Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases

Determinants of mutation susceptibility along the genome are largely invariant across human tissues

Abstract Background The propensity for accumulating somatic mutations varies along the genome, which critically influences somatic mosaicism, tumor evolution and the potential role of somatic mutations in the context of age-associated diseases. Genomic factors contributing to the...

Integrated metabolomics data analysis to generate mechanistic hypotheses with MetaProViz

ABSTRACT With the growing number of metabolomics and lipidomics studies, robust strategies for bioinformatic analyses are increasingly important. However, the absence of standardized and reproducible workflows, coupled with ambiguous metabolite annotations, hampers effective anal...

PLCG2 downregulation impairs synaptic function and increases Alzheimer’s disease hallmarks in neuronal cultures

We developed a high-content screening to investigate how Alzheimer’s disease (AD) genetic risk factors may affect synaptic mechanisms in rat primary neuronal cultures. Of the target genes identified, we found that Plcg2 downregulation in mouse dentate gyrus neurons consistently d...

Development of a multi-species luciferase-based double-antigen ELISA for the detection of antibodies against influenza A virus H5 clade 2.3.4.4b

ABSTRACT The highly pathogenic avian influenza viruses of subtype H5N1 represent a major threat to animal and public health. The current panzootic with H5 clade 2.3.4.4b has caused numerous, widespread outbreaks in various domestic and wild avian species with high mortalities, ma...

Mechanism of Autophagic Extracellular Vesicles Revealed

Recent work by Mao and colleagues identifies a distinct class of small extracellular vesicles, termed autophagic extracellular vesicles (AEVs), generated from amphisomes upon autophagy induction. In this commentary, we discuss how this study provides important mechanistic insight...

An N-terminal CDC42 T43I variant reveals the mechanism of pyrin inflammasome activation

Heterozygous carboxyl-terminal variants in the RHO guanosine triphosphatase (GTPase) CDC42 are known to cause severe autoinflammatory syndromes. Here, we identified a heterozygous amino-terminal p.T43I (Thr 43 →Ile) CDC42 variant in patients with autoinflammation and uncovered a...

A genotype-first approach reveals the molecular basis of pyrin inflammasome activation

Mutations in the MEFV gene, which encodes pyrin, are associated with a spectrum of inflammatory conditions called pyrin-associated autoinflammatory diseases (PAADs). Of the 400 MEFV variants listed in the Infevers database, most are classified as variants of uncertain significanc...

Nutrient stress activates RAB5B-mediated autophagy to remodel the synaptic proteome

Abstract Synaptic proteostasis is crucial for maintaining neuronal function and plasticity, yet how synapses adapt to metabolic stress remains poorly understood. Here, we show that nutrient deprivation, particularly serum withdrawal, induces robust autophagy-dependent remodeling...