Forced mobilization accelerates pathogenesis: characterization of a preclinical surgical model of osteoarthritis

Preclinical osteoarthritis (OA) models are often employed in studies investigating disease-modifying OA drugs (DMOADs). In this study we present a comprehensive, longitudinal evaluation of OA pathogenesis in a rat model of OA, including histologic and biochemical analyses of articular cartilage degradation and assessment of subchondral bone sclerosis. Male Sprague-Dawley rats underwent joint destabilization surgery by anterior cruciate ligament transection and partial medial meniscectomy. The contralateral joint was evaluated as a secondary treatment, and sham surgery was performed in a separate group of animals (controls). Furthermore, the effects of walking on a rotating cylinder (to force mobilization of the joint) on OA pathogenesis were assessed. Destabilization-induced OA was investigated at several time points up to 20 weeks after surgery using Osteoarthritis Research Society International histopathology scores, in vivo micro-computed tomography (CT) volumetric bone mineral density analysis, and biochemical analysis of type II collagen breakdown using the CTX II biomarker. Expression of hypertrophic chondrocyte markers was also assessed in articular cartilage. Cartilage degradation, subchondral changes, and subchondral bone loss were observed as early as 2 weeks after surgery, with considerable correlation to that seen in human OA. We found excellent correlation between histologic changes and micro-CT analysis of underlying bone, which reflected properties of human OA, and identified additional molecular changes that enhance our understanding of OA pathogenesis. Interestingly, forced mobilization exercise accelerated OA progression. Minor OA activity was also observed in the contralateral joint, including proteoglycan loss. Finally, we observed increased chondrocyte hypertrophy during pathogenesis. We conclude that forced mobilization accelerates OA damage in the destabilized joint. This surgical model of OA with forced mobilization is suitable for longitudinal preclinical studies, and it is well adapted for investigation of both early and late stages of OA. The time course of OA progression can be modulated through the use of forced mobilization

ERFVII action and modulation through oxygen-sensing in Arabidopsis thaliana

Oxygen is a key signalling component of plant biology, and whilst an oxygen-sensing mechanism was previously described in Arabidopsis thaliana, key features of the associated PLANT CYSTEINE OXIDASE (PCO) N-degron pathway and Group VII ETHYLENE RESPONSE FACTOR (ERFVII) transcription factor substrates remain untested or unknown. We demonstrate that ERFVIIs show non-autonomous activation of root hypoxia tolerance and are essential for root development and survival under oxygen limiting conditions in soil. We determine the combined effects of ERFVIIs in controlling gene expression and define genetic and environmental components required for proteasome-dependent oxygen-regulated stability of ERFVIIs through the PCO N-degron pathway. Using a plant extract, unexpected amino-terminal cysteine sulphonic acid oxidation level of ERFVIIs was observed, suggesting a requirement for additional enzymatic activity within the pathway. Our results provide a holistic understanding of the properties, functions and readouts of this oxygen-sensing mechanism defined through its role in modulating ERFVII stability

Working Group on Governance of the Regional Database & Estimation System (WGRDBES-GOV; Outputs from 2020 meeting)

The Working Group on Governance of the Regional Database & Estimation System (WGRDBESGOV) provides the governance function for both the existing Regional Database (RDB) and the new Regional Database & Estimation System (RDBES) that is currently in development. It is composed of representatives from ICES member countries and EU Regional Coordination Groups (RCGs). In this report, the WGRDBESGOV reviews the RDBES developments performed during 2020 and plans for the work required in 2021 and beyond. It also considers how RDB data has been used and proposes changes required to the current Data Policy. The RDBES is currently planned to replace both the existing ICES InterCatch and RDB database systems and has an important part to play in increasing transparency and improving the quality of stock assessment within ICES. To this end, two workshops have been planned for 2021 which will help data submitters with the transition to the new system. A new working group is also proposed to enable the ICES community to move forward with estimation using the RDBES data model. Following on from the data call issued in 2020, another test data call is also planned for 2021 which will give further motivation for people to become involved and provide a robust test of the process. The RDB and RDBES must ensure that data can be used by the RCGs and authorised groups in ICES whilst ensuring that only permitted users have access to the confidential data – the rules relating to this have previously been defined in the RDB Data Policy. In line with discussions at the ICES Data and Information Group (DIG), it is proposed to split the current Data Policy into two new documents: a Data License, and a Data Governance document. It is important to remember that the ultimate success of the RDBES will rely on the effort and contributions from a large number of people in the wider ICES/EU data collection community and not just the relatively small groups who attend the WGRDBESGOV or Core Group meetings. The WGRDBESGOV continues to encourage these contributions

Impulsive noise pollution in the Northeast Atlantic: Reported activity during 2015-2017

Underwater noise pollution from impulsive sources (e.g. explosions, seismic airguns, percussive pile driving) can affect marine fauna through mortality, physical injury, auditory damage, physiological stress, acoustic masking, and behavioural responses. Given the potential for large-scale impact on marine ecosystems, some countries are now monitoring impulsive noise activity, coordinated internationally through Regional Seas Conventions. Here, we assess impulsive noise activity in the Northeast Atlantic reported during 2015-2017 to the first international impulsive noise register (INR), established in 2016 under the OSPAR Convention. Seismic airgun surveys were the dominant noise source (67%-83% of annual activity) and declined by 38% during 2015-2017. Reported pile driving activity increased 46%. Explosions and sonar/acoustic deterrent devices both had overall increases in reported activity. Some increases were attributable to more comprehensive reporting in later years. We discuss utilising the INR for risk assessment, target setting, and forward planning, and the implementation of similar systems in other regions

Have the changes introduced by the 2004 Higher Education Act made higher education admissions in England wider and fairer?

'Widening participation' and 'fair access' have been contested policy areas in English higher education since at least the early 1990s. They were key facets of the 2003 White Paper - The Future of Higher Education - and the subsequent 2004 Higher Education Act, with stated objectives that the reach of higher education should be wider and fairer. In particular, there has been considerable concern about admissions to 'top universities', which have remained socially as well as academically exclusive. The principal policy tools used by the Act were the introduction of variable tuition fees, expanded student grants, discretionary bursaries and the new Office for Fair Access (OFFA). This paper draws on publicly available statistics to assess whether the changes implemented by the 2004 Act have indeed made access to English higher education wider and fairer in relation to young people progressing from state schools and colleges and from lower socio-economic groups. It concludes that, while there is some evidence for modest improvements, these have been concentrated outside the 'top universities', which have seen slippage relative to the rest of the sector. The paper concludes with a discussion of the reasons why financial inducements appear to be a flawed and naive approach to influencing student demand. © 2011 Taylor & Francis

Working group on ecosystem assessment of Western European shelf seas (WGEAWESS)

The ICES Working Group on Ecosystem Assessment of Western European Shelf Seas (WGEA-WESS) aims to provide high quality science in support to holistic, adaptive, evidence-based man-agement in the Celtic seas, Bay of Biscay and Iberian coast regions. The group works towards developing integrated ecosystem assessments for both the (i) Celtic Seas and (ii) Bay of Biscay and Iberian Coast which are summarized in the Ecosystem Overviews (EOs) advice products that were recently updated. Integrated Trend Analysis (ITA) were performed for multiple sub-ecoregions and used to develop an understanding of ecosystem responses to pressures at varying spatial scales. Ecosystem models (primarily Ecopath with Ecosim; EwE) were developed and identified for fisheries and spatial management advice. The updated Celtic Seas EO represents a large step forward for EOs, with the inclusion of novel sections on climate change, foodweb and productivity, the first application of the new guidelines for building the conceptual diagram, inclusion of socio-economic indicators, and progress made toward complying with the Transparent Assessment Framework (TAF). We highlight ongoing issues relevant to the development and communication of EO conceptual diagrams. A common methodology using dynamic factor analysis (DFA) was used to perform ITA in a comparable way for seven subregions. This was supported by the design and compilation of the first standardized cross-regional dataset. A comparison of the main trends evidenced among subregions over the period 1993–2020 was conducted and will be published soon. A list of available and developing EWE models for the region was also generated. Here, we re-port on the advances in temporal and spatial ecosystem modelling, such as their capacity to model the impacts of sector activities (e.g. renewables and fisheries) and quantify foodweb indi-cators. We also reflect on model quality assessment with the key run of the Irish sea EwE model. The group highlighted the hurdles and gaps in current models in support of EBM, such as the choice of a relevant functional, spatial, and temporal scales and the impacts of model structure on our capacity to draw comparisons from models of different regions. The group aims to ad-dress these issues in coming years and identify routes for ecosystem model derived information into ICES advice.info:eu-repo/semantics/publishedVersio

Influence of deformation and fluids on Ar retention in white mica: Dating the Dover Fault, Newfoundland Appalachians

White mica 40Ar/39Ar analyses may provide useful constraints on the timing of tectonic processes, but complex geological and thermal histories can perturb Ar systematics in a variety of ways. Ductile shear zones represent excellent case studies for exploring the link(s) between dynamic re-/neo-crystallization of white mica and coeval enhanced fluid flow, and their effect on 40Ar/39Ar dates. White mica 40Ar/39Ar dates were collected from compositionally similar granites that record different episodes of deformation with proximity to the Dover Fault, a terrane-bounding strike-slip shear zone in the Appalachian orogen, Newfoundland, Canada. 40Ar/39Ar data were collected in situ by laser ablation and by step heating single crystals. Results were compared to each other and against complementary U-Pb zircon and monazite, and K-Ar fault gouge analysis. Although step-heat 40Ar/39Ar is a widely applied method in orogenic settings, this dataset shows that relatively flat step-heat 40Ar/39Ar spectra are in contradiction with wide spreads in in-situ 40Ar/39Ar dates from the same samples, and that plateau dates in some cases yielded mixed dates of equivocal geological significance. This result indicates that the step-wise release of Ar from white mica likely homogenizes and obscures spatially-controlled Ar isotope reservoirs in white mica from sheared rocks. In contrast, in situ laser ablation 40Ar/39Ar analysis preserves the spatial resolution of 40Ar reservoirs that have been variably reset by deformation and fluid interaction. This study therefore suggests that laser ablation is the best method for dating the timing of deformation recorded by white mica. Final interpretation of results should be guided by microstructural analysis, estimation of deformation temperature, chemical characterization of white mica, and complementary chronometers. Overall the dataset shows that granitic protoliths were emplaced between 430-422 Ma (U-Pb zircon). High strain deformation along the Wing Pond Shear Zone occurred between ca. 422-405 Ma (U-Pb monazite and 40Ar/39Ar). Subsequent patchy Ar loss in white mica occurred locally during low T shear (40Ar/39Ar). K-Ar dating of authigenic illite in fault gouge from the broadly co-linear brittle Hermitage Bay Fault indicates that slip along the terrane boundary persisted until at least the Mississippian

Changes in appetite, energy intake, body composition and circulating ghrelin constituents during an incremental trekking ascent to high altitude

Purpose Circulating acylated ghrelin concentrations are associated with altitude-induced anorexia in laboratory environments, but have never been measured at terrestrial altitude. This study examined time course changes in appetite, energy intake, body composition, and ghrelin constituents during a high-altitude trek. Methods Twelve participants [age: 28(4) years, BMI 23.0(2.1) kg m−2] completed a 14-day trek in the Himalayas. Energy intake, appetite perceptions, body composition, and circulating acylated, des-acylated, and total ghrelin concentrations were assessed at baseline (113 m, 12 days prior to departure) and at three fixed research camps during the trek (3619 m, day 7; 4600 m, day 10; 5140 m, day 12). Results Relative to baseline, energy intake was lower at 3619 m (P = 0.038) and 5140 m (P = 0.016) and tended to be lower at 4600 m (P = 0.056). Appetite perceptions were lower at 5140 m (P = 0.027) compared with baseline. Acylated ghrelin concentrations were lower at 3619 m (P = 0.046) and 4600 m (P = 0.038), and tended to be lower at 5140 m (P = 0.070), compared with baseline. Des-acylated ghrelin concentrations did not significantly change during the trek (P = 0.177). Total ghrelin concentrations decreased from baseline to 4600 m (P = 0.045). Skinfold thickness was lower at all points during the trek compared with baseline (P ≤ 0.001) and calf girth decreased incrementally during the trek (P = 0.010). Conclusions Changes in plasma acylated and total ghrelin concentrations may contribute to the suppression of appetite and energy intake at altitude, but differences in the time course of these responses suggest that additional factors are also involved. Interventions are required to maintain appetite and energy balance during trekking at terrestrial altitudes

Global Spatial Risk Assessment of Sharks Under the Footprint of Fisheries

Effective ocean management and conservation of highly migratory species depends on resolving overlap between animal movements and distributions and fishing effort. Yet, this information is lacking at a global scale. Here we show, using a big-data approach combining satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively) and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of high-seas fishing effort. Results demonstrate an urgent need for conservation and management measures at high-seas shark hotspots and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real time, dynamic management