102,230 research outputs found
A Meaning of Baroque in terms of Space Syntax
A city is a spatial system that is generated in the process of searching for an ideal form. From the structure of a city, we can find paradigms of the past in which worldviews of the society are instilled. Baroque, to be studied in this paper, is interpreted as a change from ′limitation′ to ′infinity′. There are many studies that investigated Baroque but they see the change from a single viewpoint of either cosmology or practicality. The purpose of this study is, therefore, to combine these two viewpoints for a comprehensive understanding of what paradigm has formed Baroque cities. Practicality is revealed by means of Space Syntax and our new concept, Urban Entropy Coefficient (: UEC), which is then related to cosmology. We conclude that the intention of Baroque was to configure a Multi-Center layout for the dynamic function of the city
Shivji, Issa G. Law, State and the Working Class in Tanzania, c. 1920-1964
Gutkind Peter C. Shivji, Issa G. Law, State and the Working Class in Tanzania, c. 1920-1964. In: Cahiers d'études africaines, vol. 27, n°107-108, 1987. Mémoires, Histoires, Identités. pp. 450-452
PRECOG: PREdicting COupling probabilities of G-protein coupled receptors
G-protein coupled receptors (GPCRs) control multiple physiological states by transducing a multitude of extracellular stimuli into the cell via coupling to intra-cellular heterotrimeric G-proteins. Deciphering which G-proteins couple to each of the hundreds of GPCRs present in a typical eukaryotic organism is therefore critical to understand signalling. Here, we present PRECOG (precog.russelllab.org): a web-server for predicting GPCR coupling, which allows users to: (i) predict coupling probabilities for GPCRs to individual G-proteins instead of subfamilies; (ii) visually inspect the protein sequence and structural features that are responsible for a particular coupling; (iii) suggest mutations to rationally design artificial GPCRs with new coupling properties based on predetermined coupling features
Intercontinental dissemination of IMP-13-producing Pseudomonas aeruginosa belonging in Sequence Type 621
IMP-type metallo-β-lactamases (MBLs) were the first acquired MBLs detected in Gram-negative pathogens, in the early 1990s, and are among the most relevant due to their worldwide distribution.Fil: Santella, Gisela Natalia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Pollini, Simona. Universita Degli Studi Di Siena; ItaliaFil: Docquier, Jean-Denis. Universita Degli Studi Di Siena; ItaliaFil: Mereuta, Ana Irina. Universitatea de Medicina si Farmacie “Grigore T. Popa”; RumaniaFil: Gutkind, Gabriel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Rossolini, Gian Maria. Universita Degli Studi Di Siena; ItaliaFil: Radice, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin
Prevalence of Plasmid Mediated Quinolone Resistance Determinants among Oxyiminocephalosporin Resistant Enterobacteriaceae in Argentina.
High quinolone resistance rates were observed among oxyiminocephalosporin resistant enterobacteria. In the present study, we searched for the prevalence of plasmid mediated quinolone resistance (PMQR) genes within the 55 oxyiminocephalosporin resistant enterobacteria collected in a previous survey. The main PMQR determinants were aac(6´)-Ib-cr and qnrB corresponding to 42.4% and 33.3%, respectively. aac(6?)-Ib-cr was more frequently present in CTX-M-15 producing isolates, while QnrB was homogeneously distributed in all CTX-M producers.Fil: Rincón Cruz, Giovanna. Universidad Industrial Santander; Colombia;Fil: Radice, Marcela Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina;Fil: Sennati, Samanta. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Inmunologia, Genetica y Metabolismo; Argentina;Fil: Pallecchi, Lucia. Università de Sienna; Italia;Fil: Rosollini, Gian Maria. Università de Sienna; Italia;Fil: Gutkind, Gabriel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Inmunologia, Genetica y Metabolismo; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;Fil: Di Conza, José Alejandro. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Cátedra de Microbiología Parasitología e Inmunologia; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Cross talk between the bombesin neuropeptide receptor and Sonic hedgehog pathways in small cell lung carcinoma
Small cell lung carcinoma (SCLC) often features the upregulation of the Sonic hedgehog (Shh) pathway leading to activation of Gli transcription factors. SCLC cells secrete bombesin (BBS)-like neuropeptides that act as autocrine growth factors. Here, we show that SCLC tumor samples feature co-expression of Shh and BBS-cognate receptor (gastrin-releasing peptide receptor (GRPR)). We also demonstrate that BBS activates Gli in SCLC cells, which is crucial for BBS-mediated SCLC proliferation, because cyclopamine, an inhibitor of the Shh pathway, hampered the BBS-mediated effects. BBS binding to GRPR stimulated Gli through its downstream Gαq and Gα12/13 GTPases, and consistently, other Gαq and Gα13 coupled receptors (such as muscarinic receptor, m1, and thrombin receptor, PAR-1) and constitutively active GαqQL and Gα12/13QL mutants stimulated Gli. By using cells null for Gαq and Gα12/13, we demonstrate that these G proteins are strictly necessary for Gli activation by BBS. Moreover, by using constitutively active Rho small G-protein (Rho QL) as well as its inhibitor, C3 toxin, we show that Rho mediates G-protein-coupled receptor (GPCR)-, Gαq- and Gα12/13-dependent Gli stimulation. At the molecular level, BBS caused a significant increase in Shh gene transcription and protein secretion that was dependent on BBS-induced GPCR/Gαq-12/13/Rho mediated activation of nuclear factor κB (NFκB), which can stimulate a NF-κB response element in the Shh gene promoter. Our data identify a novel molecular network acting in SCLC linking autocrine BBS and Shh circuitries and suggest Shh inhibitors as novel therapeutic strategies against this aggressive cancer type
Interaction of cefotetan and the metallo-beta-lactamases produced in Aeromonas spp. and in vitro activity
Aeromonas spp. are increasingly being recognized as human pathogens. The presence of metallo-beta-lactamases in these organisms represents a potential problem in antimicrobial therapy. Mechanism-based inactivators of beta-lactamases are used to overcome the resistance of clinical pathogens to beta-lactam antibiotics, but no clinical useful inhibitors of the metallo-beta-lactamases are presently known. Studying the interaction between cefotetan and Aeromonas spp. producing metallo-beta-lactamase activity, we observed that cefotetan behaved as a transient inactivator for both the crude extracts of Aeromonas strains and the purified enzymes from Aeromonas hydrophila AE036 and Aeromonas schubertii MNSA20. The direct hydrolysis of cefotetan showed that it was a poor substrate for both purified enzymes. In view of the minimum inhibitory concentrations, cefotetan shows to be a useful antimicrobial agent against Aeromonas spp. Copyright (C) 2000 S. Karger AG, Basel
Interaction of cefotetan and the metallo-β-lactamases produced in Aeromonas spp. and in vitro activity
Aeromonas spp, are increasingly being recognized as human pathogens. The presence of metallo-β-lactamases in these organisms represents a potential problem in antimicrobial therapy. Mechanism-based inactivators of β-lactamases are used to overcome the resistance of clinical pathogens to β-lactam antibiotics, but no clinical useful inhibitors of the metallo-β-lactamases are presently known. Studying the interaction between cefotetan and Aeromonas spp. producing metallo-β-lactamase activity, we observed that cefotetan behaved as a transient inactivator for both the crude extracts of Aeromonas strains and the purified enzymes from Aeromonas hydrophila AE036 and Aeromonas schubertii MNSA20. The direct hydrolysis of cefotetan showed that it was a poor substrate for both purified enzymes. In view of the minimum inhibitory concentrations, cefotetan shows to be a useful antimicrobial agent against Aeromonas spp. Copyright (C) 2000 S. Karger AG. Basel
Cross talk between the bombesin neuropeptide receptor and Sonic hedgehog pathways in small cell lung carcinoma
Small cell lung carcinoma (SCLC) often features the upregulation of the Sonic hedgehog (Shh) pathway leading to activation of Gli transcription factors. SCLC cells secrete bombesin (BBS)-like neuropeptides that act as autocrine growth factors. Here, we show that SCLC tumor samples feature co-expression of Shh and BBS-cognate receptor (gastrin-releasing peptide receptor (GRPR)). We also demonstrate that BBS activates Gli in SCLC cells, which is crucial for BBS-mediated SCLC proliferation, because cyclopamine, an inhibitor of the Shh pathway, hampered the BBS-mediated effects. BBS binding to GRPR stimulated Gli through its downstream Gαq and Gα12/13 GTPases, and consistently, other Gαq and Gα13 coupled receptors (such as muscarinic receptor, m1, and thrombin receptor, PAR-1) and constitutively active GαqQL and Gα12/13QL mutants stimulated Gli. By using cells null for Gαq and Gα12/13, we demonstrate that these G proteins are strictly necessary for Gli activation by BBS. Moreover, by using constitutively active Rho small G-protein (Rho QL) as well as its inhibitor, C3 toxin, we show that Rho mediates G-protein-coupled receptor (GPCR)-, Gαq- and Gα12/13-dependent Gli stimulation. At the molecular level, BBS caused a significant increase in Shh gene transcription and protein secretion that was dependent on BBS-induced GPCR/Gαq-12/13/Rho mediated activation of nuclear factor κB (NFκB), which can stimulate a NF-κB response element in the Shh gene promoter. Our data identify a novel molecular network acting in SCLC linking autocrine BBS and Shh circuitries and suggest Shh inhibitors as novel therapeutic strategies against this aggressive cancer type
The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor promotes endothelial cell survival through the activation of Akt/protein kinase B
The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor (KSHV-GPCR) is a key molecule in the pathogenesis of Kaposi's sarcoma, playing a central role in the promotion of vascular endothelial growth factor (VEGF)-driven angiogenesis and spindle cell proliferation. We previously have shown that KSHV-GPCR has oncogenic potential when overexpressed in fibroblasts and is responsible for the expression and secretion of VEGF through the regulation of different intracellular signaling pathways (A. Sodhi et al., Cancer Res., 60: 4873-4880, 2000; C. Bais et al., Nature, 391: 86-89, 1998). Here, we describe that this constitutively active G protein-coupled receptor is able to promote cell survival in primary human umbilical vein endothelial cells and that this effect is independent of its ability to secrete VEGF because it is not prevented by the expression of antisense constructs for VEGF or the addition of VEGF-blocking antibodies. Instead we found that ectopic expression of KSHV-GPCR potently induces the kinase activity of Akt/protein kinase B in a dose-dependent manner and triggers its translocation to the plasma membrane. This signaling pathway requires the function of phosphatidylinositol 3'-kinase and is dependent on betagamma subunits released from both pertussis toxin-sensitive and -insensitive G proteins. Furthermore, we found that KSHV-GPCR is able to protect human umbilical vein endothelial cells from the apoptosis induced by serum deprivation and that both wortmannin and the expression of a kinase-deficient Akt K179M mutant are able to block this effect. Finally, we observed that the Akt K179M protein also inhibits the activation of nuclear factor-KB induced by KSHV-GPCR, suggesting that this transcription factor may represent one of the putative downstream targets for Akt in the survival-signaling pathway. These results provide further knowledge in the elucidation of the signal transduction pathways activated by KSHV-GPCR and support its key role in promoting the survival of viral-infected cells. Moreover, the present findings also emphasize the importance of this G protein-coupled receptor in the development of KSHV-related neoplasias
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