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排序方式: 共有596条查询结果,搜索用时 15 毫秒
551.
Federico ávila-Moreno Leonel Armas-López Aldo M. álvarez-Moran Zoila López-Bujanda Blanca Ortiz-Quintero Alfredo Hidalgo-Miranda Francisco Urrea-Ramírez R. María Rivera-Rosales Eugenia Vázquez-Manríquez Erika Pe?a-Mirabal José Morales-Gómez Juan C. Vázquez-Minero José L. Téllez-Becerra Roberto Ramírez-Mendoza Alejandro ávalos-Bracho Enrique Guzmán de Alba Karla Vázquez-Santillán Vilma Maldonado-Lagunas Patricio Santillán-Doherty Patricia Pi?a-Sánchez Joaquin Zú?iga-Ramos 《PloS one》2014,9(12)
Lung cancer is the leading cause of death from malignant diseases worldwide, with the non-small cell (NSCLC) subtype accounting for the majority of cases. NSCLC is characterized by frequent genomic imbalances and copy number variations (CNVs), but the epigenetic aberrations that are associated with clinical prognosis and therapeutic failure remain not completely identify. In the present study, a total of 55 lung cancer patients were included and we conducted genomic and genetic expression analyses, immunohistochemical protein detection, DNA methylation and chromatin immunoprecipitation assays to obtain genetic and epigenetic profiles associated to prognosis and chemoresponse of NSCLC patients. Finally, siRNA transfection-mediated genetic silencing and cisplatinum cellular cytotoxicity assays in NSCLC cell lines A-427 and INER-37 were assessed to describe chemoresistance mechanisms involved. Our results identified high frequencies of CNVs (66–51% of cases) in the 7p22.3–p21.1 and 7p15.3–p15.2 cytogenetic regions. However, overexpression of genes, such as MEOX2, HDAC9, TWIST1 and AhR, at 7p21.2–p21.1 locus occurred despite the absence of CNVs and little changes in DNA methylation. In contrast, the promoter sequences of MEOX2 and TWIST1 displayed significantly lower/decrease in the repressive histone mark H3K27me3 and increased in the active histone mark H3K4me3 levels. Finally these results correlate with poor survival in NSCLC patients and cellular chemoresistance to oncologic drugs in NSCLC cell lines in a MEOX2 and TWIST1 overexpression dependent-manner. In conclusion, we report for the first time that MEOX2 participates in chemoresistance irrespective of high CNV, but it is significantly dependent upon H3K27me3 enrichment probably associated with aggressiveness and chemotherapy failure in NSCLC patients, however additional clinical studies must be performed to confirm our findings as new probable clinical markers in NSCLC patients. 相似文献
552.
Antonio Javier Moreno-Pérez Mónica Venegas-Calerón Fabián E. Vaistij Joaquin J. Salas Tony R. Larson Rafael Garcés Ian A. Graham Enrique Martínez-Force 《Planta》2014,239(3):667-677
The substrate specificity of the acyl–acyl carrier protein (ACP) thioesterases significantly determines the type of fatty acids that are exported from plastids. Thus, designing acyl-ACP thioesterases with different substrate specificities or kinetic properties would be of interest for plant lipid biotechnology to produce oils enriched in specialty fatty acids. In the present work, the FatA thioesterase from Helianthus annuus was used to test the impact of changes in the amino acids present in the binding pocket on substrate specificity and catalytic efficiency. Amongst all the mutated enzymes studied, Q215W was especially interesting as it had higher specificity towards saturated acyl-ACP substrates and higher catalytic efficiency compared to wild-type H. annuus FatA. Null, wild type and high-efficiency alleles were transiently expressed in tobacco leaves to check their effect on lipid biosynthesis. Expression of active FatA thioesterases altered the composition of leaf triacylglycerols but did not alter total lipid content. However, the expression of the wild type and the high-efficiency alleles in Arabidopsis thaliana transgenic seeds resulted in a strong reduction in oil content and an increase in total saturated fatty acid content. The role and influence of acyl-ACP thioesterases in plant metabolism and their possible applications in lipid biotechnology are discussed. 相似文献
553.
554.
Geiziane Tessarolo Richard Ladle Thiago Rangel Joaquin Hortal 《Ecology and evolution》2017,7(17):6863-6870
Spatial and/or temporal biases in biodiversity data can directly influence the utility, comparability, and reliability of ecological and evolutionary studies. While the effects of biased spatial coverage of biodiversity data are relatively well known, temporal variation in data quality (i.e., the congruence between recorded and actual information) has received much less attention. Here, we develop a conceptual framework for understanding the influence of time on biodiversity data quality based on three main processes: (1) the natural dynamics of ecological systems—such as species turnover or local extinction; (2) periodic taxonomic revisions, and; (3) the loss of physical and metadata due to inefficient curation, accidents, or funding shortfalls. Temporal decay in data quality driven by these three processes has fundamental consequences for the usage and comparability of data collected in different time periods. Data decay can be partly ameliorated by adopting standard protocols for generation, storage, and sharing data and metadata. However, some data degradation is unavoidable due to natural variations in ecological systems. Consequently, changes in biodiversity data quality over time need be carefully assessed and, if possible, taken into account when analyzing aging datasets. 相似文献
555.
Development of a citrus genome-wide EST collection and cDNA microarray as resources for genomic studies 总被引:2,自引:0,他引:2
Forment J Gadea J Huerta L Abizanda L Agusti J Alamar S Alos E Andres F Arribas R Beltran JP Berbel A Blazquez MA Brumos J Canas LA Cercos M Colmenero-Flores JM Conesa A Estables B Gandia M Garcia-Martinez JL Gimeno J Gisbert A Gomez G Gonzalez-Candelas L Granell A Guerri J Lafuente MT Madueno F Marcos JF Marques MC Martinez F Martinez-Godoy MA Miralles S Moreno P Navarro L Pallas V Perez-Amador MA Perez-Valle J Pons C Rodrigo I Rodriguez PL Royo C Serrano R Soler G Tadeo F Talon M Terol J 《Plant molecular biology》2005,57(3):375-391
556.
Julien Claron Julie Royo Fabrice Arcizet Thomas Deffieux Mickael Tanter Pierre Pouget 《PLoS biology》2022,20(5)
In both human and nonhuman primates (NHP), the medial prefrontal region, defined as the supplementary eye field (SEF), can indirectly influence behavior selection through modulation of the primary selection process in the oculomotor structures. To perform this oculomotor control, SEF integrates multiple cognitive signals such as attention, memory, reward, and error. As changes in pupil responses can assess these cognitive efforts, a better understanding of the precise dynamics by which pupil diameter and medial prefrontal cortex activity interact requires thorough investigations before, during, and after changes in pupil diameter. We tested whether SEF activity is related to pupil dynamics during a mixed pro/antisaccade oculomotor task in 2 macaque monkeys. We used functional ultrasound (fUS) imaging to examine temporal changes in brain activity at the 0.1-s time scale and 0.1-mm spatial resolution concerning behavioral performance and pupil dynamics. By combining the pupil signals and real-time imaging of NHP during cognitive tasks, we were able to infer localized cerebral blood volume (CBV) responses within a restricted part of the dorsomedial prefrontal cortex, referred to as the SEF, an area in which antisaccade preparation activity is also recorded. Inversely, SEF neurovascular activity measured by fUS imaging was found to be a robust predictor of specific variations in pupil diameter over short and long-time scales. Furthermore, we directly manipulated pupil diameter and CBV in the SEF using reward modulations. These results bring a novel understanding of the physiological links between pupil and SEF, but it also raises questions about the role of anterior cingulate cortex (ACC), as CBV variations in the ACC seems to be negligible compared to CBV variations in the SEF.Ultrafast functional imaging reveals short- and long-term covariations between pupil diameter and activity in the Supplementary Eye Field (SEF) of awake behaving non-human primates, yielding a novel understanding of the physiological links between the pupil and SEF. 相似文献
557.
Polymer Therapeutics have enormously evolved in the past decades. Several polymeric drugs as well as polymer-protein conjugates have been in the market since the 90s, but although polymer-drug conjugates are already in clinical trials they still need to reach this final goal. There are four main convergent strategies to move this platform technology further. First, exploitation of new molecular targets in cancer therapy and design of polymer-drug conjugates as treatments for other diseases. Second, the development of combination therapy. Third, attempts to improve polymer chemistry, including the use of new well-defined architectures and the optimization of the advanced characterization techniques essential to transform a promising conjugate into a candidate for clinical evaluation. Finally, increased understanding of polymer conjugate features that govern clinical risk-benefit is leading to an appreciation of clinical biomarkers that will open new possibilities for personalized therapy. 相似文献
558.
Bailey L. McCurdy Cayla E. Jewett Alexander J. Stemm-Wolf Huy Nguyen Duc Molishree Joshi Joaquin M. Espinosa Rytis Prekeris Chad G. Pearson 《Molecular biology of the cell》2022,33(8)
Trisomy 21, the source of Down syndrome, causes a 0.5-fold protein increase of the chromosome 21-resident gene Pericentrin (PCNT) and reduces primary cilia formation and signaling. We investigate how PCNT imbalances disrupt cilia. Using isogenic RPE-1 cells with increased chromosome 21 dosage, we find PCNT accumulates around the centrosome as a cluster of enlarged cytoplasmic puncta that localize along microtubules (MTs) and at MT ends. Cytoplasmic PCNT puncta impact the density, stability, and localization of the MT trafficking network required for primary cilia. The PCNT puncta appear to sequester cargo peripheral to centrosomes in what we call pericentrosomal crowding. The centriolar satellite proteins PCM1, CEP131, and CEP290, important for ciliogenesis, accumulate at enlarged PCNT puncta in trisomy 21 cells. Reducing PCNT when chromosome 21 ploidy is elevated is sufficient to decrease PCNT puncta and pericentrosomal crowding, reestablish a normal density of MTs around the centrosome, and restore ciliogenesis to wild-type levels. A transient reduction in MTs also decreases pericentrosomal crowding and partially rescues ciliogenesis in trisomy 21 cells, indicating that increased PCNT leads to defects in the MT network deleterious to normal centriolar satellite distribution. We propose that chromosome 21 aneuploidy disrupts MT-dependent intracellular trafficking required for primary cilia. 相似文献
559.
1400W, a potent selective inducible NOS inhibitor, improves histopathological outcome following traumatic brain injury in rats. 总被引:3,自引:0,他引:3
M Jafarian-Tehrani G Louin N C Royo V C Besson G A Bohme M Plotkine C Marchand-Verrecchia 《Nitric oxide》2005,12(2):61-69
There are conflicting data regarding the role of nitric oxide (NO) produced by inducible NO synthase (iNOS) in the pathophysiology of traumatic brain injury (TBI). In this report, we evaluated the effect of a potent selective (iNOS) inhibitor, 1400W, on histopathological outcome following TBI in a rat model of lateral fluid percussion brain injury. First, to design an appropriate treatment protocol, the parallel time courses of iNOS and neuronal NOS (nNOS) gene expression, protein synthesis, and activity were investigated. Early induction of iNOS gene was observed in the cortex of injured rats, from 6 to 72 h with a peak at 24 h. Similarly, iNOS protein was detected from 24 to 72 h and de novo synthesized iNOS was functionally active, as measured by Ca2+-independent NOS activity. The kinetic studies of nNOS showed discrepancies, since nNOS gene expression and protein synthesis were constant in the cortex of injured rats from 24 to 72 h, while Ca2+-dependent constitutive NOS activity was markedly decreased at 24 h, persisting up to 72 h. Second, treatment with 1400W, started as a bolus of 20 mg kg-1 (s.c.) at 18 h post-TBI, followed by s.c.-infusion at a rate of 2.2 mg kg-1 h-1 between 18 and 72 h, reduced by 64% the brain lesion volume at 72 h. However, the same treatment paradigm initiated 24 h post-TBI did not have any effect. In conclusion, administration of a selective iNOS inhibitor, 1400W, even delayed by 18 h improves histopathological outcome supporting a detrimental role for iNOS induction after TBI. 相似文献
560.