2,749 research outputs found

    Collagen-mimetic peptide-modifiable hydrogels for articular cartilage regeneration

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    Regenerative medicine strategies for restoring articular cartilage face significant challenges to recreate the complex and dynamic biochemical and biomechanical functions of native tissues. As an approach to recapitulate the complexity of the extracellular matrix, collagen-mimetic proteins offer a modular template to incorporate bioactive and biodegradable moieties into a single construct. We modified a Streptococcal collagen-like 2 protein with hyaluronic acid (HA) or chondroitin sulfate (CS)-binding peptides and then cross-linked with a matrix metalloproteinase 7 (MMP7)-sensitive peptide to form biodegradable hydrogels. Human mesenchymal stem cells (hMSCs) encapsulated in these hydrogels exhibited improved viability and significantly enhanced chondrogenic differentiation compared to controls that were not functionalized with glycosaminoglycan-binding peptides. Hydrogels functionalized with CS-binding peptides also led to significantly higher MMP7 gene expression and activity while the HA-binding peptides significantly increased chondrogenic differentiation of the hMSCs. Our results highlight the potential of this novel biomaterial to modulate cell-mediated processes and create functional tissue engineered constructs for regenerative medicine applications

    Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1α : modulation by p38 MAPK

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    The transcriptional coactivator PPAR gamma coactivator 1 α (PGC-1α) is a key regulator of metabolic processes such as mitochondrial biogenesis and respiration in muscle and gluconeogenesis in liver. Reduced levels of PGC-1α in humans have been associated with type II diabetes. PGC-1α contains a negative regulatory domain that attenuates its transcriptional activity. This negative regulation is removed by phosphorylation of PGC-1α by p38 MAPK, an important kinase downstream of cytokine signaling in muscle and β-adrenergic signaling in brown fat. We describe here the identification of p160 myb binding protein (p160MBP) as a repressor of PGC-1α. The binding and repression of PGC-1α by p160MBP is disrupted by p38 MAPK phosphorylation of PGC-1α. Adenoviral expression of p160MBP in myoblasts strongly reduces PGC-1α's ability to stimulate mitochondrial respiration and the expression of the genes of the electron transport system. This repression does not require removal of PGC-1α from chromatin, suggesting that p160MBP is or recruits a direct transcriptional suppressor. Overall, these data indicate that p160MBP is a powerful negative regulator of PGC-1α function and provide a molecular mechanism for the activation of PGC-1α by p38 MAPK. The discovery of p160MBP as a PGC-1α regulator has important implications for the understanding of energy balance and diabetes

    Summaries of Remarks by Commentators

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    Sensitivity of a shark nursery habitat to a changing climate

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    Nursery area habitats such as estuaries are vital for the success of many fish populations. Climate change is altering conditions in these areas, which can thus impact the availability of suitable nursery habitat. The sandbar shark Carcharhinus plumbeus uses Chesapeake Bay (USA) as a nursery habitat during the summer months from birth up to 10 yr of age. To assess the impacts of climate change on juvenile sandbar sharks, we developed a habitat model using longline data collected from a fishery-independent survey within Chesapeake Bay. With this model, we projected contemporary and future distributions of suitable habitat for juvenile sandbar sharks in Chesapeake Bay under varying environmental regimes. Predicted suitable juvenile sandbar shark habitat was negatively impacted by future increases in temperature, but positively influenced by future decreases in dissolved oxygen. The latter trend was likely related to the habitat partitioning that occurs between different life stages. Changes in salinity had relatively small impacts. By end-of-century the projected amount of suitable bottom habitat decreased; however, when incorporating the entire water column, projected suitable habitat increased. This suggests that juvenile sandbar sharks may need to make a behavioral shift to avoid non-preferred conditions, which could alter their foraging ecology or refuge strategies. As nursery habitats change with climate change, it is crucial to understand how a species may be impacted during this vital life stage when trying to predict overall species success in the future

    Estimating Shifts in Phenology and Habitat Use of Cobia in Chesapeake Bay Under Climate Change

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    Cobia (Rachycentron canadum) is a large coastal pelagic fish species that represents an important fishery in many coastal Atlantic states of the U.S. They are heavily fished in Virginia when they migrate into Chesapeake Bay during the summer to spawn and feed. These coastal habitats have been subjected to warming and increased hypoxia which in turn could impact the timing of migration and the habitat suitability of Chesapeake Bay. With conditions expected to worsen, we project current and future habitat suitability of Chesapeake Bay for cobia and predict changes in their arrival and departure times as conditions shift. To do this we developed a depth integrated habitat model from archival tagging and physiology data from cobia that used Chesapeake Bay, and applied the model to contemporary and future temperature and oxygen output from a coupled hydrodynamic-biogeochemical model of Chesapeake Bay. We found that estimated arrival occurs earlier and estimated departure time occurs later when temperatures are warmer and that by mid- and end-of-century cobia may spend on average up to 30 and 65 more days, respectively, in Chesapeake Bay. By mid-century we do not expect habitat suitability to change substantially for cobia, but by end-of-century we project it will significantly decline and shift closer to the mouth of Chesapeake Bay. Our study provides evidence that cobia will have the capacity to withstand near term impacts of climate change, but that their migration phenology varies from year to year with changing temperatures. These findings emphasize the need to incorporate the relationship between fishes and their environment into how fisheries are managed. This information can also help guide managers when deciding the timing and allocation of a fishery

    Pratiques d’affaires et performance des PME camerounaises

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    La compétitivité des entreprises, est l’un des enjeux auxquels sont confrontés quotidiennement les propriétaires dirigeants de PME, peu importe les pays, les secteurs et la nature de l’activité. Pour faire face à cet enjeu, les PME doivent mettre en place les facteurs de leur réussite dont elles mesureront les résultats grâce à la gestion de leur performance. La littérature permet d’identifier de nombreux facteurs déterminants de la performance, mais ceux-ci ont été mis au jour principalement par l’étude d’entreprises localisées dans les pays développés où le contexte et l’écosystème d’affaires ne sont pas représentatifs de ce qui existe dans les pays en développement. Quels sont les déterminants de la performance des PME africaines ? Notre étude permet de répondre à cette question grâce à l’analyse de PME manufacturières camerounaises. Une analyse typologique a permis aussi de regrouper les entreprises en trois clusters, à partir desquels on observe des comportements différents et un usage des pratiques d’affaires variable selon les groupes. Les configurations d’entreprises obtenues ne se distinguent toutefois pas au niveau de leur performance, ce qui signifie que les entreprises ont su identifier les pratiques d’affaires qu’elles avaient besoin pour rencontrer leurs objectifs

    A Quasi-Classical Model of Intermediate Velocity Particle Production in Asymmetric Heavy Ion Reactions

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    The particle emission at intermediate velocities in mass asymmetric reactions is studied within the framework of classical molecular dynamics. Two reactions in the Fermi energy domain were modelized, 58^{58}Ni+C and 58^{58}Ni+Au at 34.5 MeV/nucleon. The availability of microscopic correlations at all times allowed a detailed study of the fragment formation process. Special attention was paid to the physical origin of fragments and emission timescales, which allowed us to disentangle the different processes involved in the mid-rapidity particle production. Consequently, a clear distinction between a prompt pre- equilibrium emission and a delayed aligned asymmetric breakup of the heavier partner of the reaction was achieved.Comment: 8 pages, 7 figures. Final version: figures were redesigned, and a new section discussing the role of Coulomb in IMF production was include
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