Gutenberg Open Science (Univ. Mainz)
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DNA flipping as facile mechanism for transmembrane signaling in synthetic cells
No full textTransmembrane signaling is essential for cellular communication, yet reconstituting such mechanisms in synthetic systems remains challenging. Here, we report a simple and robust DNA-based mechanism for transmembrane signaling in synthetic cells using cholesterol-modified single-stranded DNA (Chol-ssDNA). We discovered that anchored Chol-ssDNA spontaneously flips across the membrane of giant unilamellar lipid vesicles (GUVs) in a nucleation-driven, defect-mediated process. This flipping enables internal signal processing through hybridization with encapsulated complementary DNA and activation of downstream processes such as RNA transcription. The phenomenon shows a high transduction efficiency, is generic across DNA sequences and lipid compositions, and can be enhanced by glycerol, which modulates membrane dynamics. Mechanistic insights using fluorescence microscopy, nuclease degradation assays, and membrane permeability assays reveal that flipping is dominated by transient membrane pores. Leveraging this facile translocation process, we demonstrate selective transcriptional activation inside synthetic cells, underscoring the potential of Chol-ssDNA flipping as a programmable tool for synthetic biology and bottom-up synthetic cell design
Adverse competition-related cognitions and it’s relation to satisfaction and subjective performance : a validation study in a sample of English-speaking athletes
No full textThis study aimed at examining the reliability and validity of the Adverse Competition-related Cognitions Questionnaire (ACCQ) in an English-speaking sample of athletes. The ACCQ is a performance-focused measure that captures six different areas of adverse competition-related cognitions– athletic comparison, coach devaluation, devaluation of one’s own performance, appreciation by coach and family, inner resistance against competitions, and general exhaustion. Data from 278 athletes (Mage = 27.64, age range = 16–68 years) from different sports were collected and subjected to confirmatory factor analysis, which confirmed the 6-factor solution of the translated ACCQ (CFI = 0.915; RMSEA = 0.056). In addition, the different subscales of the ACCQ showed sufficient internal consistency (Cronbach’s alpha > 0.60). Furthermore, we examined the relationships with cognitive interference, satisfaction in three different domains (i.e., general in life, sporting development, and athletic performance) and athletes’ subjective performance evaluations (i.e., performance and peak performance in the previous season and confidence in achieving their goals in the upcoming season). Results indicated positive correlations with athletes’ cognitive interference (i.e., construct validity in terms of a nomological network), low negative relations with athletes’ satisfaction in the three different domains and with the three parameters of subjective performance evaluation (i.e., concurrent validity). Implications of these findings and perspectives for future research are discussed
Extended coverage of human serum glycosphingolipidome by 4D-RP-LC TIMS-PASEF unravels association with Parkinson’s disease
No full textGlycosphingolipids (GSLs) are important targets in immune, infectious, lysosomal storage diseases, cancer, and neurodegenerative diseases. Circulatory GSLs profiling in clinical samples is restricted by the lack of mid- and high-throughput analytical methods and deep coverage of long-chain sialylated glycosphingolipidome. We present a 4-dimensional (4D)-glycosphingolipidomics platform for routine glycosphingolipidome profiling encompassing: extraction and fractionation of sialylated GSLs with 3 to 15 monosaccharides, neutral GSLs and sulfatides; µL-flow reversed-phase LC-TIMS-PASEF MS analysis; semi-quantification strategy adapted for fractionated glycosphingolipidome, and referential CCS, RT, and m/z values for GSLs annotation. 4D-glycosphingolipidomics of human serum reveals a high structural heterogeneity, amounting to 376 GSLs: 159 GSLs of ganglio- and neolacto-series, 145 neutral GSLs and 72 sulfatides. Here we demonstrate the platform’s utility for clinical profiling of Parkinson’s disease (PD) sera. 41 neolacto- and ganglio-species discriminate PD patients from controls and 14 GSLs differentiate sex subgroups, laying the foundation for further functional GSL studies with PD
Perceptual and semantic maps in individual humans share structural features that predict creative abilities
No full textBuilding perceptual and associative links between internal representations is a fundamental neural process, allowing individuals to structure their knowledge about the world and combine it to enable efficient and creative behavior. In this context, the representational similarity between pairs of represented entities is thought to reflect their associative linkage at different levels of sensory processing, ranging from lower-order perceptual levels up to higher-order semantic levels. While recently specific structural features of semantic representational maps were linked with creative abilities of individual humans, it remains unclear if these features are also shared on lower level, perceptual maps. Here, we address this question by presenting 148 human participants with psychophysical scaling tasks, using two sets of independent and qualitatively distinct stimuli, to probe representational map structures in the lower-order auditory and the higher-order semantic domain. We quantify individual representational features with graph-theoretical measures and demonstrate a robust correlation of representational structures in the perceptual auditory and semantic modality. We delineate these shared representational features to predict multiple verbal standard measures of creativity, observing that both, semantic and auditory features, reflect creative abilities. Our findings indicate that the general, modality-overarching representational geometry of an individual is a relevant underpinning of creative thought
Die Unterscheidung von Myopie und Glaukom anhand der Optischen Kohärenztomographie
No full text116 Seiten ; Illustrationen, Diagramm
Einfluss des Schweregrades der obstruktiven Schlafapnoe auf die Häufigkeit der zentralen Apnoen im REM-Schlaf, sowie auf die Mikrostruktur der cortikalen respiratorischen Arousals
No full textOSA ist eine multifaktoriell bedingte Erkrankung, mit vielfältigen Symptomen und auch diversen komorbiden Erkrankungen. Trotz dessen beruht die Festlegung der Diagnose und auch die Einteilung des Schweregrades auf einem singulären Parameter, dem AHI. Mit dieser Arbeit, sollte an den neuesten, wissenschaftlichen Stand Anschluss genommen werden, dass ein singulärer Parameter zur Beschreibung des Schweregrades einer solch komplexen Erkrankung nicht ausreicht. Dahingehend wurden in einer retroperspektiven Studie, Zusammenhänge zwischen einem möglichen neuen Parameter, der „area under the curve of respiratory arousal“, kurz arousal-AUC und bereits bekannten Parametern, wie dem „hypoxic burden“, AHI und dem „arousal index“ gesucht. Ganz bewusst wurde sich für diese Darstellung ein Verfahren aus dem Bereich des Maschinellen Lernens entschieden, um auch dort an neuste Forschung Anschluss zu nehmen.
Dabei wurde in den polysomnographischen Datensätzen, der von OSA betroffenen Probanden und Probandinnen, eine klinisch bisher nicht beschriebene Auffälligkeit gefunden: Die Mehrheit der Probanden und Probandinnen hatten keinerlei zentralen Apnoen (CAE) im REM-Schlaf. Weiterhin konnte aufgezeigt werden, dass durch die Anpassung der REM-Schlafzeit auf die gesamte Schlafdauer, nur schwer betroffene OSA-Patienten vermehrt CAE im NREM, im Gegensatz zum REM-Schlaf, hatten. Daraus ist eine Folgepublikation entstanden, mit dem Ziel, in einer retroperspektiven, explorativen Studie, diesen neuen Befund zu beschreiben und mögliche, pathophysiologische Erklärungen zu finden.I, 32 Seiten : Illustrationen, Diagramme, Tabelle
Greening the future of healthcare : implementation of sustainability strategies in German hospitals and beyond : a review
No full textThis study explores the implementation of sustainability measures within German hospitals, emphasizing their critical role in mitigating environmental impacts and promoting public health. The healthcare sector significantly contributes to global greenhouse gas emissions, necessitating urgent reforms in energy use, waste management, construction, transportation, and food systems. Key findings highlight the potential for hospitals to enhance energy efficiency, adopt renewable energy sources, and reduce waste through innovative technologies and sustainable practices. Initiatives such as green hospital designs, climate-conscious food systems, and sustainable procurement strategies are central to reducing the ecological footprint. Despite these opportunities, barriers such as workforce shortages, insufficient funding, and technical complexity hinder progress. Addressing these challenges through leadership commitment, resource allocation, and staff engagement is essential for aligning the healthcare sector with national and international sustainability goals. By prioritizing sustainability, hospitals can achieve long-term economic benefits, improve patient outcomes, and foster a healthier, more resilient society
Electrochemical one-step synthesis of alkyne sulfonates and sulfonamides : building blocks for highly substituted alkenes and 1,3-butadienes
No full textAlkyne motifs have a central place in organic synthesis due to their versatility as building blocks for complex molecule construction. The development of efficient and sustainable strategies for the synthesis of functionalized alkynes remains an utmost challenge in modern organic chemistry. Herein, we report a novel and efficient electrochemical multicomponent reaction (eMCR) that enables the one-step synthesis of valuable alkyne sulfonates and sulfonamides using SO2 stock solutions and electric current as a clean oxidant. The generated alkynyl sulfonates and sulfonamides serve as powerful synthetic intermediates, undergoing diverse downstream transformations, including regio- and stereoselective copper-catalyzed dimerizations, hydroarylations, and cyclizations, to access 1,3-dienes, highly substituted alkenes, and heterocycles. Moreover, this method enables late-stage functionalization of complex molecules and pharmaceuticals, demonstrating its significant potential for natural product synthesis, medicinal chemistry, and materials science. The study underscores the promise of electrochemical MCRs as sustainable and versatile tools in modern synthetic methodology
Effects of cisplatin on the radiation response and DNA damage markers in peripheral blood lymphocytes ex vivo
No full textPlatinum-based radiochemotherapy is associated with hematologic side effects, impacting patient outcomes. However, the clinical mechanisms of cisplatin and its interaction with ionizing radiation (IR), including in biodosimetry for radiotherapy, have not yet been fully clarified. For this purpose, healthy donors’ peripheral blood lymphocytes (PBLs) were pretreated with cisplatin in a pulse (1–4 h) or continuous (24 h) regimen followed by X-rays. DNA damage was assessed as DNA double-strand breaks using repair foci of γH2AX and 53BP1 after 0.5 h and 24 h in G1 PBLs and a proliferation-based cytokinesis-block micronucleus assay. Additionally, cell death and proliferation activity were measured. Unlike a 1 h pulse, a 24 h cisplatin pretreatment caused a concentration-dependent increase in cisplatin-induced foci while decreasing IR-induced foci, especially 24 h after irradiation. This was accompanied by increased apoptosis, with cisplatin and IR having additive effects. Both genotoxins alone caused a dose-dependent increase in micronuclei, while cisplatin significantly reduced binuclear cells, especially after the 24 h treatment, leading to lower micronuclei frequencies post-irradiation. Our results show that prolonged cisplatin exposure, even at low concentrations, impacts the vitality and division activity of PBLs, with significantly stronger effects post-irradiation. This has major implications and must be considered for the detection of DNA damage-associated biomarkers in PBLs used in clinical prediction or biodosimetry during radiotherapy
Xsurvey : web tool to query the set of homorepeats of all reference proteomes
No full textHomorepeats are low complexity regions in protein sequences composed of repetitions of one specific amino acid residue. There is currently no automatic way to compare the set of homorepeats between two or more species. Here we present Xsurvey, a web tool to query the set of homorepeats of 23,150 completely-sequenced proteomes. The polyX usage values can be easily compared visually, which simplifies the interpretation of the results