A5101411409- Receptor Mechanisms and Signaling
- Biochemical Analysis and Sensing Techniques
- Regulation of Appetite and Obesity
- Neuroinflammation and Neurodegeneration Mechanisms
- Adenosine and Purinergic Signaling
- Neuropeptides and Animal Physiology
- Ion Transport and Channel Regulation
- Phagocytosis and Immune Regulation
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- Adipokines, Inflammation, and Metabolic Diseases
- Cholesterol and Lipid Metabolism
- Effects and risks of endocrine disrupting chemicals
- Cancer-related Molecular Pathways
- Liver Disease Diagnosis and Treatment
- Chemokine receptors and signaling
- Diet, Metabolism, and Disease
- Animal Genetics and Reproduction
- RNA Interference and Gene Delivery
- Diabetes Treatment and Management
- Neuroscience and Neuropharmacology Research
- Neuroendocrine regulation and behavior
- RNA and protein synthesis mechanisms
- Immune cells in cancer
Leipzig University
2015-2025
IFB Adiposity Diseases
2013-2017
McGill University
2016-2017
University of Freiburg
2000
Freie Universität Berlin
1998
During adult hippocampal neurogenesis, most newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent the spillover of intracellular contents. Here, we propose that phagocytosis is not merely passive corpse removal but has an active role in maintaining neurogenesis. First, found neurogenesis was disrupted male female mice chronically deficient for two pathways: purinergic receptor P2Y12, tyrosine kinases TAM family Mer kinase (MerTK)/Axl. In contrast,...
Abstract Parabens are preservatives widely used in consumer products including cosmetics and food. Whether low-dose paraben exposure may cause adverse health effects has been discussed controversially recent years. Here we investigate the effect of prenatal on childhood overweight by combining epidemiological data from a mother–child cohort with experimental approaches. Mothers reporting use paraben-containing cosmetic have elevated urinary concentrations. For butyl (BuP) positive...
To characterize LysM-Cre mediated gene targeting in mice, we crossed mice to two independent reporter-mouse lines (tdTomato or YFP). Surprisingly, found that more than 90% of cells with recombination the brain were neurons, rather myeloid cells, such as microglia. Hence, by using mouse line for conditional knockout approaches, a significant neuronal needs be considered. Lysozymes are enzymes innate immune system plants, animals, bacteria, and fungi cleave peptidoglycanes bacterial cell...
Exposure to endocrine-disrupting chemicals can alter normal physiology and increase susceptibility non-communicable diseases like obesity. Especially the prenatal early postnatal period is highly vulnerable adverse effects by environmental exposure, promoting developmental reprogramming epigenetic alterations. To obtain a deeper insight into role of bisphenol A (BPA) exposure in children's overweight development, we combine epidemiological data with experimental models BPA-dependent DNA...
Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide prevalence. Understanding complex network food intake energy balance regulation an essential prerequisite for pharmacological intervention obesity. G protein-coupled receptors (GPCRs) are among main modulators metabolism balance. They, instance, regulate appetite satiety in certain hypothalamic neurons, as well glucose lipid hormone secretion from adipocytes. Mutations some GPCRs, such...
The X-chromosomal GPR34 gene encodes an orphan Gi protein-coupled receptor that is highly conserved among vertebrates. To evaluate the physiological relevance of GPR34, we generated a GPR34-deficient mouse line. mice were vital, reproduced normally, and showed no gross abnormalities in anatomical, histological, laboratory chemistry, or behavioral investigations under standard housing. Because expressed mononuclear cells immune system, specifically tested for altered functions these cell...
GPR34 is a G i/o protein‐coupled receptor (GPCR) of the nucleotide P2Y 12 ‐like group. This highly expressed in microglia, however, functional relevance these glial cells unknown. Previous results suggested an impaired immune response GPR34‐deficient mice infected with Cryptococcus neoformans . Here we show that deficiency morphological changes retinal and cortical microglia. RNA sequencing analysis microglia revealed number differentially transcripts involved cell motility phagocytosis. We...
Non-alcoholic fatty liver disease (NAFLD) is the most common in industrialized countries and increasing prevalence. The pathomechanisms, however, are poorly understood. This study assessed unexpected role of Hedgehog pathway adult lipid metabolism. Using transgenic mice with conditional hepatocyte-specific deletion Smoothened mice, we showed that hepatocellular inhibition signaling leads to steatosis by altering abundance transcription factors GLI1 GLI3. steatotic 'Gli-code' caused...
Succinate is a pivotal tricarboxylic acid cycle metabolite but also specifically activates the G i ‐ and q ‐coupled succinate receptor 1 (SUCNR1). Contradictory roles of succinate‐SUCNR1 signaling include reports about its anti‐ or pro‐inflammatory effects. The link between cellular metabolism localization‐dependent SUCNR1 qualifies as potential cause for reported conflicts. To systematically address this connection, we used diverse set methods, including several bioluminescence resonance...
Synonymous single nucleotide variants (sSNVs), traditionally seen as neutral, are now recognized for their biological impact. To assess relevance, we developed SyMetrics, a framework that integrates predictors of splicing, RNA stability, evolutionary conservation, codon usage, synonymous variation effects, sequence properties, and allele frequency. We analyzed all possible sSNVs across the human genome, our machine-learning model achieved 97% accuracy in distinguishing deleterious from...
Most genes are not yet fully annotated, and the extent of their transcript diversity roles significance specific isoforms is understood. This information therefore lacking for disease genes. The CLN3 gene underlies classic juvenile disease, also known as neuronal ceroid lipofuscinosis, a rare paediatric neurodegenerative disorder. most common cause this biallelic disorder 1–kb intragenic deletion that removes two internal coding exons (exons 7 8). Here, we report findings from first...
Loss-of-function mutations in the V2 vasopressin receptor (AVPR2) gene have been identified as a molecular basis for X-linked nephrogenic diabetes insipidus (NDI). Herein, we describe novel deletion mutation at nucleotide position 102 (delG102) found Russian family resulting frameshift and truncated protein. Furthermore, analyzed AVPR2 of two other unrelated boys with NDI from our patient clientele. These patients showed previously described (R137H, R181C). In-depth characterization three...
The prevalence of antibody to hantaviruses in Slovakia (serum panel n = 2,133) was lower the western part (0.54%) and higher eastern (1.91%) country found be significantly enhanced a group forest workers from (5.88%). One-third IgM-negative convalescent phase sera patients with hemorrhagic fever renal syndrome exhibited antibodies reacting predominantly Puumala virus antigen, while two-thirds had directed mainly against Hantaan antigen. Fine analysis two virus-reactive by focus reduction...
Obese melanocortin-4-receptor-deficient (MC4R-/-) male mice are reported to have erectile dysfunction, while homozygous MC4R-/- female apparently fertile. A recently established obese mouse strain, carrying an inactivating mutation in the MC4R gene, revealed difficulties breeding for mice. This prompted us determine presence of follicles and corpora lutea (CL) ovaries aged 3-6 months comparison wild type (MC4R+/+) littermates. Serial sections formaldehyde-fixed with vaginal signs estrus...
Intense neuronal activity in the sensory retina is associated with a volume increase of cells (Uckermann et al., J. Neurosci. 2004, 24:10149) and decrease osmolarity extracellular space fluid (Dmitriev Vis. 1999, 16:1157). Here, we show existence an endogenous purinergic mechanism that prevents hypoosmotic swelling retinal glial (Müller) mice. In contrast to from wild-type mice, stress induced rapid cell somata slices mice deficient P2Y(1), adenosine A(1) receptors, or ecto-5'-nucleotidase...
Based on the now available crystallographic data of G-protein-coupled receptor (GPCR) prototype rhodopsin, many studies have been undertaken to build or verify models other GPCRs. Here, we mined evolution as an additional source structural information that may guide GPCR model generation well mutagenesis studies. The sequence 61 cloned orthologs a P2Y-like (GPR34) enabled us identify motifs and residues are important for maintaining function. were compared with sequences 77 rhodopsin...
Lyso-PS (lyso-phosphatidylserine) has been shown to activate the Gi/o-protein-coupled receptor GPR34. Since in vitro and vivo studies provided controversial results assigning lyso-PS as endogenous agonist for GPR34, we investigated evolutionary conservation of specificity more detail. Except some fish GPR34 subtypes, no or very weak agonistic activity at most vertebrate orthologues investigated. Using chimaeras identified single positions second extracellular loop transmembrane helix 5 carp...
Background: Mutations of monocarboxylate transporter 8 (MCT8), a thyroid hormone (TH)-specific transmembrane transporter, cause severe neurodevelopmental disorder, the Allan-Herndon-Dudley syndrome. In MCT8 deficiency, TH is not able to reach those areas brain where uptake depends on MCT8. Currently, therapeutic options for MCT8-deficient patients are missing, as treatment successful in improving neurological deficits. Available data protein and transcript levels indicate complex expression...