Workflows for Quantitative Data Analysis in The Social Sciences

The background is given to how statistical analysis is used by quantitative social scientists. Developing statistical analyses requires substantial effort, yet there are important limitations in current practice. This has motivated the authors to create a more systematic and effective methodology with supporting tools. The approach to modelling quantitative data analysis in the social sciences is presented. Analysis scripts are treated abstractly as mathematical functions and concretely as web services. This allows individual scripts to be combined into high-level workflows. A comprehensive set of tools allows workflows to be defined, automatically validated and verified, and automatically implemented. The workflows expose opportunities for parallel execution, can define support for proper fault handling, and can be realised by non-technical users. Services, workflows and datasets can also be readily shared. The approach is illustrated with a realistic case study that analyses occupational position in relation to health

Global distribution of two fungal pathogens threatening endangered sea turtles

This work was supported by grants of Ministerio de Ciencia e Innovación, Spain (CGL2009-10032, CGL2012-32934). J.M.S.R was supported by PhD fellowship of the CSIC (JAEPre 0901804). The Natural Environment Research Council and the Biotechnology and Biological Sciences Research Council supported P.V.W. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Thanks Machalilla National Park in Ecuador, Pacuare Nature Reserve in Costa Rica, Foundations Natura 2000 in Cape Verde and Equilibrio Azul in Ecuador, Dr. Jesus Muñoz, Dr. Ian Bell, Dr. Juan Patiño for help and technical support during samplingPeer reviewedPublisher PD

Distinct Mechanisms for Induction and Tolerance Regulate the Immediate Early Genes Encoding Interleukin 1β and Tumor Necrosis Factor α

Interleukin-1β and Tumor Necrosis Factor α play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes. In contrast, unstimulated IL1B displayed very low levels of both TBP and paused Pol II, requiring the lineage-specific Spi-1/PU.1 (Spi1) transcription factor as an anchor for induction-dependent interaction with two TLR-activated transcription factors, C/EBPβ and NF-κB. Activation and DNA binding of these two pre-expressed factors resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of elongation factor P-TEFb. This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Furthermore, the dependence on phosphoinositide 3-kinase for P-TEFb recruitment to IL1B paralleled a greater sensitivity to the metabolic state of the cell and a lower sensitivity to the phenomenon of endotoxin tolerance than was evident for TNF. Such differences in induction mechanisms argue against the prevailing paradigm that all IE genes possess paused Pol II and may further delineate the specific roles played by each of these rapidly expressed immune modulators. © 2013 Adamik et al

The reactive species interactome: evolutionary emergence, biological significance, and opportunities for redox metabolomics and personalized medicine

SIGNIFICANCE: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not administration of antioxidants is ineffective, suggesting our current understanding of the underlying regulatory processes is incomplete. Recent Advances. Similar to reactive oxygen and nitrogen species (ROS, RNS), reactive sulfur species (RSS) are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept coined the reactive species interactome (RSI). The RSI is a primeval multi-level redox-regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stresses to enhance fitness and resilience at the local and whole-organism level. CRITICAL ISSUES: To better characterise the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems and effects on cellular, organ and whole-organism bioenergetics using systems-level/network analyses. FUTURE DIRECTIONS: Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other stresses will provide new prevention/intervention opportunities for personalized medicine

Indivo: a personally controlled health record for health information exchange and communication

<p>Abstract</p> <p>Background</p> <p>Personally controlled health records (PCHRs), a subset of personal health records (PHRs), enable a patient to assemble, maintain and manage a secure copy of his or her medical data. Indivo (formerly PING) is an open source, open standards PCHR with an open application programming interface (API).</p> <p>Results</p> <p>We describe how the PCHR platform can provide standard building blocks for networked PHR applications. Indivo allows the ready integration of diverse sources of medical data under a patient's control through the use of standards-based communication protocols and APIs for connecting PCHRs to existing and future health information systems.</p> <p>Conclusion</p> <p>The strict and transparent personal control model is designed to encourage widespread participation by patients, healthcare providers and institutions, thus creating the ecosystem for development of innovative, consumer-focused healthcare applications.</p

Flip-Flop of Phospholipids in Proteoliposomes Reconstituted from Detergent Extract of Chloroplast Membranes: Kinetics and Phospholipid Specificity

Eukaryotic cells are compartmentalized into distinct sub-cellular organelles by lipid bilayers, which are known to be involved in numerous cellular processes. The wide repertoire of lipids, synthesized in the biogenic membranes like the endoplasmic reticulum and bacterial cytoplasmic membranes are initially localized in the cytosolic leaflet and some of these lipids have to be translocated to the exoplasmic leaflet for membrane biogenesis and uniform growth. It is known that phospholipid (PL) translocation in biogenic membranes is mediated by specific membrane proteins which occur in a rapid, bi-directional fashion without metabolic energy requirement and with no specificity to PL head group. A recent study reported the existence of biogenic membrane flippases in plants and that the mechanism of plant membrane biogenesis was similar to that found in animals. In this study, we demonstrate for the first time ATP independent and ATP dependent flippase activity in chloroplast membranes of plants. For this, we generated proteoliposomes from Triton X-100 extract of intact chloroplast, envelope membrane and thylakoid isolated from spinach leaves and assayed for flippase activity using fluorescent labeled phospholipids. Half-life time of flipping was found to be 6±1 min. We also show that: (a) intact chloroplast and envelope membrane reconstituted proteoliposomes can flip fluorescent labeled analogs of phosphatidylcholine in ATP independent manner, (b) envelope membrane and thylakoid reconstituted proteoliposomes can flip phosphatidylglycerol in ATP dependent manner, (c) Biogenic membrane ATP independent PC flipping activity is protein mediated and (d) the kinetics of PC translocation gets affected differently upon treatment with protease and protein modifying reagents

Galactic Winds across the Gas-rich Merger Sequence. I. Highly Ionized N v and O vi Outflows in the QUEST Quasars*

Abstract This program is part of QUEST (Quasar/ULIRG Evolutionary Study) and seeks to examine the gaseous environments of z ≲ 0.3 quasars and ULIRGs as a function of host galaxy properties and age across the merger sequence from ULIRGs to quasars. This first paper in the series focuses on 33 quasars from the QUEST sample and on the kinematics of the highly ionized gas phase traced by the N v λ λ 1238,1243 and O vi λ λ 1032,1038 absorption lines in high-quality Hubble Space Telescope (HST) Cosmic Origins Spectrograph (COS) data. N v and O vi outflows are present in about 60% of the QUEST quasars and span a broad range of properties, both in terms of equivalent widths (from 20 mÅ to 25 Å) and kinematics (outflow velocities from a few×100 km s−1 up to ∼10,000 km s−1). The rate of incidence and equivalent widths of the highly ionized outflows are higher among X-ray weak or absorbed sources. The weighted outflow velocity dispersions are highest among the X-ray weakest sources. No significant trends are found between the weighted outflow velocities and the properties of the quasars and host galaxies, although this may be due to the limited dynamic range of properties of the current sample. These results will be re-examined in an upcoming paper where the sample is expanded to include the QUEST ULIRGs. Finally, a lower limit of ∼0.1% on the ratio of time-averaged kinetic power to bolometric luminosity is estimated in the 2–4 objects with blueshifted P v λ λ 1117,1128 absorption features.</jats:p

Imaging Mass Spectrometry Detection of Gangliosides Species in the Mouse Brain following Transient Focal Cerebral Ischemia and Long-Term Recovery

Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of ganglioside species using matrix-assisted laser desorption/ionization (MALDI) imaging (IMS) following middle cerebral artery occlusion (MCAO) reperfusion injury in the mouse. IMS is a powerful method to not only discriminate gangliosides by their oligosaccharide components, but also by their carbon length within their sphingosine base. Mice were subjected to a 30 min unilateral MCAO followed by long-term survival (up to 28 days of reperfusion). Brain sections were sprayed with the matrix 5-Chloro-2-mercaptobenzothiazole, scanned and analyzed for a series of ganglioside molecules using an Applied Biosystems 4800 MALDI TOF/TOF. Traditional histological and immunofluorescence techniques were performed to assess brain tissue damage and verification of the expression of gangliosides of interest. Results revealed a unique anatomical profile of GM1, GD1 and GT1b (d18∶1, d20∶1 as well as other members of the glycosphingolipid family). There was marked variability in the ratio of expression between ipsilateral and contralateral cortices for the various detected ganglioside species following MCAO-reperfusion injury. Most interestingly, MCAO resulted in the transient induction of both GM2 and GM3 signals within the ipsilateral hemisphere; at the border of the infarcted tissue. Taken together, the data suggest that brain region specific expression of gangliosides, particularly with respect to hydrocarbon length, may play a role in neuronal responses to injury

Molecular Evolution of the Rice Blast Resistance Gene Pi-ta in Invasive Weedy Rice in the USA

The Pi-ta gene in rice has been effectively used to control rice blast disease caused by Magnaporthe oryzae worldwide. Despite a number of studies that reported the Pi-ta gene in domesticated rice and wild species, little is known about how the Pi-ta gene has evolved in US weedy rice, a major weed of rice. To investigate the genome organization of the Pi-ta gene in weedy rice and its relationship to gene flow between cultivated and weedy rice in the US, we analyzed nucleotide sequence variation at the Pi-ta gene and its surrounding 2 Mb region in 156 weedy, domesticated and wild rice relatives. We found that the region at and around the Pi-ta gene shows very low genetic diversity in US weedy rice. The patterns of molecular diversity in weeds are more similar to cultivated rice (indica and aus), which have never been cultivated in the US, rather than the wild rice species, Oryza rufipogon. In addition, the resistant Pi-ta allele (Pi-ta) found in the majority of US weedy rice belongs to the weedy group strawhull awnless (SH), suggesting a single source of origin for Pi-ta. Weeds with Pi-ta were resistant to two M. oryzae races, IC17 and IB49, except for three accessions, suggesting that component(s) required for the Pi-ta mediated resistance may be missing in these accessions. Signatures of flanking sequences of the Pi-ta gene and SSR markers on chromosome 12 suggest that the susceptible pi-ta allele (pi-ta), not Pi-ta, has been introgressed from cultivated to weedy rice by out-crossing