Gutenberg Open Science (Univ. Mainz)
Not a member yet
11784 research outputs found
Sort by
Deep Learning-basierte Aszitesquantifikation in der CT-Bildgebung bei Hepatozellulärem Karzinom – Machbarkeit und erste Anwendungen
No full textV, 66 Seiten ; Diagramm
Einfluss von Diabetes mellitus auf die Anwendbarkeit des Animal Naming Tests zur Detektion einer minimalen hepatischen Enzephalopathie bei Patienten mit Leberzirrhose
Get PDFVIII, 120 Seiten ; Illustrationen, Diagramm
A bifunctional iron-nickel oxygen reduction/oxygen evolution catalyst for high-performance rechargeable zinc-air batteries
Get PDFEfficient and robust electrocatalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are crucial for fuel cells, metal-air batteries, and other energy technologies. Here, a highly stable, efficient bifunctional OER/ORR electrocatalyst (FeNi-NC@MWCNTs) is reported and demonstrated its integration and robust performance in an aqueous Zinc–air battery (ZAB). The catalyst is based on neighboring iron/nickel sites (FeNiN6) which are atomically dispersed on porous nitrogen-doped carbon particles. The particles are wrapped in electrically conductive multi-walled carbon nanotubes for enhanced electrical conductivity. Electrocatalytic analyses show high OER and ORR performance (OER/ORR voltage difference = 0.69 V). Catalyst integration in a ZAB results in excellent performance metrics, including an open circuit voltage of 1.44 V, a specific capacity of 782 mAh g−1 (at j = 15 mA cm−2), a peak power density of 218 mW cm−2 (at j = 260 mA cm−2) and long-term durability over 600 charge/discharge cycles. Combined experimental and theoretical (density functional theory) analyses provide an in-depth understanding of the physical and electronic structure of the catalyst and the role of the FeNi dual atom reaction site. The study therefore provides critical insights into the structure and reactivity of high-performance bifunctional OER/ORR catalysts based on atomically dispersed non-critical metals
Raw data for "Direct observation of triplet-triplet energy transfer in DNA between energy donor and acceptor C-nucleotides"
No full textInvestigating the migration of excited-state energy in DNA is crucial for a deep understanding of protection mechanisms and light-induced DNA damage. While numerous reports focused on single electron transfer and Förster-type energy transfer in DNA, studies on the Dexter-type triplet-triplet energy transfer are scarce, in particular those with direct detection of photoexcited triplet states. Herein, we present direct measurements of the distance-dependent triplet-triplet energy transfer rates through DNA by using transient absorption spectroscopy. This was achieved through the synthetic incorporation of thioxanthone as an energy donor and naphthalene as an energy acceptor into a DNA double strand at defined positions. The energy transfer rates strongly depend on the number of A-T base pairs (up to four) separating the energy donor from the energy acceptor. We observed a fast energy transfer rate with a time constant of 17 ns for the DNA sample in which the donor and acceptor are directly adjacent in the DNA. By analyzing two additional donor-acceptor distances, a steep exponential distance dependence with an attenuation factor of 1.15 Å^-1 could be obtained. Our results demonstrate that DNA acts as a poor conductor of triplet energy when energy donors with triplet energies below 2.7 eV are used, complementing more indirect studies on sensitized DNA damage.Experiment
Keeping the balance: investigating covalent affinity and passive permeability of protease Inhibitors
Get PDFX, 284 Seiten ; Illustrationen, Diagramm
One Shot inverse scattering revisited
Get PDFWe develop and discuss a novel reconstruction algorithm for the inverse source problem and the inverse scattering problem for the Helmholtz equation with well-separated compactly supported sources or scatterers in two-dimensional free space from far field observations of a single radiated or scattered wave. We show that a rational approximation of a Laurent polynomial formed by the low order Fourier coefficients of the given far field pattern can be used to determine straight lines connecting the support of the sources or scatterers to the origin. After repeating this procedure for many different choices of the origin, we apply a filtered backprojection algorithm to recover information on the number and the location of the unknown sources or scatterers. We give numerical examples to illustrate the performance and limitations of our reconstruction algorithm
Transcriptional similarities of non-lymphoid tissue regulatory T cells in health, acute inflammation and cancer
Get PDFRegulatory T cells (Treg) are an anti-inflammatory, immune-regulatory T cell type. Besides their classical function in immune regulation, a highly activated subset of Treg cells can also migrate into tissues and promote homeostasis as well as regeneration. This non lymphoid tissue subset is characterized by the expression of tissue-specific marker genes and their highly regenerative and suppressive function. Previous research had highlighted the importance of tissue-specific Treg cells in regeneration upon organ damage and inflammation, but less is known in the context of tumor progression. In this study we therefore aimed to characterize murine Treg cells from three different tumor types (colorectal carcinoma, B16-F10 melanoma, MC38 adenocarcinoma) by their gene expression pattern and asses their clonal expansion via single cell RNA/TCR-sequencing.
Under steady-state conditions, Treg cells across different tissues exhibit a shared molecular program with only a few tissue-specific genes. Our studies did not identify a uniform tumor-specific phenotype across all investigated tumor models. Instead, our findings emphasize the dynamic and adaptable nature of Treg cells, revealing tissue- and tumor-type-specific variations in their clonal sharing, expansion, cell interaction and recruitment patterns. Notably, these results suggest a potential role for the SLE as a priming environment for tumor-associated Tregs, with temporal dependencies in their migration and induction patterns differing between melanoma and colorectal tumor models. These insights provide a foundation for further research into antigen specificity, migration signals, and potential therapeutic targets.
Finally, we identified genes that are specifically upregulated in the tumor context and thus indicate specific programs active in tumor-associated Treg cells, but absent in healthy non-lymphoid tissue Treg cells. These findings suggest potential targets or prognostic markers for Treg cell-specific immunotherapies and give valuable insights in the migration capacity of Treg cells in the context of cancer.199 Seiten ; Illustrationen, Diagramm
Multi-scale simulations of MUT-16 scaffold protein phase separation and client recognition
Get PDFPhase separation of proteins plays a critical role in cellular organization. How phase-separated protein condensates underpin biological function and how condensates achieve specificity remain elusive. We investigated the phase separation of MUT-16, a scaffold protein in Mutator foci, and its role in recruiting the client protein MUT-8, a key component in RNA silencing in Caenorhabditis elegans. We employed a multi-scale approach that combined coarse-grained (residue-level CALVADOS2 and near-atomistic Martini3) and atomistic simulations. Simulations across different resolutions provide a consistent perspective on how MUT-16 condensates recruit MUT-8, enabling the fine-tuning of chemical details and balancing the computational cost. Both coarse-grained models (CALVADOS2 and Martini3) predicted the relative phase-separation propensities of MUT-16’s disordered regions, which we confirmed through in vitro experiments. Simulations also identified key sequence features and residues driving phase separation and revealed differences in residue interaction propensities between CALVADOS2 and Martini3. Furthermore, Martini3 and 350-μs atomistic simulations on Folding@Home of MUT-8’s N-terminal prion-like domain with MUT-16 M8BR cluster highlighted the importance of cation- interactions between Tyr residues of MUT-8 and Arg residues of MUT-16 M8BR. Lys residues were observed to be more prone to interact in Martini3. Atomistic simulations revealed that the guanidinium group of Arg also engages in -
interactions and hydrogen bonds with the backbone of Tyr, possibly contributing to the greater strength of Arg-Tyr interactions compared to Lys-Tyr, where these additional favorable contacts are absent. In agreement with our simulations, in vitro co-expression pull-down experiments demonstrated a progressive loss of MUT-8 recruitment after the mutation of Arg in MUT-16 M8BR to Lys or Ala, confirming the critical role of Arg in this interaction. These findings advance our understanding of MUT-16 phase separation and subsequent MUT-8 recruitment, key processes in assembling Mutator foci that drive RNA silencing in C. elegans.
Previous articl
From in vitro screens to telomeric phenotypes: identification and initial characterisation of two novel telomere-associated proteins in saccharomyces cerevisiae
Get PDFA telomere (literally, “end piece” from Greek télos “end” and méros “part”) is a specialised nucleoprotein structure located at each end of a linear eukaryotic chromosome. Its presence is essential for genome stability and the integrity of DNA termini, ensuring their intactness by preventing gratuitous fusion and recombination events from occurring. In addition, telomeres, together with the enzyme telomerase, facilitate the replication and maintenance of chromosomal ends, thereby preventing premature onset of senescence and the progressive loss of genetic material.
In most organisms, telomeric DNA consists of short, repetitive sequences. The nominally canonical TTAGGG repeat is believed to be ancient and broadly conserved among eukaryotes. It is all the more remarkable, then, that telomeric repeat sequences in Saccharomycotina yeasts are exceptionally diverse – typically TG-degenerated, generally not G/C-rich, and varying in both the overall length and tandem repeat sequence patterns among species.
One of the most widely used model organisms, the budding yeast Saccharomyces cerevisiae, is evolutionarily young on the yeast phylogenetic tree. Interestingly, species from more basal clades tend to retain greater similarity to the canonical TTAGGG repeat, whereas more derived species show increasing divergence. Consequently, telomere-binding and telomere-associated proteins (TBPs) in yeasts are not necessarily conserved and may vary across clades, occasionally even swapping their functional roles.
In this thesis, species-specific telomeric repeat sequences were used in in vitro pull-down assays to investigate the co-evolution of TBPs within the Ascomycota group of yeasts, with the aim of identifying novel telomere binders. As a result, two TBPs – transcription factors and paralogs, Tda9 and Rsf2 – were identified as telomere-binding proteins in several yeast species in vitro, and also confirmed to bind telomeric DNA in vivo in S. cerevisiae. Subsequent experiments focused on S. cerevisiae, revealing that deletion of these proteins impacts several telomeric features. These include changes in telomere length and telomeric silencing, impaired formation of Type II survivors during replicative senescence and telomere lengthening upon overexpression of one of the two proteins.
Overall, this study aims to contribute to the broader understanding of telomere integrity in yeast and, more generally, to expand our knowledge of telomere biology, composition and function. In doing so, it offers an incremental yet meaningful perspective that could, in time, support advances in therapeutic strategies related to cancer and healthy ageing.133 Seiten ; Illustrationen, Diagramm
Immunoproteomische Untersuchung von Tränenflüssigkeit und Serum von Patienten mit früher, intermediärer und fortgeschrittener AMD, sowie Patienten mit treatment-naiver neovaskulärer AMD (TEAM)
Get PDFDie altersbedingte Makuladegeneration (AMD) ist eine degenerative Augenerkrankung, welche die äußere Netzhaut und das retinale Pigmentepithel betrifft. Sie wird in zwei Formen unterteilt: das Frühstadium, die trockene AMD (mit Drusen, betrifft 80%) und das Spätstadium, die neovaskuläre oder feuchte AMD (mit choroidale Neovaskularisationen und oder Atrophie, führt schneller zu einer vollständigen Erblindung). Die trockene AMD kann durch die Ausbildung choroidaler Neovaskularisationen in eine feuchte AMD übergehen. Die AMD betrifft in der Regel beide Augen, 26% der Partneraugen entwickeln innerhalb von 5 Jahren ebenfalls eine feuchte AMD.
Das Krankheitsbild der AMD ist die Hauptursache für Blindheit in westlichen Ländern.
Die Behandlungsmöglichkeiten der trockenen AMD sind sehr limitiert, wohingegen die feuchte AMD therapierbar ist. Den aktuellen Goldstandard stellt die Therapie gegen Vascular Endothelial Growth Factor (VEGF) als intravitrealen Injektionen dar.
Im Rahmen dieser monozentrische explorative Beobachtungsstudie im Bereich der Grundlagenforschung soll untersucht werden, ob Veränderungen der retinalen Antigene der Patienten mit dem Schweregrad der Erkrankung korrelieren und so eine Unterscheidung der einzelnen AMD-Subgruppen ermöglichen. Darüber hinaus sollen neue Zielstrukturen/-moleküle in Serum und Tränenflüssigkeit für Diagnose und Therapie identifiziert werden. Durch die Ergebnisse unserer Studie wird ein besseres Verständnis der AMD auf molekularer Ebene erreicht werden, was unabdingbar für die Weiterentwicklung der Diagnose und Entwicklung neuer Therapieoptionen ist.
Es wurden insgesamt 80 Probanden eingeschlossen, unterteilt in gesunde Kontrollprobanden und die verschiedenen AMD-Einteilungsgruppen.
Die prospektive, kontrollierte, monozentrische, nicht-verblindete Studie untersucht die immunologische Komponente der altersbedingten Makuladegeneration (AMD). Es dient einem rein wissenschaftlichen Ziel für die Verbesserung der künftigen Entwicklung von diagnostischen und therapeutischen Verfahren und der Gewinnung von Erkenntnissen über die Pathogenese und Prognose.
Ziel der Studie ist die Identifizierung von retinalen Antigenen im Serum von AMD-Patienten und das Aufzeigen möglicher Unterschiede zwischen den einzelnen AMD-Patientengruppen. Weiterhin soll die Verteilung von retinalen Antikörpern in Serum- und Tränenproben von AMD-Patienten untersucht werden, die mit dem Schweregrad der Erkrankung korrelieren. Die Studie ist im Bereich der Grundlagenforschung angesiedelt und die Ergebnisse sollen zu einem besseren Verständnis der molekularen Vorgänge bei AMD beitragen. Dies bildet die Grundlage für eine erfolgreiche Weiterentwicklung der Diagnose und die Entwicklungen neuer Therapien.91 Seiten ; Illustrationen, Diagramm