302 research outputs found
Epithelial Development Based on a Branching Morphogenesis Program: The Special Condition of Thymic Epithelium
Numerous epithelia undergo tubulogenesis and branching morphogenesis during their development (i.e., lung, salivary gland, pancreas) in order to establish sufficient available surface for their proper functioning. The thymus is a primary lymphoid organ constituted by pharyngeal-derived epithelium necessary to produce immunocompetent lymphocytes whose mechanisms of development are not fully known. In the current chapter, we review histological, cellular, and molecular mechanisms governing early thymic epithelium development emphasizing its resemblance with the process of branching morphogenesis and tubulogenesis occurring in other epithelial organs in which epithelial-mesenchyme interactions determine the tissue patterning through specific combinations of common molecular signaling pathways
Eph/ephrins-mediated thymocyte–thymic epithelial cell interactions control numerous processes of thymus biology
Numerous studies emphasize the relevance of thymocyte–thymic epithelial cell (TECs) interactions for the functional maturation of intrathymic T lymphocytes. The tyrosine kinase receptors, Ephs (erythropoietin-producing hepatocyte kinases) and their ligands, ephrins (Eph receptor interaction proteins), are molecules known to be involved in the regulation of numerous biological systems in which cell-to-cell interactions are particularly relevant. In the last years, we and other authors have demonstrated the importance of these molecules in the thymic functions and the T-cell development. In the present report, we review data on the effects of Ephs and ephrins in the functional maturation of both thymic epithelial microenvironment and thymocyte maturation as well as on their role in the lymphoid progenitor recruitment into the thymus
Synthesis, In Silico Studies, Antiprotozoal and Cytotoxic Activities of Quinoline‐Biphenyl Hybrids
This is the pre-peer reviewed version of the following article: Synthesis, In Silico Studies, Antiprotozoal and Cytotoxic Activities of Quinoline‐Biphenyl Hybrids, which has been published in final form at https://doi.org/10.1002/slct.201903835. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThe synthesis, in silico studies, antiprotozoal and cytotoxic activities of eleven quinoline‐biphenyl hybrids are described herein. The structure of the synthesized products was elucidated by a combination of spectrometric analyses. The synthesized compounds were evaluated against Plasmodium falciparum, and amastigotes forms both Leishmania (V) panamensis and Trypanosoma cruzi. Cytotoxicity was evaluated against human U‐937 macrophages. 8‐phenylquinoline (4 a) showed similar activity than meglumine antimoniate and 4‐(quinolin‐8‐yl)phenol (4 b) exhibited an activity similar to that of benznidazole. 8‐(3,4‐dimethoxyphenyl) quinoline (4 k) showed the best activity against P. falciparum. Although these compounds were toxic for mammalian U‐937 cells, however they may still have potential to be considered as candidates for drug development because of their antiparasite activity. Molecular docking was used to determine the in silico inhibition of some of the designed compounds against PfLDH and cruzipain, two important pharmacological targets involved in antiparasitic diseases. All hybrids were docked to the three‐dimensional structures of PfLDH and T. cruzi cruzipain as enzymes using AutoDock Vina. Notably, the docking results showed that the most active compounds 4‐(quinolin‐8‐yl)phenol (4 b, CE50: 11.33 μg/mL for T. cruzi) and 8‐(3,4‐dimethoxyphenyl) quinoline (4 k, CE50: 8.84 μg/mL for P. falciparum) exhibited the highest scoring pose (−7.5 and −7.7 kcal/mol, respectively). This result shows a good correlation between the predicted scores with the experimental data profile, suggesting that these ligands could act as competitive inhibitors of PfLDH or T. cruzi cruzipain enzymes, respectively. Finally, in silico ADME studies of the quinoline hybrids showed that these novel compounds have suitable drug‐like properties, making them potentially promising agents for antiprotozoal therapy
Enzymatic hydrolysis of cassava stalk pretreated with the alkaline method
This study was developed with the aim of evaluating the pH, enzymatic complex load and temperature effects on the saccharification of pretreated cassava stalks (CS) using the response surface methodology (RSM). The factor levels evaluated were temperature 35 - 40°C, pH 4.0 - 5.0 and dose of enzymatic complex Accellerase 1500™ 2.9 - 14.5 FPU/g of substrate. The reducing sugar (RS) response was used. The pH was controlled through the use of hydrochloric acid and sodium hydroxide solutions and the system was shaken orbitally at 120 rpm with a solids loading of 10% w/v. The fitted model showed that the optimal operating conditions were: pH 4.0, 38°C and enzyme dose of 14.5 FPU/g substrate, reaching a sugar concentration of 18.4 g L-1
Influencia de la inclusión del efecto materno en la estimación de parámetros genéticos del peso al destete en un hato de ganado de carne
ABSTRACT: The component of (co)variance and genetic parameters for weaning weight trait in animals of pure
(Brahman) or crossbreed (Zebu cattle) breeds were estimated, with the aim to estimate and to compare
the genetic parameters and genetic value with or without including the maternal genetic effects by mean
of Animal model, using MTDFREML program. Five models were considered including 1) the maternal
genetic group, 2) calving, and 3) contemporary group as fixed effects, 4) direct and maternal genetic effects
and 5) maternal permanent environmental effects, as random effects, and finally the residual error effect.
Direct heritability coefficients varied form median to low (h2
a, 0.10 to 0.29) in all models. Models that included the maternal genetic effect presented the lowest values of maternal heritability (h2
m, 0.07 to 0.17).
The genetic correlations between direct and maternal effects were negative and with low magnitude (-0.18
and -0.29). The models were compared between each other using the Maximum Likelihood method (- 2 log
L) based on a X2 test, and it gave as result that the best model was the five one (Y = Xb + Z1a + Z3m + Z2ep
+ e) which included all effects.RESUMEN: En el presente trabajo se estimaron componentes de (co)varianza y parámetros genéticos para la
característica peso al destete en animales de las razas brahman y cebú comercial. El objetivo general fue
estimar y comparar los parámetros genéticos incluyendo o no el efecto genético materno por medio del
Modelo Animal, usando el programa MTDFREML. Se consideraron cinco modelos que incluyeron como
efectos fijos el grupo genético materno, el número de partos y el grupo contemporáneo, y como aleatorios los
efectos genéticos directos y maternos y los efectos del ambiente permanente materno, además del efecto del
error residual. Los coeficientes de heredabilidad directa fueron de medios a bajos (h2
a, 0.10 a 0.29) en todos
los modelos. Los modelos que incluyeron el efecto genético materno presentaron valores de heredabilidad
materna bajos (h2
m, 0.07 a 0.17). Las correlaciones genéticas entre los efectos directo y materno fueron
de baja magnitud y negativas (-0.18 y -0.29). Se compararon los modelos entre sí realizando la prueba de
máxima verosimilitud (-2LogL) a través de la prueba de ji cuadrado, obteniéndose como resultado que el
mejor modelo fue el número 5 (Y = Xβ + Z1a + Z3m + Z2ep + e), el cual tuvo en cuenta todos los efectos
Gene expression in primate liver during viral hemorrhagic fever
<p>Abstract</p> <p>Background</p> <p>Rhesus macaques infected with lymphocytic choriomeningitis virus (LCMV) provide a model for human Lassa fever. Disease begins with flu-like symptoms and progresses rapidly with fatal consequences. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al J. Virol. 2007) showing distinct pre-viremic and viremic stages that discriminated virulent from benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased.</p> <p>Results</p> <p>Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a broader effect on liver cell function than did infection with non-virulent LCMV-Armstrong. During the first few days after infection, LCMV altered expression of genes associated with energy production, including fatty acid and glucose metabolism. The transcriptome profile resembled that of an organism in starvation: mRNA for acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis was reduced while genes for enzymes in gluconeogenesis were up-regulated. Expression was also altered for genes associated with complement and coagulation cascades, and with signaling pathways involving STAT1 and TGF-β.</p> <p>Conclusion</p> <p>Most of the 4500 differentially expressed transcripts represented a general response to both virulent and mild infections. However, approximately 250 of these transcripts had significantly different expression in virulent infections as compared to mild infections, with approximately 30 of these being differentially regulated during the pre-viremic stage of infection. The genes that are expressed early and differently in mild and virulent disease are potential biomarkers for prognosis and triage of acute viral disease.</p
Dinámica de transmisión del dengue clásico con control mecánico y profilaxis
Se modela la dinámica de transmisión del dengue clásico en una región endémica considerando el uso de medidas preventivas y de control mecánico en la reducción de la transmisión de la enfermedad. Se plantea un sistema de ecuaciones diferenciales ordinarias que describe la dinámica y mediante simulación numérica se determina su evolución en el tiempo. Se comparan diferentes estrategias de control mecánico y profilaxis con la situación sin control. Se determina el número básico de reproducción , mostrando que si hay un alto riesgo de epidemia y que en caso contrario la enfermedad se mantiene en niveles de bajo impacto; estos resultados se contratan con los obtenidos numéricamente. Se concluye que si bien la profilaxis y el control mecánico por si solos brindan resultados efectivos en el control de la enfermedad, cuando se combinan ambos controles los niveles de infección se ven reducidos significativamente. Niveles de control mecánico y profilaxis cercanos al 60 % son los que brindan resultados adecuados en el control del brote de dengu
Identificación de bacterias de la familia Anaplasmataceae en un albergue canino del municipio de Caldas, Antioquia
Objetive. It was to detect the circulation of microorganisms of the family Anaplasmataceae in a canine albergo of the municipality of Caldas. Materials and methods. In view of the above, a descriptive study was conducted in 46 dogs (Canis lupus familiaris) to evaluate the presence of Ehrlichia spp. and Anaplasma spp. by molecular techniques or by immunodiagnostic, in a dog shelter of the municipality of Caldas. The DNA extraction was done in whole blood samples with EDTA. Primers were used against dsb and groEL genes to detect Ehrlichia and Anaplasma sequences respectively and phylogenetic analyzes of the sequences obtained were also carried out. On the other hand, SNAP 4DX® was used for serodiagnosis. Results. In the molecular testing, five positive samples were obtained for the Ehrlichia test and three for the Anaplasma test. In the serological tests, three individuals were positive for Ehrlichia spp., three for Anaplasma spp. and for the other trials measured by the SNAP (Dirofilaria immitis y Borrelia burgdorfe) the result was negative. Conclusions. It demonstrated the circulation of Ehrlichia canis and Anaplasma platys in a dog shelter of the municipality of Caldas, Antioquia.Objetivo. Fue detectar la circulación de microorganismos de la familia Anaplasmataceae en un alberge canino del municipio de Caldas. Materiales y métodos. Se realizó un estudio descriptivo en 46 perros (Canis lupus familiaris) para evaluar por técnicas moleculares o por inmunodiagnóstico la presencia de Ehrlichia spp. y Anaplasma spp., en un albergue canino del município de Caldas. Se hizo extracción de ADN en muestras de sangre entera con EDTA y se utilizaron cebadores contra los genes dsb y groEl, para detectar secuencias de Ehrlichia y Anaplasma respectivamente y análisis filogenéticos de las secuencias obtenidas. Por otro lado se usó el SNAP 4DX® para el serodiagnóstico. Resultados. En las pruebas moleculares se obtuvieron cinco muestras positivas para Ehrlichia y tres para Anamaplasma. En las pruebas serológicas, tres individuos fueron positivos para Ehrlichia spp., tres para Anaplasma spp. y negativos para los demás ensayos medidos por el SNAP (Dirofilaria immitis y Borrelia burgdorferi). Conclusiones. Se demostró la circulación de Ehrlichia canis y Anaplasma platys en un albergue del municipio de Caldas, Antioquia
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