T-Cell Memory Responses Elicited by Yellow Fever Vaccine are Targeted to Overlapping Epitopes Containing Multiple HLA-I and -II Binding Motifs

The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env) and nonstructural (NS) proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4+ and CD8+ T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines. © 2013 de Melo et al

Animal Performance in Signalgrass Monoculture or in Silvopastoral Systems

Silvopastoral systems (SPS) can increase overall productivity and long-term income due to the simultaneous production of trees, forage, and livestock. This 2-yr study evaluated animal performance and herbage responses in C4-grass monoculture or in SPS in the sub-humid tropical region of Brazil. The experimental design was randomized complete block with three replications. Treatments were: Urochloa decumbens (Stapf.) R. Webster (Signalgrass) + Mimosa caesalpiniifolia Benth (SPS-Mimosa); Signalgrass + Gliricidia sepium (Jacq.) Kunth ex Walp (SPS-Gliricidia); and Signalgrass monoculture (SM). Response variables included herbage and livestock responses. Cattle were managed under continuous stocking with variable stocking rate. There was interaction between treatment × month for herbage mass. Green herbage accumulation rate ranged from 20 to 80 kg DM ha-1d-1 across months, with SPS-Mimosa presenting lower rates. Average daily gain was greater in SPS-Gliricidia, followed by SM, and SPS-Mimosa, respectively (0.77; 0.56; 0.23 kg d-1), varying across months. Stocking rate ranged from 0.86 to 1.6 AU ha-1. Total gain per area during the experimental period was greater for SPS-Gliricidia (423 kg BW ha-1), followed by signalgrass in monoculture (347 kg BW ha-1), and SPS-Mimosa (50 kg BW ha-1). Silvopasture systems using signalgrass and gliricidia enhanced livestock gains compared with signalgrass in monoculture, and mimosa trees outcompeted signalgrass, reducing livestock gains. Silvopasture systems with tree legumes have potential to provide numerous ecosystem services and reduce C footprint of livestock systems in the tropics, however, the choice of tree species is key and determined by which ecosystem service is prioritized

Effects of the aqueous extract of hyptis pectinata on liver regeneration after 70% partial hepatectomy preliminar results

O uso de plantas medicinais tem aumentado bastante na população mundial. O objetivo desta pesquisa é avaliar os efeitos do extrato aquoso das folhas da Hyptis pectinata, popularmente conhecida como "sambacaitá" ou "canudinho", sobre a regeneração hepática após hepatectomia parcial de 70%. Foram utilizados 24 ratos, divididos em 4 grupos: grupo OS, em que se realizou operação simulada e aplicação oral de água destilada por 4 dias; grupo OSD200, também submetido à laparotomia com manipulação do fígado e aplicação de 200 mg de extrato/Kg de animal durante o mesmo período; grupo HP, hepatectomizado a 70% após 4 dias de aplicação por via oral de água destilada; e grupo HPD200, hepatectomizado a 70% após 4 dias de administração de 200 mg extrato/Kg de animal. Foram dosadas fosfatase alcalina, bilirrubina total e as aminotransferases e estudou-se o estado III da função mitocondrial. O grupo OSD200, quando comparado ao OS, apresentou redução significativa da fosfatase alcalina. O grupo HPD200, em comparação ao HP, teve redução estatisticamente significativa no nível da AST e do estado III da função mitocondrial. _________________________________________________________________________________________ ABSTRACT: The use of medicinal plants has strongly increased by the world population. The objetive of this study is to assess the effects of the aqueous extract of Hyptis pectinata leaves, popularly known as "sambacaitá" or "canudinho", on liver regeneration after 70% partial hepatectomy. Twenty four rats were divided into 4 groups: group OS, submitted to sham operation and oral administration of distilled water during 4 days; group OSD200, also submitted to sham operation and ingestion of 200 mg of extract/Kg of animal for the same period of time; group HP, which underwent 70% hepatectomy after 4 days of distilled water administration; and group HPD200, which underwent 70% hepatectomy after 4 days of oral administration of 200 mg of extract/Kg of animal. Alkaline phosphatase, total bilirubin and the serum level of aminotransferases were measured and state III of mitochondrial respiratory activity was assessed. Group OSD200, when compared to OS, presented significant decrease of alcaline fosfatase. Group HPD200, when compared to HP, showed statistically significant decrease of AST level and state III respiratory process

Soil biochemistry and microbial activity in vineyards under conventional and organic management at Northeast Brazil.

The São Francisco Submedium Valley is located at the Brazilian semiarid region and is an important center for irrigated fruit growing. This region is responsible for 97% of the national exportation of table grapes, including seedless grapes. Based on the fact that orgThe São Francisco Submedium Valley is located at the Brazilian semiarid region and is an important center for irrigated fruit growing. This region is responsible for 97% of the national exportation of table grapes, including seedless grapes. Based on the fact that organic fertilization can improve soil quality, we compared the effects of conventional and organic soil management on microbial activity and mycorrhization of seedless grape crops. We measured glomerospores number, most probable number (MPN) of propagules, richness of arbuscular mycorrhizal fungi (AMF) species, AMF root colonization, EE-BRSP production, carbon microbial biomass (C-MB), microbial respiration, fluorescein diacetate hydrolytic activity (FDA) and metabolic coefficient (qCO2). The organic management led to an increase in all variables with the exception of EE-BRSP and qCO2. Mycorrhizal colonization increased from 4.7% in conventional crops to 15.9% in organic crops. Spore number ranged from 4.1 to 12.4 per 50 g-1 soil in both management systems. The most probable number of AMF propagules increased from 79 cm-3 soil in the conventional system to 110 cm-3 soil in the organic system. Microbial carbon, CO2 emission, and FDA activity were increased by 100 to 200% in the organic crop. Thirteen species of AMF were identified, the majority in the organic cultivation system. Acaulospora excavata, Entrophospora infrequens, Glomus sp.3 and Scutellospora sp. were found only in the organically managed crop. S. gregaria was found only in the conventional crop. Organically managed vineyards increased mycorrhization and general soil microbial activity

BCS to Bose Crossover in Anisotropic Superconductors

In this work we use functional integral techniques to examine the nearest neighbour attractive Hubbard model on a quasi-2D lattice. It is a simple phenomenological model for the high-Tc cuprates that allows both extended (non-local) s- and d-wave singlet superconductivity as well as mixed symmetry states. The Hartree-Gor'kov mean field theory of the model has a finite temperature phase diagram which shows a transition from pure s-wave to pure d-wave superconductivity, via a mixed symmetry s+id state, as a function of doping. Including Gaussian fluctuations we examine the crossover from weak-coupling BCS superconductivity to the strong-coupling Bose-Einstein condensation of composite s- or d-wave bosons and comment on the origin and symmetry of the pseudogap.Comment: 20 pages inc. 13 figure

Galaxy Collisions - Dawn of a New Era

The study of colliding galaxies has progressed rapidly in the last few years, driven by observations with powerful new ground and space-based instruments. These instruments have used for detailed studies of specific nearby systems, statistical studies of large samples of relatively nearby systems, and increasingly large samples of high redshift systems. Following a brief summary of the historical context, this review attempts to integrate these studies to address the following key issues. What role do collisions play in galaxy evolution, and how can recently discovered processes like downsizing resolve some apparently contradictory results of high redshift studies? What is the role of environment in galaxy collisions? How is star formation and nuclear activity orchestrated by the large scale dynamics, before and during merger? Are novel modes of star formation involved? What are we to make of the association of ultraluminous X-ray sources with colliding galaxies? To what do degree do mergers and feedback trigger long-term secular effects? How far can we push the archaeology of individual systems to determine the nature of precursor systems and the precise effect of the interaction? Tentative answers to many of these questions have been suggested, and the prospects for answering most of them in the next few decades are good.Comment: 44 pages, 9 figures, review article in press for Astrophysics Update Vol.

Testing CPT- and Lorentz-odd electrodynamics with waveguides

We study CPT- and Lorentz-odd electrodynamics described by the Standard Model Extension. Its radiation is confined to the geometry of hollow conductor waveguide, open along $z$. In a special class of reference frames, with vanishing both 0-th and $z$ components of the background field, $(k_{\rm AF})^\mu$, we realize a number of {\em huge and macroscopically detectable} effects on the confined waves spectra, compared to standard results. Particularly, if $(k_{\rm AF})^\mu$ points along $x$ (or $y$) direction only transverse electric modes, with $E_z=0$, should be observed propagating throughout the guide, while all the transverse magnetic, $B_z=0$, are absent. Such a strong mode suppression makes waveguides quite suitable to probe these symmetry violations using a simple and easily reproducible apparatus.Comment: 11pages, double-spacing, tex forma

Endotoxin tolerance and cross-tolerance in mast cells involves TLR4, TLR2 and FcεR1 interactions and SOCS expression: perspectives on immunomodulation in infectious and allergic diseases

<p>Abstract</p> <p>Background</p> <p>The study of the endotoxin tolerance phenomenon in light of the recently defined roles of mast cells and toll-like receptors as essential components of the innate immune response and as orchestrators of acquired immunity may reveal potentially useful mechanisms of immunomodulation of infectious and allergic inflammatory responses, such as sepsis or asthma. Here we evaluated the phenomenon of direct tolerance of endotoxins, as well as the induction of cross-tolerance and synergism by stimulation with toll-like receptor-2 (TLR2) and FcεR1 agonists, in murine mast cells prestimulated with lipopolysaccharide (LPS). Additionally, we evaluated some stimulatory and inhibitory signaling molecules potentially involved in these phenomena.</p> <p>Methods</p> <p>MC/9 cells and primary bone marrow-derived mast cells obtained from C57BL/6 and TLR4^-/-knock-out mice were sensitized to DNP-HSA (antigen) by incubation with DNP-IgE and were prestimulated with LPS for 18 hr prior to stimulation. Cultures were stimulated with LPS or Pam3Cys-Ser-(Lys)4 3HCl (P3C), a TLR2 agonist, individually or in combination with antigen. The production of IL-6 and TNFα, the phosphorylation of NFκB and p38 MAPK, and the expression of TLR4 and SOCS-1 and -3 were analyzed.</p> <p>Results</p> <p>We found that production of TNFα and IL-6 in murine mast cells that have been pretreated with LPS and challenged with TLR4 (LPS) or -2 (P3C) agonists was reduced, phenomena described as endotoxin tolerance (LPS) and cross-tolerance (P3C), respectively. The expression of TLR4 was not affected by LPS pretreatment. Our results show that the FcεR1 agonist DNP-HSA (antigen) interacts synergistically with LPS or P3C to markedly enhance production of cytokines (TNFα and IL-6). This synergistic effect with LPS and P3C was also attenuated by LPS pretreatment and was mediated by TLR4. These results may be attributed to the reduction in phosphorylation of the mitogen-activated protein kinase (MAPK), p38, and the transcription factor NFκB, as well as to an increase in the expression of the suppressors of cytokine signaling (SOCS)-1 and -3 proteins in LPS-pretreated mast cells.</p> <p>Conclusions</p> <p>These findings can be explored with respect to the modulation of inflammatory responses associated with infectious and allergic processes in future studies.</p