Chemical genetic analysis of FTY720- and Ca 2+ -sensitive mutants reveals a functional connection between FTY720 and membrane trafficking

FTY720, a sphingosine-1-phosphate (S1P) analog, is used as an immune modulator for the treatment of multiple sclerosis. Collecting evidence has suggested mode of action of FTY720 independent of S1P modulators. In fission yeast, FTY720 induces increased levels of intracellular Ca2 + and ROS. We have previously identified 49 genes that lead to the elimination of FTY720 sensitivity.

Here, we characterized the mutant FTY720-sensitive in terms of its relevance to Ca2 + homeostasis and identified 16 FTY720- and Ca2 + – sensitive mutant (mutant FCS). Most of FTY720-sensitive mutants showed increased Ca2 + levels and exhibited Ca2 + dysregulation by FTY720 treatment. One functional category between a gene deletion makes the cells vulnerable to FTY720 and Ca2 + including membrane trafficking Golgi / endosomal.

Specifically, FTY720, but not phosphorylated FTY720 able to stimulate Ca2 + increase, inhibit secretion of acid phosphatase in wild type cells. Importantly, defective secretion of Golgi / endosomal trafficking mutants, Vps45, or Ryh1 deletion, which is further exacerbated by FTY720. Our FCS screen also identified a mutant protein adenylyl cyclase CAP1 related and homologous Rictor Ste20, the real elimination of aggravated decrease secretion of FTY720-sensitive. Collectively, our data may suggest the synergistic effects of FTY720 in combination with interference on proliferation and secretion of Ca2 + homeostasis.

Chemical genetic analysis of FTY720- and Ca 2+ -sensitive mutants reveals a functional connection between FTY720 and membrane trafficking
Chemical genetic analysis of FTY720- and Ca 2+ -sensitive mutants reveals a functional connection between FTY720 and membrane trafficking

Chemical and Microstructural Characterization of pH and [Ca 2+] Dependent Sol-Gel Transition in mucin Biopolymers

Mucus is responsible for controlling the transport and barrier function in biological systems, and its properties can be significantly influenced by changes in the composition and the environment. In this study, the effects of pH and CaCl2 checked on the transition-to-gel solution of mucin, the main structural component of mucus. micro structural changes that correlate with macroscale viscoelastic behavior as a function of pH and adding calcium to use rheology, dynamic light scattering, zeta potential, surface tension, and FTIR spectroscopic characterization. mucin solution switched from the solution to the behavior of gel between pH 4-5 and correspondingly shown an increase of more than tenfold viscoelastic modulus.

Addition of CaCl2 increase the sol-gel transition to a pH value of ca. 6, with a two-fold increase in the loss modulus at low frequencies and a tenfold increase in storage modulus. Changing special ionic conditions [H +] and [Ca2 +] -modulated sol-gel transition pH, isoelectric point, and the viscoelastic properties for such reversible conformational changes with mucin form a network structure via non-covalent cross-links between chains of mucin.

efficient strategies in enhancing sensitivity important for ultrasensitive detection of tumor markers. In this work, based on a strategy of chemical adsorption-assisted label conversion triggered electroactivity sensing interface, the Ag / AgCl were made to improve the sensitivity of built sandwich-type amperometric immunosensor for ultrasensitive detection of carbohydrate antigen 19-9 (CA19-9).

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Briefly, polydopamine-Ag nanoparticles (Ag NP PDA), a precursor signal, combined with labeled antibody served as a label and melamine graphene oxide (GO-MA) substrate with the absorption capacity of the chemicals applied as intelligent sensing interface. After a successful incubation label, there is no response primitive at this time because of poor conductivity between the label and the electrodes. However, the presence of H2O2, Ag NP of labels can be engraved Ag ions, which are absorbed by the GO-MA to establish GO-MA-Ag as electroactive substrates.