Sonic hedgehog-Dependent Induction of MicroRNA 31 and MicroRNA 150 Regulates Mycobacterium bovis BCG-Driven Toll-Like Receptor 2 Signaling

Hedgehog (HH) signaling is a significant regulator of cell fate decisions during embryogenesis, development, and perpetuation of various disease conditions. Testing whether pathogen-specific HH signaling promotes unique innate recognition of intracellular bacteria, we demonstrate that among diverse Gram-positive or Gram-negative microbes, Mycobacterium bovis BCG, a vaccine strain, elicits a robust activation of Sonic HH (SHH) signaling in macrophages. Interestingly, sustained tumor necrosis factor alpha (TNF-alpha) secretion by macrophages was essential for robust SHH activation, as TNF-alpha(-/-) macrophages exhibited compromised ability to activate SHH signaling. Neutralization of TNF-alpha or blockade of TNF-alpha receptor signaling significantly reduced the infection-induced SHH signaling activation both in vitro and in vivo. Intriguingly, activated SHH signaling downregulated M. bovis BCG-mediated Toll-like receptor 2 (TLR2) signaling events to regulate a battery of genes associated with divergent functions of M1/M2 macrophages. Genome-wide expression profiling as well as conventional gain-of-function or loss-of-function analysis showed that SHH signaling-responsive microRNA 31 (miR-31) and miR-150 target MyD88, an adaptor protein of TLR2 signaling, thus leading to suppression of TLR2 responses. SHH signaling signatures could be detected in vivo in tuberculosis patients and M. bovis BCG-challenged mice. Collectively, these investigations identify SHH signaling to be what we believe is one of the significant regulators of host-pathogen interactions.

Sonic hedgehog-responsive lipoxygenases and cyclooxygenase-2 modulate Dectin-1-induced inflammatory cytokines

Immune responses during fungal infections are predominately mediated by 5/15-lipoxygenases (LO)-or cyclooxygenase (COX)-2-catalysed bioactive eicosanoid metabolites like leukotrienes, lipoxins and prostaglandins. Although few host mediators of fungi-triggered eicosanoid production have been established, the molecular mechanism of expression and regulation of 5-LO, 15-LO and COX-2 are not well-defined. Here, we demonstrate that, macrophages infected with representative fungi Candida albicans, Aspergillus flavus or Aspergillus fumigatus or those treated with Curdlan, a selective agonist of pattern recognition receptor for fungi Dectin-1, displays increased expression of 5-LO, 15-LO and COX-2. Interestingly, Dectin-1-responsive Syk pathway activates mTOR-sonic hedgehog (SHH) signaling cascade to stimulate the expression of these lipid metabolizing enzymes. Loss-of-function analysis of the identified intermediaries indicates that while Syk-mTOR-SHH pathway-induced 5-LO and 15-LO suppressed the Dectin-l-responsive pro-inflammatory signature cytokines like TNE-alpha, IL-1 beta and IL-12, Syk-mTOR-SHH-induced COX-2 positively regulated these cytokines. Dectin-1-stimulated IL-6, however, is dependent on 5-LO, 15-LO and COX-2 activity. Together, the current study establishes Dectin-1-arbitrated host mediators that direct the differential regulation of immune responses during fungal infections and thus are potential candidates of therapeutic intervention. (C) 2015 Elsevier Ltd. All rights reserved.

Mycobacteria-responsive sonic hedgehog signaling mediates programmed death-ligand 1-and prostaglandin E-2-induced regulatory T cell expansion

CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) are exploited by mycobacteria to subvert the protective host immune responses. The Treg expansion in the periphery requires signaling by professional antigen presenting cells and in particularly dendritic cells (DC). However, precise molecular mechanisms by which mycobacteria instruct Treg expansion via DCs are not established. Here we demonstrate that mycobacteria-responsive sonic hedgehog (SHH) signaling in human DCs leads to programmed death ligand-1 (PD-L1) expression and cyclooxygenase (COX)-2-catalyzed prostaglandin E-2 (PGE(2)) that orchestrate mycobacterial infection-induced expansion of Tregs. While SHH-responsive transcription factor GLI1 directly arbitrated COX-2 transcription, specific microRNAs, miR-324-5p and miR-338-5p, which target PD-L1 were downregulated by SHH signaling. Further, counter-regulatory roles of SHH and NOTCH1 signaling during mycobacterial-infection of human DCs was also evident. Together, our results establish that Mycobacterium directs a fine-balance of host signaling pathways and molecular regulators in human DCs to expand Tregs that favour immune evasion of the pathogen.

Cultura de consumo y ciudadanía activa en la sociedad contemporánea: discursos y prácticas convencionales y post-convencionales en la generación del baby-boom

627 p.

Report on sonic tracking of salmon - Ribble Estuary, 1980-82

The report looks at trials and results of sonic tracking devices. The report includes an appendix on a salmon tracking exercise using oxygen sensing ultrasonic transmitting tags which was carried out on the Ribble Estuary during the period 8th July 1982 to 19th July, 1982. The tags used were developed and manufactured by Aberdeen University and Zootelemetry Research Laboratory Ltd. of Aberdeen, working under contract from the Water Research Centre.

Redclaw crayfish aquaculture in Ecuador: the new boom?

Introduction of red claw crayfish (Cherax quadricarinatus) in Ecuador is presented together with the status and future of crayfish culture in the country.

Os fatores determinantes do boom do mercado imobiliário residencial do Rio de Janeiro entre 2005 e 2010

O mercado imobiliário brasileiro está passando pelo maior boom que já ocorreu no mundo que, por sua vez, envolve uma complexa interação entre os agentes de oferta e de demanda. Os principais fatores que têm impactado a demanda por imóveis no período recente são o aumento da renda média e a expansão do mercado de crédito. Pelo lado da oferta, é a escassez de terrenos edificáveis, dificultada, ainda, pela legislação de proteção ao meio ambiente, justificando o alto déficit habitacional. O resultado dos três fatores que, juntos, pressionam a demanda para cima e a oferta para baixo, acarreta no aumento dos preços dos imóveis residenciais em todo o país. No caso específico do Rio de Janeiro, levam-se em conta as externalidades positivas geradas pelo aumento dos investimentos em infraestrutura para a realização da Copa do Mundo de 2014 e dos Jogos Olímpicos de 2016, incluindo a redução da violência em determinadas áreas com a implantação das Unidades de Polícia Pacificadora (UPPs).

Molecular characterization of common carp (Cyprinus carpio) Sonic Hedgehog and discovery of its maternal expression

Sonic hedgehog (Shh), one of important homologous members of the hedgehog (Hh) family in vertebrates, encodes a signaling molecule that is involved in short- or long-range patterning processes during embryogenesis. In zebrafish, maternal activity of Hh was found to be contributing to the formation of primary motoneurons. However, we found that all of the known Hh members were not maternally expressed in zebrafish. In the present study, full-length cDNA of common carp (Cyprinus carpio) Shh (cShh) was gained by degenerate reverse-transcription PCR (RT-PCR) and rapid amplification of cDNA ends. Sequence comparison shows that cShh coding sequence shares 93.4% identity with zebrafish Shh coding sequence, and their corresponding protein sequences have 91.9% similarity. Comparative analysis of Shh genomic sequences and Hh protein sequences from different species revealed that the genomic structures of Hh are conserved from invertebrate to vertebrate. In contrast to zebrafish Shh, cShh transcripts were detectable from one-cell stage by RT-PCR analysis. Whole mount in situ hybridization verified the maternal expression of Shh in common carp, which is, to our knowledge, the first report of that in vertebrates, suggesting that Shh might be responsible for the maternal Hh activity in common carp.

Sonic Geography, Place and Race in the Formation of Local Identity: Liverpool and Scousers

The concept of identity has attracted significant academic attention. This article unpacks what constitutes the Scouse identity, how it is constructed and its different dimensions, with particular reference to place, phonology and race. Its novelty lies in developing the underused concept of “sonic geography” to examine the extent to which sound, for example a distinctive accent and/or dialect, affects the construction of local identity. Empirically this is conducted through a detailed analysis of the Scouse, or Liverpudlian, identity. The article also deploys the concept of “sonic exclusion” to examine the role a distinguishing vernacular plays in shaping local identity and the extent to which it determines “who is in” and “who is out” as a Scouser. The conclusion is that an effective understanding of a Scouser is not only spatial – someone born in Liverpool – because the sonoric landscape of spoken Scouse, and thereby Scouse identity, extends beyond the contemporary political and geographic boundaries of the City of Liverpool.