The SseC translocon component in Salmonella enterica serovar Typhimurium is chaperoned by SscA

Background: Salmonella enterica is a causative agent of foodborne gastroenteritis and the systemic disease known as typhoid fever. This bacterium uses two type three secretion systems (T3SSs) to translocate protein effectors into host cells to manipulate cellular function. Salmonella pathogenicity island (SPI)-2 encodes a T3SS required for intracellular survival of the pathogen. Genes in SPI-2 include apparatus components, secreted effectors and chaperones that bind to secreted cargo to coordinate their release from the bacterial cell. Although the effector repertoire secreted by the SPI-2 T3SS is large, only three virulence-associated chaperones have been characterized. Results: Here we report that SscA is the chaperone for the SseC translocon component. We show that SscA and SseC interact in bacterial cells and that deletion of sscA results in a loss of SseC secretion, which compromises intracellular replication and leads to a loss of competitive fitness in mice. Conclusions: This work completes the characterization of the chaperone complement within SPI-2 and identifies SscA as the chaperone for the SseC translocon

RpoE fine tunes expression of a subset of SsrB-regulated virulence factors in Salmonella enterica serovar Typhimurium

<p>Abstract</p> <p>Background</p> <p>The survival of <it>Salmonella enterica </it>within the intracellular host niche requires highly co-ordinated expression of virulence effectors predominantly regulated by the SsrAB two-component regulatory system. <it>S. enterica </it>serovar Typhimurium mutants lacking the <it>ssrAB </it>genes are avirulent in mice, highlighting the importance of this regulatory system <it>in vivo</it>. Mutants lacking the gene encoding the alternative sigma factor σ^E(<it>rpoE</it>) are also highly attenuated for intracellular survival, pointing to a potential connection with the SsrAB regulatory system.</p> <p>Results</p> <p>In this study we demonstrate that RpoE is involved in fine-tuning the expression of a subset of SsrB-regulated genes found in the <it>Salmonella </it>pathogenicity island-2 (SPI-2) genetic locus that encodes a horizontally acquired type III secretion system, and unlinked genes integrated into this regulon that are required for virulence in host animals.</p> <p>Conclusion</p> <p>These data point to a potential connection between the virulence phenotype of strains lacking <it>ssrB </it>and <it>rpoE</it>, and highlight new transcriptional regulation that might be essential for appropriate temporal and spatial control of the virulence-associated type III secretion system during host infection.</p

The non-motile phenotype of Salmonella hha ydgT mutants is mediated through PefI-SrgD

<p>Abstract</p> <p>Background</p> <p>Two ancestral nucleoid-associated proteins called Hha and YdgT contribute to the negative regulation of several virulence-associated genes in <it>Salmonella enterica </it>serovar Typhimurium. Our previous work showed that Hha and YdgT proteins are required for negative regulation of <it>Salmonella </it>Pathogenicity Island-2 and that <it>hha ydgT </it>double mutants are attenuated for murine infection. Interestingly, <it>hha ydgT </it>mutant bacteria exhibited a non-motile phenotype suggesting that Hha and YdgT have a role in flagellar regulation.</p> <p>Results</p> <p>In this study we show that the non-motile phenotype of <it>hha ydgT </it>mutants is due to decreased levels of the master transcriptional regulator FlhD₄C₂resulting in down-regulation of class II/III and class III flagellar promoters and lack of surface flagella on these cells. The horizontally acquired <it>pefI-srgD </it>region was found to be partially responsible for this phenotype since deletion of <it>pefI-srgD </it>in a <it>hha ydgT </it>deletion background resulted in transient restoration of class II/III and III transcription, expression of surface flagella, and motility in the quadruple mutant.</p> <p>Conclusion</p> <p>These data extend our current understanding of the mechanisms through which Hha and YdgT regulate flagellar biosynthesis and further describe how <it>S</it>. Typhimurium has integrated horizontal gene acquisitions into ancestral regulatory networks.</p

Positive living: visual activism and art in HIV/AIDS rights campaigns

Using the exhibition ‘Positive Living: Art and AIDS in South Africa’ (Peltz Gallery, London, 2016) as a starting point, this article offers itself as a short history of some key visual strategies developed to raise political consciousness in South Africa and internationally over one of the darkest periods in South Africa’s history from 1999 to 2006 when former President Thabo Mbeki, in denial about the relationship between HIV and AIDS withheld life-saving treatment from hundreds of thousands of the most vulnerable South African citizens who were only just emerging from the scourge of apartheid. The article examines the strategies deployed by fine artists engaged in raising awareness and support from the international community in order to put pressure on the South African government, together with visual strategies sometimes assigned as ‘craft’ or ‘therapy’ and produced as local and often rural community responses to the HIV crisis. ‘Positive Living’ is concerned to provoke a more comparative debate about the relative values and limitations of different visual strategies as part of a wider commitment to the ways in which visual and material culture (notwithstanding shortcomings) can produce powerful tools for social change

Evaluation of peak-picking algorithms for protein mass spectrometry

Peak picking is an early key step in MS data analysis. We compare three commonly used approaches to peak picking and discuss their merits by means of statistical analysis. Methods investigated encompass signal-to-noise ratio, continuous wavelet transform, and a correlation-based approach using a Gaussian template. Functionality of the three methods is illustrated and discussed in a practical context using a mass spectral data set created with MALDI-TOF technology. Sensitivity and specificity are investigated using a manually defined reference set of peaks. As an additional criterion, the robustness of the three methods is assessed by a perturbation analysis and illustrated using ROC curves

Pattern recognition in lymphoid malignancies using CytoGPS and Mercator

BACKGROUND: There have been many recent breakthroughs in processing and analyzing large-scale data sets in biomedical informatics. For example, the CytoGPS algorithm has enabled the use of text-based karyotypes by transforming them into a binary model. However, such advances are accompanied by new problems of data sparsity, heterogeneity, and noisiness that are magnified by the large-scale multidimensional nature of the data. To address these problems, we developed the Mercator R package, which processes and visualizes binary biomedical data. We use Mercator to address biomedical questions of cytogenetic patterns relating to lymphoid hematologic malignancies, which include a broad set of leukemias and lymphomas. Karyotype data are one of the most common form of genetic data collected on lymphoid malignancies, because karyotyping is part of the standard of care in these cancers. RESULTS: In this paper we combine the analytic power of CytoGPS and Mercator to perform a large-scale multidimensional pattern recognition study on 22,741 karyotype samples in 47 different hematologic malignancies obtained from the public Mitelman database. CONCLUSION: Our findings indicate that Mercator was able to identify both known and novel cytogenetic patterns across different lymphoid malignancies, furthering our understanding of the genetics of these diseases

Health-related quality-of-life outcome measures in paediatric palliative care: A systematic review of psychometric properties and feasibility of use

BACKGROUND: The number of children worldwide requiring palliative care services is increasing due to advances in medical care and technology. The use of outcome measures is important to improve the quality and effectiveness of care. AIM: To systematically identify health-related quality-of-life outcome measures that could be used in paediatric palliative care and examine their feasibility of use and psychometric properties. DESIGN: A systematic literature review and analysis of psychometric properties. DATA SOURCES: PsychInfo, Medline and EMBASE were searched from 1 January 1990 to 10 December 2014. Hand searches of the reference list of included studies and relevant reviews were also performed. RESULTS: From 3460 articles, 125 papers were selected for full-text assessment. A total of 41 articles met the eligibility criteria and examined the psychometric properties of 22 health-related quality-of-life measures. Evidence was limited as at least half of the information on psychometric properties per instrument was missing. Measurement error was not analysed in any of the included articles and responsiveness was only analysed in one study. The methodological quality of included studies varied greatly. CONCLUSION: There is currently no 'ideal' outcome assessment measure for use in paediatric palliative care. The domains of generic health-related quality-of-life measures are not relevant to all children receiving palliative care and some domains within disease-specific measures are only relevant for that specific population. Potential solutions include adapting an existing measure or developing more individualized patient-centred outcome and experience measures. Either way, it is important to continue work on outcome measurement in this field

Design and synthesis of 5-hydroxytryptamine analogues: The photochemistry of certain steroids

Design and Synthesis of 5-Hydroxytryptamine Analogues. - The primary processes of drug absorption, distribution, and metabolism are outlined, and their possible influence upon attempted correlations between chemical structure and pharmacological action emphasised. Theories concerning the mode of action of drugs and in particular the role of the receptor theory are reviewed. The general pharmacological and physiological properties of 5-hydroxytryptamine and related compounds are also discussed. Current views concerning the role of endogenous 5-hydroxytryptamine and the nature of the 5-hydroxytryptamine receptor are included. Certain previously reported compounds which may be regarded as "less flexible" analogues of 5-hydroxytryptamine and tryptamine are noted and attempts to prepare other similarly "rigid" analogues are described. Such compounds should prove useful in investigations aimed at determining the structural requirements of the 5-hydroxytryptamine receptor. Routes to 4- and 5-amino-1,3,4,5-tetrahydrobenz [c,d]indole and the corresponding 6-hydroxy derivatives, 3-amino-6-hydroxy-1,2,3,4-tetrahydrocarbazole, and 3-amino-7-hydroxy-1,2,3,4-tetrahydrocyclopent[b]indole are investigated, and successful syntheses are recorded. The Photochemistry of Certain Steroids.- The transformations by which light-sensitive compounds are modified under the influence of ultraviolet light are briefly outlined according to the chromophore responsible for the initial excitation; examples of such transformations are drawn, wherever possible, from previously reported light-induced reactions of pharmacologically and physiologically active molecules. The photochemistry of cortisone acetate, 11-ketoprogesterone and progesterone in ethanol is reported; the major products isolated from these reactions were the corresponding 5 beta-dihydrosteroids resulting from photochemically-induced reduction of the C (4,5) double bond. The photochemistry of certain 3-substituted 6-nitrocholest-5-enes is also reported; 3beta-chloro-, 3beta-acetoxy- and 3beta-trifluoroacetoxy-6-nitrocholest-5-enes in ethanol gave, as the major product, cholest-4-ene-3,6-dione-3-oxime. The 3beta-hydroxy derivative (6-nitrocholesterol), however, gave no oxime but 3beta-hydroxycholest-4-en-6-one and 6beta-nitrocholest-4-en-3beta-ol as major products. The mechanism of formation of these photo-products is discussed; the nature of the product would appear to depend upon the solvent employed for the irradiation, the C(3) substituent, and the wavelength of the radiation employed