The lymphoid-specific tyrosine phosphatase (Lyp) has generated enormous interest because a single-nucleotide polymorphism in the gene (PTPN22) encoding Lyp produces a gain-of-function mutant phosphatase that is associated with several autoimmune diseases, including type I diabetes, rheumatoid arthritis, Graves disease, and systemic lupus erythematosus. Thus, Lyp represents a potential target for a broad spectrum of autoimmune disorders. Unfortunately, no Lyp inhibitor has been reported. In addition, little is known about the structure and biochemical mechanism that directly regulates Lyp function. Here, we report the identification of a bidentate salicylic acid-based Lyp inhibitor I-C11 with excellent cellular efficacy. Structural and mutational analyses indicate that the inhibitor binds both the active site and a nearby peripheral site unique to Lyp, thereby furnishing a solid foundation upon which inhibitors with therapeutic potency and selectivity can be developed. Moreover, a comparison of the apo-and inhibitor-bound Lyp structures reveals that the Lypspecific region S 35 TKYKADK 42 , which harbors a PKC phosphorylation site, could adopt either a loop or helical conformation. We show that Lyp is phosphorylated exclusively at Ser-35 by PKC both in vitro and in vivo. We provide evidence that the status of Ser-35 phosphorylation may dictate the conformational state of the insert region and thus Lyp substrate recognition. We demonstrate that Ser-35 phosphorylation impairs Lyp's ability to inactivate the Src family kinases and down-regulate T cell receptor signaling. Our data establish a mechanism by which PKC could attenuate the cellular function of Lyp, thereby augmenting T cell activation.crystal structure ͉ enzyme regulation ͉ Lyp inhibitor ͉ phosphorylation
Ketonic carbonyl groups are catalytic active sites for oxidative dehydrogenation (ODH) reactions on carbon nanotubes. The quantity of these groups could be calculated from chemical titration with hydrazine compounds. ODH catalytic activity of nanocarbon is directly correlated with surface concentration of ketonic carbonyl groups, and the turnover frequency normalized by the number of active sites reflects the intrinsic activity of nanocarbon catalysts.
Ferroalloys are added during secondary steelmaking to impart special properties to the steel. Depending upon the ferroalloy quality this may lead to the formation of inclusions. The present knowledge lacks in the exact content of the individual elements and the nature of inclusions dispersed in the ferroalloys. In order to broaden the knowledge concerning ferroalloy quality, eight different ferroalloys (i.e. FeMo, FeNb, HCFeMn, LCFeMn, FeTi70, FeTi35, FeSi75 and FeP) were characterised for their impurity content. The samples were investigated for chemical analysis (inductively coupled plasma atomic emission spectroscopy and Leco combustion technique) and microstructural analysis (SEM energy dispersive spectroscopy). These impurities are linked to the ferroalloy manufacturing route. The inclusions observed in the microstructure are in good agreement with the inclusions extracted by the dissolution technique. In the present manuscript, the possible influence of ferroalloy quality over steel cleanliness is evaluated in the context of the impurities extracted and observed in the ferroalloys.
Physical and chemical insights into the nature and quantity of the active sites and the intrinsic catalytic activity of nanocarbon materials in alkane oxidative dehydrogenation (ODH) reactions are reported using a novel in situ chemical titration process. A study on the structure-function relationship reveals that the active sites are identical both in nature and function on various nanocarbon catalysts. Additionally, the quantity of the active sites could be used as a metric to normalize the reaction rates, and thus to evaluate the intrinsic activity of nanocarbon catalysts. The morphology of the nanocarbon catalysts at the microscopic scale exhibits a minor influence on their intrinsic ODH catalytic activity. The number of active sites calculated from the titration process indicates the number of catalytic centers that are active (that is, working) under the reaction conditions.
Domain of unknown function 1644 (DUF1644) is a highly conserved amino acid sequence motif present only in plants. Analysis of expression data of the family of DUF1644-containing genes indicated that they may regulate responses to abiotic stress in rice. Here we present our discovery of the role of OsSIDP366, a member of the DUF1644 gene family, in response to drought and salinity stresses in rice. Transgenic rice plants overexpressing OsSIDP366 showed enhanced drought and salinity tolerance and reduced water loss as compared to that in the control, whereas plants with downregulated OsSIDP366 expression levels using RNA interference (RNAi) were more sensitive to salinity and drought treatments. The sensitivity to abscisic acid (ABA) treatment was not changed in OsSIDP366-overexpressing plants, and OsSIDP366 expression was not affected in ABA-deficient mutants. Subcellular localization analysis revealed that OsSIDP366 is presented in the cytoplasmic foci that colocalized with protein markers for both processing bodies (PBs) and stress granules (SGs) in rice protoplasts. Digital gene expression (DGE) profile analysis indicated that stress-related genes such as SNAC1, OsHAK5 and PRs were upregulated in OsSIDP366-overexpressing plants. These results suggest that OsSIDP366 may function as a regulator of the PBs/SGs and positively regulate salt and drought resistance in rice.
The importance of recycling and producing rare earth (RE) materials has been highlighted by the critical raw materials study in the European Union (EU). Oxide-fluoride electrolysis is one of the dominant technologies to produce rare earth metals (REMs) or alloys. The solubility of rare earth oxides (REOs) is one of the critical issues during this process. In this research, a model is developed to predict the REO solubility in molten fluorides, based on the systematic analysis of different influential factors and fundamental understanding of the dissolution reactions. The average relative deviation of the model from the experimental data extracted from the literature is 8% for Nd 2 O 3 and 7% for Y 2 O 3 , respectively, which is well within the experimental uncertainty. The fitting parameters can indicate the influence of different composition quantitatively. It is also found that the solubility is correlated with the ion charge density of the cations in the molten salts.
Nucleophilic
sites on nanocarbon catalysts act as promoters for
homolytic cleavage of aliphatic C–H bond. In this study, we
report a hybrid catalyst composed of Mo2C and nitrogen-doped
onion-like carbon (NOLC) with enhanced capability for C–H bond
activation in direct dehydrogenation (DH) reaction of ethylbenzene
(EB). The enhanced activity of the Mo2C/NOLC catalyst over
unmodified NOLC in EB DH is attributable to the promoted C–H
bond activation by Mo2C, as characterized by the lower
activation energy and the kinetic isotope effect using deuterated
EB. Our XPS, XRD, and Raman spectroscopy results show that the hybrid
catalyst is structurally robust under the reaction condition. The
increase in nucleophilicity of the oxygen active sites in NOLC is
evidenced by an overall shift of the O 1s peaks to lower binding energies
after Mo2C modification. The DFT calculation further provides
mechanistic insights into the electron-transfer process from Mo2C to the ketonic carbonyl groups.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.