Parallel-propagated frame along null geodesics in higher-dimensional black hole spacetimes

In [arXiv:0803.3259] the equations describing the parallel transport of orthonormal frames along timelike (spacelike) geodesics in a spacetime admitting a non-degenerate principal conformal Killing-Yano 2-form h were solved. The construction employed is based on studying the Darboux subspaces of the 2-form F obtained as a projection of h along the geodesic trajectory. In this paper we demonstrate that, although slightly modified, a similar construction is possible also in the case of null geodesics. In particular, we explicitly construct the parallel-transported frames along null geodesics in D=4,5,6 Kerr-NUT-(A)dS spacetimes. We further discuss the parallel transport along principal null directions in these spacetimes. Such directions coincide with the eigenvectors of the principal conformal Killing-Yano tensor. Finally, we show how to obtain a parallel-transported frame along null geodesics in the background of the 4D Plebanski-Demianski metric which admits only a conformal generalization of the Killing-Yano tensor.Comment: 17 pages, no figure

Bi-Legendrian manifolds and paracontact geometry

We study the interplays between paracontact geometry and the theory of bi-Legendrian manifolds. We interpret the bi-Legendrian connection of a bi-Legendrian manifold M as the paracontact connection of a canonical paracontact structure induced on M and then we discuss many consequences of this result both for bi-Legendrian and for paracontact manifolds. Finally new classes of examples of paracontact manifolds are presented.Comment: to appear in Int. J. Geom. Meth. Mod. Phy

Hidden symmetries and Killing tensors on curved spaces

Higher order symmetries corresponding to Killing tensors are investigated. The intimate relation between Killing-Yano tensors and non-standard supersymmetries is pointed out. In the Dirac theory on curved spaces, Killing-Yano tensors generate Dirac type operators involved in interesting algebraic structures as dynamical algebras or even infinite dimensional algebras or superalgebras. The general results are applied to space-times which appear in modern studies. One presents the infinite dimensional superalgebra of Dirac type operators on the 4-dimensional Euclidean Taub-NUT space that can be seen as a twisted loop algebra. The existence of the conformal Killing-Yano tensors is investigated for some spaces with mixed Sasakian structures.Comment: 12 pages; talk presented at Group 27 Colloquium, Yerevan, Armenia, August 200

A Deformation of Sasakian Structure in the Presence of Torsion and Supergravity Solutions

We discuss a deformation of Sasakian structure in the presence of totally skew-symmetric torsion by introducing odd dimensional manifolds whose metric cones are K\"ahler with torsion. It is shown that such a geometry inherits similar properties to those of Sasakian geometry. As an example of them, we present an explicit expression of local metrics and see how Sasakian structure is deformed by the presence of torsion. We also demonstrate that our example of the metrics admits the existence of hidden symmetries described by non-trivial odd-rank generalized closed conformal Killing-Yano tensors. Furthermore, using these metrics as an {\it ansatz}, we construct exact solutions in five dimensional minimal (un-)gauged supergravity and eleven dimensional supergravity. Finally, we discuss the global structures of the solutions and obtain regular metrics on compact manifolds in five dimensions, which give natural generalizations of Sasaki--Einstein manifolds $Y^{p,q}$ and $L^{a,b,c}$. We also discuss regular metrics on non-compact manifolds in eleven dimensions.Comment: 38 pages, 1 table, v2: version to appear in Class. Quant. Gra

The Prolyl Isomerase Pin1 Modulates Development of CD8+ cDC in Mice

We have identified a novel role for Pin1 as a modulator of CD8+ cDC development. Consistent with reduced numbers of CD8+ cDC in Pin1-null mice, we find that the absence of Pin1 impairs CD8+ T cell proliferation in response to infection with Listeria monocytogenes. These data suggest that, via regulation of CD8+ cDC production, Pin1 may serve as an important modulator of adaptive immunity

Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae

The benzylisoquinoline alkaloids (BIAs) are a diverse class of metabolites that exhibit a broad range of pharmacological activities and are synthesized through plant biosynthetic pathways comprised of complex enzyme activities and regulatory strategies. We have engineered yeast to produce the key intermediate reticuline and downstream BIA metabolites from a commercially available substrate. An enzyme tuning strategy was implemented that identified activity differences between variants from different plants and determined optimal expression levels. By synthesizing both stereoisomer forms of reticuline and integrating enzyme activities from three plant sources and humans, we demonstrated the synthesis of metabolites in the sanguinarine/berberine and morphinan branches. We also demonstrated that a human P450 enzyme exhibits a novel activity in the conversion of (R)-reticuline to the morphinan alkaloid salutaridine. Our engineered microbial hosts offer access to a rich group of BIA molecules and associated activities that will be further expanded through synthetic chemistry and biology approaches

NFIL3 Is a Regulator of IL-12 p40 in Macrophages and Mucosal Immunity

Regulation of innate inflammatory responses against the enteric microbiota is essential for the maintenance of intestinal homeostasis. Key participants in innate defenses are macrophages. In these studies, the basic leucine zipper protein, NFIL3, is identified as a regulatory transcription factor in macrophages, controlling IL-12 p40 production induced by bacterial products and the enteric microbiota. Exposure to commensal bacteria and bacterial products induced NFIL3 in cultured macrophages and in vivo. The Il12b promoter has a putative DNA-binding element for NFIL3. Basal and LPS-activated NFIL3 binding to this site was confirmed by chromatin immunoprecipitation. LPS-induced Il12b promoter activity was inhibited by NFIL3 expression and augmented by NFIL3-short hairpin RNA in an Il12b-bacterial artificial chromosome-GFP reporter macrophage line. Il12b inhibition by NFIL3 does not require IL-10 expression, but a C-terminal minimal repression domain is necessary. Furthermore, colonic CD11b+ lamina propria mononuclear cells from Nfil3−/− mice spontaneously expressed Il12b mRNA. Importantly, lower expression of NFIL3 was observed in CD14+ lamina propria mononuclear cells from Crohn’s disease and ulcerative colitis patients compared with control subjects. Likewise, no induction of Nfil3 was observed in colons of colitis-prone Il10−/− mice transitioned from germ-free to a conventional microbiota. In conclusion, these experiments characterize NFIL3 as an Il12b transcriptional inhibitor. Interactions of macrophages with the enteric microbiota induce NFIL3 to limit their inflammatory capacity. Furthermore, altered intestinal NFIL3 expression may have implications for the pathogenesis of experimental and human inflammatory bowel diseases

Potent Activity of the HIV-1 Maturation Inhibitor Bevirimat in SCID-hu Thy/Liv Mice

The HIV-1 maturation inhibitor, 3-O-(3',3'-dimethylsuccinyl) betulinic acid (bevirimat, PA-457) is a promising drug candidate with 10 nM in vitro antiviral activity against multiple wild-type (WT) and drug-resistant HIV-1 isolates. Bevirimat has a novel mechanism of action, specifically inhibiting cleavage of spacer peptide 1 (SP1) from the C-terminus of capsid which results in defective core condensation.Oral administration of bevirimat to HIV-1-infected SCID-hu Thy/Liv mice reduced viral RNA by >2 log(10) and protected immature and mature T cells from virus-mediated depletion. This activity was observed at plasma concentrations that are achievable in humans after oral dosing, and bevirimat was active up to 3 days after inoculation with both WT HIV-1 and an AZT-resistant HIV-1 clinical isolate. Consistent with its mechanism of action, bevirimat caused a dose-dependent inhibition of capsid-SP1 cleavage in HIV-1-infected human thymocytes obtained from these mice. HIV-1 NL4-3 with an alanine-to-valine substitution at the N-terminus of SP1 (SP1/A1V), which is resistant to bevirimat in vitro, was also resistant to bevirimat treatment in the mice, and SP1/AIV had replication and thymocyte kinetics similar to that of WT NL4-3 with no evidence of fitness impairment in in vivo competition assays. Interestingly, protease inhibitor-resistant HIV-1 with impaired capsid-SP1 cleavage was hypersensitive to bevirimat in vitro with a 50% inhibitory concentration 140 times lower than for WT HIV-1.These results support further clinical development of this first-in-class maturation inhibitor and confirm the usefulness of the SCID-hu Thy/Liv model for evaluation of in vivo antiretroviral efficacy, drug resistance, and viral fitness