Decorin protein core affects the global gene expression profile of the tumor microenvironment in a triple-negative orthotopic breast carcinoma xenograft model

Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal) and Homo sapiens (epithelial) tissue origins. We found that decorin protein core modulated the differential expression of 374 genes within the stromal compartment of the tumor xenograft. Further, our top gene ontology classes strongly suggests an unexpected and preferential role for decorin protein core to inhibit genes necessary for immunomodulatory responses while simultaneously inducing expression of those possessing cellular adhesion and tumor suppressive gene properties. Rigorous verification of the top scoring candidates led to the discovery of three genes heretofore unlinked to malignant breast cancer that were reproducibly found to be induced in several models of tumor stroma. Collectively, our data provide highly novel and unexpected stromal gene signatures as a direct function of systemic administration of decorin protein core and reveals a fundamental basis of action for decorin to modulate the tumor stroma as a biological mechanism for the ascribed anti-tumorigenic properties

Geochemical and microstructural characterisation of two species of cool-water bivalves (Fulvia tenuicostata and Soletellina biradiata) from Western Australia

The shells of two marine bivalve species (Fulvia tenuicostata and Soletellina biradiata) endemic to south Western Australia have been characterised using a combined crystallographic, spectroscopic and geochemical approach. Both species have been described previously as purely aragonitic; however, this study identified the presence of three phases, namely aragonite, calcite and Mg-calcite, using XRD analysis. Data obtained via confocal Raman spectroscopy, electron probe microanalysis and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) show correlations between Mg • S and Mg • P in F. tenuicostata and between Sr • S and S • Ba in S. biradiata. The composition of the organic macromolecules that constitute the shell organic matrix (i.e. the soluble phosphorus-dominated and/or insoluble sulfur-dominated fraction) influences the incorporation of Mg, Sr and Ba into the crystal lattice. Ionic substitution, particularly Ca2+ by Mg2+ in calcite in F. tenuicostata, appears to have been promoted by the combination of both S- and P-dominated organic macromolecules. The elemental composition of these two marine bivalve shells is species specific and influenced by many factors, such as crystallographic structure, organic macromolecule composition and environmental setting. In order to reliably use bivalve shells as proxies for paleoenvironmental reconstructions, both the organic and inorganic crystalline material need to be characterised to account for all influencing factors and accurately describe the "vital effect"

An in vivo genetic screen for genes involved in spliced leader trans-splicing indicates a crucial role for continuous de novo spliced leader RNP assembly

ACKNOWLEDGEMENTS Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). We would also like to thank Prof. Shohei Mitani,at the National Bioresource Project for the Experimental Animal ‘Nematode C. elegans’, Japan, for FX3079. We are grateful to Prof. Tom Blumenthal (University of Colorado, Boulder) for suggestions and support of this work; and to Kathrine Wood for her contribution to the initial stages of part of this work. Author contributions. L.P., G.P., R.F., N.H., J.P. and B.M. performed experiments; B.M., J.P. and B.C. designed and lead the study; B.M. and J.P. drafted the manuscript. All authors reviewed the manuscript. FUNDING Biotechnology and Biological Sciences Research Council (BBSRC) [Project grant BB/J007137/1]; Medical Research Council (MRC) Confidence in Concept 2014 - University of Aberdeen Award(MC PC 14114v.2); University of Aberdeen Elphinstone Scholarship (to R.F.) and TET Fund support through Adekunle Ajasin University, Nigeria (to R.F.). Funding for open access charge: Biotechnology and Biological Sciences Research Council and Medical Research Council.Peer reviewedPublisher PD

Ethnic variation in outcome of people hospitalised during the first COVID-19 epidemic wave in Wales (UK):an analysis of national surveillance data using Onomap, a name-based ethnicity classification tool

Objective To identify ethnic differences in proportion positive for SARS-CoV-2, and proportion hospitalised, proportion admitted to intensive care and proportion died in hospital with COVID-19 during the first epidemic wave in Wales.Design Descriptive analysis of 76 503 SARS-CoV-2 tests carried out in Wales to 31 May 2020. Cohort study of 4046 individuals hospitalised with confirmed COVID-19 between 1 March and 31 May. In both analyses, ethnicity was assigned using a name-based classifier.Setting Wales (UK).Primary and secondary outcomes Admission to an intensive care unit following hospitalisation with a positive SARS-CoV-2 PCR test. Death within 28 days of a positive SARS-CoV-2 PCR test.Results Using a name-based ethnicity classifier, we found a higher proportion of black, Asian and ethnic minority people tested for SARS-CoV-2 by PCR tested positive, compared with those classified as white. Hospitalised black, Asian and minority ethnic cases were younger (median age 53 compared with 76 years; p<0.01) and more likely to be admitted to intensive care. Bangladeshi (adjusted OR (aOR): 9.80, 95% CI 1.21 to 79.40) and ‘white – other than British or Irish’ (aOR: 1.99, 95% CI 1.15 to 3.44) ethnic groups were most likely to be admitted to intensive care unit. In Wales, older age (aOR for over 70 years: 10.29, 95% CI 6.78 to 15.64) and male gender (aOR: 1.38, 95% CI 1.19 to 1.59), but not ethnicity, were associated with death in hospitalised patients.Conclusions This study adds to the growing evidence that ethnic minorities are disproportionately affected by COVID-19. During the first COVID-19 epidemic wave in Wales, although ethnic minority populations were less likely to be tested and less likely to be hospitalised, those that did attend hospital were younger and more likely to be admitted to intensive care. Primary, secondary and tertiary COVID-19 prevention should target ethnic minority communities in Wales

Current transfusion practice and need for new blood products to ensure blood supply for patients with major hemorrhage in Europe

Background: New blood products are considered for treatment of patients with major hemorrhage. The aim of this report is to describe the current transfusion practices in Europe for patients with major hemorrhage and explore the need for new or modified blood products to ensure prehospital and in-hospital blood supply. Study Design and Method: The European Blood Alliance (EBA) Working Group on Innovation and New Blood Products' subgroup on major hemorrhage performed a survey among the EBA member states. Results: The response rate was 58% (17 responses from 15 of the 26 EBA member states). Of these, sixteen (94%) provide massive transfusion packages (MTPs) with balanced ratio of red blood cells and plasma. Seven of the respondents included platelets from the start of treatment. Eleven (65%) provide prehospital blood products, mainly red cell concentrates or dried and/or thawed plasma with 5 days of extended storage. Two countries provide prehospital whole blood. Twelve respondents (71%) saw a need for implementation of new or modified blood components in their institution. The top three priorities were whole blood (12 of 12, 100%), dried plasma (8 of 12, 67%), and cold-stored platelets (7 of 12, 58%). Discussion: Current national guidelines for use of blood products in patients with major hemorrhage in Europe agree on the use of balanced transfusion, however the timing and source of platelets differ. Blood products for prehospital transfusion are available in several European countries. An interest in new or modified blood products for patients with major hemorrhage was observed, especially for whole blood.publishedVersio

Impact of Cytomegalovirus and Grafts versus Host Disease on the Dynamics of CD57+CD28−CD8+ T Cells After Bone Marrow Transplant

OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05). A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94%, p<0.01) and an increase in CD57+ lymphocytes (5.60%, p<0.01). This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant), also had an impact on the CD57+ subset, triggering an increase of 4.9% in CD57+ lymphocytes (p<0.05). CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia

Phylogenetic relationship among Kenyan sorghum germplasms based on aluminium tolerance

Eighty nine (89) sorghum lines sourced from various parts of Kenya were used to determine phylogenetic relationships based on 10 DNA fragments at AltSB loci with SbMATE, ORF9 and MITE primers. Nine lines of varying aluminium tolerance levels were selected to compare their SbMATE gene expression via the real-time PCR quantification of SbMATE gene expression. The sorghum line MSCR O2 expressed a thousandfold more SbMATEgene activity than the sensitive lines (MSCRM49, MSCRN84 and MSCRN61) under Al treatment. Analysis was done by agarose gel electrophoresis stained with ethidium bromide. The objective of this study was to assess the level of phylogenetic relationships among the Kenyan sorghum germplasms at a known Al tolerance locus. Hierarchical cluster analysis joined at 70% simple matching coefficient using average linkage similarity level produced nine groups in which 67 lines fell in three major clusters of 39, 15 and 13 lines each. The three Al tolerant lines MSCRO2, MSCRC1 and MSCRN60 were clustered together. Lines MSCRO2, MSCRC1 and MSCRN60, screened to be Al tolerant were genetically related at 70% average linkage similarity level and therefore recommend their further development as a food security measure in Kenya.Keywords: Aluminium (Al) toxicity, Sorghum bicolor, Sorghum bicolor multi-drug, toxic extrusion compound (SbMATE) gene expressionAfrican Journal of Biotechnology Vol. 12(22), pp. 3528-353

Interactive Visual System

Mobile computing devices are being endowed with ever-increasing functionality. To demonstrate the augmentation of human cognition in an interactive visual recognition task, we reengineered a PC-based system called CAVIAR (Computer Assisted Visual Interactive System) for a handheld computer with camera system. The resulting Interactive Visual System exploits the pattern recognition capabilities of humans and the computational power of a computer to identify flowers based on features that are interactively extracted from an image and submitted for comparison to a species database. While IVS has similar functionality to that of CAVIAR, because it runs on a handheld computer, it offers complete portability for use in the field. We find that the handheld IVS and PC-based CAVIAR systems outperform humans alone both on speed and accuracy and machines alone on accuracy

Non-Formal Education in a World Context

During the past decade the role of non-formal education throughout the world has become an important topic. Educators realize that the formal system cannot solve the diversified and complex problems which face a society today. As a consequence a closer look is now being taken at educational activities outside the established system--especially those non-formal processes which have a relationship to socio-economic development. While many societies have a long tradition of non-formal education, little attempt has been made to utilize this base to provide individuals with a flexible and diversified range of useful learning opportunities. Recently, however, the innate potential of non-formal education is being realized. Today education is being viewed as a life-long process rather than the specified knowledge transmitted in a formal school system. As interest in the field of non-formal education developed, attempts have been made to collect and exchange useful information. Toward this end, the Center for International Education, University of Massachusetts, hosted a World Education Conference and invited educators to share ideas on non-formal education. This booklet contains the papers delivered at that Conference. Some papers are exploratory and some definitive, some are brief overviews, and others are detailed accounts; however, all the papers make a worthwhile contribution to the field. The papers have been organized according to geographical areas

The development of the nursing profession in a globalised context: a qualitative case study in Kerala, India

In the paper, we are looking at the relationship between globalisation and the professional project, using nursing in Kerala as an exemplar. Our focus is on the intersection of the professional project, gender and globalisation processes. Included in our analysis are the ways in which gender affects the professional project in the global south, and the development of a professional project which it is closely tied to global markets and global migration, revealing the political-economic, historical, and cultural factors that influence the shape and consequences of nurse migration. The phenomenon that enabled our analysis, by showing these forces at work in a particular time and place, was an outbreak of strikes by nurses working in private hospitals in Kerala in 2011–2012