Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases

Leptin-sensitive hypothalamic Lepr+/Glp1r+ neurons limit hyperphagia and weight gain in diet-induced obesity

Abstract Despite loss of responsiveness to exogenous leptin in obesity, endogenous leptin continues to restrain feeding, although the neural substrates that remain sensitive and mediate this effect remain unknown. Combining spatial transcriptomics with single-nucleus RNA sequenci...

Geriatric co-managed prehabilitation before esophagectomy in patients aged ≥ 65 years with esophageal cancer: a prospective feasibility study with matched historical controls

Abstract Purpose Older patients undergoing esophagectomy remain at high risk for perioperative morbidity. This study evaluated the feasibility, safety and adherence of a multimodal prehabilitation program integrated with geriatric co-management in patients aged ≥ 65 years schedul...

Interest in geriatric medicine training among health and social care professionals: the roles of experience and attitudes. Findings from the online survey of the COST Action PROGRAMMING 21122

Abstract Background The growth of ageing populations is increasing the requirement for professionals trained to care for older adults. Aims To explore factors associated with interest in further training in geriatrics across health and social care professionals. Methods The COST...

Maternal metformin treatment in obese pregnant dams normalizes neonatal sensory-motor reflexes

BACKGROUND: Maternal overweight and obesity have reached epidemic proportions over recent decades, with detrimental effects on offspring metabolism and neurodevelopment. Metformin, commonly used to treat type 2 diabetes mellitus and gestational diabetes, is being investigated for...

VEGF ‐A Antisense Oligonucleotide Therapy Inhibits Corneal Neovascularisation and Enhances Graft Survival in Murine High‐Risk Corneal Transplantation

BACKGROUND: To investigate, for the first time, whether an unconjugated VEGF-A antisense oligonucleotide (ASO) can inhibit corneal neovascularisation and improve graft survival in a murine high-risk corneal transplantation model. METHODS: A suture-induced corneal neovascularisati...

Effectiveness of an on-site vaccination campaign for patients with cancer

Abstract Background Patients with haematological or oncological malignancies are at increased risk of severe infections. Vaccination is a key preventive strategy and is recommended by National Immunization Technical Advisory Groups (NITAGs). Yet, vaccination rates in this populat...

A pancreatic cancer organoid-macrophage co-culture using starPEG-heparin hydrogel deciphers tumor-immune cell interactions

Abstract Macrophages are among the most abundant immune cells in the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) and play a key role in regulating the immunosuppressive niche that facilitates tumor growth. Although recent three-dimensional (3D) culture sy...

Redox-dependent synaptic clustering of gephyrin

ABSTRACT Reactive oxygen species (ROS) play a central role in enhancing inhibitory signal transmission, thus extending their role beyond oxidative stress in disease and aging. However, the underlying molecular mechanisms mediating these functions have remained elusive. At inhibit...

INPP5E interactome reveals novel connections to growth factor signaling

Abstract Primary cilia are sensory cell membrane protrusions whose malfunction causes diseases known as ciliopathies. Joubert syndrome (JBTS) is a rare recessive ciliopathy causing brain malformations and kidney cysts, among other manifestations. A key player in JBTS is INPP5E, a...

A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease

ABSTRACT Inflammatory bowel disease (IBD) is a chronic condition caused by altered cytokine signaling, maladaptive immunity, dysbiosis, and intestinal barrier dysfunction. Patients with IBD receive therapy to correct these imbalances and achieve remission. However, most patients...

A targetable dependency on nonsense-mediated decay for cellular homeostasis and immune control in small cell lung cancer

Abstract Small cell lung cancer (SCLC) is one of the most aggressive malignancies, characterized by rapid metastatic dissemination and poor overall survival. Despite harboring excessive alterations, expectedly resulting in immunogenic neoantigens, patients with SCLC remain largel...

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...

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...

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...

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...