Microtermolides A and B from termite-associated Streptomyces sp. and structural revision of vinylamycin

Microtermolides A (1) and B (2) were isolated from a Streptomyces sp. strain associated with fungus-growing termites. The structures of 1 and 2 were determined by 1D- and 2D-NMR spectroscopy and high-resolution mass spectrometry. Structural elucidation of 1 led to the re-examination of the structure originally proposed for vinylamycin (3). Based on a comparison of predicted and experimental (1)H and (13)C NMR chemical shifts, we propose that vinylamycin's structure be revised from 3 to 4.     

Spectroscopic and photophysical properties of dUTP and internally DNA bound fluorophores for optimized signal detection in biological formats

Efficient signal generation in DNA-based assays requires understanding of the influence of fluorophore's interactions on the spectroscopic properties. The resulting changes in fluorescence intensity, quantum yield, emission anisotropy, and fluorescence lifetime provide straightforward tools for the study of molecular dynamics and interaction between labels and nucleic acids. Searching for bright fluorescent reporters for rolling circle amplification (RCA) as efficient signal enhancement strategy for biological formats, we investigated the spectroscopic properties of seven dyes: cyanines, rhodamines, and BODIPYs. They spectrally resemble Cy3, the most frequently used fluorophore in biodetection formats, and are measured in six samples (free dye, dye-dUTP, internally labeled ssDNA and dsDNA-single- and triple-labeled) using steady-state and time-resolved fluorometry. Special emphasis was dedicated to characterizing the nature of the interaction of these fluorophores differing in dye class, charge, and rigidity. Our results suggest dye charge and structure as main factors governing the dye's interactions, with DY-555 and Cy3B presenting the best candidates for our envisaged signal amplification strategy. This label comparison underlines the importance of a proper understanding of structure-property relations and dye-biomolecule interactions for reporter choice and presents a road map towards the design and interpretation of experiments using these labels on DNA of known sequence.     

The effects of binaural spectral resolution mismatch on Mandarin speech perception in simulated electric hearing

This study assessed the effects of binaural spectral resolution mismatch on the intelligibility of Mandarin speech in noise using bilateral cochlear implant simulations. Noise-vocoded Mandarin speech, corrupted by speech-shaped noise at 0 and 5?dB signal-to-noise ratios, were presented unilaterally or bilaterally to normal-hearing listeners with mismatched spectral resolution between ears. Significant binaural benefits for Mandarin speech recognition were observed only with matched spectral resolution between ears. In addition, the performance of tone identification was more robust to noise than that of sentence recognition, suggesting factors other than tone identification might account more for the degraded sentence recognition in noise.     

Molybdenum Cofactor Deficiency in Humans

Molybdenum cofactor (Moco) deficiency (MoCD) is characterized by neonatal-onset myoclonic epileptic encephalopathy and dystonia with cerebral MRI changes similar to hypoxic–ischemic lesions. The molecular cause of the disease is the loss of sulfite oxidase (SOX) activity, one of four Moco-dependent enzymes in men. Accumulating toxic sulfite causes a secondary increase of metabolites such as S-sulfocysteine and thiosulfate as well as a decrease in cysteine and its oxidized form, cystine. Moco is synthesized by a three-step biosynthetic pathway that involves the gene products of MOCS1, MOCS2, MOCS3, and GPHN. Depending on which synthetic step is impaired, MoCD is classified as type A, B, or C. This distinction is relevant for patient management because the metabolic block in MoCD type A can be circumvented by administering cyclic pyranopterin monophosphate (cPMP). Substitution therapy with cPMP is highly effective in reducing sulfite toxicity and restoring biochemical homeostasis, while the clinical outcome critically depends on the degree of brain injury prior to the start of treatment. In the absence of a specific treatment for MoCD type B/C and SOX deficiency, we summarize recent progress in our understanding of the underlying metabolic changes in cysteine homeostasis and propose novel therapeutic interventions to circumvent those pathological changes.     

Ordinary Papers

This paper deals with the systems of algebraic equations arising in the application of implicit Runge-Kutta methods.Equivalent conditions under which three wide classes of differential equations have unique solutions are presented. In addition, sufficient conditions for their existence are given.     

Experimental demonstration of hydrogen formation following the interaction of protons with positronium

In support of the positronium based reaction scheme for antihydrogen formation an experiment has been performed which has demonstrated hydrogen formation following proton impact on positronium. The cross section has been experimentally determined at proton energies of 11.3 keV, 13.3 keV and 15.8 keV, values of σ_H = 26(±9), 7.8(±2.3) and 7.6(± 4.4) × 10⁻¹⁶ cm² were obtained. The determination is in reasonable agreement with several recent calculations of the cross section and provides a well characterised process for antihydrogen formation. This revised version was published online in August 2006 with corrections to the Cover Date.     

A Catalytic Oxidative Quinone Heterofunctionalization Method: Synthesis of Strongylophorine‐26

The preparation of heteroatom‐substituted p‐quinones is ideally performed by direct addition of a nucleophile followed by in situ reoxidation. Albeit an appealing strategy, the reactivity of the p‐quinone moiety is not easily tamed and no broadly applicable method for heteroatom functionalization exists. Shown herein is that Co(OAc)₂ and Mn(OAc)₃?2 H₂O act as powerful catalysts for oxidative p‐quinone functionalization with a collection of O, N, and S nucleophiles, using oxygen as the terminal oxidant. Preliminary mechanistic observations and the first synthesis of the cytotoxic natural product strongylophorine‐26 is presented.