Search

ABSTRACTEscapin is an l-amino acid oxidase that acts on lysine to produce hydrogen peroxide (H2O2), ammonia, and equilibrium mixtures of several organic acids collectively called escapin intermediate products (EIP). Previous work showed that the combination of synthetic EIP and H2O2functions synergistically as an antimicrobial toward diverse planktonic bacteria. We initiated the present study to investigate how the combination of EIP and H2O2affected bacterial biofilms, using Pseudomonas aeruginosaas a model. Specifically, we examined concentrations of EIP and H2O2that inhibited biofilm formation or fostered disruption of established biofilms. High-throughput assays of biofilm formation using microtiter plates and crystal violet staining showed a significant effect from pairing EIP and H2O2, resulting in inhibition of biofilm formation relative to biofilm formation in untreated controls or with EIP or H2O2alone. Similarly, flow cell analysis and confocal laser scanning microscopy revealed that the EIP and H2O2combination reduced the biomass of established biofilms relative to that of the controls. Area layer analysis of biofilms posttreatment indicated that disruption of biomass occurs down to the substratum. Only nanomolar to micromolar concentrations of EIP and H2O2were required to impact biofilm formation or disruption, and these concentrations are significantly lower than those causing bactericidal effects on planktonic bacteria. Micromolar concentrations of EIP and H2O2combined enhanced P. aeruginosaswimming motility compared to the effect of either EIP or H2O2alone. Collectively, our results suggest that the combination of EIP and H2O2may affect biofilms by interfering with bacterial attachment and destabilizing the biofilm matrix.

This patent review covers the contents of Hoffman-La Roche and Siena Biotech's patent application WO2012156284 titled ‘1,3-Oxazines as BACE1 and/or BACE2 Inhibitors.' Beta-site amyloid precursor protein-converting enzyme (BACE1) and BACE2 activities are reported to support the claimed compounds' use as therapeutics for Alzheimer's disease and type II diabetes, respectively. A common core motif of the claimed compounds is the six-membered 1,3-oxazine system. To gain access to the S3 and S3 subpocket of the BACE1 active site, various linkers are described including nitrogen- and oxygen-based, aryl, and amide-based linkers. Of the 65 compounds claimed, 6 had IC50s less than 100 nM in the BACE1 cell assay. Cellular BACE2 inhibition data are reported for 20 compounds with 2 under 100 nM.

We spend a significant part of our lives chatting about other people. In other words, we all gossip. Although sometimes a contentious topic, various researchers have shown gossip to be fundamental to social life---from small groups to large, formal organizations. Adopting the Enron email dataset and natural language techniques, we present the first study of gossip in a large CMC corpus. We find that workplace gossip is common at all levels of the organizational hierarchy, with people most likely to gossip with their peers and that it is more likely for an email to contain gossip if targeted to a smaller audience. Also, gossip appears as often in personal exchanges as it does in formal business communication. Exploring the sentiment of gossip, we observe that gossip is in fact quite often negative. Our study provides empirical evidence of an under-researched yet important societal phenomenon and provides empirical insights by testing existing gossip theories originating from anthropology, on a real world large email dataset.

The GriPhyN virtual data system provides a suite of components and services for data‐intensive sciences that enables scientists to systematically and efficiently describe, discover, and share large‐scale data and computational resources. We describe the design and implementation of such middleware services in terms of a virtual data system interface called Chiron, and present virtual data integration examples from the QuarkNet education project and from functional‐MRI‐based neuroscience research. The Chiron interface also serves as an online ‘educator’ for virtual data applications. Copyright © 2005 John Wiley & Sons, Ltd.

Recent studies of peptide dimers linked by Trp‐Trp (ditryptophan) crosslinks suggest that the crosslinks can reinforce antiparallel β‐structure. Depending on environment, gramicidins A, B and C form either helical ion channels with parallel β‐structure or non‐functional pores with antiparallel β‐structure. In the channel conformation of the gramicidins Trp9 and Trp15 are close in space, but in the pore conformation Trp9 and Trp15 are far apart. We hypothesized that a ditryptophan crosslink between Trp9 and Trp15 could pre‐organize gramicidin in an active conformation. To test the potential for pre‐organization, an intramolecular ditryptophan crosslink was formed between Trp9 and Trp15 in a W13F mutant of gramicidin B. Photooxidative conditions were shown to generate ditryptophan crosslinks in low yields. While not preparatively useful, photooxidative tryptophan crosslinking may have implications for protein aging processes like cataract formation. The ditryptophan crosslink in the gramicidin B mutant substantially lowered the antibiotic activity of the gramicidin B mutant, unlike the ditryptophan crosslink in the antibiotic X‐indolicidin. The biaryl chromophore generated diagnostic Cotton effects in the CD spectrum that revealed the absolute stereochemistry of the biaryl chromophore, but the biaryl chromophore obscured diagnostic features below 220 nm. However, changes in peptide conformation were reflected in changes in the biaryl region of the CD spectrum above 240 nm. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.

Study objective:Medical chart reviews are often used in emergency medicine research. However, the reliability of data abstracted by chart reviews is seldom examined critically. The objective of this investigation was to determine the proportion of emergency medicine research articles that use data from chart reviews and the proportions that report methods of case selection, abstractor training, monitoring and blinding, and interrater agreement. Methods:Research articles published in three emergency medicine journals from January 1989 through December 1993 were identified. The articles that used chart reviews were analyzed. Results:Of 986 original research articles that were identified, 244 (25%; 95% confidence interval [CI], 22% to 28%) relied on chart reviews. Inclusion criteria were described in 98% (95% CI, 96% to 99%), and 73% (95% CI, 67% to 79%) defined the variables being analyzed. Other methods were seldom mentioned: abstractor training, 18% (95% CI, 13% to 23%); standardized abstraction forms, 11% (95% CI, 7% to 15%); periodic abstractor monitoring, 4% (95% CI, 2% to 7%); and abstractor blinding to study hypotheses, 3% (95% CI, 1% to 6%). Interrater reliability was mentioned in 5% (95% CI, 3% to 9%) and tested statistically in .4% (95% CI, 0% to 2%). A 15% random sample of articles was reassessed by a second investigator; interrater agreement was high for all eight criteria. Conclusion:Chart review is a common method of data collection in emergency medicine research. Yet, information about the quality of the data is usually lacking. Chart reviews should be held to higher methodologic standards, or the conclusions of these studies may be in error. [Gilbert EH, Lowenstein SR, Koziol-McLain J, Barta DC, Steiner J: Chart reviews in emergency medicine research: Where are the methods? Ann Emerg MedMarch 1996;27:305-308.]

The use of biofilms for the degradation of recalcitrant environmental contaminants or for the production of secondary metabolites necessitates understanding and controlling gene expression. In this work, dual labeling with green fluorescent protein (GFP) variants was used to investigate inducible gene expression in a biofilm. Colocalization of GFP emissions was used to determine regions of attached cells and to correlate structure and activity within the biofilm. The labeling strategy reported here is unique in that the two GFP signals were distinguished by differential excitation rather than differential emission.