Adrenal steroids modulate the immune response during Brucella abortus infection by a mechanism that depends on the regulation of cytokine production

Human brucellosis is a protean disease with a diversity of clinical signs and symptoms resulting from infection with Brucella species. Recent reports suggest a cross-regulation between adrenal steroids (cortisol and dehydroepiandrosterone [DHEA]) and the immune system. Monocytes and macrophages are the main replication niche for Brucella. Therefore, we investigated the role of adrenal hormones on the modulation of the immune response mediated by macrophages in B. abortus infection. Cortisol treatment during B. abortus infection significantly inhibits cytokine, chemokine, and MMP-9 secretion. In contrast, DHEA treatment had no effect. However, DHEA treatment increases the expression of costimulatory molecules (CD40, CD86), the adhesion molecule CD54, and major histocompatibility complex class I (MHC-I) and MHC-II expression on the surface of B. abortus-infected monocytes. It is known that B. abortus infection inhibits MHC-I and MHC-II expression induced by gamma interferon (IFN-γ) treatment. DHEA reverses B. abortus downmodulation of the MHC-I and -II expression induced by IFN-γ. Taken together, our data indicate that DHEA immune intervention may positively affect monocyte activity during B. abortus infection.Fil: Gentilini, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Velasquez, Lis Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Arriola Benitez, Paula Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentin

Identification of mutations in the PYRIN-containing NLR genes (NLRP) in head and neck squamous cell carcinoma

Head and Neck Squamous Cell Carcinoma (HNSCC) encompasses malignancies that arise in the mucosa of the upper aerodigestive tract. Recent high throughput DNA sequencing revealed HNSCC genes mutations that contribute to several cancer cell characteristics, including dysregulation of cell proliferation and death, intracellular proinflammatory signaling, and autophagy. The PYRIN-domain containing NLR (Nucleotide-binding domain, Leucine rich Repeats - containing) proteins have recently emerged as pivotal modulators of cell death, autophagy, inflammation, and metabolism. Their close physiologic association with cancer development prompted us to determine whether mutations within the NLRP (PYRIN-containing NLR ) gene family were associated with HNSCC genome instability and their clinicopathologic correlations. Catastrophic mutational events underlie cancer cell genome instability and mark a point-of-no-return in cancer cell development and generation of heterogeneity. The mutation profiles of 62 patients with primary conventional type HNSCC excluding other histologic variants were analyzed. Associations were tested using Fisher's Exact test or Mann-Whitney U test. Mutations in NLRP were associated with elevated genome instability as characterized by higher mutation rates. Clinically, NLRP mutations were more frequently found in HNSCC arising in the floor of mouth (50.0%) in comparison with HNSCC at other head and neck locations (14.8%). These mutations were clustered at the leucine rich repeats region of NLRP proteins, and affected NLRP genes were mostly localized at chromosomes 11p15.4 and 19q13.42-19q13.43. Twenty novel NLRP mutations were identified in HNSCC, and mutations in this group of genes were correlated with increased cancer cell genome mutation rates, and such features could be a potential molecular biomarker of HNSCC genome instability. © 2014 Lei et al

Using fuzzy PROMETHEE to select countries for developmental Aid

Wealthy nations continue to demonstrate their unwavering support to improving conditions and the general well-being of poor countries in spite of the recent economic crises. However, as developmental aid relatively shrinks, both Aid donors and recipient countries have shown keen interest in methodologies used in evaluating developmental assistance programs. Evaluation of aid programs is seen as a complex task mainly because of the several non-aid factors that tend to affect overall outcomes. Adding to the complexity are the subjective sets of criteria used in Aid evaluations programs. This paper proposes a two stage framework of fuzzy TOPSIS and sensitivity analysis to demonstrate how aid-recipient countries can be evaluated to deepen transparency, fairness, value for money and sustainability of such aid programs. Using the Organisation for Economic Co-operation and Development (OECD) set of subjective criteria for evaluating aid programs; a numerical examplepre-defined by linguistic terms parameterized by triangular fuzzy numbers is provided to evaluate aid programs. Fuzzy PROMETHEE is used in the first stage to evaluate and rank aid-recipients followed by a comparative analysis with Fuzzy VIKOR and Fuzzy TOPSIS to ascertain an accurateness of the method used. A sensitivity analysis is further added that anticipates possible influences from lobbyists and examines the effect of that bias in expert ratings on the evaluation process. The result shows a framework that can be employed in evaluating aid effectiveness of recipient-countries

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Search for Charged Higgs Bosons in e+e- Collisions at \sqrt{s} = 189 GeV

A search for pair-produced charged Higgs bosons is performed with the L3 detector at LEP using data collected at a centre-of-mass energy of 188.6 GeV, corresponding to an integrated luminosity of 176.4 pb^-1. Higgs decays into a charm and a strange quark or into a tau lepton and its associated neutrino are considered. The observed events are consistent with the expectations from Standard Model background processes. A lower limit of 65.5 GeV on the charged Higgs mass is derived at 95 % confidence level, independent of the decay branching ratio Br(H^{+/-} -> tau nu)

Genome-wide analysis reveals the extent of EAV-HP integration in domestic chicken

Background: EAV-HP is an ancient retrovirus pre-dating Gallus speciation, which continues to circulate in modern chicken populations, and led to the emergence of avian leukosis virus subgroup J causing significant economic losses to the poultry industry. We mapped EAV-HP integration sites in Ethiopian village chickens, a Silkie, Taiwan Country chicken, red junglefowl Gallusgallus and several inbred experimental lines using whole-genome sequence data. Results: An average of 75.22 ± 9.52 integration sites per bird were identified, which collectively group into 279 intervals of which 5% are common to 90% of the genomes analysed and are suggestive of pre-domestication integration events. More than a third of intervals are specific to individual genomes, supporting active circulation of EAV-HP in modern chickens. Interval density is correlated with chromosome length (P<2.31−6), and 27 % of intervals are located within 5 kb of a transcript. Functional annotation clustering of genes reveals enrichment for immune-related functions (P<0.05). Conclusions: Our results illustrate a non-random distribution of EAV-HP in the genome, emphasising the importance it may have played in the adaptation of the species, and provide a platform from which to extend investigations on the co-evolutionary significance of endogenous retroviral genera with their hosts

Human major histocompatibility complex class II-associated invariant chain gene promoter : functional analysis and in vitro protein/DNA interactions of constitutive and IFN-γ-induced expression

Major histocompatibility complex (MHC) class II-associated invariant chain (Ii) gene and the MHC class II molecules are physically and functionally associated within clans II-expressing cell types. These genes are generally co-expressed in various cell types and coordinately induced by cytokines such as interferon-γ (IFN-γ). Human Ii gene shares a regulatory mechanism with MHC class II genes via the X and Y cis-acting elements. Ii X and Y are required for constitutive expression in B lymphoid cell lines and for induction by IFN-γ in a glioblastoma cell line. The Servenius element (S) contributes 5-fold transcriptional activity to class II gene HLA-DRA and an S homologue has been implied in Ii gene regulation.Major histocompatibility complex (MHC) class II-associated invariant chain (Ii) gene and the MHC class II molecules are physically and functionally associated within clans II-expressing cell types. These genes are generally co-expressed in various cell types and coordinately induced by cytokines such as interferon-γ (IFN-γ). Human Ii gene shares a regulatory mechanism with MHC class II genes via the X and Y cis-acting elements. Ii X and Y are required for constitutive expression in B lymphoid cell lines and for induction by IFN-γ in a glioblastoma cell line. The Servenius element (S) contributes 5-fold transcriptional activity to class II gene HLA-DRA and an S homologue has been implied in Ii gene regulation

Respective impacts of Arctic sea ice decline and increasing greenhouse gases concentration on Sahel precipitation

The impact of climate change on Sahel precipitation is uncertain and has to be widely documented. Recently, it has been shown that Arctic sea ice loss leverages the global warming effects worldwide, suggesting a potential impact of Arctic sea ice decline on tropical regions. However, defining the specific roles of increasing greenhouse gases (GHG) concentration and declining Arctic sea ice extent on Sahel climate is not straightforward since the former impacts the latter. We avoid this dependency by analysing idealized experiments performed with the CNRM-CM5 coupled model. Results show that the increase in GHG concentration explains most of the Sahel precipitation change. We found that the impact due to Arctic sea ice loss depends on the level of atmospheric GHG concentration. When the GHG concentration is relatively low (values representative of 1980s), then the impact is moderate over the Sahel. However, when the concentration in GHG is levelled up, then Arctic sea ice loss leads to increased Sahel precipitation. In this particular case the ocean-land meridional gradient of temperature strengthens, allowing a more intense monsoon circulation. We linked the non-linearity of Arctic sea ice decline impact with differences in temperature and sea level pressure changes over the North Atlantic Ocean. We argue that the impact of the Arctic sea ice loss will become more relevant with time, in the context of climate change