Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice

Gut-dwelling helminthes induce potent IL-4 and IL-13 dominated type 2 T helper cell (T H 2) immune responses, with IL-13 production being essential for Nippostrongylus brasiliensis expulsion. This T H 2 response results in intestinal inflammation associated with local infiltration by T cells and macrophages. The resulting increased IL-4/IL-13 intestinal milieu drives goblet cell hyperplasia, alternative macrophage activation and smooth muscle cell hypercontraction. In this study we investigated how IL-4-promoted T cells contributed to the parasite induced effects in the intestine. This was achieved using pan T cell-specific IL-4 receptor alpha-deficient mice (iLck cre IL-4Rα −/lox ) and IL-4Rα-responsive control mice. Global IL-4Rα −/− mice showed, as expected, impaired type 2 immunity to N. brasiliensis . Infected T cell-specific IL-4Rα-deficient mice showed comparable worm expulsion, goblet cell hyperplasia and IgE responses to control mice. However, impaired IL-4-promoted T H 2 cells in T cell-specific IL-4Rα deficient mice led to strikingly reduced IL-4 production by mesenteric lymph node CD4 + T cells and reduced intestinal IL-4 and IL-13 levels, compared to control mice. This reduced IL-4/IL-13 response was associated with an impaired IL-4/IL-13-mediated smooth muscle cell hypercontractility, similar to that seen in global IL-4Rα −/− mice. These results demonstrate that IL-4-promoted T cell responses are not required for the resolution of a primary N. brasiliensis infection. However, they do contribute significantly to an important physiological manifestation of helminth infection; namely intestinal smooth muscle cell-driven hypercontractility

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

Prevalência da doença de Chagas em gestantes da região sul do Rio Grande do Sul Prevalence of Chagas disease among pregnant women in the southern region of Rio Grande do Sul

Anticorpos antiTrypanosoma cruzi no cordão umbilical de 351 parturientes da Cidade de Pelotas, RS foram pesquisados a fim de investigar a prevalência da doença de Chagas em gestantes. Um (0,3%) caso foi identificado, não sendo detectada transmissão congênita. Salienta-se a importância da investigação da doença de Chagas em gestantes de zonas endêmicas ou provenientes destas.<br>Anti-Trypanosoma cruzi antibodies in the umbilical cord of 351 parturients in the city of Pelotas, Rio Grande do Sul were investigated to determine the prevalence of Chagas disease among pregnant women. One case was identified (0.3%), without detection of congenital transmission. This highlights the importance of investigating Chagas disease among pregnant women living in or originating from endemic areas

A diplodocid sauropod survivor from the early cretaceous of South America.

Diplodocids are by far the most emblematic sauropod dinosaurs. They are part of Diplodocoidea, a vast clade whose other members are well-known from Jurassic and Cretaceous strata in Africa, Europe, North and South America. However, Diplodocids were never certainly recognized from the Cretaceous or in any other southern land mass besides Africa. Here we report a new sauropod, Leikupal laticauda gen. et sp. nov., from the early Lower Cretaceous (Bajada Colorada Formation) of Neuquén Province, Patagonia, Argentina. This taxon differs from any other sauropod by the presence of anterior caudal transverse process extremely developed with lateroventral expansions reinforced by robust dorsal and ventral bars, very robust centroprezygapophyseal lamina in anterior caudal vertebra and paired pneumatic fossae on the postzygapophyses in anterior-most caudal vertebra. The phylogenetic analyses support its position not only within Diplodocidae but also as a member of Diplodocinae, clustering together with the African form Tornieria, pushing the origin of Diplodocoidea to the Middle Jurassic or even earlier. The new discovery represents the first record of a diplodocid for South America and the stratigraphically youngest record of this clade anywhere

Antiviral propierties of 5,5'-dithiobis-2-nitrobenzoic acid and bacitracin against T-tropic human immunodeficiency virus type 1

<p>Abstract</p> <p>Bacitracin and the membrane-impermeant thiol reagent 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) are agents known to inhibit protein disulfide isomerase (PDI), a cell-surface protein critical in HIV-1 entry therefore they are fusion inhibitors (FI). Here we investigated the possibility that Bacitracin and or DTNB might have other antiviral activities besides FI. By means of residual activity assays, we found that both compounds showed antiviral activity only to viruses T-tropic HIV-1 strain. Cell-based fusion assays showed inhibition on HeLa-CD4-LTR-β-gal (CD4) and HL2/3 cells treated with Bacitracin, and DTNB with the latest compound we observed fusion inhibition on both cells but strikingly in HL2/3 cells (expressing Env) indicating a possible activity on both, the cell membrane and the viral envelope. A time-of-addition experiment showed that both compounds act on HIV entry inhibition but DTNB also acts at late stages of the viral cycle. Lastly, we also found evidence of long-lasting host cell protection <it>in vitro </it>by DTNB, an important pharmacodynamic parameter for a topical microbicide against virus infection, hours after the extracellular drug was removed; this protection was not rendered by Bacitracin. These drugs proved to be leading compounds for further studies against HIV showing antiviral characteristics of interest.</p