Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice.

Background: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infection are still largely unknown. Results: As a step towards mapping these genes, we applied a genome wide linkage analysis approach to a mouse model. A large F2 intercross population, obtained by mating P. aeruginosa-resistant C3H/HeOuJ, and susceptible A/J mice, was used for quantitative trait locus (QTL) mapping. The F2 progenies were challenged with a P. aeruginosa clinical strain and monitored for the survival time up to 7 days post-infection, as a disease phenotype associated trait. Selected phenotypic extremes of the F2 distribution were genotyped with high-density single nucleotide polymorphic (SNP) markers, and subsequently QTL analysis was performed. A significant locus was mapped on chromosome 6 and was named P. aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment and inflammatory processes. Conclusions: We propose a set of genes involved in the pathogenesis of P. aeruginosa infection that may be explored to complement human studie

Extensive necrosis of visceral melanoma metastases after immunotherapy

<p>Abstract</p> <p>Background</p> <p>The prognosis for metastatic melanoma remains poor even with traditional decarbazine or interferon therapy. 5-year survival is markedly higher amongst patients undergoing metastatectomy. Unfortunately not all are suitable for metastatectomy. Alternative agents for systemic therapy have, to date, offered no greater rates of survival beyond traditional therapy. A toll-like receptor 9 agonist, PF-3512676 (formerly known as CPG 7909) is currently being evaluated for its potential.</p> <p>Case presentation</p> <p>We present the case of a 54-year-old Caucasian male with completely resected metastatic cutaneous melanoma after immunotherapy. The patient initially progressed during adjuvant high-dose interferon, with metastases to the liver, spleen, and pelvic lymph nodes. During an 18-month treatment period with PF-3512676 (formerly known as CPG 7909), a synthetic cytosine-phosphorothioate-guanine rich oligodeoxynucleotide, slow radiologic disease progression was demonstrated at the original disease sites. Subsequent excision of splenic and pelvic nodal metastases was performed, followed by resection of the liver metastases. Histologic examination of both hepatic and splenic melanoma metastases showed extensive necrosis. Subsequent disease-free status was demonstrated by serial positron emission tomography (PET).</p> <p>Conclusion</p> <p>Existing evidence from phase I/II trials suggests systemic treatment with PF-3512676 is capable of provoking a strong tumor-specific immune response and may account for the prolonged tumor control in this instance.</p

Development of a measure of model fidelity for mental health Crisis Resolution Teams

Background Crisis Resolution Teams (CRTs) provide short-term intensive home treatment to people experiencing mental health crisis. Trial evidence suggests CRTs can be effective at reducing hospital admissions and increasing satisfaction with acute care. When scaled up to national level however, CRT implementation and outcomes have been variable. We aimed to develop and test a fidelity scale to assess adherence to a model of best practice for CRTs, based on best available evidence. Methods A concept mapping process was used to develop a CRT fidelity scale. Participants (n = 68) from a range of stakeholder groups prioritised and grouped statements (n = 72) about important components of the CRT model, generated from a literature review, national survey and qualitative interviews. These data were analysed using Ariadne software and the resultant cluster solution informed item selection for a CRT fidelity scale. Operational criteria and scoring anchor points were developed for each item. The CORE CRT fidelity scale was then piloted in 75 CRTs in the UK to assess the range of scores achieved and feasibility for use in a 1-day fidelity review process. Trained reviewers (n = 16) rated CRT service fidelity in a vignette exercise to test the scale’s inter-rater reliability. Results There were high levels of agreement within and between stakeholder groups regarding the most important components of the CRT model. A 39-item measure of CRT model fidelity was developed. Piloting indicated that the scale was feasible for use to assess CRT model fidelity and had good face validity. The wide range of item scores and total scores across CRT services in the pilot demonstrate the measure can distinguish lower and higher fidelity services. Moderately good inter-rater reliability was found, with an estimated correlation between individual ratings of 0.65 (95% CI: 0.54 to 0.76). Conclusions The CORE CRT Fidelity Scale has been developed through a rigorous and systematic process. Promising initial testing indicates its value in assessing adherence to a model of CRT best practice and to support service improvement monitoring and planning. Further research is required to establish its psychometric properties and international applicability

Distribution, Population Biology, and Trophic Ecology of the Deepwater Demersal Fish Halosauropsis macrochir (Pisces: Halosauridae) on the Mid-Atlantic Ridge

Halosauropsis macrochir ranked amongst the most abundant and widespread demersal fishes on the mid-Atlantic Ridge of the North Atlantic (Iceland-Azores) with greatest abundance at 1700–3500 m. All sizes, ranging from 10–76 cm total length, occurred in the area without any apparent spatial pattern or depth trend. Using otolith sections displaying growth increments assumed to represent annuli, the age range recorded was 2–36 years, but most individuals were <20 years. Length and weight at age data were used to fit growth models. No differences between sexes in length and weight at age were observed. The majority of samples had a surplus of males. Diet analysis showed that H. macrochir feeds on Crustacea, Teleostei, Polychaeta, and Cephalopoda, but few prey could be identified to lower taxonomical levels. The mid-Atlantic Ridge constitutes a major portion of the North Atlantic living space of the abyssal halosaur where it completes its full life cycle, primarily as an actively foraging euryophagous micronekton/epibenthos and infauna feeder, becoming a partial piscivore with increasing size

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table

Antiproliferation effect of sulforaphene isolated from radish (Raphanus sativus L.) seeds on A549 cells

Sulforaphene (SFE), a major isothiocyanate in radish seeds, is a close chemical relative of sulforaphane (SFA) isolated from broccoli seeds and florets. The anti-proliferative mechanisms of SFA against cancer cells have been well investigated, but little is known about the potential anti-proliferative effects of SFE. In this study, we showed that SFE purified from radish seeds inhibited the growth of six cancer cell lines (A549, CHO, HeLa, Hepa1c1c7, HT-29, and LnCaP), with relative half maximal inhibitory concentration values ranging from 1.37 to 3.31 μg/mL. Among the six cancer cell lines, SFE showed the greatest growth inhibition against A549 lung cancer cells, where it induced apoptosis by changing the levels of poly(ADP-ribose) polymerase and caspase-3, -8, and -9. Our results indicate that SFE from radish seeds may have significant anti-proliferative potency against a broad range of human cancer cells via induction of apoptosis

Defining functional diversity for lignocellulose degradation in a microbial community using multi-omics studies

Abstract\ud \ud Background\ud Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere. Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments. While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform “community-level” metabolism of lignocellulose. Single-species approaches are, therefore, likely to miss important aspects of lignocellulose degradation that will be central to optimizing commercial processes.\ud \ud \ud Results\ud Here, we investigated the microbial degradation of wheat straw in liquid cultures that had been inoculated with wheat straw compost. Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks. Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment. Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera. The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance. A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant. This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation. The expression of these activities correlated to the changes in the biomass composition observed by FTIR and ssNMR measurements.\ud \ud \ud Conclusions\ud A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks. In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.This work was funded by Biotechnology and Biological Sciences Research\ud Council (BBSRC) Grants BB/1018492/1, BB/K020358/1 and BB/P027717/1, the\ud BBSRC Network in Biotechnology and Bioenergy BIOCATNET and São Paulo\ud Research Foundation (FAPESP) Grant 10/52362-5. ERdA thanks EMBRAPA\ud Instrumentation São Carlos and Dr. Luiz Alberto Colnago for providing the\ud NMR facility and CNPq Grant 312852/2014-2. The authors would like to thank\ud Deborah Rathbone and Susan Heywood from the Biorenewables Develop‑\ud ment Centre for technical assistance in rRNA amplicon sequencing

Design for invention: annotation of Functional Geometry Interaction for representing novel working principles

In some mechanical engineering devices the novelty or inventive step of a patented design relies heavily upon how geometric features contribute to device functions. Communicating the functional interactions between geometric features in existing patented designs may increase a designer’s awareness of the prior art and thereby avoid conflict with their emerging design. This paper shows how functional representations of geometry interactions can be developed from patent claims to produce novel semantic graphical and text annotations of patent drawings. The approach provides a quick and accurate means for the designer to understand the patent that is well suited to the designer’s natural way of understanding the device. Through several example application cases we show the application of a detailed representation of Functional Geometry Interactions that captures the working principle of familiar mechanical engineering devices described in patents. A computer tool that is being developed to assist the designer to understand prior art is also described

How authentic leadership influences team performance:the mediating role of team reflexivity

This study examines how authentic leadership influences team performance via the mediating mechanism of team reflexivity. Adopting a self-regulatory perspective, we propose that authentic leadership will predict the specific team regulatory process of reflexivity, which in turn will be associated with two outcomes of team performance; effectiveness and productivity. Using survey data from 53 teams in three organizations in the United Kingdom and Greece and controlling for collective trust, we found support for our stated hypotheses with the results indicating a significant fully mediated relationship. As predicted the self-regulatory behaviors inherent in the process of authentic leadership served to collectively shape team behavior, manifesting in the process of team reflexivity, which, in turn, positively predicted team performance. We conclude with a discussion of how this study extends theoretical understanding of authentic leadership in relation to teamwork and delineate several practical implications for leaders and organizations