No abstract

Ricin is one of the most feared bioweapons in the world due to its extreme toxicity and easy access. Since no antidote exists, it is of paramount importance to identify the pathways underlying ricin toxicity. Here, we demonstrate that the Golgi GDP-fucose transporter Slc35c1 and fucosyltransferase Fut9 are key regulators of ricin toxicity. Genetic and pharmacological inhibition of fucosylation renders diverse cell types resistant to ricin via deregulated intracellular trafficking. Importantly, cells from a patient with SLC35C1 deficiency are also resistant to ricin. Mechanistically, we confirm that reduced fucosylation leads to increased sialylation of Lewis X structures and thus masking of ricin-binding sites. Inactivation of the sialyltransferase responsible for modifications of Lewis X (St3Gal4) increases the sensitivity of cells to ricin, whereas its overexpression renders cells more resistant to the toxin. Thus, we have provided unprecedented insights into an evolutionary conserved modular sugar code that can be manipulated to control ricin toxicity.

Bartonella henselae causes cat scratch disease and several other clinical entities. Infections with B. henselae are frequently occurring; however, the infection is only rarely diagnosed, mainly due to a lack of knowledge in the medical community. Microscopic immunofluorescence assays (IFA) are widely used for the serodiagnosis of B. henselae infections but are laborious and time-consuming, and interpretation is subjective. An easy and reliable method for the serological diagnosis of B. henselae infections is needed to overcome the shortcomings of the current IFA. Here, we report the development of an ELISA detecting human anti-B. henselae antibodies from serum samples. By separating the water-insoluble fraction of B. henselae Houston-1 via ion-exchange chromatography, 16 subfractions were generated and tested for immunoreactivity via line blotting. One particular fraction (fraction 24) was selected and spotted on ELISA plates using an industrial production platform. By use of well-characterized human sera from the strictly quality-controlled serum library of the German National Consiliary Laboratory for Bartonella infections, the sensitivity of this ELISA was 100% for PCR-proven infections and 76% for clinically suspected infections at a specificity of 93%. This ELISA is therefore a reliable high-throughput method allowing the serodiagnosis of B. henselae infections.

In dem Artikel “Berechnung von Stahlverbundträgern – Ein Rechenmodell zur Berücksichtigung von verformbaren, teiltragfähigen Verbundanschlüssen” [1] wurde ein Rechenmodell vorgestellt, um die Verformbarkeit und die Teiltragfähigkeit von Verbundanschlüssen in der Statischen Berechnung zu berücksichtigen. In diesem Artikel folgt nun ein Rechenbeispiel, um den Rechenhergang zu veranschaulichen. Für einen Verbundanschluß im Statischen System werden die Kennwerte “Steifigkeit”, “Tragfähigkeit” und “Verdrehungsfähigkeit” ermittelt. Anschließend werden die Nachweise für die Biegetragfähigkeit im Feld und im Verbundanschluß im rechnerischen Bruchzustand (ULS) geführt sowie der Nachweis der Durchbiegung in Feldmitte im Gebrauchszustand (SLS).