Decoding drivers of carbon flux attenuation in the oceanic biological pump.

The biological pump supplies carbon to the oceans' interior, driving long-term carbon sequestration and providing energy for deep-sea ecosystems1,2. Its efficiency is set by transformations of newly formed particles in the euphotic zone, followed by vertical flux attenuation via mesopelagic processes3. Depth attenuation of the particulate organic carbon (POC) flux is modulated by multiple processes involving zooplankton and/or microbes4,5. Nevertheless, it continues to be mainly parameterized using an empirically derived relationship, the 'Martin curve'6. The derived power-law exponent is the standard metric used to compare flux attenuation patterns across oceanic provinces7,8. Here we present in situ experimental findings from C-RESPIRE9, a dual particle interceptor and incubator deployed at multiple mesopelagic depths, measuring microbially mediated POC flux attenuation. We find that across six contrasting oceanic regimes, representing a 30-fold range in POC flux, degradation by particle-attached microbes comprised 7-29 per cent of flux attenuation, implying a more influential role for zooplankton in flux attenuation. Microbial remineralization, normalized to POC flux, ranged by 20-fold across sites and depths, with the lowest rates at high POC fluxes. Vertical trends, of up to threefold changes, were linked to strong temperature gradients at low-latitude sites. In contrast, temperature played a lesser role at mid- and high-latitude sites, where vertical trends may be set jointly by particle biochemistry, fragmentation and microbial ecophysiology. This deconstruction of the Martin curve reveals the underpinning mechanisms that drive microbially mediated POC flux attenuation across oceanic provinces.

Environment and Genotype Influence Quantitative and Qualitative Variation in Condensed Tannins in Aspen.

Condensed tannins (CTs) are abundant, ecologically-relevant secondary metabolites in many plants, which respond to variables associated with anthropogenic environmental change. While many studies have reported how genetic and environmental factors affect CT concentrations, few have explored how they influence CT molecular structure. Here, using trembling aspen (Populus tremuloides) as a model organism, we report how foliar CT concentrations, polymer sizes, representation of procyanidins and prodelphinidins, and stereochemistry vary in response to changes in air temperature (warming and freeze damage), air composition (elevated CO2 and O3), soil quality (nutrients and microbiome), and herbivory (mammal and lepidopteran). Use of multiple aspen genotypes enabled assessment of genetic influences on aspen CTs. CT concentration and composition were analyzed by thiolysis-ultra high performance liquid chromatography/mass spectrometry in archived leaf samples from prior experiments. All environmental variables explored except for soil microbiome influenced both CT quantity and quality, with climate factors appearing to have larger effect magnitudes than herbivory. Climate, soil, and herbivory effects varied among genotypes, while air composition effects were consistent across genotypes. Considering that CT properties (concentrations and molecular structures) mediate functions at the organismal through ecosystem scales, intraspecific variation in responses of CT properties to environmental factors could provide a pathway through which environmental change exerts selective pressure on Populus populations. Future studies are needed to identify the molecular-level mechanisms by which environmental factors influence CT concentrations and structures, and to establish their ecological and evolutionary significance.

Phenotypic Variation in Phytochemical Defense of Trembling Aspen in Western North America: Genetics, Development, and Geography.

Trembling aspen (Populus tremuloides) is arguably the most important deciduous tree species in the Intermountain West of North America. There, as elsewhere in its range, aspen exhibits remarkable genetic variation in observable traits such as morphology and phenology. In contrast to Great Lakes populations, however, relatively little is known about phytochemical variation in western aspen. This survey of phytochemistry in western aspen was undertaken to assess how chemical expression varies among genotypes, cytotypes (diploid vs. triploid), and populations, and in response to development and mammalian browsing. We measured levels of foliar nitrogen, salicinoid phenolic glycosides (SPGs) and condensed tannins (CTs), as those constituents influence organismal interactions and ecosystem processes. Results revealed striking genotypic variation and considerable population variation, but minimal cytotype variation, in phytochemistry of western aspen. Levels of SPGs and nitrogen declined, whereas levels of CTs increased, with tree age. Browsed ramets had much higher levels of SPGs, and lower levels of CTs, than unbrowsed ramets of the same genotype. We then evaluated how composite chemical profiles of western aspen differ from those of Great Lakes aspen (assessed in earlier research). Interestingly, mature western aspen trees maintain much higher levels of SPGs, and lower levels of CTs, than Great Lakes aspen. Phenotypic variation in chemical composition of aspen - a foundation species - in the Intermountain West likely has important consequences for organismal interactions and forest ecosystem dynamics. Moreover, those consequences likely play out over spatial and temporal scales somewhat differently than have been documented for Great Lakes aspen.

Growing up aspen: ontogeny and trade-offs shape growth, defence and reproduction in a foundation species.

BACKGROUND AND AIMS: Intraspecific variation in foundation species of forest ecosystems can shape community and ecosystem properties, particularly when that variation has a genetic basis. Traits mediating interactions with other species are predicted by simple allocation models to follow ontogenetic patterns that are rarely studied in trees. The aim of this research was to identify the roles of genotype, ontogeny and genotypic trade-offs shaping growth, defence and reproduction in aspen. METHODS: We established a common garden replicating >500 aspen genets in Wisconsin, USA. Trees were measured through the juvenile period into the onset of reproduction, for growth, defence chemistry (phenolic glycosides and condensed tannins), nitrogen, extrafloral nectaries, leaf morphology (specific leaf area), flower production and foliar herbivory and disease. We also assayed the TOZ19 sex marker and heterozygosity at ten microsatellite loci. KEY RESULTS: We found high levels of genotypic variation for all traits, and high heritabilities for both the traits and their ontogenetic trajectories. Ontogeny strongly shaped intraspecific variation, and trade-offs among growth, defence and reproduction supported some predictions while contradicting others. Both direct resistance (chemical defence) and indirect defence (extrafloral nectaries) declined during the juvenile stage, prior to the onset of reproduction. Reproduction was higher in trees that were larger, male and had higher individual heterozygosity. Growth was diminished by genotypic allocation to both direct and indirect defence as well as to reproduction, but we found no evidence of trade-offs between defence and reproduction. CONCLUSIONS: Key traits affecting the ecological communities of aspen have high levels of genotypic variation and heritability, strong patterns of ontogeny and clear trade-offs among growth, defence and reproduction. The architecture of aspen's community genetics - its ontogeny, trade-offs and especially its great variability - is shaped by both its broad range and the diverse community of associates, and in turn further fosters that diversity.

Root Secondary Metabolites in Populus tremuloides: Effects of Simulated Climate Warming, Defoliation, and Genotype.

Climate warming can influence interactions between plants and associated organisms by altering levels of plant secondary metabolites. In contrast to studies of elevated temperature on aboveground phytochemistry, the consequences of warming on root chemistry have received little attention. Herein, we investigated the effects of elevated temperature, defoliation, and genotype on root biomass and phenolic compounds in trembling aspen (Populus tremuloides). We grew saplings of three aspen genotypes under ambient or elevated temperatures (+4-6 °C), and defoliated (by 75%) half of the trees in each treatment. After 4 months, we harvested roots and determined their condensed tannin and salicinoid (phenolic glycoside) concentrations. Defoliation reduced root biomass, with a slightly larger impact under elevated, relative to ambient, temperature. Elevated temperature decreased condensed tannin concentrations by 21-43% across the various treatment combinations. Warming alone did not alter salicinoid concentrations but eliminated a small negative impact of defoliation on those compounds. Graphical vector analysis suggests that effects of warming and defoliation on condensed tannins and salicinoids were predominantly due to reduced biosynthesis of these metabolites in roots, rather than to changes in root biomass. In general, genotypes did not differ in their responses to temperature or temperature by defoliation interactions. Collectively, our results suggest that future climate warming will alter root phytochemistry, and that effects will vary among different classes of secondary metabolites and be influenced by concurrent ecological interactions such as herbivory. Temperature- and herbivory-mediated changes in root chemistry have the potential to influence belowground trophic interactions and soil nutrient dynamics.

Linking plant genes to insect communities: Identifying the genetic bases of plant traits and community composition.

Community genetics aims to understand the effects of intraspecific genetic variation on community composition and diversity, thereby connecting community ecology with evolutionary biology. Thus far, research has shown that plant genetics can underlie variation in the composition of associated communities (e.g., insects, lichen and endophytes), and those communities can therefore be considered as extended phenotypes. This work, however, has been conducted primarily at the plant genotype level and has not identified the key underlying genes. To address this gap, we used genome-wide association mapping with a population of 445 aspen (Populus tremuloides) genets to identify the genes governing variation in plant traits (defence chemistry, bud phenology, leaf morphology, growth) and insect community composition. We found 49 significant SNP associations in 13 Populus genes that are correlated with chemical defence compounds and insect community traits. Most notably, we identified an early nodulin-like protein that was associated with insect community diversity and the abundance of interacting foundation species (ants and aphids). These findings support the concept that particular plant traits are the mechanistic link between plant genes and the composition of associated insect communities. In putting the "genes" into "genes to ecosystems ecology", this work enhances understanding of the molecular genetic mechanisms that underlie plant-insect associations and the consequences thereof for the structure of ecological communities.

Analysis of condensed tannins in Populus spp. using reversed phase UPLC-PDA-(-)esi-MS following thiolytic depolymerisation.

INTRODUCTION: Condensed tannins (CTs) are proanthocyanidin heteropolymers that are widely distributed among plants. Their biochemical properties are determined by molecular structure (e.g. polymer size, hydroxylation, stereochemistry). In Populus, genetically and environmentally-determined CT concentrations have been related to ecological effects, while the potential role of CT molecular structure has received little attention. OBJECTIVE: Evaluate CT polymerisation, major constituent monomers, stereochemistry and overall content in Populus tremuloides foliage using ultra-high-performance liquid chromatography with photodiode array and mass spectrometry (UPLC-PDA-(-)esi-MS) detection following thiolytic depolymerisation of the CTs. METHODOLOGY: CTs were extracted from dried foliage of six P. tremuloides genotypes into methanol and thiolytically depolymerised into constituent monomers. Calibration standards were prepared by thiolysis of CT mixtures isolated from P. tremuloides foliage on Sephadex LH-20, followed by preparative high-performance liquid chromatography (HPLC). RESULTS: Populus tremuloides CTs contained predominantly repeating subunits of three putative stereoisomers each of catechin and gallocatechin. Linear calibrations for standards of these subunits and their thioethers (purities 44-87%, UPLC-(-)esi-MS) were generally stable over the course of 10 months. CT polymer size, hydroxylation, stereochemistry and concentrations differed among genotypes. CONCLUSION: This thiolysis-UPLC-PDA-(-)esiMS method was optimised for analysis of CT polymer size, hydroxylation, stereochemistry, and total concentration in Populus foliage. It revealed significant variation in each of these properties among P. tremuloides genotypes, and will facilitate evaluation of how environmental factors affect CT molecular structures.

Impact of peripheral immune status on central molecular responses to facial nerve axotomy.

When facial nerve axotomy (FNA) is performed on immunodeficient recombinase activating gene-2 knockout (RAG-2-/-) mice, there is greater facial motoneuron (FMN) death relative to wild type (WT) mice. Reconstituting RAG-2-/- mice with whole splenocytes rescues FMN survival after FNA, and CD4+ T cells specifically drive immune-mediated neuroprotection. Evidence suggests that immunodysregulation may contribute to motoneuron death in amyotrophic lateral sclerosis (ALS). Immunoreconstitution of RAG-2-/- mice with lymphocytes from the mutant superoxide dismutase (mSOD1) mouse model of ALS revealed that the mSOD1 whole splenocyte environment suppresses mSOD1 CD4+ T cell-mediated neuroprotection after FNA. The objective of the current study was to characterize the effect of CD4+ T cells on the central molecular response to FNA and then identify if mSOD1 whole splenocytes blocked these regulatory pathways. Gene expression profiles of the axotomized facial motor nucleus were assessed from RAG-2-/- mice immunoreconstituted with either CD4+ T cells or whole splenocytes from WT or mSOD1 donors. The findings indicate that immunodeficient mice have suppressed glial activation after axotomy, and cell transfer of WT CD4+ T cells rescues microenvironment responses. Additionally, mSOD1 whole splenocyte recipients exhibit an increased astrocyte activation response to FNA. In RAG-2-/- + mSOD1 whole splenocyte mice, an elevation of motoneuron-specific Fas cell death pathways is also observed. Altogether, these findings suggest that mSOD1 whole splenocytes do not suppress mSOD1 CD4+ T cell regulation of the microenvironment, and instead, mSOD1 whole splenocytes may promote motoneuron death by either promoting a neurotoxic astrocyte phenotype or inducing Fas-mediated cell death pathways. This study demonstrates that peripheral immune status significantly affects central responses to nerve injury. Future studies will elucidate the mechanisms by which mSOD1 whole splenocytes promote cell death and if inhibiting this mechanism can preserve motoneuron survival in injury and disease.

Assessment of antimicrobial drug administration and antimicrobial residues in food animals in Enugu State, Nigeria.

Imprudent administration of antimicrobial drugs in food-producing animals can facilitate the development and spread of antimicrobial-resistant organisms and also enhance the occurrence of antimicrobial residue in animal products. This study was undertaken to assess antimicrobial drug administration to food animals in livestock farms in Enugu State and determine livestock farmers' awareness on the consequences of imprudent antimicrobial administration to food animals and finally the prevalence of antimicrobial drug residues in edible tissues of cattle and pigs in the state. Structured questionnaire was used to extract information on antimicrobial drug administration and consequences of irresponsible use of antimicrobials in food animals from 109 livestock farms/farmers randomly selected using multi-stage sampling technique. Premi® test technology (R-Biopharm, Germany) was used to screen for antimicrobial residues in edible tissues from 300 carcasses consisting of 165 cattle and 135 pigs slaughtered for human consumption in two major slaughterhouses in Enugu State. Tetracyclines (90.8%), penicillins and beta-lactams (89.9%), and aminoglycoside (57.8%) were the classes of antimicrobials most frequently administered to food animals in the farms surveyed. Withdrawal period was not observed in 65% of the farms. About 30% of cattle and 23% of pig carcasses screened contained detectable amounts of antimicrobial residues. There is widespread indiscriminate administration of antimicrobial drugs in food animals in Enugu State. This underscores the need for public enlightenment on prudent use of antimicrobial drugs in food-producing animals in order to preserve the therapeutic efficacy for sustainable livestock production and to safeguard human health.

Vernal freeze damage and genetic variation alter tree growth, chemistry, and insect interactions.

Anticipated consequences of climate change in temperate regions include early spring warmup punctuated by intermittent hard freezes. Warm weather accelerates leaf flush in perennial woody species, potentially exposing vulnerable young tissues to damaging frosts. We employed a 2 × 6 randomized factorial design to examine how the interplay of vernal (springtime) freeze damage and genetic variation in a hardwood species (Populus tremuloides) influences tree growth, phytochemistry, and interactions with an insect herbivore (Chaitophorus stevensis). Acute effects of freezing included defoliation and mortality. Surviving trees exhibited reduced growth and altered biomass distribution. Reflushed leaves on these trees had lower mass per area, lower lignin concentrations, and higher nitrogen concentrations, altered chemical defence profiles, and supported faster aphid population growth. Many effects varied among plant genotypes and were related with herbivore performance. This study suggests that a single damaging vernal freeze event can alter tree-insect interactions through effects on plant growth and chemistry. Differential responses of various genotypes to freeze damage suggest that more frequent vernal freeze events could also influence natural selection, favouring trees with greater freeze hardiness, and more resistance or tolerance to herbivores following damage.

Effects of Elevated Atmospheric Carbon Dioxide and Tropospheric Ozone on Phytochemical Composition of Trembling Aspen ( Populus tremuloides ) and Paper Birch ( Betula papyrifera ).

Anthropogenic activities are altering levels of atmospheric carbon dioxide (CO2) and tropospheric ozone (O3). These changes can alter phytochemistry, and in turn, influence ecosystem processes. We assessed the individual and combined effects of elevated CO2 and O3 on the phytochemical composition of two tree species common to early successional, northern temperate forests. Trembling aspen (Populus tremuloides) and paper birch (Betula papyrifera) were grown at the Aspen FACE (Free-Air Carbon dioxide and ozone Enrichment) facility under four combinations of ambient and elevated CO2 and O3. We measured, over three years (2006-08), the effects of CO2 and O3 on a suite of foliar traits known to influence forest functioning. Elevated CO2 had minimal effect on foliar nitrogen and carbohydrate levels in either tree species, and increased synthesis of condensed tannins and fiber in aspen, but not birch. Elevated O3 decreased nitrogen levels in both tree species and increased production of sugar, condensed tannins, fiber, and lignin in aspen, but not birch. The magnitude of responses to elevated CO2 and O3 varied seasonally for both tree species. When co-occurring, CO2 offset most of the changes in foliar chemistry expressed under elevated O3 alone. Our results suggest that levels of CO2 and O3 predicted for the mid-twenty-first century will alter the foliar chemistry of northern temperate forests with likely consequences for forest community and ecosystem dynamics.

Long-term evolution and transmission dynamics of swine influenza A virus.

Swine influenza A viruses (SwIV) cause significant economic losses in animal husbandry as well as instances of human disease and occasionally give rise to human pandemics, including that caused by the H1N1/2009 virus. The lack of systematic and longitudinal influenza surveillance in pigs has hampered attempts to reconstruct the origins of this pandemic. Most existing swine data were derived from opportunistic samples collected from diseased pigs in disparate geographical regions, not from prospective studies in defined locations, hence the evolutionary and transmission dynamics of SwIV are poorly understood. Here we quantify the epidemiological, genetic and antigenic dynamics of SwIV in Hong Kong using a data set of more than 650 SwIV isolates and more than 800 swine sera from 12 years of systematic surveillance in this region, supplemented with data stretching back 34 years. Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically diverse virus population whose dynamics are quantitatively different from those previously observed for human influenza viruses. Our findings indicate that increased antigenic drift is associated with reassortment events and offer insights into the emergence of influenza viruses with epidemic potential in swine and humans.

Interactions between Bacteria And Aspen Defense Chemicals at the Phyllosphere - Herbivore Interface.

Plant- and insect-associated microorganisms encounter a diversity of allelochemicals, and require mechanisms for contending with these often deleterious and broadly-acting compounds. Trembling aspen, Populus tremuloides, contains two principal groups of defenses, phenolic glycosides (salicinoids) and condensed tannins, which differentially affect the folivorous gypsy moth, Lymantria dispar, and its gut symbionts. The bacteria genus Acinetobacter is frequently associated with both aspen foliage and gypsy moth consuming that tissue, and one isolate, Acinetobacter sp. R7-1, previously has been shown to metabolize phenolic glycosides. In this study, we aimed to characterize further interactions between this Acinetobacter isolate and aspen secondary metabolites. We assessed bacterial carbon utilization and growth in response to different concentrations of phenolic glycosides and condensed tannins. We also tested if enzyme inhibitors reduce bacterial growth and catabolism of phenolic glycosides. Acinetobacter sp. R7-1 utilized condensed tannins but not phenolic glycosides or glucose as carbon sources. Growth in nutrient-rich medium was increased by condensed tannins, but reduced by phenolic glycosides. Addition of the P450 enzyme inhibitor piperonyl butoxide increased the effects of phenolic glycosides on Acinetobacter sp. R7-1. In contrast, the esterase inhibitor S,S,S,-tributyl-phosphorotrithioate did not affect phenolic glycoside inhibition of bacterial growth. Degradation of phenolic glycosides by Acinetobacter sp. R7-1 appears to alleviate the cytotoxicity of these compounds, rather than provide an energy source. Our results further suggest this bacterium utilizes additional, complementary mechanisms to degrade antimicrobial phytochemicals. Collectively, these results provide insight into mechanisms by which microorganisms contend with their environment within the context of plant-herbivore interactions.

Non-invasive Carotid Artery Imaging to Identify the Vulnerable Plaque: Current Status and Future Goals.

BACKGROUND: The current clinical practise to determine if a patient should undergo carotid intervention to prevent stroke is to determine the clinical features combined with degree of carotid stenosis. However, this does not accurately determine the individual patient's risk for future stroke. A thin fibrous cap, a large lipid core, high macrophage count, and intraplaque haemorrhage have all been identified as markers of the so-called "vulnerable" plaque being related to a higher stroke risk. There is a need to assess the accuracy of in vivo imaging to identify vulnerable plaque characteristics, thereby enabling in vivo risk stratification to guide clinical decision-making. METHODS: The aim of this topical review is to assess the roles of currently available imaging modalities that are applied in clinical practice and those experimental techniques that are close to clinical translation in defining carotid plaque characteristics and in informing clinical practice. RESULTS: Ultrasound is a low cost and ready available low-risk tool, but it lacks the accuracy to reliably detect individual plaque components and characteristics. Computed tomography is considered to be the best imaging technique to identify calcification in the carotid plaque. Magnetic resonance imaging (MRI) can identify most described plaque characteristics with moderate to good agreement. Positron emission tomography allows assessment of specific metabolic functions with tracers labelled with positron emitting radio-isotopes, but limited spatial resolution makes anatomic precision imprecise. CONCLUSION: MRI has demonstrated the most potential, with good sensitivity and specificity for most plaque characteristics. However, currently there is no single imaging modality that can reliably identify the vulnerable plaque in relation to development of future stroke.

Mechanism of Procedural Stroke Following Carotid Endarterectomy or Carotid Artery Stenting Within the International Carotid Stenting Study (ICSS) Randomised Trial.

OBJECTIVE: To decrease the procedural risk of carotid revascularisation it is crucial to understand the mechanisms of procedural stroke. This study analysed the features of procedural strokes associated with carotid artery stenting (CAS) and carotid endarterectomy (CEA) within the International Carotid Stenting Study (ICSS) to identify the underlying pathophysiological mechanism. MATERIALS AND METHODS: Patients with recently symptomatic carotid stenosis (1,713) were randomly allocated to CAS or CEA. Procedural strokes were classified by type (ischaemic or haemorrhagic), time of onset (intraprocedural or after the procedure), side (ipsilateral or contralateral), severity (disabling or non-disabling), and patency of the treated artery. Only patients in whom the allocated treatment was initiated were included. The most likely pathophysiological mechanism was determined using the following classification system: (1) carotid-embolic, (2) haemodynamic, (3) thrombosis or occlusion of the revascularised carotid artery, (4) hyperperfusion, (5) cardio-embolic, (6) multiple, and (7) undetermined. RESULTS: Procedural stroke occurred within 30 days of revascularisation in 85 patients (CAS 58 out of 791 and CEA 27 out of 819). Strokes were predominately ischaemic (77; 56 CAS and 21 CEA), after the procedure (57; 37 CAS and 20 CEA), ipsilateral to the treated artery (77; 52 CAS and 25 CEA), and non-disabling (47; 36 CAS and 11 CEA). Mechanisms of stroke were carotid-embolic (14; 10 CAS and 4 CEA), haemodynamic (20; 15 CAS and 5 CEA), thrombosis or occlusion of the carotid artery (15; 11 CAS and 4 CEA), hyperperfusion (9; 3 CAS and 6 CEA), cardio-embolic (5; 2 CAS and 3 CEA) and multiple causes (3; 3 CAS). In 19 patients (14 CAS and 5 CEA) the cause of stroke remained undetermined. CONCLUSION: Although the mechanism of procedural stroke in both CAS and CEA is diverse, haemodynamic disturbance is an important mechanism. Careful attention to blood pressure control could lower the incidence of procedural stroke.

Aspen defense chemicals influence midgut bacterial community composition of gypsy moth.

Microbial symbionts are becoming increasingly recognized as mediators of many aspects of plant - herbivore interactions. However, the influence of plant chemical defenses on gut associates of insect herbivores is less well understood. We used gypsy moth (Lymantria dispar L.), and differing trembling aspen (Populus tremuloides Michx.) genotypes that vary in chemical defenses, to assess the influence of foliar chemistry on bacterial communities of larval midguts. We evaluated the bacterial community composition of foliage, and of midguts of larvae feeding on those leaves, using next-generation high-throughput sequencing. Plant defense chemicals did not influence the composition of foliar communities. In contrast, both phenolic glycosides and condensed tannins affected the bacterial consortia of gypsy moth midguts. The two most abundant operational taxonomic units were classified as Ralstonia and Acinetobacter. The relative abundance of Ralstonia was higher in midguts than in foliage when phenolic glycoside concentrations were low, but lower in midguts when phenolic glycosides were high. In contrast, the relative abundance of Ralstonia was lower in midguts than in foliage when condensed tannin concentrations were low, but higher in midguts when condensed tannins were high. Acinetobacter showed a different relationship with host chemistry, being relatively more abundant in midguts than with foliage when condensed tannin concentrations were low, but lower in midguts when condensed tannins were high. Acinetobacter tended to have a greater relative abundance in midguts of insects feeding on genotypes with high phenolic glycoside concentrations. These results show that plant defense chemicals influence herbivore midgut communities, which may in turn influence host utilization.

Influence of Genotype, Environment, and Gypsy Moth Herbivory on Local and Systemic Chemical Defenses in Trembling Aspen (Populus tremuloides).

Numerous studies have explored the impacts of intraspecific genetic variation and environment on the induction of plant chemical defenses by herbivory. Relatively few, however, have considered how those factors affect within-plant distribution of induced defenses. This work examined the impacts of plant genotype and soil nutrients on the local and systemic phytochemical responses of trembling aspen (Populus tremuloides) to defoliation by gypsy moth (Lymantria dispar). We deployed larvae onto foliage on individual tree branches for 15 days and then measured chemistry in leaves from: 1) branches receiving damage, 2) undamaged branches of insect-damaged trees, and 3) branches of undamaged control trees. The relationship between post-herbivory phytochemical variation and insect performance also was examined. Plant genotype, soil nutrients, and damage all influenced phytochemistry, with genotype and soil nutrients being stronger determinants than damage. Generally, insect damage decreased foliar nitrogen, increased levels of salicinoids and condensed tannins, but had little effect on levels of a Kunitz trypsin inhibitor, TI3. The largest damage-mediated tannin increases occurred in leaves on branches receiving damage, whereas the largest salicinoid increases occurred in leaves of adjacent, undamaged branches. Foliar nitrogen and the salicinoid tremulacin had the strongest positive and negative relationships, respectively, with insect growth. Overall, plant genetics and environment concomitantly influenced both local and systemic phytochemical responses to herbivory. These findings suggest that herbivory can contribute to phytochemical heterogeneity in aspen foliage, which may in turn influence future patterns of herbivory and nutrient cycling over larger spatial scales.

Guideline Promotion Increases Prescription of Bone Protection with Steroids in Hospitalised Patients.

Guidelines for the prevention of glucocorticoid (GC) induced osteoporosis (GIOP) were implemented in a level 5 Irish Hospital with cross sectional audit of inpatient prescribing undertaken before and after. Prior to guideline implementation, elemental calcium (Ca) with Vitamin D (VitD) was prescribed for 11/66 (17%) of patients on GCs with 2/66 (3%) also receiving bisphosphonate (BP) therapy. Subsequent to guideline implementation, Ca with VitD was prescribed for 19/55 (35%) of patients on GCs with 11/55 (20%) also receiving BP therapy, representing a 2 and 6 fold respective increase. Internal promotion of guidelines is an effective strategy for healthcare improvement but needs refinement with or without repetition to achieve better patient outcomes.

Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers.

OBJECTIVES: Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy Register of the risk of MCMs after monotherapy exposure to valproate, carbamazepine and lamotrigine. METHODS: Fifteen-year prospective observational study from 1996 until 2012. The main outcome measure is the MCM rate. RESULTS: Informative outcomes were available for 5206 cases. 1290 women were exposed to valproate monotherapy, 1718 to carbamazepine monotherapy and 2198 to lamotrigine monotherapy. The MCM risk with valproate monotherapy exposure in utero was 6.7% (95% CI 5.5% to 8.3%) compared with 2.6% with carbamazepine (95% CI 1.9% to 3.5%) and 2.3% with lamotrigine (95% CI 1.8% to 3.1%). A significant dose effect was seen with valproate (p=0.0006) and carbamazepine (p=0.03) exposed pregnancies. A non-significant trend towards higher MCM rate with increasing dose was found with lamotrigine. MCM rate for high-dose lamotrigine (>400 mg daily) was lower than the MCM rate for pregnancies exposed to <600 mg daily of valproate, but this was not significant (3.4% vs 5.0%, p=0.31). CONCLUSIONS: In utero exposure to valproate carries a significantly higher MCM risk than lamotrigine (p=0.0001) and carbamazepine (p=0.0001) monotherapy. In contrast to prior findings, high-dose lamotrigine was associated with fewer MCMs than all doses of valproate. While lamotrigine has a favourable profile compared with valproate for adverse pregnancy outcomes, the requirements for seizure control should not be overlooked.

Work stress and cancer researchers: an exploration of the challenges, experiences and training needs of UK cancer researchers.

Work stress is a significant issue for many UK healthcare professionals, in particular those working in the field of oncology. However, there have been very few attempts to explore the challenges, experiences or training needs of researchers working in cancer research. In doing so, we will be better positioned to support and develop these researchers. Eighteen UK oncology researchers from a variety of backgrounds took part in a semi-structured interview. Interviews were transcribed and analysed using thematic analysis. The analysis identified two overarching themes: logistical research issues (workload, accessing/recruiting participants, finances) and sensitive research issues (emotional demands, professional boundaries, sensitivity around recruitment). One cross-cutting theme, supportive strategies (support and training, coping mechanisms), was seen to influence both logistical and sensitive research issues. While further research is needed to fully understand the causes and impact of work stress on cancer researchers, three specific issues were highlighted: emotional demands are relevant to quantitative and mixed methods researchers as well as those engaged in qualitative research; the researchers' background (experience; clinical/non-clinical) was influential and an exploration of effective coping strategies is required; and there is a clear need for adequate support systems and training to be available, particularly for early career researchers.