RESUMO
A primary goal of collective population behavior studies is to determine the rules governing crowd distributions in order to predict future behaviors in new environments. Current top-down modeling approaches describe, instead of predict, specific emergent behaviors, whereas bottom-up approaches must postulate, instead of directly determine, rules for individual behaviors. Here, we employ classical density functional theory (DFT) to quantify, directly from observations of local crowd density, the rules that predict mass behaviors under new circumstances. To demonstrate our theory-based, data-driven approach, we use a model crowd consisting of walking fruit flies and extract two functions that separately describe spatial and social preferences. The resulting theory accurately predicts experimental fly distributions in new environments and provides quantification of the crowd "mood". Should this approach generalize beyond milling crowds, it may find powerful applications in fields ranging from spatial ecology and active matter to demography and economics.
RESUMO
The cacao pathogen Moniliophthora roreri belongs to the mushroom-forming family Marasmiaceae, but it has never been observed to produce a fruiting body, which calls to question its capacity for sexual reproduction. In this study, we identified potential A (HD1 and HD2) and B (pheromone precursors and pheromone receptors) mating genes in M. roreri. A PCR-based method was subsequently devised to determine the mating type for a set of 47 isolates from across the geographic range of the fungus. We developed and generated an 11-marker microsatellite set and conducted association and linkage disequilibrium (standardized index of association, IA(s)) analyses. We also performed an ancestral reconstruction analysis to show that the ancestor of M. roreri is predicted to be heterothallic and tetrapolar, which together with sliding window analyses support that the A and B mating loci are likely unlinked and follow a tetrapolar organization within the genome. The A locus is composed of a pair of HD1 and HD2 genes, whereas the B locus consists of a paired pheromone precursor, Mr_Ph4, and receptor, STE3_Mr4. Two A and B alleles but only two mating types were identified. Association analyses divided isolates into two well-defined genetically distinct groups that correlate with their mating type; IA(s) values show high linkage disequilibrium as is expected in clonal reproduction. Interestingly, both mating types were found in South American isolates but only one mating type was found in Central American isolates, supporting a prior hypothesis of clonal dissemination throughout Central America after a single or very few introductions of the fungus from South America.
Assuntos
Agaricales/genética , Cacau/microbiologia , Genes Fúngicos Tipo Acasalamento , Agaricales/fisiologia , América Central , DNA Fúngico/genética , Marcadores Genéticos , Desequilíbrio de Ligação , Repetições de Microssatélites , Feromônios/genética , Filogenia , Receptores de Feromônios/genética , América do SulRESUMO
PURPOSE: To evaluate the effect of 2 different protocols of intra-articular hyaluronic acid (HA, hylan G-F20) to articular cartilage regeneration in acute full-thickness chondral defects. MATERIALS AND METHODS: Full-thickness chondral defects of 3 x 6 mm were performed into the lateral femoral condyles of New Zealand rabbits, treated with a single or three doses of HA. The animals were sacrified at 12 weeks and the regenerated tissue was evaluated by direct observation and histology with the ICRS scale. Macroscopically, in both groups treated with HA the defects were filled with irregular tissue with areas similar to hyaline cartilage and others in which depressed areas with exposed subchondral bone were observed. Histological analysis showed in both groups treated with HA a hyaline-like cartilage compared to control group. However, the score of the International Cartilage Repair Society (ICRS) scale did not show differences between the groups treated with HA. CONCLUSION: The use of single dose or 3 doses of AH in acute chondral lesions has a limited and similar benefit in articular cartilage regeneration.
Assuntos
Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/fisiologia , Ácido Hialurônico/análogos & derivados , Regeneração/efeitos dos fármacos , Viscossuplementos/uso terapêutico , Animais , Modelos Animais de Doenças , Ácido Hialurônico/uso terapêutico , Masculino , Peso Molecular , Osteoartrite do Joelho/terapia , CoelhosRESUMO
Quinone-containing molecules have been developed against cancer mainly for their redox cycling ability leading to reactive oxygen species (ROS) formation. We have previously shown that donor-acceptor phenylaminonaphthoquinones are biologically active against a panel of cancer cells. In this report, we explored the mechanisms involved in cancer cell growth inhibition caused by two phenylaminonaphthoquinones, namely Q7 and Q9, with or without ascorbate (ASC). The results show that Q7 and Q9 are both redox cyclers able to form ROS, which strongly inhibit the proliferation of T24 cells. Q9 was a better redox cycler than Q7 because of marked stabilization of the semiquinone radical species arising from its reduction by ascorbate. Indeed, ASC dramatically enhances the inhibitory effect of Q9 on cell proliferation. Q9 plus ASC impairs the cell cycle, causing a decrease in the number of cells in the G2/M phase without involving other cell cycle regulating key proteins. Moreover, Q9 plus ASC influences the MAPK signaling pathways, provoking the appearance of a senescent cancer cell phenotype and ultimately leading to necrotic-like cell death. Because cellular senescence limits the replicative capacity of cells, our results suggest that induction of senescence may be exploited as a basis for new approaches to cancer therapy.
Assuntos
Antineoplásicos/farmacologia , Ácido Ascórbico/farmacologia , Naftoquinonas/farmacologia , Neoplasias da Bexiga Urinária/patologia , Aminofenóis/farmacologia , Compostos de Anilina/farmacologia , Caspase 3/análise , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Senescência Celular , Sinergismo Farmacológico , Humanos , Imidazóis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Naftoquinonas/síntese química , Necrose , Oxirredução , Fenótipo , Piridinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Bexiga Urinária/metabolismoRESUMO
The effects of juglone on T24 cells were assessed in the presence and absence of ascorbate. The EC(50) value for juglone at 24 h decreased from 28.5 µM to 6.3 µM in the presence of ascorbate. In juglone-treated cells, ascorbate increased ROS formation (4-fold) and depleted GSH (65%). N-acetylcysteine or catalase restricted the juglone/ascorbate-mediated effects, highlighting the role of oxidative stress in juglone cytotoxicity. Juglone alone or associated with ascorbate did not cause caspase-3 activation or PARP cleavage, suggesting necrosis-like cell death. DNA damage and the mild ER stress caused by juglone were both enhanced by ascorbate. In cells treated with juglone (1-5 µM), a concentration-dependent decrease in cell proliferation was observed. Ascorbate did not impair cell proliferation but its association with juglone led to a clonogenic death state. The motility of ascorbate-treated cells was not affected. Juglone slightly restricted motility, but cells lost their ability to migrate most noticeably when treated with juglone plus ascorbate. We postulate that juglone kills cells by a necrosis-like mechanism inhibiting cell proliferation and the motility of T24 cells. These effects are enhanced in the presence of ascorbate.
Assuntos
Antineoplásicos/farmacologia , Ácido Ascórbico/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Naftoquinonas/farmacologia , Estresse Oxidativo , Bexiga Urinária/citologia , Bexiga Urinária/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , OxirreduçãoRESUMO
The development of new MRI technologies has favoured the use of sequences that significantly improve the spatial resolution of this imaging method, thus yielding thin-section images that allow volumetric analysis. We present our experience at Clínica Vespucio related to a routine knee MRI protocol, performed on 45 patients who underwent conventional proton density-weighted spin-echo sequence (PDFS) 3-mm section thickness along with proton density-weighted sequence of 1.2- mm thin-section, both with fat suppression technique. In most cases, the thin-section PDFS allows a better anatomical characterization of lesions, particularly meniscal and condral injuries, with a minimum increase in image acquisition time.
El desarrollo de nuevas tecnologías en resonancia magnética ha favorecido el uso de secuencias que mejoran significativamente la resolución espacial del método, obteniendo imágenes de cortes finos que permiten análisis volumétrico. Se presenta la experiencia en Clínica Vespucio en un protocolo rutinario de estudio de rodilla, con evaluación de 45 pacientes consecutivos a los que se les realizó secuencia tradicional de densidad protónica con saturación grasa (DPFS) de corte grueso (3 mm) y secuencia DPFS volumétrica de corte fino (1,2 mm). En la mayoría de los casos es posible realizar mejor caracterización anatómica de las lesiones, principalmente meniscales y condrales, con un mínimo aumento en el tiempo de estudio.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Joelho/anatomia & histologia , Traumatismos do Joelho/diagnósticoRESUMO
Synthesis of (+)-cyclozonarone (1) has been achieved using (-)-polygodial (3) as chiral starting material. The absolute configuration of naturally occurring (-)-cyclozonarone was established as 5R,10R by comparison of spectral data and optical rotation with those of (+)-cyclozonarone.
Assuntos
Phaeophyceae/química , Sesquiterpenos/síntese química , Espectroscopia de Ressonância Magnética , Conformação Molecular , Sesquiterpenos/químicaRESUMO
By the end of the 1800s, international trade and steam navigation made way for the third bubonic plague pandemy, which started in China in 1891 and reached America in 1898. This calamity apparently arrived in Columbia's coast between 1913 and 1915, during the apex of Pasteur medicine. The deficiencies of Columbian public scientific and sanitary apparat, concerning the emerging bacteriology and epidemiology, prevented the government and the medical body from reacting against the fear and rumor of epidemy, which negatively affected the trade. The authorities were also unable to fight this problem with adequate diagnosis, enferms treatment, urban sanitation, and isolation of infected places. These difficulties led to a confrontation between the government and the medical body, inciting an argument about the existence of the plague. This discussion was settled by the North American official medicine that, in its verdict, gave preference to the commercial interests of the United States, ignoring the sanitary urgencies of the Columbian Atlantic coast.
Assuntos
Surtos de Doenças/história , Peste/história , Administração em Saúde Pública/história , Colômbia , História do Século XX , Opinião PúblicaRESUMO
Previous studies have shown that palmitoyl-carnitine is an anti-proliferative agent and a protein kinase C inhibitor. Two new palmitoyl-carnitine analogs were synthesized by replacing the ester bond with a metabolically more stable ether bond. An LD50 value in the nM range was found in anti-proliferative assays using HL-60 cells and was dependent on the alkyl-chain length. The inhibitory action of these water-soluble compounds on protein kinase C in vitro was greatly increased with respect to palmitoyl-carnitine and was dependent on the length of the alkyl chain. Its effect was mediated by an increase in the enzyme's requirement for phosphatidylserine. Inhibition of the in situ phosphorylation of a physiological platelet protein kinase C substrate and of phorbol ester-induced differentiation of HL-60 cells was also observed. Finally, to test for isoenzyme selectivity, several human recombinant protein kinase C isoforms were used. Only the Ca2+-dependent classic protein kinase Cs (alpha, betaIota, betaIotaIota and gamma) were inhibited by these compounds, yet the activities of casein kinase I, Ca2+/calmodulin-dependent kinase and cAMP-dependent protein kinase were unaffected. Thus, these novel inhibitors appear to be both protein kinase C and isozyme selective. They may be useful in assessing the individual roles of protein kinase C isoforms in cell proliferation and tumor development and may be rational candidates for anti-neoplasic drug design.
Assuntos
Carnitina/análogos & derivados , Inibidores Enzimáticos/farmacologia , Isoenzimas/antagonistas & inibidores , Proteína Quinase C/antagonistas & inibidores , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Encéfalo/enzimologia , Carnitina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Desenho de Fármacos , Células HL-60 , Humanos , Técnicas In Vitro , Indóis/farmacologia , Ratos , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
A series of quinones (3a-i, 4-9, 11) and aromatic compounds (2a, 2d, 2g) containing the thiophene ring were tested in vitro against the trypomastigote form of Trypanosoma cruzi and the promastigote forms of Leishmania. The quinones 3a-i, 4, 5a, b, 6 and 9 having the thiophene ring fused to a quinone nucleus were the most active members of the series. The electron affinities of the benzo[b]thiophene-4,7-quinones 3, evaluated by their LUMO energies and halfwave potentials, are reported.