De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8.

The RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between homologous αvβ6 and αvβ8 and other RGD integrins, stabilize specific conformational states, and have high thermal stability could have considerable therapeutic utility. Existing small molecule and antibody inhibitors do not have all these properties, and hence new approaches are needed.

Weakly Supervised Identification and Localization of Drug Fingerprints Based on Label-Free Hyperspectral CARS Microscopy.

Understanding drug fingerprints in complex biological samples is essential for the development of a drug. Hyperspectral coherent anti-Stokes Raman scattering (HS-CARS) microscopy, a label-free nondestructive chemical imaging technique, can profile biological samples based on their endogenous vibrational contrast. Here, we propose a deep learning-assisted HS-CARS imaging approach for the investigation of drug fingerprints and their localization at single-cell resolution.

design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8.

The RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between the two closely related integrin proteins and other RGD integrins, stabilize specific conformational states, and have sufficient stability enabling tissue restricted administration could have considerable therapeutic utility. Existing small molecules and antibody inhibitors do not have all of these properties, and hence there is a need for new approaches.

The Indigo Isomer Epindolidione as a Redox-Active Bridging Ligand for Diruthenium Complexes.

Epindolidione (H L), a heteroatom-modified analogue of tetracene and a structural isomer of indigo, forms dinuclear complexes with [RuX ] , X=bpy (2,2'-bipyridine, [1] ) or pap (2-phenylazopyridine, [2] ), in its doubly deprotonated bridging form μ-L . The dications in compounds meso-[1](ClO ) and meso-[2](ClO ) , [X Ru(μ-L)RuX ](ClO ) , contain five-membered chelate rings N-C-C-O-Ru with π bridged metals at an intramolecular distance of 7.19 Å.

Recapitulating early development of mouse musculoskeletal precursors of the paraxial mesoderm .

Body skeletal muscles derive from the paraxial mesoderm, which forms in the posterior region of the embryo. Using microarrays, we characterize novel mouse presomitic mesoderm (PSM) markers and show that, unlike the abrupt transcriptome reorganization of the PSM, neural tube differentiation is accompanied by progressive transcriptome changes. The early paraxial mesoderm differentiation stages can be efficiently recapitulated using mouse and human pluripotent stem cells.