multiplex imaging of dynamic neurochemical networks with designed far-red dopamine sensors.

Neurochemical signals like dopamine (DA) play a crucial role in a variety of brain functions through intricate interactions with other neuromodulators and intracellular signaling pathways. However, studying these complex networks has been hindered by the challenge of detecting multiple neurochemicals simultaneously. To overcome this limitation, we developed a single-protein chemigenetic DA sensor, HaloDA1.

Long-Term Single-Molecule Tracking in Living Cells using Weak-Affinity Protein Labeling.

Single-particle tracking (SPT) has become a powerful tool to monitor the dynamics of membrane proteins in living cells. However, permanent labeling strategies for SPT suffer from photobleaching as a major limitation, restricting observation times, and obstructing the study of long-term cellular processes within single living cells. Here, we use exchangeable HaloTag Ligands (xHTLs) as an easy-to-apply labeling approach for live-cell SPT and demonstrate extended observation times of individual living cells of up to 30 minutes.

Gentle Rhodamines for Live-Cell Fluorescence Microscopy.

Rhodamines have been continuously optimized in brightness, biocompatibility, and color to fulfill the demands of modern bioimaging. However, the problem of phototoxicity caused by the excited fluorophore under long-term illumination has been largely neglected, hampering their use in time-lapse imaging. Here we introduce cyclooctatetraene (COT) conjugated rhodamines that span the visible spectrum and exhibit significantly reduced phototoxicity.

Impaired Suppression of Plasma Lipid Extraction and its Partitioning Away from Muscle by Insulin in Humans with Obesity.

Context: Humans with obesity and insulin resistance exhibit lipid accumulation in skeletal muscle, but the underlying biological mechanisms responsible for the accumulation of lipid in the muscle of these individuals remain unknown.

Objective: We investigated how plasma insulin modulates the extraction of circulating triglycerides (TGs) and non-esterified fatty acids (NEFAs) from ingested and endogenous origin in the muscle of lean, insulin-sensitive humans (Lean-IS) and contrasted these responses to those in humans with obesity and insulin resistance (Obese-IR).

Methods: The studies were performed in a postprandial state associated with steady-state plasma TG concentrations.

Metal-free introduction of primary sulfonamide into electron-rich aromatics.

We report herein a direct and practical synthesis of arylsulfonamides from electron-rich aromatic compounds by using generated -sulfonylamine as the active electrophile. Substrates include derivatives of aniline, indole, pyrrole, furan, styrene and so on. The reaction proceeds under mild conditions and tolerates many sensitive functional groups such as alkyne, acetate, the trifluoromethoxy group or acetoxymethyl ester.