RESUMEN

Frontal boundaries have been shown to cause large changes in CO2 mole-fractions, but clouds and the complex vertical structure of fronts make these gradients difficult to observe. It remains unclear how the column average CO2 dry air mole-fraction (XCO2) changes spatially across fronts, and how well airborne lidar observations, data assimilation systems, and numerical models without assimilation capture XCO2 frontal contrasts (ΔXCO2, i.e., warm minus cold sector average of XCO2). We demonstrated the potential of airborne Multifunctional Fiber Laser Lidar (MFLL) measurements in heterogeneous weather conditions (i.e., frontal environment) to investigate the ΔXCO2 during four seasonal field campaigns of the Atmospheric Carbon and Transport-America (ACT-America) mission. Most frontal cases in summer (winter) reveal higher (lower) XCO2 in the warm (cold) sector than in the cold (warm) sector. During the transitional seasons (spring and fall), no clear signal in ΔXCO2 was observed. Intercomparison among the MFLL, assimilated fields from NASA's Global Modeling and Assimilation Office (GMAO), and simulations from the Weather Research and Forecasting--Chemistry (WRF-Chem) showed that (a) all products had a similar sign of ΔXCO2 though with different levels of agreement in ΔXCO2 magnitudes among seasons; (b) ΔXCO2 in summer decreases with altitude; and (c) significant challenges remain in observing and simulating XCO2 frontal contrasts. A linear regression analyses between ΔXCO2 for MFLL versus GMAO, and MFLL versus WRF-Chem for summer-2016 cases yielded a correlation coefficient of 0.95 and 0.88, respectively. The reported ΔXCO2 variability among four seasons provide guidance to the spatial structures of XCO2 transport errors in models and satellite measurements of XCO2 in synoptically-active weather systems.

RESUMEN

Salinity-induced lipid alterations have been reported in many plant species; however, how lipid biosynthesis and metabolism are regulated and how lipids work in plant salt tolerance are much less studied. Here, a constitutively much higher phosphatidylserine (PS) content in the plasma membrane (PM) was found in the euhalophyte Salicornia europaea than in Arabidopsis. A gene encoding PS synthase (PSS) was subsequently isolated from S. europaea, named SePSS, which was induced by salinity. Multiple alignments and phylogenetic analysis suggested that SePSS belongs to a base exchange-type PSS, which localises to the endoplasmic reticulum. Knockdown of SePSS in S. europaea suspension cells resulted in reduced PS content, decreased cell survival rate, and increased PM depolarization and K+ efflux under 400 or 800 mM NaCl. By contrast, the upregulation of SePSS leads to increased PS and phosphatidylethanolamine levels and enhanced salt tolerance in Arabidopsis, along with a lower accumulation of reactive oxygen species, less membrane injury, less PM depolarization and higher K+/Na+ in the transgenic lines than in wild-type (WT). These results suggest a positive correlation between PS levels and plant salt tolerance, and that SePSS participates in plant salt tolerance by regulating PS levels, hence PM potential and permeability, which help maintain ion homeostasis. Our work provides a potential strategy for improving plant growth under multiple stresses.

Asunto(s)

CDPdiacilglicerol-Serina O-Fosfatidiltransferasa/fisiología , Membrana Celular/fisiología , Chenopodiaceae/enzimología , Proteínas de Plantas/fisiología , Arabidopsis , CDPdiacilglicerol-Serina O-Fosfatidiltransferasa/genética , CDPdiacilglicerol-Serina O-Fosfatidiltransferasa/metabolismo , Membrana Celular/metabolismo , Chenopodiaceae/genética , Chenopodiaceae/metabolismo , Chenopodiaceae/fisiología , Retículo Endoplásmico/enzimología , Técnicas de Silenciamiento del Gen , Fosfatidilserinas/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Estrés Salino , Tolerancia a la Sal , Alineación de Secuencia

RESUMEN

Purpose: Interleukin-31 receptor α (IL31RA) usually mediates IL-31 induced inflammation and allergic diseases. However, the functional roles of IL-31/IL31RA signaling in basal-like breast cancer (BLBC) progression remain totally unclear. Methods: Tumorsphere formation, transwell, and wound healing assays were used to measure the BLBC progression. We implanted tumor cells in mammary fat pad and tail vein of nude mice to detect the growth and metastasis of BLBC cells. Luciferase and ChIP assays were employed to measure the transcriptional regulation. Western blot and real-time PCR assays as well as bio-informatics analyses were conducted to observe the expression of IL31RA. Results: We found that silencing of IL31RA suppresses the cancer stem cell-like properties, migration and invasion of BLBC cells in vitro as well as tumor growth and metastasis in vivo. Knockdown of IL31RA ameliorates IL-31-mediated pro-oncogenic functions. Overexpression of IL31RA in luminal breast cancer cells enhances the cancer stem cell-like properties and cell motility. Our data further identified IL31RA as a target gene of Twist/BRD4 transcription complex. Conclusion: Overall, these data indicate that IL31RA promotes basal-like breast cancer progression and metastasis, suggesting that targeting of IL-31/IL31RA axis might be beneficial to treatment of BLBC.

RESUMEN

BET bromodomain inhibitors (BETi), such as JQ1, have been demonstrated to effectively kill multiple types of cancer cells. However, the underlying mechanisms for BETi resistance remain largely unknown. Our evidences show that JQ1 treatment evicts BRD4 from the FOXD3-localized MIR548D1 gene promoter, leading to repression of miR-548d-3p. The loss of miRNA restores JunD expression and subsequent JunD-dependent transcription of RPS6KA2 gene. ERK1/2/5 kinases phosphorylate RSK3 (RPS6KA2), resulting in the enrichment of activated RSK3 and blockade of JQ1 killing effect. Dual inhibition of MEKs/ERKs or single EGFR inhibition are able to mimic the effect of JunD/RSK3-knockdown to reverse BETi resistance. Collectively, our study indicates that loss of BRD4/FOXD3/miR-548d-3p axis enhances JunD/RSK3 signalling and determines BET inhibition resistance, which can be reversed by targeting EGFR-MEK1/2/5-ERK1/2/5 signalling.

Asunto(s)

Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/metabolismo , Resistencia a Antineoplásicos , Factores de Transcripción Forkhead/metabolismo , MicroARNs/genética , Proteínas Proto-Oncogénicas c-jun/metabolismo , Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismo , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismo , Antineoplásicos/farmacología , Azepinas/farmacología , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Factores de Transcripción Forkhead/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Fosforilación , Regiones Promotoras Genéticas , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-jun/genética , Proteínas Quinasas S6 Ribosómicas 90-kDa/genética , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/genética , Triazoles/farmacología

RESUMEN

PA28α/ß activated immunoproteasome frequently participates in MHC class I antigen processing, however, whether it is involved in breast tumor progression remains largely unclear. Here, our evidences show that PA28α/ß proteins are responsible for breast cancer cell migration, invasion, and metastasis. Knockdown of immunoproteasome core subunit ß5i also robustly suppresses the tumor cell migration and invasion. Interestingly, silencing of PA28α/ß and ß5i up-regulates the protein expression of cyclin-dependent kinase 15 (CDK15). Our data further indicate that the loss of CDK15 is important for breast tumor cell invasion and metastasis. Taken together, this study implicates that targeting of PA28α/ß represents a potential way for treatment of metastatic breast cancer.

RESUMEN

BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or CDK6 significantly overcomes the resistance of luminal breast cancer cells to AKT inhibitors in vitro and in vivo. Our study reports the involvement of BRD4/FOXO3a/CDK6 axis in AKTi resistance and provides potential therapeutic strategies for treating resistant breast cancer.

Asunto(s)

Neoplasias de la Mama/metabolismo , Quinasa 6 Dependiente de la Ciclina/metabolismo , Proteína Forkhead Box O3/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factores de Transcripción/metabolismo , Acetilación/efectos de los fármacos , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Proteínas de Ciclo Celular , Línea Celular Tumoral , Núcleo Celular/genética , Núcleo Celular/metabolismo , Quinasa 6 Dependiente de la Ciclina/genética , Femenino , Proteína Forkhead Box O3/genética , Regulación de la Expresión Génica , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Humanos , Ratones , Ratones Desnudos , Proteínas Nucleares/química , Proteínas Nucleares/genética , Oxadiazoles/administración & dosificación , Regiones Promotoras Genéticas , Unión Proteica/efectos de los fármacos , Dominios Proteicos , Inhibidores de Proteínas Quinasas/administración & dosificación , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , Pirimidinas/administración & dosificación , Pirroles/administración & dosificación , Sirtuinas/genética , Sirtuinas/metabolismo , Factores de Transcripción/química , Factores de Transcripción/genética

RESUMEN

MAIN CONCLUSION: The V-ATPase subunit A participates in vacuolar Na + compartmentalization in Salicornia europaea regulating V-ATPase and V-PPase activities. Na+ sequestration into the vacuole is an efficient strategy in response to salinity in many halophytes. However, it is not yet fully understood how this process is achieved. Particularly, the role of vacuolar H+-ATPase (V-ATPase) in this process is controversial. Our previous proteomic investigation in the euhalophyte Salicornia europaea L. found a significant increase of the abundance of V-ATPase subunit A under salinity. Here, the gene encoding this subunit named SeVHA-A was characterized, and its role in salt tolerance was demonstrated by RNAi directed downregulation in suspension-cultured cells of S. europaea. The transcripts of genes encoding vacuolar H+-PPase (V-PPase) and vacuolar Na+/H+ antiporter (SeNHX1) also decreased significantly in the RNAi cells. Knockdown of SeVHA-A resulted in a reduction in both V-ATPase and vacuolar H+-PPase (V-PPase) activities. Accordingly, the SeVHA-A-RNAi cells showed increased vacuolar pH and decreased cell viability under different NaCl concentrations. Further Na+ staining showed the reduced vacuolar Na+ sequestration in RNAi cells. Taken together, our results evidenced that SeVHA-A participates in vacuolar Na+ sequestration regulating V-ATPase and V-PPase activities and thereby vacuolar pH in S. europaea. The possible mechanisms underlying the reduction of vacuolar V-PPase activity in SeVHA-A-RNAi cells were also discussed.

Asunto(s)

Chenopodiaceae/enzimología , Pirofosfatasa Inorgánica/metabolismo , ATPasas de Translocación de Protón Vacuolares/metabolismo , Adaptación Fisiológica , Chenopodiaceae/genética , Chenopodiaceae/fisiología , Pirofosfatasa Inorgánica/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Interferencia de ARN , Salinidad , Tolerancia a la Sal , Plantas Tolerantes a la Sal , Sodio/metabolismo , Intercambiadores de Sodio-Hidrógeno/genética , Intercambiadores de Sodio-Hidrógeno/metabolismo , Estrés Fisiológico , ATPasas de Translocación de Protón Vacuolares/genética

RESUMEN

KEY MESSAGE: A Salicornia europaea L. in vitro cell transformation system was developed and further applied to SeNHX1 function investigation. The exploration of salt-tolerant genes from halophyte has seriously been limited by the lack of self-dependent transformation system. Here, an Agrobacterium tumefaciens-mediated in vitro cell transformation system of euhalophyte Salicornia europaea L. was developed. Calli derived from hypocotyl of S. europaea were co-cultured for 3 days with Agrobacterium at OD600 ranging from 1.0 to 1.5 and then selected with 25 mg/L hygromycin (Hyg). The transformed cells were identified from Hyg positive calli by GUS assay and qRT-PCR, and the transformation efficiency was up to 74.4%. The practicality of this system was further tested via genetic manipulation of S. europaea Na+/H+ antiporter 1 (SeNHX1) gene by creating the overexpressing, silencing, and empty vector cells. Survival ratio and Na+ distribution under salt treatment showed obvious differences in SeNHX1-overexpressing, -silencing, and empty vector cells, indicating the feasibility of this system to analyze gene function. This investigation is enlightening for studies in other non-model plants lacking of self-dependent transformation system.

Asunto(s)

Chenopodiaceae/metabolismo , Agrobacterium tumefaciens/genética , Chenopodiaceae/efectos de los fármacos , Chenopodiaceae/genética , Hipocótilo/efectos de los fármacos , Hipocótilo/genética , Hipocótilo/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/efectos de los fármacos , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Tolerancia a la Sal/genética , Plantas Tolerantes a la Sal/efectos de los fármacos , Plantas Tolerantes a la Sal/genética , Plantas Tolerantes a la Sal/metabolismo , Cloruro de Sodio/farmacología , Intercambiadores de Sodio-Hidrógeno/genética , Intercambiadores de Sodio-Hidrógeno/metabolismo , Transformación Genética/genética

RESUMEN

Certain studies have suggested that the tumor necrosis factor-α (TNF-α) -857 C/T polymorphism is associated with risk of ankylosing spondylitis. However, the conclusions remain controversial. Therefore, we performed a meta-analysis to provide a more precise conclusion. Such databases as PubMed, Embase, CBM, CNKI, and Wanfang Data were searched to identify relevant studies up to August 26, 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between TNF-α -857 C/T polymorphism and ankylosing spondylitis susceptibility. A total of 10 studies were included in the meta-analysis. Overall, an elevated risk between TNF-α -857 C/T polymorphism and ankylosing spondylitis was observed in three genetic model (T vs. C: OR 1.86, 95% CI 1.19-2.92; CT vs. CC: OR 2.51, 95% CI 1.49-4.23; TT + CT vs. CC: OR 2.46, 95% CI 1.40-4.30), except in homozygote model (TT vs. CC: OR 2.41, 95% CI 0.96-6.06) and recessive model (TT vs. CT + CC: OR 1.54, 95% CI 0.71-3.35). Sensitivity analysis showed the overall results were robust. Subgroup analyses according to Hardy-Weinberg equilibrium and ethnicity showed that the increased risk of ankylosing spondylitis were predominant in Asian population. This meta-analysis indicated that TNF-α -857 C/T polymorphism might increase the susceptibility of ankylosing spondylitis, especially in Asians. Further studies were needed to verify the conclusion.

RESUMEN

This study evaluates the capability of atmospheric CO2 column measurements under cloudy conditions using an airborne intensity-modulated continuous-wave integrated-path-differential-absorption lidar operating in the 1.57-µm CO2 absorption band. The atmospheric CO2 column amounts from the aircraft to the tops of optically thick cumulus clouds and to the surface in the presence of optically thin clouds are retrieved from lidar data obtained during the summer 2011 and spring 2013 flight campaigns, respectively. For the case of intervening thin cirrus clouds with an average cloud optical depth of about 0.16 over an arid/semi-arid area, the CO2 column measurements from 12.2 km altitude were found to be consistent with the cloud free conditions with a lower precision due to the additional optical attenuation of the thin clouds. The clear sky precision for this flight campaign case was about 0.72% for a 0.1-s integration, which was close to previously reported flight campaign results. For a vegetated area and lidar path lengths of 8 to 12 km, the precision of the measured differential absorption optical depths to the surface was 1.3 - 2.2% for 0.1-s integration. The precision of the CO2 column measurements to thick clouds with reflectance about 1/10 of that of the surface was about a factor of 2 to 3 lower than that to the surface owing to weaker lidar returns from clouds and a smaller CO2 differential absorption optical depth compared to that for the entire column.

RESUMEN

Improving crop nitrogen (N) use efficiency under salinity is essential for the development of sustainable agriculture in marginal lands. Salicornia europaea is a succulent euhalophyte that can survive under high salinity and N-deficient habitat conditions, implying that a special N assimilation mechanism may exist in this plant. In this study, phenotypic and physiological changes of S. europaea were investigated under different nitrate and NaCl levels. The results showed that NaCl had a synergetic effect with nitrate on the growth of S. europaea. In addition, the shoot nitrate concentration and nitrate uptake rate of S. europaea were increased by NaCl treatment under both low N and high N conditions, suggesting that nitrate uptake in S. europaea was NaCl facilitated. Comparative proteomic analysis of root plasma membrane (PM) proteins revealed 81 proteins, whose abundance changed significantly in response to NaCl and nitrate. These proteins are involved in metabolism, cell signalling, transport, protein folding, membrane trafficking, and cell structure. Among them, eight proteins were calcium signalling components, and the accumulation of seven of the above-mentioned proteins was significantly elevated by NaCl treatment. Furthermore, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) was significantly elevated in S. europaea under NaCl treatment. The application of the Ca(2+) channel blocker LaCl3 not only caused a decrease in nitrate uptake rate, but also attenuated the promoting effects of NaCl on nitrate uptake rates. Based on these results, a possible regulatory network of NaCl-facilitated nitrate uptake in S. europaea focusing on the involvement of Ca(2+) signalling was proposed.

Asunto(s)

Señalización del Calcio/efectos de los fármacos , Chenopodiaceae/metabolismo , Proteínas de la Membrana/metabolismo , Nitratos/metabolismo , Proteínas de Plantas/metabolismo , Proteómica , Cloruro de Sodio/farmacología , Membrana Celular/metabolismo , Raíces de Plantas/metabolismo , Plantas Tolerantes a la Sal/metabolismo

RESUMEN

High salinity and nitrogen (N) deficiency in soil are two key factors limiting crop productivity, and they usually occur simultaneously. Here we firstly found that H(+) -PPase is involved in salt-stimulated NO3 (-) uptake in the euhalophyte Salicornia europaea. Then, two genes (named SeVP1 and SeVP2) encoding H(+) -PPase from S. europaea were characterized. The expression of SeVP1 and SeVP2 was induced by salt stress and N starvation. Both SeVP1 or SeVP2 transgenic Arabidopsis and wheat plants outperformed the wild types (WTs) when high salt and low N occur simultaneously. The transgenic Arabidopsis plants maintained higher K(+) /Na(+) ratio in leaves and exhibited increased NO3 (-) uptake, inorganic pyrophosphate-dependent vacuolar nitrate efflux and assimilation capacity under this double stresses. Furthermore, they had more soluble sugars in shoots and roots and less starch accumulation in shoots than WT. These performances can be explained by the up-regulated expression of ion, nitrate and sugar transporter genes in transgenic plants. Taken together, our results suggest that up-regulation of H(+) -PPase favours the transport of photosynthates to root, which could promote root growth and integrate N and carbon metabolism in plant. This work provides potential strategies for improving crop yields challenged by increasing soil salinization and shrinking farmland.

Asunto(s)

Arabidopsis/fisiología , Chenopodiaceae/genética , Pirofosfatasa Inorgánica/fisiología , Proteínas de Plantas/fisiología , Triticum/fisiología , Arabidopsis/genética , Metabolismo de los Hidratos de Carbono , Pirofosfatasa Inorgánica/genética , Nitrógeno/metabolismo , Proteínas de Plantas/genética , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Plantas Modificadas Genéticamente/fisiología , Potasio/metabolismo , Cloruro de Sodio/metabolismo , Estrés Fisiológico/genética , Triticum/genética

RESUMEN

Despite the importance of NHX1 (Na(+)/H(+) exchanger 1) in plant salt tolerance, little is known about its other functions. In this study, intriguingly, it was found that NHX1 participated in plant disease defence against Phytophthora parasitica var. nicotianae (Ppn) in Nicotiana benthamiana. NbNHX1 was originally isolated from N. benthamiana, and characterized. The subcellular localization of NbNHX1 with its C-terminus fused with green fluorescent protein indicated that NbNHX1 localized primarily to the tonoplast. Tobacco rattle virus-induced NbNHX1 silencing led to reduced H(+) efflux from the vacuole to cytoplasts, and decreased Ppn resistance in N. benthamiana. After attack by Ppn, NbNHX1-silenced plants exhibited impaired ability to scavenge reactive oxidative species (ROS) induced by the pathogen. Pea early browning virus-mediated ectopic expression of SeNHX1 (from Salicornia europaea) or AtNHX1 (from Arabidopsis thaliana) both conferred enhanced Ppn resistance to N. benthamiana, with a lower H2O2 concentration after Ppn inoculation. Further investigation of the role of NHX1 demonstrated that transient overexpression of NbNHX1 improved the vacuolar pH and cellular ROS level in N. benthamiana, which was coupled with an enlarged NAD(P) (H) pool and higher expression of ROS-responsive genes. In contrast, NbNHX1 silencing led to a lower pH in the vacuole and a lower cellular ROS level in N. benthamiana, which was coupled with a decreased NAD(P) (H) pool and decreased expression of ROS-responsive genes. These results suggest that NHX1 is involved in plant disease defence; and regulation of vacuolar pH by NHX1, affecting the cellular oxidation state, primes the antioxidative system which is associated with Ppn resistance in tobacco.

Asunto(s)

Resistencia a la Enfermedad , Regulación de la Expresión Génica de las Plantas , Nicotiana/inmunología , Phytophthora/fisiología , Enfermedades de las Plantas/inmunología , Intercambiadores de Sodio-Hidrógeno/metabolismo , Secuencia de Aminoácidos , Antioxidantes/metabolismo , Genes Reporteros , Peróxido de Hidrógeno/metabolismo , Concentración de Iones de Hidrógeno , Datos de Secuencia Molecular , Hojas de la Planta , Alineación de Secuencia , Intercambiadores de Sodio-Hidrógeno/genética , Nicotiana/citología , Nicotiana/genética , Vacuolas/metabolismo

RESUMEN

BACKGROUND: Halophytes such as Salicornia europaea have evolved to exhibit unique mechanisms controlled by complex networks and regulated by numerous genes and interactions to adapt to habitats with high salinity. However, these mechanisms remain unknown. METHODS: To investigate the mechanism by which halophytes tolerate salt based on changes in the whole transcriptome, we performed transcriptome sequencing and functional annotation by database search. Using the unigene database, we conducted digital gene expression analysis of S. europaea at various time points after these materials were treated with NaCl. We also quantified ion uptakes. Gene functional enrichment analysis was performed to determine the important pathways involved in this process. RESULTS: A total of 57,151 unigenes with lengths of >300 bp were assembled, in which 57.5% of these unigenes were functionally annotated. Differentially expressed genes indicated that cell wall metabolism and lignin biosynthetic pathways were significantly enriched in S. europaea to promote the development of the xylem under saline conditions. This result is consistent with the increase in sodium uptake as ions pass through the xylem. Given that PSII efficiency remained unaltered, salt treatment activated the expression of electron transfer-related genes encoded by the chloroplast chromosome. Chlorophyll biosynthesis was also inhibited, indicating the energy-efficient state of the electron transfer system of S. europaea. CONCLUSIONS: The key function of adjusting important primary metabolic pathways in salt adaption was identified by analyzing the changes in the transcriptome of S. europaea. These pathways could involve unique salt tolerance mechanisms in halophytes. This study also provided information as the basis of future investigations on salt response genes in S. europaea. Ample gene resources were also provided to improve the genes responsible for the salt tolerance ability of crops.

Asunto(s)

Chenopodiaceae/genética , Chenopodiaceae/metabolismo , Redes y Vías Metabólicas , Salinidad , Tolerancia a la Sal/genética , Transcriptoma , Chenopodiaceae/efectos de los fármacos , Chenopodiaceae/crecimiento & desarrollo , Análisis por Conglomerados , Biología Computacional , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Anotación de Secuencia Molecular , Fenotipo , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Brotes de la Planta/genética , Brotes de la Planta/metabolismo , Cloruro de Sodio/farmacología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo

RESUMEN

Current status data arise due to only one feasible examination such that the failure time of interest occurs before or after the examination time. If the examination time is intrinsically related to the failure time of interest, the examination time is referred to as an informative censoring time. Such data may occur in many fields, for example, epidemiological surveys and animal carcinogenicity experiments. To avoid severely misleading inferences resulted from ignoring informative censoring, we propose a class of semiparametric transformation models with log-normal frailty for current status data with informative censoring. A shared frailty is used to account for the correlation between the failure time and censoring time. The expectation-maximization (EM) algorithm combining a sieve method for approximating an infinite-dimensional parameter is employed to estimate all parameters. To investigate finite sample properties of the proposed method, simulation studies are conducted, and a data set from a rodent tumorigenicity experiment is analyzed for illustrative purposes.

Asunto(s)

Modelos Estadísticos , 2-Acetilaminofluoreno/toxicidad , Algoritmos , Animales , Carcinógenos/toxicidad , Relación Dosis-Respuesta a Droga , Femenino , Ratones , Neoplasias/inducido químicamente , Pruebas de Toxicidad

RESUMEN

Despite that advances in neonatal medicine have significantly reduced the early mortality of premature infants, a considerable number of them are still prone to develop chronic lung disease (CLD) later. To find a method of early prevention, we investigated the efficacy of using certain early proinflammatory responses to predict the development of CLD. In the present study, 34 premature infants who required endotracheal intubation within 4 h of birth were recruited for analysis of IL-8, IL-10, and TNF-alpha levels in their bronchoalveolar lavage (BAL) fluid and blood. It was found that level of IL-8 but not TNF-alpha or IL-10 in initial BAL fluid was significantly correlated to neutrophils in the BAL and inversely correlated to the gestational age of prematurity. Elevation of IL-8 level in BAL on the first day of life was correlated to the development of CLD. Further studies showed that neonatal cord blood released significantly higher IL-8 but lower TNF-alpha levels after stimulation by endotoxin. The augmented IL-8 mRNA expression in cord blood was inhibited by actinomycin D but enhanced by cycloheximide, suggesting that IL-8 production is controlled by de novo transcriptional induction as well as posttranscriptional up-regulation of IL-8 by neonatal leukocytes, relating to the development of CLD. Thus, an appropriate modulation of initial IL-8 production in premature infants might be beneficial for the prevention of the development of CLD.

Asunto(s)

Regulación de la Expresión Génica , Interleucina-8/biosíntesis , Enfermedades Pulmonares/metabolismo , Procesamiento Postranscripcional del ARN , Adulto , Líquido del Lavado Bronquioalveolar , Enfermedad Crónica , Cicloheximida/farmacología , Citocinas/metabolismo , Dactinomicina/farmacología , Endotoxinas/metabolismo , Femenino , Sangre Fetal/efectos de los fármacos , Sangre Fetal/metabolismo , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Interleucina-10/biosíntesis , Interleucina-8/metabolismo , Leucocitos/metabolismo , Masculino , Inhibidores de la Síntesis de la Proteína/farmacología , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Transcripción Genética , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba

RESUMEN

Granulocytes play an important role in inflammatory diseases. Neonates tend to develop granulocytopenia under sepsis and stress. It remains unclear whether apoptosis of neonatal granulocytes is different from that of adult granulocytes. In this study, we analyzed the discrepancy of granulocyte apoptosis between cord blood (CB) and adult blood (AB). We found that spontaneous and tumor necrosis factor-alpha (TNFalpha)-induced granulocyte apoptosis as determined by phosphatidylserine expression and DNA fragmentation were more prominent in CB granulocytes than AB granulocytes. CD95 ligand and TNFalpha levels were significantly higher in CB than in AB (p = 0.001 and p < 0.001, respectively). TNF receptor-2 and CD95 expression on CB granulocytes were not different from those on AB granulocytes. However, the TNF receptor-1 (TNFR1) expression was lower on CB granulocytes than that on AB granulocytes (69.98 +/- 7.32 versus 89.04 +/- 3.73%, p = 0.029). This decrease of TNFR1 expression on neonatal granulocytes might be related to a higher plasma TNFalpha level associated with an intrinsic defect on the dynamic change of membrane TNFR1 expression in neonatal granulocytes. The expression of anti-apoptotic molecule Bcl-2 in neonatal granulocytes was also lower than that in adult granulocytes (4.64 +/- 0.51 versus 7.24 +/- 1.17 unit/mg protein, p = 0.032). Moreover, another anti-apoptotic signal, nuclear factor-kappaB nuclear translocation, was also lower in CB than AB granulocytes. Results from this study suggest that higher plasma death ligands associated with lower anti-apoptotic molecules in granulocytes may act an important role in triggering neonatal granulocyte apoptosis.

Asunto(s)

Apoptosis , Granulocitos/citología , Granulocitos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Transporte Activo de Núcleo Celular , Adulto , Western Blotting , Membrana Celular/metabolismo , Fragmentación del ADN , Regulación hacia Abajo , Sangre Fetal/metabolismo , Citometría de Flujo , Humanos , Técnicas para Inmunoenzimas , Recién Nacido , Inflamación , Ligandos , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Receptor fas/biosíntesis , Receptor fas/química

RESUMEN

OBJECTIVE: To investigate a new method to construct tissue-engineering bone that will be applicable clinically. METHODS: The cultured 5th generation rabbit bone marrow stroma osteoblasts (MSO) was dissolved in 3% sodium alginate solution (the final concentration of sodium alginate in the solution being 1%, and MSO, 5x10(6)/L), and then inoculated into prepared true bone ceramic (TBC) and gelatinized the bone by dribbling with calcium gluconate. The standard bone defect models were made in 48 adult New Zealand rabbit's both radius. Among the 48 rabbits, 24 were in Groups A and B, in which the left radius was implanted with gelatinized MSO-TBC (Group A) and right radius implanted with autograft-bone (Group B); and the other 24 were in control group whose left radius was implanted with non-gelatinized MSO-TBC (Group C) and right radius implanted with gelatinized TBC (Group D). Outcomes of the implanted bones were assessed by radiology, pathological histology, osteogenetic quantitative analysis, and biomechanics at 2, 4, 8, 12 weeks postoperatively. RESULTS: In Groups A and B, a satisfactory bone reparation and bony union was noted within 12 weeks. In Groups C and D, bone reparation was not satisfied compared with Group A in terms of ostogenetic quantity and biomechanics. CONCLUSIONS: Gelatinized MSO-TBC is an ideal artificial active bone that overcomes TBC shortcomings of fragileness and smooth surface that is not eligible for seed cell's adhesion. It is promising to put into clinical use extensively.

Asunto(s)

Enfermedades Óseas/terapia , Células de la Médula Ósea/citología , Sustitutos de Huesos , Osteoblastos/citología , Osteoblastos/trasplante , Ingeniería de Tejidos/métodos , Animales , Biomasa , Enfermedades Óseas/diagnóstico por imagen , Enfermedades Óseas/patología , Cerámica , Modelos Animales de Enfermedad , Femenino , Gelatina , Masculino , Osteogénesis , Conejos , Radiografía , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/lesiones , Radio (Anatomía)/patología , Radio (Anatomía)/cirugía , Células del Estroma/citología , Células del Estroma/trasplante , Resultado del Tratamiento

RESUMEN

<p><b>OBJECTIVE</b>To investigate a new method to construct tissue-engineering bone that will be applicable clinically.</p><p><b>METHODS</b>The cultured 5th generation rabbit bone marrow stroma osteoblasts (MSO) was dissolved in 3% sodium alginate solution (the final concentration of sodium alginate in the solution being 1%, and MSO, 5x10(6)/L), and then inoculated into prepared true bone ceramic (TBC) and gelatinized the bone by dribbling with calcium gluconate. The standard bone defect models were made in 48 adult New Zealand rabbit's both radius. Among the 48 rabbits, 24 were in Groups A and B, in which the left radius was implanted with gelatinized MSO-TBC (Group A) and right radius implanted with autograft-bone (Group B); and the other 24 were in control group whose left radius was implanted with non-gelatinized MSO-TBC (Group C) and right radius implanted with gelatinized TBC (Group D). Outcomes of the implanted bones were assessed by radiology, pathological histology, osteogenetic quantitative analysis, and biomechanics at 2, 4, 8, 12 weeks postoperatively.</p><p><b>RESULTS</b>In Groups A and B, a satisfactory bone reparation and bony union was noted within 12 weeks. In Groups C and D, bone reparation was not satisfied compared with Group A in terms of ostogenetic quantity and biomechanics.</p><p><b>CONCLUSIONS</b>Gelatinized MSO-TBC is an ideal artificial active bone that overcomes TBC shortcomings of fragileness and smooth surface that is not eligible for seed cell's adhesion. It is promising to put into clinical use extensively.</p>

Asunto(s)

Animales , Femenino , Masculino , Conejos , Biomasa , Enfermedades Óseas , Diagnóstico por Imagen , Patología , Terapéutica , Células de la Médula Ósea , Biología Celular , Sustitutos de Huesos , Cerámica , Modelos Animales de Enfermedad , Gelatina , Osteoblastos , Biología Celular , Trasplante , Osteogénesis , Radiografía , Radio (Anatomía) , Diagnóstico por Imagen , Heridas y Lesiones , Patología , Cirugía General , Células del Estroma , Biología Celular , Trasplante , Ingeniería de Tejidos , Métodos , Resultado del Tratamiento

RESUMEN

A 34-year-old woman was brought to our emergency department because of sudden loss of consciousness. Ventricular tachycardia and fibrillation were noted on electrocardiographic monitoring and reverted to sinus rhythm after repeated defibrillation. She was treated as a case of thyroid storm. Although tachycardia and fever normalized after 2 days, she remained comatose and died. This is an unusual case because the patient's initial presentation was cardiac arrest without previous history of cardiac disease. To our knowledge, this is the first reported case where ventricular tachyarrhythmia was the initial presenting sign of thyroid storm.

Asunto(s)

Taquicardia Ventricular/etiología , Crisis Tiroidea/complicaciones , Adulto , Reanimación Cardiopulmonar , Electrocardiografía , Resultado Fatal , Femenino , Paro Cardíaco/etiología , Humanos , Taquicardia Ventricular/fisiopatología , Crisis Tiroidea/sangre , Crisis Tiroidea/fisiopatología , Triyodotironina/sangre