TGF-β1 induction of the adenine nucleotide translocator 1 in astrocytes occurs through Smads and Sp1 transcription factors

Background  

The adenine nucleotide translocator 1 (Ant1) is an inner mitochondrial membrane protein involved with energy mobilization during oxidative phosphorylation. We recently showed that rodent Ant1 is upregulated by transforming growth factor-beta (TGF-β) in reactive astrocytes following CNS injury. In the present study, we describe the molecular mechanisms by which TGF-β1 regulates Ant1 gene expression in cultured primary rodent astrocytes.     

Laurent-Padé approximants to four kinds of Chebyshev polynomial expansions. Part II: Clenshaw-Lord type approximants

Laurent-Padé (Chebyshev) rational approximantsP _m (w, w ⁻¹)/Q _n (w, w ⁻¹) of Clenshaw-Lord type [2,1] are defined, such that the Laurent series ofP _m /Q _n matches that of a given functionf(w, w ⁻¹) up to terms of orderw ^±(m+n) , based only on knowledge of the Laurent series coefficients off up to terms inw ^±(m+n) . This contrasts with the Maehly-type approximants [4,5] defined and computed in part I of this paper [6], where the Laurent series ofP _m matches that ofQ _n f up to terms of orderw ^±(m+n ), but based on knowledge of the series coefficients off up to terms inw ^±(m+2n). The Clenshaw-Lord method is here extended to be applicable to Chebyshev polynomials of the 1st, 2nd, 3rd and 4th kinds and corresponding rational approximants and Laurent series, and efficient systems of linear equations for the determination of the Padé-Chebyshev coefficients are obtained in each case. Using the Laurent approach of Gragg and Johnson [4], approximations are obtainable for allm≥0,n≥0. Numerical results are obtained for all four kinds of Chebyshev polynomials and Padé-Chebyshev approximants. Remarkably similar results of formidable accuracy are obtained by both Maehly-type and Clenshaw-Lord type methods, thus validating the use of either.     

Laurent–Padé Approximants to Four Kinds of Chebyshev Polynomial Expansions. Part I. Maehly Type Approximants

Laurent Padé–Chebyshev rational approximants, A _m (z,z ^–1)/B _n (z,z ^–1), whose Laurent series expansions match that of a given function f(z,z ^–1) up to as high a degree in z,z ^–1 as possible, were introduced for first kind Chebyshev polynomials by Clenshaw and Lord [2] and, using Laurent series, by Gragg and Johnson [4]. Further real and complex extensions, based mainly on trigonometric expansions, were discussed by Chisholm and Common [1]. All of these methods require knowledge of Chebyshev coefficients of f up to degree m+n. Earlier, Maehly [5] introduced Padé approximants of the same form, which matched expansions between f(z,z ^–1)B _n (z,z ^–1) and A _m (z,z ^–1). The derivation was relatively simple but required knowledge of Chebyshev coefficients of f up to degree m+2n. In the present paper, Padé–Chebyshev approximants are developed not only to first, but also to second, third and fourth kind Chebyshev polynomial series, based throughout on Laurent series representations of the Maehly type. The procedures for developing the Padé–Chebyshev coefficients are similar to that for a traditional Padé approximant based on power series [8] but with essential modifications. By equating series coefficients and combining equations appropriately, a linear system of equations is successfully developed into two sub-systems, one for determining the denominator coefficients only and one for explicitly defining the numerator coefficients in terms of the denominator coefficients. In all cases, a type (m,n) Padé–Chebyshev approximant, of degree m in the numerator and n in the denominator, is matched to the Chebyshev series up to terms of degree m+n, based on knowledge of the Chebyshev coefficients up to degree m+2n. Numerical tests are carried out on all four Padé–Chebyshev approximants, and results are outstanding, with some formidable improvements being achieved over partial sums of Laurent–Chebyshev series on a variety of functions. In part II of this paper [7] Padé–Chebyshev approximants of Clenshaw–Lord type will be developed for the four kinds of Chebyshev series and compared with those of the Maehly type.     

Carbanion reactivity, kinetic and equilibrium studies of sigma-adduct formation and elimination in the reactions of 4-nitrobenzofurazan derivatives with nitroalkane anions

1H NMR studies are reported of the reactions in [2H(6)]-DMSO of 4-nitrobenzofurazan, 2a, and its 7-chloro- and 7-methoxy-derivatives, 2b and 2c respectively, with anions derived from nitromethane, 3, nitroethane, 4, and 2-nitropropane, 5. The initial reactions result in sigma-adduct formation by carbanion attack at the 5-position of 2a-c and in the case of reaction of 2a with 5 the adduct at the 7-position is also observed. These reactions may be followed by base catalysed elimination of nitrous acid to yield anionic alkene derivatives. Kinetic and equilibrium measurements of these reactions were made spectrophotometrically in methanol. The carbon nucleophilicities of the carbanions decrease in the order 3> 4> 5, as also found in their reactions with benzhydrylium cations, and are much lower than the nucleophilicities of some cyano-substituted carbanions. Comparison with corresponding sigma-adduct forming reactions of 1,3,5-trinitrobenzene, TNB, show that here 2 and TNB have similar electrophilicity, although the value of the intrinsic rate coefficient k(o) = 0.05, for reaction of 2 is rather lower than that, k(o) = 0.20, for the TNB reactions. Literature data suggest that for reaction with a variety of nucleophiles 2 and TNB show similar electrophilicities. Measurements of the rates of elimination of nitrous acid from some 5-adducts in methanol catalysed by methoxide ions are reported. Values of rate constants may be influenced both by steric requirements at the reaction centre and by the electronic effects of the 7-substituent.     

Reaction prospecting by 31P NMR: enantioselective rhodium-DuPhos catalysed addition of ZnMe2 to diphenylphosphinoylimines

Chiral shift ³¹P NMR spectroscopy allows the identification of ligand leads in asymmetric catalyst systems for ZnMe₂ addition to ArCHNP(O)Ph₂. Subsequent GC-based optimisation shows [RhCl(CH₂CH₂)₂]₂ and (R,R)-MeDuPhos to be the optimal pre-catalyst combination (product in 78–93% ee). Transmetallation of [(MeDuPhos)Rh{N(P(O)Ph₂–CHMeAr}] with ZnMe₂ appears to be the rate limiting step of the catalytic cycle as competing coordination by the imine starting material leads to Ph₂P(O)NHCH₂Ar via MVP hydrogen-transfer. This limitation can largely be overcome by the slow addition of the imine.     

Kinetic and equilibrium studies of anilinoalkanesulfonate formation

(1)H NMR studies of the reactions of some hydroxyalkanesulfonates, 1, with aniline derivatives, 2, show the formation at equilibrium of anilinoalkanesulfonates, 3. Kinetic studies in water are consistent with a mechanism involving dissociation of 1 to give the parent aldehyde, which reacts with 2 to give a carbinolamine. Acid-catalysed dehydration of the carbinolamine yields an iminium ion which reacts rapidly with sulfite to give the product 3. Study of the variation with pH of the rate constants of the reaction indicates a change in the nature of the rate-determining step from carbinolamine formation to carbinolamine dehydration as the pH is increased. Variations in values of rate and equilibrium constants with the nature of 1 and 2 are discussed in terms of electronic and steric effects.     

Formation of aminosilane-functionalized mica for atomic force microscopy imaging of DNA

Factors affecting the functionalization of mica with aminosilanes, in particular, aminopropyltriethoxysilane (APTES-mica), formed from the vapor phase have been systematically studied. The relative humidity (RH) during vapor deposition has been varied, and postdeposition treatment through baking has been used, as well as the comparison of mono and trifunctionality, to investigate how optimal surfaces for AFM imaging of DNA are formed. It is found that the stability of the APTES layers is a consequence of lateral polymerization and not covalent attachment to the mica substrate. At low RH (<25%), DNA adopts an open, well-resolved conformation, whereas at >25% RH, DNA surface-induced condensation occurs. Contact mode AFM scratching experiments show that two main structures of the silane layer exist at different humidity: a monolayer exists at RH < 25%, and a bilayer structure exists at RH > 25%. Finally, structural changes that these two layer types undergo after baking at 150 degrees C were investigated by AFM and X-ray photoelectron spectroscopy (XPS), and these now prevented DNA from binding to the APTES-mica, except in the presence of Mg(II) ions.     

Protonation Preferentially Stabilizes Minor Tautomers of the Halouracils: IRMPD Action Spectroscopy and Theoretical Studies

Tautomerization induced by protonation of halouracils may increase their efficacy as anti-cancer drugs by altering their reactivity and hydrogen bonding characteristics, potentially inducing errors during DNA and RNA replication. The gas-phase structures of protonated complexes of five halouracils, including 5-fluorouracil, 5-chlorouracil, 5-bromouracil, 5-iodouracil, and 6-chlorouracil are examined via infrared multiple photon dissociation (IRMPD) action spectroscopy and theoretical electronic structure calculations. IRMPD action spectra were measured for each complex in the IR fingerprint region extending from ~1000 to 1900?cm(-1) using the free electron laser (FELIX). Correlations are made between the measured IRMPD action spectra and the linear IR spectra for the stable low-energy tautomeric conformations computed at the B3LYP/6-311+G(2d,2p)//B3LYP/6-31G* level of theory. Absence of an intense band(s) in the IRMPD spectrum arising from the carbonyl stretch(es) that are expected to appear near 1825?cm(-1) provides evidence that protonation induces tautomerization and preferentially stabilizes alternative, noncanonical tautomers of these halouracils where both keto functionalities are converted to hydroxyl groups upon binding of a proton. The weak, but measurable absorption, which does occur for these systems near 1835?cm(-1) suggests that in addition to the ground-state conformer, very minor populations of excited, low-energy conformers that contain keto functionalities are also present in these experiments.     

Laurent-Padé approximants to four kinds of Chebyshev polynomial expansions. Part I. Maehly type approximants

Laurent Padé-Chebyshev rational approximants,A _m (z,z ⁻¹)/B _n (z, z ⁻¹), whose Laurent series expansions match that of a given functionf(z,z ⁻¹) up to as high a degree inz, z ⁻¹ as possible, were introduced for first kind Chebyshev polynomials by Clenshaw and Lord [2] and, using Laurent series, by Gragg and Johnson [4]. Further real and complex extensions, based mainly on trigonometric expansions, were discussed by Chisholm and Common [1]. All of these methods require knowledge of Chebyshev coefficients off up to degreem+n. Earlier, Maehly [5] introduced Padé approximants of the same form, which matched expansions betweenf(z,z ⁻¹)B _n (z, z ⁻¹)). The derivation was relatively simple but required knowledge of Chebyshev coefficients off up to degreem+2n. In the present paper, Padé-Chebyshev approximants are developed not only to first, but also to second, third and fourth kind Chebyshev polynomial series, based throughout on Laurent series representations of the Maehly type. The procedures for developing the Padé-Chebyshev coefficients are similar to that for a traditional Padé approximant based on power series [8] but with essential modifications. By equating series coefficients and combining equations appropriately, a linear system of equations is successfully developed into two sub-systems, one for determining the denominator coefficients only and one for explicitly defining the numerator coefficients in terms of the denominator coefficients. In all cases, a type (m, n) Padé-Chebyshev approximant, of degreem in the numerator andn in the denominator, is matched to the Chebyshev series up to terms of degreem+n, based on knowledge of the Chebyshev coefficients up to degreem+2n. Numerical tests are carried out on all four Padé-Chebyshev approximants, and results are outstanding, with some formidable improvements being achieved over partial sums of Laurent-Chebyshev series on a variety of functions. In part II of this paper [7] Padé-Chebyshev approximants of Clenshaw-Lord type will be developed for the four kinds of Chebyshev series and compared with those of the Maehly type.     

Detecting and approximating fault lines from randomly scattered data

Discretely defined surfaces that exhibit vertical displacements across unknown fault lines can be difficult to approximate accurately unless a representation of the faults is known. Accurate representations of these faults enable the construction of constrained approximation models that can successfully overcome common problems such as over-smoothing. In this paper we review an existing method for detecting fault lines and present a new detection approach based on data triangulations and discrete Gaussian curvature (DGC). Furthermore, we show that if the fault line can be described non-parametrically, then accurate support vector machine (SVM) models can be constructed that are independent of the type of triangulation used in the detection algorithms. We shall also see that SVM models are particularly effective when the data produced by the detection algorithms are noisy. We compare the performances of the various new and established models.