The bone marrow compartment is modified in the absence of galectin-3

Galectin-3 (gal-3) is a β-galactoside binding protein present in multivalent complexes with an extracellular matrix and with cell surface glycoconjugates. In this context, it can deliver a variety of intracellular signals to modulate cell activation, differentiation and survival. In the hematopoietic system, it was demonstrated that gal-3 is expressed in myeloid cells and surrounding stromal cells. Furthermore, exogenous and surface gal-3 drive the proliferation of myeloblasts in a granulocyte–macrophage colony-stimulating factor (GM-CSF)-dependent manner. Here, we investigated whether gal-3 regulates the formation of myeloid bone marrow compartments by studying galectin-3−/− mice (gal-3−/−) in the C57BL/6 background. The bone marrow histology of gal-3−/− mice was significantly modified and the myeloid compartments drastically disturbed, in comparison with wild-type (WT) animals. In the absence of gal-3, we found reduced cell density and diaphyseal disorders containing increased trabecular projections into the marrow cavity. Moreover, myeloid cells presented limited capacity to differentiate into mature myeloid cell populations in gal-3−/− mice and the number of hematopoietic multipotent progenitors was increased relative to WT animals. In addition, bone marrow stromal cells of these mice had reduced levels of GM-CSF gene expression. Taken together, our data suggest that gal-3 interferes with hematopoiesis, controlling both precursors and stromal cells and favors terminal differentiation of myeloid progenitors rather than proliferation

Boomerang: Rebounding the consequences of reputation feedback on crowdsourcing platforms

Paid crowdsourcing platforms suffer from low-quality workand unfair rejections, but paradoxically, most workers and requesters have high reputation scores. These inflated scores, which make high-quality work and workers difficult to find,stem from social pressure to avoid giving negative feedback. We introduce Boomerang, a reputation system for crowdsourcing that elicits more accurate feedback by rebounding the consequences of feedback directly back onto the person who gave it. With Boomerang, requesters find that their highly rated workers gain earliest access to their future tasks, and workers find tasks from their highly-rated requesters at the top of their task feed. Field experiments verify that Boomerang causes both workers and requesters to provide feedback that is more closely aligned with their private opinions. Inspired by a game-theoretic notion of incentive-compatibility, Boomerang opens opportunities for interaction design to incentivize honest reporting over strategic dishonesty

Relation between CYP2C19 phenotype and amitriptyline demethylation metabolic ratios in healthy volunteers

A enzima CYP2C19 é a principal responsável pela metabolização da amitriptilina, com a formação de nortriptilina. Após fenotipagem com omeprazol em um grupo de 38 voluntários saudáveis, 5 voluntários com variados fenótipos (1 metabolizador lento, 1 metabolizador ultra-rápido e 3 metabolizadores rápidos) receberam uma dose oral única de amitriptilina e os níveis plasmáticos de amitriptilina e de seu metabólito principal nortriptilina foram monitorados. As razões de desmetilação de amitriptilina foram marcantemente diferentes entre indivíduos com diferentes fenótipos e correlacionadas com as razões metabólicas obtidas com omeprazol. As concentrações plasmáticas de amitriptilina e nortriptilina obtidas após uma dose oral de amitriptilina podem ser utilizadas para predição da exposição ao fármaco e para o ajuste precoce da posologia.CYP2C19 is the main responsible enzyme by amitriptyline metabolism, leading to the formation of nortriptyline. After phenotyping with omeprazole in a group of 38 healthy volunteers, 5 volunteers with different phenotypes (1 poor metabolizer, 1 ultra-extensive metabolizer and 3 extensive metabolizer) received a single oral dose of amitriptyline and the plasma levels of both amitriptyline and its main metabolite nortriptyline were monitored. Amitriptyline demethylation ratios were markedly different among individuals with different phenotypes and were correlated with omeprazole hydroxilation ratios. Plasma levels of amitriptyline and nortriptyline obtained after a single oral dose of amitriptyline can be used to prediction of drug exposure and to the early adjustment of the dosage regimen.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Cytotoxicity assays to evaluate tannery effluents treated by photoelectrooxidation

The advanced oxidation process (AOP) is used to increase the treatment efficiency of effluents however, it is necessary to compare the toxicity of treated and untreated effluents to evaluate if the decontamination process does not cause any biological harm. Cultured cells have been previously used to assess the genotoxic and cytotoxic potential of various compounds. Hence, the aim of this work was to assess the applicability of cytotoxicity assays to evaluate the toxicity related to the AOP treatment. Samples of an industrial effluent were collected after their treatment by a conventional method. Cytotoxicity of standard and AOP treated effluents was assessed in CRIB and HEp-2 cell line using the MTT and neutral red assays. We observed decrease at cell viability in the both assays (50% MTT and 13% NRU) when cells were exposed to the AOP treatment in the highest concentration. Thus, cytotoxic assays in cultured cells can be explored as an useful method to evaluate toxicity as well as to optimize effluents treatment process

Evaluation of genotoxicity and cytotoxicity of water samples from the Sinos River Basin, southern Brazil

Some water bodies in the Sinos River Basin (SRB) have been suffering the effects of pollution by residential, industrial and agroindustrial wastewater. The presence of cytotoxic and genotoxic compounds could compromise the water quality and the balance of these ecosystems. In this context, the research aimed to evaluate the genotoxicity and cytotoxicity of the water at four sites along the SRB (in the cities of Santo Antônio da Patrulha, Parobé, Campo Bom and Esteio), using bioassays in fish and cell culture. Samples of surface water were collected and evaluated in vitro using the Astyanax jacuhiensis fish species (micronucleus test and comet assay) and the Vero lineage of cells (comet assay and cytotoxicity tests, neutral red - NR and tetrazolium MTT). The micronucleus test in fish showed no significant differences between the sampling sites, and neither did the comet assay and the MTT and NR tests in Vero cells. The comet assay showed an increase in genetic damage in the fish exposed to water samples collected in the middle and lower sections of the basin (Parobé, Campo Bom and Esteio) when compared to the upper section of the basin (Santo Antônio da Patrulha). The results indicate contamination by genotoxic substances starting in the middle section of the SRB.</p