The dS/CFT Correspondence

A holographic duality is proposed relating quantum gravity on dS_D (D-dimensional de Sitter space) to conformal field theory on a single S^{D-1} ((D-1)-sphere), in which bulk de Sitter correlators with points on the boundary are related to CFT correlators on the sphere, and points on I^+ (the future boundary of dS_D) are mapped to the antipodal points on S^{D-1} relative to those on I^-. For the case of dS_3, which is analyzed in some detail, the central charge of the CFT_2 is computed in an analysis of the asymptotic symmetry group at I^\pm. This dS/CFT proposal is supported by the computation of correlation functions of a massive scalar field. In general the dual CFT may be non-unitary and (if for example there are sufficently massive stable scalars) contain complex conformal weights. We also consider the physical region O^- of dS_3 corresponding to the causal past of a timelike observer, whose holographic dual lives on a plane rather than a sphere. O^- can be foliated by asymptotically flat spacelike slices. Time evolution along these slices is generated by L_0+\bar L_0, and is dual to scale transformations in the boundary CFT_2.Comment: Assorted errors and typos corrected, references addde

A modified colorimetric method for the estimation of N-acetylamino sugars

originalFil: Reissig, José L.. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaFil: Strominger, Jack L.. National Institute of Arthritis and Metabolic Diseases. National Institutes of Health. Bethesda. Maryland; Estados UnidosFil: Leloir, Luis Federico. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaBlanco y negro8 páginas en pdfLFL-PI-O-ART. Artículos científicosUnidad documental simpleAR-HYL-201

Formation of a WIP-, WASp-, actin-, and myosin IIA–containing multiprotein complex in activated NK cells and its alteration by KIR inhibitory signaling

The tumor natural killer (NK) cell line YTS was used to examine the cytoskeletal rearrangements required for cytolysis. A multiprotein complex weighing ∼1.3 mD and consisting of WASp-interacting protein (WIP), Wiskott-Aldrich syndrome protein (WASp), actin, and myosin IIA that formed during NK cell activation was identified. After induction of an inhibitory signal, the recruitment of actin and myosin IIA to a constitutive WIP–WASp complex was greatly decreased. Both actin and myosin IIA were recruited to WIP in the absence of WASp. This recruitment correlated with increased WIP phosphorylation, which was mediated by PKCθ. Furthermore, the disruption of WIP expression by WIP RNA interference prevented the formation of this protein complex and led to almost complete inhibition of cytotoxic activity. Thus, the multiprotein complex is important for NK cell function, killer cell immunoglobulin-like receptor inhibitory signaling affects proteins involved in cytoskeletal rearrangements, and WIP plays a central role in the formation of the complex and in the regulation of NK cell activity

The Selective Downregulation of Class I Major Histocompatibility Complex Proteins by HIV-1 Protects HIV-Infected Cells from NK Cells

AbstractTo avoid detection by CTL, HIV encodes mechanisms for removal of class I MHC proteins from the surface of infected cells. However, class I downregulation potentially exposes the virus-infected cell to attack by NK cells. Human lymphoid cells are protected from NK cell cytotoxicity primarily by HLA-C and HLA-E. We present evidence that HIV-1 selectively downregulates HLA-A and HLA-B but does not significantly affect HLA-C or HLA-E. We then identify the residues in HLA-C and HLA-E that protect them from HIV downregulation. This selective downregulation allows HIV-infected cells to avoid NK cell–mediated lysis and may represent for HIV a balance between escape from CTL and maintenance of protection from NK cells. These results suggest that subpopulations of CTL and NK cells may be uniquely suited for combating HIV

Cyclosporin A and FK506 Block Induction of the Epstein-Barr Virus Lyric Cycle by Anti-Immunoglobulin

AbstractThe Epstein-Barr virus (EBV) BZLF1 gene is expressed early upon induction of the viral lytic cycle and its protein product is unique in its ability to disrupt viral latency in some latently infected cell lines. Anti-immunoglobulin (anti-Ig) treatment of the Burkitt's lymphoma cell line Akata, which bears surface IgG, has previously been shown to synchronously induce transcription of the BZLF1 gene (K. Takada and Y. Ono, 1989, J. Virol. 63, 445-449). We have previously shown that anti-Ig induction of Akata cells activates expression of the tumor necrosis factor alpha (TNF-α) gene via a calcineurin-dependent mechanism (Goldfeld et al., 1992, Proc. Natl. Acad. Sci. USA 89, 12198-12201). Here, we report that anti-Ig induction of the EBV lytic cycle in Akata cells can be blocked by the immunosuppressants cyclosporin A and FK506. Furthermore, we demonstrate that synergistic induction by phorbol ester and calcium ionophore of a BZLF1 promoter-driven reporter construct in an EBV-negative BL cell line can be inhibited by addition of cyclosporin A. Thus, analogous to activation of TNF-α gene in Akata cells, anti-Ig induction of the BZLF1 promoter is most likely mediated by calcineurin and probably involves translocation to the nucleus of a transcription factor sequestered in the cytoplasm. As such, immunosuppressants may be useful probes for dissecting B cell activation pathways involved in regulating EBV gene transcription

Amelioration of Proteolipid Protein 139–151-Induced Encephalomyelitis in SJL Mice by Modified Amino Acid Copolymers and Their Mechanisms

Copolymer 1 [Cop1, glatiramer acetate, Copaxone, poly(Y,E,A,K)n] is widely used in the treatment of relapsing/remitting multiple sclerosis in which it reduces the frequency of relapses by ≈30%. In the present study, copolymers with modified amino acid compositions (based on the binding motif of myelin basic protein 85–99 to HLA-DR2) have been developed with the aim of suppressing multiple sclerosis more effectively. The enhanced efficacy of these copolymers in experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with proteolipid protein 139–151 was demonstrated by using three protocols: (i) simultaneous administration of autoantigen and copolymer (termed prevention), (ii) pretreatment with copolymers (vaccination), or (iii) administration of copolymers after disease onset (treatment). Strikingly, in the treatment protocol administration of soluble VWAK and FYAK after onset of disease led to stasis of its progression and suppression of histopathological evidence of EAE. The mechanisms by which these effects are achieved have been examined in several types of assays: binding of copolymers to I-As in competition with proteolipid protein 139–151 (blocking), cytokine production by T cells (T helper 2 polarization), and transfer of protection by CD3+ splenocytes or, notably, by copolymer-specific T cell lines (induction of regulatory T cells). The generation of these copolymerspecific regulatory T cells that secrete IL-4 and IL-10 and are independent of the immunizing autoantigen is very prominent among the multiple mechanisms that account for the observed suppressive effect of copolymers in EAE