Gutenberg Open Science (Univ. Mainz)
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Phosphatidylinositol 3-phosphate metabolism impacts cellular a-synuclein localization in Saccharomyces cerevisiae
Get PDFAlpha-synuclein (αSyn), a hallmark protein of synucleino pathies such as Parkinson’s disease (PD), is likely to be
involved in neuronal membrane trafficking and synaptic
vesicle dynamics at axon terminals. Its specific binding to
anionic phospholipids, such as phosphatidylinositol phos phates that are essential for intracellular signaling and mem brane trafficking, suggests an involvement in vesicular
transport processes. In Saccharomyces cerevisiae, a model or ganism for cell biological PD research, human αSyn localizes
to the plasma membrane via the secretory machinery.
Employing this yeast model, we investigated the impact of
αSyn on cellular quality control mechanisms. Additionally, we
focused on the effect of αSyn expression in yeast mutants
impaired in specific phospholipid biosynthesis and transport
pathways, including endovacuolar trafficking and autophagy.
In the deletion strains vps34Δ and vps15Δ, lacking phospha tidylinositol 3-phosphate (PI3P) biosynthesis, αSyn mis localizes in the cytosol, and significantly reduces cell viability.
In these strains, αSyn species containing an intact lipid binding N terminus also form large perivacuolar, lipid-rich
accumulations. In wild type cells, αSyn expression alters the
morphology of PI3P-rich membrane structures and upregu lates transcription of SEC4, which encodes a key regulator of
the late secretory pathway. Moreover, αSyn colocalizes with
overexpressed Sec4 at the emerging cell bud. Our findings
demonstrate that PI3P is critical for the targeting of αSyn to
the yeast plasma membrane via the secretory pathway,
revealing a potential entry point into this complex machinery.
Understanding the relationship between αSyn and vesicular
trafficking in this system will enhance our knowledge of αSyn trafficking in mammalian cells and, eventually, in PD, offering
new research avenues
Unraveling the Molecular Mechanisms of the BmrA Function: From Intramolecular Interactions to Membrane-Dependent Regulation
Get PDF145 Seiten ; Illustrationen, Diagramm
Politisch-philosophische Urteilsfähigkeit in der schulischen Bildung : ein Modell eines guten politischen Urteils und wie philosophiedidaktische Ansätze helfen können, die Urteilsqualität im Politikunterricht zu verbessern
Get PDFIII, 69 Seite
Expressionsanalyse und prädiktive Wertigkeit von Biopsien der Karzinome des oberen gastrointestinalen Traktes vor neoadjuvanter Therapie
Get PDFIX, 79 Seiten ; Illustrationen, Diagramm
»… den Generalbass recht nach der Kunst zu schlagen« : die Generalbasslehre im Aschaffenburger Clavierbuch
Get PDFDas Aschaffenburger Clavierbuch ist eines der wenigen erhaltenen Manuskripte aus der Zeit um 1700, das nahezu alle zum damaligen Studienrepertoire für Tasteninstrumente zählenden Bereiche umfasst: Der dem Kurmainzer Umfeld in Aschaffenburg zuzurechnende Hauptschreiber des Manuskripts stellte viele anonym und hier erstmalig überlieferte Werke mit besonders wertvollen Klavierkompositionen aus verbreiteten Druckwerken seiner Zeit etwa von Johann Kuhnau oder Johann Pachelbel zusammen, kopierte Generalbassübungen aus der in Süddeutschland verbreiteteten Chirologia von Justinus Will und fügte als Exempla Sätze aus zwei Liedsammlungen des späten 17. Jahrhunderts unter anderem von Laurentius von Schnüffis und Jakob Kremberg hinzu. Die Edition der Generalbasslehre und der Lieder des Bands im Open Access im Rahmen der Schriftenreihe der Hochschule für Musik Mainz ergänzt eine Edition der Clavierkompositionen in der Reihe »Musik am Mittelrhein« (Mainz 2025).55 Seite
Hilbert properties of varieties, rational points, and dynamical systems
Get PDFAn integral variety has the Hilbert property if its rational points are not thin. Corvaja–Zannier showed that a smooth projective integral variety with the Hilbert property over a finitely generated field k of characteristic 0 admits no non-trivial étale covers, motivating the refined notion of the “weak Hilbert property”. Conjecturally, every smooth projective integral k-variety with a dense set of k-rational points should have the weak Hilbert property – a question originally posed by Corvaja–Zannier. This extends to quasi-projective varieties by replacing rational points with near-integral points on arithmetic models. This thesis provides new evidence for this conjecture in the quasi-projective setting. We prove that the Hilbert property and weak Hilbert property for arithmetic schemes are stable under products, generalizing results for varieties by Bary-Soroker–Fehm–Petersen and Corvaja–Demeio–Javanpeykar–Lombardo–Zannier, and other persistence properties. We also prove the conjecture for all algebraic groups, extending known results for linear algebraic groups and abelian varieties. Combined with a conjecture of Campana, Corvaja–Zannier’s question predicts that a variety with a dense set of rational points over a number field satisfies the integral weak Hilbert property even after removing a closed subscheme of codimension at least 2. We verify this “punctured” conjecture for all linear algebraic groups83 Seite
Accelerating the hit-to-lead optimization of a SARS-CoV-2 Mpro inhibitor series by combining high-throughput medicinal chemistry and computational simulations
Get PDFIn this study, we performed the hit-to-lead optimization of a SARS-CoV-2 Mpro diazepane hit (identified by computational methods in a previous work) by combining computational simulations with high-throughput medicinal chemistry (HTMC). Leveraging the 3D structural information of Mpro, we refined the original hit by targeting the S1 and S2 binding pockets of the protein. Additionally, we identified a novel exit vector pointing toward the S1′ pocket, which significantly enhanced the binding affinity. This strategy enabled us to transform, rapidly with a limited number of compounds synthesized, a 14 μM hit into a potent 16 nM lead compound, for which key pharmacological properties were subsequently evaluated. This result demonstrated that combining computational technologies such as machine learning, molecular docking, and molecular dynamics simulation with HTMC can efficiently accelerate hit identification and subsequent lead generation
On the physical processes controlling warm conveyor belt moisture transport into the upper troposphere and lower stratosphere
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Modernism in conflict : Bauhaus legacy amid functional demands, political ruptures and spatial appropriation
Get PDFDessau and Tel Aviv are linked by the architecture of modernism — as taught at the Staatliches Bauhaus, but also realised by numerous other architects. More than a century after their creation, these buildings merit renewed attention: their preservation, their contemporary use, and their socio-cultural context. What becomes clear is that modernist architecture is being questioned from multiple sides: by residents adapting their homes to everyday needs; by society, which transforms their urban integration and current use; and by shifting political circumstances.
Both countries — Germany and Israel — and both cities — Dessau and Tel Aviv-Yafo — have been shaped by a long history, by war, conflict, destruction, and reconstruction.
This publication examines the original Bauhaus buildings in Dessau, designed under Walter Gropius and Hannes Meyer. It follows the footsteps of Bauhaus student Arieh Sharon to the British Mandate territory of Palestine and his early residential project, Me‘onot Hod, in Tel Aviv. Yet the focus is not solely on the buildings’ original appearance: rather, the study explores their ongoing transformation — shaped in Dessau by wartime destruction
and socialist reconstruction after 1945, and in Jaffa, the historic capital of Palestine, by the British Mandate authorities and, from 1949 onwards, the State of Israel.
At its core, this work addresses a central question: how we engage with the architectural heritage of both modernity and pre-modernity.
The pursuit of this question was undertaken within the framework of a transnational and interdisciplinary exchange involving students from Germany, Israel, and Poland. As part of a two-part workshop held in 2023 at the Bauhaus Dessau and the Max Liebling Haus in Tel Aviv, participants engaged critically with the legacy of modernist architecture in historically charged urban contexts. This volume presents a selection of their research outcomes, offering diverse perspectives on the challenges of preservation, adaptation, and interpretation of architectural heritage across cultural and political boundaries.225 Seite
Image analysis : 68Ga-FAPI-46 PET derived texture parameters improve the differentiation of malignant and benign pulmonary lesions
Get PDFBackground
Pulmonary lesions inconclusive in 18F-FDG PET/CT are a known clinical problem. Both texture analysis and 68Ga-FAPI-46 have shown potential in thoracic oncological problems but their combination has not been assessed yet. This initial analysis aims to evaluate the utility of 68Ga-FAPI-46 PET texture parameters to differentiate between lung cancer and benign pulmonary lesions inconclusive in 18F-FDG PET/CT.
Materials and methods
20 histologically confirmed pulmonary lesions (13 lung cancer, 7 benign) in 19 patients were evaluated. All patients underwent an inconclusive 18F-FDG PET/CT before 68Ga-FAPI-46 PET/CT. 64 texture parameters and conventional parameters (SUVs, TBRs) were analyzed. Texture parameters with significant (P < 0.05) differences between lung cancer and benign lesions were detected by the Mann-Whitney U test. Boxplots and a scatter plot matrix were created. Principal component analyses and Spearman correlations were performed. Receiver operating characteristics curves with area under the curve (AUC) values were created for univariable and bivariable logistic regression.
Results
The texture parameters HIST Maximum grey level (AUC = 0.901), HIST Mean (AUC = 0.802), HIST Mode (AUC = 0.835), HIST Range (AUC = 0.901) and GLCM Information correlation 1 (AUC = 0.824) showed significant differences between lung cancer and benign pulmonary lesions. AUC values of conventional parameters (SUVmax, SUVmean, TBR(SUVmax), TBR(SUVmean)) were 0.791, 0.868, 0.802 and 0.857, respectively. Maximum AUC values of bivariable logistic regression were 0.967 and 0.978 for two texture parameters and the combination of conventional and texture parameters, respectively. Correlations between texture parameter pairs were mainly moderate (0.4≤ρ≤0.59). 2/5 texture parameters (HIST Mean, HIST Mode) displayed no very strong correlations (0.8≤ρ≤1.00) to any conventional parameters or lesion volume.
Conclusion
68Ga-FAPI-46 PET texture parameters show great potential to differentiate between lung cancer and benign pulmonary lesions inconclusive in 18F-FDG/PET. Spearman correlations indicate additional information value of texture parameters