Acute-Phase CD8 T Cell Responses That Select for Escape Variants Are Needed to Control Live Attenuated Simian Immunodeficiency Virus

The overall CD8 T cell response to human/simian immunodeficiency virus (HIV/SIV) targets a collection of discrete epitope specificities. Some of these epitope-specific CD8 T cells emerge in the weeks and months following infection and rapidly select for sequence variants, whereas other CD8 T cell responses develop during the chronic infection phase and rarely select for sequence variants. In this study, we tested the hypothesis that acute-phase CD8 T cell responses that do not rapidly select for escape variants are unable to control viral replication in vivo as well as those that do rapidly select for escape variants. We created a derivative of live attenuated SIV (SIVmac239Δnef) in which we ablated five epitopes that elicit early CD8 T cell responses and rapidly accumulate sequence variants in SIVmac239-infected Mauritian cynomolgus macaques (MCMs) that are homozygous for the M3 major histocompatibility complex (MHC) haplotype. This live attenuated SIV variant was called m3KOΔnef. Viremia was significantly higher in M3 homozygous MCMs infected with m3KOΔnef than in either MHC-mismatched MCMs infected with m3KOΔnef or MCMs infected with SIVmac239Δnef. Three CD8 T cell responses, including two that do not rapidly select for escape variants, predominated during early m3KOΔnef infection in the M3 homozygous MCMs, but these animals were unable to control viral replication. These results provide evidence that acute-phase CD8 T cell responses that have the potential to rapidly select for escape variants in the early phase of infection are needed to establish viral control in vivo.     

Genomic affinities in Arachis section Arachis (Fabaceae): molecular and cytogenetic evidence

Section Arachis is the largest of nine sections in the genus Arachis and includes domesticated peanut, A. hypogaea L. Most species are diploids (x=10) with two tetraploids and a few aneuploids. Three genome types have been recognized in this section (A, B and D), but the genomes are not well characterized and relationships of several newly described species are uncertain. To clarify genomic relationships in section Arachis, cytogenetic information and molecular data from amplified fragment length polymorphism (AFLP) and the trnT-F plastid region were used to provide an additional insight into genome composition and species relationships. Cytogenetic information supports earlier observations on genome types of A. cruziana, A. herzogii, A. kempff-mercadoi and A. kuhlmannii but was inconclusive about the genome composition of A. benensis, A. hoehnei, A. ipaensis, A. palustris, A. praecox and A. williamsii. An AFLP dendrogram resolved species into four major clusters and showed A. hypogaea grouping closely with A. ipaensis and A. williamsii. Sequence data of the trnT-F region provided genome-specific information and showed for the first time that the B and D genomes are more closely related to each other than to the A genome. Integration of information from cytogenetics and biparentally and maternally inherited genomic regions show promise in understanding genome types and relationships in Arachis.     

Ex Vivo SIV-Specific CD8 T Cell Responses in Heterozygous Animals Are Primarily Directed against Peptides Presented by a Single MHC Haplotype

The presence of certain MHC class I alleles is correlated with remarkable control of HIV and SIV, indicating that specific CD8 T cell responses can effectively reduce viral replication. It remains unclear whether epitopic breadth is an important feature of this control. Previous studies have suggested that individuals heterozygous at the MHC class I loci survive longer and/or progress more slowly than those who are homozygous at these loci, perhaps due to increased breadth of the CD8 T cell response. We used Mauritian cynomolgus macaques with defined MHC haplotypes and viral inhibition assays to directly compare CD8 T cell efficacy in MHC-heterozygous and homozygous individuals. Surprisingly, we found that cells from heterozygotes suppress viral replication most effectively on target cells from animals homozygous for only one of two potential haplotypes. The same heterozygous effector cells did not effectively inhibit viral replication as effectively on the target cells homozygous for the other haplotype. These results indicate that the greater potential breadth of CD8 T cell responses present in heterozygous animals does not necessarily lead to greater antiviral efficacy and suggest that SIV-specific CD8 T cell responses in heterozygous animals have a skewed focus toward epitopes restricted by a single haplotype.     

R/qtl: QTL mapping in experimental crosses

SUMMARY: R/qtl is an extensible, interactive environment for mapping quantitative trait loci (QTLs) in experimental populations derived from inbred lines. It is implemented as an add-on package for the freely-available statistical software, R, and includes functions for estimating genetic maps, identifying genotyping errors, and performing single-QTL and two-dimensional, two-QTL genome scans by multiple methods, with the possible inclusion of covariates. AVAILABILITY: The package is freely available at http://www.biostat.jhsph.edu/~kbroman/qtl.     

Isolation and characterization of Campylobacter jejuni subsp. jejuni from macaroni penguins (Eudyptes chrysolophus) in the subantarctic region

On Bird Island, South Georgia, albatrosses (n = 140), penguins (n = 100), and fur seals (n = 206) were sampled for Campylobacter jejuni. C. jejuni subsp. jejuni was recovered from three macaroni penguins (Eudyptes chrysolophus). These isolates, the first reported for the subantarctic region, showed low genetic diversity and high similarity to Northern Hemisphere C. jejuni isolates, possibly suggesting recent introduction to the area.     

Myoelectric signal conduction velocity and spectral parameters: influence of force and time

Reports on measurement of muscle fiber conduction velocity in humans are scarce. Inferences on the behavior of conduction velocity have been drawn from the behavior of myoelectric spectral parameters. The present report contains information on conduction velocity and spectral parameters studied at various muscle contraction levels and during and after sustained contractions. The following results have been obtained from measurements on the tibialis anterior muscle. Conduction velocity demonstrated a positive correlation with limb circumference and with muscle force output. Thus we conclude that the diameters of the muscle fibers of high-threshold motor units are, on an average, larger than those of low-threshold motor units. The study of a sustained contraction and on the recovery after such a contraction revealed that conduction velocity consistently decreased during a strong contraction as did various myoelectric spectral parameters. However, the spectral parameters decreased approximately twice as much as did the conduction velocity, and we conclude that factors other than the conduction velocity along the muscle fibers affect the myoelectric signal during a high-level contraction. These other factors appertain to changes in the firing statistics of individual motor units as well as the correlation between the firings of different motor units.     

Quantitative trait loci x maternal cytoplasmic environment interaction for development rate in Oncorhynchus mykiss

Effects of maternal cytoplasmic environment (MCE) on development rate in rainbow trout were evaluated within a quantitative trait loci (QTL) analysis framework. Previous research had identified QTL for development rate in doubled haploid (DH) progeny produced from a cross between the Oregon State University (OSU) and the Swanson (SW) River rainbow trout clonal lines. In this study, progeny for QTL mapping were produced from a cross between the OSU and Clearwater (CW) River clonal lines. Doubled haploids were produced from the OSU x CW F1 by androgenesis using eggs from different females (or MCEs); with androgenesis, the maternal nuclear genome was destroyed by irradiation and diploidy was restored by blocking the first embryonic cleavage by heat shock. All embryos were incubated at the same temperature and development rate quantified as time to hatch. Using a linkage map constructed primarily with AFLP markers, QTL mapping was performed, including MCE covariates and QTL x MCE effects in models for testing. The major QTL for development rate in the OSU x SW cross overlaps with the major QTL found in this OSU x CW cross; effects at this locus were the same across MCEs. Both MCE and QTL x MCE effects contribute to variability in development rate, but QTL x MCE were minor and detected only at small-effect QTL.     

Recombination rate variation in mice from an isolated island

Recombination rate is a heritable trait that varies among individuals. Despite the major impact of recombination rate on patterns of genetic diversity and the efficacy of selection, natural variation in this phenotype remains poorly characterized. We present a comparison of genetic maps, sampling 1212 meioses, from a unique population of wild house mice (Mus musculus domesticus) that recently colonized remote Gough Island. Crosses to a mainland reference strain (WSB/EiJ) reveal pervasive variation in recombination rate among Gough Island mice, including subchromosomal intervals spanning up to 28% of the genome. In spite of this high level of polymorphism, the genomewide recombination rate does not significantly vary. In general, we find that recombination rate varies more when measured in smaller genomic intervals. Using the current standard genetic map of the laboratory mouse to polarize intervals with divergent recombination rates, we infer that the majority of evolutionary change occurred in one of the two tested lines of Gough Island mice. Our results confirm that natural populations harbour a high level of recombination rate polymorphism and highlight the disparities in recombination rate evolution across genomic scales.