University of Erlangen-Nuremberg

About: University of Erlangen-Nuremberg is a education organization based out in Erlangen, Bayern, Germany. It is known for research contribution in the topics: Population & Immune system. The organization has 42405 authors who have published 85600 publications receiving 2663922 citations.

Adaptive optical microscopy: the ongoing quest for a perfect image

Abstract: Adaptive optics is becoming a valuable tool for high resolution microscopy, providing correction for aberrations introduced by the refractive index structure of specimens. This is proving particularly promising for applications that require images from deep within biological tissue specimens. We review recent developments in adaptive microscopy, including methods and applications. A range of advances in different microscope modalities is covered and prospects for the future are discussed. Adaptive optics is used to improve image quality across a wide range of microscopy techniques. Martin Booth from the University of Oxford in the UK reviews how technologies such as deformable mirrors and spatial light modulators, which compensate for aberrations by locally controlling the wavefront of a light wave, are now improving the performance of multiphoton, confocal, widefield and super-resolution microscopes. The benefits of such improvements are especially appealing for images captured from within biological tissue (focal distances of tens to hundreds of micrometres), where low-order aberrations associated with smooth phase variations occur. One future challenge is the development of efficient measurement and correction schemes for higher-order phase variations.

Matrix as a modulator of hepatic fibrogenesis.

Abstract: The extracellular matrix (ECM) provides cells with positional information and a mechanical scaffold for adhesion and migration. It consists of collagens, glycoproteins, proteoglycans, glycosaminoglycans and molecules that are bound specifically by the ECM, such as certain growth factors/cytokines, matrix metalloproteinases (MMPs) and processing enzymes such as tissue transglutaminase and procollagen propeptidases. This finely tuned ecosystem is dysbalanced in chronic fibrogenesis, which can be regarded as a continuous wound-healing process and which results in scar formation. Importantly, the ECM directs cellular differentiation, migration, proliferation, and fibrogenic activation or deactivation. Partially via defined oligopeptide sequences or structural domains, the ECM transfers specific signals to cells that act in concert with growth factors/cytokines. These signals either confer stress activation, with a resultant fibrogenic response, or stress relaxation, with a fibrolytic response. Alternatively, ECM-derived peptides can modulate angiogenesis, or growth factor and MMP availability and activity. Current ECM-related antifibrotic strategies are based on the identification and in vivo application of ECM-derived biomodulatory peptides, peptide sequences, or their nonpeptidic mimetics. The latter open the opportunity of oral application and an extended biological half-life. Examples are peptides derived from collagens VI (stress activation) and XIV (stress relaxation), or collagenous consensus peptides that remove ECM-bound MMPs and growth factors. Furthermore, certain peptides can be used as targeting structures to the fibrogenic lesion.

Induction of inflammatory and immune responses by HMGB1–nucleosome complexes: implications for the pathogenesis of SLE

Abstract: Autoantibodies against double-stranded DNA (dsDNA) and nucleosomes represent a hallmark of systemic lupus erythematosus (SLE). However, the mechanisms involved in breaking the immunological tolerance against these poorly immunogenic nuclear components are not fully understood. Impaired phagocytosis of apoptotic cells with consecutive release of nuclear antigens may contribute to the immune pathogenesis. The architectural chromosomal protein and proinflammatory mediator high mobility group box protein 1 (HMGB1) is tightly attached to the chromatin of apoptotic cells. We demonstrate that HMGB1 remains bound to nucleosomes released from late apoptotic cells in vitro. HMGB1–nucleosome complexes were also detected in plasma from SLE patients. HMGB1-containing nucleosomes from apoptotic cells induced secretion of interleukin (IL) 1β, IL-6, IL-10, and tumor necrosis factor (TNF) α and expression of costimulatory molecules in macrophages and dendritic cells (DC), respectively. Neither HMGB1-free nucleosomes from viable cells nor nucleosomes from apoptotic cells lacking HMGB1 induced cytokine production or DC activation. HMGB1-containing nucleosomes from apoptotic cells induced anti-dsDNA and antihistone IgG responses in a Toll-like receptor (TLR) 2–dependent manner, whereas nucleosomes from living cells did not. In conclusion, HMGB1–nucleosome complexes activate antigen presenting cells and, thereby, may crucially contribute to the pathogenesis of SLE via breaking the immunological tolerance against nucleosomes/dsDNA.