Growth/differentiation factor-15 (GDF-15) is a widely expressed distant member of the TGF-beta superfamily with prominent neurotrophic effects on midbrain dopaminergic neurons. We show here that GDF-15-deficient mice exhibit progressive postnatal losses of spinal, facial, and trigeminal motoneurons. This deficit reaches a approximately 20% maximum at 6 months and is accompanied by losses of mot...

OBJECTIVE Growth-differentiation factor 15 (GDF-15), a stress-responsive member of the transforming growth factor beta cytokine superfamily, has emerged as a biomarker of increased mortality in cardiovascular disease. However, the exact pathophysiological mechanisms of GDF-15 in the cardiovascular system and in acute ST-elevation myocardial infarction (STEMI) are not well defined. The aim of th...

RATIONALE The molecular mechanisms underlying the muscle atrophy of intensive care unit-acquired weakness (ICUAW) are poorly understood. We hypothesised that increased circulating and muscle growth and differentiation factor-15 (GDF-15) causes atrophy in ICUAW by changing expression of key microRNAs. OBJECTIVES To investigate GDF-15 and microRNA expression in patients with ICUAW and to elucid...

Dendritic cells (DCs) play a key role in the initiation stage of an antigen-specific immune response. A variety of tumor-derived factors (TDFs) can suppress DC maturation and function, resulting in defects in the tumor-specific immune response. To identify unknown TDFs that may suppress DCs maturation and function, we established a high-throughput screening technology based on a human liver tum...

Complex production systems can produce more than one part type. For these systems, production rate and priority of production for each part type is determined by production controllers. In this paper, genetic fuzzy logic control (GFLC) methodology is used to develop two production control architectures namely ‘‘genetic distributed fuzzy” (GDF), and ‘‘genetic supervisory fuzzy” (GSF) controllers...

INTRODUCTION Chemotherapy-related endothelial damage contributes to the early development of cardiovascular morbidity in testicular cancer patients. We aimed to identify relevant mechanisms of and search for candidate biomarkers for this endothelial damage. METHODS Human micro-vascular endothelial cells (HMEC-1) were exposed to bleomycin or cisplatin with untreated samples as control. 18k cDN...

Non healing bone defects remain a worldwide health problem and still only few osteoinductive growth factors are available for clinical use in bone regeneration. By introducing BMP-2 residues into growth and differentiation factor (GDF)-5 we recently produced a mutant GDF-5 protein BB-1 which enhanced heterotopic bone formation in mice. Designed to combine positive features of GDF-5 and BMP-2, w...

Growth differentiation factor 5 (GDF-5), a member of the transforming growth factor beta (TGF-β) superfamily expressed in periodontal tissues, promotes extracellular matrix (ECM) in periodontal ligament (PDL) cells. Matrix metalloproteinases (MMP) are proteolytic enzymes that degrade ECM and are expressed in PDL cells. To date, little is known about the regulation of MMP synthesis and secretion...

AIMS Growth-differentiation factor-15 (GDF-15) has emerged as a biomarker of increased mortality and recurrent myocardial infarction (MI) in patients diagnosed with non-ST-elevation acute coronary syndrome. We explored the usefulness of GDF-15 for early risk stratification in 479 unselected patients with acute chest pain. METHODS AND RESULTS Sixty-nine per cent of the patients presented with ...