α-CGRP disrupts amylin fibrillization and regulates insulin secretion: implications on diabetes and migraine

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).     

Conjugated enynes as a new type of substrates for olefin metathesis

[reaction: see text] It has been demonstrated for the first time that conjugated enynes can be employed as a facile substrate in olefin metathesis with the use of a bispyridine-substituted ruthenium benzylidene catalyst. Cross-metathesis of the enynes with alkenes turns out to proceed with preferential formation of (Z)-isomers over (E)-isomers up to >25:1 in moderate to good yields. The intramolecular version of conjugated enynes affords novel butadienyl cycloalkenes, which are a highly useful synthetic building blocks, in acceptable yields.     

Mono- and Dinuclear d(10) Metal Complexes of Hexakis(3,5-dimethylpyrazolyl)cyclotriphosphazene. Synthesis, Structures, and Unusual Solution Dynamic Behavior

Synthesis, structures, and unusual solution dynamic processes of d(10) metal complexes of hexakis(3,5-dimethylpyrazolyl)cyclotriphosphazene (L) are reported. Reaction systems with three MX(n):L mole ratios (MX(n) = d(10) metal halide) in CH(2)Cl(2) have resulted in the formation of [ICu(&mgr;,eta(3),eta(3)-L)CuI] (1), [Cl(2)Zn(&mgr;,eta(2),eta(3)-L)ZnCl(2)] (2), [Cl(2)Cd(&mgr;,eta(3),eta(3)-L)CdCl(2)] (3), and [(eta(3)-L)HgCl(2)] (4). These compounds were characterized by single crystal X-ray diffraction studies, and crystallographic data are given in the order of compound: crystal system; space group; unit cell parameters; Z; unique data (I > 2sigma(I)); R(1). 1.0.5CH(2)Cl(2): monoclinic; P2(1)/c; a = 8.268(4) ?; b = 22.365(5) ?; c = 23.325(8) ?, beta = 93.06(1) degrees; 4; 5736; 4.82. 2.CH(3)CN: monoclinic; P2(1)/c; a = 17.021(3) ?; b = 12.161(2) ?; c = 23.608(5) ?; beta = 107.72(1) degrees; 4; 5469; 3.16. 3.CH(2)Cl(2): monoclinic; P2(1)/n; a = 18.585(5) ?; b = 17.585(4) ?; c = 14.404(3) ?; beta = 102.71(2) degrees; 4; 3814; 3.65. The structure of 4 was attempted but resulted in data of low precision. Reaction of L with CuI and ZnCl(2) in an equimolar ratio afforded [ICu(&mgr;,eta(3),eta(3)-L)ZnCl(2)] (5) which crystallizes in monoclinic space group P2(1)/n with a = 22.876(5) ?, b = 21.594(4) ?, c = 9.177(2) ?, beta = 93.54(2) degrees, Z = 4, and R(1) = 7.00 for 3806 (I > 2sigma(I)) data. In all cases, metal halide centers except the Td zinc site in 2 are coordinated by L via a kappa(3)N binding core consisting of two nongeminal pyrazolyl nitrogen atoms and one phosphazene ring nitrogen atom. The eta(2)-N(2) coordination in 2 involves two geminal pyrazolyl nitrogen atoms. Factors which govern the nuclearity of the complex were partially demonstrated. The intermetallic distances in dinuclear metallophosphazenes range from 6.790 to 7.195 ?. The solution behavior of five compounds was studied by variable temperature (31)P{(1)H}, (1)H, and (113)Cd FT NMR spectroscopy. Compounds 1 and 4 are associated with fluxional motions involving A(2)B low-temperature limit spectrum while compounds 2 and 5 show solvent-dependent dynamic processes with ABX and A(2)B low-temperature limit spectral patterns. Compounds 3 constitutes a fluxional system involving three A(2)B species. Accounts of solution NMR spectra were attempted by using PANIC, by assuming the formation of new solution metallophosphazene species and by considering several types of dynamic processes such as a ring-around type hopping motion for the kappa(3)N metal site, a Td conformational change for the geminal pyrazolyl kappa(2)N metal site, and a wigwag motion for the nongeminal pyrazolyl kappa(2)N metal unit.     

Electrokinetic properties of sepiolite suspensions in different electrolyte media

The present paper deals with the electrokinetic characterization of sepiolite. A series of systematic zeta potential measurements have been carried out to determine the isoelectric point (iep) and potential-determining ions (pdi), and the effect of mono-, di-, and trivalent electrolytes such as NaCl, KCl, LiCl, NaNO(3), NaCH(3)COO, MgCl(2), CaCl(2), BaCl(2), CoCl(2), CuCl(2), Pb(NO(3))(2), Na(2)CO(3), Na(2)SO(4), AlCl(3), FeCl(3), and Na(3)PO(4) on the zeta potential of sepiolite. Zeta potential has been calculated with the aid of Smoluchowski's equation. Sepiolite yields an isoelectric point at pH 6.6. The zeta potential for the sepiolite has ranged from +23.3 mV at pH approximately 2 to -22.4 mV at pH approximately 8 at 20 +/- 2 degrees C in water. The valency of the ions have proven to have a great influence on the electrokinetic behavior of the suspension. Monovalent cations were found to have a weak effect, while di- and trivalent cations made the zeta potential positive. Charge reversal was observed for divalent cations at 1 x 10(-2) M and for trivalent cations at 3 x 10(-4) M. As a result, it can be said that monovalent cations are indifferent ions when di- and trivalent cations are potential-determining ions.     

Evaluation of interfacial toughness curve of bimaterial in submicron scale

A novel method combining the experimental data at only two different mixed mode fractures and an empirical interface toughness function has been proposed to establish the interfacial toughness function of a bimaterial in submicron scale. The modified four-point bend specimen was used in experiment to evaluate the first type of mixed mode fracture, while the sandwiched cantilever specimen was employed to get the second one. An empirical interface toughness function reflecting quite accurately the delamination behavior was adopted as a typical one. The obtained results investigated that the proposed method could be used to calibrate not only the interfacial fracture criteria at pure modes but also at any mixed mode fracture of bimaterials in submicron scale.     

Dimesogenic liquid crystal consisting of cholesterol and Schiff base moieties: dependence of LC properties on the spacer length and fluorination of the alkoxy tails

The liquid crystalline properties of two series of non‐symmetric liquid crystal dimers consisting of cholesterol and Schiff base moieties interconnected by ω‐oxyalkanoyl spacers of varying length are compared: one series (SBOC‐ n ) carry the octyloxy tail on the Schiff base mesogen, and the other (SBOF‐ n ) a perfluoroheptylmethyloxy tail. In general, compounds with the fluorinated alkoxy tail exhibited mesophases over a much wider temperature range than those with the alkoxy tail. The latter series favoured the formation of more diverse mesophases than the former. SBOC‐4, ‐5 and ‐7, and SBOF‐4, ‐5 and ‐10 formed the chiral smectic C phase.     

Improved Compatibility of Styrene-Maleic Anhydride Copolymer/Polyethylene Blends Through Reactive Mixing

Abstract

To improve the compatibility of styrene-maleic anhydride copolymer/low density polyethylene (SMA/LDPE) blends, LDPE grafted with 2-hydroxyethyl methacrylate-isophorone diisocyanate (LDPE-g-HI) was prepared and blended with SMA of which anhydride was converted to carboxylic acid (SMAAc). The infrared spectra of LDPE-g-HI established the presence of isocyanate group. In the blend morphology, some adhesions between the two phases and much finer dispersions were observed in the SMAAc/LDPE-g-HI blends, indicating that chemical reactions took place during the melt blending. The lower heat capacity change at the glass transition temperature demonstrated that chemical bonds were produced in the SMAAc/LDPE-g-HI blends. From the results of the rheological test, it was found that strong positive deviation from the mixing rule occurred in viscosity for the SMAAc/LDPE-g-HI blends, concerning with good adhesion and finer dispersions. In the measurement of tensile property, the improved mechanical properties for the SMAAc/LDPE-g-HI blends were shown.     

Unexpected formation of dinaphthoaza-17-crown-5 ether containing γ-aminopiperidine subunit

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