An observational prospective study of topical acidified nitrite for killing methicillin-resistant Staphylococcus aureus (MRSA) in contaminated wounds

Background Endogenous nitric oxide (NO) kills bacteria and other organisms as part of the innate immune response. When nitrite is exposed to low pH, NO is generated and has been used as an NO delivery system to treat skin infections. We demonstrated eradication of MRSA carriage from wounds using a topical formulation of citric acid (4.5%) and sodium nitrite (3%) creams co-applied for 5 days to 15 wounds in an observational prospective pilot study of 8 patients. Findings Following treatment with topical citric acid and sodium nitrite, 9 of 15 wounds (60%) and 3 of 8 patients (37%) were cleared of infection. MRSA isolates from these patients were all sensitive to acidified nitrite in vitro compared to methicillin-sensitive S. aureus and a reference strain of MRSA. Conclusions Nitric oxide and acidified nitrite offer a novel therapy for control of MRSA in wounds. Wounds that were not cleared of infection may have been re-contaminated or the bioavailability of acidified nitrite impaired by local factors in the tissue

The Importance of Dietary Carbohydrate in Human Evolution

We propose that plant foods containing high quantities of starch were essential for the evolution of the human phenotype during the Pleistocene. Although previous studies have highlighted a stone tool-mediated shift from primarily plant-based to primarily meat-based diets as critical in the development of the brain and other human traits, we argue that digestible carbohydrates were also necessary to accommodate the increased metabolic demands of a growing brain. Furthermore, we acknowledge the adaptive role cooking played in improving the digestibility and palatability of key carbohydrates. We provide evidence that cooked starch, a source of preformed glucose, greatly increased energy availability to human tissues with high glucose demands, such as the brain, red blood cells, and the developing fetus. We also highlight the auxiliary role copy number variation in the salivary amylase genes may have played in increasing the importance of starch in human evolution following the origins of cooking. Salivary amylases are largely ineffective on raw crystalline starch, but cooking substantially increases both their energy-yielding potential and glycemia. Although uncertainties remain regarding the antiquity of cooking and the origins of salivary amylase gene copy number variation, the hypothesis we present makes a testable prediction that these events are correlate

Microbial laboratory evolution in the era of genome-scale science

Advances in DNA sequencing, high-throughput technologies, and genetic manipulation systems have enabled empirical studies of the molecular and genomic bases of adaptive evolution. This review discusses key insights learned from direct observation of the evolution process

Model predictions of dynamic instability threshold for boiling flow systems

Boiling flow systems such as boiling water nuclear reactors and once-through steam generators may be susceptible to dynamic instabilities of various types. The most common among these is a low frequency (0.1 to 2 Hz, typically) oscillatory flow instability of the limit-cycle type termed ''density-wave oscillations (DWO)''. In the present paper, two different computer models have been used to predict the DWO threshold power input for various operating conditions of an experimental system which features an electrically-heated test section assembly and water as the experimental fluid. One of the models, a frequency-domain model, has been in use for quite some time in the nuclear industry. The other is an improved version of a time-domain two-fluid model proposed by us recently

Dilatometry in the Gleeble: What did you really measure?

The Gleeble is an oft-used tool for welding metallurgy research. Besides producing synthetic weld specimens, it is used to determine phase transformation temperatures and kinetics via dilatometry. Experimental data and an FEM model are used to examine measured dilatation errors because of non-uniform heating of the dilatometer and other sources such as sample elastic and plastic deformation. Both isothermal and constant heating/cooling rate scenarios are considered. Further errors which may be introduced when the dilatation is incorrectly assumed to be linearly related to the volume fraction transformed are also discussed

The Drosophila Dbf4 Ortholog Chiffon Forms A Complex with Gcn5 That Is Necessary for Histone Acetylation and Viability

Metazoans contain two homologs of the Gcn5-binding protein Ada2, Ada2a and Ada2b, which nucleate formation of the ATAC and SAGA complexes respectively. In Drosophila melanogaster, there are two splice isoforms of Ada2b: Ada2b-PA and Ada2b-PB. Here we show only the Ada2b-PB isoform is in SAGA; in contrast, Ada2b-PA associates with Gcn5, Ada3, Sgf29 and Chiffon forming the Chiffon Histone Acetyltransferase (CHAT) complex. Chiffon is theDrosophila ortholog of Dbf4, which binds and activates the cell cycle kinase Cdc7 to initiate DNA replication. In flies, Chiffon and Cdc7 are required in ovary follicle cells for gene amplification, a specialized form of DNA re-replication. Although chiffon was previously reported to be dispensable for viability, here we find that Chiffon is required for both histone acetylation and viability in flies. Surprisingly, we show that chiffon is a dicistronic gene that encodes distinct Cdc7- and CHAT-binding polypeptides. Although the Cdc7-binding domain of Chiffon is not required for viability in flies, Chiffon’s CHAT-binding domain is essential for viability but is not required for gene amplification, arguing against a role in DNA replication

Particle Velocity and Deposition Efficiency in the Cold Spray Process

Copper powder was sprayed by the cold-gas dynamic method. In-flight particle velocities were measured with a laser-two-focus system as a function of process parameters such as gas temperature, gas pressure, and powder feed rate. Particle velocities were uniform in a relatively large volume within the plume and agreed with theoretical predictions. The presence of the substrate was found to have no significant effect on particle velocities. Cold-spray deposition efficiencies were measured on aluminum substrates as a function of particle velocity and incident angle of the plume. Deposition efficiencies of up to 95% were achieved. The critical velocity for deposition was determined to be about 640 meters per second. This work investigates both the in-flight characteristics of copper particles in a supersonic cold-spray plume and the build-up of the subsequent coating on aluminum substrates. Velocities were found to be relatively constant within a large volume of the plume. Particle counts dropped off sharply away from the central axis. The presence of a substrate was found to have no effect on the velocity of the particles. A substantial mass-loading effect on the particle velocity was observed; particle velocities begin to drop as the mass ratio of powder to gas flow rates exceeds 3%. The measured variation of velocity with gas pressure and pre-heat temperature was in fairly good agreement with theoretical predictions. Helium may be used as the driving gas instead of air in order to achieve higher particle velocities for a given temperature and pressure. Coating deposition efficiencies were found to increase with particle velocity and decrease with gun- substrate angle. There did not appear to be any dependence of the deposition efficiency on coating thickness. A critical velocity for deposition of about 640 mk appears to fit the data well. The cold-spray technique shows promise as a method for the deposition of materials which are thermally sensitive or may experience rapid oxidation under typical thermal spray conditions. High deposition efficiencies are achievable for certain coating-substrate conditions. Work remains to determine the material and microstructural properties which govern the coating process

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

Nitrosative stress treatment of E. coli targets distinct set of thiol-containing proteins

Reactive nitrogen species (RNS) function as powerful antimicrobials in host defence, but so far little is known about their bacterial targets. In this study, we set out to identify Escherichia coli proteins with RNS-sensitive cysteines. We found that only a very select set of proteins contain cysteines that undergo reversible thiol modifications upon nitric oxide (NO) treatment in vivo . Of the 10 proteins that we identified, six (AtpA, AceF, FabB, GapA, IlvC, TufA) have been shown to harbour functionally important thiol groups and are encoded by genes that are considered essential under our growth conditions. Media supplementation studies suggested that inactivation of AceF and IlvC is, in part, responsible for the observed NO-induced growth inhibition, indicating that RNS-mediated modifications play important physiological roles. Interestingly, the majority of RNS-sensitive E. coli proteins differ from E. coli proteins that harbour H 2 O 2 -sensitive thiol groups, implying that reactive oxygen and nitrogen species affect distinct physiological processes in bacteria. We confirmed this specificity by analysing the activity of one of our target proteins, the small subunit of glutamate synthase. In vivo and in vitro activity studies confirmed that glutamate synthase rapidly inactivates upon NO treatment but is resistant towards other oxidative stressors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72397/1/j.1365-2958.2007.05964.x.pd