Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response

The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low-dose recombinant human TNF (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF treatment is only effective when administered within 24h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti-TNF impaired fracture healing. Addition of rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rhTNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization

Habitat model forecasts suggest potential redistribution of marine predators in the southern Indian Ocean

International audienceAim: Climate change will likely lead to a significant redistribution of biodiversity inmarine ecosystems. We examine the potential redistribution of a community of marinepredators by comparing current and future habitat distribution projections. Weexamine relative changes among species, indicative of potential future community-levelchanges and consider potential consequences of these changes for conservationand management.Location: Southern Indian Ocean.Methods: We used tracking data from 14 species (10 seabirds, 3 seals and 1 cetacean,totalling 538 tracks) to model the habitat selection of predators around thePrince Edward Islands. Using random forest classifiers, we modelled habitat selectionas a response to a static environmental covariate and nine dynamic environmental covariates obtained from eight IPCC-classclimate models. To project the potentialdistribution of the predators in 2071–2100,we used climate model outputs assumingtwo greenhouse gas emission scenarios: RCP 4.5 and RCP 8.5.Results: Analogous climates are projected to predominantly shift to the southeast andsouthwest. Species’ potential range shifts varied in direction and magnitude, but overallshifted slightly to the southwest. Despite the variable shifts among species, currentspecies co-occurrencepatterns and future projections were statistically similar.Our projections show that at least some important habitats will shift out of nationalwaters and marine protected areas by 2100, but important habitat area will increasein the Convention on the Conservation of Antarctic Marine Living Resources Area.Predicted areas of common use among predators decreased north of the islands andincreased to the south, suggesting that multiple predator species may use southerlyhabitats more intensively in the future. Consequently, Southern Ocean managementauthorities could implement conservation actions to partially offset these shifts.Main conclusions: Overall, we predict that marine predator biodiversity in the southernIndian Ocean will be redistributed, with ecological, conservation and managementimplications

Mechanical and radiological assessment of the influence of rhTGFbeta-3 on bone regeneration in a segmental defect in the ovine tibia: pilot study

Limitations in the use of autologous bone graft, which is the gold standard therapy in bone defect healing, drive the search for alternative treatments. In this study the influence of rhTGFbeta-3 on mechanical and radiological parameters of a healing bone defect in the sheep tibia was assessed. In the sheep, an 18-mm long osteoperiosteal defect in the tibia was treated by rhTGFbeta-3 seeded on a poly(L/DL-lactide) carrier (n = 4). In a second group (n = 4), the defect was treated by the carrier only, in a third group (n = 4) by autologous cancellous bone graft, and in a fourth group (n = 2) the defect remained blank. The healing process of the defect was assessed by weekly in vivo stiffness measurements and radiology as well as by quantitative computed tomographic assessment of bone mineral density (BMD) every 4 weeks. The duration of the experiment was 12 weeks under loading conditions. In the bone graft group, a marginally significant higher increase in stiffness was observed than in the PLA/rhTGFbeta-3 group (p = 0.06) and a significantly higher increase than in the PLA-only group (p = 0.03). The radiographic as well as the computed tomographic evaluation yielded significant differences between the groups (p = 0.03), indicating the bone graft treatment (bone/per area, 83%; BMD, 0.57 g/cm(3)) performing better than the PLA/rhTGFbeta-3 (38%; 0.23 g/cm(3)) and the PLA-only treatment (2.5%; 0.09 g/cm(3)), respectively. Regarding the mechanical and radiological parameters assessed in this study, we conclude that rhTGFbeta-3 has a promoting effect on bone regeneration. However, under the conditions of this study, this effect does not reach the potential of autologous cancellous bone graft transplantation

Habitat model forecasts suggest potential redistribution of marine predators in the Southern Indian ocean

AIM : Climate change will likely lead to a significant redistribution of biodiversity in marine ecosystems. We examine the potential redistribution of a community of ma-rine predators by comparing current and future habitat distribution projections. We examine relative changes among species, indicative of potential future community- level changes and consider potential consequences of these changes for conservation and management. LOCATION : Southern Indian Ocean. METHODS : We used tracking data from 14 species (10 seabirds, 3 seals and 1 ceta-cean, totalling 538 tracks) to model the habitat selection of predators around the Prince Edward Islands. Using random forest classifiers, we modelled habitat selection as a response to a static environmental covariate and nine dynamic environmental covariates obtained from eight IPCC-class climate models. To project the potential distribution of the predators in 2071–2100, we used climate model outputs assuming two greenhouse gas emission scenarios: RCP 4.5 and RCP 8.5. RESULTS : Analogous climates are projected to predominantly shift to the southeast and southwest. Species’ potential range shifts varied in direction and magnitude, but over-all shifted slightly to the southwest. Despite the variable shifts among species, cur-rent species co-occurrence patterns and future projections were statistically similar. Our projections show that at least some important habitats will shift out of national waters and marine protected areas by 2100, but important habitat area will increase in the Convention on the Conservation of Antarctic Marine Living Resources Area. Predicted areas of common use among predators decreased north of the islands and increased to the south, suggesting that multiple predator species may use southerly habitats more intensively in the future. Consequently, Southern Ocean management authorities could implement conservation actions to partially offset these shifts. MAIN CONCLUSIONS : Overall, we predict that marine predator biodiversity in the south-ern Indian Ocean will be redistributed, with ecological, conservation and management implications.WWF-UK; Scientific Committee on Antarctic Research; National Research Foundation.http://www.wileyonlinelibrary.com/journal/ddidm2022Mammal Research InstituteZoology and Entomolog

Habitat model forecasts suggest potential redistribution of marine predators in the southern Indian Ocean

Aim: Climate change will likely lead to a significant redistribution of biodiversity in marine ecosystems. We examine the potential redistribution of a community of marine predators by comparing current and future habitat distribution projections. We examine relative changes among species, indicative of potential future community-level changes and consider potential consequences of these changes for conservation and management. Location: Southern Indian Ocean. Methods: We used tracking data from 14 species (10 seabirds, 3 seals and 1 cetacean, totalling 538 tracks) to model the habitat selection of predators around the Prince Edward Islands. Using random forest classifiers, we modelled habitat selection as a response to a static environmental covariate and nine dynamic environmental covariates obtained from eight IPCC-class climate models. To project the potential distribution of the predators in 2071–2100, we used climate model outputs assuming two greenhouse gas emission scenarios: RCP 4.5 and RCP 8.5.Results: Analogous climates are projected to predominantly shift to the southeast and southwest. Species’ potential range shifts varied in direction and magnitude, but overall shifted slightly to the southwest. Despite the variable shifts among species, current species co-occurrence patterns and future projections were statistically similar. Our projections show that at least some important habitats will shift out of national waters and marine protected areas by 2100, but important habitat area will increase in the Convention on the Conservation of Antarctic Marine Living Resources Area. Predicted areas of common use among predators decreased north of the islands and increased to the south, suggesting that multiple predator species may use southerly habitats more intensively in the future. Consequently, Southern Ocean management authorities could implement conservation actions to partially offset these shifts. Main conclusions: Overall, we predict that marine predator biodiversity in the southern Indian Ocean will be redistributed, with ecological, conservation and management implications.</p

Scaffold-based bone engineering by using genetically modified cells

10.1016/j.gene.2004.12.040Gene34711-10GENE