed the binding of these
compounds to Mpro with high affinity. Cytotoxity results showed that rosmarinic acid and
luteolin were not cytotoxic toward MRC-5 cells, whereas hypericin and isorhamnetin showed
slightl toxicity. These findings highlight hypericin’s potential as a lead compound for further
development in antiviral drug discovery as a pan-anti-coronaviral agent by binding to and
inhibiting Mpro of several human-pathogenic coronaviruses.
The receptor-binding domain (RBD) within the S1 subunit plays a pivotal role in binding to
the angiotensin-converting enzyme 2 (ACE2) receptor on host cells, facilitating viral entry,
represents a promising target for therapeutic intervention. We demonstrated that a
diketopiperazine/piperidine alkaloid and natural isoquinoline derivatives inhibited SARS-CoV-
2 pseudovirus and live virus entry in host cells while showing low toxicity. Microscale
thermophoresis revealed these compounds strongly bound to the RBDs of SARS-CoV-2,III
SARS-CoV-2 XBB, SARS-CoV-1, MERS-CoV, and HCoV-HKU1, with their Kd values
increasing as RBD sequence similarity decreased. These findings showed that these
compounds, should be considered for further development as potential pan-coronavirus entry
inhibitors.Getrennte Zählungen ; Illustrationen, Diagramm
A dilatant visco-elasto-viscoplasticity model with globally continuous tensile cap : stable two-field mixed formulation
Full text linkRocks break if shear stresses exceed their strength. It is therefore important for typical geoscientific applications to take shear failure mechanism and the subsequent development of mode-II shear bands or faults into account. Many existing codes incorporate non-associated Drucker-Prager or Mohr-Coulomb plasticity models to simulate this behavior. Yet, when effective mean stress becomes extensional, for example when fluid pressure becomes large, the dominant failure mode changes to a mode-I (opening) mode, which initiates plastic volumetric deformation. It is rather difficult to represent both failure modes in numerical models in a self-consistent manner, while also accounting for the nonlinear visco-elastic host rock rheology, which varies from being nearly incompressible in the mantle to being compressible in surface-near regions. Here, we present a simple plasticity model that is designed to overcome these difficulties. We employ a combination of a linearized Drucker-Prager shear failure envelope with a circular tensile cap function in way that ensures continuity and smoothness of both yield surface and flow potential in the entire stress space. A Perzyna-type viscoplastic regularization ensures that the resulting localization zones are mesh-insensitive. To deal with the near incompressibility condition, a mixed two-field finite element formulation is employed. The local nonlinear iterations at the integration-point level are used to determine the stress increments. The global Newton-Raphson iterations are applied to solve the discretized momentum and continuity residual equations. The presented plasticity model is implemented in an open-source 2D unstructured finite element code GeoTech2D. The results of several typical test cases that range from crustal scale deformation to the propagation of fluid-induced tensile failure zones demonstrate rapid convergence. The robustness of the solution scheme is enhanced by the adaptive time stepping algorithm
