Bioactive Secondary Metabolites from a New Terrestrial Streptomyces sp. TN262

During our search for Streptomyces spp. as new producers of bioactive secondary metabolites, the ethyl acetate extract of the new terrestrial Streptomyces isolate TN262 delivered eight antimicrobially active compounds. They were identified as 1-acetyl-β-carboline (1), tryptophol (2), cineromycin B (3), 2,3-dihydrocineromycin B (4), cyclo-(tyrosylprolyl) (5), 3-(hydroxyacetyl)-indole (6), brevianamide F (7), and cis-cyclo-(l-prolyl-l-leucyl) (8). Three further metabolites were detected in the unpolar fractions using GC–MS and tentatively assigned as benzophenone (9), N-butyl-benzenesulfonamide (10), and hexanedioic acid-bis-(2-ethylhexyl) ester (11). This last compound is known as plasticizer derivatives, but it has never been described from natural sources. In this article, we describe the identification of the new Streptomyces sp. isolate TN262 using its cultural characteristics, the nucleotide sequence of the corresponding 16S rRNA gene and the phylogenetic analysis, followed by optimization, large-scale fermentation, isolation of the bioactive constituents, and determination of their structures. The biological activity of compounds (2), (3), (4), and those of the unpolar fractions was addressed as well

Comparison of the fracture resistance of endodontically treated teeth restored with prefabricated posts and composite resin cores with different post lenghts

OBJECTIVE: This study evaluated the fracture strengths of endodontically treated teeth restored with prefabricated posts with different post lengths. MATERIAL AND METHODS: Thirty freshly extracted canines were endodontically treated. They were randomly divided into groups of 10 teeth and prepared according to 3 experimental protocols, as follows; Group 1/3 PP: teeth restored with prefabricated post and composite resin core (Z250) with post length of 5.0mm; Group 1/2 PP and Group 2/3 PP: teeth restored with prefabricated post and composite resin core (Z250) with different combinations of post length of 7.5mm and 10mm, respectively. All teeth were restored with full metal crowns. The fracture resistance (N) was measured in a universal testing machine (crosshead speed 0.5mm/min) at 45 degrees to the tooth long axis until failure. Data were analyzed by one-way analysis of variance (alpha=.05). RESULTS: The one-way analysis of variance demonstrated no significant difference among the different post lengths (P>;.05) (Groups 1/3 PP = 405.4 N, 1/2 PP = 395.6 N, 2/3 PP = 393.8 N). Failures occurred mainly due to core fracture. CONCLUSIONS: The results of this study showed that an increased post length in teeth restored with prefabricated posts did not significantly increase the fracture resistance of endodontically treated teeth

Nanomechanical detection of antibiotic-mucopeptide binding in a model for superbug drug resistance

The alarming growth of the antibiotic-resistant superbugs methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) is driving the development of new technologies to investigate antibiotics and their modes of action. We report the label-free detection of vancomycin binding to bacterial cell wall precursor analogues (mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically relevant concentrations in blood serum. Differential measurements quantified binding constants for vancomycin-sensitive and vancomycin-resistant mucopeptide analogues. Moreover, by systematically modifying the mucopeptide density we gain new insights into the origin of surface stress. We propose that stress is a product of a local chemical binding factor and a geometrical factor describing the mechanical connectivity of regions affected by local binding in terms of a percolation process. Our findings place BioMEMS devices in a new class of percolative systems. The percolation concept will underpin the design of devices and coatings to significantly lower the drug detection limit and may also impact on our understanding of antibiotic drug action in bacteria.Comment: Comments: This paper consists of the main article (6 pages, 5 figures) plus Supplemental Material (6 pages, 3 figures). More details are available at http://www.london-nano.co

A framework to analyze multiple time series data: A case study with Streptomyces coelicolor

Transcriptional regulation in differentiating microorganisms is highly dynamic involving multiple and interwinding circuits consisted of many regulatory genes. Elucidation of these networks may provide the key to harness the full capacity of many organisms that produce natural products. A powerful tool evolved in the past decade is global transcriptional study of mutants in which one or more key regulatory genes of interest have been deleted. To study regulatory mutants of Streptomyces coelicolor , we developed a framework of systematic analysis of gene expression dynamics. Instead of pair-wise comparison of samples in different combinations, genomic DNA was used as a common reference for all samples in microarray assays, thus, enabling direct comparison of gene transcription dynamics across different isogenic mutants. As growth and various differentiation events may unfold at different rates in different mutants, the global transcription profiles of each mutant were first aligned computationally to those of the wild type, with respect to the corresponding growth and differentiation stages, prior to identification of kinetically differentially expressed genes. The genome scale transcriptome data from wild type and a Δ absA1 mutant of Streptomyces coelicolor were analyzed within this framework, and the regulatory elements affected by the gene knockout were identified. This methodology should find general applications in the analysis of other mutants in our repertoire and in other biological systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47950/1/10295_2005_Article_34.pd

Management control systems in innovation companies: A literature based framework

Past research has traditionally argued that management control systems (MCSs) may present a hindrance to the creativity of innovation companies. This theoretical paper surveys the literature to focus an investigation on the MCSs of innovation companies. Within the object of control paradigm the paper develops and presents a theoretical model of the impact of eleven external, organisational and innovation related contingency factors on the MCSs in companies that engage in innovation activities. We also suggest measures for further empirical research. By formulating hypotheses on 43 potential interactions the model predicts contradictory influences on two direct control categories, results and action control, but stresses the importance of two indirect categories, personnel and cultural control. More specifically, the high levels of technological complexity and innovation capability in this type of company are expected to be negatively associated with the application of results and action control, whereas personnel and cultural seem to be more appropriate. Furthermore, important sources of finance, venture capital and public funding, are both hypothesised to be positively associated with the application of results, action and personnel control; whereas only public funding is predicted to be positively related to the application of cultural control. The principal contribution of this paper lies in synthesising the literature to provide a model of the impact of a unique set of eleven contingency factors for innovation companies on a broad scope of controls. In addition, the contingency model, if empirically validated, would add value by inferring the particular forms of management control which would be beneficial in innovative company settings. © 2014 Springer-Verlag Berlin Heidelberg

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics