P16-52. HIV-activated human plasmacytoid DCs induce Tregs through an indoleamine 2,3-dioxygenase-dependent mechanism

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Dynamical scaling of the DNA unzipping transition

We report studies of the equilibrium and the dynamics of a general set of lattice models which capture the essence of the force-induced or mechanical DNA unzipping transition. Besides yielding the whole equilibrium phase diagram in the force vs temperature plane, which reveals the presence of an interesting re-entrant unzipping transition for low T, these models enable us to characterize the dynamics of the process starting from a non-equilibrium initial condition. The thermal melting of the DNA strands displays a model dependent time evolution. On the contrary, our results suggest that the dynamical mechanism for the unzipping by force is very robust and the scaling behaviour does not depend on the details of the description we adopt.Comment: 6 pages, 4 figures, A shorter version of this paper appeared in Phys. Rev. Lett. 88, 028102 (2002

Theory of Chiral Order in Random Copolymers

Recent experiments have found that polyisocyanates composed of a mixture of opposite enantiomers follow a chiral ``majority rule:'' the chiral order of the copolymer, measured by optical activity, is dominated by whichever enantiomer is in the majority. We explain this majority rule theoretically by mapping the random copolymer onto the random-field Ising model. Using this model, we predict the chiral order as a function of enantiomer concentration, in quantitative agreement with the experiments, and show how the sharpness of the majority-rule curve can be controlled.Comment: 13 pages, including 4 postscript figures, uses REVTeX 3.0 and epsf.st

Sequence randomness and polymer collapse transitions

Contrary to expectations based on Harris' criterion, chain disorder with frustration can modify the universality class of scaling at the theta transition of heteropolymers. This is shown for a model with random two-body potentials in 2D on the basis of exact enumeration and accurate Monte Carlo results. When frustration grows beyond a certain finite threshold, the temperature below which disorder becomes relevant coincides with the theta one and scaling exponents definitely start deviating from those valid for homopolymers.Comment: 4 pages, 4 eps figure

Lifelongα-tocopherol supplementation increases the median life span of C57BL/6 mice in the cold but has only minor effects on oxidative damage

The effects of dietary antioxidant supplementation on oxidative stress and life span are confused. We maintained C57BL/6 mice at 7 ± 2°C and supplemented their diet with α-tocopherol from 4 months of age. Supplementation significantly increased (p = 0.042) median life span by 15% (785 days, n = 44) relative to unsupplemented controls (682 days, n = 43) and also increased maximum life span (oldest 10%, p = 0.028). No sex or sex by treatment interaction effects were observed on life span, with treatment having no effect on resting or daily metabolic rate. Lymphocyte and hepatocyte oxidative DNA damage and hepatic lipid peroxidation were unaffected by supplementation, but hepatic oxidative DNA damage increased with age. Using a cDNA macroarray, genes associated with xenobiotic metabolism were significantly upregulated in the livers of female mice at 6 months of age (2 months supplementation). At 22 months of age (18 months supplementation) this response had largely abated, but various genes linked to the p21 signaling pathway were upregulated at this time. We suggest that α-tocopherol may initially be metabolized as a xenobiotic, potentially explaining why previous studies observe a life span extension generally when lifelong supplementation is initiated early in life. The absence of any significant effect on oxidative damage suggests that the life span extension observed was not mediated via any antioxidant properties of α-tocopherol. We propose that the life span extension observed following α-tocopherol supplementation may be mediated via upregulation of cytochrome p450 genes after 2 months of supplementation and/or upregulation of p21 signaling genes after 18 months of supplementation. However, these signaling pathways now require further investigation to establish their exact role in life span extension following α-tocopherol supplementation

Why is the DNA Denaturation Transition First Order?

We study a model for the denaturation transition of DNA in which the molecules are considered as composed of a sequence of alternating bound segments and denaturated loops. We take into account the excluded-volume interactions between denaturated loops and the rest of the chain by exploiting recent results on scaling properties of polymer networks of arbitrary topology. The phase transition is found to be first order in d=2 dimensions and above, in agreement with experiments and at variance with previous theoretical results, in which only excluded-volume interactions within denaturated loops were taken into account. Our results agree with recent numerical simulations.Comment: Revised version. To appear in Phys. Rev. Let

Statistical Properties of Contact Maps

A contact map is a simple representation of the structure of proteins and other chain-like macromolecules. This representation is quite amenable to numerical studies of folding. We show that the number of contact maps corresponding to the possible configurations of a polypeptide chain of N amino acids, represented by (N-1)-step self avoiding walks on a lattice, grows exponentially with N for all dimensions D>1. We carry out exact enumerations in D=2 on the square and triangular lattices for walks of up to 20 steps and investigate various statistical properties of contact maps corresponding to such walks. We also study the exact statistics of contact maps generated by walks on a ladder.Comment: Latex file, 15 pages, 12 eps figures. To appear on Phys. Rev.

Electron Tomography of the Contact between T Cells and SIV/HIV-1: Implications for Viral Entry

The envelope glycoproteins of primate lentiviruses, including human and simian immunodeficiency viruses (HIV and SIV), are heterodimers of a transmembrane glycoprotein (usually gp41), and a surface glycoprotein (gp120), which binds CD4 on target cells to initiate viral entry. We have used electron tomography to determine the three-dimensional architectures of purified SIV virions in isolation and in contact with CD4+ target cells. The trimeric viral envelope glycoprotein surface spikes are heterogeneous in appearance and typically ∼120 Å long and ∼120 Å wide at the distal end. Docking of SIV or HIV-1 on the T cell surface occurs via a neck-shaped contact region that is ∼400 Å wide and consistently consists of a closely spaced cluster of five to seven rod-shaped features, each ∼100 Å long and ∼100 Å wide. This distinctive structure is not observed when viruses are incubated with T lymphocytes in the presence of anti-CD4 antibodies, the CCR5 antagonist TAK779, or the peptide entry inhibitor SIVmac251 C34. For virions bound to cells, few trimers were observed away from this cluster at the virion–cell interface, even in cases where virus preparations showing as many as 70 envelope glycoprotein trimers per virus particle were used. This contact zone, which we term the “entry claw”, provides a spatial context to understand the molecular mechanisms of viral entry. Determination of the molecular composition and structure of the entry claw may facilitate the identification of improved drugs for the inhibition of HIV-1 entry

Nucleocapsid Protein Zinc-Finger Mutants of Simian Immunodeficiency Virus Strain Mne Produce Virions That Are Replication Defectivein Vitroandin Vivo

AbstractAll retroviruses (except the spumaretroviruses) contain a nucleocapsid (NC) protein that encodes one or two copies of the Zn2+-finger sequence -Cys-X2-Cys-X4-His-X4-Cys-. This region has been shown to be essential for recognition and packaging of the genomic RNA during virion particle assembly. Additionally, this region has been shown to be involved in early infection events in a wide spectrum of retroviruses, including mammalian type C [e.g., murine leukemia virus (MuLV)], human immunodeficiency virus type 1 (HIV-1),Rous sarcomavirus, and other retroviruses. Mutations in the two Zn2+-fingers of the NC protein of simian immunodeficiency virus strain Mne [SIV(Mne)] have been generated. The resulting virions contained the normal complement of processed viral proteins with densities indistinguishable from wild-type SIV(Mne). All of the mutants had electron micrograph morphologies similar to those of immature particles observed in wild-type preparations. RNA packaging was less affected by mutations in the NC protein of SIV(Mne) than has been observed for similar mutants in the MuLV and HIV-1 systems. Nevertheless,in vitroreplication of SIV(Mne) NC mutants was impaired to levels comparable to those observed for MuLV and HIV-1 NC mutants; replication defective NC mutants are typically 105- to 106-fold less infectious than similar levels of wild-type virus. One mutant, ΔCys33–Cys36, was also found to be noninfectiousin vivowhen mutant virus was administered intravenously to a pig-tailed macaque. NC mutations can therefore be used to generate replication defective virions for candidate vaccines in the SIV macaque model for primate lentiviral diseases

Formation of helical states in wormlike polymer chains

We propose a potential for wormlike polymer chains which can be used to model the low-temperature conformational structures. We successfully reproduced helix ground states up to 6.5 helical loops, using the multicanonical Monte Carlo simulation method. We demonstrate that the coil-helix transition involves four distinct phases: coil(gaslike), collapsed globular(liquidlike), and two helical phases I and II (both solidlike). The helix I phase is characterized by a helical structure with dangling loose ends, and the helix II phase corresponds to a near perfect helix ordering in the entire crystallized chain.Comment: 5 pages, 2 figures, Submitted to PR