Early Interferon-γ Production in Human Lymphocyte Subsets in Response to Nontyphoidal Salmonella Demonstrates Inherent Capacity in Innate Cells

Background Nontyphoidal Salmonellae frequently cause life-threatening bacteremia in sub-Saharan Africa. Young children and HIV-infected adults are particularly susceptible. High case-fatality rates and increasing antibiotic resistance require new approaches to the management of this disease. Impaired cellular immunity caused by defects in the T helper 1 pathway lead to intracellular disease with Salmonella that can be countered by IFNγ administration. This report identifies the lymphocyte subsets that produce IFNγ early in Salmonella infection. Methodology Intracellular cytokine staining was used to identify IFNγ production in blood lymphocyte subsets of ten healthy adults with antibodies to Salmonella (as evidence of immunity to Salmonella), in response to stimulation with live and heat-killed preparations of the D23580 invasive African isolate of Salmonella Typhimurium. The absolute number of IFNγ-producing cells in innate, innate-like and adaptive lymphocyte subpopulations was determined. Principal Findings Early IFNγ production was found in the innate/innate-like lymphocyte subsets: γδ-T cells, NK cells and NK-like T cells. Significantly higher percentages of such cells produced IFNγ compared to adaptive αβ-T cells (Student's t test, P<0.001 and ≤0.02 for each innate subset compared, respectively, with CD4+- and CD8+-T cells). The absolute numbers of IFNγ-producing cells showed similar differences. The proportion of IFNγ-producing γδ-T cells, but not other lymphocytes, was significantly higher when stimulated with live compared with heat-killed bacteria (P<0.0001). Conclusion/Significance Our findings indicate an inherent capacity of innate/innate-like lymphocyte subsets to produce IFNγ early in the response to Salmonella infection. This may serve to control intracellular infection and reduce the threat of extracellular spread of disease with bacteremia which becomes life-threatening in the absence of protective antibody. These innate cells may also help mitigate against the effect on IFNγ production of depletion of Salmonella-specific CD4+-T lymphocytes in HIV infection

Early affective changes and increased connectivity in preclinical Alzheimer's disease.

IntroductionAffective changes precede cognitive decline in mild Alzheimer's disease and may relate to increased connectivity in a "salience network" attuned to emotionally significant stimuli. The trajectory of affective changes in preclinical Alzheimer's disease, and its relationship to this network, is unknown.MethodsOne hundred one cognitively normal older adults received longitudinal assessments of affective symptoms, then amyloid-PET. We hypothesized amyloid-positive individuals would show enhanced emotional reactivity associated with salience network connectivity. We tested whether increased global connectivity in key regions significantly related to affective changes.ResultsIn participants later found to be amyloid positive, emotional reactivity increased with age, and interpersonal warmth declined in women. These individuals showed higher global connectivity within the right insula and superior temporal sulcus; higher superior temporal sulcus connectivity predicted increasing emotional reactivity and decreasing interpersonal warmth.ConclusionsAffective changes should be considered an early preclinical feature of Alzheimer's disease. These changes may relate to higher functional connectivity in regions critical for social-emotional processing

Marriage, Intimacy and Risk of HIV Infection in South West Uganda

Long-term, monogamous, relationships are often portrayed as protective in HIV prevention campaigns. Focusing on marriage in a community in south west Uganda, we examine why and how people enter long term relationships, what their expectations are and what factors sustain those relationships. Qualitative data were collected using in-depth interviews with 50 men and women randomly selected from a General Population Cohort. The results showed that managing expectations to sustain marriage is challenging; however the socio-economic and cultural benefits of marriage: having children, property acquisition as well as securing societal status tend to overshadow the costs associated with risks from infidelity such as sexually transmitted infections (including HIV). Recognising the compromises that couples may make to sustain their marriage is an important step towards acknowledging that `being faithful’ may be about staying together and showing commitment, not sexual exclusivity. Keywords: marriage; long-term relationship; HIV epidemic; UgandaLes relations monogames à long terme, sont souvent dépeintes comme une protection dans les campagnes de prévention du VIH. En mettant l'accent sur le mariage dans une communauté dans le sud ouest de l'Ouganda, nous examinons pourquoi et comment les gens entrent dans des relations à long terme, quelles sont leurs attentes et quels facteurs soutiennent ces relations. Les données qualitatives ont été recueillies au moyen d'entrevues en profondeur avec 50 hommes et femmes choisis au hasard à partir d'une population générale cohorte. Les résultats ont montré que la gestion des attentes pour soutenir le mariage est difficile, mais les avantages socio-économiques et culturels du mariage: avoir des enfants, acquis de la propriété ainsi que l’obtention d’un bon état-civil dans la société, ont tendance à éclipser les coûts associés aux risques de l'infidélité telles que les infections sexuellement transmissibles (y compris le VIH). La reconnaissance des compromis que les couples peuvent faire pour soutenir leur mariage, est une étape importante vers la reconnaissance du fait que « être fidèle» peut signifier rester ensemble et de faire preuve de l'engagement, pas l'exclusivité sexuelle. Mots clés: mariage; relation à long terme; Épidémie de VIH; Ougand

The Medical Research Council (UK)/Uganda Virus Research Institute Uganda Research Unit on AIDS--'25 years of research through partnerships'.

For the past 25 years, the Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS has conducted research on HIV-1, coinfections and, more recently, on non-communicable diseases. Working with various partners, the research findings of the Unit have contributed to the understanding and control of the HIV epidemic both in Uganda and globally, and informed the future development of biomedical HIV interventions, health policy and practice. In this report, as we celebrate our silver jubilee, we describe some of these achievements and the Unit's multidisciplinary approach to research. We also discuss the future direction of the Unit; an exemplar of a partnership that has been largely funded from the north but led in the south

Vanishing Viscosity Limits and Boundary Layers for Circularly Symmetric 2D Flows

We continue the work of Lopes Filho, Mazzucato and Nussenzveig Lopes [LMN], on the vanishing viscosity limit of circularly symmetric viscous flow in a disk with rotating boundary, shown there to converge to the inviscid limit in $L^2$-norm as long as the prescribed angular velocity $\alpha(t)$ of the boundary has bounded total variation. Here we establish convergence in stronger $L^2$ and $L^p$-Sobolev spaces, allow for more singular angular velocities $\alpha$, and address the issue of analyzing the behavior of the boundary layer. This includes an analysis of concentration of vorticity in the vanishing viscosity limit. We also consider such flows on an annulus, whose two boundary components rotate independently. [LMN] Lopes Filho, M. C., Mazzucato, A. L. and Nussenzveig Lopes, H. J., Vanishing viscosity limit for incompressible flow inside a rotating circle, preprint 2006

Pole structure of the Hamiltonian ζ\zeta-function for a singular potential

We study the pole structure of the $\zeta$-function associated to the Hamiltonian $H$ of a quantum mechanical particle living in the half-line $\mathbf{R}^+$, subject to the singular potential $g x^{-2}+x^2$. We show that $H$ admits nontrivial self-adjoint extensions (SAE) in a given range of values of the parameter $g$. The $\zeta$-functions of these operators present poles which depend on $g$ and, in general, do not coincide with half an integer (they can even be irrational). The corresponding residues depend on the SAE considered.Comment: 12 pages, 1 figure, RevTeX. References added. Version to appear in Jour. Phys. A: Math. Ge

Abelian Duality

We show that on three-dimensional Riemannian manifolds without boundaries and with trivial first real de Rham cohomology group (and in no other dimensions) scalar field theory and Maxwell theory are equivalent: the ratio of the partition functions is given by the Ray-Singer torsion of the manifold. On the level of interaction with external currents, the equivalence persists provided there is a fixed relation between the charges and the currents.Comment: 11 pages, LaTeX, no figures, a reference added, submitted to Phys. Rev.

Strong ellipticity and spectral properties of chiral bag boundary conditions

We prove strong ellipticity of chiral bag boundary conditions on even dimensional manifolds. From a knowledge of the heat kernel in an infinite cylinder, some basic properties of the zeta function are analyzed on cylindrical product manifolds of arbitrary even dimension.Comment: 16 pages, LaTeX, References adde