The hyaluronan-binding serine protease from human plasma cleaves HMW and LMW kininogen and releases bradykinin

The influence of the hyaluronanbinding protease (PHBSP), a plasma enzyme with FVII- and pro-urokinase-activating potency, on components of the contact phase (kallikrein/kinin) system was investigated. No activation or cleavage of the proenzymes involved in the contact phase system was observed. The procofactor high molecular weight kininogen (HK), however, was cleaved in vitro by PHBSP in the absence of any charged surface, releasing the activated cofactor and the vasoactive nonapeptide bradykinin. Glycosoaminoglycans strongly enhanced the reaction. The cleavage was comparable to that of plasma kallikrein, but clearly different from that of coagulation factor FXIa. Upon extended incubation with PHBSP, the light chain was further processed, partially removing about 60 amino acid residues from the Nterminus of domain D5 of the light chain. These cleavage site(s) were distinct from plasma kallikrein or FXIa cleavage sites. PHBSP and, more interestingly, also plasma kallikrein could cleave low molecular weight kininogen in vitro, indicating that domains D5(H) and D6(H) are no prerequisite for kininogen cleavage. PHBSP was also able to release bradykinin from HK in plasma where the pro-cofactor circulates predominantly in complex with plasma kallikrein or FXI. In conclusion, PHBSP represents a novel kininogen-cleaving and bradykinin-releasing enzyme in plasma that shares significant catalytic similarities with plasma kallikrein. Since they are structurally unrelated in their heavy chains (propeptide), their similar in vivo catalytic activities might be directed at distinct sites where PHBSP could induce processes that are related to the kallikrein/kinin system

Handlungsbedarf trotz Krankenhausstrukturgesetz: Elf Thesen zur Reform der Notfallversorgung

Trotz der Reformen durch das Krankenhausstrukturgesetz ist insbesondere im Bereich der Notfallversorgung noch viel zu tun. Diese RWI Position fasst die wichtigsten offenen Punkte mit Handlungsbedarf in elf Thesen zusammen. Schwerpunkte sind insbesondere die klare Definition des Notfalls, eine höhere Qualität von Fachkräften und Prozessen, eine verbesserte Patientensteuerung sowie eine eigene notfallspezifische Forschung. Ein zentraler Reformvorschlag, die Einrichtung von Intersektoralen Notfallzentren (INZ) in einer Region, wird darüber hinaus ausführlicher beleuchtet.With the new "Krankenhausstrukturgesetz", policy makers took many steps into the right direction of reforming Germany's health care system. Nevertheless, especially in regard to providing the set up for a sustainable future emergency care there is a lot still to be done. In eleven claims, this RWI Position points out those areas in which action is most urgently needed. Among these are setting up a clear definition of an emergency case, assuring a higher quality of medical professionals and caring processes, and initiating a specific strand of research on emergency care. In addition, we provide a detailed description of one of the most crucial reform ideas, namely establishing intersectoral emergency care centres (Intersektorale Notfallzentren) in each region

Hyb:A bioinformatics pipeline for the analysis of CLASH (crosslinking, ligation and sequencing of hybrids) data

Peer reviewedPublisher PD

Serial optical coherence microscopy for label-free volumetric histopathology

The observation of histopathology using optical microscope is an essential procedure for examination of tissue biopsies or surgically excised specimens in biological and clinical laboratories. However, slide-based microscopic pathology is not suitable for visualizing the large-scale tissue and native 3D organ structure due to its sampling limitation and shallow imaging depth. Here, we demonstrate serial optical coherence microscopy (SOCM) technique that offers label-free, high-throughput, and large-volume imaging of ex vivo mouse organs. A 3D histopathology of whole mouse brain and kidney including blood vessel structure is reconstructed by deep tissue optical imaging in serial sectioning techniques. Our results demonstrate that SOCM has unique advantages as it can visualize both native 3D structures and quantitative regional volume without introduction of any contrast agents

Whole-Brain Analysis of Cells and Circuits by Tissue Clearing and Light-Sheet Microscopy

In this photo essay, we present a sampling of technologies from laboratories at the forefront of whole-brain clearing and imaging for high-resolution analysis of cell populations and neuronal circuits. The data presented here were provided for the eponymous Mini-Symposium presented at the Society for Neuroscience's 2018 annual meeting

The cytosolic DnaJ-like protein Djp1p is involved specifically in peroxisomal protein import

The Saccharomyces cerevisiae DJP1 gene encodes a cytosolic protein homologous to Escherichia coli DnaJ. DnaJ homologues act in conjunction with molecular chaperones of the Hsp70 protein family in a variety of cellular processes. Cells with a DJP1 gene deletion are viable and exhibit a novel phenotype among cytosolic J-protein mutants in that they have a specific impairment of only one organelle, the peroxisome. The phenotype was also unique among peroxisome assembly mutants: peroxisomal matrix proteins were mislocalized to the cytoplasm to a varying extent, and peroxisomal structures failed to grow to full size and exhibited a broad range of buoyant densities. Import of marker proteins for the endoplasmic reticulum, nucleus, and mitochondria was normal. Furthermore, the metabolic adaptation to a change in carbon source, a complex multistep process, was unaffected in a DJP1 gene deletion mutant. We conclude that Djp1p is specifically required for peroxisomal protein import

Dentition in beef cattle in northern Australia

Estimation of age of cattle is important to north Australian cattle producers who sell cattle on the basis of carcass classification, by description or to premium markets. Age at eruption of permanent incisor teeth of 52 Shorthorn and 42 Brahman x British steers grazing spear grass pastures in north Queensland was determined. Shorthorn steers cut each pair of incisor teeth when younger than Brahman X British steers (P<0.01). The 95% ranges for age at eruption in days for the four pairs were: 631 to 823, 772 to 1066, 951 to 1321 and 1181 to 1611 for Shorthorn and 679 to 871, 848 to 1142, 1055 to 1425 and 1306 to 1736 for Brahman X British, respectively. This large variation and overlap between successive pairs shows the limitations of dentition as an indicator of age of cattle for use in marketing