Notes

Assays for finding arrestin discussion using GPCRs.
Methyl-coenzyme M reductase (MCR), which contains the nickel hydrocorphinoid cofactor F430, is responsible for biological methane generation under anaerobic conditions via a reaction mechanism which has not been completely elucidated. In OTX008 cost , myoglobin reconstituted with an artificial cofactor, nickel(I) tetradehydrocorrin (NiI(TDHC)), is used as a protein-based functional model for MCR. The reconstituted protein, rMb(NiI(TDHC)), is found to react with methyl donors such as methyl p-toluenesulfonate and trimethylsulfonium iodide with methane evolution observed in aqueous media containing dithionite. Moreover, rMb(NiI(TDHC)) is found to convert benzyl bromide derivatives to reductively debrominated products without homocoupling products. The reactivity increases in the order of primary > secondary > tertiary benzylic carbons, indicating steric effects on the reaction of the nickel center with the benzylic carbon in the initial step. In addition, Hammett plots using a series of para-substituted benzyl bromides exhibit enhancement of the reactivity with introduction of electron-withdrawing substituents, as shown by the positive slope against polar substituent constants. These results suggest a nucleophilic SN2-type reaction of the Ni(I) species with the benzylic carbon to provide an organonickel species as an intermediate. The reaction in D2O buffer at pD 7.0 causes a complete isotope shift of the product by +1 mass unit, supporting our proposal that protonation of the organonickel intermediate occurs during product formation. Although the turnover numbers are limited due to inactivation of the cofactor by side reactions, the present findings will contribute to elucidating the reaction mechanism of MCR-catalyzed methane generation from activated methyl sources and dehalogenation.In recent years, the search for glassy and ceramic Li+ superionic conductors has received significant attention, mainly due to the renaissance of interest in all-solid-state batteries. Here, we report the mechanochemical synthesis of metastable Li7GeS5Br, which is, to the best of our knowledge, the first compound of the Li2S-GeS2-LiBr system. Applying combined synchrotron X-ray diffraction and neutron powder diffraction, we show Li7GeS5Br to crystallize in the F4̅3m space group and to be isostructural with argyrodite-type Li6PS5Br, but with a distinct difference in the S2-/Br- site disorder (and improved anodic stability). Electrochemical impedance spectroscopy indicates an electrical (ionic) conductivity of 0.63 mS cm-1 at 298 K, with an activation energy for conduction of 0.43 eV. This is supported by temperature-dependent 7Li pulsed-field gradient-nuclear magnetic resonance spectroscopy measurements. Overall, the results demonstrate that novel (metastable) argyrodite-type solid electrolytes can be prepared via mechanochemistry that are not accessible by conventional solid-state synthesis routes.A luminescent lanthanide-titanium oxo cluster of Eu2Ti4(μ2-O)2(μ3-O)4(phen)2(tbza)10·4CH3CN (1, Eu2Ti4-phen-tbza, phen = 1,10-phenanthroline, Htbza = 4-tert-butylbenzoic acid) was prepared through the reaction of phen, Htbza, Eu(Ac)3·xH2O, and Ti(O i Pr)4 in acetonitrile. Its overall absolute quantum yield is 65.4% in solid state and 30.2% in CH2Cl2, and the detection limit of 1 for the nitrobenzene (NB) is 10.5 ppb. When the concentration of NB is 40 ppm, the luminescence quenching of 1 can be observed with the naked eye. Time-resolved excited-state decay measurements indicate that the static quenching process is dominated across the NB concentration of 0-9 ppm. The distinguishable shifts in 1H NMR spectra of NB together with 1 confirm the presence of π···π stacking interactions between the organic ligands in 1 and the NB, which plays a key contribution for the quenching of luminescence.Trivalent actinides generally exhibit ninefold coordination in solution. 2,6-Bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine (nPr-BTP), a tridentate nitrogen donor ligand, is known to form ninefold coordinated 13 complexes, [An(nPr-BTP)3]3+ (An = U, Pu, Am, Cm) in solution. We report a Cm(III) complex with tenfold coordination in solution, [Cm(nPr-BTP)3(NO3)]2+. This species was identified using time-resolved laser fluorescence spectroscopy (TRLFS), vibronic side band spectroscopy (VSBS), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT). Adding nitrate to a solution of the [Cm(nPr-BTP)3]3+ complex in 2-propanol shifts the Cm(III) emission band from 613.1 to 617.3 nm. This bathochromic shift is due to a higher coordination number of the Cm(III) ion in solution, in agreement with the formation of the [Cm(nPr-BTP)3(NO3)]2+ complex. The formation of this complex exhibits slow kinetics in the range of 5 to 12 days, depending on the water content of the solvent. Formation of a complex [Cm(nPtained if the nitrate is positioned on the C 2 axis of the D3 symmetrical [Cm(nPr-BTP)3]3+ complex with a bond distance of 413 pm. Combining results from TRLFS, VSBS, XPS, and DFT provides sound evidence for a unique tenfold coordinated Cm(III) complex in solution-a novelty in An(III) solution chemistry.l-Carnitine is essential in the intermediary metabolism of eukaryotes and is involved in the β-oxidation of medium- and long-chain fatty acids; thus, it has applications for medicinal purposes and as a dietary supplement. In addition, l-carnitine plays roles in bacterial physiology and metabolism, which have been exploited by the industry to develop biotechnological carnitine production processes. Here, on the basis of studies of l-carnitine metabolism in Escherichia coli and its activation by the transcriptional activator CaiF, a biosensor was developed. #link# It expresses a fluorescent reporter gene that responds in a dose-dependent manner to crotonobetainyl-CoA, which is an intermediate of l-carnitine metabolism in E. coli and is proposed to be a coactivator of CaiF. Moreover, a dual-input biosensor for l-carnitine and crotonobetaine was developed. As an application of the biosensor, potential homologues of the betaineCoA ligase CaiC from Citrobacter freundii, Proteus mirabilis, and Arcobacter marinus were screened and shown to be functionally active CaiC variants. These variants and the developed biosensor may be valuable for improving l-carnitine production processes.Amyloid-β (Aβ) aggregates are believed to be one of the main causes of Alzheimer's disease. Aβ peptides form fibrils having cross β-sheet structures mainly through primary nucleation, secondary nucleation, and elongation. In particular, self-catalyzed secondary nucleation is of great interest. Here, we investigate the adsorption of Aβ42 peptides to the Aβ42 fibril to reveal a role of adsorption as a part of secondary nucleation. We performed extensive molecular dynamics simulations based on replica exchange with solute tempering 2 (REST2) to two systems a monomeric Aβ42 in solution and a complex of an Aβ42 peptide and Aβ42 fibril. Results of our simulations show that the Aβ42 monomer is extended on the fibril. Furthermore, we find that the hairpin structure of the Aβ42 monomer decreases but the helix structure increases by adsorption to the fibril surface. These structural changes are preferable for forming fibril-like aggregates, suggesting that the fibril surface serves as a catalyst in the secondary nucleation process. In addition, the stabilization of the helix structure of the Aβ42 monomer on the fibril indicates that the strategy of a secondary nucleation inhibitor design for Aβ40 can also be used for Aβ42.The field of optogenetics uses genetically encoded photoswitches to modulate biological phenomena with high spatiotemporal resolution. We report a set of rationally designed optogenetic photoswitches that use the photolyase homology region of A. thaliana cryptochrome 2 (Cry2PHR) as a building block and exhibit highly efficient and tunable clustering in a blue-light dependent manner. CL6mN (Cry2-mCherry-LRP6c with N mutated PPPAP motifs) proteins were designed by mutating and/or truncating five crucial PPP(S/T)P motifs near the C-terminus of the optogenetic Wnt activator Cry2-mCherry-LRP6c, thus eliminating its Wnt activity. Light-induced CL6mN clusters have significantly greater dissociation half-lives than clusters of wild-type Cry2PHR. Moreover, the dissociation half-lives can be tuned by varying the number of PPPAP motifs, with the half-life increasing as much as 6-fold for a variant with five motifs (CL6m5) relative to Cry2PHR. Finally, we demonstrate the compatibility of CL6mN with previously reported Cry2-based photoswitches by optogenetically activating RhoA in mammalian cells.Alloying is an efficient chemistry to diversify the properties of metal nanoparticles; however, the atomic-level understandings of the composition-dependent physicochemical properties and their related biological performance are presently lacking. Here, we developed a full spectrum of alloy metal nanoclusters (NCs), Au x Ag25-x(MHA)18 (MHA = 6-mercaptohexanoic acid) with x = 0-25, and investigated their composition-dependent antimicrobial performance. Interestingly, we observed a U-shape antimicrobial behavior of Au x Ag25-x(MHA)18 NCs, where the alloy NCs showed decreased antimicrobial ability instead of the common trend of increasing. Detailed atomic-level characterizations of the AuAg NCs suggest that the decreased performance of alloy NCs is due to their enhanced stability after alloying, which can deactivate their capability in generating reactive oxygen species (ROS) that can kill the bacteria. More interestingly, the transition point of the antimicrobial performance was only obtained with our full-spectrum Au x Ag25-x(MHA)18 NCs, which indicates the importance of exploring the composition-dependent properties and application performance in a full-spectrum composition range. link2 A library of full-spectrum alloy NCs also provides a good platform to investigate other composition-dependent physicochemical and biological properties of metal NCs.Lattice resonances, the collective modes supported by periodic arrays of metallic nanoparticles, give rise to very strong and spectrally narrow optical responses. Thanks to these properties, which emerge from the coherent multiple scattering enabled by the periodic ordering of the array, lattice resonances are used in a variety of applications such as nanoscale lasing and biosensing. Here, we investigate the lattice resonances supported by bipartite nanoparticle arrays. We find that, depending on the relative position of the two particles within the unit cell, these arrays can support lattice resonances with a super- or subradiant character. While the former result in large values of reflectance with broad lineshapes due to the increased radiative losses, the latter give rise to very small linewidths and maximum absorbance, consistent with a reduction of the radiative losses. Furthermore, by analyzing the response of arrays with finite dimensions, we demonstrate that the subradiant lattice resonances of bipartite arrays require a much smaller number of elements to reach a given quality factor than the lattice resonances of arrays with single-particle unit cells. link3 The results of this work, in addition to advancing our knowledge of the optical response of periodic arrays of nanostructures, provide an efficient approach to obtain narrow lattice resonances that are robust to fabrication imperfections.
Read More: https://www.selleckchem.com/products/otx008.html