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BACKGROUND: Few studies characterize feeding performance in the NICU when predicting neurodevelopmental outcomes. Our objective was to investigate the relationship between time to full oral feeds (FULL-PO) and neurodevelopmental and feeding outcomes in the first 2 years in preterm infants admitted to the NICU. METHODS: This retrospective study included infants born between 01/01/2014-07/31/2017, gestational age <â32 weeks and/or birth weight <â1500âg. We examined feeding difficulties, cerebral palsy, and Bayley scores for those reaching FULL-PO at a post menstrual age (PMA)≤38.0 weeks (EARLY) vs.>38.0 weeks (LATE). Additionally, the oral feeding achieved at various timepoints between 36- and 42-weeks postmenstrual age (PMA) was measured to construct a timeline of oral feeding acquisition. RESULTS: Of 192 infants, 147(77%) achieved FULL-PO EARLY and 45(23%) LATE. Comorbidities and length of stay were higher and unadjusted Bayley scores were lower at 12 months corrected age (CA) and 24 months chronological age (CH) in the LATE group. Feeding difficulties were higher in the LATE group at 24 months CH. Infants born <â27-28 weeks GA were more likely to achieve oral feeding at a later PMA. Infants with bronchopulmonary dysplasia (BPD) had significant feeding and developmental delays. CONCLUSIONS: Establishing full oral feeds by 38.0 weeks PMA may be used as a predictor for feeding difficulties at 24 months CH. Infants born <â27-28 weeks GA and those with BPD are more likely to take extended amounts of time to achieve full oral feeding and need additional feeding support. Infants with BPD are high risk for neurodevelopmental delays.
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Displasia Broncopulmonar , Recien Nacido Prematuro , Lactante , Recién Nacido , Humanos , Preescolar , Estudios Retrospectivos , Estudios de Seguimiento , Edad Gestacional , Peso al Nacer , Displasia Broncopulmonar/epidemiología , Recién Nacido de muy Bajo PesoRESUMEN
BACKGROUND: The optimal composition of lipid emulsions in parenteral nutrition (PN) for premature infants remains controversial. This study examined the effects of a combination of soybean oil-based (SoyLE) and fish oil-based (FishLE) lipid emulsions compared to FishLE as monotherapy on the lipid and fatty acid profiles and clinical outcomes of premature infants requiring prolonged PN. METHODS: 42 premature infants received FishLE+SoyLE or FishLE. Serum concentrations of lipoproteins and 29 fatty acids (FA) were measured at baseline, 4, and 8 weeks of PN and growth and neurodevelopmental outcomes were measured at 3, 6, 12, 18, and 24 months of life. RESULTS: Lipid profiles were similar between groups. Plasma concentrations of ω-6 fatty acids tended to decrease over time in both groups. Concentrations of most ω-3 fatty acids, in particular docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid, were significantly increased over time in the FishLE+SoyLE group whereas they did not change in the FishLE alone group. However, serum concentrations of almost all fatty acids were similar between groups at the end of the study period. No differences in growth parameters including weight, height, fronto-occipital circumference (FOC), and body mass index (BMI) were observed up to two years of age. Similarly, there were no differences in neurodevelopmental test scores at 6, 12, 18, and 24 months of age. CONCLUSIONS: No substantial differences in lipid profiles and short clinical outcomes were found in infants exposed to FishLE+SoyLE when compared to FishLE.
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The eukaryotic flagellum propels sperm cells and simultaneously detects physical and chemical cues that modulate the waveform of the flagellar beat. Most previous studies have characterized the flagellar beat and swimming trajectories in two space dimensions (2D) at a water/glass interface. Here, using refined holographic imaging methods, we report high-quality recordings of three-dimensional (3D) flagellar bending waves. As predicted by theory, we observed that an asymmetric and planar flagellar beat results in a circular swimming path, whereas a symmetric and non-planar flagellar beat results in a twisted-ribbon swimming path. During swimming in 3D, human sperm flagella exhibit torsion waves characterized by maxima at the low curvature regions of the flagellar wave. We suggest that these torsion waves are common in nature and that they are an intrinsic property of beating axonemes. We discuss how 3D beat patterns result in twisted-ribbon swimming paths. This study provides new insight into the axoneme dynamics, the 3D flagellar beat, and the resulting swimming behavior.
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Flagelos , Natación , Humanos , Masculino , EspermatozoidesRESUMEN
Sperm are highly specialized cells, which have been subject to substantial evolutionary pressure. Whereas some sperm features are highly conserved, others have undergone major modifications. Some of these variations are driven by adaptation to mating behaviours or fitness at the organismic level. Others represent alternative solutions to the same task. Sperm must find the egg for fertilization. During this task, sperm rely on long slender appendages termed flagella that serve as sensory antennas, propellers and steering rudders. The beat of the flagellum is periodic. The resulting travelling wave generates the necessary thrust for propulsion in the fluid. Recent studies reveal that, for steering, different species rely on different fundamental features of the beat wave. Here, we discuss some examples of unity and diversity across sperm from different species with a particular emphasis on the steering mechanisms. This article is part of the Theo Murphy meeting issue 'Unity and diversity of cilia in locomotion and transport'.
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Movimiento Celular/fisiología , Cilios/fisiología , Espermatozoides/fisiología , Animales , Humanos , MasculinoRESUMEN
Protein arginine methyltransferase 1 (PRMT1) is dysregulated in a number of human cancers. Herein, we report that PRMT1 expression is directly associated with epithelial-mesenchymal transition (EMT) in hepatic carcinoma cells. Firstly, we find that PRMT1 expression is higher in hepatic carcinoma tissues than that in normal liver tissues at both mRNA and protein levels, and higher expression of PRMT1 correlates with poor survival in liver tumors. The data in vitro reveals that PRMT1 knockdown inhibits the abilities of proliferation, migration and invasion, while PRMT1 overexpression promotes the above behaviors in hepatic carcinoma cells. Further studies indicate that PRMT1 knockdown remarkably decreases the expression of mesenchymal markers including Vimentin, Snail and N-cadherin, and upregulates expression of epithelial markers E-cadherin. Conversely, PRMT1 overexpression results in the opposite effects. Additionally, we identified that PRMT1 knockdown resulted in downregulation of TGF-ß1, p-Smad2 and p-Smad3, while PRMT1 overexpression activated TGF-ß1, p-Smad2 and p-Smad3. These findings suggest that PRMT1 promotes EMT in hepatic carcinoma cells probably via TGF-ß1/Smad pathway, and might represent a novel anti-liver cancer strategy.
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Carcinoma Hepatocelular/metabolismo , Transición Epitelial-Mesenquimal , Neoplasias Hepáticas/metabolismo , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteínas Represoras/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Hepáticas/patología , Transducción de Señal , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
The objective of this study is to determine the contribution of Chile's 2005 child restraint legislation to the reduction of child passenger fatalities and severe injuries. We analysed motor vehicle injury and fatality data from Chile's National Road Safety Commission of the Ministry of Transport from 2000 to 2012 to determine the effect of Chile's 2005 mandatory child restraint legislation. Using interrupted time-series Poisson regression models, we assessed the effect of the law on two dependent variables: (1) number of child fatalities in car and (2) number of children severely injured. The independent variable was the 2005 enactment of Chile's mandatory child restraint legislation. Coefficients from the interrupted time-series Poisson regression models indicate that Chile's enactment of child restraint legislation in 2005 is significantly associated with a total of 35% reduction in child passenger severely injured but only three years after its enactment, and significant associations between this policy and child fatalities were less evident.
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Accidentes de Tránsito/mortalidad , Accidentes de Tránsito/estadística & datos numéricos , Conducción de Automóvil/legislación & jurisprudencia , Sistemas de Retención Infantil , Heridas y Lesiones/epidemiología , Automóviles/estadística & datos numéricos , Niño , Preescolar , Chile/epidemiología , Humanos , Lactante , Recién Nacido , Análisis de Series de Tiempo Interrumpido , Distribución de Poisson , Índices de Gravedad del TraumaRESUMEN
Although hepatocellular carcinoma (HCC) is usually response to radiation therapy, radioresistance is still the major obstacle that limits the efficacy of radiotherapy for HCC patients. Therefore, further investigation of underlying mechanisms in radioresistant HCC cells is warranted. In this study, we determined the effect of early growth response factor (Egr-1) on irradiation-induced autophagy and radioresistance in HCC cell lines SMMC-7721 and HepG2. We showed that autophagy-related gene 4B (Atg4B) is induced by Egr-1 upon ionizing radiation (IR) in HCC cells. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) revealed that Egr-1 binds to the Atg4B promoter to upregulate its expression in HCC cells. Suppression of Egr-1 function by dominant-negative Egr-1 dampens IR-induced autophagy, cell migration, and increases cell sensitivity to radiotherapy. Together, these results suggest that Egr-1 contributes to HCC radioresistance through directly upregulating target gene Atg4B, which may serve as a protective mechanism by preferential activation of the autophagy.
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PTEN serves as an intrinsic brake on neurite outgrowth, but the regulatory mechanism that governs its action is not clear. In the present study, miR-29a was found to increase neurite outgrowth by decreasing PTEN expression. Results showed that miR-92a-1, miR-29a, miR-92b, and miR-29c expression levels increased during nerve growth factor (NGF)-induced differentiation of PC12 cells. Based on in silico analysis of possible miR-29a targets, PTEN mRNA may be a binding site for miR-29a. A protein expression assay and luciferase reporter assay showed that miR-29a could directly target the 3'-UTRs (untranslated regions) of PTEN mRNA and down-regulate the expression of PTEN. PC12 cells infected with lentiviral pLKO-miR-29a showed far higher levels of miR-29a and Akt phosphorylation level than those infected with control. This promoted neurite outgrowth of PC12 cells. Collectively, these results indicate that miR-29a is an important regulator of neurite outgrowth via targeting PTEN and that it may be a promising therapeutic target for neural disease.
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MicroARNs/metabolismo , Neuritas/fisiología , Fosfohidrolasa PTEN/metabolismo , Regiones no Traducidas 3' , Animales , Western Blotting , Aumento de la Célula , Vectores Genéticos , Inmunohistoquímica , Lentivirus/genética , MicroARNs/genética , Factor de Crecimiento Nervioso/metabolismo , Células PC12 , Fosfohidrolasa PTEN/genética , Fosforilación/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/metabolismo , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , TransfecciónRESUMEN
Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT) might be a key event for cancer progression. The upregulation of Snail1, one of the most extensively studied EMT regulators, has been implicated in cancer metastasis, but the underlying mechanisms remain unclear. This study aims to identify that Snail1 targets regulating EMT-associated cancer cell migration. Human lung carcinoma A549 cells were treated with transforming growth factor beta 1 (TGF-ß1), and EMT-associated phenotypic and functional alterations were monitored. TGF-ß1 induced typical EMT-like morphological changes, 'cadherin switching' and cell migration in A549 cells. TGF-ß1 stimulation induced rapid and persistent upregulation of Snail1. Moreover, Snail1 upregulation was required for EMT-associated cell migration. Several metastasis suppressors with putative Snail1-binding sites in their promoters were dramatically repressed in A549 cells during TGF-ß1-induced EMT. Gain- and loss-of Snail1 function experiments demonstrated that scavenger receptor class A member 5 (SCARA5) was negatively regulated by Snail1. Importantly, SCARA5 downregulation was essential for EMT-induced migration in A549 cells. The chromatin immunoprecipitation assay revealed that Snail1 could bind to the E-box elements in SCARA5 promoter, implying that SCARA5 is a direct Snail1 target modulating cancer cell mobility during EMT. In addition, we showed that DNA methyltransferase 1 was physically associated with Snail1 to silence SCARA5 expression with an unidentified DNA methylation-independent mechanism, suggesting the complexity of Snail1-mediated epigenetic regulation. Collectively, our data demonstrated that EMT-regulator Snail1 suppresses the expression of SCARA5 to promote cancer progression, highlighting the possibility to target Snail1 and SCARA5 for cancer treatment.
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The objective of this study was to examine the possibility of applying visible and near-infrared spectroscopy to the quantitative detection of irradiation dose of irradiated milk powder. A total of 150 samples were used: 100 for the calibration set and 50 for the validation set. The samples were irradiated at 5 different dose levels in the dose range 0 to 6.0 kGy. Six different pretreatment methods were compared. The prediction results of full spectra given by linear and nonlinear calibration methods suggested that Savitzky-Golay smoothing and first derivative were suitable pretreatment methods in this study. Regression coefficient analysis was applied to select effective wavelengths (EW). Less than 10 EW were selected and they were useful for portable detection instrument or sensor development. Partial least squares, extreme learning machine, and least squares support vector machine were used. The best prediction performance was achieved by the EW-extreme learning machine model with first-derivative spectra, and correlation coefficients=0.97 and root mean square error of prediction=0.844. This study provided a new approach for the fast detection of irradiation dose of milk powder. The results could be helpful for quality detection and safety monitoring of milk powder.
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Irradiación de Alimentos/métodos , Leche/efectos de la radiación , Animales , Productos Lácteos/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Polvos , Espectroscopía Infrarroja Corta , Análisis Espectral/métodosRESUMEN
With the global climate warming, reducing greenhouse gas emissions becomes a focused problem for the world. The carbon capture and storage (CCS) techniques could mitigate CO2 into atmosphere, but there is a risk in case that the CO2 leaks from underground. The objective of this paper is to study the chlorophyll contents (SPAD value), relative water contents (RWC) and leaf spectra changing features of beetroot under CO2 leakage stress through field experiment. The result shows that the chlorophyll contents and RWC of beetroot under CO2 leakage stress become lower than the control beetroot', and the leaf reflectance increases in the 550 nm region and decreases in the 680nm region. A new vegetation index (R550/R680) was designed for identifying beetroot under CO2 leakage stress, and the result indicates that the vegetation index R550/R680 could identify the beetroots after CO2 leakage for 7 days. The index has strong sensitivity, stability and identification for monitoring the beetroots under CO2 stress. The result of this paper has very important meaning and application values for selecting spots of CCS project, monitoring and evaluating land-surface ecology under CO2 stress and monitoring the leakage spots by using remote sensing.
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Atmósfera , Dióxido de Carbono , Monitoreo del Ambiente/métodos , Hojas de la Planta , Carbono , Clorofila/análisis , Clima , Calentamiento Global , Análisis Espectral , Estrés Fisiológico , AguaRESUMEN
Based on aquatic optics Monte Carlo hyperspectral simulation, the interactions between spectral characteristics of chlorophyll a, total suspended matter (TSM) and colored dissolved organic matter (CDOM) were discussed. The result shows that the nonlinear and spectrally varying interactions between different water components are extremely highly asymmetric. The existing of chlorophyll a and CDOM has little effects on the characteristic wavebands selection and information retrieval of TSM, while the effects of TSM on chlorophyll a are obvious. With the stepwise additions of TSM, the response of chlorophyll a to its concentration becomes weak. When the concentration of TSM increases to a certain degree, the spectral response of chlorophyll a concentration will disappear. Even at the sensitivity waveband of chlorophyll a such as 670 nm, when the TSM is in high concentration, the spectral reflectance will not change with chlorophyll a concentration, which lead to difficulty to extract the chlorophyll a concentration in turbid water dominated by suspended matter. The existing of CDOM causes the blue and green band ratio algorithm to fail when the chlorophyll a is in middle to high concentration. The spectral effects on CDOM of the water body dominated by TSM are more obvious than that dominated by chlorophyll a. There are strong inhibition effects of TSM on the CDOM spectral properties in the short bands. The research results can provide theoretical basis for characteristic waveband selection, the application scope of water component concentration inversion algorithm and the waveband setting for case 2 water remote sensing.
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We have recently identified ZNF185 as a gene that is downregulated in prostate cancer (PCa), in part via epigenetic alteration, and maybe associated with disease progression. In this study, we cloned the ZNF185 cDNA from normal human prostate tissues and investigated its biological function. We show that ZNF185 is a novel actin-cytoskeleton-associated Lin-l 1, Isl-1 and Mec-3 (LIM) domain-containing protein that localizes to F-actin structures, and is enriched at focal adhesions. We find that the NH(2)-terminal region, which we designate the actin-targeting domain, facilitates ZNF185 binding to actin in vitro and is both necessary and sufficient to mediate actin-cytoskeleton targeting of ZNF185, whereas the LIM domain, which is localized in the COOH-terminus is dispensable for this phenomenon. Interestingly, ectopic expression of full-length ZNF185, but not a mutant lacking the actin-targeting domain, could suppress proliferation and anchorage-independent growth of PCa cells. Together, our data suggest that ZNF185 may function as a tumor-suppressor protein by associating with the actin-cytoskeleton.
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Actinas/metabolismo , Proteínas de Unión al ADN/fisiología , Proteínas de Homeodominio/metabolismo , Neoplasias de la Próstata/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , División Celular , Línea Celular Tumoral , Proteínas del Citoesqueleto , ADN Complementario , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Evolución Molecular , Proteínas con Dominio LIM , Masculino , Datos de Secuencia Molecular , Neoplasias de la Próstata/patología , Unión Proteica , Homología de Secuencia de AminoácidoRESUMEN
OBJECTIVE: This study describes the incidence, correlates and subsequent morbidities of hyperglycemia, a highly prevalent condition in extremely low birth weight (ELBW) infants. STUDY DESIGN: A retrospective chart review of 169 infants with birth weight (BW)<1000 g was conducted. Hyperglycemia was defined as plasma glucose level > or =150 mg/dl during the first 2 weeks of life. Data were analyzed by logistic regression, multivariate analysis and Fisher exact test. RESULTS: Overall, 88% of the study sample developed hyperglycemia in the first 2 weeks of life. Both gestational age (GA) (odds ratio (OR) 0.11, 95% confidence interval (CI)=0.01-0.89) and chorioamnionitis (OR 0.10, 95% CI=0.01-0.64) were inversely associated with hyperglycemia, whereas BW, sepsis and postnatal steroid exposure were not. After adjusting for GA, BW and postnatal steroids, hyperglycemia was associated with a statistically significant increase in retinopathy of prematurity (ROP) (OR 4.6, 95% CI 1.12-18.9). No association was found with bronchopulmonary dysplasia, intraventricular hemorrhage, death or prolonged hospital stay. CONCLUSION: Lower GA was identified as the main factor associated with hyperglycemia in ELBW infants during the first 2 weeks of life. Hyperglycemia was associated with an increased incidence of ROP; further studies need to determine if this association is causal.
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Corioamnionitis/etnología , Hispánicos o Latinos , Hiperglucemia/etnología , Recien Nacido con Peso al Nacer Extremadamente Bajo , Retinopatía de la Prematuridad/etiología , Femenino , Edad Gestacional , Glucosa/farmacocinética , Humanos , Hiperglucemia/etiología , Recién Nacido , Recien Nacido Prematuro , Modelos Logísticos , Masculino , Análisis Multivariante , Nutrición Parenteral/estadística & datos numéricos , Embarazo , Pronóstico , Estudios Retrospectivos , Sepsis/epidemiologíaRESUMEN
The application of atrazine in China during the last ten years has led to some environmental problems. In this paper, the multimedia model of atrazine in soil-plant-groundwater system at Baiyangdian Lake area in Northern China was established using a fugacity approach, and verified with observed values. The model involved 7 environmental compartments which are air, groundwater, soil, corn roots, corn stem, corn leaf and kernel of corn. The results showed that the relative errors between calculated and observed values have a mean value of 24.7%, the highest value is 48% and the lowest value is 1.4%. All these values indicated that this multimedia model can be used to simulate the environmental fate of atrazine. Both the calculated and observed values of concentrations of atrazine in plant compartments are in the following order: in corn roots > in corn stem > in kernel of corn > in corn leaf, it exhibited a good regularity. The prediction results indicated that concentrations of atrazine in the groundwater and kernel of corn will override the limitation of 3 micrograms/L and 0.05 mg/kg respectively.
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Atrazina/farmacocinética , Herbicidas/farmacocinética , Modelos Teóricos , Multimedia , Atrazina/análisis , Predicción , Herbicidas/análisis , Raíces de Plantas , Plantas , Contaminantes del Suelo , Distribución Tisular , Contaminantes del Agua , Zea mays/químicaRESUMEN
BACKGROUND: Conventional methods for measuring the total bilirubin concentration in blood require the use of serum or plasma, but physically separating red blood cells from plasma by centrifugation is a time-consuming and potentially dangerous process that does not lend itself to rapid, near-patient testing. Therefore, we have sought to determine whether spectrophotometric measurements of total bilirubin concentration are feasible in unaltered whole blood. METHODS: We modified an Hb-Quick hemoglobinometer (Avox Systems, Inc., San Antonio, TX), a relatively new, portable, battery-powered instrument that uses disposable cuvettes and a reagentless system to measure total hemoglobin in nonhemolyzed, whole blood. The prototype consisted of an Hb-Quick equipped with light-emitting diodes with emissions at five different wavelengths to measure total bilirubin and total hemoglobin. Using blood samples from neonates with suspected hyperbilirubinemia, we made measurements on plasma from centrifuged samples and on hemolyzed and nonhemolyzed aliquots of the same blood samples. RESULTS: In the first series of experiments, we compared the Unistat bilirubinometer's readings with the prototype's measurements of bilirubin in plasma. There was a close linear correlation between the prototype's measurements and those of the reference instrument (slope=1.01, r(2)=0.991). Subsequently, we used the prototype's measurements on plasma as the reference method and compared them with readings on hemolyzed and nonhemolyzed aliquots of each sample. Readings on hemolyzed and nonhemolyzed aliquots were significantly correlated with the measurements in plasma, but the regression lines did not have a slope of 1. However, when the measurements on hemolyzed and nonhemolyzed blood were scaled appropriately to compensate for the fact that red cells "dilute" the bilirubin in plasma, the correlation coefficients improved, and there was then a 1:1 relationship between the measurements in whole blood and plasma. CONCLUSIONS: These preliminary findings demonstrate the feasibility of developing a portable instrument to measure total bilirubin in unaltered whole blood. The advantages of this method are speed, elimination of centrifugation or other sample preparation, and instrument portability. The disadvantage is that the concentration units are unconventional, i.e., milligrams of bilirubin per volume of whole blood. However, the instrument can be programmed to display the total bilirubin concentration in traditional units, e.g., milligrams of bilirubin per volume of plasma.
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Bilirrubina/sangre , Análisis Químico de la Sangre/instrumentación , Espectrofotometría/métodos , Estudios de Factibilidad , HumanosRESUMEN
In this paper, the concentration distribution and environmental fate of atrazine in a crop-soil-groundwater system at Baiyangdian Lake area of North China were studied. The concentration of the herbicide in spatial and vertical soils, and in roots, stem, leaf, corncob and kernel of corn, and in groundwater were measured by HPLC. The results showed that the variation of spatial concentration of atrazine in soil can be described by first-order kinetics equation which has a half-life of 360 days and a rate constant of 0.0019 d-1. The vertical variation of atrazine concentration with soil depth follows the exponential decay law. After 120 days following atrazine application, the mass distributions of this herbicide in crop-soil-groundwater system are 71% in soil, 20% in groundwater and 1% in crop respectively, and 8% due to loss by degradation or often removal processes. The order of atrazine concentration in every part of corn crop is in roots > in corncob > in kernel of corn > in leaf.
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Atrazina/análisis , Herbicidas/análisis , Contaminantes del Suelo/análisis , Contaminantes Químicos del Agua/análisis , China , Productos Agrícolas/metabolismo , Agua Dulce/análisis , Cinética , Estructuras de las Plantas/metabolismo , Suelo/análisisRESUMEN
In recent studies using freshly isolated rat cholangiocytes, we established that water crosses the cholangiocyte membrane by a channel-mediated mechanism involving aquaporins, a family of water-channel proteins. Our goal was to address the importance of channel-mediated water transport in ductal bile formation by employing a physiologic experimental model, the enclosed, polarized rat intrahepatic bile duct unit (IBDU). Expansion and reduction of luminal areas as a reflection of water movement into and out of IBDUs prepared from livers of normal rats were measured by quantitative computer-assisted image analysis. When enclosed IBDUs were exposed to inward or outward osmotic gradients, their luminal area rapidly increased (approximately 25%) or decreased (approximately 20%) reflecting net water secretion or absorption, respectively. These effects were specifically inhibited by 2 water channel blockers, DMSO and HgCl2. In both instances, beta-mercaptoethanol reversed the inhibitory effects. In the absence of an osmotic gradient, choleretic agents (secretin and forskolin) and a cholestatic hormone (somatostatin) induced a significant increase or decrease of IBDU luminal area by 21% and 22%, respectively. These effects were also inhibited by DMSO and reversed by beta-mercaptoethanol. Under our experimental conditions, DMSO did not interfere with either forskolin-induced cAMP synthesis or the generation of osmotic driving forces via the apical chloride-bicarbonate exchanger. Protamine, an inhibitor of the paracellular pathway, had no effect on hypotonic or forskolin-induced water secretion in IBDUs. These results in a physiologically relevant model of ductal bile formation provide additional support for the concept that osmotically driven and agonist-stimulated water movement into (secretion) and out of (absorption) the biliary ductal lumen is transcellular and water channel-mediated.
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Conductos Biliares Intrahepáticos/metabolismo , Canales Iónicos/fisiología , Agua/metabolismo , Animales , Conductos Biliares Intrahepáticos/citología , Conductos Biliares Intrahepáticos/efectos de los fármacos , Colforsina/farmacología , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Masculino , Ósmosis , Ratas , Ratas Endogámicas F344 , Secretina/farmacología , Somatostatina/farmacologíaRESUMEN
Mutations in the homeotic gene, Ultrabithorax (Ubx), result in the transformation of the third thoracic (T3) segment into the second thoracic (T2) segment. Although it has been well established that these mutations have striking effects on adult epidermal structures in T3, the effect of these mutations on the adult musculature has been controversial. In this study, a series of Ubx regulatory mutations, anterobithorax, bithorax, postbithorax, and bithoraxoid, as well as combinations of these alleles were used to reevaluate the role of Ubx in the patterning of the T3 musculature. Homeotic indirect and direct flight muscles (IFMs and DFMs) were identified in the transformed T3 segment of all alleles and allelic combinations with the exception of postbithorax. We critically evaluated the pattern and amount of these muscles and found that while the amount and/or quality of homeotic IFMs increased, the amount of homeotic DFMs did not vary significantly as the severity of the ectodermal transformation increased. Because Ubx is not expressed in the adult mesoderm of T3, these results suggest that inductive cues play a major role in the patterning of adult thoracic muscles. We provide a model that illustrates the central role of inductive cues in generating the final adult muscle pattern in the thorax.