Pathogenicity of Staphylococcus aureus phage type 3A/3C/55/71 and Staphylococcus sciuri in germfree euthymic and athymic mice after intravenous infection

To evaluate the possibility ofprotecting our colonies of small laboratory animals against Staphylococcus aureus infections by preassociation with the rodent specific Staphylococcus sciuri, it was first of all necessary to determine the pathogenicity of the S. sciuri strain under consideration. Germfree euthymic Han: NMRI and athymic (T-cell deficient) Han:NMRInu/nu mice were injected intravenously with increasing doses of S. sciuri strain 908/1. S. aureus (phage type 3A/3C/55/71) which is known to cause health problems in SPF colonies of the above mentioned strains of mice was used for comparison.S. aureus infections exhibited a dosedependent morbidity and mortality in both strains of mice. In contrast, S. sciuri did not cause any lethal infection but produced sporadically mild purulent processes in the euthymic mice. Due to the use of relatively small groups a statistical evaluation can only show tendenc1es

An mRNA Blueprint for C-4 Photosynthesis Derived from Comparative Transcriptomics of Closely Related C-3 and C-4 Species

Bräutigam A, Kajala K, Wullenweber J, et al. An mRNA Blueprint for C-4 Photosynthesis Derived from Comparative Transcriptomics of Closely Related C-3 and C-4 Species. Plant Physiology. 2011;155(1):142-156.C-4 photosynthesis involves alterations to the biochemistry, cell biology, and development of leaves. Together, these modifications increase the efficiency of photosynthesis, and despite the apparent complexity of the pathway, it has evolved at least 45 times independently within the angiosperms. To provide insight into the extent to which gene expression is altered between C-3 and C-4 leaves, and to identify candidates associated with the C-4 pathway, we used massively parallel mRNA sequencing of closely related C-3 (Cleome spinosa) and C-4 (Cleome gynandra) species. Gene annotation was facilitated by the phylogenetic proximity of Cleome and Arabidopsis (Arabidopsis thaliana). Up to 603 transcripts differ in abundance between these C-3 and C-4 leaves. These include 17 transcription factors, putative transport proteins, as well as genes that in Arabidopsis are implicated in chloroplast movement and expansion, plasmodesmatal connectivity, and cell wall modification. These are all characteristics known to alter in a C-4 leaf but that previously had remained undefined at the molecular level. We also document large shifts in overall transcription profiles for selected functional classes. Our approach defines the extent to which transcript abundance in these C-3 and C-4 leaves differs, provides a blueprint for the NAD-malic enzyme C-4 pathway operating in a dicotyledon, and furthermore identifies potential regulators. We anticipate that comparative transcriptomics of closely related species will provide deep insight into the evolution of other complex traits

Structural diversity of biologically interesting datasets: a scaffold analysis approach

ABSTRACT:The recent public availability of the human metabolome and natural product datasets has revitalized "metabolite-likeness" and "natural product-likeness" as a drug design concept to design lead libraries targeting specific pathways. Many reports have analyzed the physicochemical property space of biologically important datasets, with only a few comprehensively characterizing the scaffold diversity in public datasets of biological interest. With large collections of high quality public data currently available, we carried out a comparative analysis of current day leads with other biologically relevant datasets.In this study, we note a two-fold enrichment of metabolite scaffolds in drug dataset (42%) as compared to currently used lead libraries (23%). We also note that only a small percentage (5%) of natural product scaffolds space is shared by the lead dataset. We have identified specific scaffolds that are present in metabolites and natural products, with close counterparts in the drugs, but are missing in the lead dataset. To determine the distribution of compounds in physicochemical property space we analyzed the molecular polar surface area, the molecular solubility, the number of rings and the number of rotatable bonds in addition to four well-known Lipinski properties. Here, we note that, with only few exceptions, most of the drugs follow Lipinski's rule. The average values of the molecular polar surface area and the molecular solubility in metabolites is the highest while the number of rings is the lowest. In addition, we note that natural products contain the maximum number of rings and the rotatable bonds than any other dataset under consideration.Currently used lead libraries make little use of the metabolites and natural products scaffold space. We believe that metabolites and natural products are recognized by at least one protein in the biosphere therefore, sampling the fragment and scaffold space of these compounds, along with the knowledge of distribution in physicochemical property space, can result in better lead libraries. Hence, we recommend the greater use of metabolites and natural products while designing lead libraries. Nevertheless, metabolites have a limited distribution in chemical space that limits the usage of metabolites in library design.14 page(s

Comparison of Liquid Chromatography Mass Spectrometry and Enzyme-Linked Immunosorbent Assay Methods to Measure Salivary Cotinine Levels in Ill Children.

Objective: Cotinine is the preferred biomarker to validate levels of tobacco smoke exposure (TSE) in children. Compared to enzyme-linked immunosorbent assay methods (ELISA) for quantifying cotinine in saliva, the use of liquid chromatography tandem mass spectrometry (LC-MS/MS) has higher sensitivity and specificity to measure very low levels of TSE. We sought to compare LC-MS/MS and ELISA measures of cotinine in saliva samples from children overall and the associations of these measures with demographics and TSE patterns. Method: Participants were nonsmoking children (N = 218; age mean (SD) = 6.1 (5.1) years) presenting to a pediatric emergency department. Saliva samples were analyzed for cotinine using both LC-MS/MS and ELISA. Limit of quantitation (LOQ) for LC-MS/MS and ELISA was 0.1 ng/ml and 0.15 ng/ml, respectively. Results: Intraclass correlations (ICC) across methods = 0.884 and was consistent in sex and age subgroups. The geometric mean (GeoM) of LC-MS/MS = 4.1 (range: < LOQ - 382 ng/mL; 3% < LOQ) which was lower (p < 0.0001) than the ELISA GeoM = 5.7 (range: < LOQ - 364 ng/mL; 5% < LOQ). Similar associations of cotinine concentrations with age ( < -0.10, p < 0.0001), demographic characteristics (e.g., income), and number of cigarettes smoked by caregiver ( > 0.07, p < 0.0001) were found regardless of cotinine detection method; however, cotinine associations with sex and race/ethnicity were only found to be significant in models using LC-MS/MS-derived cotinine. Conclusions: Utilizing LC-MS/MS-based cotinine, associations of cotinine with sex and race/ethnicity of child were revealed that were not detectable using ELISA-based cotinine, demonstrating the benefits of utilizing the more sensitive LC-MS/MS assay for cotinine measurement when detecting low levels of TSE in children