Helmholtz Institute Mainz

The growing resistance of Enterobacterales to last-resort antibiotics such as carbapenems puts a significant burden on healthcare systems, also due to plasmids driving a rapid spread of carbapenem resistance. We here evaluate the use of long-read nanopore sequencing to investigate carbapenem resistance dynamics and the role of plasmid transfers and environmental reservoirs in the hospital setting. Over 13 months, routine clinical diagnostics identified recurring isolates of carbapenem-resistant Citrobacter species carrying Klebsiella pneumoniae carbapenemases (KPCs) and/or OXA-48-like carbapenemases from patient screening and hospital drain samples. While routine diagnostic approaches provided limited insights into the carbapenem resistance dynamics, we show that near-complete de novo assembly of chromosomes and plasmids by long-read nanopore sequencing allowed for high-resolution strain identification, plasmid profiling, and antibiotic resistance gene detection. Notably, genomically nearly indistinguishable Citrobacter freundii of the high-risk sequence type ST91 genomes were recovered from screening samples collected in the same hospital room 1 year apart. We further provide evidence of a KPC-2-encoding IncN plasmid that is likely to have spread across bacterial species and between patient and drain isolates, which emphasizes the role of contaminated drains in the persistence and dissemination of antimicrobial resistance within the hospital environment. Overall, this study demonstrates the value of long-read nanopore sequencing for uncovering the complex dynamics of carbapenem resistance spread and persistence in the hospital setting and its potential implications for infection prevention and control.

H3 K27-altered diffuse midline glioma (DMG) is a molecularly defined, highly aggressive tumor entity since the 2016 revision of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS). It has been most extensively characterized in children and adolescents and continues to pose significant challenges to treating physicians due to its growth along the midline structures of the brain and its ability to progress distantly leading to poor prognosis. Clinical and molecular determinants of distant progression and its impact on patient survival particularly in adults have not been thoroughly characterized. This retrospective multicenter cohort study of 52 adult patients with DMG was analyzed for clinical and molecular predictors of distant tumor progression using gene panel sequencing and genome-wide DNA methylation arrays. Distant progression including leptomeningeal disease occurred in 10 out of 52 adult patients (19%), seven of which had a primary spinal tumor location (70%, p < 0.001) and almost 80% of patients with spinal DMG experienced distant progression. Across the entire cohort, distant progression was associated with worse progression free survival (PFS) (4.5 vs. 13 months; p = 0.037). However, we could not identify a genetic or methylation-based signature that was significantly correlated with the occurrence of distant progression. Adult DMGs with spinal location are at a high risk of early distant progression. As there were no molecular determinants of distant progression from differential methylation, copy number alterations (CNA) or panel sequencing, adult patients with DMG should undergo routine craniospinal MRI, particularly in spinal tumor location.

We are using optical and microwave fields to excite Rydberg states in trapped cold ions. We employ a single ion and observe spectroscopically in the manifold of a principal quantum number n = 49 the dressing of Rydberg states of angular momentum states S and P. We compare our experimental spectra with a multi-level calculation of dressed states and find good agreement. The results are important for controlling the interaction of single ions in Rydberg states with electric fields of the ion trap and for tailoring the interactions in an ion crystal in Rydberg states.

High-risk (HR) neuroblastoma (NBL) patients often receive standardized treatment despite wide variations in clinical outcomes, underscoring the need for improved stratification tools. A distinguishing feature of NBL is the patient-specific expression of gangliosides (GGs), particularly GD2, which may serve as biomarkers. We analyzed GG profiles in 18 patient-derived tumors and 11 NBL cell lines using thin-layer chromatography and mass spectrometry. Expression of 0-, a-, and b-series GGs was examined and correlated with clinical risk, outcome, and gene expression data. Low-risk (LR) tumors expressed higher levels of complex b-series GGs. In HR tumors, five GG profiles (A-E) were identified. Profile A featured complex b-series GGs; B showed GD2 dominance; C showed synthesis arrest at GM3 or GD3 due to low expression of the GM2/GD2 synthase, encoded by the B4GALNT1 gene; D included complex a- and b-series GGs; and E was marked by GM2 and GD1a prevalence. B4GALNT1 expression served as a prognostic marker. Relapsed tumors following anti-GD2 therapy typically exhibited reduced GD2 levels, except for one profile A tumor that displayed a ceramide anchor shorter than those found in LR tumors. Astonishingly, the ceramide anchor composition of GD2 itself appears to separate LR and HR NBL, hinting at a role of ceramide synthases in NBL biology. All cell lines expressed GM2, but exhibited very low levels of complex b-series GGs. Profile C was found only in cell lines of the mesenchymal subtype. These findings support further investigation of GG composition and associated enzyme expression as potential biomarkers for risk stratification and treatment response in NBL.

Submicrometer helical structures possess unique properties and functionalities arising from their intrinsic twisting nature. However, existing fabrication methods are often limited to small sample sizes, hindering comprehensive characterization and practical implementation. In this study, a scalable self-assembly method for fabricating metallic helices through a transformation of planar microstrips into helical geometries upon their release from the substrate is presented. This technique exploits the nanoscale engineering of residual stress and gradient strains within the metallic strips to induce spontaneous folding and twisting. This method allows for large-scale production while providing precise control over structural parameters. Notably, the ability to produce centimeter-scale samples has facilitated the characterization of chiroptical properties using standard spectrometers. Experimental measurements and numerical simulations reveal pronounced chiroptical responses in the mid- and near-infrared regions for helices with radii on the order of hundreds of nanometers. These findings clarify the geometric factors that influence the excitation of chiral eigenmodes and thereby establish a straightforward framework for designing metallic helices as chiral plasmonic structures tailored to specific operating wavelengths. This study marks a significant advancement in the fabrication of helical and 3D nanostructures, with potential implications for photonics, stereochemistry, and chiroptical spectroscopy.

Thorium ions and molecules, recognized for their distinctive nuclear and atomic attributes, are central to numerous trapped-ion experiments globally. Our study introduces an effective, compact source of thorium atomic and molecular ions produced via laser ablation of microgram-scale, salt-based samples. We thoroughly analyze the variety of ion species and charge states generated at varying laser fluences. Utilizing 10 µg of thorium fluoride crystals and laser fluences between 1.00(5) and 6.75(35) J/cm2, we produce thorium molecular ions ThFx232n+ (with x=0–3 and charge states up to n=3), including ThF2+ and ThF3+. These species are particularly relevant for spectroscopy; ThF3+ is valuable due to its stable closed-shell configuration, while ThF2+, which is isoelectronic to RaF, offers a unique probe for studying nuclear structure and fundamental symmetries due to its simple electronic structure with a single unpaired electron. Density-functional-theory-based calculations of the electric charge distribution aid in understanding the formation of the observed species. Positive charges are found to be mainly located on the thorium atom, which points to an inhibition of immediate Coulomb explosion, thus supporting the existence of the observed ion species. The simplicity of the method and similarities among the actinide elements suggest that our approach will also be applicable to other actinide species.

Abstract Man-made superheavy elements (SHE) are produced as energetic recoils in complete-fusion reactions and need to be thermalized in a gas-filled chamber for chemical studies. The ever-shorter half-lives and decreasing production rates of the elements beyond Fl (atomic number Z = 114)-the heaviest element chemically studied today-require the development of novel techniques for quantitative thermalization and fast extraction efficiency. The Universal high-density gas stopping Cell (UniCell), currently under construction, was proposed to achieve this. Within this work, we propose an Ion Transfer by Gas Flow (ITGF) device, which serves as a UniCell ejector to interface with a gas chromatography detector array for chemical studies. Detailed parameter optimizations, using gas dynamics and Monte Carlo ion-trajectory simulations, promise fast (within a few ms) and highly efficient (up to 100%) ion extraction across a wide mass range. These ions can then be transmitted quantitatively through the ITGF into the high-pressure environment needed for further chemical studies.

This review presents a comprehensive summary of theoretical investigations and experimental searches for spin-dependent interactions beyond the standard model. These interactions may be mediated by various types of exotic bosons, and their existence and properties may, in turn, explain the nature of dark matter and dark energy. The described experiments also probe the discrete fundamental symmetries of nature.

The heaviest elements in the periodic table have a low production yield. In order to increase the production yield of the superheavy elements, thicker targets are required than the present molecular plating technique can offer. Therefore, lanthanide thin films, as lighter homologues to the actinides, were prepared by a new electrodeposition method. The trifluoromethanesulfonates (triflates) of the lanthanide salts were dissolved in Dimethylformamide (DMF) and then electrochemically deposited onto substrates of different geometries. These thin films were irradiated with different swift heavy ion beams with energies of over 200 MeV. Thin films were analyzed spectroscopically by Raman and IR measurements before and after irradiation, to investigate chemical changes induced by irradiation.