Pilus chaperones represent a new type of protein-folding catalyst

Adhesive type 1 pili from uropathogenic Escherichia coli strains have a crucial role during infection by mediating the attachment to and potentially the invasion of host tissue. These filamentous, highly oligomeric protein complexes are assembled by the 'chaperone-usher' pathway, in which the individual pilus subunits fold in the bacterial periplasm and form stoichiometric complexes with a periplasmic chaperone molecule that is essential for pilus assembly. The chaperone subsequently delivers the subunits to an assembly platform (usher) in the outer membrane, which mediates subunit assembly and translocation to the cell surface. Here we show that the periplasmic type 1 pilus chaperone FimC binds non-native pilus subunits and accelerates folding of the subunit FimG by 100-fold. Moreover, we find that the FimC-FimG complex is formed quantitatively and very rapidly when folding of FimG is initiated in the presence of both FimC and the assembly-competent subunit FimF, even though the FimC-FimG complex is thermodynamically less stable than the FimF-FimG complex. FimC thus represents a previously unknown type of protein-folding catalyst, and simultaneously acts as a kinetic trap preventing spontaneous subunit assembly in the periplasm.     

Release of bradykinin as related to the esterase activity of trypsin and of the venom ofBothrops jararaca

Zusammenfassung Die proteolytische Aktivität des Giftes vonBothrops jararaca wird durch Erhitzen leicht zerstört und dabei eine Esterase mit grösserer Hitzeresistenz abgetrennt. Nach Hitzefraktionierung des Giftes steht die Aktivität dieser Esterase in direktem Verhältnis zum abgegebenen Bradykinin und zur Gerinnung des frischen Plasmas.     

Einfluss der Passagegeschwindigkeit auf die Resorption von Glucose im Dünndarm der Ratte

Summary Loops of rat's small intestine have been perfused with 5% glucose solution at different flow rates. The absorption of glucose has been investigated. The results showed that, with increasing flow rates, absorption rate of glucose is also increased. Therefore contact time seems to be no limiting factor in intestinal absorption.

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Mit Unterstützung des Österr. Fonds zur Förderung der wissenschaftlichen Forschung, Projekt Nr. 650.     

Applying Frameworks for Cognitive Services in IIoT

The technology,which enables creating new types of products,processes and services(i.e.,things),which outcomes alter traditional competition and industry boundaries and create new lasting value.The digitalization process uses digital technologies to provide the possibilities of new revenue and value-producing,i.e.,it changes business models and offers new value propositions.This change is ongoing.The most important ten strategic technology trends in 2019 include Edge computing,Blockchain,event and data-driven strategies,Digital Twins,and the maintenance of transparency(i.e.,traceability),Intelligent Apps and Analytics(Gartner 2018).In this paper,we experiment with the capabilities of intelligent applications to match the industrial business needs.This paper aims to bring insights closer to business objectives.Digitalization’s technological advantages can be achieved through data-driven strategies and wherein cognitive services are integrated into IoT(Internet of Things)and big data.We experiment with the Industrial IoT(IIoT)business models and value propositions to match the intelligent insights of cognitive solutions to business objectives.The IIoTs support and demand transparency and thus also data-driven objective insights,and because cognitive solutions can enhance insights on a product,a process or service and therefore provide measurable business objectives.Functional indicators enable interconnected smart things to collaborate.     

Neural crest origins of the neck and shoulder

The neck and shoulder region of vertebrates has undergone a complex evolutionary history. To identify its underlying mechanisms we map the destinations of embryonic neural crest and mesodermal stem cells using Cre-recombinase-mediated transgenesis. The single-cell resolution of this genetic labelling reveals cryptic cell boundaries traversing the seemingly homogeneous skeleton of the neck and shoulders. Within this assembly of bones and muscles we discern a precise code of connectivity that mesenchymal stem cells of both neural crest and mesodermal origin obey as they form muscle scaffolds. The neural crest anchors the head onto the anterior lining of the shoulder girdle, while a Hox-gene-controlled mesoderm links trunk muscles to the posterior neck and shoulder skeleton. The skeleton that we identify as neural crest-derived is specifically affected in human Klippel-Feil syndrome, Sprengel's deformity and Arnold-Chiari I/II malformation, providing insights into their likely aetiology. We identify genes involved in the cellular modularity of the neck and shoulder skeleton and propose a new method for determining skeletal homologies that is based on muscle attachments. This has allowed us to trace the whereabouts of the cleithrum, the major shoulder bone of extinct land vertebrate ancestors, which seems to survive as the scapular spine in living mammals.     

Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin

Nephronophthisis (NPHP) is the most frequent genetic cause of chronic renal failure in children. Identification of four genes mutated in NPHP subtypes 1-4 (refs. 4-9) has linked the pathogenesis of NPHP to ciliary functions. Ten percent of affected individuals have retinitis pigmentosa, constituting the renal-retinal Senior-Loken syndrome (SLSN). Here we identify, by positional cloning, mutations in an evolutionarily conserved gene, IQCB1 (also called NPHP5), as the most frequent cause of SLSN. IQCB1 encodes an IQ-domain protein, nephrocystin-5. All individuals with IQCB1 mutations have retinitis pigmentosa. Hence, we examined the interaction of nephrocystin-5 with RPGR (retinitis pigmentosa GTPase regulator), which is expressed in photoreceptor cilia and associated with 10-20% of retinitis pigmentosa. We show that nephrocystin-5, RPGR and calmodulin can be coimmunoprecipitated from retinal extracts, and that these proteins localize to connecting cilia of photoreceptors and to primary cilia of renal epithelial cells. Our studies emphasize the central role of ciliary dysfunction in the pathogenesis of SLSN.     

Effect of weld microstructure on brittle fracture initiation in the thermally-aged boiling water reactor pressure vessel head weld metal

Effects of the weld microstructure and inclusions on brittle fracture initiation are investigated in a thermally aged ferritic high-nickel weld of a reactor pressure vessel head from a decommissioned nuclear power plant.As-welded and reheated regions mainly consist of acicular and polygonal ferrite,respectively.Fractographic examination of Charpy V-notch impact toughness specimens reveals large inclusions(0.5-2.5μm)at the brittle fracture primary initiation sites.High impact energies were measured for the specimens in which brittle fracture was initiated from a small inclusion or an inclusion away from the V-notch.The density,geometry,and chemical composition of the primary initiation inclusions were investigated.A brittle fracture crack initiates as a microcrack either within the multiphase oxide inclusions or from the debonded interfaces between the uncracked inclusions and weld metal matrix.Primary fracture sites can be determined in all the specimens tested in the lower part of the transition curve at and below the 41-J reference impact toughness energy but not above the mentioned value because of the changes in the fracture mechanism and resulting changes in the fracture appearance.