Strain-dependent host transcriptional responses to toxoplasma infection are largely conserved in mammalian and avian hosts

Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response. © 2011 Ong et al

Morteros macroporosos para asentamiento y revestimiento.

The envelope of a building is responsible for its physical protection against external agents, including humidity and temperature. Thus, the present work seeks to evaluate the effect of air entraining admixtures (AEA) in mortars for laying and coating to improve their physical and thermal performances. The AEA generates macropores, interrupting the system of canaliculi that allows the capillary absorption of water. The AEA used is based on biodegradable surfactant molecules of Linear Alkyl Benzene Sodium Sulfonate. Results compare physical tests (water absorption, capillary coefficient, specific gravity, and mechanical strength), and thermal evaluation (thermal conductivity and specific heat) from two mortars mixtures with varying levels of AEA. Scanning electron microscopy (SEM) of the pore system were also analysed. All mixtures studied presented higher workability and cohesion, reduced thermal conductivity, decreased specific heat, and a reduction in the effects of water absorption, capillary elevation and specific gravity (density). In this sense, the durability of mortars to humidity effect is potentially improved, along with several other properties. Therefore, this work seeks to contribute to the quality of built environments, as well as to promote the technological development of cement-based composites.Los cerramientos de un edificio son responsables de su protecci?n f?sica contra agentes externos, incluida la humedad y la temperatura. Por lo tanto, el presente trabajo busca evaluar el efecto de los aditivos inclusores de aire (AEA) en los morteros para asentamiento y revestimiento para mejorar 30 sus rendimientos f?sicos y t?rmicos. Los AEA generan macroporos, interrumpiendo el sistema de canal?culos que permiten la absorci?n capilar del agua. El AEA utilizado se basa en mol?culas de un surfactante biodegradables - alquil benceno sulfonato de sodio lineal. Los resultados comparan pruebas f?sicas (absorci?n de agua, coeficiente capilar, masa espec?fica y resistencia mec?nica) y evaluaci?n t?rmica (conductividad t?rmica y calor espec?fico) de dos mezclas de morteros con niveles variables de AEA. Tambi?n se analiz? la microscop?a electr?nica de barrido (SEM) del sistema de poros. Todas las mezclas estudiadas presentaron mayor trabajabilidad y cohesi?n, reducci?n de la conductividad t?rmica, disminuci?n del calor espec?fico y reducci?n de los efectos de la absorci?n de agua, elevaci?n del capilar y gravedad espec?fica (densidad). En este sentido, la durabilidad de los morteros al efecto de la humedad es potencialmente mejorada, junto con varias otras propiedades. Por lo tanto, este trabajo busca contribuir a la calidad de los entornos construidos, as? como a promover el desarrollo tecnol?gico de compuestos de matriz cementicia

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Imaging Trans-Cellular Neurexin-Neuroligin Interactions by Enzymatic Probe Ligation

Neurexin and neuroligin are transmembrane adhesion proteins that play an important role in organizing the neuronal synaptic cleft. Our lab previously reported a method for imaging the trans-synaptic binding of neurexin and neuroligin called BLINC (Biotin Labeling of INtercellular Contacts). In BLINC, biotin ligase (BirA) is fused to one protein while its 15-amino acid acceptor peptide substrate (AP) is fused to the binding partner. When the two fusion proteins interact across cellular junctions, BirA catalyzes the site-specific biotinylation of AP, which can be read out by staining with streptavidin-fluorophore conjugates. Here, we report that BLINC in neurons cannot be reproduced using the reporter constructs and labeling protocol previously described. We uncover the technical reasons for the lack of reproducibilty and then re-design the BLINC reporters and labeling protocol to achieve neurexin-neuroligin BLINC imaging in neuron cultures. In addition, we introduce a new method, based on lipoic acid ligase instead of biotin ligase, to image trans-cellular neurexin-neuroligin interactions in human embryonic kidney cells and in neuron cultures. This method, called ID-PRIME for Interaction-Dependent PRobe Incorporation Mediated by Enzymes, is more robust than BLINC due to higher surface expression of lipoic acid ligase fusion constructs, gives stronger and more localized labeling, and is more versatile than BLINC in terms of signal readout. ID-PRIME expands the toolkit of methods available to study trans-cellular protein-protein interactions in living systems.National Institutes of Health (U.S.) (DP1 OD003961

Mast Cells Express 11 beta-hydroxysteroid Dehydrogenase Type 1: A Role in Restraining Mast Cell Degranulation:a role in restraining mast cell degranulation

Mast cells are key initiators of allergic, anaphylactic and inflammatory reactions, producing mediators that affect vascular permeability, angiogenesis and fibrosis. Glucocorticoid pharmacotherapy reduces mast cell number, maturation and activation but effects at physiological levels are unknown. Within cells, glucocorticoid concentration is modulated by the 11β-hydroxysteroid dehydrogenases (11β-HSDs). Here we show expression and activity of 11β-HSD1, but not 11β-HSD2, in mouse mast cells with 11β-HSD activity only in the keto-reductase direction, regenerating active glucocorticoids (cortisol, corticosterone) from inert substrates (cortisone, 11-dehydrocorticosterone). Mast cells from 11β-HSD1-deficient mice show ultrastructural evidence of increased activation, including piecemeal degranulation and have a reduced threshold for IgG immune complex-induced mast cell degranulation. Consistent with reduced intracellular glucocorticoid action in mast cells, levels of carboxypeptidase A3 mRNA, a glucocorticoid-inducible mast cell-specific transcript, are lower in peritoneal cells from 11β-HSD1-deficient than control mice. These findings suggest that 11β-HSD1-generated glucocorticoids may tonically restrain mast cell degranulation, potentially influencing allergic, anaphylactic and inflammatory responses

The Challenges of the External Vote

UID/CPO/04627/2019Over the last few decades, emigrants all over the world have gained expanded voting rights. Despite the normative debates about this issue, there are few empirical studies on why states decide to implement external voting and how electoral systems perform. This chapter seeks to fill this gap by looking at the Portuguese case. Our study suggests that a combination of political and socio-economic factors explains the implementa tion of external voting. On the other hand, the interests of political parties and the low level of civil society engagement are key factors in the failure of both electoral reforms and attempts to overcome the shortcomings of external voting.publishersversionpublishe