Triclosan: An Instructive Tale

The Food and Drug Administration (FDA) recently released a final rule to ban triclosan and 18 other antimicrobial chemicals from soaps. We applaud this rule specifically because of the associated risks that triclosan poses to the spread of antibiotic resistance throughout the environment. This persistent chemical constantly stresses bacteria to adapt, and behavior that promotes antibiotic resistance needs to be stopped immediately when the benefits are null

Overlapping Protein-Encoding Genes in Pseudomonas fluorescens Pf0-1

The annotated genome sequences of prokaryotes seldom include overlapping genes encoded opposite each other by the same stretch of DNA. However, antisense transcription is becoming recognized as a widespread phenomenon in eukaryotes, and examples have been linked to important biological processes. Pseudomonas fluorescens inhabits aquatic and terrestrial environments, and can be regarded as an environmental generalist. The genetic basis for this ecological success is not well understood. In a previous search for soil-induced genes in P. fluorescens Pf0-1, ten antisense genes were discovered. These were termed ‘cryptic’ genes, as they had escaped detection by gene-hunting algorithms, and lacked easily recognizable promoters. In this communication, we designate such genes as ‘non-predicted’ or ‘hidden’. Using reverse transcription PCR, we show that at each of six non-predicted gene loci chosen for study, transcription occurs from both ‘sense’ and ‘antisense’ DNA strands. Further, at least one of these hidden antisense genes, iiv14, encodes a protein, as does the sense transcript, both identified by poly-histidine tags on the C-terminus of the proteins. Mutational and complementation studies showed that this novel antisense gene was important for efficient colonization of soil, and multiple copies in the wildtype host improved the speed of soil colonization. Introduction of a stop codon early in the gene eliminated complementation, further implicating the protein in colonization of soil. We therefore designate iiv14 “cosA”. These data suggest that, as is the case with eukaryotes, some bacterial genomes are more densely coded than currently recognized

Consumer antibacterial soaps: Effective or just risky?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55477/1/Consumer antibacterial soaps Effective or just risky.web 2007 aiello.pd

Proteomic Detection of Non-Annotated Protein-Coding Genes in Pseudomonas fluorescens Pf0-1

Genome sequences are annotated by computational prediction of coding sequences, followed by similarity searches such as BLAST, which provide a layer of possible functional information. While the existence of processes such as alternative splicing complicates matters for eukaryote genomes, the view of bacterial genomes as a linear series of closely spaced genes leads to the assumption that computational annotations that predict such arrangements completely describe the coding capacity of bacterial genomes. We undertook a proteomic study to identify proteins expressed by Pseudomonas fluorescens Pf0-1 from genes that were not predicted during the genome annotation. Mapping peptides to the Pf0-1 genome sequence identified sixteen non-annotated protein-coding regions, of which nine were antisense to predicted genes, six were intergenic, and one read in the same direction as an annotated gene but in a different frame. The expression of all but one of the newly discovered genes was verified by RT-PCR. Few clues as to the function of the new genes were gleaned from informatic analyses, but potential orthologs in other Pseudomonas genomes were identified for eight of the new genes. The 16 newly identified genes improve the quality of the Pf0-1 genome annotation, and the detection of antisense protein-coding genes indicates the under-appreciated complexity of bacterial genome organization

Antibacterial cleaning products and drug resistance

http://deepblue.lib.umich.edu/bitstream/2027.42/55419/1/Aiello A, Antibacterial cleaning products and drug resistance, 2005.pd

Integrating Escherichia coli Antimicrobial Susceptibility Data from Multiple Surveillance Programs

Collaboration between networks presents opportunities to increase analytical power and cross-validate findings. Multivariate analyses of 2 large, international datasets (MYSTIC and SENTRY) from the Global Advisory on Antibiotic Resistance Data program explored temporal, geographic, and demographic trends in Escherichia coli resistance from 1997 to 2001. Elevated rates of nonsusceptibility were seen in Latin America, southern Europe, and the western Pacific, and lower rates were seen in North America. For most antimicrobial drugs considered, nonsusceptibility was higher in isolates from men, older patients, and intensive care unit patients. Nonsusceptibility to ciprofloxacin was higher in younger patients, rose with time, and was not associated with intensive care unit status. In univariate analyses, estimates of nonsusceptibility from MYSTIC were consistently higher than those from SENTRY, but these differences disappeared in multivariate analyses, which supports the epidemiologic relevance of findings from the 2 programs, despite differences in surveillance strategies

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

The EDGE-CALIFA survey: validating stellar dynamical mass models with CO kinematics

Deriving circular velocities of galaxies from stellar kinematics can provide an estimate of their total dynamical mass, provided a contribution from the velocity dispersion of the stars is taken into account. Molecular gas (e.g., CO) on the other hand, is a dynamically cold tracer and hence acts as an independent circular velocity estimate without needing such a correction. In this paper we test the underlying assumptions of three commonly used dynamical models, deriving circular velocities from stellar kinematics of 54 galaxies (S0-Sd) that have observations of both stellar kinematics from the CALIFA survey, and CO kinematics from the EDGE survey. We test the Asymmetric Drift Correction (ADC) method, as well as Jeans, and Schwarzschild models. The three methods each reproduce the CO circular velocity at 1Re to within 10%. All three methods show larger scatter (up to 20%) in the inner regions (R < 0.4Re) which may be due to an increasingly spherical mass distribution (which is not captured by the thin disk assumption in ADC), or non-constant stellar M/L ratios (for both the JAM and Schwarzschild models). This homogeneous analysis of stellar and gaseous kinematics validates that all three models can recover Mdyn at 1Re to better than 20%, but users should be mindful of scatter in the inner regions where some assumptions may break down.Comment: 22 pages, 18 figures, Accepted for publication in MNRA

A general modeling and visualization tool for comparing different members of a group: application to studying tau-mediated regulation of microtubule dynamics

<p>Abstract</p> <p>Background</p> <p>Innumerable biological investigations require comparing collections of molecules, cells or organisms to one another with respect to one or more of their properties. Almost all of these comparisons are performed manually, which can be susceptible to inadvertent bias as well as miss subtle effects. The development and application of computer-assisted analytical and interpretive tools could help address these issues and thereby dramatically improve these investigations.</p> <p>Results</p> <p>We have developed novel computer-assisted analytical and interpretive tools and applied them to recent studies examining the ability of 3-repeat and 4-repeat tau to regulate the dynamic behavior of microtubules in vitro. More specifically, we have developed an automated and objective method to define growth, shortening and attenuation events from real time videos of dynamic microtubules, and demonstrated its validity by comparing it to manually assessed data. Additionally, we have used the same data to develop a general strategy of building different models of interest, computing appropriate dissimilarity functions to compare them, and embedding them on a two-dimensional plot for visualization and easy comparison. Application of these methods to assess microtubule growth rates and growth rate distributions established the validity of the embedding procedure and revealed non-linearity in the relationship between the tau:tubulin molar ratio and growth rate distribution.</p> <p>Conclusion</p> <p>This work addresses the need of the biological community for rigorously quantitative and generally applicable computational tools for comparative studies. The two-dimensional embedding method retains the inherent structure of the data, and yet markedly simplifies comparison between models and parameters of different samples. Most notably, even in cases where numerous parameters exist by which to compare the different samples, our embedding procedure provides a generally applicable computational strategy to detect subtle relationships between different molecules or conditions that might otherwise escape manual analyses.</p

Search for heavy neutrinos mixing with tau neutrinos

We report on a search for heavy neutrinos (\nus) produced in the decay D_s\to \tau \nus at the SPS proton target followed by the decay \nudecay in the NOMAD detector. Both decays are expected to occur if \nus is a component of $\nu_{\tau}$.\ From the analysis of the data collected during the 1996-1998 runs with $4.1\times10^{19}$ protons on target, a single candidate event consistent with background expectations was found. This allows to derive an upper limit on the mixing strength between the heavy neutrino and the tau neutrino in the \nus mass range from 10 to 190 $\rm MeV$. Windows between the SN1987a and Big Bang Nucleosynthesis lower limits and our result are still open for future experimental searches. The results obtained are used to constrain an interpretation of the time anomaly observed in the KARMEN1 detector.\Comment: 20 pages, 7 figures, a few comments adde