Environmental risk assessment of genetically modified crops: The use of molecular markers to trace insect and wind dispersal of Brassica napus pollen.

End of Project ReportThis project aimed to develop a better understanding of the potential risks of gene flow and to generate isolation distances required for genetically modified (GM) OSR. The study examined biotic (insect) and abiotic (wind) pollen dispersal over two seasons. A considerable portion of work was devoted to the development of molecular markers, to differentiate Brassica napus varieties from each other to distinguish them from their wild relatives. The project broadly aimed to study gene flow, via pollen movement, from OSR but specifically aimed to: ! Characterise B. napus cv. Marinka using molecular markers. ! Elucidate the distance travelled by OSR pollen by biotic dispersal. ! Elucidate the distance travelled by OSR pollen by abiotic dispersal. ! Elucidate pollination/seed set at various distances from a source crop using male sterile bait plants. ! Develop risk assessment/containment strategies

Recreational Diving Impacts on Coral Reefs and the Adoption of Environmentally Responsible Practices within the SCUBA Diving Industry

Recreational diving on coral reefs is an activity that has experienced rapidly growing levels of popularity and participation. Despite providing economic activity for many developing coastal communities, the potential role of dive impacts in contributing to coral reef damage is a concern at heavily dived locations. Management measures to address this issue increasingly include the introduction of programmes designed to encourage environmentally responsible practices within the dive industry. We examined diver behaviour at several important coral reef dive locations within the Philippines and assessed how diver characteristics and dive operator compliance with an environmentally responsible diving programme, known as the Green Fins approach, affected reef contacts. The role of dive supervision was assessed by recording dive guide interventions underwater, and how this was affected by dive group size. Of the 100 recreational divers followed, 88 % made contact with the reef at least once per dive, with a mean (±SE) contact rate of 0.12 ± 0.01 per min. We found evidence that the ability of dive guides to intervene and correct diver behaviour in the event of a reef contact decreases with larger diver group sizes. Divers from operators with high levels of compliance with the Green Fins programme exhibited significantly lower reef contact rates than those from dive operators with low levels of compliance. The successful implementation of environmentally responsible diving programmes, which focus on influencing dive industry operations, can contribute to the management of human impacts on coral reefs

The Origin and Evolution of Magnetic Fabrics in Mafic Sills

Studying extinct volcanoes where erosion has exposed dykes and sills provides direct access to the fossil remnants of magma movement, however, linking crystallized magma to emplacement dynamics is challenging. This study investigates how magma flow varies across the thickness of a thin (6 m thick) mafic sill. We use a high-resolution sampling regime to measure micro-scale variations in magnetic anisotropy, which is associated with the orientation of the magnetic particles present within the crystalline rock. Fieldwork was conducted on exposed sills of the British and Irish Palaeogene Igneous Province, Isle of Skye, Scotland. Here Jurassic sedimentary rocks have been intruded by a series of sills, of picrite to crinanite composition, from the Little Minch Sill Complex (c.60 Ma). Anisotropy of magnetic susceptibility (AMS) and anisotropy of anhysteretic remanent magnetization (AARM) signals have been used to separate a crinanite sill into distinct magnetic groupings. We identified two AMS groups (the upper and lower sill margins, and the central region) and four AARM groups (the lower margin, the middle region, a region just below the upper margin, and the upper margin). Both AMS and AARM signals originate from titanomagnetite of multi-domain or vortex-state to single-domain sized grains, respectively. The AMS and AARM fabrics are aligned with each other in the margin regions preserving a history of magma flow toward the North during initial emplacement. However, in the sill interior the magnetic fabrics are oblique to each other, thus reflecting multiple origins. We suggest the AMS fabrics have recorded magma flow during sill growth, and AARM fabrics have recorded melt percolation flow as the interstitial melt migrated upward through a solidifying crystal mush. We demonstrate that when AMS and AARM are used in combination they enable a detailed understanding of magma flow and solidification dynamics to be obtained, from initial emplacement to solidification. Overall, our detailed sampling and analysis indicates that magnetic fabrics can be highly variable over small distances, supporting the suggestion of horizontal flow restriction and propagation path migration within growing sills, and that previous reports of magma flow and solidification dynamics based on under-sampled bodies may require reconsideration

Enhanced hepatic respiratory capacity and altered lipid metabolism support metabolic homeostasis during short-term hypoxic stress.

BACKGROUND: Tissue hypoxia is a key feature of several endemic hepatic diseases, including alcoholic and non-alcoholic fatty liver disease, and organ failure. Hypoxia imposes a severe metabolic challenge on the liver, potentially disrupting its capacity to carry out essential functions including fuel storage and the integration of lipid metabolism at the whole-body level. Mitochondrial respiratory function is understood to be critical in mediating the hepatic hypoxic response, yet the time-dependent nature of this response and the role of the respiratory chain in this remain unclear. RESULTS: Here, we report that hepatic respiratory capacity is enhanced following short-term exposure to hypoxia (2 days, 10% O2) and is associated with increased abundance of the respiratory chain supercomplex III2+IV and increased cardiolipin levels. Suppression of this enhanced respiratory capacity, achieved via mild inhibition of mitochondrial complex III, disrupted metabolic homeostasis. Hypoxic exposure for 2 days led to accumulation of plasma and hepatic long chain acyl-carnitines. This was observed alongside depletion of hepatic triacylglycerol species with total chain lengths of 39-53 carbons, containing palmitic, palmitoleic, stearic, and oleic acids, which are associated with de novo lipogenesis. The changes to hepatic respiratory capacity and lipid metabolism following 2 days hypoxic exposure were transient, becoming resolved after 14 days in line with systemic acclimation to hypoxia and elevated circulating haemoglobin concentrations. CONCLUSIONS: The liver maintains metabolic homeostasis in response to shorter term hypoxic exposure through transient enhancement of respiratory chain capacity and alterations to lipid metabolism. These findings may have implications in understanding and treating hepatic pathologies associated with hypoxia.GlaxoSmithKlin

Microbiome and environment explain the absence of correlations between consumers and their diet in Bornean microsnails

Classical ecological theory posits that species partition resources such that each species occupies a unique resource niche. In general, the availability of more resources allows more species to co‐occur. Thus, a strong relationship between communities of consumers and their resources is expected. However, correlations may be influenced by other layers in the food web, or by the environment. Here we show, by studying the relationship between communities of consumers (land snails) and individual diets (from seed plants), that there is in fact no direct, or at most a weak but negative, relationship. However, we found that the diversity of the individual microbiome positively correlates with both consumer community diversity and individual diet diversity in three target species. Moreover, these correlations were affected by various environmental variables, such as anthropogenic activity, habitat island size, and a possibly important nutrient source, guano runoff from nearby caves. Our results suggest that the microbiome and the environment explain the absence of correlations between diet and consumer community diversity. Hence, we advocate that microbiome inventories are routinely added to any community dietary analysis, which our study shows can be done with relatively little extra effort. Our approach presents the tools to quickly obtain an overview of the relationships between consumers and their resources. We anticipate our approach to be useful for ecologists and environmentalist studying different communities in a local food web

Establishing effective conservation management strategies for a poorly known endangered species: A case study using Australia’s night parrot (Pezoporus occidentalis)

An evidence-based approach to the conservation management of a species requires knowledge of that species’ status, distribution, ecology, and threats. Coupled with budgets for specific conservation strategies, this knowledge allows prioritisation of funding toward activities that maximise benefit for the species. However, many threatened species are poorly known, and determining which conservation strategies will achieve this is difficult. Such cases require approaches that allow decision-making under uncertainty. Here we used structured expert elicitation to estimate the likely benefit of potential management strategies for the Critically Endangered and, until recently, poorly known Night Parrot (Pezoporus occidentalis). Experts considered cat management the single most effective management strategy for the Night Parrot. However, a combination of protecting and actively managing existing intact Night Parrot habitat through management of grazing, controlling feral cats, and managing fire specifically to maintain Night Parrot habitat was thought to result in the greatest conservation gains. The most cost-effective strategies were thought to be fire management to maintain Night Parrot habitat, and intensive cat management using control methods that exploit local knowledge of cat movements and ecology. Protecting and restoring potentially suitable, but degraded, Night Parrot habitat was considered the least effective and least cost-effective strategy. These expert judgements provide an informed starting point for land managers implementing on-ground programs targeting the Night Parrot, and those developing policy aimed at the species’ longer-term conservation. As a set of hypotheses, they should be implemented, assessed, and improved within an adaptive management framework that also considers the likely co-benefits of these strategies for other species and ecosystems. The broader methodology is applicable to conservation planning for the management and conservation of other poorly known threatened species

Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors.

The essential enzyme CYP121 is a target for drug development against antibiotic resistant strains of Mycobacterium tuberculosis. A triazol-1-yl phenol fragment 1 was identified to bind to CYP121 using a cascade of biophysical assays. Synthetic merging and optimization of 1 produced a 100-fold improvement in binding affinity, yielding lead compound 2 (KD = 15 μM). Deconstruction of 2 into its component retrofragments allowed the group efficiency of structural motifs to be assessed, the identification of more LE scaffolds for optimization and highlighted binding affinity hotspots. Structure-guided addition of a metal-binding pharmacophore onto LE retrofragment scaffolds produced low nanomolar (KD = 15 nM) CYP121 ligands. Elaboration of these compounds to target binding hotspots in the distal active site afforded compounds with excellent selectivity against human drug-metabolizing P450s. Analysis of the factors governing ligand potency and selectivity using X-ray crystallography, UV-vis spectroscopy, and native mass spectrometry provides insight for subsequent drug development.MEK was supported by a Commonwealth (University of Cambridge) Scholarship awarded in conjunction with the Cambridge Commonwealth Trust and Cambridge Overseas Trust. AGC and KJM were supported by grants from the BBSRC (Grant No: BB/I019669/1 and BB/I019227/1). GGJ received funding from the Ogden Trust and the Isaac Newton Trust administered through the University of Cambridge Bursary Scheme. DSCH was supported by a Croucher Cambridge International Scholarship awarded in conjunction between the Croucher Foundation and the Cambridge Overseas Trust. SAH was supported by an Oliphant Cambridge Australia Scholarship (App No: 10132070) awarded by the Cambridge Commonwealth Trust. The contributions of LBM and LPSC were supported by funds from the Francis Crick Institute, which receives its core funding principally from Wellcome Trust, Cancer Research UK, and the UK Medical Research Council (to LPSC - MC_UP_A253_1111) and funds from FAPESP, CNPq and CAPES-PDSE (to LBM - 2011/21232-1, 140079/2013-0, 99999.003125/2014-09).This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/acs.jmedchem.6b0000

HLA-B*35-Px–mediated acceleration of HIV-1 infection by increased inhibitory immunoregulatory impulses

A subset of HLA-B*35 alleles, B*35-Px, are strongly associated with accelerated HIV-1 disease progression for reasons that are not understood. Interestingly, the alternative set of B*35 subtypes, B*35-PY, have no detectable impact on HIV-1 disease outcomes, even though they can present identical HIV-1 epitopes as B*35-Px molecules. Thus, the differential impact of these alleles on HIV-1 disease progression may be unrelated to interactions with HIV-1–specific CD8+ T cells. Here, we show that the B*35-Px molecule B*3503 binds with greater affinity to immunoglobulin-like transcript 4 (ILT4), an inhibitory MHC class I receptor expressed on dendritic cells, than does the B*35-PY molecule B*3501, even though these two B*35 molecules differ by only one amino acid and present identical HIV-1 epitopes. The preferential recognition of B*3503 by ILT4 was associated with significantly stronger dendritic cell dysfunction in in vitro functional assays. Moreover, HIV-1–infected carriers of B*3503 had poor dendritic cell functional properties in ex vivo assessments when compared with carriers of the B*3501 allele. Differential interactions between HLA class I allele subtypes and immunoregulatory MHC class I receptors on dendritic cells thus provide a novel perspective for the understanding of MHC class I associations with HIV-1 disease progression and for the manipulation of host immunity against HIV-1

Recommendations for and compliance with social restrictions during implementation of school closures in the early phase of the influenza A (H1N1) 2009 outbreak in Melbourne, Australia

Background Localized reactive school and classroom closures were implemented as part of a suite of pandemic containment measures during the initial response to influenza A (H1N1) 2009 in Melbourne, Australia. Infected individuals, and those who had been in close contact with a case, were asked to stay in voluntary home quarantine and refrain from contact with visitors for seven days from the date of symptom onset or exposure to an infected person. Oseltamivir (Tamiflu®) was available for treatment or prophylaxis. Methods We surveyed affected families through schools involved in the closures. Analyses of responses were descriptive. We characterized recommendations made to case and contact households and quantified adherence to guidelines and antiviral therapy. Results Of the 314 respondent households, 51 contained a confirmed case. The prescribed quarantine period ranged from 1-14 days, reflecting logistic difficulties in reactive implementation relative to the stated guidelines. Household-level compliance with the requirement to stay at home was high (84.5%, 95% CI 79.3,88.5) and contact with children outside the immediate family infrequent. Conclusions Levels of compliance with recommendations in our sample were high compared with other studies, likely due to heightened public awareness of a newly introduced virus of uncertain severity. The variability of reported recommendations highlighted the difficulties inherent in implementing a targeted reactive strategy, such as that employed in Melbourne, on a large scale during a public health emergency. This study emphasizes the need to understand how public health measures are implemented when seeking to evaluate their effectiveness

Implications of a high-definition multileaf collimator (HD-MLC) on treatment planning techniques for stereotactic body radiation therapy (SBRT): a planning study

<p>Abstract</p> <p>Purpose</p> <p>To assess the impact of two multileaf collimator (MLC) systems (2.5 and 5 mm leaf widths) on three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and dynamic conformal arc techniques for stereotactic body radiation therapy (SBRT) of liver and lung lesions.</p> <p>Methods</p> <p>Twenty-nine SBRT plans of primary liver (n = 11) and lung (n = 18) tumors were the basis of this study. Five-millimeter leaf width 120-leaf Varian Millennium (M120) MLC-based plans served as reference, and were designed using static conformal beams (3DCRT), sliding-window intensity-modulated beams (IMRT), or dynamic conformal arcs (DCA). Reference plans were either re-optimized or recomputed, with identical planning parameters, for a 2.5-mm width 120-leaf BrainLAB/Varian high-definition (HD120) MLC system. Dose computation was based on the anisotropic analytical algorithm (AAA, Varian Medical Systems) with tissue heterogeneity taken into account. Each plan was normalized such that 100% of the prescription dose covered 95% of the planning target volume (PTV). Isodose distributions and dose-volume histograms (DVHs) were computed and plans were evaluated with respect to target coverage criteria, normal tissue sparing criteria, as well as treatment efficiency.</p> <p>Results</p> <p>Dosimetric differences achieved using M120 and the HD120 MLC planning were generally small. Dose conformality improved in 51.7%, 62.1% and 55.2% of the IMRT, 3DCRT and DCA cases, respectively, with use of the HD120 MLC system. Dose heterogeneity increased in 75.9%, 51.7%, and 55.2% of the IMRT, 3DCRT and DCA cases, respectively, with use of the HD120 MLC system. DVH curves demonstrated a decreased volume of normal tissue irradiated to the lower (90%, 50% and 25%) isodose levels with the HD120 MLC.</p> <p>Conclusion</p> <p>Data derived from the present comparative assessment suggest dosimetric merit of the high definition MLC system over the millennium MLC system. However, the clinical significance of these results warrants further investigation in order to determine whether the observed dosimetric advantages translate into outcome improvements.</p