2,410 research outputs found

    PNL20 UTILIZATION OF IMMUNOMODULATORY DRUG THERAPIES IN MULTIPLE SCLEROSIS (MS) IN NOVA SCOTIA, CANADA 1998—2003

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    Dissecting pathways to thrombocytopenia in a mouse model of visceral leishmaniasis

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    Visceral leishmaniasis is an important yet neglected parasitic disease caused by infection with Leishmania donovani or L infantum. Disease manifestations include fever, weight loss, hepatosplenomegaly, immune dysregulation, and extensive hematological complications. Thrombocytopenia is a dominant hematological feature seen in both humans and experimental models, but the mechanisms behind this infection-driven thrombocytopenia remain poorly understood. Using a murine model of experimental visceral leishmaniasis (EVL), we demonstrated a progressive decrease in platelets from day 14 after infection, culminating in severe thrombocytopenia by day 28. Plasma thrombopoietin (TPO) levels were reduced in infected mice, at least in part because of the alterations in the liver microenvironment associated with granulomatous inflammation. Bone marrow (BM) megakaryocyte cytoplasmic maturation was significantly reduced. In addition to a production deficit, we identified significant increases in platelet clearance. L donovani–infected splenectomized mice were protected from thrombocytopenia compared with sham operated infected mice and had a greater response to exogenous TPO. Furthermore, infection led to higher levels of platelet opsonization and desialylation, both associated with platelet clearance in spleen and liver, respectively. Critically, these changes could be reversed rapidly by drug treatment to reduce parasite load or by administration of TPO agonists. In summary, our findings demonstrate that the mechanisms underpinning thrombocytopenia in EVL are multifactorial and reversible, with no obvious residual damage to the BM microenvironment

    Partial pathogen protection by tick-bite sensitization and epitope recognition in peptide-immunized HLA DR3 transgenic mice

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    Ticks are notorious vectors of disease for humans, and many species of ticks transmit multiple pathogens, sometimes in the same tick bite. Accordingly, a broad-spectrum vaccine that targets vector ticks and pathogen transmission at the tick/host interface, rather than multiple vaccines against every possible tickborne pathogen, could become an important tool for resolving an emerging public health crisis. The concept for such a tick protective vaccine comes from observations of an acquired tick resistance (ATR) that can develop in non-natural hosts of ticks following sensitization to tick salivary components. Mice are commonly used as models to study immune responses to human pathogens but normal mice are natural hosts for many species of ticks and fail to develop ATR. We evaluated HLA DR3 transgenic (tg) “humanized” mice as a potential model of ATR and assessed the possibility of using this animal model for tick protective vaccine discovery studies. Serial tick infestations with pathogen-free Ixodes scapularis ticks were used to tick-bite sensitize HLA DR3 tg mice. Sensitization resulted in a cytokine skew favoring a Th2 bias as well as partial (57%) protection to infection with Lyme disease spirochetes (Borrelia burgdorferi) following infected tick challenge when compared to tick naïve counterparts. I. scapularis salivary gland homogenate (SGH) and a group of immunoinformatic-predicted T cell epitopes identified from the I. scapularis salivary transcriptome were used separately to vaccinate HLA DR3 tg mice, and these mice also were assessed for both pathogen protection and epitope recognition. Reduced pathogen transmission along with a Th2 skew resulted from SGH vaccination, while no significant protection and a possible T regulatory bias was seen in epitope-vaccinated mice. This study provides the first proof-of-concept for using HLA DR tg “humanized” mice for studying the potential tick protective effects of immunoinformatic- or otherwise-derived tick salivary components as tickborne disease vaccines

    A de Sitter Hoedown

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    Rotating black holes in de Sitter space are known to have interesting limits where the temperatures of the black hole and cosmological horizon are equal. We give a complete description of the thermal phase structure of all allowed rotating black hole configurations. Only one configuration, the rotating Nariai limit, has the black hole and cosmological horizons both in thermal and rotational equilibrium, in that both the temperatures and angular velocities of the two horizons coincide. The thermal evolution of the spacetime is shown to lead to the pure de Sitter spacetime, which is the most entropic configuration. We then provide a comprehensive study of the wave equation for a massless scalar in the rotating Nariai geometry. The absorption cross section at the black hole horizon is computed and a condition is found for when the scattering becomes superradiant. The boundary-to-boundary correlators at finite temperature are computed at future infinity. The quasinormal modes are obtained in explicit form. Finally, we obtain an expression for the expectation value of the number of particles produced at future infinity starting from a vacuum state with no incoming particles at past infinity. Some of our results are used to provide further evidence for a recent holographic proposal between the rotating Nariai geometry and a two-dimensional conformal field theory.Comment: 35 + 1 pages, 9 figures; v3: typos correcte

    Body odor quality predicts behavioral attractiveness in humans

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    Growing effort is being made to understand how different attractive physical traits co-vary within individuals, partly because this might indicate an underlying index of genetic quality. In humans, attention has focused on potential markers of quality such as facial attractiveness, axillary odor quality, the second-to-fourth digit (2D:4D) ratio and body mass index (BMI). Here we extend this approach to include visually-assessed kinesic cues (nonverbal behavior linked to movement) which are statistically independent of structural physical traits. The utility of such kinesic cues in mate assessment is controversial, particularly during everyday conversational contexts, as they could be unreliable and susceptible to deception. However, we show here that the attractiveness of nonverbal behavior, in 20 male participants, is predicted by perceived quality of their axillary body odor. This finding indicates covariation between two desirable traits in different sensory modalities. Depending on two different rating contexts (either a simple attractiveness rating or a rating for long-term partners by 10 female raters not using hormonal contraception), we also found significant relationships between perceived attractiveness of nonverbal behavior and BMI, and between axillary odor ratings and 2D:4D ratio. Axillary odor pleasantness was the single attribute that consistently predicted attractiveness of nonverbal behavior. Our results demonstrate that nonverbal kinesic cues could reliably reveal mate quality, at least in males, and could corroborate and contribute to mate assessment based on other physical traits

    Holography at an Extremal De Sitter Horizon

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    Rotating maximal black holes in four-dimensional de Sitter space, for which the outer event horizon coincides with the cosmological horizon, have an infinite near-horizon region described by the rotating Nariai metric. We show that the asymptotic symmetry group at the spacelike future boundary of the near-horizon region contains a Virasoro algebra with a real, positive central charge. This is evidence that quantum gravity in a rotating Nariai background is dual to a two-dimensional Euclidean conformal field theory. These results are related to the Kerr/CFT correspondence for extremal black holes, but have two key differences: one of the black hole event horizons has been traded for the cosmological horizon, and the near-horizon geometry is a fiber over dS_2 rather than AdS_2.Comment: 15 page

    The Heat Kernel on AdS_3 and its Applications

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    We derive the heat kernel for arbitrary tensor fields on S^3 and (Euclidean) AdS_3 using a group theoretic approach. We use these results to also obtain the heat kernel on certain quotients of these spaces. In particular, we give a simple, explicit expression for the one loop determinant for a field of arbitrary spin s in thermal AdS_3. We apply this to the calculation of the one loop partition function of N=1 supergravity on AdS_3. We find that the answer factorizes into left- and right-moving super Virasoro characters built on the SL(2, C) invariant vacuum, as argued by Maloney and Witten on general grounds.Comment: 46 pages, LaTeX, v2: Reference adde
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