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Background: The Gifsy-1 phage integrates into the Salmonella Typhimurium chromosome via an integrase mediated, site-specific recombination mechanism. Excision of the Gifsy-1 phage requires three proteins, the Gifsy-1 integrase (Int), the Gifsy-1 excisionase (Xis) protein, and host encoded Integration Host Factor (IHF). The Gifsy-1 xis gene encodes the 94-residue Gifsy-1 excisionase protein that has a molecular weight of 11.2 kDa and a pI of 10.2. EMSA (Electrophoretic Mobility Shift Assays) suggested at least one region of the protein is responsible for protein-DNA interactions with a tripartite DNA binding site composed of three direct imperfect repeats. Here we have undertaken experiments to dissect and model the structural motifs of Gifsy-1 Xis necessary for its observed DNA binding activity. Results: Diethyl sulfate mutagenesis (DES) and mutagenic PCR techniques were used to generate Gifsy-1 xis mutants. Mutant Xis proteins that lacked activity in vivo were purified and tested by

IntroductionDevic's neuromyelitis optica is an inflammatory demyelinating disease that targets the optic nerves and spinal cord. It has a worldwide distribution and distinctive features that distinguish it from multiple sclerosis. There has been no previous report of neuromyelitis optica from our practice environment, and we are not aware of any case associated with antiphospholipid syndrome in an African person.Case presentationWe report the case of a 28-year-old Nigerian woman who presented with neck pain, paroxysmal tonic spasms, a positive Lhermitte's sign and spastic quadriplegia. She later developed bilateral optic neuritis and had clinical and biochemical features of antiphospholipid syndrome. Her initial magnetic resonance imaging showed a central linear hyperintense focus in the intramedullary portion of C2 to C4. Repeat magnetic resonance imaging after treatment revealed resolution of the signal intensity noticed earlier. Conclusion: Neuromyelitis optica should be considered

Background: The rate of mRNA transcription is controlled by transcription factors that bind to specific DNA motifs in promoter regions upstream of protein coding genes. Recent results indicate that not only the presence of a motif but also motif context (for example the orientation of a motif or its location relative to the coding sequence) is important for gene regulation. Results: In this study we present ContextFinder, a tool that can identify cases where motif context is likely to affect gene regulation. We used ContextFinder to examine the role of motif context in S. cerevisiae both for DNA binding by transcription factors and effects on gene expression. For DNA binding we found significant patterns of motif location bias, whereas motif orientations did not seem to matter. Motif context appears to affect gene expression even more than it affects DNA binding, as biases in both motif location and orientation were more frequent in promoters of co-expressed genes. We validated our re

Background: There is wide recognition that pragmatic randomised trials are the best vehicle for economic evaluation. This is because trials provide the best chance of ensuring internal validity, not least through the rigorous prospective collection of patient-specific data. Furthermore the marginal cost of collecting economic data alongside clinical data is typically modest. UK Clinical Research Collaboration (UKCRC) does not require a standard operating procedure (SOP) for economic evaluation as a prerequisite for trial unit registration. We judge that such a SOP facilitates the integration of health economics into trials. Methods: A collaboration between health economists and trialists at Bangor University led to the development of a SOP for economic evaluation alongside pragmatic trials, in addition to the twenty SOPs required by UKCRC for registration, which include randomisation, data management and statistical analysis. Results: Our recent telephone survey suggests that no oth

Background: Several lines of evidence indicate that the central cannabinoid receptor 1 (CNR1) as well as the major endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA) and monoglyceride lipase (MGLL) are implicated in mediating the orexigenic effects of cannabinoids. The aim of this study was to analyse whether nucleotide sequence variations in the CNR1, FAAH, NAAA and MGLL genes are associated with anorexia nervosa (AN). Methods: We analysed the association of a previously described (AAT)n repeat in the 3' flanking region of CNR1 as well as a total of 15 single nucleotide polymorphisms (SNPs) representative of regions with restricted haplotype diversity in CNR1, FAAH, NAAA or MGLL in up to 91 German AN trios (patient with AN and both biological parents) using the transmission-disequilibrium-test (TDT). One SNP was additionally analysed in an independent case-control study comprising 113 patients with AN and 178 normal

Background: Organophosphates are broad class of chemicals widely used as pesticides throughout the world. We performed a cross-sectional study of associations between dialkylphosphate metabolites of organophosphates and seminal quality among Peruvian pesticide applicators of organophosphates pesticide from Majes (Arequipa), Peru. Methods: 31 men exposed to organophosphate (OPs) pesticides and 31 non-exposed were recruited (age 20-60 years). In exposed subjects, semen and a blood sample were obtained one day after the last pesticide application. Subjects were grouped according levels of OP metabolites in urine. Semen samples were analyzed for sperm concentration, percentage of sperm motility, percentage of normal morphology, semen leucocytes and measurements of fructose and zinc concentrations. Exposure to OPs was assessed by measuring six urinary OPs metabolites (DMP, DMTP, DMDTP, DEP, DETP, and DEDTP) by gas chromatography using a single flame photometric detector. Results: DEDTP (p=

IntroductionProstate cancer has a high tendency to spread to bone. Pulmonary metastasis and generalized lymphadenopathy commonly develop after pelvic and bone involvement have already occurred. Few patients with prostate cancer initially present with symptomatic metastatic lung lesions and lymphadenopathy, but without any other concomitant distant dissemination. Case Presentation We report a case of a 73-year male who sought medical help for symptoms of cough, hemoptysis, and dyspnea. A chest X-ray was done revealing multiple "cannon ball" infiltrates involving all segments of the lung parenchyma. Fine-needle aspiration cytology (FNAC) under CT-guidance of a subpleural lesion revealed adenocarcinoma cells. Despite the absence of other detectable osseous lesions but with the presence of multiple hilar, mediastinal, para-aortic, and pelvic lymphadenopathy, the patient had a complete paraclinical assessment in search for the primary adenocarcinoma. His prostate specific antigen (PSA) was

Background: Large-scale compilation of gene expression microarray datasets across diverse biological phenotypes has led to the identification and annotation of bimodal genes in the mouse and the human genome. These switch-like genes consist of 15% of known human genes, and are enriched with genes coding for extracellular and membrane proteins. The microarray data is typically comprised of thousands of measurements for a few samples and it is of interest to determine the prediction potential of bimodal genes for class discovery in large-scale datasets. Results: Use of a model-based clustering algorithm accurately classified more than 400 microarray samples into 19 different tissue types on the basis of bimodal gene expression. The algorithm demonstrated similar accuracy in the classification of microarray data corresponding to hepatitis C, influenza, HIV-1 and malaria infection. Classification accuracy was exceptional even with class-specific sample sizes between ten and twenty array

Background: The Ras-dependent ERK1/2 MAP kinase signaling pathway plays a central role in cell proliferation control and is frequently activated in human colorectal cancer. Small-molecule inhibitors of MEK1/MEK2 are therefore viewed as attractive drug candidates for the targeted therapy of this malignancy. However, the exact contribution of MEK1 and MEK2 to the pathogenesis of colorectal cancer remains to be established. Methods: Wild type and constitutively active forms of MEK1 and MEK2 were ectopically expressed by retroviral gene transfer in the normal intestinal epithelial cell line IEC-6. We studied the impact of MEK1 and MEK2 activation on cellular morphology, cell proliferation, survival, migration, invasiveness, and tumorigenesis in mice. RNA interference was used to test the requirement for MEK1 and MEK2 function in maintaining the proliferation of human colorectal cancer cells. Results: We found that expression of activated MEK1 or MEK2 is sufficient to morphologically trans

Background: In Catalonia (Spain) breast cancer mortality has declined since the beginning of the 1990s. The dissemination of early detection by mammography and the introduction of adjuvant treatments are among the possible causes of this decrease, and both were almost coincident in time. Thus, understanding how these procedures were incorporated into use in the general population and in women diagnosed with breast cancer is very important for assessing their contribution to the reduction in breast cancer mortality. We have modeled the dissemination of periodic mammography and described repeat mammography behavior in Catalonia from 1975 to 2006. Methods: Cross-sectional data from three Catalan health Surveys for the calendar years 1994, 2002 and 2006 was used. The dissemination of mammography by birth cohort was modeled using a mixed effects model and repeat mammography behavior was described by age and survey year. Results: For women born from 1938 to 1952, mammography clearly had a pe