Transthyretin is not necessary for thyroid hormone metabolism in conditions of increased hormone demand

Thyroid hormones circulate in blood mainly bound to plasma proteins. Transthyretin is the major thyroxine plasma carrier in mice. Studies in transthyretin-null mice revealed that the absence of transthyretin results in euthyroid hypothyroxinemia and normal thyroid hormone tissue distribution, with the exception of the choroid plexus in the brain. Therefore, transthyretin does not influence normal thyroid hormone homeostasis under standard laboratory conditions. To investigate if transthyretin has a buffer/storage role we challenged transthyretin-null and wild-type mice with conditions of increased hormone demand: (i) exposure to cold, which elicits thermogenesis, a process that requires thyroid hormones; and (ii) thyroidectomy, which abolishes thyroid hormone synthesis and secretion and induces severe hypothyroidism. Transthyretin-null mice responded as the wild-type both to changes induced by stressful events, namely in body weight, food intake and thyroid hormone tissue content, and in the mRNA levels of genes whose expression is altered in such conditions. These results clearly exclude a role for transthyretin in thyroid hormone homeostasis even under conditions of increased hormone demand.POCTI/NSE/37315/2001, from Fundação para a Ciência e Tecnologia (Portugal) and FEDER; J C S is a recipient of a PhD fellowship from Fundação para a Ciência e Tecnologia (Portugal

Preparação e características de pastas de amêndoas de castanha de caju e amendoim.

bitstream/CNPAT-2010/11576/1/cot-144.pd

Mycobacterium tuberculosis strains are differentially recognized by TLRs with an impact on the immune response

Tuberculosis associates with a wide spectrum of disease outcomes. The Beijing (Bj) lineage of Mycobacterium tuberculosis (Mtb) is suggested to be more virulent than other Mtb lineages and prone to elicit non-protective immune responses. However, highly heterogeneous immune responses were reported upon infection of innate immune cells with Bj strains or stimulation with their glycolipids. Using both in vitro and in vivo mouse models of infection, we here report that the molecular mechanism for this heterogeneity may be related to distinct TLR activations. Among this Mtb lineage, we found strains that preferentially activate TLR2, and others that also activate TLR4. Recognition of Mtb strains by TLR4 resulted in a distinct cytokine profile in vitro and in vivo, with specific production of type I IFN. We also uncover a novel protective role for TLR4 activation in vivo. Thus, our findings contribute to the knowledge of the molecular basis underlying how host innate immune cells handle different Mtb strains, in particular the intricate host-pathogen interaction with strains of the Mtb Bj lineage.This work has been funded by Fundacao para a Ciencia e Tecnologia, Portugal. Project grants: PTDC/SAU-MII/101977/2008 and PTDC/BIA-BCM/102776/2008. Personal grants: SFRH/BD/35981/2007 to JC; SFRH/BPD/3306/2007 to AC; SFRH/BPD/77399/2011 to LMT; SFRH/BI/33456/2008 to CS; and SFRH/BPD/33959/2009 to NSO. MS is a Ciencia 2007 fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Characterization of Neossolos Regolíticos (Psamments) through a pluviometric gradient in Brazilian semiarid.

There is still little information about Neossolos Regoliticos ( Neosols) , therefore, generating information about fertility, genesis and mineralogy is important to define the proper use and management. The work aimed to characterize morphologically, physically, chemically and mineralogically three Neossolos Regoliticos (Psamments) along a pluviometric gradient ( 400 and 600 mm). For this purpose, trenches were opened, where the description and collection of soil samples proceeded. It was not possible to notice rainfall interference in the differentiation of horizons and depth of soils. However, increased clay contents from very dry soil to the sub-humid zone, showing the influence to rainfall that is also reflected in the natural fertility of Neossolos Regoliticos (Psamments). No Brasil, o conhecimento sobre esses solos é escasso, o que demanda geração de informações sobre a sua fertilidade, gênese e mineralogia, entre outros aspectos, para o uso e manejo adequados. O objetivo desse trabalho foi realizar a caracterização morfológica, física, química e mineralógica de Neossolos Regolíticos ao longo de um gradiente pluviométrico no semiárido Paraibano. Para tanto, dividiu-se a região em três zonas de acordo com a precipitação média anual: muito seca (_> 400 e 600 mm) onde foram abertas três trincheiras para coleta e descrição dos solos em cada horizonte. Não foi possível notar interferência da pluviometria na diferenciação dos horizontes e na profundidade dos solos. Os teores de argila aumentaram do solo da zona muito seca para a subúmida, evidenciando a influência das precipitações pluviométricas que também se refletiram na fertilidade natural dos Neossolos Regolíticos. A mineralogia da fração argila mostrou-se relativamente semelhante entre os solos estudados com caulinita, quartzo, feldspato e mica

Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell–Driven Protective Response

Nucleoside hydrolases (NHs) show homology among parasite protozoa, fungi and bacteria. They are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. Immune protection against NHs would prevent disease at the early infection of several pathogens. We have identified the domain of the NH of L. donovani (NH36) responsible for its immunogenicity and protective efficacy against murine visceral leishmaniasis (VL). Using recombinant generated peptides covering the whole NH36 sequence and saponin we demonstrate that protection against L. chagasi is related to its C-terminal domain (amino-acids 199–314) and is mediated mainly by a CD4+ T cell driven response with a lower contribution of CD8+ T cells. Immunization with this peptide exceeds in 36.73±12.33% the protective response induced by the cognate NH36 protein. Increases in IgM, IgG2a, IgG1 and IgG2b antibodies, CD4+ T cell proportions, IFN-γ secretion, ratios of IFN-γ/IL-10 producing CD4+ and CD8+ T cells and percents of antibody binding inhibition by synthetic predicted epitopes were detected in F3 vaccinated mice. The increases in DTH and in ratios of TNFα/IL-10 CD4+ producing cells were however the strong correlates of protection which was confirmed by in vivo depletion with monoclonal antibodies, algorithm predicted CD4 and CD8 epitopes and a pronounced decrease in parasite load (90.5–88.23%; p = 0.011) that was long-lasting. No decrease in parasite load was detected after vaccination with the N-domain of NH36, in spite of the induction of IFN-γ/IL-10 expression by CD4+ T cells after challenge. Both peptides reduced the size of footpad lesions, but only the C-domain reduced the parasite load of mice challenged with L. amazonensis. The identification of the target of the immune response to NH36 represents a basis for the rationale development of a bivalent vaccine against leishmaniasis and for multivalent vaccines against NHs-dependent pathogens

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13