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101.
Amber L. H. Gray Aleksandra Antevska Benjamin A. Link Bryan Bogin Susan J. Burke Samuel D. Dupuy J. Jason Collier Zachary A. Levine Michael D. Karlstad Thanh D. Do 《Chemical science》2021,12(16):5853
Despite being relatively benign and not an indicative signature of toxicity, fibril formation and fibrillar structures continue to be key factors in assessing the structure–function relationship in protein aggregation diseases. The inability to capture molecular cross-talk among key players at the tissue level before fibril formation greatly accounts for the missing link toward the development of an efficacious therapeutic intervention for Type II diabetes mellitus (T2DM). We show that human α-calcitonin gene-related peptide (α-CGRP) remodeled amylin fibrillization. Furthermore, while CGRP and/or amylin monomers reduce the secretion of both mouse Ins1 and Ins2 proteins, CGRP oligomers have a reverse effect on Ins1. Genetically reduced Ins2, the orthologous version of human insulin, has been shown to enhance insulin sensitivity and extend the life-span in old female mice. Beyond the mechanistic insights, our data suggest that CGRP regulates insulin secretion and lowers the risk of T2DM. Our result rationalizes how migraine might be protective against T2DM. We envision the new paradigm of CGRP : amylin interactions as a pivotal aspect for T2DM diagnostics and therapeutics. Maintaining a low level of amylin while increasing the level of CGRP could become a viable approach toward T2DM prevention and treatment.CGRP concentration is elevated in migraine conditions. The protective effect of migraine against type 2 diabetes is attributed to the ability of CGRP to remodel human amylin aggregation and to suppress the secretion of mouse insulin 2 (the orthologue of human insulin). 相似文献
102.
García-Santos Mdel P González-Mancebo S Hernández-Benito J Calle E Casado J 《Journal of the American Chemical Society》2002,124(10):2177-2182
Nitrosation reactions of amino acids with an -NH(2) group [namely, six alpha-amino acids (glycine, alanine, alpha-aminobutyric acid, alpha-aminoisobutyric acid, valine, and norvaline); two beta-amino acids (beta-alanine and beta-aminobutyric acid), and one gamma-amino acid (gamma-aminobutyric acid)] were studied. Nitrosation was carried out in aqueous acid media, mimicking the conditions of the stomach lumen. The rate equation was r = k(3)(exp)[amino acid][nitrite](2), with a maximum k(3)(exp) value in the 2.3-2.7 pH range. The existence of an isokinetic relationship supports the argument that all the reactions share a common mechanism. A nitrosation mechanism is proposed, and the following conclusions are drawn: (i) Nitrosation reactions of amino acids with a primary amino group in acid media occur with dinitrogen trioxide as the main nitrosating agent. The finding that the nitrosation rate is proportional to the square of the nitrite concentration suggests that the yield of nitrosation products in the stomach would increase sharply with higher nitrate/nitrite intakes. (ii) Stomach hypochlorhydria could be a potential enhancer of in vivo amino acid nitrosation. (iii) The reactivity (k(3)()(exp)) [alpha-amino acids > beta-amino acids > gamma-amino acids] is the same as that found in a previous work for the alkylating potential of lactones formed from nitrosation products of the same amino acids. This implies that the nitrosation reactions of the most common natural amino acids are the most efficient precursors of the most powerful alkylating agents. (iv) The order of magnitude (10(7)-10(8) M(-1) s(-1)) of the bimolecular rate constants of nitrosation shows that such reactions occur through an encounter process. 相似文献
103.
Reaction of the optically active primary amine (S)-(—)--methylbenzylamine with trimethylaluminium in heptane affords the crystalline organoaluminium dimer (S)-(—)-(S)-(—)-[(C6H5)CH(CH3)NHA1(CH3)2]2. Isolated as large, colourless, extremely air-sensitive prismatic crystals, the title compound crystallizes in the orthorhombic space group P212121 with unit cell parameters a = 8.406(3), b = 15.505(4), c = 17.547(5) Å, V = 2287 Å3 and p = 1.03 g cm−3 for Z = 4. Least-squares refinement based on 1477 observed reflections converged at R = 0.056, Rw = 0.058. Methane was eliminated during the course of the reaction due to cleavage of A1---C and N---H bonds resulting in an asymmetric A12N2 fragment at the core of the organoaluminium dimer. The mean A1---C bond distance in the dimethylaluminium units is 1.930(8), while the mean A1---N bond distance is 1.950(5) Å. Specific rotation ([]D25 in CH2C12)of the dimer is determined to be - 20.6°. 相似文献
104.
105.
106.
Samuel Drapeau Andreas H. Hamel Michael Kupper 《Set-Valued and Variational Analysis》2016,24(2):253-275
This paper provides a unique dual representation of set-valued lower semi-continuous quasiconvex and convex functions. The results are based on a duality result for increasing set-valued functions. 相似文献
107.
Chen Hui Sharma Sunil K. Sharma Priyanka R. Chi Kai Fung Eric Aubrecht Katherine Keroletswe Ngonye Chigome Samuel Hsiao Benjamin S. 《Cellulose (London, England)》2021,28(13):8611-8628
Cellulose - Mercury contamination in drinking water is a worldwide problem due to its severely harming effects on the human body. A nanostructured natural bioadsorbent, carboxycellulose nanofiber... 相似文献
108.
Abstract Poly(lactic acid) macromonomers with methacrylate terminal functionality have been synthesized from the cyclic dimer of lactic acid (referred to as lactide) with 2-hydroxyethyl methacrylate (HEMA) as initiator and stannous 2-ethyl hexanoate as catalyst. The macromonomers were characterized with FT-IR, NMR, GPC, DSC, WAXS, and CD. The molecular weights of the macromonomers ranging from M n 1425 to 19,169 are predictable from the lactide/HEMA ratio in the polymerization feeds. The properties of the macromonomers vary with the stereochemistry of the lactide and the composition. Circular dichroism measurements demonstrate that there is little racemization during polymerization. 相似文献
109.
110.
Samuel Clark Ligon Konstanze Seidler Christian Gorsche Markus Griesser Norbert Moszner Robert Liska 《Journal of polymer science. Part A, Polymer chemistry》2016,54(3):394-406
The rapid and uncontrolled nature of network formation from di(meth)acrylate monomers produces high shrinkage stress and results in polymers with oftentimes brittle mechanical properties. Methods for regulating polymerization and network formation are sought. One option is the use of addition–fragmentation chain transfer (AFCT) agents, which are well known to control molecular weight and molecular weight distribution of monofunctional (meth)acrylates. A series of novel and previously described AFCT reagents were synthesized and screened with laser flash photolysis to determine reactivity. Well‐performing AFCT reagents were then tested in polymerizations with monofunctional and difunctional methacrylates. With monofunctional monomers, the molecular weight and polydispersity of the resultant linear polymers tend to decrease with the addition of AFCT agent. In copolymerization with dimethacrylate monomers, the AFCT agents were found to substantially lower and sharpen the glass transition. Sharpness of the glass transition is here indicative of a more regular and homogenous network. After coupling of the instruments, photorheology was performed simultaneously with real‐time IR to show an increase in monomer conversion at the time of gelation, which appears to have a positive effect on reducing shrinkage stress. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 394–406 相似文献