A5091054717- Cardiomyopathy and Myosin Studies
- Infant Nutrition and Health
- Eosinophilic Esophagitis
- Inflammatory Bowel Disease
- Muscle Physiology and Disorders
- Health and Medical Studies
- RNA Research and Splicing
- Digestive system and related health
- Infant Health and Development
- Gastroesophageal reflux and treatments
- Microscopic Colitis
- Child Nutrition and Feeding Issues
- Child and Adolescent Health
- Helicobacter pylori-related gastroenterology studies
- Breastfeeding Practices and Influences
- Diet and metabolism studies
- Probiotics and Fermented Foods
- Clinical Nutrition and Gastroenterology
- RNA and protein synthesis mechanisms
- Cystic Fibrosis Research Advances
- Gut microbiota and health
- Viral Infections and Immunology Research
- Medical History and Research
- Medical and Health Sciences Research
- Congenital heart defects research
Griffith University
2025
Max Delbrück Center
2015-2024
German Centre for Cardiovascular Research
2017-2024
University of Rostock
1997-2024
Universitätsmedizin Rostock
1992-2020
Klinikum Ernst von Bergmann
2004-2018
Charité - Universitätsmedizin Berlin
2006-2018
University of Cambridge
2018
European Bioinformatics Institute
2018
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2018
Safe anaerobic metabolism Naked mole-rats live in large colonies deep underground hypoxic conditions. Park et al. found that these animals fuel glycolysis with fructose by a rewired pathway avoids tissue damage (see the Perspective Storz and McClelland). These results provide insight into adaptations this strange social rodent has to make for life underground. They also have implications medical practice, particularly understanding how protect tissues from hypoxia. Science , issue p. 307 ; see 248
The recent discovery of heterozygous human mutations that truncate full-length titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as a common cause end-stage dilated cardiomyopathy (DCM) promises new prospects for improving heart failure management. However, realization this opportunity has been hindered by the burden TTN-truncating variants (TTNtv) general population uncertainty about their consequences health or disease. To elucidate effects TTNtv, we coupled...
Mutations in the gene encoding RNA-binding protein RBM20 have been implicated dilated cardiomyopathy (DCM), a major cause of chronic heart failure, presumably through altering cardiac RNA splicing. Here, we combined transcriptome-wide crosslinking immunoprecipitation (CLIP-seq), RNA-seq, and quantitative proteomics cell culture rat human hearts to examine how regulates alternative splicing heart. Our analyses revealed presence distinct RNA-recognition element that is predominantly found...
ABSTRACT The gastrointestinal microbiota of preterm infants in a neonatal intensive care unit differs from that term infants. In particular, the colonization by bifidobacteria is delayed. A double-blind, placebo-controlled, randomized clinical study was performed on 69 to investigate role Bifidobacterium lactis Bb12 supplementation modifying gut microbiota. Both culture-dependent and culture-independent approaches were used Bifidobacterial numbers, determined fluorescence situ hybridization,...
Titin is a giant protein that in charge of the assembly and passive mechanical properties sarcomere. Cardiac titin contains unique N2B region, which has been proposed to modulate elasticity filament be important for hypertrophy signaling ischemic stress response through its binding proteins FHL2 alphaB-crystallin, respectively. To study role region systole diastole heart, we generated knockout (KO) mouse deleting only exon 49 leaving remainder gene intact. The resulting mice survived...
Objectives The aim of this study was to evaluate the nutritional efficacy and bifidogenic characteristics a new infant formula containing partially hydrolyzed whey protein, modified vegetable oil with high β-palmitic acid content, prebiotic oligosaccharides, starch. Methods In double-blind study, healthy formula-fed term infants aged younger than 2 weeks were randomized receive either (NF) or standard (SF) until age 12 weeks. Anthropometric measurements taken at enrollment, 6 weeks,...
The Coxsackievirus-adenovirus receptor (CAR) is known for its role in virus uptake and as a protein of the tight junction. It predominantly expressed developing brain heart reinduced upon cardiac remodeling disease. So far, physiological functions CAR adult are largely unknown. We have generated heart-specific inducible knockout (KO) found impaired electrical conduction between atrium ventricle that increased with progressive loss CAR. underlying mechanism relates to cross talk gap junctions...
The giant protein titin plays key roles in myofilament assembly and determines the passive mechanical properties of sarcomere. cardiac molecule has 2 mayor elastic elements, N2B PEVK region. Both have been suggested to determine heart with loss function data only available for region.The purpose this study was investigate contribution titin's proline-glutamate-valine-lysine (PEVK) region biomechanics growth heart.We removed a portion segment (exons 219 225; 282 aa) that corresponds element...
Abstract Background: Prebiotics and probiotics exert beneficial effects by modulating gut microbiota immune system. This study evaluates efficacy safety of an infant formula containing bovine milk-derived oligosaccharides Bifidobacterium animalis ssp lactis ( B. ) (CNCM I-3446) on incidence diarrhea febrile infections during the first year life (primary outcome). Methods: Full-term infants receiving Test or Control (without oligosaccharide lactis) formulae were enrolled in a multicenter,...
Dilated cardiomyopathy is the second most common cause for heart failure with no cure except a high-risk transplantation. Approximately 30% of patients harbor heritable mutations which are amenable to CRISPR-based gene therapy. However, challenges related delivery editing complex and off-target concerns hamper broad applicability CRISPR agents in heart. We employ combination viral vector AAVMYO superior targeting specificity muscle tissue base editors repair patient cardiac splice factor...
The aim of this study was to examine the pharmacokinetics orally administered omeprazole in children.Plasma concentrations were measured at steady state over a 6-h period after administration drug. Patients subset those multicenter determine dose, safety, efficacy, and tolerability treatment erosive reflux esophagitis children. Children 1-16 yr age, with pathological acid on 24 h-intraesophageal pH study. "healing dose" that which subsequent intraesophageal normalized. remained dose for 3...
Tryptophan (TRP) is the limiting amino acid in low‐protein infant formulas. This mainly due to lower α‐lactalbumin (αLA) content cow's milk whey as compared with human protein. To study effect of αLA‐enrichment on TRP supply, cross‐over studies were carried out 20 healthy infants up 3 months age. In this study, two protein‐reduced (1.3%) formulas (moderate 1.88% and higher 2.10%) alternately fed over a 2 week period groups infants. Serum levels formula‐fed did not differ significantly from...
Children and adolescents suffering from inflammatory bowel disease (IBD) are at risk of developing osteoporosis as a result treatment with corticosteroids well nonsteroidal factors like inflammation malnutrition. To study the impact these on development osteopathy, we compared rate in steroid-naive steroid-treated pediatric IBD patients.In 90 patients (50 girls) (34 steroid-naive, 53 steroid-treated, 3 not known) aged 8.8 to 19.2 (14.4 +/- 2.2) years 52 controls (27 6.1 17.6 (12.9 3.0)...
The giant muscle protein titin is an essential structural component of the sarcomere. It forms a continuous periodic backbone along myofiber that provides resistance to mechanical strain. Thus, filament has been regarded as blueprint for sarcomere assembly and prerequisite stability. Here, novel titin-eGFP knockin mouse provided evidence sarcomeric more dynamic than previously suggested. To study mobility in embryonic neonatal cardiomyocytes, we used fluorescence recovery after...
Heart failure with preserved ejection fraction (HFpEF) and pathological cardiac aging share a complex pathophysiology, including extracellular matrix remodelling (EMR). Protease-activated receptor 2 (PAR2) deficiency is associated EMR. The roles of PAR1 PAR2 have not been studied in HFpEF, age-dependent fibrosis, or diastolic dysfunction (DD).Evaluation endomyocardial biopsies from patients HFpEF (n = 14) revealed that reduced expression was aggravated DD increased myocardial fibrosis (r...
Titin is a giant elastic protein that spans the half-sarcomere from Z-disk to M-band. It acts as molecular spring and mechanosensor has been linked striated muscle disease. The pathways govern titin-dependent cardiac growth contribute disease are diverse difficult dissect.To study titin deficiency versus dysfunction, authors generated compared specific knockouts (KOs) with progressive postnatal loss of complete by removing exon 2 (E2-KO) or an M-band truncation eliminates proper sarcomeric...
Abstract Proximity proteomics has greatly advanced the analysis of native protein complexes and subcellular structures in culture, but not been amenable to study development disease vivo. Here, we have generated a knock-in mouse with biotin ligase (BioID) inserted at titin’s Z-disc region identify networks that connect sarcomere signal transduction metabolism. Our census sarcomeric proteome from neonatal adult heart quadriceps reveals how perinatal signaling, homeostasis shift energy...
Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), syndrome increasing prevalence and no treatment. Both collagen the giant sarcomeric protein titin determine function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as therapeutic target. We RBM20-dependent cardiac isoform expression in N2B knockout mouse increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not...
Heart failure with preserved ejection fraction (HFpEF) is prevalent and deadly, but so far, there no targeted therapy. A main contributor to the disease impaired ventricular filling, which we improved antisense oligonucleotides (ASOs) targeting cardiac splice factor RBM20. In adult mice increased wall stiffness, weekly application of ASOs over 2 months expression compliant titin isoforms function as determined by echocardiography conductance catheter. RNA sequencing confirmed RBM20-dependent...