Investigations into the Toxicology of Spirolides, a Group of Marine Phycotoxins

Spirolides are marine phycotoxins produced by the dinoflagellates Alexandrium ostenfeldii and A. peruvianum. Here we report that 13-desmethyl spirolide C shows little cytotoxicity when incubated with various cultured mammalian cell lines. When administered to mice by intraperitoneal (ip) injection, however, this substance was highly toxic, with an LD50 value of 6.9 µg/kg body weight (BW), showing that such in vitro cytotoxicity tests are not appropriate for predicting the in vivo toxicity of this toxin. Four other spirolides, A, B, C, and 20-methyl spirolide G, were also toxic to mice by ip injection, with LD50 values of 37, 99, 8.0 and 8.0 µg/kg BW respectively. However, the acute toxicities of these compounds were lower by at least an order of magnitude when administration by gavage and their toxic effects were further diminished when administered with food. These results have implications for future studies of the toxicology of these marine toxins and the risk assessment of human exposure

Where's all the 'good' sports journalism? Sports media research, the sociology of sport, and the question of quality sports reporting

Across newsrooms and journalism schools, questions as to what constitutes or ‘counts’ as excellent reporting are currently inciting much debate. Among the various frameworks being put forward to describe and encourage ‘excellent’ journalism in its various forms, sport is seldom mentioned – a legacy perhaps of its perennial dismissal as trivial subject matter. This essay grew from our curiosity as to whether the reverse was also true: that is, whether and what those who study sports journalism and sports media – in particular sociologists of sport – have contributed to understandings of ‘best’ and even excellent journalistic practice. We identified and analysed 376 articles from eight leading scholarly journals that feature sports media research with the aim of examining instances where ‘excellent’ sports reporting was either highlighted, described or advocated. After outlining the major themes that emerged from this analysis, we reflect on why so few of the sampled articles explicitly advise on what best practice sports journalism might look like – especially when it comes to coverage of the sport-related social issues that sociologists of sport tend to focus on – and why so little theoretical attention has been afforded to the question of excellent sports journalism more generally. While there are good sociological reasons for focusing on problematic sports reporting, on structural and systemic issues in which media are implicated, and on producing alternatives to hegemonic sports media, we conclude that it is high time for instances of excellent sports journalism to be afforded the theoretical and empirical attention long granted to their ‘bad’ journalistic counterparts

Genetic analysis and natural history of Charcot-Marie-Tooth disease CMTX1 due to GJB1 variants

Charcot-Marie-Tooth disease (CMT) due to GJB1 variants (CMTX1) is the second most common form of CMT. It is an X-linked disorder characterised by progressive sensory and motor neuropathy with males affected more severely than females. Many reported GJB1 variants remain classified as variants of uncertain significance (VUS). In this large, international, multicentre study we prospectively collected demographic, clinical and genetic data on patients with CMT associated with GJB1 variants. Pathogenicity for each variant was defined using adapted American College of Medical Genetics criteria. Baseline and longitudinal analyses were conducted to study genotype-phenotype correlations, to calculate longitudinal change using the CMT Examination Score (CMTES), to compare males versus females, and pathogenic/likely pathogenic (P/LP) variants versus VUS. We present 387 patients from 295 families harbouring 154 variants in GJB1. Of these, 319 patients (82.4%) were deemed to have P/LP variants, 65 had VUS (16.8%) and 3 benign variants (0.8%; excluded from analysis); an increased proportion of patients with P/LP variants compared with using ClinVar's classification (74.6%). Male patients (166/319, 52.0%, P/LP only) were more severely affected at baseline. Baseline measures in patients with P/LP variants and VUS showed no significant differences, and regression analysis suggested the disease groups were near identical at baseline. Genotype-phenotype analysis suggested c.-17G>A produces the most severe phenotype of the five most common variants, and missense variants in the intracellular domain are less severe than other domains. Progression of disease was seen with increasing CMTES over time up to 8 years follow-up. Standard response mean (SRM), a measure of outcome responsiveness, peaked at 3 years with moderate responsiveness (change in CMTES (ΔCMTES) = 1.3 ± 2.6, p = 0.00016, SRM = 0.50). Males and females progressed similarly up to 8 years, but baseline regression analysis suggested that over a longer period, females progress more slowly. Progression was most pronounced for mild phenotypes (CMTES = 0-7; 3-year ΔCMTES = 2.3 ± 2.5, p = 0.001, SRM = 0.90). Enhanced variant interpretation has yielded an increased proportion of GJB1 variants classified as P/LP and will aid future variant interpretation in this gene. Baseline and longitudinal analysis of this large cohort of CMTX1 patients describes the natural history of the disease including the rate of progression; CMTES showed moderate responsiveness for the whole group at 3 years and higher responsiveness for the mild group at 3, 4 and 5 years. These results have implications for patient selection for upcoming clinical trials

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Biosynthesis of 13-Desmethyl Spirolide C by the dinoflagellate Alexandrium ostenfeldii

Biosynthetic origins of the cyclic imine toxin 13-desmethyl spirolide C were determined by supplementing cultures of the toxigenic dinoflagellate Alexandrium ostenfeldii with stable isotope-labeled precursors [1,2-13C2]acetate, [1-13C]acetate, [2-13CD3]acetate, and [1,2-13C2,15N]glycine and measuring the incorporation patterns by 13C NMR spectroscopy. Despite partial scrambling of the acetate labels, the results show that most carbons of the macrocycle are polyketide-derived and that glycine is incorporated as an intact unit into the cyclic imine moiety. This work represents the first conclusive evidence that such cyclic imine toxins are polyketides and provides support for biosynthetic pathways previously defined for other polyether dinoflagellate toxins.Peer reviewed: YesNRC publication: Ye

Characterization of a Dispiroketal Spirolide Subclass from Alexandrium ostenfeldii

A new subclass of spirolide marine toxins, represented by spirolides H (1) and I (2), were isolated from the marine dino\ufb02agellate Alexandrium ostenfeldii. Spirolides H and I are structurally distinct from other spirolides in that they contain a 5:6 dispiroketal ring system rather than the trispiroketal ring system characteristic of previously isolated spirolides. The structures were assigned using a combination of spectrometric and spectroscopic techniques. Previously isolated spirolides containing a cyclic imine moiety showed toxicity in the mouse bioassay. Spirolide H contains this cyclic imine moiety but does not show toxicity in the mouse assay, suggesting that the presence of the cyclic imine moiety is not the only structural requirement for toxicity.Peer reviewed: YesNRC publication: Ye

A 1000-year record of dry conditions in the eastern Canadian prairies reconstructed from oxygen and carbon isotope measurements on Lake Winnipeg sediment organics

A short sediment core (162 cm), covering the period AD 920-1999, was sampled from the south basin of Lake Winnipeg for a suite of multi-proxy analyses leading towards a detailed characterisation of the recent millennial lake environment and hydroclimate of southern Manitoba, Canada. Information on the frequency and duration of major dry periods in southern Manitoba, in light of the changes that are likely to occur as a result of an increasingly warming atmosphere, is of specific interest in this study. Intervals of relatively enriched lake sediment cellulose oxygen isotope values (δ18Ocellulose) were found to occur from AD 1180 to 1230 (error range: AD 1104-1231 to 1160-1280), 1610-1640 (error range: AD 1571-1634 to 1603-1662), 1670-1720 (error range: AD 1643-1697 to 1692-1738) and 1750-1780 (error range: AD 1724-1766 to 1756-1794). Regional water balance, inferred from calculated Lake Winnipeg water oxygen isotope values (δ18Oinf-lw), suggest that the ratio of lake evaporation to catchment input may have been 25-40% higher during these isotopically distinct periods. Associated with the enriched dδ18Ocellulose intervals are some depleted carbon isotope values associated with more abundantly preserved sediment organic matter (dδ13COM). These suggest reduced microbial oxidation of terrestrially derived organic matter and/or subdued lake productivity during periods of minimised input of nutrients from the catchment area. With reference to other corroborating evidence, it is suggested that the AD 1180-1230, 1610-1640, 1670-1720 and 1750-1780 intervals represent four distinctly drier periods (droughts) in southern Manitoba, Canada. Additionally, lower-magnitude and duration dry periods may have also occurred from 1320 to 1340 (error range: AD 1257-1363), 1530-1540 (error range: AD 1490-1565 to 1498-1572) and 1570-1580 (error range: AD 1531-1599 to 1539-1606). © 2009 John Wiley & Sons, Ltd