Four novel bis-(naphtho-gamma-pyrones) isolated from Fusarium species as inhibitors of HIV-1 integrase

Integration of viral DNA into host cell DNA is an essential step in retroviral (HIV-1) replication and is catalyzed by HIV-1 integrase. HIV-1 integrase is a novel therapeutic target and is the focus of efforts to identify effective inhibitors that will prevent/or cure HIV infections. Four novel naphtho-gamma-pyrones, belonging to the chaetochromin and ustilaginoidin family, were discovered as inhibitors of HIV-1 integrase from the screening of fungal extracts using a recombinant in vitro assay. These compounds inhibit both the coupled and strand transfer activity of HIV-1 integrase with IC(50) values of 1-3 and 4-12 microM, respectively. The discovery, structure elucidation, chemical modification and the structure-activity relationship of these compounds are described.     

Zinc ions stimulate the cooperative RNA binding of hordeiviral gammab protein

A small regulatory gammab protein of the Poa semilatent hordeivirus (PSLV) contains two zinc finger-like motifs separated by a basic motif in the N-terminal part and a C-terminal coiled-coil motif. Interactions of the recombinant PSLV gammab protein and its mutants with various RNAs (ssRNA, dsRNA, ssRNA oligonucleotides) and ssDNA were studied in gel-shift assays. The results demonstrated that zinc ions are essential for effective nucleic-acid-binding activity of the gammab protein, suggesting the important role of zinc finger motifs in these interactions. Deletion of the C-proximal coiled-coil region did not affect highly cooperative RNA-protein binding, indicating that the N-terminal part of the protein contributes to the protein-protein interactions needed for the protein-RNA cooperativity.     

Mouse to human comparative genetics reveals a novel immunoglobulin E-controlling locus on Hsa8q12

Atopy is a predisposition to hyperproduction of immunoglobulin E (IgE) against common environmental allergens. It is often associated with development of allergic diseases such as asthma, rhinitis, and dermatitis. Production of IgE is influenced by genetic and environmental factors. In spite of progress in the study of heredity of atopy, the genetic mechanisms of IgE regulation have not yet been completely elucidated. The analysis of complex traits can benefit considerably from integration of human and mouse genetics. Previously, we mapped a mouse IgE-controlling locus Lmr9 on chromosome 4 to a segment of <9 Mb. In this study, we tested levels of total IgE and 25 specific IgEs against inhalant and food allergens in 67 Czech atopic families. In the position homologous to Lmr9 on chromosome 8q12 marked by D8S285, we demonstrated a novel human IgE-controlling locus exhibiting suggestive linkage to composite inhalant allergic sensitization (limit of detection, LOD = 2.11, P = 0.0009) and to nine specific IgEs, with maximum LOD (LOD = 2.42, P = 0.0004) to plantain. We also tested 16 markers at previously reported chromosomal regions of atopy. Linkage to plant allergens exceeding the LOD > 2.0 was detected at 5q33 (D5S1507, LOD = 2.11, P = 0.0009) and 13q14 (D13S165, LOD = 2.74, P = 0.0002). The significant association with plant allergens (quantitative and discrete traits) was found at 7p14 (D7S2250, corrected P = 0.026) and 12q13 (D12S1298, corrected P = 0.043). Thus, the finding of linkage on chromosome 8q12 shows precision and predictive power of mouse models in the investigation of complex traits in humans. Our results also confirm the role of loci at 5q33, 7p14, 12q14, and 13q13 in control of IgE. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Dynamic formation of optically trapped microstructure arrays for biosensor applications

We explore the dynamic properties of multiple-beam optical traps to manipulate arrays of microstructures for biosensor applications. Multiple optical traps are generated by a virtually loss-less transformation of input phase patterns into high-intensity trapping-beams. A direct image projection of the phase patterns enables an adjustable number of optical traps in addition to instantaneous control of the position, size, shape and intensity of each trapping-beam. We present experimental results showing various colloidal formations through dynamic optical manipulation of polystyrene microspheres and yeast cells in aqueous media. The experimental configurations are geared towards the use of multiple-beam optical traps for biosensor applications.