Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice

Deafness is the most common form of sensory impairment in humans. Mutations in unconventional myosins have been found to cause deafness in humans and mice. The mouse recessive deafness mutation, Snell's waltzer, contains an intragenic deletion in an unconventional myosin, myosin VI (locus designation, Myo6). The requirement for Myo6 for proper hearing in mice makes this gene an excellent candidate for a human deafness disorder. Here we report the cloning and characterization of the human unconventional myosin VI (locus designation, MYO6) cDNA. The MYO6 gene maps to human chromosome 6q13. The isolation of the human gene makes it now possible to determine if mutations in MYO6 contribute to the pathogenesis of deafness in the human population.     

Characterization of the elastin binding domain in the cell-surface 25-kDa elastin-binding protein of staphylococcus aureus (EbpS)

Our previous studies have established that a cell-surface 25-kDa elastin-binding protein of Staphylococcus aureus (EbpS) mediates binding of this pathogen to the extracellular matrix protein elastin. Results from binding assays examining the activity of various EbpS fragments suggested that the elastin recognition domain is contained within the first 59 amino acids. In this report, we have used functional analyses with synthetic peptides and recombinant truncated forms of EbpS to localize the elastin binding domain to a 21-amino acid region contained within residues 14-34 of EbpS. Further evidence for the importance of this domain was obtained by demonstrating that the inhibitory activity of anti-EbpS antibodies on staphylococcal elastin binding was neutralized when these antibodies were pre-absorbed with a truncated recombinant EbpS construct containing residues 1-34. Overlapping synthetic peptides corresponding to EbpS residues 14-36 were then generated and tested for elastin binding activity to define further the elastin binding domain, and results from these studies showed that sequences spanning amino acids Gln14-Asp23, Asp17-Asp23, and Thr18-Glu34 inhibit binding of Staphylococcus aureus to elastin. Our analyses indicate that the hexameric sequence Thr18-Asn-Ser-His-Gln-Asp23 is the minimal sequence common to all active synthetic peptides, proteolytic fragments, and recombinant constructs of EbpS. Furthermore, substitution of Asp23 with Asn abrogated the blocking activity of the synthetic peptides, demonstrating the requirement for a charged amino acid at this location. The composite data indicate that staphylococcal elastin binding is mediated by a discrete domain defined by short peptide sequences in the amino-terminal extracellular region of EbpS.     

High performance low power array multiplier using temporal tiling

Digital multipliers are a major source power dissipation in digital signal processors. Array architecture is a popular technique to implement these multipliers due to its regular compact structure. High power dissipation in these structures is mainly due to the switching of a large number of gates during multiplication. In addition, much power is also dissipated due to a large number of spurious transitions on internal nodes. Timing analysis of a full adder, which is a basic building block in array multipliers, has resulted in a different array connection pattern that reduces power dissipation due to the spurious transition activity. Furthermore, this connection pattern also improves the multiplier throughput. This array pattern is based on creating a compact tiled structure, wherein the shape of a tile represents the delay through that tile. That is, a compact structure created using these tiles is nothing but a structure with high throughput. Such a temporal tiling technique can also be applied to other digital circuits. Based on our simulation studies, a temporally tiled array multiplier achieves 50% and 35% improvements in delay and power dissipation compared to a conventional array multiplier. Improvement in delay can be traded for power using voltage reduction techniques     

The folding of centromeric DNA strands into intercalated structures: a physicochemical and computational study

We have carried out a physicochemical and computational analysis on the stability of the intercalated structures formed by cytosine-rich DNA strands. In the computational study, the electrostatic energy components have been calculated using a Poisson-Boltzmann model, and the non-polar energy components have been computed with a van der Waals function and/or a term dependent on the solvent-accessible surface area of the molecules. The results have been compared with those obtained for Watson-Crick duplexes and with thermodynamic data derived from UV experiments. We have found that intercalated DNA is mainly stabilized by very favorable electrostatic interactions between hydrogen-bonded protonated and neutral cytosines, and by non-polar forces including the hydrophobic effect and enhanced van der Waals contacts. Cytosine protonation electrostatically promotes the association of DNA strands into a tetrameric structure. The electrostatic interactions between stacked C.C+ pairs are strongly attenuated by the reaction field of the solvent, and are modulated by a complex interplay of geometric and protonation factors. The forces stabilizing intercalated DNA must offset an entropic penalty due to the uptake of protons for cytosine protonation, at neutral pH, and also the electrostatic contribution to the solvation free energy. The latter energy component is less favorable for protonated DNA due to the partial neutralization of the negative charge of the molecule, and probably affects other protonated DNA and RNA structures such as C+-containing triplexes.     

Effect of roundup and tordon 202C herbicides on antibody production in mice

Female CD-1 mice were exposed to Tordon 202C (2,4-dichlorophenoxyacetic acid [2,4-D] and picloram) or Roundup (glyphosate) in drinking water for 26 d at concentrations ranging from 0 to 0.42% or from 0 to 1.05%, respectively. The mice were inoculated with sheep red blood cells to produce a T-lymphocyte, macrophage dependent antibody response on day 21 of the herbicide exposure period. Tordon 202C dosing reduced weight gain and water consumption at the 0.42% level of exposure. Roundup exposure did not alter weight gain or water consumption. Antibody production was unaffected by Roundup dosing, suggesting that Roundup is unlikely to cause immune dysfunction under normal application conditions. In contrast, all levels of Tordon 202C exposure reduced antibody production by as much as 45%. The immunosuppressive activity of Tordon 202C was associated with levels more than 12 x the normal application level, although it was not determined which component of the formulation was responsible for the immunosuppression effect. The presence of immune alteration subsequent to exposure to Tordon 202C at levels marginally above the normal application levels suggests that chronic exposure to Tordon 202C in the environment has the potential to alter immune function.     

Thoracoscopic-assisted pulmonary resection in lung cancer

BACKGROUND: Thoracoscopic-assisted pulmonary resection for lung cancer is controversial. The appropriateness of this approach has to be compared with the golden standard of an open resection. METHODS: This study consists of 66 patients with a clinical stage 1 disease. A thoracoscopic exploration was executed in 41 patients. Only in 16 cases was a thoracoscopic resection finally possible. The clinical and pathological TNM classification, the histological types and the surgical procedure are reported. The reasons for conversion are documented. RESULTS: To investigate the appropriateness of the thoracoscopic approach we evaluated only the pathologically proven stage 1 disease in both groups. Postoperative complications, hospital stay and survival are compared. CONCLUSION: Until now we can conclude that there is no adverse effect on survival because of the thoracoscopic approach.