Interferon-γ Induced by In Vitro Re-Stimulation of CD4+ T-Cells Correlates with In Vivo FMD Vaccine Induced Protection of Cattle against Disease and Persistent Infection

The immune defense against FMDV has been correlated to the antibody mediated component. However, there are occasions when some animals with high virus neutralising (VN) antibody are not protected following challenge and some with low neutralising antibody which do not succumb to disease. The importance of cell mediated immunity in clinical protection is less clear and so we investigated the source and production of interferon-gamma (IFN-γ) in re-stimulated whole blood of FMDV immunized cattle and its correlation to vaccine induced protection and FMDV persistence. We were able to show a positive correlation between IFN-γ response and vaccine induced protection as well as reduction of long term persistence of FMD virus. When combining this IFN-γ response in re-stimulated blood with virus neutralizing antibody titer in serum on the day of challenge, a better correlation of vaccine-induced protection with IFN-γ and VN antibody was predicted. Our investigations also showed that CD4+ T-cells are the major proliferating phenotype and IFN-γ producing cells.     

Population structure among African and derived populations of Drosophila simulans: evidence for ancient subdivision and recent admixture.

Previous studies based on allozyme variation have found little evidence for genetic differentiation in Drosophila simulans. On the basis of DNA sequence variation at two nuclear loci in four African populations of D. simulans, we show that there is significant structure to D. simulans populations within Africa. Variation at one of the loci, vermilion, appears to be neutral and supports an eastern African origin for European and American populations. Samples from the West Indies, Europe, and North America had a nucleotide diversity lower than that of African populations at vermilion and show nonequilibrium haplotype distributions at both vermilion and G6pd, consistent with a hypothesis of recent bottleneck and possibly also admixture in the history of these populations. Directional selection, previously documented at G6pd, appears to have occurred within the coalescence time of the species, obscuring deep population history.     

Characterization of the chemotaxis protein CheW from Rhodobacter sphaeroides and its effect on the behaviour of Escherichia coli

In contrast to the situation in enteric bacteria, chemotaxis in Rhodobacter sphaeroides requires transport and partial metabolism of chemoattractants. A chemotaxis operon has been identified containing homologues of the enteric cheA , cheW , cheR genes and two homologues of the cheY gene. However, mutations in these genes have only minor effects on chemotaxis. In enteric species, CheW transmits sensory information from the chemoreceptors to the histidine protein kinase, CheA. Expression of R. sphaeroides cheW in Escherichia coli showed concentration-dependent inhibition of wild-type behaviour, increasing counter-clockwise rotation and thus smooth swimming — a phenotype also seen when E. coli cheW is overexpressed in E. coli . In contrast, overexpression of R. sphaeroides cheW in wild-type R. sphaeroides inhibited motility completely, the equivalent of inducing tumbly motility in E. coli . Expression of R. sphaeroides cheW in an E. coli Δ cheW chemotaxis mutant complemented this mutation, confirming that CheW is involved in chemosensory signal transduction. However, unlike E. coli Δ cheW mutants, in-frame deletion of R. sphaeroides cheW did not affect either swimming behaviour or chemotaxis to weak organic acids, although the responses to sugars were enhanced. Therefore, although CheW may act as a signal-transduction protein in R. sphaeroides , it may have an unusual role in controlling the rotation of the flagellar motor. Furthermore, the ability of a Δ cheW mutant to swim normally and show wild-type responses to weak acids supports the existence of additional chemosensory signal-transduction pathways.     

Confronting a tough issue: Fertility control and translocation for over-abundant Koalas on Kangaroo Island, South Australia

How does society influence the management of an introduced native mammal that is destroying its own habitat – especially when that animal is considered threatened on parts of the mainland, is aesthetically pleasing, and is important to the tourism industry? If control through sterilization and translocation is part of the answer, what lessons can be learned from this program?     

Essential role of caveolae in interleukin-6- and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells

Caveolae, specialized flask-shaped lipid rafts on the cell surface, are composed of cholesterol, sphingolipids, and structural proteins termed caveolins; functionally, these plasma membrane microdomains have been implicated in signal transduction and transmembrane transport. In the present study, we examined the role of caveolin-1 in multiple myeloma cells. We show for the first time that caveolin-1, which is usually absent in blood cells, is expressed in multiple myeloma cells. Analysis of myeloma cell-derived plasma membrane fractions shows that caveolin-1 is co-localized with interleukin-6 receptor signal transducing chain gp130 and with insulin-like growth factor-I receptor. Cholesterol depletion by beta-cyclodextrin results in the loss of caveola structure in myeloma cells, as shown by transmission electron microscopy, and loss of caveolin-1 function. Interleukin-6 and insulin-like growth factor-I, growth and survival factors in multiple myeloma, induce caveolin-1 phosphorylation, which is abrogated by pre-treatment with beta-cyclodextrin. Importantly, inhibition of caveolin-1 phosphorylation blocks both interleukin-6-induced protein complex formation with caveolin-1 and downstream activation of the phosphatidylinositol 3-kinase/Akt-1 pathway. beta-Cyclodextrin also blocks insulin-like growth factor-I-induced tyrosine phosphorylation of insulin-responsive substrate-1 and downstream activation of the phosphatidylinositol 3-kinase/Akt-1 pathway. Therefore, cholesterol depletion by beta-cyclodextrin abrogates both interleukin-6- and insulin-like growth factor-I-triggered multiple myeloma cell survival via negative regulation of caveolin-1. Taken together, this study identifies caveolin-1 and other structural membrane components as potential new therapeutic targets in multiple myeloma.     

Estimation of heritability from varietal trials data

We present the estimation of heritabilities of an observed trait in situations where evaluation of several pure breeding lines is performed in a trial at a single location and in trials from several locations. For the single location situation, we evaluate exact confidence intervals, the probability of invalid estimates, and the percentage points of the distribution of heritability. Simulations were performed to numerically verify the results. Additionally, approximations to the bias and standard error of the estimate were obtained and are presented along with their simulated values and coefficients of skewness and kurtosis. For trials in several locations, explicit expressions for exact values of confidence limits are not available. Further, one would require knowledge of one more parameter, represented by the ratio of genotype x environment (G x E) interaction variance to error variance, in addition to the number of genotypes, replication and true heritability value. Approximations were made for bias and the standard error of estimates of heritability. The evaluation of the distribution of heritability and its moments was recognized as a problem of the linear function of an independent chi-square. The methods have been illustrated by data from experiments on grain and straw yield of 64 barley genotypes evaluated at three locations.