Pyruvate dehydrogenase kinase 1 and 2 deficiency reduces high-fat diet-induced hypertrophic obesity and inhibits the differentiation of preadipocytes into mature adipocytes

Obesity is now recognized as a disease. This study revealed a novel role for pyruvate dehydrogenase kinase (PDK) in diet-induced hypertrophic obesity. Mice with global or adipose tissue-specific PDK2 deficiency were protected against diet-induced obesity. The weight of adipose tissues and the size of adipocytes were reduced. Adipocyte-specific PDK2 deficiency slightly increased insulin sensitivity in HFD-fed mice. In studies with 3T3-L1 preadipocytes, PDK2 and PDK1 expression was strongly increased during adipogenesis. Evidence was found for epigenetic induction of both PDK1 and PDK2. Gain- and loss-of-function studies with 3T3-L1 cells revealed a critical role for PDK1/2 in adipocyte differentiation and lipid accumulation. PDK1/2 induction during differentiation was also accompanied by increased expression of hypoxia-inducible factor-1α (HIF1α) and enhanced lactate production, both of which were absent in the context of PDK1/2 deficiency. Exogenous lactate supplementation increased the stability of HIF1α and promoted adipogenesis. PDK1/2 overexpression-mediated adipogenesis was abolished by HIF1α inhibition, suggesting a role for the PDK-lactate-HIF1α axis during adipogenesis. In human adipose tissue, the expression of PDK1/2 was positively correlated with that of the adipogenic marker PPARγ and inversely correlated with obesity. Similarly, PDK1/2 expression in mouse adipose tissue was decreased by chronic high-fat diet feeding. We conclude that PDK1 and 2 are novel regulators of adipogenesis that play critical roles in obesity.Subject terms: Mechanisms of disease, Obesity     

Culture age and drying time as variables of the AOAC Sporicidal Test

In the United States, the AOAC Sporicidal Activity of Disinfectants Method 966.04 is the standard for identifying a liquid chemical germicide as a sterilant. Furthermore, the highest level of a disinfectant must also be a sterilant as defined by Method 966.04, when used in its sterilant mode for a longer exposure time. The AOAC Sporicidal Test is also used as a part of the standard test methods to define a sterilant for Australia and the European Union. Many laboratories have identified variables of this test that can affect the sterilization exposure time for sterilants, or even the ability to classify a chemical as a sterilant. Method 966.04 requires spore-labeled porcelain penicylinders (cylinders) and silk suture loops, collectively referred to as carriers, to be dried for 24 h, but allows these carriers to be used for at least 7 days, in effect allowing a drying time of 24 h to at least 7 days. We tested the resistance of cylinders that had been labeled with Bacillus subtilis spores cultured for 72, 96, and 120 h, and dried for 24, 48, and 72 h against a 60 min exposure to 2.0% alkaline glutaraldehyde, and 2, 5, 10, 15, and 20 min exposures to 2.5N HCl. All the culture incubation and drying times met the standard of resistance to 2.5N HCI for at least 2.0 min at 20 degrees C, and all carriers contained at least 10(5) colony-forming units (CFU) of B. subtilis per carrier. However, for 3 repeated tests, regardless of incubation time, an average of 96% of the carriers were sterilized by the 2.0% glutaraldehyde after drying for 24 h, and an average of 61 % were sterilized after drying for 48 or 72 h. We propose that the variable of drying time be eliminated from Method 966.04.     

Separation of ritalin racemate and its by-product racemates by capillary electrophoresis

Ritalin, [(+)-threo]methylphenidate hydrochloride, is a chiral drug substance with two chiral centers. The drug substance may contain three pairs of enantiomers, [(+)-threo], [(-)-threo], [(+)-erythro] and [(-)-erythro] isomers, and its degradation products, threoritalinic acid racemate. Determination of the optical purity of ritalin drug substance and the amount of its by-product isomers is a critical step in the single-isomer drug development. In order to efficiently recognize the three pairs of enantiomers by one method, capillary electrophoresis (CE) was employed for the separation. The three pairs of enantiomers in CE showed different enantioselectivities with eight different types of CDs. Only 2,6-di-o-methyl-beta-cyclodextrin (DM-beta-CD) and carboxymethyl-beta-cyclodextrin (CM-beta-CD) showed enantioselectivity to all these pairs of enantiomers. With respect to separation resolution and efficiency, DM-beta-CD was chosen as the chiral selector. For optimization of the separation conditions, the concentration of DM-beta-CD, pH of the buffer solution, and temperature of the capillary were further studied.     

Synthesis and spectroscopic Investigation of Mixed-Ligand Copper Chelates containing 2-hydroxyaryloximes and N-disubstituted dithiocarbamates. Crystal and molecular structure of trans-bis[propanone, 1-(2-hydroxy-phenyl)oximato] copper(II)

A series of mixed-ligand copper(II) chelates containing the anion of 2-hydroxyaryloxime(oxime) and N,N-disubstituted dithiocarbamate(dtc), [Cu(dtc)(oxime)], was prepared and characterised. The spectra (IR, ESR, electronic excitation) indicate that the CuNOS₂ chromophore attains square planar geometry. The ESR observables suggest appreciable covalency. In the case of [Cu(Et₂dtc)(oxime)] chelates, however, the observed data suggest distortion from square planar arrangement to a square pyramidal, indicative of a possible dimerism. In addition, the structure of the trans-bis[propanone, 1-(2-hydroxyphenyl)-oximato]copper(II), Cu(C₉H₁₀NO₂)₂ was determined by X-ray diffraction (monoclinic, space group P2₁/n, a = 12.072(7) Å, b = 5.204(2) Å, c = 13.571(6) Å, β = 103.72(1)°, Z = 2). The molecule consists of discrete Cu(ppox)₂ monomeric units, where the Cu atom is in the equatorial plane bonded to two nitrogen atoms and two oxygen at distances of 1.949(2) and 1.882(2) Å, respectively.     

New organo-soluble polyimides for optical,microelectronic and fiber applications

A novel class of organo-soluble polyimides has been developed based on monomers containing twisted-biphenyl structures. Thus, 2, 2'-disubstituted-4, 4'-diaminobiphenyls and 2, 2'-disubstituted-4, 4', 5, 5'-biphenyltetracarboxylic dianhydrides have been prepared and polymerized in refluxing phenolic solvents. The polyimides, some of which are soluble in ketone and ether solvents, can be readily solution cast into colorless thin films. The rigid polymer chains align parallel to the substrate surface (in-plane orientation) during the casting process, which results in anisotropy in the film properties. The anisotropy in the refractive index has been used in the development of compensation layers for liquid crystal displays. The polymers have also been dry jet-wet spun from phenolic solutions to afford fibers that display tensile strengths of 3.5 GPa and moduli of 130 GPa.     

Silicon-29 NMR study of the formation of monomethoxysilicic acid in methanolic alkaline silicate solutions

Silicon-29 NMR spectra were obtained for more than 20 aqueous alkaline silicate solutions containing methanol. A signal assigned to CH₃OSi(OH)₃ or one of its deprotonated congeners was studied in detail for the first time for the solution conditions involved. Its appearance was monitored as a function of the solution compositions. The pseudo-equilibrium constant for its formation is of the order of 0.65. Copyright © 2001 John Wiley & Sons, Ltd.     

Applications of quantum cascade lasers for sensitive trace gas measurements of CO, CH4, N2O and HCHO

We describe here a sensitive quantum cascade laser absorption spectrometer (QCLAS) employed for aircraft based measurements during the GABRIEL 2005 and HOOVER 2006 and 2007 campaigns. This 3-channel instrument measures CO, HCHO, CH₄ and N₂O using a 64-m path double corner cube White cell. Performance of the instrument was examined for the four species and precisions for CO, N₂O and CH₄ were measured in the field to be 0.5, 0.5 and 0.7% respectively (2σ). The 1σ detection limit for HCHO was ∼500 pptv for a 2 s average, while signal averaging of the HCHO over a 2 min time interval resulted in a 150 pptv detection limit with a duty cycle of 60%. PACS  82.80.Gk; 07.88.+y; 42.62.-b; 92.60.H-     

Mechanochemistry: opportunities for new and cleaner synthesis

The aim of this critical review is to provide a broad but digestible overview of mechanochemical synthesis, i.e. reactions conducted by grinding solid reactants together with no or minimal solvent. Although mechanochemistry has historically been a sideline approach to synthesis it may soon move into the mainstream because it is increasingly apparent that it can be practical, and even advantageous, and because of the opportunities it provides for developing more sustainable methods. Concentrating on recent advances, this article covers industrial aspects, inorganic materials, organic synthesis, cocrystallisation, pharmaceutical aspects, metal complexes (including metal-organic frameworks), supramolecular aspects and characterization methods. The historical development, mechanistic aspects, limitations and opportunities are also discussed (314 references).     

Surface-enhanced Raman scattering study of the kinetics of self-assembly of carboxylate-terminated n-alkanethiols on silver

Adsorption of 11-mercaptoundecanoic acid (MUA) on silver from methanol and aqueous solutions was monitored in situ by surface-enhanced Raman scattering (SRES) spectroscopy. While adsorption of MUA from methanol is a one-step formation of a thiol-bound monolayer, SERS spectra reveal that monolayer formation from aqueous solution involves interactions of both carboxylate and thiol groups of MUA with the silver surface. Several Raman scattering bands, including the ν(C-S), ν(s)(COO(-)), and ν(C-C), were used to investigate the evolution of the structure of adsorbed MUA on silver surfaces. The time-dependent profiles of these bands for assembly from aqueous solution indicate a multistep process, which is initiated by the binding of both carboxylate and thiol groups to silver, producing a mixture of gauche and trans conformations. In a subsequent step, the COO-Ag interactions are displaced by stronger S-Ag bonds, leading to ordering of the resulting monolayer with formation of a complete SAM with all-trans conformations. The results also showed that the adsorption process depended strongly on the solution pH and surface potential of the metal. These factors can significantly affect the participation and displacement of -COO(-) during self-assembly of MUA from aqueous solution.     

Galois representations,automorphic forms,and the Sato-Tate Conjecture

The present text consists of notes of several lectures on the proof of the Sato-Tate Conjecture given up through 2008. The goal of the lectures was to explain the statement and the main ideas of the proof. The notes are somewhat dated; shortly after they were written, the author, together with Bernet-Lamb, Geraghty, and Taylor, were able to prove the analogue of the Sato-Tate conjecture for all elliptic modular forms. In particular, Theorems 2.4 and 2.5 are not conditional, and the condition on the j-invariant in Theorem 1.1 is superfluous. Moreover, the methods of proof outlined in sections 3 and 4 have been generalized and extended in a number of ways, notably in a series of articles by Barnet-Lamb, Gee, Geraghty, and Taylor, by Thorne, and by Calegari and Geraghty.