Origin of AIDS: contaminated polio vaccine theory refuted

Despite strong evidence to the contrary, speculation continues that the AIDS virus, human immunodeficiency virus type 1 (HIV-1), may have crossed into humans as a result of contamination of the oral polio vaccine (OPV). This 'OPV/AIDS theory' claims that chimpanzees from the vicinity of Stanleyville--now Kisangani in the Democratic Republic of Congo--were the source of a simian immunodeficiency virus (SIVcpz) that was transmitted to humans when chimpanzee tissues were allegedly used in the preparation of OPV. Here we show that SIVcpz is indeed endemic in wild chimpanzees of this region but that the circulating virus is phylogenetically distinct from all strains of HIV-1, providing direct evidence that these chimpanzees were not the source of the human AIDS pandemic.     

The Ph1 locus is needed to ensure specific somatic and meiotic centromere association

The correct pairing and segregation of chromosomes during meiosis is essential for genetic stability and subsequent fertility. This is more difficult to achieve in polyploid species, such as wheat, because they possess more than one diploid set of similar chromosomes. In wheat, the Ph1 locus ensures correct homologue pairing and recombination. Although clustering of telomeres into a bouquet early in meiosis has been suggested to facilitate homologue pairing, centromeres associate in pairs in polyploid cereals early during floral development. We can now extend this observation to root development. Here we show that the Ph1 locus acts both meiotically and somatically by reducing non-homologous centromere associations. This has the effect of promoting true homologous association when centromeres are induced to associate. In fact, non-homologously associated centromeres separate at the beginning of meiosis in the presence, but not the absence, of Ph1. This permits the correction of homologue association during the telomere-bouquet stage in meiosis. We conclude that the Ph1 locus is not responsible for the induction of centromere association, but rather for its specificity.     

Human infection by genetically diverse SIVSM-related HIV-2 in west Africa.

Our understanding of the biology and origins of human immunodeficiency virus type 2 (HIV-2) derives from studies of cultured isolates from urban populations experiencing epidemic infection and disease. To test the hypothesis that such isolates might represent only a subset of a larger, genetically more diverse group of viruses, we used nested polymerase chain reactions to characterize HIV-2 sequences in uncultured mononuclear blood cells of two healthy Liberian agricultural workers, from whom virus isolation was repeatedly unsuccessful, and from a culture-positive symptomatic urban dweller. Analysis of pol, env and long terminal repeat regions revealed the presence of three highly divergent HIV-2 strains, one of which (from one of the healthy subjects) was significantly more closely related to simian immunodeficiency viruses infecting sooty mangabeys and rhesus macaques (SIVSM/SIVMAC) than to any virus of human derivation. This subject also harboured multiply defective viral genotypes that resulted from hypermutation of G to A bases. Our results indicate that HIV-2, SIVSM and SIVMAC comprise a single, highly diverse group of lentiviruses which cannot be separated into distinct phylogenetic lineages according to species of origin.     

Dynamic Dominating Set and Turbo-Charging Greedy Heuristics

The main purpose of this paper is to exposit two very different, but very general, motivational schemes in the art of parameterization and a concrete example connecting them. We introduce a dynamic version of the DOMINATING SET problem and prove that it is fixed-parameter tractable（FPT）. The problem is motivated by settings where problem instances evolve. It also arises in the quest to improve a natural greedy heuristic for the DOMINATING SET problem.     

SB-restricted presentation of influenza and herpes simplex virus antigens to human T-lymphocyte clones

The HLA-D region of the human major histocompatibility complex (MHC) has been shown to be homologous to the murine I region in terms of both structure and function. Both regions encode class II MHC molecules which restrict T-lymphocyte interactions with antigen-presenting cells. We have recently described the MHC restriction and antigen specificities of human T-lymphocyte clones directed at strain A influenza virus. The majority of T-lymphocyte clones recognized antigen in the context of cell surface interaction products encoded by HLA-D/DR genes. However, a few clones recognized antigen presented by cells histoincompatible for D/DR antigens. We report here that some of these clones recognized viral antigens in association with antigens encoded by genes identical with or closely linked to the recently described secondary B-cell (SB) locus of the MHC. This is the first report that SB-restricted antigen recognition may form an integral part of normal, human immune responses.     

Mapping of mutation causing Friedreich's ataxia to human chromosome 9

Friedreich's ataxia is an autosomal recessive disease with progressive degeneration of the central and peripheral nervous system. The biochemical abnormality underlying the disorder has not been identified. Prompted by the success in localizing the mutations causing Duchenne muscular dystrophy, Huntington's disease and cystic fibrosis, we have undertaken molecular genetic linkage studies to determine the chromosomal site of the Friedreich's ataxia mutation as an initial step towards the isolation and characterization of the defective gene. We report the assignment of the gene mutation for this disorder to chromosome 9p22-CEN by genetic linkage to an anonymous DNA marker MCT112 and the interferon-beta gene probe. In contrast to the clinical variation seen for the disorder, no evidence of genetic heterogeneity is observed.     

Three-dimensional structural dynamics of myosin V by single-molecule fluorescence polarization

The structural change that generates force and motion in actomyosin motility has been proposed to be tilting of the myosin light chain domain, which serves as a lever arm. Several experimental approaches have provided support for the lever arm hypothesis; however, the extent and timing of tilting motions are not well defined in the motor protein complex of functioning actomyosin. Here we report three-dimensional measurements of the structural dynamics of the light chain domain of brain myosin V using a single-molecule fluorescence polarization technique that determines the orientation of individual protein domains with 20-40-ms time resolution. Single fluorescent calmodulin light chains tilted back and forth between two well-defined angles as the myosin molecule processively translocated along actin. The results provide evidence for lever arm rotation of the calmodulin-binding domain in myosin V, and support a 'hand-over-hand' mechanism for the translocation of double-headed myosin V molecules along actin filaments. The technique is applicable to the study of real-time structural changes in other biological systems.