Human pharmacology of 5-epi-sisomicin (Sch 22591) following intramuscular administration

5-epi-sisomicin was given as a single intramuscular injection of 1 mg/kg to six healthy male adults. Serum peak concentrations averaged 3.07 mg/l, the mean elimination half life was 179 min and the mean 24 h urinary recovery was 85.3%. Local and systemic tolerance was goo

Fecal Viral Community Responses to High-Fat Diet in Mice.

Alterations in diet can have significant impact on the host, with high-fat diet (HFD) leading to obesity, diabetes, and inflammation of the gut. Although membership and abundances in gut bacterial communities are strongly influenced by diet, substantially less is known about how viral communities respond to dietary changes. Examining fecal contents of mice as the mice were transitioned from normal chow to HFD, we found significant changes in the relative abundances and the diversity in the gut of bacteria and their viruses. Alpha diversity of the bacterial community was significantly diminished in response to the diet change but did not change significantly in the viral community. However, the diet shift significantly impacted the beta diversity in both the bacterial and viral communities. There was a significant shift away from the relatively abundant Siphoviridae accompanied by increases in bacteriophages from the Microviridae family. The proportion of identified bacteriophage structural genes significantly decreased after the transition to HFD, with a conserved loss of integrase genes in all four experimental groups. In total, this study provides evidence for substantial changes in the intestinal virome disproportionate to bacterial changes, and with alterations in putative viral lifestyles related to chromosomal integration as a result of shift to HFD.IMPORTANCE Prior studies have shown that high-fat diet (HFD) can have profound effects on the gastrointestinal (GI) tract microbiome and also demonstrate that bacteria in the GI tract can affect metabolism and lean/obese phenotypes. We investigated whether the composition of viral communities that also inhabit the GI tract are affected by shifts from normal to HFD. We found significant and reproducible shifts in the content of GI tract viromes after the transition to HFD. The differences observed in virome community membership and their associated gene content suggest that these altered viral communities are populated by viruses that are more virulent toward their host bacteria. Because HFD also are associated with significant shifts in GI tract bacterial communities, we believe that the shifts in the viral community may serve to drive the changes that occur in associated bacterial communities

Large Quantum Superpositions and Interference of Massive Nanometer-Sized Objects

We propose a method to prepare and verify spatial quantum superpositions of a nanometer-sized object separated by distances of the order of its size. This method provides unprecedented bounds for objective collapse models of the wave function by merging techniques and insights from cavity quantum optomechanics and matter wave interferometry. An analysis and simulation of the experiment is performed taking into account standard sources of decoherence. We provide an operational parameter regime using present day and planned technology.Comment: 4 pages, 2 figures, to appear in PR

Helicobacter pylori interstrain restriction-modification diversity prevents genome subversion by chromosomal DNA from competing strains

Helicobacter pylori, bacteria that colonize the human gastric mucosa, possess a large number of genes for restriction‐modification (R‐M) systems, and essentially, every strain possesses a unique complement of functional and partial R‐M systems. Nearly half of the H.pylori strains studied possess an active type IIs R‐M system, HpyII, with the recognition sequence GAAGA. Recombination between direct repeats that flank the R‐M cassette allows for its deletion whereas strains lacking hpyIIRM can acquire this cassette through natural transformation. We asked whether strains lacking HpyII R‐M activity can acquire an active hpyIIRM cassette [containing a 1.4 kb kanamycin resistance (aphA) marker], whether such acquisition is DNase sensitive or resistant and whether restriction barriers limit acquisition of chromosomal DNA. Our results indicate that natural transformation and conjugation‐like mechanisms may contribute to the transfer of large (4.8 kb) insertions of chromosomal DNA between H.pylori strains, that inactive or partial R‐M systems can be reactivated upon recombination with a functional allele, consistent with their being contingency genes, and that H.pylori R‐M diversity limits acquisition of chromosomal DNA fragments of ≥1 kb

A high-reflectivity high-Q micromechanical Bragg-mirror

We report on the fabrication and characterization of a micromechanical oscillator consisting only of a free-standing dielectric Bragg mirror with high optical reflectivity and high mechanical quality. The fabrication technique is a hybrid approach involving laser ablation and dry etching. The mirror has a reflectivity of 99.6%, a mass of 400ng, and a mechanical quality factor Q of approximately 10^4. Using this micromirror in a Fabry Perot cavity, a finesse of 500 has been achieved. This is an important step towards designing tunable high-Q high-finesse cavities on chip.Comment: 3 pages, 2 figure

Self-cooling of a micro-mirror by radiation pressure

We demonstrate passive feedback cooling of a mechanical resonator based on radiation pressure forces and assisted by photothermal forces in a high-finesse optical cavity. The resonator is a free-standing high-reflectance micro-mirror (of mass m=400ng and mechanical quality factor Q=10^4) that is used as back-mirror in a detuned Fabry-Perot cavity of optical finesse F=500. We observe an increased damping in the dynamics of the mechanical oscillator by a factor of 30 and a corresponding cooling of the oscillator modes below 10 K starting from room temperature. This effect is an important ingredient for recently proposed schemes to prepare quantum entanglement of macroscopic mechanical oscillators.Comment: 11 pages, 9 figures, minor correction

Role of Amoxicillin Serum Levels for Successful Prophylaxis of Experimental Endocarditis Due to Tolerant Streptococci

The importance of amoxicillin serum profiles for successful prophylaxis of experimental endocarditis in rats was assessed. Animals with catheter-induced vegetations were challenged intravenously with large inocula of Streptococcus sanguis and received one of the following amoxicillin dosages: single or multiple bolus injection of 40 mg/kg; 40 mg/kg administered as a continuous infusion over 12 h; or either 9 or 18 mg/kg administered over 12 or 24 h, respectively. The regimen producing a single transient high peak serum level failed to prevent experimental endocarditis; in contrast, a second injection 6 h after the first resulted in successful prophylaxis. Likewise, the three regimens of continuous, relatively low-dose regimens prevented infections. Thus, the most important parameter for successful prophylaxis was the duration of inhibitory concentration of the drug in the serum. The total dose of antibiotic, the peak serum levels, or the area-under-the-curve values were not predictive of successful prophylaxi

Evidence of host-virus co-evolution in tetranucleotide usage patterns of bacteriophages and eukaryotic viruses

BACKGROUND: Virus taxonomy is based on morphologic characteristics, as there are no widely used non-phenotypic measures for comparison among virus families. We examined whether there is phylogenetic signal in virus nucleotide usage patterns that can be used to determine ancestral relationships. The well-studied model of tail morphology in bacteriophage classification was used for comparison with nucleotide usage patterns. Tetranucleotide usage deviation (TUD) patterns were chosen since they have previously been shown to contain phylogenetic signal similar to that of 16S rRNA. RESULTS: We found that bacteriophages have unique TUD patterns, representing genomic signatures that are relatively conserved among those with similar host range. Analysis of TUD-based phylogeny indicates that host influences are important in bacteriophage evolution, and phylogenies containing both phages and their hosts support their co-evolution. TUD-based phylogeny of eukaryotic viruses indicates that they cluster largely based on nucleic acid type and genome size. Similarities between eukaryotic virus phylogenies based on TUD and gene content substantiate the TUD methodology. CONCLUSION: Differences between phenotypic and TUD analysis may provide clues to virus ancestry not previously inferred. As such, TUD analysis provides a complementary approach to morphology-based systems in analysis of virus evolution

Campylobacter jejuni strains from patients with Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS), an acute demyelinating peripheral neuropathy, may be triggered by an acute infectious illness; infection with Campylobacter jejuni is the most frequently reported antecedent event. In Japan, O:19 is the most common serotype among GBS-associated C. jejuni strains. To determine whether serotype O:19 occurs among GBS-associated strains in the United States and Europe, we serotyped seven such strains and found that two (29%) of seven GBS-associated strains from patients in the United States and Germany were serotype O:19. To determine whether GBS-associated strains may be resistant to killing by normal human serum (NHS), we studied the serum susceptibility of 17 GBS- and 27 enteritis-associated strains (including many O:19 and non-O:19 strains) using C. jejuni antibody positive (pool 1) or negative (pool 2) human serum. Using pool 1 serum we found that one (6%) of 18 serotype O:19 strains compared with 11 (42%) of 26 non-O:19 strains were killed; results using pool 2 serum were nearly identical. Finally, 8 O:19 and 8 non-O:19 strains were not significantly different in their ability to bind complement component C3. Serotype O:19 C. jejuni strains were overrepresented among GBS-associated strains in the United States and Germany and were significantly more serum-resistant than non-O:19 strains. The mechanism of this resistance appears unrelated to C3 binding