Laminin-derived peptide AG73 regulates migration, invasion, and protease activity of human oral squamous cell carcinoma cells through syndecan-1 and beta 1 integrin

Squamous cell carcinoma is a prevalent head and neck tumor with high mortality. We studied the role played by laminin alpha 1 chain peptide AG73 on migration, invasion, and protease activity of cells (OSCC) from human oral squamous cell carcinoma. Immunohistochemistry and immunofluorescence analyzed expression of laminin alpha 1 chain and MMP9 in oral squamous cells carcinoma in vivo and in vitro. Migratory activity of AG73-treated OSCC cells was investigated by monolayer wound assays and in chemotaxis chambers. AG73-induced invasion was assessed in Boyden chambers. Invasion depends on MMPs. Conditioned media from cells grown on AG73 was subjected to zymography. We searched for AG73 receptors related to these activities in OSCC cells. Immunofluorescence analyzed AG73induced colocalization of syndecan-1 and beta 1 integrin. Cells had these receptors silenced by siRNA, followed by treatment with AG73 and analysis of migration, invasion, and protease activity. Oral squamous cell carcinoma expresses laminin alpha 1 chain and MMP9. OSCC cells treated with AG73 showed increased migration, invasion, and protease activity. AG73 induced colocalization of syndecan-1 and beta 1 integrin. Knockdown of these receptors decreased AG73-dependent migration, invasion, and protease activity. Syndecan-1 and beta 1 integrin signaling downstream of AG73 regulate migration, invasion, and MMP production by OSCC cells.

Cloud condensation nuclei from biomass burning during the Amazonian dry-to-wet transition season

Aircraft measurements of cloud condensation nuclei (CCN) during the Large-Scale Biosphere-Atmosphere Experiment in Amazonia (LBA) were conducted over the Southwestern Amazon region in September-October 2002, to emphasize the dry-to-wet transition season. The CCN concentrations were measured for values within the range 0.1-1.0% of supersaturation. The CCN concentration inside the boundary layer revealed a general decreasing trend during the transition from the end of the dry season to the onset of the wet season. Clean and polluted areas showed large differences. The differences were not so strong at high levels in the troposphere and there was evidence supporting the semi-direct aerosol effect in suppressing convection through the evaporation of clouds by aerosol absorption. The measurements also showed a diurnal cycle following biomass burning activity. Although biomass burning was the most important source of CCN, it was seen as a source of relatively efficient CCN, since the increase was significant only at high supersaturations.

Phylogenetic relationships and infrageneric classification of Epidendrum subgenus Amphiglottium (Laeliinae, Orchidaceae)

Epidendrum L. is the largest genus of Orchidaceae in the Neotropical region; it has an impressive morphological diversification, which imposes difficulties in delimitation of both infrageneric and interspecific boundaries. In this study, we review infrageneric boundaries within the subgenus Amphiglottium and try to contribute to the understanding of morphological diversification and taxa delimitation within this group. We tested the monophyly of the subgenus Amphiglottium sect. Amphiglottium, expanding previous phylogenetic investigations and reevaluated previous infrageneric classifications proposed. Sequence data from the trnL-trnF region were analyzed with both parsimony and maximum likelihood criteria. AFLP markers were also obtained and analyzed with phylogenetic and principal coordinate analyses. Additionally, we obtained chromosome numbers for representative species within the group. The results strengthen the monophyly of the subgenus Amphiglottium but do not support the current classification system proposed by previous authors. Only section Tuberculata comprises a well-supported monophyletic group, with sections Carinata and Integra not supported. Instead of morphology, biogeographical and ecological patterns are reflected in the phylogenetic signal in this group. This study also confirms the large variability of chromosome numbers for the subgenus Amphiglottium (numbers ranging from 2n = 24 to 2n = 240), suggesting that polyploidy and hybridization are probably important mechanisms of speciation within the group.

Gradual Decline in Malaria-Specific Memory T Cell Responses Leads to Failure to Maintain Long-Term Protective Immunity to Plasmodium chabaudi AS Despite Persistence of B Cell Memory and Circulating Antibody

The mechanisms responsible for the generation and maintenance of immunological memory to Plasmodium are poorly understood and the reasons why protective immunity in humans is so difficult to achieve and rapidly lost remain a matter for debate. A possible explanation for the difficulty in building up an efficient immune response against this parasite is the massive T cell apoptosis resulting from exposure to high-dose parasite Ag. To determine the immunological mechanisms required for long-term protection against P. chabaudi malaria and the consequences of high and low acute phase parasite loads for acquisition of protective immunity, we performed a detailed analysis of T and B cell compartments over a period of 200 days following untreated and drug-treated infections in female C57BL/6 mice. By comparing several immunological parameters with the capacity to control a secondary parasite challenge, we concluded that loss of full protective immunity is not determined by acute phase parasite load nor by serum levels of specific IgG2a and IgG1. Abs, but appears to be a consequence of the progressive decline in memory T cell response to parasites, which occurs similarly in untreated and drug-treated mice with time after infection. Furthermore, by analyzing adoptive transfer experiments, we confirmed the major role of CD4(+) T cells for guaranteeing long-term full protection against P. chabaudi malaria. The Journal of Immunology, 2008, 181: 8344-8355.

Hospital-based Surveillance to Evaluate the Impact of Rotavirus Vaccination in Sao Paulo, Brazil

Background: Brazil implemented routine immunization with the human rotavirus vaccine, Rotarix, in 2006 and vaccination coverage reached 81% in 2008 in Sao Paulo. Our aim was to assess the impact of immunization on the incidence of severe rotavirus acute gastroenteritis (AGE). Methods: We performed a 5-year (2004-2008) prospective surveillance at a sentinel hospital in Sao Paulo, with routine testing for rotavirus in all children less than 5 years of age hospitalized with AGE. Genotypes of positive samples were determined by reverse transcription polymerase chain reaction. Results: During the study, 655 children hospitalized with AGE were enrolled; of whom 169 (25.8%) were positive for rotavirus. In the post-vaccine period, a 59% reduction in the number of hospitalizations of rotavirus AGE and a 42.2% (95% confidence interval [CI], 18.6%-59.0%; P = 0.001) reduction in the proportion of rotavirus-positive results among children younger than 5 years were observed, with the greatest decline among infants (69.2%; 95% CI, 24.7%-87.4%; P = 0.004). Furthermore, the number of all-cause hospitalizations for AGE was reduced by 29% among children aged <5 years. The onset and peak incidences of rotavirus AGE occurred 3 months later in the 2007 and 2008 seasons compared with previous years. Genotype G2 accounted for 15%, 70%, and 100% of all cases identified, respectively, in 2006, 2007, and 2008. Conclusions: After vaccine implementation, a marked decline in rotavirus AGE hospitalizations was demonstrated among children younger than 5 years of age, with the greatest reduction in the age groups targeted for vaccination. The predominance of genotype G2P[4] highlights the need of continued postlicensure surveillance studies.

Thionicotinamide SAM on Gold: Adsorption Studies and Electroactivity

STM and impedance results of the self-assembled monolayer (SAM) formed with thionicotinamide (TNA) on gold indicate the presence of defects that increase with the immersion time of the electrode in the TNA solution affecting the SAM electroactivity toward the electron transfer reaction of the cytochrome e metalloprotein and [Fe(CN)(6)](4-) and [Ru(NH(3))(6)](3+) complexes. It was observed that this electroactivity was also affected by the pH of the electrolyte solution. SERS and STM data indicate sulfur coordination to the surface with contribution of the NH(2) group. From the dependence of the TNA surface coverage on the temperature and concentration in solution, thermodynamic parameters of adsorption were determined.

Alkaloids from the Bark of Guatteria hispida and Their Evaluation as Antioxidant and Antimicrobial Agents

Phytochemical investigation of the bark of Guatteria hispida afforded three new alkaloids, 9-methoxy-O-methylmoschatoline (1), 9-methoxyisomoschatoline (2), and isocerasonine (3), along with 10 known alkaloids, 8-oxopseudopalmatine (4), O-methylmoschatoline (5), lysicamine (6), liriodenine (7), 10-methoxyliriodenine (8), nornuciferine (9), anonaine (10), xylopine (11), coreximine (12), and isocoreximine (13). The major compounds, 2, 6, 12, and 13, showed significant antioxidant capacity in the ORAC(FL), assay. Compounds 5, 6, and 7 were active against S. epidermidis and C. dubliniensis, with MIC values in the range 12.5-100 mu g mL(-1).

Novel insights for dihydroorotate dehydrogenase class 1A inhibitors discovery

The enzyme dihydroorotate dehydrogenase (DHODH) has been suggested as a promising target for the design of trypanocidal agents. We report here the discovery of novel inhibitors of Trypanosoma cruzi DHODH identified by a combination of virtual screening and ITC methods. Monitoring of the enzymatic reaction in the presence of selected ligands together with structural information obtained from X-ray crystallography analysis have allowed the identification and validation of a novel site of interaction (S2 site). This has provided important structural insights for the rational design of T cruzi and Leishmania major DHODH inhibitors. The most potent compound (1) in the investigated series inhibits TcDHODH enzyme with K(i)(app) value of 19.28 mu M and possesses a ligand efficiency of 0.54 kcal mol(-1) per non-H atom. The compounds described in this work are promising hits for further development. (C) 2010 Elsevier Masson SAS. All rights reserved.