Among the pleiotropic effects of Nef proteins of HIV and simian immunodeficiency virus (SIV), down-modulation of cell surface expression of CD4 is a prominent phenotype. It has been presumed that Nef proteins accelerate endocytosis of CD4 by linking the receptor to the AP-2 clathrin adaptor. However, the related AP-1 and AP-3 adaptors have also been shown to interact with Nef, hinting at role(s...

In this study the construction is described of HIV-1 molecular clones in which CTL epitopes from RT or Env late proteins were inserted into the Nef early protein. The ectopic epitopes were efficiently processed from the recombinant Nef proteins, were recognized by their cognate CTL in cytolytic assays, and did not perturb virus replication or viral protein expression in vitro. These recombinant...

Recent data suggest that Nef-mediated downmodulation of TCR-CD3 may protect SIVsmm-infected sooty mangabeys (SMs) against the loss of CD4+ T cells. However, the mechanisms underlying this protective effect remain unclear. To further assess the role of Nef in nonpathogenic SIV infection, we cloned nef alleles from 11 SIVsmm-infected SMs with high (>500) and 15 animals with low (<500) CD4+ T-cell...

C ells with a defective spindle get delayed—stuck in a mitotic checkpoint—but eventually escape mitosis. In vertebrate cells, say Daniela Brito and Conly Rieder (Wadsworth Center, New York State Department of Health, Albany, NY), that escape is a gradual limp rather than a sudden exit. The temporary stalling of the cell cycle in a checkpoint gives the cell time to repair damage before continuin...

The transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) plays a complex role during the replication of primate lentiviruses. On the one hand, NF-κB is essential for induction of efficient proviral gene expression. On the other hand, this transcription factor contributes to the innate immune response and induces expression of numerous cellular antiviral ge...

The Nef protein of HIV-1 is important for AIDS pathogenesis, but it is not targeted by current antiviral strategies. Here, we describe a single-domain antibody (sdAb) that binds to HIV-1 Nef with a high affinity (K(d) = 2 × 10(-9)M) and inhibited critical biologic activities of Nef both in vitro and in vivo. First, it interfered with the CD4 down-regulation activity of a broad panel of nef alle...

Microarrays have been used to identify genes involved in cancer progression. We have now developed an algorithm that identifies dysregulated pathways from multiple expression array data sets without a priori definition of gene expression thresholds. Integrative microarray analysis of pathways (IMAP) was done using existing expression array data from localized and metastatic prostate cancer. Com...

Microarrays have been used to identify genes involved in cancer progression. We have now developed an algorithm that identifies dysregulated pathways from multiple expression array data sets without a priori definition of gene expression thresholds. Integrative microarray analysis of pathways (IMAP) was done using existing expression array data from localized and metastatic prostate cancer. Com...

Given a complex projective manifold X and divisor D with normal crossings, we say that the logarithmic tangent bundle $$T_X(-\hbox {log}\, D)$$ is R-flat if its pull-back to normalization of any rational curve contained in trivial vector bundle. If moreover $$-(K_X+D)$$ nef, then log canonical $$K_X+D$$ torsion maximally rationally chain connected fibration turns out be smooth locally typical f...

Background and Aims: DNA constructs containing HCV antigens have become one of the vaccine candidates for induction of anti-HCV cellular and humoral immunity. In this study, we constructed a novel expressing vector harboring a fusion sequence derived from an overlapping fragment in the middle of NS3 and a truncated core fragment to avoid troubles reported to be associated with full gene express...