Protein interaction data curation: the International Molecular Exchange (IMEx) consortium.

The International Molecular Exchange (IMEx) consortium is an international collaboration between major public interaction data providers to share literature-curation efforts and make a nonredundant set of protein interactions available in a single search interface on a common website (http://www.imexconsortium.org/). Common curation rules have been developed, and a central registry is used to manage the selection of articles to enter into the dataset. We discuss the advantages of such a service to the user, our quality-control measures and our data-distribution practices.

On problems of calculating energy expenditure and substrate utilization from respiratory exchange data.

Indirect calorimetry based on respiratory exchange measurement has been successfully used from the beginning of the century to obtain an estimate of heat production (energy expenditure) in human subjects and animals. The errors inherent to this classical technique can stem from various sources: 1) model of calculation and assumptions, 2) calorimetric factors used, 3) technical factors and 4) human factors. The physiological and biochemical factors influencing the interpretation of calorimetric data include a change in the size of the bicarbonate and urea pools and the accumulation or loss (via breath, urine or sweat) of intermediary metabolites (gluconeogenesis, ketogenesis). More recently, respiratory gas exchange data have been used to estimate substrate utilization rates in various physiological and metabolic situations (fasting, post-prandial state, etc.). It should be recalled that indirect calorimetry provides an index of overall substrate disappearance rates. This is incorrectly assumed to be equivalent to substrate "oxidation" rates. Unfortunately, there is no adequate golden standard to validate whole body substrate "oxidation" rates, and this contrasts to the "validation" of heat production by indirect calorimetry, through use of direct calorimetry under strict thermal equilibrium conditions. Tracer techniques using stable (or radioactive) isotopes, represent an independent way of assessing substrate utilization rates. When carbohydrate metabolism is measured with both techniques, indirect calorimetry generally provides consistent glucose "oxidation" rates as compared to isotopic tracers, but only when certain metabolic processes (such as gluconeogenesis and lipogenesis) are minimal or / and when the respiratory quotients are not at the extreme of the physiological range. However, it is believed that the tracer techniques underestimate true glucose "oxidation" rates due to the failure to account for glycogenolysis in the tissue storing glucose, since this escapes the systemic circulation. A major advantage of isotopic techniques is that they are able to estimate (given certain assumptions) various metabolic processes (such as gluconeogenesis) in a noninvasive way. Furthermore when, in addition to the 3 macronutrients, a fourth substrate is administered (such as ethanol), isotopic quantification of substrate "oxidation" allows one to eliminate the inherent assumptions made by indirect calorimetry. In conclusion, isotopic tracers techniques and indirect calorimetry should be considered as complementary techniques, in particular since the tracer techniques require the measurement of carbon dioxide production obtained by indirect calorimetry. However, it should be kept in mind that the assessment of substrate oxidation by indirect calorimetry may involve large errors in particular over a short period of time. By indirect calorimetry, energy expenditure (heat production) is calculated with substantially less error than substrate oxidation rates.

The mzTab Data Exchange Format: Communicating Mass-spectrometry-based Proteomics and Metabolomics Experimental Results to a Wider Audience.

The HUPO Proteomics Standards Initiative has developed several standardized data formats to facilitate data sharing in mass spectrometry (MS)-based proteomics. These allow researchers to report their complete results in a unified way. However, at present, there is no format to describe the final qualitative and quantitative results for proteomics and metabolomics experiments in a simple tabular format. Many downstream analysis use cases are only concerned with the final results of an experiment and require an easily accessible format, compatible with tools such as Microsoft Excel or R. We developed the mzTab file format for MS-based proteomics and metabolomics results to meet this need. mzTab is intended as a lightweight supplement to the existing standard XML-based file formats (mzML, mzIdentML, mzQuantML), providing a comprehensive summary, similar in concept to the supplemental material of a scientific publication. mzTab files can contain protein, peptide, and small molecule identifications together with experimental metadata and basic quantitative information. The format is not intended to store the complete experimental evidence but provides mechanisms to report results at different levels of detail. These range from a simple summary of the final results to a representation of the results including the experimental design. This format is ideally suited to make MS-based proteomics and metabolomics results available to a wider biological community outside the field of MS. Several software tools for proteomics and metabolomics have already adapted the format as an output format. The comprehensive mzTab specification document and extensive additional documentation can be found online.

Genetic diversity and genetic exchange in Trypanosoma cruzi: dual drug-resistant "progeny" from episomal transformants

Extensive characterisation of Trypanosoma cruzi by isoenzyme phenotypes has separated the species into three principal zymodeme groups, Z1, Z2 and Z3, and into many individual zymodemes. There is marked diversity within Z2. A strong correlation has been demonstrated between the strain clusters determined by isoenzymes and those obtained using random amplified polymorphic DNA (RAPD) profiles. Polymorphisms in ribosomal RNA genes, in mini-exon genes, and microsatellite fingerprinting indicate the presence of at least two principal T. cruzi genetic lineages. Lineage 1 appears to correspond with Z2 and lineage 2 with Z1. Z1 (lineage 2) is associated with Didelphis. Z2 (lineage 1) may be associated with a primate host. Departures from Hardy-Weinberg equilibrium and linkage disequilibrium indicate that propagation of T. cruzi is predominantly clonal. Nevertheless, two studies show putative homozygotes and heterozygotes circulating sympatrically: the allozyme frequencies for phosphoglucomutase, and hybrid RAPD profiles suggest that genetic exchange may be a current phenomenon in some T. cruzi transmission cycles. We were able to isolate dual drug-resistant T. cruzi biological clones following copassage of putative parents carrying single episomal drug-resistant markers. A multiplex PCR confirmed that dual drug-resistant clones carried both episomal plasmids. Preliminary karyotype analysis suggests that recombination may not be confined to the extranuclear genome.

Plutonium from above-ground nuclear tests in milk teeth: investigation of placental transfer in children born between 1951 and 1995 in Switzerland.

BACKGROUND: Occupational risks, the present nuclear threat, and the potential danger associated with nuclear power have raised concerns regarding the metabolism of plutonium in pregnant women. OBJECTIVE: We measured plutonium levels in the milk teeth of children born between 1951 and 1995 to assess the potential risk that plutonium incorporated by pregnant women might pose to the radiosensitive tissues of the fetus through placenta transfer. METHODS: We used milk teeth, whose enamel is formed during pregnancy, to investigate the transfer of plutonium from the mother's blood plasma to the fetus. We measured plutonium using sensitive sector field inductively coupled plasma mass spectrometry techniques. We compared our results with those of a previous study on strontium-90 ((90)Sr) released into the atmosphere after nuclear bomb tests. RESULTS: Results show that plutonium activity peaks in the milk teeth of children born about 10 years before the highest recorded levels of plutonium fallout. By contrast, (90)Sr, which is known to cross the placenta barrier, manifests differently in milk teeth, in accordance with (90)Sr fallout deposition as a function of time. CONCLUSIONS: These findings demonstrate that plutonium found in milk teeth is caused by fallout that was inhaled around the time the milk teeth were shed and not from any accumulation during pregnancy through placenta transfer. Thus, plutonium may not represent a radiologic risk for the radiosensitive tissues of the fetus.

Constitutively active G protein-coupled receptor mutants: implications on receptor function and drug action.

Mutations of GPCRs can increase their constitutive (agonist-independent) activity. Some of these mutations have been artificially introduced by site-directed mutagenesis; others occur spontaneously in human diseases. The analysis of constitutively active GPCR mutants has attracted a large interest in the past decade, providing an important contribution to our understanding of the molecular mechanisms underlying receptor function and drug action.

Annual Report of the Needle & Syringe Exchange Scheme for the period 1st April 2013 to 31st March 2014.

This report summarises data that is collected on the operation of the Northern Ireland Needle and Syringe Exchange Scheme (NSES). It relates to the twelve-month period between 1st April 2013 and 31st March 2014. The anonymised data is collected by the 14 pharmacies and 1 Trust-based service that participate in the Northern Ireland Needle and Syringe Exchange Scheme (NSES) which was introduced in April 2001.

Historical review: Negative efficacy and the constitutive activity of G-protein-coupled receptors.

The idea that a receptor can produce signalling without agonist intervention and that several antagonists can be 'active' in repressing such spontaneous activity is contained in the concept of ligand-induced conformational changes. Yet, this idea was neglected by pharmacologists for many years. In this article, we review the events that brought inverse agonism and constitutive activity to general attention and made this phenomenon a topic of current research. We also suggest a classification of antagonists based on the cooperativity that links their primary site of interaction with other functional domains of the receptor.

What Price Salvation? The Exchange of Salvation goods between India and the West

Does Weber's notion of salvation goods, along with the connected one of the religious market, apply to the modern history of yoga? The case study chosen here (the yoga of Pattabhi Jois) clearly shows that these notions highlight many aspects of the expansion of yoga into a global market product. However, the notion of salvation goods resists the new hermeneutical situation of encounter and has to be adapted to the present situation of religious "patchwork". The notion of religious market lacks depth to describe the various understandings and appropriations of yoga in precise historical situations. Other aspects of the current global status of yoga may be highlighted by applying the concept of pilgrimage. La notion de bien de salut que nous lègue Max Weber et la notion de marché religieux qui en découle peuvent-elles s'appliquer à l'histoire moderne du yoga? L'étude de cas que nous consacrons au yoga de Pattabhi Jois montre que ces notions éclairent bien certains aspects de l'expansion du yoga en tant que produit d'un marché globalisé. Cependant la notion de bien de salut résiste à une réflexion de type herméneutique sur les processus de rencontres et doit être adaptée à la situation contemporaine, ou` les religions se présentent comme des ensembles composites. La notion de marché religieux ne permet pas d'expliquer les diverses compréhensions et appropriations du yoga dans des situations historiques précises. D'autres aspects de la situation du yoga sont mieux explicités si on prend le concept de pèlerinage comme point de référence.

An Ontology for Open Rubric Exchange on the Web

While the Internet has given educators access to a steady supply of Open Educational Resources, the educational rubrics commonly shared on the Web are generally in the form of static, non-semantic presentational documents or in the proprietary data structures of commercial content and learning management systems.With the advent of Semantic Web Standards, producers of online resources have a new framework to support the open exchange of software-readable datasets. Despite these advances, the state of the art of digital representation of rubrics as sharable documents has not progressed.This paper proposes an ontological model for digital rubrics. This model is built upon the Semantic Web Standards of the World Wide Web Consortium (W3C), principally the Resource Description Framework (RDF) and Web Ontology Language (OWL).

'Greek' and 'Roman' in Latin Medical Texts. Studies in Cultural Change and Exchange in Ancient Medicine : [Proceedings of the 10th International Conference "Ancient Latin Medical Texts", Lausanne, 2010, November 3rd-6th November]

Latin medical texts transmit medical theories and practices that originated mainly in Greece. This interaction took place through juxtaposition, assimilation and transformation of ideas. 'Greek' and 'Roman' in Latin Medical Texts studies the ways in which this cultural interaction influenced the development of the medical profession and the growth of knowledge of human and animal bodies, and especially how it provided the foundations for innovations in the areas of anatomy, pathology and pharmacology, from the earliest Latin medical texts until well into the medieval world.

Direct analysis of dried blood spots coupled with mass spectrometry: concepts and biomedical applications.

Because of the emergence of dried blood spots (DBS) as an attractive alternative to conventional venous plasma sampling in many pharmaceutical companies and clinical laboratories, different analytical approaches have been developed to enable automated handling of DBS samples without any pretreatment. Associated with selective and sensitive MS-MS detection, these procedures give good results in the rapid identification and quantification of drugs (generally less than 3 min total run time), which is desirable because of the high throughput requirements of analytical laboratories. The objective of this review is to describe the analytical concepts of current direct DBS techniques and to present their advantages and disadvantages, with particular focus on automation capacity and commercial availability. Finally, an overview of the different biomedical applications in which these concepts could be of major interest will be presented.

Nonself vegetative fusion and genetic exchange in the arbuscular mycorrhizal fungus Glomus intraradices.

Arbuscular mycorrhizal fungi (AMF) form symbioses with the majority of plants and form extensive underground hyphal networks simultaneously connecting the roots of different plant species. No empirical evidence exists for either anastomosis between genetically different AMF or genetic exchange.Five isolates of one population of Glomus intraradices were used to study anastomosis between hyphae of germinating spores. We show that genetically distinct AMF, from the same field, anastomose, resulting in viable cytoplasmic connections through which genetic exchange could potentially occur.Pairs of genetically different isolates were then co-cultured in an in vitro system.Freshly produced spores were individually germinated to establish new cultures.Using several molecular tools, we show that genetic exchange occurred between genetically different AMF. Specific genetic markers from each parent were transmitted to the progeny. The progeny were viable, forming symbioses with plant roots. The phenotypes of some of the progeny were significantly different from either parent.Our results indicate that considerable promiscuity could occur in these fungi because nine out of 10 combinations of different isolates anastomosed. The ability to perform genetic crosses between AMF experimentally lays a foundation for understanding the genetics and evolutionary biology of these important plants symbionts.

Distinct chitinases are expressed during various growth phases of the human pathogen Paracoccidioides brasiliensis

The aim of this work was the partial purification and subsequent evaluation of chitinase expression during the various growth phases of Paracoccidioides brasiliensis. Initially, PbCTS1r was expressed as a recombinant protein and displayed enzymatic activity against 4-MU-[N-acetylglucosamine (GlcNAc)]3 and 4-MU-(GlcNAc)2. Two proteins, 45 kDa and 39 kDa in size, were partially purified from P. brasiliensis yeast crude extract using cation-exchange chromatography coupled with HPLC and were characterised as PbCTS1 and PbCTS2, respectively. Anti-PbCTS1r antibody recognised two proteins in the crude extracts of yeast and the transitional stage between mycelial and yeast phases. In crude extracts of mycelium, only the 45 kDa protein was detected. However, quantitative real-time polymerase chain reaction led to the detection of small quantities of Pbcts2 transcript in the mycelial phase. In the yeast cell wall extract, only the 39 kDa protein was detected. Moreover, both proteins were secreted by the yeast parasitic phase, suggesting that these proteins participate in the modulation of the fungal environment. Phylogenetic analysis of the predicted PbCTS1 and PbCTS2 proteins indicated that they code for distinct chitinases in P. brasiliensis. During evolution, P. brasiliensis could have acquired the paralogues Pbcts1 and Pbcts2 for growth and survival in diverse environments in both saprophytic and parasitic phases.