Significance: The kinesin-3 family is one of the largest among the kinesin superfamily and its members play important roles in a variety of cellular functions ranging from intracellular transport to mitosis. Defects in kinesin-3 transport have been implicated in a variety of neurodegenerative, developmental, and cancer diseases, yet the molecular mechanisms of kinesin-3 regulation and cargo transport are largely unknown. We show that kinesin-3 motors undergo cargo-mediated dimerization to transport cellular cargoes. We also show that dimerization results in kinesin-3 motors that are fast and superprocessive. Such high processivity has not been observed for any other motor protein and suggests that kinesin-3 motors are evolutionarily adapted to serve as the marathon runners of the cellular world.
Two water-soluble compounds based on a coumarin–pyridinium scaffold were synthesized for rapid and selective detection of sulfite. The detection strategy is possible through a Michael addition reaction of the sulfite to the cyano-vinyl double bond, distinguishable through the hypsochromic shifts in absorption and emission maxima. The probes exhibited high selectivity for sulfite, with a detection limit of 1.47 μM for dye 1 and 2.8 μM for dye 2 and a near instant response time of 10–20 seconds over other analytes and reactive sulfur species. Importantly, the probes also exhibit a robust colorimetric response in the presence of sulfite. Cellular imaging studies have demonstrated that the probes are non-toxic and suitable for the detection of sulfite levels in cells. Additionally, the probes have demonstrated sensitivity to detect endogenous sulfite levels in hepatic cancer cells.
1 January 2020 in Journal of Photochemistry and Photobiology B: Biology
Alcoholic liver disease (ALD) alters gut microbiota and tight junctions, causing bacterial components to enter the portal vein and induce oxidative stress-induced inflammation in the liver. Only corticosteroids and liver transplants are treatment options for severe alcoholic hepatitis. ALD’s pathophysiology is unknown. However, acetaldehyde’s toxic effects cause oxidative stress and intestinal permeability. This study investigates the influence of a synbiotic (a combination of aged garlic extract (AGE) and Lactobacillus rhamnosus MTCC1423) on colonic oxidative stress and inflammation in ALD male Wistar rats and Caco2 cells. MDA measurement by HPLC in CaCo2 cells, blood serum, and colon tissue demonstrated that synbiotic treatment in the ALD model reduces oxidative stress. Further, fecal high-throughput 16S rRNA gene sequencing revealed the microbiome’s shift towards Firmicutes in the synbiotic group compared to ethanol. In addition, DCFDA labeling and H/E staining demonstrate that the synbiotic is beneficial in inhibiting the development of ALD. In the colon, the synbiotic reduces the activation of CYP2E1 and the inflammatory markers TNF-a and IL-6 while elevating the mRNA expression of ZO-1, occludin, and IL-10. Synbiotics colonize Lactobacillus to restore barrier function and microbiota and reduce colon oxidative stress. Thus, a synbiotic combination can be used in ALD treatment.
27 January 2021 in Organic & Biomolecular Chemistry