The relationship between the stiffness and the mineral content of bone

The modulus of elasticity (E) of bone increases very rapidly with increase in mineral content, and in this is atypical of most composite materials. It is proposed that this apparent anomaly is caused by the end-to-end fusion of apatite crystals as the matrix becomes saturated with mineral. There is electron microscopic evidence that this occurs. Calculations using a fairly simple model show that this mechanism could be effective in life.     

The fungal pathogen Cryptococcus neoformans manipulates macrophage phagosome maturation

Phagocytosis by cells of the innate immune system, such as macrophages, and the subsequent successful maturation of the phagosome, is key for the clearance of pathogens. The fungal pathogen Cryptococcus neoformans is known to overcome killing by host phagocytes and both replicate within these cells and also escape via a non‐lytic process termed vomocytosis. Here we demonstrate that, during intracellular growth, cryptococci modify phagolysosome maturation. Live cryptococci, but not heat‐killed pathogens or inert targets, induce the premature removal of the early phagosome markers Rab5 and Rab11. In addition, significant acidification of the phagosome, calcium flux and protease activity is hindered, thus rendering the phagosome permissive for cryptococcal proliferation. Interestingly, several attenuated cryptococcal mutants retain this ability to subvert phagosomal maturation, suggesting that hitherto unidentified pathogen mechanisms regulate this process.     

Tubular frameworks guiding orderly bone formation in the antler of the red deer (Cervus elaphus)

Deer antler is a bony tissue which re-grows every year after shedding. Growth speed and material properties of this tissue are truly remarkable, making it an interesting model for bone regeneration. Surprisingly, not much is known about the ultrastructure of the calcified tissues and the temporal sequence of their development during antler growth. We use a combination of imaging tools based on light and electron microscopy to characterize antler tissue at various stages of development. We observe that mineralized cartilage is first transformed into a bone framework with low degree of collagen fibril ordering at the micron level. This framework has a honeycomb-like appearance with the cylindrical pores oriented along the main antler axis. Later, this tissue is filled with primary osteons, whose collagen fibrils are mainly oriented along the pores, thus improving the antler's mechanical properties. This strongly suggests that to achieve very fast organ growth it is advantageous to have a longitudinal porous framework as an intermediate step in bone formation. The example of antler shows that geometric features of this framework are crucial, and a tubular geometry with a diameter in the order of hundred micrometers seems to be a good solution for fast framework-mediated bone formation.     

Complete inhibition of the Pdr5p multidrug efflux pump ATPase activity by its transport substrate clotrimazole suggests that GTP as well as ATP may be used as an energy source

The yeast Pdr5p transporter is a 160 kDa protein that effluxes a large variety of xenobiotic compounds. In this study, we characterize its ATPase activity and demonstrate that it has biochemical features reminiscent of those of other ATP-binding cassette multidrug transporters: a relatively high Km for ATP (1.9 mM), inhibition by orthovanadate, and the ability to specifically bind an azidoATP analogue at the nucleotide-binding domains. Pdr5p-specific ATPase activity shows complete, concentration-dependent inhibition by clotrimazole, which is also known to be a potent transport substrate. Our results indicate, however, that this inhibition is noncompetitive and caused by the interaction of clotrimazole with the transporter at a site that is distinct from the ATP-binding domains. Curiously, Pdr5p-mediated transport of clotrimazole continues at intracellular concentrations of substrate that should eliminate all ATPase activity. Significantly, however, we observed that the Pdr5p has GTPase and UTPase activities that are relatively resistant to clotrimazole. Furthermore, the Km(GTPase) roughly matches the intracellular concentrations of the nucleotide reported for yeast. Using purified plasma membrane vesicles, we demonstrate that Pdr5p can use GTP to fuel substrate transport. We propose that Pdr5p increases its multidrug transport substrate specificity by using more than one nucleotide as an energy source.     

Social organization of Galagos in Kenyan coastal forests: I. Galago zanzibaricus

The social organization of Galago zanzibaricus was studied for the first time and the study included data from two different sites in the coastal forests of Kenya. A combination of mark-recapture and radio-tracking techniques was used to investigate patterns of inter- and intrasexual home range overlap. Associations in sleeping groups indicated social ties between individuals. Patterns of range use were established by radio-tracking focal individuals. Adult males generally had nonoverlapping ranges, shared with one or two females and their offspring with which the male regularly slept. Young females remained longer in their natal ranges than males and reproduced within their natal ranges. Range size and distance traveled per night were similar between the sexes; both sexes probably defended territories. None of the other galago (bushbaby) species studied to date show the degree of close male-female association found in G. zanzibaricus. This study thus extends the variety of social organization documented in nocturnal prosimians.