GR 20 Parallel Session A3: Modified Gravity

This is the contribution representing Parallel Session A3, on Modified Gravity, in the Proceedings of the GR 20 Conference (July 2013, Warszawa, Poland). It consists of three invited chapters, selected by the Session Chair (P.H.) to represent the broad spectrum of topics discussed in the Session, which ranged from theoretical and phenomenological, to experimental, observational and numerical aspects of gravity. The three chapters are "Einstein-Aether Theory: Thermodynamics of Universal Horizons" by Arif Mohd, "The Curious Case of Conformal Anomalies in Horava-Lifshitz Gravity" by Charles M. Melby-Thompson, and "Detectability of Scalar Gravitational-Wave Bursts with LIGO and Virgo" by Peter Shawhan.Comment: 12 pages, 2 figure

Cuantificación de citocinas caninas mediante reacción en cadena de la polimerasa de transcriptasa reversa en tiempo real

Introduction. Canines are the principal domestic reservoirs of visceral leishmaniasis in both the Old and New World. The development of highly sensitive and quantitative methods, such as real time reverse transcriptase polymerase chain reaction for measurement of canine cytokines has not been exploited in studies of visceral leishmaniasis.Objective. To standardize the relative quantification of canine IFN-g, IL-4, IL-10, IL-12p40 and IL-12p35 using real time reverse transcriptase polymerase chain reaction.Materials and methods. RNA was isolated from PBMCs from 1 year–old foxhounds and cultured with or without Con A, LPS orStaphylococcus aureus extract. This RNA was used in one-step real time reverse transcriptase polymerase chain reaction to optimize the concentrations of the cytokine primers and probes, generate standard curves for each cytokine, confirm equivalent amplification efficiency of cytokine and normalizer (18S rRNA) RNA, and to quantify the expression of the cytokine RNA. The comparative Ct method was used to determine the relative levels of gene expression in the samples, expressed as the fold-increase relative to the control samples.Results. The regression coefficient for the standard curves and the amplification efficiencies of the cytokine and normalizer RNA indicated that the quantification was reliable over a broad concentration range of input RNA. Relative to control cells, activation of PBMCs led to increased expression of IFN-g (132-fold), IL-4 (8.8-fold), IL-10 (7.2-fold), and IL-12p40 (275-fold). Basal expression of IL-12p35 was also detected.Conclusion. This approach provides several advantages over conventional assays for cytokine measurement and can be exploited in the study of the immunopathogenesis and immunity in canine leishmaniasis.Introducción. Los caninos son el principal reservorio domestico de la leishmaniasis visceral en el Nuevo y Viejo mundo. La reacción en cadena de la polimerasa de transcriptasa reversa en tiempo real para la medición de citocinas caninas no ha sido implementada para el estudio de la leishmaniasis visceral.Objetivo. Estandarizar la cuantificación relativa de IFN-g, IL-4, IL-10, IL-12p40 y IL-12p35 caninas utilizando reacción en cadena de la polimerasa de transcriptasa reversa en tiempo real.Materiales y métodos. Células mononucleares de sangre periférica de perros Fox-Hound fueron estimuladas con ConA, LPS y extracto de Staphylococcus aureus. El ARN fue utilizado en la reacción en cadena de la polimerasa de transcriptasa reversa en tiempo real de un solo paso para optimizar las concentraciones de iniciadores y sondas especificas de cada citocina, generar curvas estándar, confirmar la eficiencia de amplificación de las citocinas y del normalizador (18S ARNr) y cuantificar la expresión de ARN. El método comparativo Ct fue utilizado para determinar los niveles relativos de expresión de ARN en las muestras, expresado como el incremento en el número de veces comparado con los controles.Resultados. El coeficiente de regresión para las curvas estándar y las eficiencias de amplificación de las citocinas y el normalizador, indicaron que la cuantificación fue confiable en un amplio rango de concentraciones de ARN. La activación de células mononucleares de sangre periférica resultó en un incremento en la expresión de IFN-g (132), IL-4 (8.8), IL-10 (7,2), y IL-12p40 (275), relativo a células control. La expresión basal de IL-12p35 fue también detectada.Conclusión. Esta metodología, comparada con los métodos convencionales disponibles para la medición de citocinas, ofrece varias ventajas y podría ser utilizada en estudios sobre inmunopatogenia e inmunidad en leishmaniasis visceral canina

Duplex real-time reverse transcriptase PCR to determine cytokine mRNA expression in a hamster model of New World cutaneous leishmaniasis

<p>Abstract</p> <p>Background</p> <p>The Syrian hamster, <it>Mesocricetus auratus</it>, has distinct immunological features and is uniquely susceptible to intracellular pathogens. Studies in hamsters are limited by the relative unavailability of tools to conduct immunological studies. To address this limitation we developed duplex real-time reverse transcriptase (RT) PCR assays for the relative quantification of the mRNAs of hamster cytokines, chemokines, and related immune response molecules.</p> <p>Results</p> <p>Real-time RT-PCR primers and probes were synthesized for analysis of interleukin (IL)-4, IFN-γ, TNF-α, IL-10, IL-12p40, TGF-β, IL-13, IL-21, chemokine ligand (CCL) 22, CCL17, Chemokine (C-C motif) receptor 4 and FoxP3 expression. Standard curves and validation experiments were performed for each real-time RT-PCR assay, allowing us to use the comparative Ct (2^-ΔΔCt) method to calculate changes in gene expression. Application of the real-time RT PCR assays to a biological model was demonstrated by comparing mRNA expression in skin and lymph node tissues between uninfected and <it>Leishmania panamensis </it>infected hamsters.</p> <p>Conclusions</p> <p>The duplex real-time RT PCR assays provide a powerful approach for the quantification of cytokine transcription in hamsters, and their application to a model of cutaneous leishmaniasis suggests that a balanced type 1 and type 2 cytokine response contributes to the chronic, nonprogressive course of disease. These new molecular tools will further facilitate investigation into the mechanisms of disease in the hamster, not only for models of leishmaniasis, but also for other viral, bacterial, fungal, and parasitic infections.</p

Stunting is preceded by intestinal mucosal damage and microbiome changes and Is associated with systemic inflammation in a cohort of Peruvian infants

Stunting, defined as height-for-ag

Inflammatory stimuli alter bone marrow composition and compromise bone health in the malnourished host

Inflammation has a role in the pathogenesis of childhood malnutrition. We investigated the effect of malnutrition and inflammatory challenge on bone marrow composition and bone health. We studied an established murine model of moderate acute malnutrition at baseline and after acute inflammatory challenge with bacterial lipopolysaccharide (LPS), a surrogate of Gram-negative bacterial sepsis, or Leishmania donovani, the cause of visceral leishmaniasis. Both of these infections cause significant morbidity and mortality in malnourished children. Of the 2 stimuli, LPS caused more pronounced bone marrow changes that were amplified in malnourished mice. LPS challenge led to increased inflammatory cytokine expression (Il1b, Il6, and Tnf), inflammasome activation, and inflammatory monocyte accumulation in the bone marrow of malnourished mice. Depletion of inflammatory monocytes in Csfr1-LysMcre-DT malnourished mice significantly reduced the inflammasome activation and IL1-ß production after LPS challenge. The inflammatory challenge also led to increased expansion of mesenchymal stem cells (MSCs), bone marrow adiposity, and expression of genes (Pparg, Adipoq, and Srbp1) associated with adipogenesis in malnourished mice. This suggests that inflammatory challenge promotes differentiation of BM MSCs toward the adipocyte lineage rather than toward bone-forming osteoblasts in the malnourished host. Concurrent with this reduced osteoblastic potential there was an increase in bone-resorbing osteoclasts, enhanced osteoclast activity, upregulation of inflammatory genes, and IL-1B involved in osteoclast differentiation and activation. The resulting weakened bone formation and increased bone resorption would contribute to the bone fragility associated with malnutrition. Lastly, we evaluated the effect of replacing lipid rich in omega-6 fatty acids (corn oil) with lipid-rich in omega-3 fatty acids (fish oil) in the nutrient-deficient diet. LPS-challenged malnourished mice that received dietary fish oil showed decreased expression of inflammatory cytokines and Rankl and reduced osteoclast differentiation and activation in the bone marrow. This work demonstrates that the negative effect of inflammatory challenge on bone marrow is amplified in the malnourished host. Increasing dietary intake of omega-3 fatty acids may be a means to reduce inflammation and improve bone health in malnourished children

Identification of Small Molecule Lead Compounds for Visceral Leishmaniasis Using a Novel Ex Vivo Splenic Explant Model System

Visceral leishmaniasis is a life threatening parasitic disease present in several countries of the world. New drugs are needed to treat this disease because treatments are becoming increasingly ineffective. We established a novel system to screen for new anti-leishmanial compounds that utilizes spleen cells from hamsters infected with the parasite Leishmania donovani. The parasite strain we used was genetically engineered to emit light by the incorporation of the firefly luciferase gen. This laboratory test system has the advantage of reproducing the cellular environment where the drug has to combat the infection. The efficacy of the compounds is easily determined by measuring the light emitted by the surviving parasites in a luminometer after exposing the infected cells to the test compounds. The screening of more than 4,000 molecules showed that 84 (2.1%) of them showed anti-leishmanial activity and had an acceptable toxicity evaluation. Eighty two percent of these molecules, which had varied chemical structures, were previously unknown to have anti-leishmanial activity. Further studies in animals of these new chemical entities may identify drug candidates for the treatment of visceral leishmaniasis

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad