SUPPRESSOR T LYMPHOCYTES IN PREGNANCY

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Outbreak of Burkholderia cepacia bloodstream infections traced to the use of Ringer lactate solution as multiple-dose vial for catheter flushing, Phnom Penh, Cambodia

AbstractThe Burkholderia cepacia complex is a group of Gram-negative bacteria known as respiratory pathogens in cystic fibrosis patients, but also increasingly reported as a cause of healthcare associated infections. We describe an outbreak of B. cepacia bloodstream infections in a referral hospital in Phnom Penh, Cambodia. Over a 1.5-month period, blood cultures from eight adult patients grew B. cepacia. Bloodstream infection occurred after a median of 2.5 days of hospitalisation. Three patients died: 7, 10 and 17 days after blood cultures were sampled. As part of the outbreak investigation, patient files were reviewed and environmental sampling was performed. All patients had peripheral venous catheters that were flushed with Ringer lactate drawn from a 1 L bag, used as multiple-dose vial at the ward. Cultures of unopened Ringer lactate and disinfectants remained sterile but an in-use bag of Ringer lactate solution and the dispensing pin grew B. cepacia. The isolates from patients and flushing solution were identified as B. cepacia by recA gene sequence analysis, and random amplified polymorphic DNA typing confirmed clonal relatedness. The onset of the outbreak had coincided with the introduction of a dispensing pin with a screw fit that did not allow proper disinfection. Re-enforcement of aseptic procedures with sterile syringe and needle has ended the outbreak. Growth of B. cepacia should alert the possibility of healthcare associated infection also in tropical resource-limited settings. The use of multiple-dose vials should be avoided and newly introduced procedures should be assessed for infection control risks

Traditional and digital literacy. The literacy hypothesis, technologies of reading and writing, and the ‘grammatized’ body

This article discusses, from a theoretical and philosophical perspective, the meaning and the importance of basic literacy training for education in an age in which digital technologies have become ubiquitous. I discuss some arguments, which I draw from the so-called literacy hypothesis approach (McLuhan, Goody, Havelock, Ong), in order to understand the significance of a ‘traditional’ initiation into literacy. I then use the work of Bernard Stiegler on bodily gestures and routines, related to different (traditional and digital) technologies, in order to elaborate and criticize the claims the literacy hypothesis makes. Bringing together insights from both the literacy hypothesis approach and Stiegler's work, I defend the view that there exists an essential difference between traditional and digital literacy, and I try to argue for the introduction of a spelling and grammar of the digital in the educational curriculum

ORegAnno: an open-access community-driven resource for regulatory annotation

ORegAnno is an open-source, open-access database and literature curation system for community-based annotation of experimentally identified DNA regulatory regions, transcription factor binding sites and regulatory variants. The current release comprises 30 145 records curated from 922 publications and describing regulatory sequences for over 3853 genes and 465 transcription factors from 19 species. A new feature called the ‘publication queue’ allows users to input relevant papers from scientific literature as targets for annotation. The queue contains 4438 gene regulation papers entered by experts and another 54 351 identified by text-mining methods. Users can enter or ‘check out’ papers from the queue for manual curation using a series of user-friendly annotation pages. A typical record entry consists of species, sequence type, sequence, target gene, binding factor, experimental outcome and one or more lines of experimental evidence. An evidence ontology was developed to describe and categorize these experiments. Records are cross-referenced to Ensembl or Entrez gene identifiers, PubMed and dbSNP and can be visualized in the Ensembl or UCSC genome browsers. All data are freely available through search pages, XML data dumps or web services at: http://www.oreganno.org

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.

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“Ten Commandments” for the Appropriate use of Antibiotics by the Practicing Physician in an Outpatient Setting

A multi-national working group on antibiotic stewardship, from the International Society of Chemotherapy, put together ten recommendations to physicians prescribing antibiotics to outpatients. These recommendations are: (1) use antibiotics only when needed; teach the patient how to manage symptoms of non-bacterial infections; (2) select the adequate ATB; precise targeting is better than shotgun therapy; (3) consider pharmacokinetics and pharmacodynamics when selecting an ATB; use the shortest ATB course that has proven clinical efficacy; (4) encourage patients’ compliance; (5) use antibiotic combinations only in specific situations; (6) avoid low quality and sub-standard drugs; prevent prescription changes at the drugstore; (7) discourage self-prescription; (8) follow only evidence-based guidelines; beware those sponsored by drug companies; (9) rely (rationally) upon the clinical microbiology lab; and (10) prescribe ATB empirically – but intelligently; know local susceptibility trends, and also surveillance limitations

Education, digitization and literacy training. A historical and cross-cultural perspective.

In this article, I deal with the transition from traditional ‘school’ forms of instruction to educational processes that are fully mediated by digital technologies. Against the background of the idea the very institution ‘school’ is closely linked to the invention of the alphabetic writing system and to the need of initiating new generations into a literate culture, I focus on the issue of literacy training. I argue that with the digitization of education, a fundamental transition takes place regarding what it means to be literate, but also what it means to educate and to be educated. I do so by developing a ‘techno-somatic’ approach, which means that I look at the use of concrete instructional technologies, and the bodily disciplines that are involved. I set out a double comparison in which I contrast existing, ‘traditional’ ways of learning how to read/write with the way in which literacy training looked like before the nineteenth century, on the one hand, and with the initiation into literacy in the Chinese/Japanese language, on the other hand. I argue that these comparisons shed light on the differences between traditional and digital literacy. More precisely, I show that in each case, a different relation toward what it means to produce script is involved. As such, both forms of literacy go together with different spaces of experience and senses of being-able, and therefore with altogether different ideas of what education is all about

Phototriggered release of tetrapeptide AAPV from coumarinyl and pyrenyl cages

Ala-Ala-Pro-Val (AAPV) is a bioactive tetrapeptide that inhibits human neutrophil elastase (HNE), an enzyme involved in skin chronic inflammatory diseases like psoriasis. Caged derivatives of this peptide were prepared by proper N- and C-terminal derivatisation through a carbamate or ester linkage, respectively, with two photoactive moieties, namely 7-methoxycoumarin-2-ylmethyl and pyren-2-ylmethyl groups. These groups were chosen to assess the influence of the photosensitive group and the type of linkage in the controlled photorelease of the active molecule. The caged peptides were irradiated at selected wavelengths of irradiation (254, 300, and 350 nm), and the photolytic process was monitored by HPLC-UV. The results established the applicability of the tested photoactive groups for the release of AAPV, especially for the derivative bearing the carbamate-linked pyrenylmethyl group, which displayed the shortest irradiation times for the release at the various wavelengths of irradiation (ca. 4 min at 254 nm, 8 min at 300 nm and 46 min at 350 nm).Thanks are due to the Fundação para a Ciência e Tecnologia (FCT, Portugal) for financial support to the portuguese NMR network (PTNMR, Bruker Avance III 400- Univ. Minho), FCT and FEDER (European Fund for Regional Development)- COMPETE-QREN-EU for financial support through the Chemistry Research Centre of the University of Minho (Ref. UID/QUI/00686/2013 and UID/QUI/0686/2016). A PhD grant to A.M.S. (SFRH/BD/80813/2011) is also acknowledged.info:eu-repo/semantics/publishedVersio

Reverse Engineering the Yeast RNR1 Transcriptional Control System

Transcription is controlled by multi-protein complexes binding to short non-coding regions of genomic DNA. These complexes interact combinatorially. A major goal of modern biology is to provide simple models that predict this complex behavior. The yeast gene RNR1 is transcribed periodically during the cell cycle. Here, we present a pilot study to demonstrate a new method of deciphering the logic behind transcriptional regulation. We took regular samples from cell cycle synchronized cultures of Saccharomyces cerevisiae and extracted nuclear protein. We tested these samples to measure the amount of protein that bound to seven different 16 base pair sequences of DNA that have been previously identified as protein binding locations in the promoter of the RNR1 gene. These tests were performed using surface plasmon resonance. We found that the surface plasmon resonance signals showed significant variation throughout the cell cycle. We correlated the protein binding data with previously published mRNA expression data and interpreted this to show that transcription requires protein bound to a particular site and either five different sites or one additional sites. We conclude that this demonstrates the feasibility of this approach to decipher the combinatorial logic of transcription

Rosetta FlexPepDock ab-initio: Simultaneous Folding, Docking and Refinement of Peptides onto Their Receptors

Flexible peptides that fold upon binding to another protein molecule mediate a large number of regulatory interactions in the living cell and may provide highly specific recognition modules. We present Rosetta FlexPepDock ab-initio, a protocol for simultaneous docking and de-novo folding of peptides, starting from an approximate specification of the peptide binding site. Using the Rosetta fragments library and a coarse-grained structural representation of the peptide and the receptor, FlexPepDock ab-initio samples efficiently and simultaneously the space of possible peptide backbone conformations and rigid-body orientations over the receptor surface of a given binding site. The subsequent all-atom refinement of the coarse-grained models includes full side-chain modeling of both the receptor and the peptide, resulting in high-resolution models in which key side-chain interactions are recapitulated. The protocol was applied to a benchmark in which peptides were modeled over receptors in either their bound backbone conformations or in their free, unbound form. Near-native peptide conformations were identified in 18/26 of the bound cases and 7/14 of the unbound cases. The protocol performs well on peptides from various classes of secondary structures, including coiled peptides with unusual turns and kinks. The results presented here significantly extend the scope of state-of-the-art methods for high-resolution peptide modeling, which can now be applied to a wide variety of peptide-protein interactions where no prior information about the peptide backbone conformation is available, enabling detailed structure-based studies and manipulation of those interactions