The first direct evaluation of the two-active site mechanism for chitin synthase

Chitin synthase polymerizes UDP-GlcNAc to form chitin (poly-beta(1,4)-GlcNAc) and is essential for fungal cell wall biosynthesis. The alternating orientation of the GlcNAc residues within the chitin chain has led to the proposal that chitin synthase possesses two active sites. We report the results of the first direct test of this possibility. Two simple uridine-derived dimeric inhibitors are shown to exhibit 10-fold greater inhibition than a monomeric control, consistent with the presence of two active sites. This observation has important implications for the development of antifungal agents, as well as the understanding of polymerizing glycosyltransferases.     

Modulating the efficiency of Ru(II) luminescence via ion binding-induced conformational restriction of bipyridyl ligands

Conformational restriction imposed upon Ru(bpy)32+ crown ether complexes by metal ion binding leads to enhanced luminescence.     

Thorium

Ohne Zusammenfassung     

Nachweis des Kobalts in Gegenwart von Nickel

Ohne Zusammenfassung     

Effectiveness of Photodynamic Therapy in Elimination of HPV‐16 and HPV‐18 Associated with CIN I in Mexican Women

This study aimed to determine the effectiveness of photodynamic therapy (PDT), using δ‐aminolevulinic acid (5‐ALA), in the elimination of premalignant cervical lesions in Mexican patients with human papillomavirus (HPV) infection and/or cervical intraepithelial neoplasia (CIN). Thirty women diagnosed with CIN I and/or positive for HPV participated in the study. Topical 6% 5‐ALA in gel form was applied to the uterine cervix; after 4 h, the lesion area was irradiated with a light dose of 200 J cm^?2 at 635 nm. This procedure was performed three times at 48‐h intervals. Clinical follow‐up was performed at 3, 6, and 12 months after the initial PDT administration, by colposcopy, cervical cytology, histopathological analysis, polymerase chain reaction, and hybrid capture. Of HPV‐infected patients without evidence of CIN I, 80% cleared the infection, while HPV associated with CIN I was eliminated in 83% of patients (P < 0.05). At 12 months, CIN I had regressed in 57% of patients, although this response was not statistically significant. PDT using 6% 5‐ALA is concluded to be effective in eliminating HPV infection associated or not with CIN I.     

Hilbert's objectivity

Detlefsen (1986) reads Hilbert's program as a sophisticated defense of instrumentalism, but Feferman (1998) has it that Hilbert's program leaves significant ontological questions unanswered. One such question is of the reference of individual number terms. Hilbert's use of admittedly “meaningless” signs for numbers and formulae appears to impair his ability to establish the reference of mathematical terms and the content of mathematical propositions ( and ). The paper traces the history and context of Hilbert's reasoning about signs, which illuminates Hilbert's account of mathematical objectivity, axiomatics, idealization, and consistency.     

Ein neues Verfahren zur Arsenbestimmung in organischen Substanzen

Ohne Zusammenfassung     

Structure Elucidation and Activity of Kolossin A,the D‐/L‐Pentadecapeptide Product of a Giant Nonribosomal Peptide Synthetase

The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium Photorhabdus luminescens. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates. Although it belongs to the growing class of D ‐/ L ‐peptide natural products, the encoded metabolite kolossin A was found to be largely devoid of antibiotic activity and is likely involved in interspecies communication. A stereoisomer of this peculiar natural product displayed high activity against Trypanosoma brucei rhodesiense, a recalcitrant parasite that causes the deadly disease African sleeping sickness.