Life Cycle-Dependent Cytoskeletal Modifications in Plasmodium falciparum Infected Erythrocytes

10.1371/journal.pone.0061170PLoS ONE84

Comparison of hypoxia transcriptome in vitro with in vivo gene expression in human bladder cancer

Hypoxia-inducible genes have been linked to the aggressive phenotype of cancer. However, nearly all work on hypoxia-regulated genes has been conducted in vitro on cell lines. We investigated the hypoxia transcriptome in primary human bladder cancer using cDNA microarrays to compare genes induced by hypoxia in vitro in bladder cancer cell line EJ28 with genes upregulated in 39 bladder tumour specimens (27 superficial and 12 invasive). We correlated array mRNA fold changes with carbonic anhydrase 9 (CA IX) staining of tumours as a surrogate marker of hypoxia. Of 6000 genes, 32 were hypoxia inducible in vitro more than two-fold, five of which were novel, including lactate transporter SLC16A3 and RNAse 4. Eight of 32 hypoxia-inducible genes in vitro were also upregulated on the vivo array. Vascular endothelial growth factor mRNA was upregulated two-fold by hypoxia and 2–18-fold in 31 out of 39 tumours. Glucose transporter 1 was also upregulated on both arrays mRNA, and fold changes on the in vivo array significantly correlated with CA IX staining of tumours (P=0.008). However, insulin-like growth factor binding protein 3 mRNA was the most strongly differentially expressed gene in both arrays and this confirmed its upregulation in urine of bladder cancer patients (n=157, P<0.01). This study defines genes suitable for an in vivo hypoxia ‘profile', shows the heterogeneity of the hypoxia response and describes new hypoxia-regulated genes

Teachers’ and school leaders’ perceptions of commercialisation in Australian public schools

© 2017, The Australian Association for Research in Education, Inc. This paper explores teachers’ and school leaders’ perceptions of commercialisation in Australian public schools, reporting on findings from an open-ended survey question from an exploratory study that sought to investigate teacher and school leader perceptions and experiences of commercialisation. Commercialisation, for the purposes of this paper, is understood as the creation, marketing and sale of education goods and services to schools by for-profit providers and often includes (but is not limited to) the provision of curriculum content, assessment services, data infrastructures, digital learning, remedial instruction, professional development and school administration support. Our account highlights that commercialisation is prevalent in the day-to-day practice of Australian public schools. The perceptions of teachers and leaders suggest that commercialisation is complex, with both affordances and challenges. Respondents acknowledged that aspects of commercialisation are necessary for successfully running schools and classrooms in the 21st century, but also noted that there is a fine line beyond which these seemingly innocuous services become perilous. Concerns focused on how particular services are leading to the deprofessionalisation of teachers as they have less autonomy over what to teach and how to teach it. Moreover, teachers and school leaders reported being perturbed by the idea that commercial providers and services might work to replace teachers in the future. Drawing on these data we argue that growing commercialisation in Australian public schools clearly requires an ethical debate that schools, education professionals, policy makers and interested publics are yet to have

The importance of sedimenting organic matter, relative to oxygen and temperature, in structuring lake profundal macroinvertebrate assemblages

We quantified the role of a main food resource, sedimenting organic matter (SOM), relative to oxygen (DO) and temperature (TEMP) in structuring profundal macroinvertebrate assemblages in boreal lakes. SOM from 26 basins of 11 Finnish lakes was analysed for quantity (sedimentation rates), quality (C:N:P stoichiometry) and origin (carbon stable isotopes, d13C). Hypolimnetic oxygen and temperature were measured from each site during summer stratification. Partial canonical correspondence analysis (CCA) and partial regression analyses were used to quantify contributions of SOM, DO and TEMP to community composition and three macroinvertebrate metrics. The results suggested a major contribution of SOM in regulating the community composition and total biomass. Oxygen best explained the Shannon diversity, whereas TEMP had largest contribution to the variation of Benthic Quality Index. Community composition was most strongly related to d13C of SOM. Based on additional d13C and stoichiometric analyses of chironomid taxa, marked differences were apparent in their utilization of SOM and body stoichiometry; taxa characteristic of oligotrophic conditions exhibited higher C:N ratios and lower C:P and N:P ratios compared to the species typical of eutrophic lakes. The results highlight the role of SOM in regulating benthic communities and the distributions of individual species, particularly in oligotrophic systems

Molecular Systematics of the Deep-Sea Hydrothermal Vent Endemic Brachyuran Family Bythograeidae: A Comparison of Three Bayesian Species Tree Methods

Brachyuran crabs of the family Bythograeidae are endemic to deep-sea hydrothermal vents and represent one of the most successful groups of macroinvertebrates that have colonized this extreme environment. Occurring worldwide, the family includes six genera (Allograea, Austinograea, Bythograea, Cyanagraea, Gandalfus, and Segonzacia) and fourteen formally described species. To investigate their evolutionary relationships, we conducted Maximum Likelihood and Bayesian molecular phylogenetic analyses, based on DNA sequences from fragments of three mitochondrial genes (16S rDNA, Cytochrome oxidase I, and Cytochrome b) and three nuclear genes (28S rDNA, the sodium–potassium ATPase a-subunit ‘NaK’, and Histone H3A). We employed traditional concatenated (i.e., supermatrix) phylogenetic methods, as well as three recently developed Bayesian multilocus methods aimed at inferring species trees from potentially discordant gene trees. We found strong support for two main clades within Bythograeidae: one comprising the members of the genus Bythograea; and the other comprising the remaining genera. Relationships within each of these two clades were partially resolved. We compare our results with an earlier hypothesis on the phylogenetic relationships among bythograeid genera based on morphology. We also discuss the biogeography of the family in the light of our results. Our species tree analyses reveal differences in how each of the three methods weighs conflicting phylogenetic signal from different gene partitions and how limits on the number of outgroup taxa may affect the results

A qualitative analysis of the enforcement of the regulation of nutrition and health claims made for foods and its implications for health

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. In common with local government organisations across the world, local authorities in the UK have responsibility for promoting health. A key part of this function is the frontline enforcement activities of officers responsible for compliance with health and nutrition claims. This study identifies attitudes, values and practices of enforcers: namely trading standards and environmental health officers, when faced with the problem of non-compliance with the Regulation. Semi-structured interviews with frontline enforcers from local authority regulatory services to investigate challenges with the enforcement of Regulation (EC) 1924/2006. Twenty participants were interviewed; sixteen were based in North West England and two in the North and two in the South of England. The participants were selected for their specialist knowledge and experience of enforcement of nutrition and health claims. Regulation (EC) No. 1924/2006 on nutrition and health claims presents particular challenges for enforcers seeking to apply an optimal strategy to flawed regulatory design. As with other regulations, when faced with non-compliance, enforcers, specifically trading standards and environmental health officers have a wide discretion to determine their response: ranging from the deterrent or accommodative styles of enforcement. The participants reported using advice rather than action and by doing so confronting their bifurcating identity of prosecutor and advisor. Enforcers used advice as a regulatory tool in enforcing the law relating to nutrition and health claims

Clinical development of new drug-radiotherapy combinations.

In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer. In the past decade, significant technical advances, such as image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic radiotherapy, and proton therapy enable higher doses of radiotherapy to be delivered to the tumour with significantly lower doses to normal surrounding tissues. However, apart from the combination of traditional cytotoxic chemotherapy with radiotherapy, little progress has been made in identifying and defining optimal targeted therapy and radiotherapy combinations to improve the efficacy of cancer treatment. The National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad) formed a Joint Working Group with representatives from academia, industry, patient groups and regulatory bodies to address this lack of progress and to publish recommendations for future clinical research. Herein, we highlight the Working Group's consensus recommendations to increase the number of novel drugs being successfully registered in combination with radiotherapy to improve clinical outcomes for patients with cancer.National Institute for Health ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/nrclinonc.2016.7