Persistent tailoring of MSC activation through genetic priming.

Mesenchymal stem/stromal cells (MSCs) are an attractive platform for cell therapy due to their safety profile and unique ability to secrete broad arrays of immunomodulatory and regenerative molecules. Yet, MSCs are well known to require preconditioning or priming to boost their therapeutic efficacy. Current priming methods offer limited control over MSC activation, yield transient effects, and often induce the expression of pro-inflammatory effectors that can potentiate immunogenicity.

Persistent tailoring of MSC activation through genetic priming.

Mesenchymal stem/stromal cells (MSCs) are an attractive platform for cell therapy due to their safety profile and unique ability to secrete broad arrays of immunomodulatory and regenerative molecules. Yet, MSCs are well known to require preconditioning or priming to boost their therapeutic efficacy. Current priming methods offer limited control over MSC activation, yield transient effects, and often induce expression of pro-inflammatory effectors that can potentiate immunogenicity.

Compact engineered human mechanosensitive transactivation modules enable potent and versatile synthetic transcriptional control.

Engineered transactivation domains (TADs) combined with programmable DNA binding platforms have revolutionized synthetic transcriptional control. Despite recent progress in programmable CRISPR-Cas-based transactivation (CRISPRa) technologies, the TADs used in these systems often contain poorly tolerated elements and/or are prohibitively large for many applications. Here, we defined and optimized minimal TADs built from human mechanosensitive transcription factors.

Discovery of 4,4'-Dipyridylsulfide Analogs as "Switchable Electrophiles" for Covalent Inhibition.

Electrophilic heterocycles offer attractive features as covalent fragments for inhibitor and probe development. A focused library of heterocycles for which protonation can enhance reactivity (called "switchable electrophiles") is screened for inhibition of the proposed drug target dimethylarginine dimethylaminohydrolase (DDAH). Several novel covalent fragments are identified: 4-chloroquinoline, 4-bromopyridazine, and 4,4-dipyridylsulfide.

Resting Metabolic Rate and Lung Function in Wild Offshore Common Bottlenose Dolphins, , Near Bermuda.

Diving mammals have evolved a suite of physiological adaptations to manage respiratory gases during extended breath-hold dives. To test the hypothesis that offshore bottlenose dolphins have evolved physiological adaptations to improve their ability for extended deep dives and as protection for lung barotrauma, we investigated the lung function and respiratory physiology of four wild common bottlenose dolphins () near the island of Bermuda. We measured blood hematocrit (Hct, %), resting metabolic rate (RMR, l O ⋅ min), tidal volume (, l), respiratory frequency (, breaths ⋅ min), respiratory flow (l ⋅ min), and dynamic lung compliance (, l ⋅ cmHO) in air and in water, and compared measurements with published results from coastal, shallow-diving dolphins.