Recognition of Host Proteins by Helicobacter Cysteine-Rich Protein C

Tetratricopeptide- and sel1-like repeat (SLR) proteins modulate various cellular activities, ranging from transcription regulation to cell-fate control. Helicobacter cysteine-rich proteins (Hcp) consist of several SLRs that are cross-linked by disulfide bridges and have been implicated in host/pathogen interactions. Using pull-down proteomics, several human proteins including Nek9, Hsp90, and Hsc71 have been identified as putative human interaction partners for HcpC. The interaction between the NimA-like protein kinase Nek9 and HcpC has been validated by ELISA and surface plasmon resonance. Recombinant Nek9 is recognized by HcpC with a dissociation constant in the lower micromolar range. This interaction is formed either directly between Nek9 and HcpC or via the formation of a complex with Hsc71. The HcpC homologue HcpA possesses no affinity for Nek9, suggesting that the reported interaction is rather specific for HcpC. These results are consistent with previous observations where Nek9 was targeted upon bacterial or viral invasion. However, further experiments will be required to show that the reported interactions also occur in viv

Prognostic value of early magnetic resonance imaging in dogs after traumatic brain injury: 50 cases

Retrospective study of dogs with TBI that underwent 1.5T MRI within 14 days after head trauma. MRI evaluators were blinded to the clinical presentation, and all images were scored based on an MRI grading system (Grade I [normal brain parenchyma] to Grade VI [bilateral lesions affecting the brainstem with or without any lesions of lesser grade]). Skull fractures, percentage of intraparenchymal lesions, degree of midline shift, and type of brain herniation were evaluated. MGCS was assessed at presentation. The presence of seizures was recorded. Outcome was assessed at 48 h (alive or dead) and at 3, 6, 12, and 24 months after TBI

Crystallization and preliminary X-ray diffraction analysis of the Sel1-like repeats of SEL1L

Terminally misfolded or unassembled proteins are selectively recognized and cleared by the ER-associated degradation (ERAD) pathway. Suppressor/enhancer of lin-12-like (SEL1L), a component of the dislocation machinery containing the E3 ubiquitin ligase Hrd1, plays an important role in selecting and transporting ERAD substrates for degradation in the endoplasmic reticulum. In this study, the purification, crystallization and preliminary X-ray diffraction analysis of recombinant mouse SEL1L (residues 348-533) are reported. The crystals were obtained by the hanging-drop vapour-diffusion method at pH 8.5 and 277 K using 30% 2-propanol as a precipitant. Optimized crystals diffracted to 3.3 angstrom resolution at a synchrotron-radiation source. Preliminary X-ray diffraction analysis revealed that the crystals belonged to space group P2(1) and contained four molecules per asymmetric unit, with a solvent content of 44%.open0

Biological activity differences between TGF-β1 and TGF-β3 correlate with differences in the rigidity and arrangement of their component monomers

[Image: see text] TGF-β1, -β2, and -β3 are small, secreted signaling proteins. They share 71–80% sequence identity and signal through the same receptors, yet the isoform-specific null mice have distinctive phenotypes and are inviable. The replacement of the coding sequence of TGF-β1 with TGF-β3 and TGF-β3 with TGF-β1 led to only partial rescue of the mutant phenotypes, suggesting that intrinsic differences between them contribute to the requirement of each in vivo. Here, we investigated whether the previously reported differences in the flexibility of the interfacial helix and arrangement of monomers was responsible for the differences in activity by generating two chimeric proteins in which residues 54–75 in the homodimer interface were swapped. Structural analysis of these using NMR and functional analysis using a dermal fibroblast migration assay showed that swapping the interfacial region swapped both the conformational preferences and activity. Conformational and activity differences were also observed between TGF-β3 and a variant with four helix-stabilizing residues from TGF-β1, suggesting that the observed changes were due to increased helical stability and the altered conformation, as proposed. Surface plasmon resonance analysis showed that TGF-β1, TGF-β3, and variants bound the type II signaling receptor, TβRII, nearly identically, but had small differences in the dissociation rate constant for recruitment of the type I signaling receptor, TβRI. However, the latter did not correlate with conformational preference or activity. Hence, the difference in activity arises from differences in their conformations, not their manner of receptor binding, suggesting that a matrix protein that differentially binds them might determine their distinct activities

The devil in literature: „A part of that force, which, always willing evil, always produces good.“

Der Teufel zählt seit jeher zu den populärsten literarischen Motiven und hat auch heute nichts an Faszination verloren. Gerade als Symbol der Grenzüberschreitung vermag er seinen Einfluss auszuüben und präsentiert sich dabei meist äußerst ansprechend. Mit den Worten Friedrich Dürrenmatts gesprochen: „Ich habe oft über das Pech nachdenken müssen, dass die interessanteste deutsche Bühnenfigur der Teufel ist.“ Der erste Teil des Artikels bietet einen kurzen Überblick über die religionswissenschaftlichen Voraussetzungen, die die Herausbildung einer Teufelsfigur ermöglichen. Das Alte Testament kennt noch keine eigenständigen dämonischen Mächte, da sich alles um die Festigung des Monotheismus dreht. Erst im Anschluss erhalten Überlegungen zu Herkunft und Rolle des Bösen sowie über dessen Verhältnis zum Schöpfergott Gewicht. Der Teufel fungiert meist als Ankläger im Hofstaat Gottes, dem eine gewisse Rolle im Heilsplan zugewiesen ist. Im zweiten Abschnitt wird die Entwicklung der Teufelsgestalt in der Literatur anhand einiger Beispiele – Dantes Divina Commedia, Miltons Paradise Lost, Goethes Faust, Bulgakows Meister und Margarita – aufgezeigt. Der Teufel verliert zusehends an Schrecken und wir immer mehr zum unfreiwilligen Partner Gottes. Baudelaires berühmtes Diktum: „Die schönste List des Teufels ist es, uns zu überzeugen, dass es ihn nicht gibt“, wirft auch heute noch die Frage auf, ob eine Personifizierung des Bösen sinnvoll und zeitgemäß ist. Daher werden abschließend die zuvor gewonnenen Einsichten noch einmal zusammengefasst und in Hinblick auf einen verantwortlichen Umgang mit der Gestalt des Teufels und dem Phänomen des Bösen – nicht zuletzt auch aus lehramtlicher Sicht – vertieft.Up to this day, the devil is one of the most popular figures in literature. Sometimes scary and very often charming, he keeps entrapping and fascinating people. Friedrich Dürrenmatt states: “I have often thought about the unlucky fact that the devil is the most interesting German stage character.” After a short history of the devil from a religious studies point of view, selected literary works and their concepts of evil are examined. This section deals with fairy tales as well as with literary classics (Dante’s The Devine Comedy, John Milton’s Paradise Lost, Goethe’s Faust, Bulgakow’s The Master and Margarita) and suggests that the devil turns more and more into God’s involuntarily partner. For Charles Baudelaire, “the greatest trick the devil ever played was convincing the world that he did not exist.” Thus, the combination of theological and literary insights in the last part should enable to determine whether the concept of a personal devil is still appropriate today

Baedekers Reisehandbücher - Funktionen und Bewertungen eines Reisebegleiters des 19. Jahrhunderts

Karl Baedeker is seen, together with the English publisher Murray, as the one establishing the modern guidebook. This work analyses the contemporary evaluations and reviews of the series “Baedeker’s Guidebooks” from 1859 to 1914. The series was aimed at a wealthy audience that could afford educational journeys. The recipients predominantly belonged to a bourgeois elite. The Baedeker was seen as an ideal guidebook and the publishing house had the reputation of having perfected the guidebook. Apart from literary classics it belonged to a tourist’s canon; in addition, the complex contents and the layout also show that the Baedeker is consulted both for the preparation and the follow-up of the journey, as well as at the sight itself.Karl Baedeker gilt - zusammen mit dem englischen Verleger Murray - als derjenige, der den modernen Reiseführer eingeführt hat. Die Arbeit analysiert die zeitgenössischen Bewertungen und Rezensionen der Reihe „Baedeker’s Reisehandbücher“ von 1859 bis 1914. Die Reihe war an ein vermögendes Publikum gerichtet, welches sich Bildungsreisen leisten konnte. Die Rezipienten gehörten überwiegend einer bürgerlichen Elite an. Der Baedeker galt als idealer Reiseführer und der Verlag hatte den Ruf, den Reiseführer perfektioniert zu haben. Neben literarischen Klassikern gehörte er zum Kanon des Touristen; der komplexe Inhalt und das Seitenlayout verdeutlichen, dass der Baedeker zur Vor- und Nachbereitung einer Reise, als auch vor der Sehenswürdigkeit selbst konsultiert werden kann

Crystal structure of SEL1L: Insight into the roles of SLR motifs in ERAD pathway

Terminally misfolded proteins are selectively recognized and cleared by the endoplasmic reticulum-associated degradation (ERAD) pathway. SEL1L, a component of the ERAD machinery, plays an important role in selecting and transporting ERAD substrates for degradation. We have determined the crystal structure of the mouse SEL1L central domain comprising five Sel1-Like Repeats (SLR motifs 5 to 9; hereafter called SEL1Lcent). Strikingly, SEL1Lcent forms a homodimer with two-fold symmetry in a head-to-tail manner. Particularly, the SLR motif 9 plays an important role in dimer formation by adopting a domain-swapped structure and providing an extensive dimeric interface. We identified that the full-length SEL1L forms a self-oligomer through the SEL1Lcent domain in mammalian cells. Furthermore, we discovered that the SLR-C, comprising SLR motifs 10 and 11, of SEL1L directly interacts with the N-terminus luminal loops of HRD1. Therefore, we propose that certain SLR motifs of SEL1L play a unique role in membrane bound ERAD machinery.ope

Vikten av provtagningskontroll vid eDNA analyser av dammlevande amphibier

The eDNA approach for monitoring aquatic species is already widely used. However, there are still uncertainties, for instance regarding the distribution of target DNA in ponds. These uncertainties need to be addressed when using eDNA in management. The current study uses individual capture and eDNA monitoring methods based on bottle trapping and 3x15 ml water sampling for Triturus cristatus in different ponds to show the importance of a carefully considered and performed study and in particular sampling design for achieving reliable results. Most of the results were received from only one pond. While here the bottle trapping resulted only in 15 catches, the eDNA method showed better results in confirming presence of the target. Examining two different primer combinations, the one with the bigger amplicon was more reliable than the one with the shorter amplicon. However, the data clearly indicated an influence of the sampling location on the eDNA results. This is also true for weather factors and / or sample time within the season. Therefore the sampling design has to be reconsidered, with respect to DNA distribution and persistence, seasonal habitation differences of the target and the primer specifics