Kinetic Modeling of the Antibody Disulfide Bond Reduction Reaction With Integrated Prediction of the Drug Load Profile for Cysteine-Conjugated ADCs.

Antibody-drug conjugates (ADC) constitute a groundbreaking advancement in the field of targeted therapy. In the widely utilized cysteine conjugation, the cytotoxic payload is attached to reduced interchain disulfides which involves a reduction of the native monoclonal antibody (mAb). This reaction needs to be thoroughly understood and controlled as it influences the critical quality attributes (CQAs) of the final ADC product, such as the drug-to-antibody ratio (DAR) and the drug load distribution (DLD).

Development of MHz X-ray phase contrast imaging at the European XFEL.

We report on recent developments that enable megahertz hard X-ray phase contrast imaging (MHz XPCI) experiments at the Single Particles, Clusters, and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX) instrument of the European XFEL facility (EuXFEL). We describe the technical implementation of the key components, including an MHz fast camera and a modular indirect X-ray microscope system based on fast scintillators coupled through a high-resolution optical microscope, which enable full-field X-ray microscopy with phase contrast of fast and irreversible phenomena. The image quality for MHz XPCI data showed significant improvement compared with a pilot demonstration of the technique using parallel beam illumination, which also allows access to up to 24 keV photon energies at the SPB/SFX instrument of the EuXFEL.

New insights into the function and molecular mechanisms of Ferredoxin-NADP reductase from Brucella ovis.

Bacterial ferredoxin(flavodoxin)-NADP reductases (FPR) primarily catalyze the transfer of reducing equivalents from NADPH to ferredoxin (or flavodoxin) to provide low potential reducing equivalents for the oxidoreductive metabolism. In addition, they can be implicated in regulating reactive oxygen species levels. Here we assess the functionality of FPR from B.

Who is in control? Longitudinal connections between marital power and parental psychological control.

The present study explored longitudinal associations between marital power dynamics and parental psychological control and tested whether partners' sense of relational autonomy mediated these connections. Self-determination theory supports that harmful marital dynamics may spill into parenting practices, such as engaging in parental psychological control, and that parents' autonomy may mediate connections. Using an actor-partner interdependence model and an actor-partner interdependence mediation model, this study examined direct associations between marital power and parental psychological control, as well as indirect associations with autonomy as a mediator.

Crystal structure of a bacterial photoactivated adenylate cyclase determined by serial femtosecond and serial synchrotron crystallography.

OaPAC is a recently discovered blue-light-using flavin adenosine dinucleotide (BLUF) photoactivated adenylate cyclase from the cyanobacterium Oscillatoria acuminata that uses adenosine triphosphate and translates the light signal into the production of cyclic adenosine monophosphate. Here, we report crystal structures of the enzyme in the absence of its natural substrate determined from room-temperature serial crystallography data collected at both an X-ray free-electron laser and a synchrotron, and we compare these structures with cryo-macromolecular crystallography structures obtained at a synchrotron by us and others. These results reveal slight differences in the structure of the enzyme due to data collection at different temperatures and X-ray sources.