Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH‐induced bone anabolism in mice

Teriparatide is a bone anabolic treatment for osteoporosis, modeled in animals by intermittent PTH (iPTH) administration, but the cellular and molecular mechanisms of action of iPTH are largely unknown. Here, we show that Teriparatide and iPTH cause a ~two‐threefold increase in the number of regulatory T cells (Tregs) in humans and mice. Attesting in vivo relevance, blockade of the Treg increase in mice prevents the increase in bone formation and trabecular bone volume and structure induced by iPTH. Therefore, increasing the number of Tregs is a pivotal mechanism by which iPTH exerts its bone anabolic activity. Increasing Tregs pharmacologically may represent a novel bone anabolic therapy, while iPTH‐induced Treg increase may find applications in inflammatory conditions and transplant medicine.     

The amino-terminal region of group A streptococcal M protein determines its molecular state of assembly and function

Group A streptococcal M protein, a major virulence factor, is an alpha-helical coiled-coil dimer on the surface of the bacteria. Limited proteolysis of type 57 streptococcus with pepsin released two fragments of the M57 molecule, with apparent molecular weights of 32,000 and 27,000 on SDS-PAGE. However, on gel filtration under nondenaturing conditions, each of these proteins eluted as two distinct molecular forms. The two forms corresponded to their dimeric and monomeric state as compared to the gel filtration characteristics of known dimeric coiled-coil proteins. The results of sedimentation equilibrium measurements were consistent with this, but further indicated that the dimeric form consisted of a dimer in rapid equilibrium with its monomer, whereas the monomeric form does not dimerize. The monomeric form was the predominant species for the 27 kD species, whereas the dimeric form predominated for the 32 kD species. Sequence analysis revealed the 27 kD species to be a truncated derivative of the 32 kD PepM57 species, lacking the N-terminal nonheptad region of the M57 molecule. These data strongly suggested that the N-terminal nonheptad region of PepM57 is important in determining the molecular state of the molecule. Consistent with this, PepM49, another nephritis-associated serotype, which lacks the nonheptad N-terminal region, also eluted as a monomer on gel filtration under nondenaturing conditions. Furthermore, removal of the N-terminal nonheptad segment of the dimeric PepM6 protein converted it into a monomeric form. The dimeric molecular form of both the 32 kD PepM57 and the 27 kD PepM57 did not represent a stable state of assembly, and were susceptible to conversion to the corresponding monomeric molecular forms by simple treatments, such as lyophilization. The 27 kD PepM57 exhibited a greater propensity than the 32 kD species to exist in the monomeric form. The 32 kD species contained the opsonic epitope of the M57 molecule, whereas the 27 kD species lacked the same. This is consistent with the previous reports on the importance of the N-terminal region of M protein for its opsonic activity. Together, these results strongly suggest that, in addition to its importance for the biological function, the N-terminal region of the M protein plays a dominant role in determining the molecular state of the M molecule, as well as its stability.     

The orientation of the alpha-helices in alpha-keratin fibres

Considerable physical evidence has been accumulated in support of the polarity of alpha-keratin fibres and is summarised here. Dielectric loss and dielectric dipole movement in dry intact fibres as they undergo thermal transition above 200 degrees C show alpha-keratin to be a polar structure. X-ray diffraction has shown that this transition corresponds to the randomisation of the organised alpha-helical structure resulting in the loss of polarity of the fibre. The piezoelectric properties of alpha-keratin can only be explained if its alpha-helical dipoles in the ordered structure alpha-keratin are synergistically aligned in the axial direction. If the alpha-helical units of the IFs of alpha-keratin fibre were in an anti-parallel conformation then dry alpha-keratin would show no polarity. FTIR measurements on alpha-keratin fibres extended in water at 21 and 95 degrees C explain the formation of anti-parallel beta-structures when fibres are extended in steam. Contrary to in vitro experimental data there is clear evidence that native alpha-keratin fibres are polar structures with the alpha-helices aligned in a parallel conformation.     

Altered aspartate in Alzheimer neurofibrillary tangles

Normal protein-boundl-aspartyl/l-asparaginyl residues may undergo post-translational modification by racemization tod-aspartate, or by isomerization to thel-isoaspartyl form in which the peptide chain links through the beta carboxyl group of the residue. Based on preliminary results reported here, proteins associated with Alzheimer neurofibrillary tangle preparations contain a significantly greater number of these modified aspartyl residues than the unaffected proteins from the surrounding gray matter or in comparable preparations from normal brains.     

THE RATE OF BACTERIOPHAGE INACTIVATION BY FILTRATES OF ESCHERICHIA COLI CULTURES

1. The rate of inactivation of an anti-coli phage by filtrates of cultures of the homologous bacteria has been studied. 2. The inactivation rate at 37°C. is proportional to phage concentration and filtrate concentration. 3. At 0°C. the rate of phage inactivation becomes proportional to the square root of the filtrate concentration. 4. A reaction scheme to account for these observations is suggested and discussed. 5. This coli-phage is also inactivated by relatively large concentrations of soluble starch, inulin, gum arabic, and acetylated gum arabic. 6. The inactivation is markedly influenced by salt concentration, being rapid at moderate salt concentrations and slow at high or extremely low salt concentrations. 7. The inactivated phage cannot be regenerated by high salt concentrations, or by soaps.     

The patterns of interaction between the young males and group members in captive groups ofMandrillus sphinx andTheropithecus gelada

The child-rearing climate ofMandrillus sphinx andTheropithecus gelada was studied for two weeks in a zoo situation. The social interactions between the young male of each group and their respective group members are described and examined in detail, noting similarities and differences. Possible factors affecting the findings are suggested (notable among them being small sample size, age differences, and group compositional differences).