Helmholtz Munich

CASyM: Chemotype Annotation through Synthesis Mapping

Abstract The identification and annotation of chemotypes is central to structure–activity relationship studies and property optimization in drug discovery. Current computational approaches rely on predefined fragmentation rules or structural similarity to identify these molecular...

Endosomal Escape of siRNA Polyplexes: A Molecular Dynamics Perspective on Underlying Mechanisms

ABSTRACT To achieve a therapeutic effect, nanoparticles delivering nucleic acids must facilitate endosomal escape (EE) of their cargo. Despite extensive research, the mechanisms that lead to an effective EE are not sufficiently understood. Herein, we compare the EE behavior of fo...

TCR sensitivity shapes recognition of tumor antigen presented by host cells and TCR-T cell efficacy in solid tumors

Despite advances in adoptive T cell therapy, therapeutic efficacy in solid tumors remains inconsistent, and the mechanistic determinants of treatment failure are incompletely understood. Increasing evidence suggests that effective antitumor responses depend not only on direct rec...

Land use intensification results in abrupt transitions between extensively and intensively managed grasslands

Abstract Understanding whether land use intensification causes regime shifts (i.e. persistent, large changes in ecosystem states) is of key importance for management, particularly if these shifts occur abruptly as thresholds in land use intensity are crossed. Further, these thres...

Olive Oil Before Oral Glucose Delays Gastric Emptying and Lowers Glycemia Through Partially Redundant Glucagon and GLP-1 Signaling in Mice

Consumption of fat before carbohydrate (preload) attenuates postprandial glucose excursions, although the underlying mechanisms remain unclear. We investigated whether an olive oil preload (OG) reduces glycemia by engaging endocrine and neural regulation of gastric emptying. Wild...

Structural dynamics and pH ‐regulated membrane binding of the TRAF2 ‐ NC trimer

Tumor necrosis factor receptor-associated factor 2 (TRAF2) is a key adaptor in TNF receptor-signaling that operates as a trimeric assembly. Here we investigate the structural and functional properties of a TRAF2 construct spanning the trimerization and receptor-binding domains (T...

Optimizing nanoLC-TIMS-TOF and lipidomics sample preparation for low volume of plasma

Abstract Lipidomics provides critical insights into disease mechanisms, biomarker discovery, and precision medicine, but conventional LC-MS workflows often require sample volumes that limit their application in minimally invasive studies. Here, we evaluated a nanoflow liquid chro...

Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of adipocyte lipid cycling

Adipocyte lipid metabolism is coordinated by circadian rhythms, diet, and environmental temperature, but how these diverse signals are molecularly integrated remains unknown. We showed that these cues converge on the orphan mitochondrial transporter SLC25A34 to orchestrate lipid...

Gut microbiome maturation in early childhood interacts with host genetics to predict type 1 diabetes risk

Prospective evidence linking early-life microbiome development and host genetics with type 1 diabetes (T1D) risk is limited. Here, we describe how gut microbiome maturation and host genetics influence T1D risk in the TEDDY study. We analysed 12,151 longitudinal metagenomes and ho...

Genome-wide analysis of social behaviour across social domains, reporters and developmental stages: a meta-regression approach

Abstract Social behaviour is a heritable trait linked to well-being and mental health, yet it varies across social context, including social domains, informants and development, which may shape its underlying genomic architecture. Here, we conducted a genome-wide meta-regression...

Do Androgens and Sex Hormone–Binding Globulin Mediate Sex Differences in the Risk of Stroke and Myocardial Infarction? The KORA Study

BACKGROUND: Sex differences in cardiovascular disease are well established, but the role of androgens and sex hormone-binding globulin (SHBG) remains unclear. We investigated whether these hormones and SHBG mediate sex differences in the risk of stroke and myocardial infarction (...

Sodium hexametaphosphate and ultrasonication − Comparing chemical and physical dispersion methods for soil organic matter fractionation

Soil organic matter (SOM) fractionation into particulate organic matter (POM) and mineral-associated organic matter (MAOM) is widely applied to investigate soil organic carbon (SOC) stabilization and turnover, yet the choice of dispersion method strongly influences fractionation...

Conditional deep generative modeling of blood-based infrared spectra enables controlled in-silico phenotyping studies

Abstract Infrared molecular fingerprinting of blood offers a scalable, minimally invasive window into human physiology, but limited follow-up, imbalanced cohorts, and restricted access to diverse phenotypes constrain systematic studies. Here, we introduce a conditional deep gener...

Parallel regulation of tissue morphogenesis and cell fate specification by RAR:RXR signalling during pancreas formation

During embryogenesis, morphologically diverse epithelial organs bud from different regions of the embryonic gut. The unique features of each nascent organ result from distinct cell fate specification and morphogenetic events elicited by organ-inducing cues. Retinoic acid is a pow...

Nanopore long-read sequencing facilitates accurate diagnosis of KMT2B-related dystonia

Abstract Diagnosis of KMT2B -related dystonia remains challenging due to the high prevalence of variants of uncertain significance and technological constraint of short-read pipelines. To overcome these limitations, we integrated nanopore-based long-read sequencing with a validat...

Nuclear Factor-κB Signaling in Murine Models of Malignant Pleural Mesothelioma

Background: Malignant pleural mesothelioma (MPM) is an aggressive asbestos-associated cancer in which inflammatory pathways may contribute to tumor behavior. NF-κB signaling is a central mediator of inflammation and cell survival, but the relative contributions of its associated...

DNA methylome responses to biotic and abiotic stress in Arabidopsis thaliana : A multi‐study analysis

Abstract Plants have evolved complex physiological and morphological strategies to cope with biotic and abiotic stress. At the molecular level, these responses are partly mediated by epigenetic mechanisms such as DNA methylation. In Arabidopsis thaliana , numerous studies have ex...

Association of three different dietary patterns with the metabolomic profiles of children: the BiomarKid project

Abstract Background and aims Metabolomics offers a promising approach to objectively assess food intake and nutrition-related health risks. Three different dietary patterns (DPs) associated with cardiometabolic health were previously identified at 2 years of age in the EU Childho...

International consensus guidance for general population screening for islet autoantibodies to diagnose early-stage type 1 diabetes: a nominal group technique process

Type 1 diabetes is an autoimmune disease that targets and destroys insulin-producing beta cells in the pancreatic islets. The incidence of type 1 diabetes is rising globally. At the clinical diagnosis of type 1 diabetes, between 20% and 67% of children and adolescents present wit...

MemBrain v2: an end-to-end tool for the analysis of membranes in cryo-electron tomography

Abstract Cryo-electron tomography provides unique insights into macromolecular complexes in their native environments, yet membrane analysis remains a major bottleneck due to low signal-to-noise ratios, missing wedge artifacts and the complexity of membrane-associated particles....