Activity-based probe for histidine kinase signaling

Bacterial two-component systems (TCSs) are signaling pathways composed of two proteins: a histidine kinase (HK) and a response regulator (RR). Upon stimulation, the HK autophosphorylates at a conserved histidine. The phosphoryl group is subsequently transferred to an aspartate on an RR, eliciting an adaptive response, often up- or downregulation of gene expression. TCS signaling controls many functions in bacteria, including development, virulence, and antibiotic resistance, making the proteins involved in these systems potential therapeutic targets. Efficient methods for the profiling of HKs are currently lacking. For direct readout of HK activity, we sought to design a probe that enables detection of the phosphotransfer event; however, analysis of the phosphohistidine species is made difficult by the instability of the P-N bond. We anticipated that use of a γ-thiophosphorylated ATP analogue, which would yield a thiophosphorylated histidine intermediate, could overcome this challenge. We determined that the fluorophore-conjugated probe, BODIPY-FL-ATPγS, labels active HK proteins and is competitive for the ATP binding site. This activity-based probe provides a new strategy for analysis of TCSs and other HK-mediated processes and will facilitate both functional studies and inhibitor identification.     

Qualitative behaviour of solutions for the two-phase Navier–Stokes equations with surface tension

The two-phase free boundary value problem for the isothermal Navier–Stokes system is studied for general bounded geometries in absence of phase transitions, external forces and boundary contacts. It is shown that the problem is well-posed in an $L_p$ -setting, and that it generates a local semiflow on the induced state manifold. If the phases are connected, the set of equilibria of the system forms a $(n+1)$ -dimensional manifold, each equilibrium is stable, and it is shown that global solutions which do not develop singularities converge to an equilibrium as time goes to infinity. The latter is proved by means of the energy functional combined with the generalized principle of linearized stability.     

„Kristallartige“ Ketten (α-Typ) in der „amorphen“ Phase des linearen Polyäthylens

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Eine Charakterisierung der Dualräume distributiver Supremumshalbverbände

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