Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties.

Osteogenesis imperfecta (OI or brittle bone disease) is a disorder of connective tissues caused by mutations in the collagen genes. We previously showed that intrauterine transplantation of human blood fetal stem/stromal cells in OI mice (oim) resulted in a significant reduction of bone fracture. This work examines the cellular mechanisms and mechanical bone modifications underlying these therapeutic effects, particularly examining the direct effects of donor collagen expression on bone material properties. In this study, we found an 84% reduction in femoral fractures in transplanted oim mice. Fetal blood stem/stromal cells engrafted in bones, differentiated into mature osteoblasts, expressed osteocalcin, and produced COL1a2 protein, which is absent in oim mice. The presence of normal collagen decreased hydroxyproline content in bones, altered the apatite crystal structure, increased the bone matrix stiffness, and reduced bone brittleness. In conclusion, expression of normal collagen from mature osteoblast of donor origin significantly decreased bone brittleness by improving the mechanical integrity of the bone at the molecular, tissue, and whole bone levels.

Strandings as indicators of marine mammal biodiversity and human interactions off the coast of North Carolina

The adjacency of 2 marine biogeographic regions off Cape Hatteras, North Carolina (NC), and the proximity of the Gulf Stream result in a high biodiversity of species from northern and southern provinces and from coastal and pelagic habitats. We examined spatiotemporal patterns of marine mammal strandings and evidence of human interaction for these strandings along NC shorelines and evaluated whether the spatiotemporal patterns and species diversity of the stranded animals reflected published records of populations in NC waters. During the period of 1997–2008, 1847 stranded animals were documented from 1777 reported events. These animals represented 9 families and 34 species that ranged from tropical delphinids to pagophilic seals. This biodiversity is higher than levels observed in other regions. Most strandings were of coastal bottlenose dolphins (Tursiops truncatus) (56%), harbor porpoises (Phocoena phocoena) (14%), and harbor seals (Phoca vitulina) (4%). Overall, strandings of northern species peaked in spring. Bottlenose dolphin strandings peaked in spring and fall. Almost half of the strandings, including southern delphinids, occurred north of Cape Hatteras, on only 30% of NC’s coastline. Most stranded animals that were positive for human interaction showed evidence of having been entangled in fishing gear, particularly bottlenose dolphins, harbor porpoises, short-finned pilot whales (Globicephala macrorhynchus), harbor seals, and humpback whales (Megaptera novaeangliae). Spatiotemporal patterns of bottlenose dolphin strandings were similar to ocean gillnet fishing effort. Biodiversity of the animals stranded on the beaches reflected biodiversity in the waters off NC, albeit not always proportional to the relative abundance of species (e.g., Kogia species). Changes in the spatiotemporal patterns of strandings can serve as indicators of underlying changes due to anthropogenic or naturally occurring events in the source populations.

The simulation of stress fibre and focal adhesion development in cells on patterned substrates.

The remodelling of the cytoskeleton and focal adhesion (FA) distributions for cells on substrates with micro-patterned ligand patches is investigated using a bio-chemo-mechanical model. We investigate the effect of ligand pattern shape on the cytoskeletal arrangements and FA distributions for cells having approximately the same area. The cytoskeleton model accounts for the dynamic rearrangement of the actin/myosin stress fibres. It entails the highly nonlinear interactions between signalling, the kinetics of tension-dependent stress-fibre formation/dissolution and stress-dependent contractility. This model is coupled with another model that governs FA formation and accounts for the mechano-sensitivity of the adhesions from thermodynamic considerations. This coupled modelling scheme is shown to capture a variety of key experimental observations including: (i) the formation of high concentrations of stress fibres and FAs at the periphery of circular and triangular, convex-shaped ligand patterns; (ii) the development of high FA concentrations along the edges of the V-, T-, Y- and U-shaped concave ligand patterns; and (iii) the formation of highly aligned stress fibres along the non-adhered edges of cells on the concave ligand patterns. When appropriately calibrated, the model also accurately predicts the radii of curvature of the non-adhered edges of cells on the concave-shaped ligand patterns.