Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling.

Cells rely on the coordinated regulation of lipid phosphoinositides and Rab GTPases to define membrane compartment fates along distinct trafficking routes. The family of disease-related myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, with poorly understood functions. We found that Drosophila MTM pseudophosphatase Sbf coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. Sbf dynamically interacts with class II phosphatidylinositol 3-kinase and stably recruits Mtm to promote turnover of a PI(3)P subpool essential for endosomal trafficking. Sbf also functions as a guanine nucleotide exchange factor that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Of importance, Sbf, Mtm, and Rab21 function together, along with Rab11-mediated endosomal trafficking, to control macrophage protrusion formation. This identifies Sbf as a critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal pathway and cortical control

Post-traumatic osteoarthritis in mice following mechanical injury to the synovial joint

We investigated the spectrum of lesions characteristic of post-traumatic osteoarthritis (PTOA) across the knee joint in response to mechanical injury. We hypothesized that alteration in knee joint stability in mice reproduces molecular and structural features of PTOA that would suggest potential therapeutic targets in humans. The right knees of eight-week old male mice from two recombinant inbred lines (LGXSM-6 and LGXSM-33) were subjected to axial tibial compression. Three separate loading magnitudes were applied: 6N, 9N, and 12N. Left knees served as non-loaded controls. Mice were sacrificed at 5, 9, 14, 28, and 56 days post-loading and whole knee joint changes were assessed by histology, immunostaining, micro-CT, and magnetic resonance imaging. We observed that tibial compression disrupted joint stability by rupturing the anterior cruciate ligament (except for 6N) and instigated a cascade of temporal and topographical features of PTOA. These features included cartilage extracellular matrix loss without proteoglycan replacement, chondrocyte apoptosis at day 5, synovitis present at day 14, osteophytes, ectopic calcification, and meniscus pathology. These findings provide a plausible model and a whole-joint approach for how joint injury in humans leads to PTOA. Chondrocyte apoptosis, synovitis, and ectopic calcification appear to be targets for potential therapeutic intervention

Coupled economic-ecological models for ecosystem-based fishery management: Exploration of trade-offs between model complexity and management needs

Ecosystem based fishery management has moved beyond rhetorical statements calling for a more holistic approach to resource management, to implementing decisions on resource use that are compatible with goals of maintaining ecosystem health and resilience. Coupled economic-ecological models are a primary tool for informing these decisions. Recognizing the importance of these models, the International Council for the Exploration of the Seas (ICES) formed a Study Group on Integration of Economics, Stock Assessment and Fisheries Management (SGIMM) to explore alternative modelling approaches that bring the multiple disciplines of economics, ecology, and stock assessment into integrated ecosystem models. The theme session was designed to be an extension of a series of workshops and theme sessions organized by the SGIMM, but highlighted the economic component of coupled models. Although economic and ecological systems are inherently complex, models are abstractions of these systems incorporating varying levels of complexity depending on available data and the management issues to be addressed. The objective of this special session was to assess the pros and cons of increasing model complexity to incorporate linkages between ecosystem components and processes. While more complex ecosystem models may provide greater insight into how management decisions and human actions propagate through the ecosystem and impact the value of ecosystem services, the resources and information required to develop and parameterize them is greater and these models tend to require trade-offs such as the inability to quantify uncertainty or model human behaviour as accurately as can be done with models of individual fisheries. The theme session was organized as a moderated panel format representing a progression of economic-ecological models from less to increasingly complex. The panel was selected to represent a range of models from fully integrated, highly detailed and dynamic economic-ecological models such as Atlantis to models that may be less detailed or not fully dynamic or integrated. The special session focused primarily on management issues that are of a longer term strategic nature such as the implications of climate change, fundamental regime change, or the role of forage species in an ecosystem. Each panellist provided an overview of their model including the management questions the model was designed to address, the data and time requirements, as well as any lessons learned. The panellist presentations were followed by an open discussion among the panellists and the audience. The abstracts for each of the panellist presentation are provided below followed by a summary of the issues raised during the moderated discussion sessio

XMM-Newton and Optical Observations of Cataclysmic Variables from SDSS

We report on XMM-Newton and optical results for 6 cataclysmic variables that were selected from Sloan Digital Sky Survey spectra because they showed strong HeII emission lines, indicative of being candidates for containing white dwarfs with strong magnetic fields. While high X-ray background rates prevented optimum results, we are able to confirm SDSSJ233325.92+152222.1 as an intermediate polar from its strong pulse signature at 21 min and its obscured hard X-ray spectrum. Ground-based circular polarization and photometric observations were also able to confirm SDSSJ142256.31-022108.1 as a polar with a period near 4 hr. Photometry of SDSSJ083751.00+383012.5 and SDSSJ093214.82+495054.7 solidifies the orbital period of the former as 3.18 hrs and confirms the latter as a high inclination system with deep eclipses.Comment: 31 pages, 14 figures. Accepted for publication in the Astronomical Journa

Molecular insight into the association between cartilage regeneration and ear wound healing in genetic mouse models: Targeting new genes in regeneration

Tissue regeneration is a complex trait with few genetic models available. Mouse strains LG/J and MRL are exceptional healers. Using recombinant inbred strains from a large (LG/J, healer) and small (SM/J, nonhealer) intercross, we have previously shown a positive genetic correlation between ear wound healing, knee cartilage regeneration, and protection from osteoarthritis. We hypothesize that a common set of genes operates in tissue healing and articular cartilage regeneration. Taking advantage of archived histological sections from recombinant inbred strains, we analyzed expression of candidate genes through branched-chain DNA technology directly from tissue lysates. We determined broad-sense heritability of candidates, Pearson correlation of candidates with healing phenotypes, and Ward minimum variance cluster analysis for strains. A bioinformatic assessment of allelic polymorphisms within and near candidate genes was also performed. The expression of several candidates was significantly heritable among strains. Although several genes correlated with both ear wound healing and cartilage healing at a marginal level, the expression of four genes representing DNA repair (Xrcc2, Pcna) and Wnt signaling (Axin2, Wnt16) pathways was significantly positively correlated with both phenotypes. Cluster analysis accurately classified healers and nonhealers for seven out of eight strains based on gene expression. Specific sequence differences between LG/J and SM/J were identified as potential causal polymorphisms. Our study suggests a common genetic basis between tissue healing and osteoarthritis susceptibility. Mapping genetic variations causing differences in diverse healing responses in multiple tissues may reveal generic healing processes in pursuit of new therapeutic targets designed to induce or enhance regeneration and, potentially, protection from osteoarthritis