Studying the intracellular bile acid concentration and toxicity in drug-induced cholestasis: Comprehensive LC-MS/MS analysis with human liver slices.

Drug-induced cholestasis (DIC) is a leading cause of drug-induced liver injury post-drug marketing, characterized by bile flow obstruction and toxic bile constituent accumulation within hepatocytes. This study investigates the toxicity associated with intracellular bile acid (BA) accumulation during DIC development. Using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, we examined intracellular BA concentrations in human precision-cut liver slices (PCLS) following the administration of cyclosporin A and chlorpromazine, both with and without an established BA mixture.

De novo design of supercharged, unfolded protein polymers, and their assembly into supramolecular aggregates.

Here we report for the first time the design and expression of highly charged, unfolded protein polymers based on elastin-like peptides (ELPs). Positively and negatively charged variants were achieved by introducing lysine and glutamic acid residues, respectively, within the repetitive pentapeptide units. Subsequently it was demonstrated that the monodisperse protein polyelectrolytes with precisely defined amino acid compositions, sequences, and stereochemistries can be transferred into superstructures exploiting their electrostatic interactions.

Transcriptome and proteome analysis of ovaries of arrhenotokous and thelytokous Venturia canescens.

Under arrhenotoky, unfertilized haploid eggs develop as males but under thelytoky they develop into diploid females after they have undergone diploidy restoration. In the parasitoid wasp Venturia canescens both reproductive modes occur. Thelytoky is genetically determined but the underlying genetics of diploidy restoration remain unknown.

A method for site-specific labeling of multiple protein thiols.

We present a generic method for the site-specific and differential labeling of multiple cysteine residues in one protein. Phenyl arsenic oxide has been employed as a protecting group of two closely spaced thiols, allowing first labeling of a single thiol. Subsequently, the protecting group is removed, making available a reactive dithiol site for labeling with a second probe.

Proteomic analysis of secreted membrane vesicles of archaeal Sulfolobus species reveals the presence of endosome sorting complex components.

The crenarchaea Sulfolobus acidocaldarius, S. solfataricus and S. tokodaii, release membrane vesicles into the medium.