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Optogenetic quantification of cardiac excitability and electrical coupling in intact hearts to explain cardiac arrhythmia initiation
Full text linkIncreased cardiac excitability and reduced electrical coupling promote cardiac arrhythmia and can be quantified by input resistance (Rm), pacing threshold (Ithr), and cardiac space constant (λ). However, their measurement in the heart was not feasible because the required homogenous current injection cannot be performed with electrical stimulation. We overcame this problem by optogenetic current injection into all illuminated cardiomyocytes of mouse hearts in different action potential phases. Precisely triggered and patterned illumination enabled measuring Rm and λ, which both were smallest at diastole. Pharmacological and depolarization-induced reduction of inwardly rectifying K+ currents (IK1), gap junction block, and cardiac infarction reduced Ithr, showing the importance of high IK1 density and intact cardiomyocyte coupling for preventing arrhythmia initiation. Combining optogenetic current injection and computer simulations was used to classify pro- and anti-arrhythmic mechanisms based on their effects on Rm and Ithr and allowed to quantify IK1 inward rectification in the intact heart, identifying reduced IK1 rectification as anti-arrhythmic concept
Lateinische Literatur des Barock : Inhalte, Formen und Funktionen
No full textDer Band enthält 15 Beiträge zur lateinischen Literatur des 17. Jahrhunderts aus mehreren europäischen Räumen (deutscher Sprachraum, Italien, England, Litauen/Polen, Estland, Skandinavien), zu verschiedenen Gattungen (Epos, Epigramm, Figurengedicht, Lyrik, Hymnus, Geschichtsschreibung, Traktat) und aus unterschiedlichen Funktionszusammenhängen (Buchpublikation, Festvortrag u.a.). Untersucht wird der Zusammenhang von Inhalt, Gattung und Funktionszusammenhang, besonders aber das jeweilige Verhältnis der lateinischen Texte zu der bereits entwickelten oder sich entwickelnden nationalsprachlichen Literatur. Hierbei stehen zwei Fragen im Vordergrund: Inwieweit führte die Konkurrenz mit der Nationalliteratur zu Innovationen in der lateinischen Literatur? Fügt sich lateinische Literatur des 17. Jahrhunderts in die etablierten Epochengrenzen und -beschreibungen
Proximity-based Therapeutic Modalities for Precise Modulation of Histone Deacetylases
Full text linkHistone deacetylases (HDACs) serve as critical epigenetic regulators that modulate gene expression through catalytic removal of acetyl groups from histone substrates. By controlling the acetylation status of both histone and non-histone proteins, HDACs orchestrate fundamental cellular processes including cell cycle, chromatin decondensation, apoptosis and angiogenesis. These pleiotropic functions have established HDACs as validated therapeutic targets in oncology, evidenced by the FDA and CFDA approval of five HDAC inhibitors for various cancer indications to date.
Despite their clinical utility, currently available HDAC inhibitors suffer from significant off-target effects, including nausea, vomiting, fatigue, and cardiotoxicity, that largely result from their pan-HDAC inhibitory activity across multiple isoforms. Developing isoform-selective HDAC modulators represents a promising strategy to overcome these limitations, as targeted pharmacological regulation of specific HDAC family members could potentially maintain therapeutic efficacy while substantially reducing adverse effects.
To address these limitations, three innovative proximity-based therapeutic modalities were designed to achieve precise control of HDAC activity. These approaches leverage targeted protein modulation to enhance isoform specificity while minimizing off-target effects, potentially overcoming the key challenges that have constrained the clinical utility of conventional HDAC inhibitors in oncology applications
Vom Realen erzählen : Zu einer Konstellation spätmoderner Literatur (1985-2015)
Full text linkDie vorliegende Arbeit unternimmt eine systematische Rahmung und Analyse von Erzähltexten der Spätmoderne bzw. der Gegenwart, die sowohl individuell als auch kollektiv wahrgenommene Krisen und Katastrophen zur Darstellung bringen. Für die Beschreibung solcher irritierter Erfahrungs- und Wahrnehmungsmuster hat sich in der kulturwissenschaftlichen Forschung die Rede vom Einbruch des Realen etabliert. Allerdings versäumen die entsprechenden Forschungen es, sowohl die Geschichte und Semantik des Realen als auch die figurativen Implikationen der Metapher des Einbruchs hinreichend zu entfalten. Dieses Versäumnis holt die vorliegende Arbeit nach und entwickelt entlang des systemtheoretischen Verständnisses von Irritation das Reale als eine Analysekategorie. Die erkennbare und zudem signifikante Phänomenalität von Einbrüchen des Realen führt die Arbeit dann am Beispiel autobiographischer und referenzintensiver Erzählliteratur vor und konfrontiert diese Literatur wiederum in einer historischen Perspektive mit realistisch verfahrenden Texte, von denen sich das Erzählen vom Realen spürbar absetzt und in Differenz dazu ein eigenständiges Profil ausbildet
Rhizospheric <em>Bacillus</em> isolates control Fusarium wilt on cotton and enhance plant biomass and root development
Full text linkCotton is a globally significant crop, serving as a source of natural fiber for the textile industry and contributing to various other products. Its economic importance is substantial, impacting livelihoods and international trade. However, cotton production faces numerous challenges, including Fusarium wilt caused by Fusarium oxysporum f. sp. vasinfectum (Fov), which can lead to significant yield and fiber quality losses. Plants alter their root exudate profiles in response to pathogens, often selectively enriching for beneficial rhizobacteria with antagonistic activity and plant growth-promoting traits. This study thus aims to characterize bacteria isolated from the rhizosphere of diseased cotton plants. The antifungal activity of 43 isolates was assessed against Fov in vitro. Eight of these inhibited Fov growth by 68.4 to 76.9%. 16S rRNA sequencing confirmed these isolates as Bacillus species. These eight Bacillus strains were further examined for their different modes of action in vitro, and their effect on cotton plants in greenhouse experiments challenged with Fov. All eight strains produced chitinases and pectinases, seven demonstrated cellulase and three protease activity, six produced urease, and five siderophores. Only B. subtilis SC11 exhibited phosphate solubilization activity. Seed treatments revealed that B. subtilis SC10 and B. subtilis SC11 were the standout treatments reducing Fov-caused symptoms by ~83% compared to Fov-inoculated control plants and most significantly improved plant growth and antioxidant activity. In detail, B. subtilis SC11 increased shoot and root dry weight by 160 and 250%, respectively. B. subtilis SC10 increased peroxidase activity by ~143% and ascorbate peroxidase activity by ~60%, while in B. subtilis SC11 treated plants superoxide dismutase activity increased by ~100%. Bacillus treatments effectively mitigated lipid peroxidation, achieving up to 91.4% reduction (B. subtilis SC10, B. halotolerans SC15), and decreased H2O2 accumulation by up to 58.4% (B. halotolerans SC32) compared to the Fov control. Principle component analysis revealed that regarding plant growth parameters, the treatments, and controls were distributed differentially across PC1 and PC2, with 60.30 and 15.62% data variance, respectively, showing the effectiveness of Bacillus isolates in greenhouse experiments. The findings of this study will contribute to the development of sustainable biocontrol strategies for managing Fusarium wilt in cotton
Amtliche Bekanntmachungen, 55. Jahrgang, Nr. 95
No full textAktualisierung des Akkreditierungsbeschlusses Strategy and International Security (M.A.) vom 4. November 202
AI-Enhanced 3D Models in Global Virtual Reality Case Conferences for Surgical Care in a Low-Income Country : Exploratory Study
Full text linkBackground: Approximately 5 billion people worldwide lack adequate access to surgical care, primarily in the Global South. Especially in crisis regions and war zones, telemedical applications may enhance health services. This study explores the feasibility of using artificial intelligence (AI)-enhanced 3D imaging and extended reality (XR) technologies for intercontinental surgical case conferences in a low-resource scenario in Uganda. Our pilot study aims to assess the value of these technologies to address the lack of surgical resources and multilateral knowledge exchange. Objective: This study intends to determine the feasibility of using new AI-enhanced image modeling technology within an immersive spatial XR scenario to collaboratively and remotely assess reconstructive patient cases in the resource-limited country of Uganda. Methods: Within a surgical camp at Lamu Medical Centre, Uganda, 3D models of patients’ conditions were created using a smartphone app. Digital models were generated from photographs taken on-site and processed into 3D formats to be visualized in virtual case conferences. Here, surgeons from Uganda and Germany used virtual reality (VR) headsets to collaboratively discuss case strategies while marking surgical approaches on each digital patient model. Results: The study included 15 patients requiring reconstructive surgery, with a diverse range of conditions. The use of XR technology facilitated detailed visualization and discussion of surgical strategies. The process was time-efficient, with a total of under 8 minutes per case for data acquisition and model creation, and resource-efficient with surgeons reporting sufficient quality of smartphone-derived models. Valuable user experience and precise interaction during the VR case processing were found, underlining its potential to improve surgical planning and patient care in resource-limited settings. Conclusions: The findings indicate that AI-enhanced 3D imaging and immersive virtual communication platforms are valuable tools for integrative surgical case assessments. The cost-effectiveness of the used consumer solutions should be especially beneficial for low-resource environments. While the study demonstrates the feasibility of this approach, further research is needed to explore a broader application and impact of these technologies in global health. The study highlights the potential of XR to enhance training and surgical precision, contributing to better health care outcomes in underserved regions
A systematic review of gender in participatory and social learning research in agriculture and land management in Africa
Full text linkWe conduct a systematic review to explore the state of knowledge on participatory and social learning research in agriculture and land management in Africa, the extent to which women and other marginalized groups are engaged in the collective development processes, and how gender issues are addressed. Grounded in gender and social inclusion concepts, guided by Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA), and using Scopus and Web of Science databases, we discover a modest and fluctuating growth in participatory and social learning research since 2005. However, many participatory studies, do not address specifically collective learning and reflection nor integrate gender. For those with in-depth gender focus, multiple approaches are adopted for stakeholder selection and engagement, enabling a detailed reflection and integration of gender dimensions in co-developing solutions. It is crucial for participatory studies to be socially inclusive and gender sensitive, and address power dynamics, which are necessary to alter gender relations and norms, tackle inequality, and enhance agency at the household and community levels
Low and facultative mycorrhization of ferns in a low-montane tropical rainforest in Ecuador
Full text linkArbuscular mycorrhizal fungi (AMF) are amongst the most studied obligate plant symbionts and regularly found in terrestrial plants. However, global estimates of AMF abundance amongst all land plants are difficult because i) the mycorrhizal status of many non-commercial, wild plant species is still unknown, ii) numerous plant species engage in facultative symbiosis, meaning that they can, but do not always do, associate with mycorrhiza, and iii) mycorrhizal status can vary within families, genera, and species. To gain deeper insights to the distribution of the plant-AMF symbiosis we investigated the mycorrhizal status in some of the oldest lineages of extant vascular plants, Polypodiophytina (ferns) and lycophytes, in one of the hotspots of natural plant diversification, the tropical rainforest. Providing a new data set of AMF abundance for 82 fern species representing 19 families, we hypothesized that (1) AMF would be found in 60–80% of the studied plants and (2) plant species with AMF symbionts would be more abundant than non-mycorrhizal species. Both hypotheses were rejected while the following observations were made: (1) AMF occurred in 30.5% of studied species, representing 63% of the studied fern families, (2) AMF colonisation was not correlated with species abundance, (3) a small proportion of AMF-hosting ferns was epiphytic (6%) and (4) mycorrhization was inconsistent among different populations of the same species (facultative mycorrhization). While these observations align with previous studies on ferns, they emphasise that mycorrhization is not a taxonomic trait and underscore the challenges in estimating the global abundance of AMF. In addition, the occurrence of AMF in epiphytic plants and no net benefits of AMF for plant abundance indicate that the mycorrhization observed in this study likely comprises the commensalism to parasitism range of the symbiosis spectrum
The Investigations on Diterpene Biosynthesis through Substrate and Protein Engineering
No full textThis cumulative doctoral dissertation "The Investigations on Diterpene Biosynthesis through Substrate and Protein Engineering" concentrates on diterpene biosynthesis from various aspects, including non-natural biotransformation, genome mining, mechanistic study and enzyme engineering.
First, seven geranylgeranyl diphosphate (GGPP) analogs named iso-GGPPs, were synthesized chemically or enzymatically, of which double bonds were replaced by various modified methylene groups, leading to novel reactivities. The subsequent biotransformations with almost 20 characterized diterpene synthases resulted in the isolation of more than 50 nonnatural diterpenes featuring novel terpene skeletons. Among them, some compounds can be regarded as the derailment products in the cyclization cascade, while others are generated from distinct cyclization modes in comparison to its natural counterparts. Apart from that, four isotope labelled substrate analogs were stereoselectively synthesized and used in the enzymatic conversions to determine the absolute configurations of isolated non-natural diterpenes. Second, two new fungal terpene synthases were also functionally characterized after bioinformatic analysis, gene cloning and protein expression, whose products were wellinvestigated for understanding their formations through isotopic labelling experiments. Third, two previously reported diterpenes, benditerpe-2,6,15-triene and venezuelaene A, with tentative biosynthetic proposals presented in the original works, were investigated for the hydride shifts in their biosynthesis through isotopic labelling studies, non-natural biotransformations, product derivations and DFT calculations. In addition, site-directed mutagenesis studies in conjunction with molecular docking on spata-13,17-diene synthase and selina-4(15),7(11)-diene synthase disclosed the function of a specific hydrophobic tunnel in these two enzymes, which enable evolving the second enzyme from a sesquiterpene synthase to a diterpene synthase. Last but not least, the well-known diterpene taxa-4,11-diene was addressed in this thesis. Unique long-proton migrations were observed in the biosynthesis of taxaxenene and cyclophomactene, two compounds generated from a non-natural enzymatic conversion with wild type taxadiene synthase and an enzyme variant, respectively.
All in all, this doctoral dissertation provides novel insights into the terpene field. The combination of various strategies enabled the discovery of novel terpenes and mechanistic investigations of utilized enzymes, which will be described in detail in this thesis