RESUMEN
BACKGROUND: Annually > 10% of patients with atrial fibrillation on oral anticoagulation undergo invasive procedures. Optimal peri-procedural management of anticoagulation, as judged by major bleeding and thromboembolic events, especially in the elderly, is still debated. METHODS: Procedures from 1442 patients were evaluated. Peri-procedural edoxaban management was guided only by the experience of the attending physician. The primary safety outcome was the rate of major bleeding. Secondary outcomes included the peri-procedural administration of edoxaban, other bleeding events, and the main efficacy outcome, a composite of acute coronary syndrome, non-hemorrhagic stroke, transient ischemic attack, systemic embolic events, deep vein thrombosis, pulmonary embolism, and mortality. RESULTS: Of the 1442 patients, 280 (19%) were < 65, 550 (38%) were 65-74, 514 (36%) 75-84, and 98 (7%) were 85 years old or older. With increasing age, comorbidities and risk scores were higher. Any bleeding complications were uncommon across all ages, ranging from 3.9% in patients < 65 to 4.1% in those 85 years or older; major bleeding rates in any age group were ≤ 0.6%. Interruption rates and duration increased with advancing age. Thromboembolic events were more common in the elderly, with all nine events occurring in those > 65, and seven in patients aged > 75 years. CONCLUSION: Despite increased bleeding risk factors in the elderly, bleeding rates were small and similar across all age groups. However, there was a trend toward more thromboembolic complications with advancing age. Further efforts to identify the optimal management to reduce ischemic complications are needed. TRIAL REGISTRATION: NCT# 02950168, October 31, 2016.
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Fibrilación Atrial/tratamiento farmacológico , Trastornos Cerebrovasculares/prevención & control , Inhibidores del Factor Xa/administración & dosificación , Piridinas/administración & dosificación , Tiazoles/administración & dosificación , Tromboembolia/prevención & control , Administración Oral , Factores de Edad , Anciano , Anciano de 80 o más Años , Asia/epidemiología , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/epidemiología , Esquema de Medicación , Europa (Continente)/epidemiología , Inhibidores del Factor Xa/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Perioperativa , Hemorragia Posoperatoria/inducido químicamente , Hemorragia Posoperatoria/epidemiología , Estudios Prospectivos , Piridinas/efectos adversos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Tiazoles/efectos adversos , Tromboembolia/diagnóstico , Tromboembolia/epidemiología , Resultado del TratamientoRESUMEN
In the present study, the impact of Salmonella Typhimurium on cell-mediated immunity (CMI) was investigated in 5 week-old immuno divergent broiler lines selected for the high and low response to phytohemagglutinin-P. The immune response was assessed in peripheral-blood mononuclear cells (PBMCs) induced with Salmonella Typhimurium at different time intervals (0 h, 0.5 h, 2 h, 4 h, 6 h, 12 h and 24 h). The differential mRNA expression patterns of IFN-γ, IL-2 and iNOS were evaluated by quantitative real time PCR. In-vitro production of nitric oxide (NO) was also estimated in the culture supernatant and correlated with iNOS mRNA expression. Present study showed higher production of NO in the high cell-mediated line (HCMI) as compared to the low cell-mediated line (LCMI) upon stimulation with Salmonella Typhimurium. Correspondingly, higher mRNA expression of iNOS and IFN-γ were observed in high response birds (HCMI); but IL-2 was down regulated in this line compared to the low response birds (LCMI). Significantly (p<0.05) higher expression of iNOS, IFN-γ and higher production of NO in high line indicated that the selection for PHA-P response might be employed for increasing the immune competence against Salmonella Typhimurium in chicken flocks.
RESUMEN
The neutron inelastic scattering of carbon-12, populating the Hoyle state, is a reaction of interest for the triple-alpha process. The inverse process (neutron upscattering) can enhance the Hoyle state's decay rate to the bound states of 12C, effectively increasing the overall triple-alpha reaction rate. The cross section of this reaction is impossible to measure experimentally but has been determined here at astrophysically-relevant energies using detailed balance. Using a highly-collimated monoenergetic beam, here we measure neutrons incident on the Texas Active Target Time Projection Chamber (TexAT TPC) filled with CO2 gas, we measure the 3α-particles (arising from the decay of the Hoyle state following inelastic scattering) and a cross section is extracted. Here we show the neutron-upscattering enhancement is observed to be much smaller than previously expected. The importance of the neutron-upscattering enhancement may therefore not be significant aside from in very particular astrophysical sites (e.g. neutron star mergers).
RESUMEN
The haematopoietic protein tyrosine phosphatase (HePTP) is a negative regulator of the MAP kinases Erk1, Erk2 and p38. HePTP binds to these kinases through a kinase-interaction motif (KIM) in its non-catalytic amino terminus and inactivates them by dephosphorylating the critical phosphorylated tyrosine residue in their activation loop. Here we show that cyclic-AMP-dependent protein kinase (PKA) phosphorylates serine residue 23 in the KIM of HePTP in vitro and in intact cells. This modification reduces binding of MAP kinases to the KIM, an effect that is prevented by mutation of serine 23 to alanine. The PKA-mediated release of MAP kinase from HePTP is sufficient to activate the kinase and to induce transcription from the c-fos promoter. Expression of a HePTP serine-23-to-alanine mutant inhibits MAP-kinase dissociation and activation and induction of transcription from the c-fos promoter. We conclude that HePTP not only controls the activity of MAP kinases, but also mediates crosstalk between the cAMP system and the MAP-kinase cascade.
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Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Tirosina Fosfatasas/metabolismo , Alanina , Sustitución de Aminoácidos , Proteínas Quinasas Dependientes de AMP Cíclico/química , Humanos , Péptidos y Proteínas de Señalización Intracelular , Células Jurkat , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/química , Modelos Químicos , Mutagénesis Sitio-Dirigida , Fosforilación , Proteína Tirosina Fosfatasa no Receptora Tipo 6 , Proteínas Tirosina Fosfatasas no Receptoras , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Serina , Transducción de Señal , Especificidad por Sustrato , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
The glass-ceramic form of phosphor materials can overcome the many serious issues of phosphor/silicone composite in commercial phosphor-converted LEDs and are considered as new-generation color converters. In this report, we have shown a novel approach of developing inorganic red phosphor [Eu3+:La2(MoO4)3] in the glass-ceramic form based on lanthanum molybdate system. The ceramic form of the compound was found to have a glass transition temperature of 1002 °C, as confirmed by TGA and DSC studies. Further, XRD, FTIR and Raman studies also confirmed that the compounds prepared at 1050 °C are in glass-ceramic form, while those prepared at 750 °C are in ceramic form. Photoluminescence studies showed that both the ceramic and glass-ceramic forms of the phosphor are red color-emitting materials. However, the glass-ceramic forms have better color purity and more radiation transition probabilities. Further, the decay kinetics of both ceramic and glass-ceramic forms confirmed that only those Eu3+ ions which exist in the grain boundaries of the ceramics go inside the glass network structure upon heating the compound at or above the glass transition temperature. On the other hand, Eu3+ ions which exist at the La-site in the bulk of the particles are retained in the ceramic form in the glass-ceramic mixture.
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In T cells, cAMP-dependent protein kinase (PKA) type I colocalizes with the T cell receptor-CD3 complex (TCR/CD3) and inhibits T cell function via a previously unknown proximal target. Here we examine the mechanism for this PKA-mediated immunomodulation. cAMP treatment of Jurkat and normal T cells reduces Lck-mediated tyrosine phosphorylation of the TCR/CD3 zeta chain after T cell activation, and decreases Lck activity. Phosphorylation of residue Y505 in Lck by COOH-terminal Src kinase (Csk), which negatively regulates Lck, is essential for the inhibitory effect of cAMP on zeta chain phosphorylation. PKA phosphorylates Csk at S364 in vitro and in vivo leading to a two- to fourfold increase in Csk activity that is necessary for cAMP-mediated inhibition of TCR-induced interleukin 2 secretion. Both PKA type I and Csk are targeted to lipid rafts where proximal T cell activation occurs, and phosphorylation of raft-associated Lck by Csk is increased in cells treated with forskolin. We propose a mechanism whereby PKA through activation of Csk intersects signaling by Src kinases and inhibits T cell activation.
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Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Activación de Linfocitos , Proteínas Tirosina Quinasas/metabolismo , Receptores de Antígenos de Linfocitos T/antagonistas & inhibidores , Linfocitos T/inmunología , Proteína Tirosina Quinasa CSK , Células Cultivadas , Activación Enzimática , Humanos , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/metabolismo , Microdominios de Membrana , Modelos Inmunológicos , Fosforilación , Transducción de Señal , Familia-src QuinasasRESUMEN
The aim of this study was to evaluate the CD4+/CD8+ ratio in peripheral blood of dogs with localized and generalized demodicosis. Sixteen dogs were examined, 8 with localized and 8 with generalized demodicosis, while 8 healthy dogs were used as controls. Peripheral blood was obtained and CD4+ and CD8+ T cells were determined by flow cytometry. Significantly higher numbers of CD8+ T cells and lower numbers of CD4+ T cells were found in dogs with generalized demodicosis compared to dogs with localized demodicosis and healthy controls. Significantly higher numbers of CD8+ T cells and lower numbers of CD4+ T cells were also found in dogs with localized demodicosis compared to healthy controls. The CD4+/CD8+ ratio was also found to be significantly lower in dogs with generalized demodicosis in comparison with dogs with localized demodicosis and healthy controls. It is concluded that significant alteration in the CD4+/CD8+ ratio may be implicated in the pathogenesis of generalized canine demodicosis.
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Ácaros y Garrapatas/patogenicidad , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Enfermedades de los Perros/inmunología , Infestaciones por Ácaros/veterinaria , Enfermedades Cutáneas Parasitarias/veterinaria , Ácaros y Garrapatas/inmunología , Animales , Relación CD4-CD8 , Enfermedades de los Perros/parasitología , Enfermedades de los Perros/patología , Perros , Citometría de Flujo , Infestaciones por Ácaros/inmunología , Infestaciones por Ácaros/parasitología , Infestaciones por Ácaros/patología , Piel/inmunología , Piel/parasitología , Piel/patología , Enfermedades Cutáneas Parasitarias/inmunología , Enfermedades Cutáneas Parasitarias/patología , Subgrupos de Linfocitos TRESUMEN
BACKGROUND: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense. The oxidative stress becomes evident as a result of accumulation of ROS in conditions of inflammation and Type 2 diabetes mellitus (T2DM). The genes involved in redox balance, which determines the susceptibility to T2DM remain unclear. In humans, the glutathione S-transferase (GST) family comprises several classes of GST isozymes, the polymorphic variants of GSTM1, T1 and P1 genes result in decreased or loss of enzyme activity. AIMS: The present study evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing T2DM in the North Indian population. SETTINGS AND DESIGN: GSTM1, T1 and P1 polymorphisms were genotyped in 100 T2DM patients and 200 healthy controls from North India to analyze their association with T2DM susceptibility. MATERIALS AND METHODS: Analysis of GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction (PCR) and GSTP1 by PCR-Restriction Fragment Length Polymorphism (RFLP). STATISTICAL ANALYSIS: Fisher's exact test and chi2 statistics using SPSS software (Version-15.0). RESULTS: We observed significant association of GSTM1 null (P=0.004, OR= 2.042, 95%CI= 1.254-3.325) and GSTP1 (I/V) (P=0.001, OR= 0.397, 95%CI=0.225-0.701) with T2DM and no significant association with GSTT1 (P=0.493). The combined analysis of the three genotypes GSTM1 null, T1 present and P1 (I/I) demonstrated an increase in T2DM risk (P= 0.005, OR= 2.431 95% CI=1.315-4.496). CONCLUSIONS: This is the first study showing the association of a combined effect of GSTM1, T1 and P1 genotypes in a representative cohort of Indian patients with T2DM. Since significant association was seen in GSTM1 null and GSTP1 (I/V) and multiple association in GSTM1 null, T1 present and P1 (I/I), these polymorphisms can be screened in the population to determine the diabetic risk.
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Diabetes Mellitus Tipo 2/genética , Gutatión-S-Transferasa pi/genética , Glutatión Transferasa/genética , Adulto , Anciano , Pueblo Asiatico/genética , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/enzimología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , India/epidemiología , Isoenzimas/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Factores de RiesgoRESUMEN
We present the diurnal and seasonal variability of ambient NH3, NO, NO2 and SO2 over Delhi, India. Ambient NH3, NO and NO2 were measured continuously during winter, summer and autumn seasons using NH3- and NOx-analyzer, which operates by chemiluminescence method with a higher estimation efficiency (> 90%) than the chemical trap method (reproducibility 4.7%). Prominent diurnal, day-to-day and seasonal variations of ambient mixing ratio of NH3, NO, NO2 and SO2 were observed during the study period. Seasonal variation with higher mixing ratio in winter was observed for all measured trace gases except NO. Day-night variation of all measured trace gases observed was higher in winter in comparison with summer. Late morning increase in NO2 mixing ratio might be attributed to conversion of NO to NO2 with the interaction of O3.
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Amoníaco/análisis , Monitoreo del Ambiente , Óxido Nítrico/análisis , Dióxido de Nitrógeno/análisis , Estaciones del Año , Dióxido de Azufre/análisis , India , LuminiscenciaRESUMEN
OBJECTIVE: The aim of this study was to explore the use of a logarithmic amplifier to improve the spatial resolution (RES) of a low-cost electrical impedance tomography (EIT) system. In an EIT system, the measured signal has a large dynamic range from µV to mV, which requires high-RES (analog to digital conversion) cards. The logarithmic amplifier reduces the dynamic range by expanding lower values and compressing higher values, thereby improving the sensitivity and at the same time preventing the signal from saturation. In addition, a low-RES analog to digital conversion (ADC) cards can be used, making the system cost effective. This work evaluates the performance of a logarithmic amplifier and a linear amplifier used for signal conditioning in a low-cost EIT system. APPROACH: Two EIT systems based on a linear amplifier and logarithmic amplifier were designed. Phantom experiments were carried out with very small amounts of current injection. The signal-to-noise ratio (SNR), image quality, minimum detectable size and minimum detectable conductivity change were obtained. MAIN RESULTS: The logarithmic amplifier-based EIT system increased the average SNR by 4 dB. It also showed improvement in the RES and contrast-to-noise ratio of the images. The minimum size detectable by the logarithmic amplifier-based system was of radius 0.25 cm in a tank of radius 11 cm and the minimum change in conductivity detectable was 11%. SIGNIFICANCE: Logarithmic amplifier-based signal conditioning is a promising technique for improving the spatial RES of a low-cost EIT system that has a low-RES ADC.
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Impedancia Eléctrica , Procesamiento de Señales Asistido por Computador , Tomografía Computarizada por Rayos X , Tomografía , Fantasmas de Imagen , Relación Señal-RuidoRESUMEN
Melatonin (N-acetyl-5-methoxytryptamine), an indole hormone, regulates various biological functions through three different receptor subtypes (Mel-1a, Mel-1b, and Mel-1c). However, the distribution of different melatonin receptor subtypes in chicken reproductive tissues was not known. In the present investigation, the partial sequences of ovarian melatonin receptor subtypes (Mel-1a, Mel-1b, and Mel-1c) were characterized. Further, the expression profile of melatonin receptor subtypes in the granulosa and theca layers of different preovulatory and postovulatory follicles (POF) were studied by semi-quantitative RT-PCR. The expression of all three subtypes of melatonin receptors were observed in the ovary of domestic chicken. Analysis of partial sequences of ovarian melatonin receptors revealed that the melatonin subtypes were identical to the brain receptors. In small white ovary follicles, we observed only the expression of mel-1b receptors, but not mel-1a or mel-1c receptors. In yellow follicles, all the three subtypes of receptors expression were noticed. Interestingly, we observed the expression of mel-1a receptor only in thecal layer, but not in granulosa layer. In contrast, mel-1b and -1c receptors were expressed in both granulosa and thecal layer. During the regression of POF, we observed significant upregulation of melatonin receptors (mel-1a and 1c) expression, that downregulated in the later stages of regression. We assume that the expression of melatonin receptors might have been influenced by the atresia or apoptosis of different follicular layers in POF. Our findings suggest that the differential distribution of melatonin receptor subtypes might have distinct downstream cellular functions in the ovarian tissues.
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Pollos/fisiología , Perfilación de la Expresión Génica/veterinaria , Ovario/metabolismo , Receptores de Melatonina/metabolismo , Animales , Clonación Molecular , Femenino , Regulación de la Expresión Génica/fisiología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Melatonina/genéticaRESUMEN
Salmonella is very important from the zoonotic point of view, as it causes many diseases in animals and humans. This study was conducted during September 2005 to February 2006 to develop rapid detection system for Salmonella from poultry samples. In the present study 300 poultry samples were screened for Salmonella. Earlier, isolation and identification of Salmonella from clinical samples by traditional cultural techniques required laborious procedures which can last upto 7 days, whereas amplification of DNA sequences unique to an organism using the PCR improves both the speed of detection and the level of sensitivity at which organisms can be detected and has been increasingly used to identify several bacterial species from food and clinical samples. In this study Salmonella were rapidly detected by targeting invA gene, giving PCR product of 284 bp size. Therefore this technique can be used for the screening of Salmonella in the routine testing.
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Pollos/microbiología , Enfermedades de las Aves de Corral/microbiología , Salmonella/aislamiento & purificación , Animales , Heces/microbiología , Reacción en Cadena de la Polimerasa , Salmonella/genéticaRESUMEN
Bacillus anthracis is considered as a biological warfare agent because it is the causative agent of the serious infectious anthrax disease. Delay in treatment leads to lethal factor-mediated toxaemia which is very critical due to lack of therapeutic options. Consequently, attempts have been made to discover potent lethal factor (LF) protease inhibitors such as small-molecule synthetic 2-thio-1,3-thiazolidine-4-one (rhodanine) compounds. But computed descriptor-based quantitative structure-activity relationship (QSAR) and drug design studies on such aspect are poorly represented. Therefore, an attempt was made for developing QSAR models using structural descriptors for 1,3-thiazolidine-4-one compounds. The models were developed on a series of 49 LF protease inhibitors using the combination of constitutional, functional group, atom-centred fragment and molecular property descriptors. The best QSAR model included four variables, namely, C-040, nR05, GVWAI-80 and ALOGP that correlated well with the anti-LF protease activity with a good correlation coefficient (r = 0.870) of good statistical significance (F4, 29 = 14.09 (α = 0.001) F4, 29 = 6.19). This model was also validated and explained 58.1% of variances of the Bacillus anthracis inhibitory activities of the studied compounds with r2pred = 0.710 which denotes external predictability. Finally, molecular docking was carried out to predict the mode of binding of some highly active congeneric compounds. It was shown that VAL 1403 is an important residue for phenyl ring. TYR 1456 and HIS 1418 are responsible for interaction with the rhodanine nucleus. Therefore, these residues are considered responsible for the inhibition of LF protease anthrax and can predict significant dimension of essential structural features of these inhibitors to evaluate, screen and help priorities of the synthesis of the candidates against anthrax bioterrorism.
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Bacillus anthracis/efectos de los fármacos , Toxinas Bacterianas/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Inhibidores de Proteasas/farmacología , Relación Estructura-Actividad Cuantitativa , Antígenos Bacterianos , Bacillus anthracis/metabolismo , Diseño de FármacosRESUMEN
The mechanism of postovulatory follicle (POF) regression in birds is still poorly understood. In the current study, expression of IL-1beta, IL-6, GM-CSF, IFN-gamma, IL-2, IL-4, IL-13, chCXCLi2, chCCLi2, chCCLi4, chCCLi7, IL-10 and TGF-beta2 mRNAs was estimated in regressing POF by semi-quantitative RT-PCR. In addition, the changes in immune cell population, histological and apoptotic changes were also studied in regressing POF. The expression of cytokines (IL-1beta, IL-6, IL-10 and TGF-beta2) and chemokines (chCXCLi2, chCCLi2, chCCLi4 and chCCLi7) was upregulated in POFs, suggesting a role for these molecules in tissue regression. The histological findings suggested a significant infiltration of immune cells, especially heterophils, lymphocytes and macrophages, into the regressing POF. The flow cytometry analysis of lymphocyte subpopulations revealed that CD3(+), CD4(+), CD8(+) and Bu-1(+) lymphocytes were significantly increased during this regression. The significant up-regulation of chemokines might have attracted the immune cells during POF regression. The percentage of apoptotic cells was significantly increased during the regression of POF. The up-regulation of IL-1beta, IL-6, IL-10 and TGF-beta2 and down-regulation of GM-CSF might have induced apoptosis during the POF regression. However, expression of IFN-gamma, IL-2, IL-4 and IL-13 was not significantly altered during POF regression. In conclusion, cytokines appear to play an important role in the regression of POF in chicken. Furthermore, the regression of chicken POF seems to be an inflammatory event similar to luteolysis of the mammalian corpus luteum.
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Quimiocinas/genética , Pollos/genética , Citocinas/genética , Folículo Ovárico/metabolismo , Animales , Apoptosis/genética , Apoptosis/fisiología , Pollos/fisiología , Femenino , Expresión Génica , Interferón gamma/genética , Interleucinas/genética , Subgrupos Linfocitarios/citología , Subgrupos Linfocitarios/metabolismo , Folículo Ovárico/citología , Ovario/citología , Ovario/metabolismo , Ovulación/genética , Ovulación/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Crecimiento Transformador beta2/genéticaRESUMEN
We report the effects of supplemental chromium (Cr) on interferon-gamma (IFN-gamma) expression in response to Newcastle disease virus (NDV) vaccine in broiler chicken. Two hundred and eighty day old straight run broiler chicks were randomly selected and allocated at random to one of the seven treatment groups replicated four times having 10 chicks in each replication. Treatment 1 (C) was a standard control diet in which no Cr was offered to birds either through feed or drinking water. In treatments 2-4 (F500, F1000 and F1500), Cr in the form of chromium picolinate (CrPic) was added at rates of 500, 1000 and 1500 ppb in diets, respectively. In treatments 5-7 (W250, W500 and W750), Cr as added to the drinking water at rates of 250, 500 and 750 ppb, respectively. The feeding was continued from 1 to 49 d of age. On 49 d, three birds from each replicate, i.e. 12 birds/treatment were inoculated intramuscularly with R(2)B strain of NDV. Twelve unvaccinated birds along with 12 vaccinated birds from each treatment (four birds each day) were then sacrificed on 1, 3 and 7 days post-immunization to study the IFN-gamma expression using quantitative real time PCR. Following the immunization, the IFN-gamma mRNA expression in spleen was significantly (P<0.01) either up-regulated or down-regulated at day 1 and day 3 post-stimulation. Whereas, IFN-gamma mRNA expression reached basal level in all the vaccinated groups at day 7 post-stimulation. IFN-gamma mRNA expression on day 1 was approximately two and four times higher than the control (C) levels in F500 and W500 groups, respectively. On 3 day post-immunization, IFN-gamma mRNA expression in spleen was about 40 and 27 times higher than controls (C) in F500 and W500 groups, respectively. Other groups (F1000, F1500, W250 and W750) showed down-regulation of IFN-gamma mRNA expression. The results suggested that the dosage of chromium modulates the expression of IFN-gamma and route has effect on the onset and duration of the response. Thus, the supplementation of chromium at appropriate dose might be helpful to enhance the IFN-gamma mRNA expression in response to NDV.
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Pollos/inmunología , Cromo/farmacología , Interferón gamma/metabolismo , Enfermedad de Newcastle/inmunología , Enfermedades de las Aves de Corral/inmunología , Vacunas Virales/inmunología , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , ARN Mensajero/metabolismoRESUMEN
Myostatin is a potent growth and differentiation factor involved in skeletal muscle tissue formation in vertebrates. However, recent studies in chicken embryo suggested that the myostatin was expressed even before the establishment of myogenic lineage. No studies have thus far been reported in birds to define the role of myostatin during the embryonic organogenesis. The present experiment was designed for studying the expression profiles of myostatin mRNA in the chicken liver, heart, brain, and intestine during their morphogenesis, using real-time PCR. The myostatin mRNA expression was significantly upregulated in liver during E15-E18. Similar results were observed during the development of chicken heart. In brain, the expression of myostatin was upregulated from E4 onwards. In intestine, the expression of myostatin was significantly increased many folds on E9-E18. Therefore, the increase in myostatin expression might be related to the growth of liver and heart on days E12-E18; morphogenesis and growth of brain during E15-E18; and morphogenesis and differentiation of intestine during E9-E18. In the present study, the tissue-specific expression of myostatin gene in chicken is similar to fishes, but different from that in mammals. Further, the inspection of chicken genome also suggested that there is no differentiation of GDF-8 and -11. A recent finding suggests that the chicken myostatin gene is closely related to mammals than fishes. Therefore, we propose that the chicken myostatin gene might have diverged in its function between teleosts and mammals. Indeed it is possible that its function might have only become fully differentiated to serve as a control of muscle mass in mammals.
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Embrión de Pollo/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Organogénesis/fisiología , Factor de Crecimiento Transformador beta/metabolismo , Animales , Encéfalo/metabolismo , Perfilación de la Expresión Génica , Corazón/fisiología , Mucosa Intestinal/metabolismo , Hígado/metabolismo , Miostatina , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Crecimiento Transformador beta/genéticaRESUMEN
G-Protein coupled receptors (GPCRs), one of the most important families of drug targets, belong to the super family of integral membrane proteins characterized by seven transmembrane helices. Because they are difficult to crystallize, the three dimensional structure of these receptors have not yet been determined by X-ray crystallography, except one. In the absence of a 3-D structure, in-silico approaches for solving the structure of this class of proteins are widely used and provide valuable information for structure based drug design. There are several web servers and computer programs available that automate the modelling process of GPCRs. Some of these include Modeller, Swiss-Model server, Homer, etc. Using these tools reliable homology models of human histamine H1 receptor (HRH1) and thrombin receptor (PAR-1) have been generated which explain the binding mode of the standard antagonists of these receptors and may be useful in designing their novel antagonists.
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Internet , Modelos Moleculares , Receptor PAR-1/química , Receptores Histamínicos H1/química , Secuencia de Aminoácidos , Humanos , Ligandos , Datos de Secuencia Molecular , Alineación de SecuenciaRESUMEN
Chicken postovulatory follicle (POF) regression occurs via the process of apoptosis. However, the signals and initiator pathways responsible for regression of the POF are unknown. In the current study, we examined gene expression patterns of various caspases (caspase-1, -2 and -3) involved in apoptosis by semi-quantitative RT-PCR. The percentage of apoptotic cells during POF regression was also quantified by flow cytometry. Expression of caspase-3 mRNA was noted in the largest preovulatory follicle (F1). However, the initiator caspases (caspase-1 and -2) were not expressed in F1. During the regression of the POF, caspase-3 was activated during initial stages, whereas the initiator caspases were upregulated at the later stages (POF4 and POF5). The percentage of apoptotic cells was significantly higher during the regression of the POF. It might be possible that levels of caspase-3 mRNA do not necessarily reflect the cell's potential for facilitating apoptosis, as activation of the caspase-3 by initiator caspases is required for its function. We presume that both caspase-1 and caspase-2 were key initiators in the regression of chicken POF and that the apoptosis-mediated regression of POFs might be similar to mammalian corpus luteum involution.
Asunto(s)
Apoptosis , Caspasas/metabolismo , Pollos/fisiología , Folículo Ovárico/fisiología , Ovulación/fisiología , Animales , Caspasas/genética , Femenino , Regulación de la Expresión Génica , ARN Mensajero/metabolismoRESUMEN
In the present experiment, we studied the spatial expression profiles of chemokines and cytokines mRNA in the granulosa (F1Gr) and theca (F1Th) layers of the largest preovulatory follicle in chicken using semi-quantitative PCR. The mRNAs of IL-1beta, IL-6, GM-CSF, chCXCLi2, chCCLi2, chCCLi4, chCCLi7, IFN-gamma, IL-4, IL-13, IL-10 and TGF-beta2 were expressed in the granulosa (F1Gr) and theca (F1Th) layers of the largest preovulatory follicle. However, the transcripts of IL-2 were not detected in any of the samples tested. Significantly higher levels of IL-6 and GM-CSF mRNA expression were noticed in F1Gr when compared to F1Th layer. Expression of chCXCLi2, a CXC chemokine, was almost similar in F1Gr and F1Th layers. However, the expression of CCL chemokines i.e. chCCLi2, chCCLi4, chCCLi7 mRNAs were almost 2 folds higher in F1Th layer in comparison to F1Gr layer. The expression of Th2 cytokines (IL-4 and IL-13) mRNA was noticed in F1Gr and F1Th layers with higher levels in the former. Expression of IFN-gamma mRNA was noticed in F1Gr and F1Th layers. Significantly higher level of TGF-beta2 expression was observed in F1Th in comparison to F1Gr layer. It was concluded from the present study that the mRNA expression of cytokines and chemokines are differentially regulated in the granulosa and theca layers of the largest preovulatory follicle in chicken.