Differential inhibition of postnatal brain,spinal cord and body growth by a growth hormone antagonist

Background  

Growth hormone (GH) plays an incompletely understood role in the development of the central nervous system (CNS). In this study, we use transgenic mice expressing a growth hormone antagonist (GHA) to explore the role of GH in regulating postnatal brain, spinal cord and body growth into adulthood. The GHA transgene encodes a protein that inhibits the binding of GH to its receptor, specifically antagonizing the trophic effects of endogenous GH.     

Fusion around the barrier for 7Li+12C

Fusion cross-sections for the ⁷Li + ¹²C reaction have been measured at energies above the Coulomb barrier by the direct detection of evaporation residues. The heavy evaporation residues with energies below 3 MeV could not be separated out from the α-particles in the spectrum and hence their contribution was estimated using statistical model calculations. The present work indicates that suppression of fusion cross-sections due to the breakup of ⁷Li may not be significant for ⁷Li + ¹²C reaction at energies around the barrier.     

Alternative synthetic routes to N-methyl-1,2,4-triazoline-3,5-dione (MeTAD) and other triazolinedione derivatives

N-Methyl-1,2,4-triazoline-3,5-dione (MeTAD) is a powerful electrophile and a versatile synthetic reagent. In this Letter we describe two methods for the synthesis of N-methylurazole, the direct precursor to MeTAD, on gram scales and in good yields. Both methods provide pure urazole while avoiding the necessity of large scale purification via column chromatography or recrystallization. One of the methods proved to be amenable for the synthesis of derivatives other than N-methyl.     

Synthesis of cis and trans bis-alkynyl complexes of Cr(III) and Rh(III) supported by a tetradentate macrocyclic amine: a spectroscopic investigation of the M(III)-alkynyl interaction

Alkynyl complexes of the type [M(cyclam)(CCR)(2)]OTf (where cyclam = 1,4,8,11-tetraazacyclotetradecane; M = Rh(III) or Cr(III); and R = phenyl, 4-methylphenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 1-naphthalenyl, 9-phenanthrenyl, and cyclohexyl) were prepared in 49% to 93% yield using a one-pot synthesis involving the addition of 2 equiv of RCCH and 4 equiv of BuLi to the appropriate [M(cyclam)(OTf)(2)]OTf complex in THF. The cis and trans isomers of the alkynyl complexes were separated using solubility differences, and the stereochemistry was characterized using infrared spectroscopy of the CH(2) rocking and NH bending region. All of the trans-[M(cyclam)(CCR)(2)]OTf complexes exhibit strong Raman bands between 2071 and 2109 cm(-1), ascribed to ν(s)(C≡C). The stretching frequencies for the Cr(III) complexes are 21-28 cm(-1) lower than for the analogous Rh(III) complexes, a result that can be interpreted in terms of the alkynyl ligands acting as π-donors. UV-vis spectra of the Cr(III) and Rh(III) complexes are dominated by strong charge transfer (CT) transitions. In the case of the Rh(III) complexes, these CT transitions obscure the metal centered (MC) transitions, but in the case of the Cr(III) complexes the MC transitions are unobscured and appear between 320 and 500 nm, with extinction coefficients (170-700 L mol(-1) cm(-1)) indicative of intensity stealing from the proximal CT bands. The Cr(III) complexes show long-lived (240-327 μs), structureless, MC emission centered between 731 and 748 nm in degassed room temperature aqueous solution. Emission characteristics are also consistent with the arylalkynyl ligands acting as π-donors. The Rh(III) complexes also display long-lived (4-21 μs), structureless, metal centered emission centered between 524 and 548 nm in degassed room temperature solution (CH(3)CN).     

Synthesis and mechanistic investigations of pH-responsive cationic poly(aminoester)s

The synthesis and degradation mechanisms of a class of pH-sensitive, rapidly degrading cationic poly(α-aminoester)s are described. These reactive, cationic polymers are stable at low pH in water, but undergo a fast and selective degradation at higher pH to liberate neutral diketopiperazines. Related materials incorporating oligo(α-amino ester)s have been shown to be effective gene delivery agents, as the charge-altering degradative behavior facilitates the delivery and release of mRNA and other nucleic acids in vitro and in vivo. Herein, we report detailed studies of the structural and environmental factors that lead to these rapid and selective degradation processes in aqueous buffers. At neutral pH, poly(α-aminoester)s derived from N-hydroxyethylglycine degrade selectively by a mechanism involving sequential 1,5- and 1,6-O→N acyl shifts to generate bis(N-hydroxyethyl) diketopiperazine. A family of structurally related cationic poly(aminoester)s was generated to study the structural influences on the degradation mechanism, product distribution, and pH dependence of the rate of degradation. The kinetics and mechanism of the pH-induced degradations were investigated by ¹H NMR, model reactions, and kinetic simulations. These results indicate that polyesters bearing α-ammonium groups and appropriately positioned N-hydroxyethyl substituents are readily cleaved (by intramolecular attack) or hydrolyzed, representing dynamic “dual function” materials that are initially polycationic and transform with changing environment to neutral products.

The synthesis and degradation mechanisms of a class of pH-sensitive, rapidly degrading cationic poly(α-aminoester)s are described.     

Activation of functional arylzincs prepared from aryl iodides and highly enantioselective addition to aldehydes

An easily available chiral ligand ( S)- 1 is found to activate the nucleophilic reaction of the arylzincs prepared in situ from the reaction of aryl iodides with Et(2)Zn. Both high yields and high enantioselectivity (up to >99% ee) for the reaction of these arylzincs with a variety of aldehydes are obtained. The mild reaction conditions and the good functional group tolerance make this catalytic asymmetric process synthetically useful.     

Detection of human and rodent 5-HT3B receptor subunits by anti-peptide polyclonal antibodies

Background  

The 5-HT₃ receptor is a member of a neurotransmitter-gated ion channel family which includes nicotinic acetylcholine, GABA_A, and glycine receptors. While antibodies specific for the 5-HT_3A receptor subunit are plentiful, and have revealed a wealth of structural and functional information, few antisera exist for the detection of 5-HT_3B receptor subunits. Here we describe the generation and characterisation of a rabbit polyclonal antiserum that specifically recognises 5-HT_3B receptor subunits     

Dibenzyl Structuresin a Macromolecular Chain. III. Dibenzyldiisocyanates Reactivity

The reactivity of the 2,2′-, 2,4′-, 4,4′-dibenzyldiisocyanate (2,2′-, 2,4′-, 4,4′-DBDI) with n-butanol in benzene has been studied. The concentrations of all species were monitored by using high performance liquid chromatography (HPLC). The reactivity of 4,4′-DBDI is similar to that of 4,4′-diphenylmethanediisocyanate (4,4′-MDI). Very strong intramolecular catalytic effects were noticed in the case of 2,2′-DBDI, probably due to the variable molecular geometry. These effects are responsible for the whole reaction pattern. The 2,4′-DBDI NCO ortho and para groups reactivities are different and comparable to that of 2,4-toluylenediisocyanate (2,4-TDI).     

Trueness, precision, and detectability for sampling and analysis of organic species in airborne particulate matter

Recovery, precision, limits of detection and quantitation, blank levels, calibration linearity, and agreement with certified reference materials were determined for two classes of organic components of airborne particulate matter, polycyclic aromatic hydrocarbons and hopanes, using typical sampling and gas chromatography/mass spectrometry analysis methods. These determinations were based on initial method proficiency tests and on-going internal quality control procedures. Recoveries generally ranged from 75% to 85% for all target analytes and collocated sample precision estimates were generally better than 20% for polycyclic aromatic hydrocarbons and better than 25% for hopanes. Results indicated substantial differences in data quality between the polycyclic aromatic hydrocarbons and hopanes. Polycyclic aromatic hydrocarbons demonstrated better collocated precision, lower method detection limits, lower blank levels, and better agreement with certified reference materials than the hopanes. The most serious area of concern was the disagreement between measured and expected values in the standard reference material for hopanes. With this exception, good data quality was demonstrated for all target analytes on all other data quality indicators.