Endocannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate.

The endocannabinoid system (ECS), a signalling network with immunomodulatory properties, is a potential therapeutic target in multiple sclerosis (MS). Dimethyl fumarate (DMF) is an approved drug for MS whose mechanism of action has not been fully elucidated; the possibility exists that its therapeutic effects could imply the ECS. With the aim of studying if DMF can modulate the ECS, the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) were determined by liquid chromatography-mass spectrometry in peripheral blood mononuclear cells from 21 healthy donors (HD) and 32 MS patients at baseline and after 12 and 24 months of DMF treatment.

Combined chemosensitivity and chromatin profiling prioritizes drug combinations in CLL.

The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has substantially improved therapeutic options for chronic lymphocytic leukemia (CLL). Although ibrutinib is not curative, it has a profound effect on CLL cells and may create new pharmacologically exploitable vulnerabilities. To identify such vulnerabilities, we developed a systematic approach that combines epigenome profiling (charting the gene-regulatory basis of cell state) with single-cell chemosensitivity profiling (quantifying cell-type-specific drug response) and bioinformatic data integration.

Global survey of the immunomodulatory potential of common drugs.

Small-molecule drugs may complement antibody-based therapies in an immune-oncology setting, yet systematic methods for the identification and characterization of the immunomodulatory properties of these entities are lacking. We surveyed the immumomodulatory potential of 1,402 small chemical molecules, as defined by their ability to alter the cell-cell interactions among peripheral mononuclear leukocytes ex vivo, using automated microscopy and population-wide single-cell image analysis. Unexpectedly, ∼10% of the agents tested affected these cell-cell interactions differentially.

Uncommon dislocation processes at the incipient plasticity of stepped gold surfaces.

Gold vicinal surfaces (788), with a high density of steps, along with (111) flat surfaces taken as a reference, have been nanoindented and their resulting penetration curves and related defect structure comparatively analyzed by AFM and atomistic simulations. Stepped surfaces are shown to yield at smaller loads than (111) ones in agreement with calculations of the critical resolved shear stress needed to nucleate a dislocation. In the stepped surfaces, a novel intermediate state is identified in which the penetration curves depart from a Hertzian behavior prior to the appearance of pop-ins.

Dielectric properties of self-assembled layers of octadecylamine on mica in dry and humid environments.

Atomic force microscopy operating in noncontact electrostatic force mode was used to study the interaction of water with films of alkylamines and alkylsilanes on mica. The films efficiently block water adsorption except in exposed mica areas, where it strongly modifies the mobility of surface ions. We also studied the molecular orientation of octadecylamine molecules forming monolayers and multilayer islands.