From signal transduction to signal interpretation: an alternative model for the molecular function of insulin receptor substrates.

The insulin receptor (IR) recruits adaptor proteins, so-called insulin receptor substrates (IRS), to connect with downstream signalling pathways. A family of IRS proteins was defined based on three major common structural elements: Amino-terminal PH and PTB domains that mediate protein-lipid or protein-protein interactions, mostly carboxy-terminal multiple tyrosine residues that serve as binding sites for proteins that contain one or more SH2 domains and serine/threonine-rich regions which may be recognized by negative regulators of insulin action. The current model for the role of IRS proteins therefore combines an adaptor function with the integration of mostly negative input from other signal transduction cascades allowing for modulation of signalling amplitude.

The phylogeny of yellow fever virus 17D vaccines.

In recent years the safety of the yellow fever live vaccine 17D came under scrutiny. The focus was on serious adverse events after vaccinations that resemble a wild type infection with yellow fever and whose reasons are still not known. Also the exact mechanism of attenuation of the vaccine remains unknown to this day.

Investigations of prion and virus safety of a new liquid IVIG product.

A highly purified, liquid, 10% immunoglobulin product stabilized with proline, referred to as IgPro10 has recently been developed. IgG was purified from human plasma by cold ethanol fractionation, octanoic acid precipitation and anion-exchange chromatography. The manufacturing process includes two distinctly different partitioning steps and virus filtration, which were also assessed for the removal of prions.

Molecular mechanism underlying B19 virus inactivation and comparison to other parvoviruses.

Background: B19 virus (B19V) is a human pathogen frequently present in blood specimens. Transmission of the virus occurs mainly via the respiratory route, but it has also been shown to occur through the administration of contaminated plasma-derived products. Parvoviridae are highly resistant to physicochemical treatments; however, B19V is more vulnerable than the rest of parvoviruses.

Short regions of sequence identity between the genomes of human and rodent parvoviruses and their respective hosts occur within host genes for the cytoskeleton, cell adhesion and Wnt signalling.

Our understanding of the mechanism(s) of pathogenesis and persistence of vertebrate parvoviruses remains incomplete. With the recent availability of the complete genome sequences of human, rat and mouse, and the ability to search these sequences and to locate matches to exact genomic regions, further insight into the interaction of parvoviruses with their human and rodent hosts is possible. To determine the extent and nature of sequence identity between candidate parvoviruses and their respective hosts, blast searches of the genome sequences of adeno-associated virus, parvovirus B19, mouse parvovirus, the prototype strain and immunosuppressant variant of minute virus of mouse, Kilham rat virus and rat parvovirus were performed against the genome(s) of their respective hosts (human, rat and mouse) using the resources of the NCBI and the Celera Discovery System.