Metric inference for social networks

Using a natural metric on the space of networks, we define a probability measure for network-valued random variables. This measure is indexed by two parameters, which are interpretable as a location parameter and a dispersion parameter. From this structure, one can develop maximum likelihood estimates, hypothesis tests and confidence regions, all in the context of independent and identically distributed networks. The value of this perspective is illustrated through application to portions of the friedship cognitive social structure data gathered by Krackhardt (1987).We thank Ove Frank, David Krackhardt, the editor and the referees for their constructive comments and suggestions.     

HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.     

Asymmetric inheritance of centrosomally localized mRNAs during embryonic cleavages

During development, different cell fates are generated by cell-cell interactions or by the asymmetric distribution of patterning molecules. Asymmetric inheritance is known to occur either through directed transport along actin microfilaments into one daughter cell or through capture of determinants by a region of the cortex inherited by one daughter. Here we report a third mechanism of asymmetric inheritance in a mollusc embryo. Different messenger RNAs associate with centrosomes in different cells and are subsequently distributed asymmetrically during division. The segregated mRNAs are diffusely distributed in the cytoplasm and then localize, in a microtubule-dependent manner, to the pericentriolar matrix. During division, they dissociate from the core mitotic centrosome and move by means of actin filaments to the presumptive animal daughter cell cortex. In experimental cells with two interphase centrosomes, mRNAs accumulate on the correct centrosome, indicating that differences between centrosomes control mRNA targeting. Blocking the accumulation of mRNAs on the centrosome shows that this event is required for subsequent cortical localization. These events produce a complex pattern of mRNA localization, in which different messages distinguish groups of cells with the same birth order rank and similar developmental potentials.     

Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14

The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35% of the 23-megabase P. falciparum genome.