135 research outputs found

    Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-beta and Runx2 in bone is required for hearing

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    Publisher version: http://www.nature.com/embor/journal/v11/n10/full/embor2010135.htmlDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEDA - 20100917 IS - 1469-3178 (Electronic) IS - 1469-221X (Linking) LA - ENG PT - JOURNAL ARTICLEPhysical cues, such as extracellular matrix stiffness, direct cell differentiation and support tissue-specific function. Perturbation of these cues underlies diverse pathologies, including osteoarthritis, cardiovascular disease and cancer. However, the molecular mechanisms that establish tissue-specific material properties and link them to healthy tissue function are unknown. We show that Runx2, a key lineage-specific transcription factor, regulates the material properties of bone matrix through the same transforming growth factor-beta (TGFbeta)-responsive pathway that controls osteoblast differentiation. Deregulated TGFbeta or Runx2 function compromises the distinctly hard cochlear bone matrix and causes hearing loss, as seen in human cleidocranial dysplasia. In Runx2(+/-) mice, inhibition of TGFbeta signalling rescues both the material properties of the defective matrix, and hearing. This study elucidates the unknown cause of hearing loss in cleidocranial dysplasia, and demonstrates that a molecular pathway controlling cell differentiation also defines material properties of extracellular matrix. Furthermore, our results suggest that the careful regulation of these properties is essential for healthy tissue functio

    Conjugative Botulinum Neurotoxin-Encoding Plasmids in Clostridium botulinum

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    Clostridium botulinum produces seven distinct serotypes of botulinum neurotoxins (BoNTs). The genes encoding different subtype neurotoxins of serotypes A, B, F and several dual neurotoxin-producing strains have been shown to reside on plasmids, suggesting that intra- and interspecies transfer of BoNT-encoding plasmids may occur. The objective of the present study was to determine whether these C. botulinum BoNT-encoding plasmids are conjugative.C. botulinum BoNT-encoding plasmids pBotCDC-A3 (strain CDC-A3), pCLJ (strain 657Ba) and pCLL (strain Eklund 17B) were tagged with the erythromycin resistance marker (Erm) using the ClosTron mutagenesis system by inserting a group II intron into the neurotoxin genes carried on these plasmids. Transfer of the tagged plasmids from the donor strains CDC-A3, 657Ba and Eklund 17B to tetracycline-resistant recipient C. botulinum strains was evaluated in mating experiments. Erythromycin and tetracycline resistant transconjugants were isolated from donor:recipient mating pairs tested. Transfer of the plasmids to the transconjugants was confirmed by pulsed-field gel electrophoresis (PFGE) and Southern hybridizations. Transfer required cell-to-cell contact and was DNase resistant. This indicates that transfer of these plasmids occurs via a conjugation mechanism.This is the first evidence supporting conjugal transfer of native botulinum neurotoxin-encoding plasmids in C. botulinum, and provides a probable mechanism for the lateral distribution of BoNT-encoding plasmids to other C. botulinum strains. The potential transfer of C. botulinum BoNT-encoding plasmids to other bacterial hosts in the environment or within the human intestine is of great concern for human pathogenicity and necessitates further characterization of these plasmids

    MFA11 (MFA 2011)

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    Catalogue of a culminating student exhibition held at the Mildred Lane Kemper Art Museum, May 6-Aug. 1, 2011. Content includes Introduction / Buzz Spector -- Patricia Olynyk -- Marshall N. Klimasewiski -- John Talbott Allen -- Meghan Bean -- Shira Berkowitz / Maggie Stanley Majors -- Darrick Byers, Bryce Olen Robinson -- Jisun Choi -- Zlatko Ćosić -- James R. Daniels -- Kara Daving -- Andrea Degener -- Kristin Fleischmann / Randi Shapiro -- William Frank / Lawrence Ypil -- Nicholas Kania -- Katherine McCullough -- Jordan McGirk / Aditi Machado -- Zachary Miller -- Esther Murphy / Maggie Stanley Majors -- Kathryn Neale -- Christopher Ottinger / Melissa Olson -- Maia Palmer -- Nicole Petrescu / Melissa Olson -- Lauren Pressler / Randi Shapiro -- Whitney Sage / Aliya A. Reich -- Donna Smith.https://openscholarship.wustl.edu/books/1005/thumbnail.jp

    Competing Tradeoff between Increasing Marine Mammal Predation and Fisheries Harvest of Chinook Salmon

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    Many marine mammal predators, particularly pinnipeds, have increased in abundance in recent decades, generating new challenges for balancing human uses with recovery goals via ecosystem-based management. We used a spatio-temporal bioenergetics model of the Northeast Pacific Ocean to quantify how predation by three species of pinnipeds and killer whales (Orcinus orca) on Chinook salmon (Oncorhynchus tshawytscha) has changed since the 1970s along the west coast of North America, and compare these estimates to salmon fisheries. We find that from 1975 to 2015, biomass of Chinook salmon consumed by pinnipeds and killer whales increased from 6,100 to 15,200 metric tons (from 5 to 31.5 million individual salmon). Though there is variation across the regions in our model, overall, killer whales consume the largest biomass of Chinook salmon, but harbor seals (Phoca vitulina) consume the largest number of individuals. The decrease in adult Chinook salmon harvest from 1975–2015 was 16,400 to 9,600 metric tons. Thus, Chinook salmon removals (harvest + consumption) increased in the past 40 years despite catch reductions by fisheries, due to consumption by recovering pinnipeds and endangered killer whales. Long-term management strategies for Chinook salmon will need to consider potential conflicts between rebounding predators or endangered predators and prey

    Evaluating changes in marine communities that provide ecosystem services through comparative assessments of community indicators

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    Fisheries provide critical provisioning services, especially given increasing human population. Understanding where marine communities are declining provides an indication of ecosystems of concern and highlights potential conflicts between seafood provisioning from wild fisheries and other ecosystem services. Here we use the nonparametric statistic, Kendall[U+05F3]s tau, to assess trends in biomass of exploited marine species across a range of ecosystems. The proportion of 'Non-Declining Exploited Species' (NDES) is compared among ecosystems and to three community-level indicators that provide a gauge of the ability of a marine ecosystem to function both in provisioning and as a regulating service: survey-based mean trophic level, proportion of predatory fish, and mean life span. In some ecosystems, NDES corresponds to states and temporal trajectories of the community indicators, indicating deteriorating conditions in both the exploited community and in the overall community. However differences illustrate the necessity of using multiple ecological indicators to reflect the state of the ecosystem. For each ecosystem, we discuss patterns in NDES with respect to the community-level indicators and present results in the context of ecosystem-specific drivers. We conclude that using NDES requires context-specific supporting information in order to provide guidance within a management framework.We would like to thank the IndiSeas Working Group, endorsed by IOC-UNESCO (www.ioc-unesco.org) and the European Network of Excellence Euroceans (www.eur-oceans.eu). KMK was supported by Conservation International and the Sea Around Us project, a collaboration between The University of British Columbia and The Pew Charitable Trusts. MC was partially supported by the EC Marie Curie CIG grant to BIOWEB and the Spanish Research Program Ramon y Cajal. LJS was supported through the South African Research Chair Initiative, funded through the South African Department of Science and Technology (DST) and administered by the South African National Research Foundation (NRF). YJS and MTT were supported by the French project EMIBIOS (FRB, contract no. APP-SCEN-2010-II). LJS and YS were also funded by the European collaborative project MEECE – Marine Ecosystem Evolution in a Changing Environment – (FP7, Contract no. 212085). CPL was supported by Defra project MF1228 (From Physics to Fisheries) and DEVOTES (DEVelopment of innovative Tools for understanding marine biodiversity and assessing good Environmental Status) funded by EU FP7 (grant Agreement no. 308392), www.devotes-project.eu. GIvdM was partially supported by the Norwegian Nature Index programme and the Institute of Marine Research, Norway. HO was funded was funded by the Estonian Ministry of Education and Research (grant SF0180005s10). MAT was funded by a predoctoral FPI fellowship from the Spanish Institute of Oceanography (IEO). MJJJ was supported by the EC Marie Curie IOF Grant, PIOF-GA-2013-628116. We acknowledge all those who conducted surveys to collect the data used in this study.Peer reviewe

    Management Strategy Evaluation: Allowing the Light on the Hill to Illuminate More Than One Species

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    Management strategy evaluation (MSE) is a simulation approach that serves as a “light on the hill” (Smith, 1994) to test options for marine management, monitoring, and assessment against simulated ecosystem and fishery dynamics, including uncertainty in ecological and fishery processes and observations. MSE has become a key method to evaluate trade-offs between management objectives and to communicate with decision makers. Here we describe how and why MSE is continuing to grow from a single species approach to one relevant to multi-species and ecosystem-based management. In particular, different ecosystem modeling approaches can fit within the MSE process to meet particular natural resource management needs. We present four case studies that illustrate how MSE is expanding to include ecosystem considerations and ecosystem models as ‘operating models’ (i.e., virtual test worlds), to simulate monitoring, assessment, and harvest control rules, and to evaluate tradeoffs via performance metrics. We highlight United States case studies related to fisheries regulations and climate, which support NOAA’s policy goals related to the Ecosystem Based Fishery Roadmap and Climate Science Strategy but vary in the complexity of population, ecosystem, and assessment representation. We emphasize methods, tool development, and lessons learned that are relevant beyond the United States, and the additional benefits relative to single-species MSE approaches
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