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We assigned the side-chain resonances of the Crimean–Congo hemorrhagic fever virus (CCHFV) glycoprotein n (Gn) cytosolic domain that is 69 amino acids long to complete the backbone resonances previously published by Estrada et al. (2011). The process was facilitated by three factors. First, sample preparation using cell-free protein synthesis (CFPS) was completed in less than 2 d and allowed for correct zinc finger formation by adding zinc ions to the reaction. Second, access to NMR platforms with standardized pulse sequences allowed for data acquisition in 18 d. Third, data analysis using the online platform NMRtist allowed sequential resonance assignments to be made in a day, and assignments were verified and finalized in less than a week. Our work thus provides an example of how NMR assignments, including side chains, of small and well-behaved proteins can be approached in a rapid routine, at protein concentrations of 150 µM.

Abstract InsectSound1000 is a dataset comprising more than 169000 labelled sound samples of 12 insects. The insect sound level spans from very loud (Bombus terrestris) to inaudible to human ears (Aphidoletes aphidimyza). The samples were extracted from more than 1000 h of recordings made in an anechoic box with a four-channel low-noise measurement microphone array. Each sample is a four-channel wave-file of 2500 kHz length, at 16 kHz sample rate and 32 bit resolution. Acoustic insect recognition holds great potential to form the basis of a digital insect sensor. Such sensors are desperately needed to automate pest monitoring and ecological monitoring. With its significant size and high-quality recordings, InsectSound1000 can be used to train data-hungry deep learning models. Used to pretrain models, it can also be leveraged to enable the development of acoustic insect recognition systems on different hardware or for different insects. Further, the methodology employed to create the dataset is presented in detail to allow for the extension of the published dataset.

Abstract Recently, a novel cyclo-heptapeptide composed of alternating d,l-amino acids and a unique thiazolidine heterocycle, called lugdunin, was discovered, which is produced by the nasal and skin commensal Staphylococcus lugdunensis. Lugdunin displays potent antimicrobial activity against a broad spectrum of Gram-positive bacteria, including challenging-to-treat methicillin-resistant Staphylococcus aureus (MRSA). Lugdunin specifically inhibits target bacteria by dissipating their membrane potential. However, the precise mode of action of this new class of fibupeptides remains largely elusive. Here, we disclose the mechanism by which lugdunin rapidly destabilizes the bacterial membrane potential using an in vitro approach. The peptide strongly partitions into lipid compositions resembling Gram-positive bacterial membranes but less in those harboring the eukaryotic membrane component cholesterol. Upon insertion, lugdunin forms hydrogen-bonded antiparallel β-sheets by the formation of peptide nanotubes, as demonstrated by ATR-FTIR spectroscopy and molecular dynamics simulations. These hydrophilic nanotubes filled with a water wire facilitate not only the translocation of protons but also of monovalent cations as demonstrated by voltage-clamp experiments on black lipid membranes. Collectively, our results provide evidence that the natural fibupeptide lugdunin acts as a peptidic channel that is spontaneously formed by an intricate stacking mechanism, leading to the dissipation of a bacterial cell’s membrane potential.

Abstract Biological membranes, composed mainly of phospholipids and cholesterol, play a vital role as cellular barriers. They undergo localized reshaping in response to environmental cues and protein interactions, with the energetics of deformations crucial for exerting biological functions. This study investigates the non-universal role of cholesterol on the structure and elasticity of saturated and unsaturated lipid membranes. Our study uncovers a highly cooperative relationship between thermal membrane bending and local cholesterol redistribution, with cholesterol showing a strong preference for the compressed membrane leaflet. Remarkably, in unsaturated membranes, increased cholesterol mobility enhances cooperativity, resulting in membrane softening despite membrane thickening and lipid compression caused by cholesterol. These findings elucidate the intricate interplay between thermodynamic forces and local molecular interactions that govern collective properties of membranes.

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The human-induced climate crisis endangers health and the foundations of life for us humans. The professional society GMDS – German Assocation for Medical Informatics, Biometry and Epidemiology – considers itself responsible for the health in society. What does this mean in times of the climate crisis? During a workshop entitled “Climate change, digitalization and health“ at GMDS2023 in Heilbronn, action areas for GMDS as a professional society and for its members were discussed. On the micro level, for example, the necessity, the anticipated benefits for human health, and the climate consequences of planned projects should be reflected upon. On the meso level, GMDS-organized events could be made climate-neutral, for example. On the macro level, GMDS could, for example, influence funding bodies to consider climate consequences in decisions regarding research proposals. We invite everyone interested to actively participate in the planned further discussions. The establishment of a GMDS project group or working group on this topic is planned. Now is the time to take responsibility for the climate. This applies at the professional level for us personally as well as for the professional society GMDS as an institution.

Vascular diseases like aneurysms or atherosclerosis belong to the leading causes of death. For diagnosis and treatment, medical imaging is essential. Standard imaging methods are Ultrasound, X-ray-based Angiography, Computed tomography or Magnet Resonant Imaging. Additionally, Intravascular Ultrasound or Optical Coherence Tomography are available for intravascular imaging. One imaging technique for direct investigation of the inner vessel is vascular endoscopy, also called angioscopy. It is based on the insertion of an optical endoscope into the blood vessel for direct imaging. Dependent on the vessel diameter, these endoscopes have to be very small. Angioscopy can provide valuable information about the condition of the vessel wall and serve for procedure observation or implant assessment. But angioscopy requires the absence of blood for a clear field of view. In prior research, we have already developed methods for the placement of a tiny optical fiber inside a catheter combination. As an essential step toward a clinical study, we now want to evaluate the flushing parameters needed to achieve a clear field of view for the endoscope. The parameters are affected by the blood flow and vessel diameter. We designed a test setup that allows angioscopic examination and the simulation of realistic conditions, such as blood flow and different vessel diameters and that includes a test pattern for image quality assessment.

(1) Background: Tumor-specific standardized data are essential for AI-based progress in research, e.g., for predicting adverse events in patients with melanoma. Although there are oncological Fast Healthcare Interoperability Resources (FHIR) profiles, it is unclear how well these can represent malignant melanoma. (2) Methods: We created a methodology pipeline to assess to what extent an oncological FHIR profile, in combination with a standard FHIR specification, can represent a real-world data set. We extracted Electronic Health Record (EHR) data from a data platform, and identified and validated relevant features. We created a melanoma data model and mapped its features to the oncological HL7 FHIR Basisprofil Onkologie [Basic Profile Oncology] and the standard FHIR specification R4. (3) Results: We identified 216 features. Mapping showed that 45 out of 216 (20.83%) features could be mapped completely or with adjustments using the Basisprofil Onkologie [Basic Profile Oncology], and 129 (60.85%) features could be mapped using the standard FHIR specification. A total of 39 (18.06%) new, non-mappable features could be identified. (4) Conclusions: Our tumor-specific real-world melanoma data could be partially mapped using a combination of an oncological FHIR profile and a standard FHIR specification. However, important data features were lost or had to be mapped with self-defined extensions, resulting in limited interoperability.

Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an increase in its pool size proportional to growth. Phosphatidylcholine and sphingomyelin, containing a choline headgroup, are constitutive membrane phospholipids, accounting for >85% of total choline, indicating that choline requirements are particularly high during growth. Daily phosphatidylcholine secretion via bile for lipid digestion and very low-density lipoproteins for plasma transport of arachidonic and docosahexaenoic acid to other organs exceed 50% of its hepatic pool. Moreover, phosphatidylcholine is required for converting pro-apoptotic ceramides to sphingomyelin, while choline is the source of betaine as a methyl donor for creatine synthesis, DNA methylation/repair and kidney function. Interrupted choline supply, as during current total parenteral nutrition (TPN), causes a rapid drop in plasma choline concentration and accumulating deficit. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) defined choline as critical to all infants requiring TPN, claiming its inclusion in parenteral feeding regimes. We performed a systematic literature search in Pubmed with the terms “choline” and “parenteral nutrition”, resulting in 47 relevant publications. Their results, together with cross-references, are discussed. While studies on parenteral choline administration in neonates and older children are lacking, preclinical and observational studies, as well as small randomized controlled trials in adults, suggest choline deficiency as a major contributor to acute and chronic TPN-associated liver disease, and the safety and efficacy of parenteral choline administration for its prevention. Hence, we call for choline formulations suitable to be added to TPN solutions and clinical trials to study their efficacy, particularly in growing children including preterm infants.

Background: To support clinical decision-making at the point of care, the “best next step” based on Standard Operating Procedures (SOPs) and actual accurate patient data must be provided. To do this, textual SOPs have to be transformed into operable clinical algorithms and linked to the data of the patient being treated. For this linkage, we need to know exactly which data are needed by clinicians at a certain decision point and whether these data are available. These data might be identical to the data used within the SOP or might integrate a broader view. To address these concerns, we examined if the data used by the SOP is also complete from the point of view of physicians for contextual decision-making. Methods: We selected a cohort of 67 patients with stage III melanoma who had undergone adjuvant treatment and mainly had an indication for a sentinel biopsy. First, we performed a step-by-step simulation of the patient treatment along our clinical algorithm, which is based on a hospital-specific SOP, to validate the algorithm with the given Fast Healthcare Interoperability Resources (FHIR)-based data of our cohort. Second, we presented three different decision situations within our algorithm to 10 dermatooncologists, focusing on the concrete patient data used at this decision point. The results were conducted, analyzed, and compared with those of the pure algorithmic simulation. Results: The treatment paths of patients with melanoma could be retrospectively simulated along the clinical algorithm using data from the patients’ electronic health records. The subsequent evaluation by dermatooncologists showed that the data used at the three decision points had a completeness between 84.6% and 100.0% compared with the data used by the SOP. At one decision point, data on “patient age (at primary diagnosis)” and “date of first diagnosis” were missing. Conclusions: The data needed for our decision points are available in the FHIR-based dataset. Furthermore, the data used at decision points by the SOP and hence the clinical algorithm are nearly complete compared with the data required by physicians in clinical practice. This is an important precondition for further research focusing on presenting decision points within a treatment process integrated with the patient data needed.

Abstract Redox signaling and cardiac function are tightly linked. However, it is largely unknown which protein targets are affected by hydrogen peroxide (H2O2) in cardiomyocytes that underly impaired inotropic effects during oxidative stress. Here, we combine a chemogenetic mouse model (HyPer-DAO mice) and a redox-proteomics approach to identify redox sensitive proteins. Using the HyPer-DAO mice, we demonstrate that increased endogenous production of H2O2 in cardiomyocytes leads to a reversible impairment of cardiac contractility in vivo. Notably, we identify the γ-subunit of the TCA cycle enzyme isocitrate dehydrogenase (IDH)3 as a redox switch, linking its modification to altered mitochondrial metabolism. Using microsecond molecular dynamics simulations and experiments using cysteine-gene-edited cells reveal that IDH3γ Cys148 and 284 are critically involved in the H2O2-dependent regulation of IDH3 activity. Our findings provide an unexpected mechanism by which mitochondrial metabolism can be modulated through redox signaling processes.