Increased Levels of BAFF and APRIL Related to Human Active Pulmonary Tuberculosis

BACKGROUND: Despite great efforts to improve diagnosis and treatment, tuberculosis (TB) remains a major health problem worldwide, especially in developing countries. Lack of concrete immune markers is still the obstacle to properly evaluate active TB. Therefore, identification of more validated biomarkers and phenotypic signatures is imperative. In particular, T cell-related biomarkers are more significant. METHODOLOGY: To understand the nature of CD4(+) T cell-derived signatures involved in infection and disease development, we examined and analyzed whole genome expression profiles of purified CD4(+) T cells from healthy individuals (HD), two distinct populations with latent infection (with low or high IFN-γ levels, LTB(L)/LTB(H)) and untreated TB patients. Following, we validated the expression profiles of genes in the peripheral CD4(+) T cells from each group and examined secretion levels of distinct cytokines in serum and pleural effusion. PRINCIPAL FINDINGS: Our bio-informatic analyses indicate that the two latent populations and clinical TB patients possess distinct CD4(+) T cell gene expression profiles. Furthermore, The mRNA and protein expression levels of B cell activating factor (BAFF), which belongs to the TNF family, and a proliferation-inducing ligand (APRIL) were markedly up-regulated at the disease stage. In particular, the dramatic enhancement of BAFF and APRIL in the pleural effusion of patients with tuberculosis pleurisy suggests that these proteins may present disease status. In addition, we found that the BAFF/APRIL system was closely related to the Th1 immune response. Our study delineates previously unreported roles of BAFF and APRIL in the development of tuberculosis, and these findings have implications for the diagnosis of the disease. Our study also identifies a number of transcriptional signatures in CD4(+) T cells that have the potential to be utilized as diagnostic and prognostic tools to combat the tuberculosis epidemic

Antibodies Against Human BLyS and APRIL Attenuate EAE Development in Marmoset Monkeys

B lymphocyte stimulator (BLyS, also indicated as BAFF (B-cell activating factor) and CD257), and A Proliferation Inducing Ligand (APRIL, CD256) are two members of the TNF superfamily with a central role in B cell survival. Antibodies against these factors have potential therapeutic relevance in autoimmune inflammatory disorders with a proven pathogenic contribution of B cells, such as multiple sclerosis (MS). In the current study we performed a multi-parameter efficacy comparison of monoclonal antibodies against human anti-BLyS and anti-APRIL in a common marmoset (Callithrix jacchus) model of experimental autoimmune encephalomyelitis (EAE). A MS-like disease was induced by immunization with recombinant human myelin/oligodendrocyte glycoprotein (rhMOG) in complete Freund's adjuvant. The results show that the anti-BLyS and anti-APRIL antibody cause significant depletion of circulating CD20+ B cells, but a small subset of CD20 + CD40highB cells was not depleted. Induction of CD20+ B cell depletion from lymph nodes was only observed in the anti-BLyS treated monkeys. Both antibodies had a significant inhibitory effect on disease development, but all monkeys developed clinically evident EAE. Anti-BLyS treated monkeys were sacrificed with the same clinical signs as saline-treated monkeys, but nevertheless displayed significantly reduced spinal cord demyelination. This effect was not observed in the anti-APRIL treated monkeys. The two antibodies had a different effect on T cell subset activation and the profiles of ex vivo released cytokines. In conclusion, treatment with anti-BLyS and anti-APRIL delays the development of neurological disease in a relevant preclinical model of MS. The two mAbs achieve this effect via different mechanisms

High pressure solid-liquid equilibria of fatty acids

The solid-liquid phase diagrams of two binary mixtures of saturated fatty acids, formed by caprylic acid (C(8:0)) + myristic acid (C(14:0)) and lauric acid (C(12:0)) + myristic acid (C(14:0)), were measured using high pressure microscopy in the range of 0. 1-90 MPa. It is shown that unlike for other long chain alkyl compounds such as alkanes the phase diagrams are only slightly affected by the pressure, even in very large pressure ranges such as studied in this work. The modeling of the measured phase diagrams was attempted using an approach previously developed by the authors for n-alkane mixtures. It is here shown that this model can provide an accurate description of the high pressure solid-liquid equilibrium of fatty acid mixtures. (C) 2007 Elsevier B.V. All rights reserved.253211812

High pressure phase behavior of carbon dioxide in 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquids

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)New standards concerning environmental and safety issues are creating an increasing interest on ionic liquids as alternative solvents for a wide range of industrial applications. In this work, a new apparatus developed to measure vapor-liquid phase equilibrium in a wide range of pressures and temperatures was used to measure the phase behavior of the binary systems of carbon dioxide (CO(2))+1-ethyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide ([C(2) mim][Tf(2)N]) and CO(2)+1-methyl-3-pentyl-imidazolium bis(trifluoromethylsulfonyl)imide ([C(5) mim][Tf(2)N]) at temperatures up to 363 K and pressures up to 50 MPa. A thermodynamic consistency test, developed for systems with incomplete PTxy data and based on the Gibbs-Duhem equation, was applied to the experimental data measured in this work and the Peng-Robinson EoS using the Wong-Sandler mixing rule was used to describe the experimental data with excellent results. (C) 2008 Elsevier B.V. All rights reserved.48299107Fundacao para a Ciencia e a Tecnologia [POCI/EQU/58152/2004]Pedroj. Carvalho [SFRH/BD/41562/2007]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao para a Ciencia e a Tecnologia [POCI/EQU/58152/2004]Pedroj. Carvalho [SFRH/BD/41562/2007]FAPESP [2006/03711-1

Measurement and prediction of speeds of sound of fatty acid ethyl esters and ethylic biodiesels

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Speed of sound of fatty esters provides important information about biodiesel injection characteristics and enables the estimation of many other important properties of biodiesels. Nevertheless, the experimental speeds of sound of fatty esters are very scant. This work provides new data on speed of sound for nine fatty acid ethyl esters and four ethylic biodiesels, measured at atmospheric pressure and temperatures ranging from 293.15 to 343.15 K. These new data is used to evaluate the ability of the Wada's group contribution method to predict the biodiesel speed of sound. It is here shown that this model provides excellent description of the experimental data, with overall average relative deviations (OARDs) of 0.25% for the ethyl esters and between 0.45% and 0.59% for the biodiesels. (C) 2013 Elsevier Ltd. All rights reserved.108840845Fundacaopara a Ciencia e a Tecnologia [SFRH/BD/51476/2011, Pest-C/CTM/LA0011/2011]FundacaoOrienteUniversity of AveiroFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundacao para a Ciencia e a Tecnologia [PEst-OE/QUI/UI0536/2011, PEst-OE/QUI/UI0612/2011]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundacaopara a Ciencia e a Tecnologia [SFRH/BD/51476/2011, Pest-C/CTM/LA0011/2011]FAPESP [2008/56258-8]CNPq [304495/2010-7, 483340/2012-0]Fundacao para a Ciencia e a Tecnologia [PEst-OE/QUI/UI0536/2011, PEst-OE/QUI/UI0612/2011