A simulation model for an Iridaea splendens (Gigartinales,Rhodophyta) population in Vancouver,Canada

Populations of Iridaea splendens at Brockton Point, Stanley Park, Vancouver, Canada were observed to alternate in dominance between the gametophytic phase in summer and tetrasporophytic phase in winter. The mechanism regulating this alternation is not clear. Using a matrix projection model to simulate population growth, we show that this alternation is possible if there are differential survival and recruitment rates of the two phases in summer and winter. Sensitivity and elasticity analyses indicate the relative importance of perennation vs. recruitment. Recruitment from tetrasporophytes and from gametophytes both contribute about 25% to the population growth. Perennation among gametophytes is more important than among tetrasporophytes. The implication of this is that if this population is to be harvested, more tetrasporophytes can be harvested than gametophytes without resulting in the depletion of the resource. This is simulated in the matrix model by comparing the relative effects on population growth of increasing the mortality rate of the perennation phase of tetrasporophyte and gametophyte by 50 to 75%, and increasing recruitment rate in either phase, from summer to winter or from winter to summer.Dedicated to Dr T. Bisalputra of the University of British Columbia on the occasion of his retirement.     

Fetal sex ratio in the rhesus (Macaca mulatta).

Fetal sex ratio was determined in several hundred timed Macaca mulatta pregnancies terminated by hysterotomy between 75 and 179 days' gestation. From 75 to 149 days' gestation a greater number of females occurred in utero, while after 150 days a greater number of males was observed. However, this difference was not statistically significant.     

Neutralization of interleukin-11 activity decreases osteoclast formation and increases cancellous bone volume in ovariectomized mice

The issue of whether interleukin-11 (IL-11) contributes to bone loss during states of estrogen deficiency has not been previously determined. We therefore randomized ovariectomized (OVX) mice to once daily interperitoneal injections of either sheep anti-murine IL-11 Ab or normal sheep IgG (NSIgG) for 21 days, and then determined the effects on bone using bone histomorphometry. Here we report that treatment of OVX mice with anti-IL-11 Ab significantly increases both trabecular width and cancellous bone volume. Osteoblast activity, as measured by the percentage of trabecular surface covered by osteoid and rates of bone formation, were also significantly increased following treatment with anti-IL-11 Ab. In contrast, treatment of OVX mice with anti-IL-11 Ab significantly decreased both osteoclast number and activity. Ex-vivo assays of osteoclast formation and activity confirmed the histomorphometric data. Thus, bone marrow cells isolated from anti-IL-11 Ab treated OVX mice formed fewer osteoclasts and resorbed less bone in culture than did marrow cells isolated from either untreated or NSIgG-treated OVX mice. Based on these results we conclude that IL-11 contributes to the bone loss which is observed during states of estrogen deficiency.     

Bactericidal Immunity to Salmonella in Africans and Mechanisms Causing Its Failure in HIV Infection

Background

Nontyphoidal strains of Salmonella are a leading cause of death among HIV-infected Africans. Antibody-induced complement-mediated killing protects healthy Africans against Salmonella, but increased levels of anti-lipopolysaccharide (LPS) antibodies in some HIV-infected African adults block this killing. The objective was to understand how these high levels of anti-LPS antibodies interfere with the killing of Salmonella.

Methodology/Principal Findings

Sera and affinity-purified antibodies from African HIV-infected adults that failed to kill invasive S. Typhimurium {"type":"entrez-nucleotide","attrs":{"text":"D23580","term_id":"427513","term_text":"D23580"}}D23580 were compared to sera from HIV-uninfected and HIV-infected subjects with bactericidal activity. The failure of sera from certain HIV-infected subjects to kill Salmonella was found to be due to an inherent inhibitory effect of anti-LPS antibodies. This inhibition was concentration-dependent and strongly associated with IgA and IgG2 anti-LPS antibodies (p<0.0001 for both). IgG anti-LPS antibodies, from sera of HIV-infected individuals that inhibit killing at high concentration, induced killing when diluted. Conversely, IgG, from sera of HIV-uninfected adults that induce killing, inhibited killing when concentrated. IgM anti-LPS antibodies from all subjects also induced Salmonella killing. Finally, the inhibitory effect of high concentrations of anti-LPS antibodies is seen with IgM as well as IgG and IgA. No correlation was found between affinity or avidity, or complement deposition or consumption, and inhibition of killing.

Conclusion/Significance

IgG and IgM classes of anti-S. Typhimurium LPS antibodies from HIV-infected and HIV-uninfected individuals are bactericidal, while at very high concentrations, anti-LPS antibodies of all classes inhibit in vitro killing of Salmonella. This could be due to a variety of mechanisms relating to the poor ability of IgA and IgG2 to activate complement, and deposition of complement at sites where it cannot insert in the bacterial membrane. Vaccine trials are required to understand the significance of lack of in vitro killing by anti-LPS antibodies from a minority of HIV-infected individuals with impaired immune homeostasis.     

The Effect of Human Factor H on Immunogenicity of Meningococcal Native Outer Membrane Vesicle Vaccines with Over-Expressed Factor H Binding Protein

The binding of human complement inhibitors to vaccine antigens in vivo could diminish their immunogenicity. A meningococcal ligand for the complement down-regulator, factor H (fH), is fH-binding protein (fHbp), which is specific for human fH. Vaccines containing recombinant fHbp or native outer membrane vesicles (NOMV) from mutant strains with over-expressed fHbp are in clinical development. In a previous study in transgenic mice, the presence of human fH impaired the immunogenicity of a recombinant fHbp vaccine. In the present study, we prepared two NOMV vaccines from mutant group B strains with over-expressed wild-type fHbp or an R41S mutant fHbp with no detectable fH binding. In wild-type mice in which mouse fH did not bind to fHbp in either vaccine, the NOMV vaccine with wild-type fHbp elicited 2-fold higher serum IgG anti-fHbp titers (P = 0.001) and 4-fold higher complement-mediated bactericidal titers against a PorA-heterologous strain than the NOMV with the mutant fHbp (P = 0.003). By adsorption, the bactericidal antibodies were shown to be directed at fHbp. In transgenic mice in which human fH bound to the wild-type fHbp but not to the R41S fHbp, the NOMV vaccine with the mutant fHbp elicited 5-fold higher serum IgG anti-fHbp titers (P = 0.002), and 19-fold higher bactericidal titers than the NOMV vaccine with wild-type fHbp (P = 0.001). Thus, in mice that differed only by the presence of human fH, the respective results with the two vaccines were opposite. The enhanced bactericidal activity elicited by the mutant fHbp vaccine in the presence of human fH far outweighed the loss of immunogenicity of the mutant protein in wild-type animals. Engineering fHbp not to bind to its cognate complement inhibitor, therefore, may increase vaccine immunogenicity in humans.     

Consequences of daily administered parathyroid hormone on myeloma growth, bone disease, and molecular profiling of whole myelomatous bone

Background

Induction of osteolytic bone lesions in multiple myeloma is caused by an uncoupling of osteoclastic bone resorption and osteoblastic bone formation. Current management of myeloma bone disease is limited to the use of antiresorptive agents such as bisphosphonates.

Methodology/Principal Findings

We tested the effects of daily administered parathyroid hormone (PTH) on bone disease and myeloma growth, and we investigated molecular mechanisms by analyzing gene expression profiles of unique myeloma cell lines and primary myeloma cells engrafted in SCID-rab and SCID-hu mouse models. PTH resulted in increased bone mineral density of myelomatous bones and reduced tumor burden, which reflected the dependence of primary myeloma cells on the bone marrow microenvironment. Treatment with PTH also increased bone mineral density of uninvolved murine bones in myelomatous hosts and bone mineral density of implanted human bones in nonmyelomatous hosts. In myelomatous bone, PTH markedly increased the number of osteoblasts and bone-formation parameters, and the number of osteoclasts was unaffected or moderately reduced. Pretreatment with PTH before injecting myeloma cells increased bone mineral density of the implanted bone and delayed tumor progression. Human global gene expression profiling of myelomatous bones from SCID-hu mice treated with PTH or saline revealed activation of multiple distinct pathways involved in bone formation and coupling; involvement of Wnt signaling was prominent. Treatment with PTH also downregulated markers typically expressed by osteoclasts and myeloma cells, and altered expression of genes that control oxidative stress and inflammation. PTH receptors were not expressed by myeloma cells, and PTH had no effect on myeloma cell growth in vitro.

Conclusions/Significance

We conclude that PTH-induced bone formation in myelomatous bones is mediated by activation of multiple signaling pathways involved in osteoblastogenesis and attenuated bone resorption and myeloma growth; mechanisms involve increased osteoblast production of anti-myeloma factors and minimized myeloma induction of inflammatory conditions.     

POPULATION SIZE AND BREEDING SEASON OF THE ANTARCTIC FUR SEAL ARCTOCEPHALUS GAZELLA AT HEARD ISLAND—1987/88

Breeding colonies of the antarctic fur seal Arctocephalus gazella on Heard Island (53°10'S, 73°30'E) are situated on the sheltered northern and eastern coasts on flat vegetated terrain near streams and pools. Pupping in the 1987/88 summer began on 21 November, with 90% of births in 26 d. The median birth date was 11 December. Pup counts at Heard Island made in seven breeding seasons from 1962/63 to 1987/88 show an exponential rate of increase of 21%, which may be inflated due to undercounting in early years. The total of 248 births in 1987/88 represents an exponential increase of 37% since the previous year, but pups may have been undercounted then. Based on the number of pups born, the breeding population is estimated at 870–1,120. During the breeding season, the largest number of animals ashore was 835. Many non-breeding fur seals began hauling out from early January and 15,000 animals were estimated to be ashore by late February, a fat larger number than expected from the size of the breeding population. Both the breeding and non-breeding components of the population may be augmented by immigration. The source of immigrants may be undiscovered breeding colonies of this species in the northwestern sector of the Kerguelen Archipelago or the concentration at South Georgia. Further censuses are required at Heard Island to monitor the population growth.     

The conformational effect of para-substituted C8-arylguanine adducts on the B/Z-DNA equilibrium

The B form of DNA exists in equilibrium with the Z form and is mainly affected by sequence, electrostatic interactions, and steric effects. C8-purine substitution shifts the equilibrium toward the Z form though how this interaction overcomes the unfavorable electrostatic interactions and decrease in stacking in the Z form has not been determined. Here, a series of C8-arylguanine derivatives, bearing a para-substituent were prepared and the B/Z equilibrium determined. B/Z ratios were measured by CD and conformational effects of the aryl substitution determined by NMR spectroscopy and molecular modeling. The para-substituent was found to have a significant effect on the B/Z DNA equilibrium caused by altering base-pair stacking of the B form and modifying the hydration/ion shell of the B form. A unique melting temperature versus salt concentration was observed and provides evidence relevant to the mechanism of B/Z conformational interconversion.     

Cranial ontogeny of otariid seals

Over 2000 otariid skulls were measured for a morphometric study of cranial ontogeny in fur seals and sea lions. Few interspecific differences in cranial ontogeny were observed in the Otariidae, with only minor differences in rates of growth. Sexual dimorphism was significant in all otariids but was more apparent in the larger species. Female otariids of each species showed monophasic development in all characteristics, whereas males expressed monophasic growth for some characters and biphasic growth for others. Biphasic development in skulls of male otariids occurred well after physical maturity had been reached, usually at a suture index of 27. The rate of development varied between skull characters; components relating to the nervous system completed growth well before the rest of the skull, whereas those related to feeding, respiration and vocalisation developed in synchrony with the overall growth of total skull length. Sutures of the calvaria, or braincase, were the first to show partial closure and those uniting the facial bones were usually the last to fuse. As with the calvaria, the orbits and otic capsules developed quickly, suggesting a need for good hearing and vision early in independent postnatal life. Development of the rostral and palatal regions required significantly longer to complete growth.