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1.
Environ Sci Pollut Res Int ; 30(11): 30948-30959, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36441314

RESUMEN

Energy is one of the critical factors for economic growth, and carbon emissions are by-products of energy use that degrade environmental quality. This research thus establishes an index of eco-output elasticity of energy consumption to find an eco-friendly production stage in which not only output increases, but also energy consumption degrades. Our observation subject is China, which employs its own energy intensity index to monitor the nexus of economy, energy, and environment. While its energy intensity index is unable to point out the eco-friendly production stage, the index of eco-output elasticity of energy consumption herein does. This paper offers three main empirical findings on China: (i) it presents an eco-friendly production stage from 2012 to 2013; (ii) it has better improvement on energy savings than CO2 reduction; and (iii) in general, its status quo is still high energy consumption, but this phenomenon is improving.


Asunto(s)
Dióxido de Carbono , Desarrollo Económico , China , Dióxido de Carbono/análisis
2.
Artículo en Inglés | MEDLINE | ID: mdl-32357429

RESUMEN

As physicians and nurses are the main medical staff in any healthcare system, an appropriate medical workforce distribution is crucial for an aging society. This study thus applies the theory of carrying capacity and the given demand side to explore the carrying capacity, carrying efficiency, and potential adjustment ratio of medical staff in Taiwan's administrative regions by using the data envelopment analysis (DEA) approach in which a lower carrying efficiency implies a higher shortage ratio. The main findings are as follows. (i) The carrying efficiency of Taiwan's medical staff is weakening year by year, while the carrying efficiency of the country's nurses is lower than that of physicians. (ii) The outlying islands of Taiwan have a more serious shortage of physicians and nurses than the main island. (iii) The central government should encourage more physicians and nurses to work in regions with a low carrying efficiency.


Asunto(s)
Fuerza Laboral en Salud , Cuerpo Médico , Médicos , Humanos , Taiwán
3.
Environ Sci Pollut Res Int ; 27(13): 14492-14502, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32043253

RESUMEN

This study investigates the relationships among emissions efficiency (Em), the emissions technology gap ratio (TGm), and room for improvement in emissions intensity (RIm), and creates target-consideration environmental Kuznets curves (TC-EKC) which are then examined and compared for countries in the European Union (EU) that are divided into those countries in the Baltic Sea region (BSR) and those in the non-Baltic Sea region (NBSR). The research results indicate that the BSR countries exhibit an inverted-U-shaped TC-EKC, but the NBSR countries do not, implying that CO2 emissions in the latter region do not achieve the target. The small TGm and the large RIm for the BSR countries indicate that this region has a low Em and is at the preliminary stage of emissions technology development.


Asunto(s)
Dióxido de Carbono , Desarrollo Económico , Unión Europea , Tecnología
4.
PLoS One ; 14(7): e0219317, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31310624

RESUMEN

Resveratrol (RSV) has been reported to influence many biological processes, including the stimulation of cellular senescence and inhibition of epithelial-mesenchymal transition (EMT). In this research, we explored the mechanisms of RSV on EMT and cellular senescence through the expression of a DNA damage response (DDR) protein, Rad9, in breast and lung cancer cell lines. Upon treating breast and lung cancer cell lines with RSV at the concentrations of 10-50 µM, Rad9 expression was increased at both transcriptional and translational levels. The results indicated that RSV-induced Rad9 expression, mediated by DNA damage and ROS, can significantly suppress proliferation by activating cellular senescence, and diminishing the expression of EMT markers with concomitant downregulation of Slug in breast and lung cancer cell lines. By using a siRNA approach, RSV was shown to mediate cellular senescence and EMT through a Rad9-dependent mechanism. The treatment with RSV can inhibit the proliferation, EMT, and increase cellular senescence of breast and lung cancer cell lines by activating Rad9. Our results suggest that the breast and lung tumor suppressive activities of RSV are, at least in part, mediated by the upregulation of Rad9.


Asunto(s)
Neoplasias de la Mama/metabolismo , Proteínas de Ciclo Celular/metabolismo , Senescencia Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias Pulmonares/metabolismo , Resveratrol/farmacología , Células A549 , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Daño del ADN/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Células MCF-7 , Invasividad Neoplásica , ARN Interferente Pequeño/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factores de Transcripción de la Familia Snail/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba , Cicatrización de Heridas
5.
J Thorac Dis ; 9(2): E109-E114, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28275492

RESUMEN

Post-esophagectomy chylothorax is a rare yet serious complication. Herein we report the case of a patient with intractable post-esophagectomy chylothorax despite medical treatment with total parenteral nutrition and octreotide, as well as prophylactic and repeated thoracic duct mass ligation. The patient was eventually treated with localization of thoracic duct using T2-weighted magnetic resonance imaging (T2W MRI), followed by video-assisted thoracoscopic thoracic duct ligation.

6.
Carcinogenesis ; 38(2): 196-206, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28007956

RESUMEN

RPA2, a subunit of the heterotrimeric replication protein A (RPA) complex, is overexpressed in various cancers. In this study, we showed a significant RPA2 upregulation in breast cancer tissues and cell lines. Ectopic expression of RPA2 in MCF7 and MDA-MB-231 cells promoted cell proliferation, adhesion, migration and invasion, and induced epithelial-mesenchymal transition (EMT) of MCF7 cells. Ablation of RPA2 in MDA-MB-231 cells induced apoptosis and suppressed colony formation, EMT and invasion. Binding assays indicated that menin, the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor gene product, interacted with RPA2. Ectopic expression of RPA2 inhibited the formation of the menin-NK-κB p65 complex and repressed the inhibitory effect of menin on expression of NF-κB-regulated genes that contribute to tumor progression. Conversely, knockdown of RPA2 promoted formation of the menin-p65 complex and repressed the expression of NF-κB-mediated genes. RPA2 expression was induced via an E2F1-dependent mechanism in MCF7 and MDA-MB-231 cells treated with NF-κB activators, TNF-alpha or lipopolysaccharide (LPS). These results suggested that RPA2-dependent tumorigenicity was mediated via enhancement of NF-κB activity by relieving the antagonistic function of menin on NF-κB-regulated transcription in breast cancer cells.


Asunto(s)
Neoplasias de la Mama/genética , Proliferación Celular/genética , Proteínas Proto-Oncogénicas/genética , Proteína de Replicación A/biosíntesis , Apoptosis/genética , Neoplasias de la Mama/patología , Carcinogénesis/genética , Adhesión Celular/genética , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , FN-kappa B/genética , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Proteínas Proto-Oncogénicas/metabolismo , Proteína de Replicación A/genética , Transducción de Señal/genética
7.
Virulence ; 6(2): 162-72, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25830726

RESUMEN

Invasive syndrome caused by Klebsiella pneumoniae (KP), including liver abscess, is mainly caused by community-acquired strains with characteristics of positive hypermucoviscosity (HV) phenotype and regulator of mucoid phenotype A (rmpA) and transcriptional activator (rmpA2) genes. Extended- spectrum ß-lactamase-producing KP (ESBL-KP) is commonly nosocomial and rarely HV-positive. We aimed to explore the reasons of the rarer prevalence of HV phenotype, rmpA and rmpA2 as well as the virulence phenotype among the ESBL-KP isolates from clinical specimens than those non-ESBL isolates. The ß-lactamase genes, rmpA, rmpA2 and genes for K capsule serotype of 440 KP isolates were analyzed. The virulence of the isolates was characterized by the mouse lethality experiments. The prevalence rates of HV phenotype (∼ 50% vs. < 10%) as well as rmpA and rmpA2 genes (∼ 50-60% vs. < 20-30%) were significantly higher in non-ESBL group than in the ESBL group (p < 0.0001). Expression of HV phenotype in the rmpA-positive KP isolates was significantly rarer in the ESBL group than in non-ESBL group (33.3% vs. 91.9%, p < 0.0001). The frameshift mutations of rmpA and/or rmpA2 corresponded to negative HV phenotype of KP isolates that harbored the rmpA and/or rmpA2, resulting in variable mouse lethality (LD50, ∼ 10(3) - >5 × 10(7) CFU). The mutation rates might significantly differ among KP isolates from various sources. Virulence was dependent on rmpA-related HV phenotype. In conclusion, ESBL-KP isolates were less hypermucoviscous and less virulent than non-ESBL KP isolates, mostly due to concurrently lower carriage and higher mutation rates of the rmpA and rmpA2 genes.


Asunto(s)
Proteínas Bacterianas/genética , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Factores de Transcripción/genética , beta-Lactamasas/metabolismo , Animales , Mutación del Sistema de Lectura , Genes Bacterianos , Klebsiella pneumoniae/enzimología , Dosificación Letal Mediana , Ratones , Fenotipo , Alineación de Secuencia , Virulencia/genética
8.
PLoS One ; 10(2): e0117821, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25679227

RESUMEN

BACKGROUND: Advances in Aeromonas taxonomy have led to the reclassification of aeromonads. Hereon, we aimed to re-evaluate the characteristics of Aeromonas bacteremia, including those of a novel species, Aeromonas dhakensis. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study of monomicrobial Aeromonas bacteremia at a medical center in southern Taiwan from 2004-2011 was conducted. Species identification was based on rpoB sequencing. Of bacteremia of 153 eligible patients, A. veronii (50 isolates, 32.7%), A. dhakensis (48, 31.4%), A. caviae (43, 28.1%), and A. hydrophila (10, 6.5%) were the principal causative species. A. dhakensis and A. veronii bacteremia were mainly community-acquired and presented as primary bacteremia, spontaneous bacterial peritonitis, or skin and soft-tissue infection, whereas A. caviae was associated with hospital-onset bacteremia. The distribution of the AmpC ß-lactamase and metallo-ß-lactamase genes was species-specific: bla(AQU-1), bla(MOX), or bla(CepH) was present in A. dhakensis, A. caviae, or A. hydrophila, respectively, and bla(CphA) was present in A. veronii, A. dhakensis, and A. hydrophila. The cefotaxime resistance rates of the A. caviae, A. dhakensis, and A. hydrophila isolates were higher than that of A. veronii (39.5%%, 25.0%, and 30% vs. 2%, respectively). A. dhakensis bacteremia was linked to the highest 14-day sepsis-related mortality rate, followed by A. hydrophila, A. veronii, and A. caviae bacteremia (25.5%, 22.2%, 14.0%, and 4.7%, respectively; P = 0.048). Multivariate analysis revealed that A. dhakensis bacteremia, active malignancies, and a Pitt bacteremia score ≥ 4 was an independent mortality risk factor. CONCLUSIONS/SIGNIFICANCE: Characteristics of Aeromonas bacteremia vary between species. A. dhakensis prevalence and its associated poor outcomes suggest it an important human pathogen.


Asunto(s)
Aeromonas/clasificación , Bacteriemia/microbiología , Infecciones por Bacterias Gramnegativas/microbiología , Adulto , Aeromonas/efectos de los fármacos , Aeromonas/genética , Anciano , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Comorbilidad , Femenino , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/mortalidad , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , beta-Lactamasas/genética
9.
J Glob Antimicrob Resist ; 3(2): 137-141, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27873663

RESUMEN

Two Klebsiella pneumoniae isolates were simultaneously recovered from blood and urine cultures of the same patient. Both isolates were identical in genomic pulsotype by pulsed-field gel electrophoresis (PFGE). However, the hypermucoviscosity phenotype was confirmed in the blood strain but not the urine strain. A previously unrelated liver abscess K. pneumoniae hypermucoviscous isolate was used as a control. PCR, DNA cloning and sequencing for the plasmid-borne rmpA and rmpA2 genes and the chromosome-borne rmpA gene (c-rmpA) revealed negative c-rmpA with natural frame-shift mutation of rmpA and rmpA2 genes in the urine strain. The blood strain was negative for c-rmpA with rmpA2 mutation but no mutation in rmpA. The control strain was positive for c-rmpA with rmpA2 mutation but no mutation in rmpA and showed the highest virulence in mouse lethality experiments [median lethal dose (LD50)=50CFU], which was followed by the blood strain (LD50=2.47×103CFU) and the urine strain (LD50>107CFU). The control and blood strains were highly serum resistant, whereas the urine strain was sensitive to serum killing. In conclusion, intrapersonal concurrent mutation of rmpA and rmpA2 genes in the absence of c-rmpA could be a reason for the negative hypermucoviscosity phenotype and low virulence in rmpA-positive K. pneumoniae.

10.
Biomed Res Int ; 2014: 342725, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25243132

RESUMEN

RecQ DNA helicases are key enzymes in the maintenance of genome integrity, and they have functions in DNA replication, recombination, and repair. In contrast to most RecQs, RecQ from Deinococcus radiodurans (DrRecQ) possesses an unusual domain architecture that is crucial for its remarkable ability to repair DNA. Here, we determined the crystal structures of the DrRecQ helicase catalytic core and its ADP-bound form, revealing interdomain flexibility in its first RecA-like and winged-helix (WH) domains. Additionally, the WH domain of DrRecQ is positioned in a different orientation from that of the E. coli RecQ (EcRecQ). These results suggest that the orientation of the protein during DNA-binding is significantly different when comparing DrRecQ and EcRecQ.


Asunto(s)
Dominio Catalítico , Deinococcus/enzimología , RecQ Helicasas/química , Adenosina Difosfato/metabolismo , Secuencia de Aminoácidos , Cristalografía por Rayos X , Datos de Secuencia Molecular , RecQ Helicasas/metabolismo , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Electricidad Estática , Homología Estructural de Proteína
11.
Oncotarget ; 5(13): 5017-28, 2014 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-24970809

RESUMEN

Grap2 and cyclin D1 interacting protein (GCIP) has been recognized as a putative tumor suppressor, but the molecular mechanisms underlying its anti-tumor properties remain undefined. Here, we report that GCIP is frequently downregulated in non-small cell lung cancer (NSCLC) tissues. Binding assays indicated that inhibitor of DNA binding/differentiation 1 (Id1) interacts with GCIP in the nucleus. Ectopic GCIP expression in the highly invasive NSCLC cell line, H1299, inhibited proliferation, colony formation, invasion and migration, and increased susceptibility to anticancer drugs. Conversely, silencing GCIP expression in the minimally invasive NSCLS cell line, A549, increased proliferation, colony formation, invasion, and migration in vitro, and increased survival and resistance to anticancer drugs. GCIP also suppresses tumorigenicity of NSCLC cells in vivo and GCIP suppresses NSCLC progression is mediated in part by interfering with Id1 signaling, which was confirmed in conditionally induced stable cell lines. In addition, GCIP downregulates the expression of Id1, and GCIP and Id1 are inversely expressed in NSCLC cell lines and specimens. Taken together, these results suggest that GCIP is a potential tumor suppressor in NSCLC and that suppression of Id1-mediated oncogenic properties may be a key mechanism by which GCIP can potently suppress NSCLC tumor progression.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteína 1 Inhibidora de la Diferenciación/metabolismo , Neoplasias Pulmonares/metabolismo , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Immunoblotting , Proteína 1 Inhibidora de la Diferenciación/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Confocal , Unión Proteica , Interferencia de ARN , Factores de Transcripción/genética , Trasplante Heterólogo , Carga Tumoral/genética , Proteínas Supresoras de Tumor/genética
12.
Carcinogenesis ; 35(7): 1481-90, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24403312

RESUMEN

Senescence and epithelial-mesenchymal transition (EMT) have opposing roles in tumor progression, in that, one is a barrier against tumorigenesis, whereas the other is required for invasive malignancies. Here, we report that the DNA damage response (DDR) protein hRAD9 contributes to induction of senescence and inhibition of EMT. Our data show that hRAD9 is frequently downregulated in breast and lung cancers. Loss of hRAD9 expression is associated with tumor stage in breast and lung cancers, as well as with acquisition of an invasive phenotype. Ectopic hRAD9 expression in highly invasive cancer cell lines, H1299 and MDA-MB 231, with low endogenous hRAD9 induced senescence by upregulation of nuclear p21, independent of the p53 status. Ectopic expression of hRAD9 also significantly attenuated cellular migration and invasion in vitro and tumor growth in a xenograft mouse model in vivo. In contrast, silencing hRAD9 in lower invasive cancer cell lines, A549 and MCF7, with high endogenous hRAD9 dramatically increased their migration and invasion abilities, and simultaneously activated EMT. Knockdown of hRAD9 increased, whereas ectopic expression of hRAD9 decreased, the expression of Slug. Moreover, hRAD9 directly bound to the promoter region of slug gene and repressed its transcriptional activity. Taken together, these results suggest that hRAD9 is a potential tumor suppressor in breast and lung cancers and that it is likely to function by upregulating p21 and inhibiting Slug to regulate tumorigenesis.


Asunto(s)
Neoplasias de la Mama/patología , Proteínas de Ciclo Celular/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/patología , Factores de Transcripción/genética , Animales , Apoptosis , Western Blotting , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Movimiento Celular , Proliferación Celular , Senescencia Celular , Inmunoprecipitación de Cromatina , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Ratones SCID , Regiones Promotoras Genéticas , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción de la Familia Snail , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismo , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Bot Stud ; 55(1): 79, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28510958

RESUMEN

BACKGROUND: The mBFP is an improved variant of NADPH-dependent blue fluorescent protein that was originally identified from the non-bioluminescent pathogenic bacteria Vibrio vulnificus CKM-1. To explore the application of mBFP in plants, the mBFP gene expression was driven by one of the three promoters, namely, leaf-specific (RbcS), hypoxia-inducible (Adh) or auxin-inducible (DR5) promoters, in different plant tissues such as leaves, roots and flowers under diverse treatments. In addition, the expressed mBFP protein was targeted to five subcellular compartments such as cytosol, endoplasmic reticulum, apoplast, chloroplast and mitochondria, respectively, in plant cells. RESULTS: When the mBFP was transiently expressed in the tobacco leaves and floral tissues of moth orchid, the cytosol and apoplast exhibited brighter blue fluorescence than other compartments. The recombinant mBFP-mS1C fusion protein exhibited enhanced fluorescence intensity that was correlated with more abundant RNA transcripts (1.8 fold) as compared with a control. In the root tips of horizontally grown transgenic Arabidopsis, mBFP could be induced as a reporter under hypoxia condition. Furthermore, the mBFP was localized to the expected subcellular compartments, except that dual targeting was found when the mBFP was fused with the mitochondria-targeting signal peptide. Additionally, the brightness of mBFP blue fluorescence was correlated with NADPH concentration. CONCLUSION: The NADPH-dependent blue fluorescent protein could serve as a useful reporter in plants under aerobic or hypoxic condition. However, to avoid masking the mitochondrial targeting signal, fusing mBFP as a fusion tag in the C-terminal will be better when the mBFP is applied in mitochondria trafficking study. Furthermore, mBFP might have the potential to be further adopted as a NADPH biosensor in plant cells. Future codon optimization of mBFP for plants could significantly enhance its brightness and expand its potential applications.

14.
Int J Antimicrob Agents ; 42(5): 456-61, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24055254

RESUMEN

Aeromonas dhakensis, a recently described Aeromonas sp. formerly called Aeromonas aquariorum, is associated with human infections. In this study, a chromosomal gene, blaAQU-1, was identified in A. dhakensis AAK1 that constitutes a 1143-bp open reading frame and is 87% identical to the gene encoding CepH in Aeromonas hydrophila. An Escherichia coli TOP10 cell transformant harbouring blaAQU-1 was resistant to cefotaxime but not to cefepime. mRNA expression of blaAQU-1 in the cefotaxime-resistant mutant strain AAK1m was 70-fold higher than in the wild strain AAK1. In all 16 A. dhakensis isolates (the major species of 51 consecutive Aeromonas blood isolates collected from June 1999 to June 2001) as well as in A. aquariorum MDC47(T) and A. hydrophila subsp. dhakensis LMG 19562(T), but not in the reference strains or clinical isolates of other A. hydrophila subspecies, Aeromonas caviae, Aeromonas veronii or Aeromonas enteropelogenes, blaAQU-1-related genes were detected by PCR. Overall, 13 (81%) of the 16 A. dhakensis blood isolates exhibited either cefotaxime resistance or the in vitro emergence of derepressed cefotaxime-resistant mutants. In vivo selection of an A. dhakensis resistant mutant was noted in a burn patient undergoing cefotaxime monotherapy. These observations suggest that AQU-1 is a chromosomal cephalosporinase in A. dhakensis. Cefotaxime monotherapy for severe A. dhakensis infections should be used cautiously.


Asunto(s)
Aeromonas/efectos de los fármacos , Aeromonas/enzimología , Cefalosporinasa/metabolismo , Infecciones por Bacterias Gramnegativas/microbiología , Aeromonas/genética , Aeromonas/aislamiento & purificación , Cefalosporinasa/genética , Análisis por Conglomerados , ADN Bacteriano/química , ADN Bacteriano/genética , Humanos , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Filogenia , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Homología de Secuencia
15.
Acta Crystallogr Sect F Struct Biol Cryst Commun ; 68(Pt 10): 1195-7, 2012 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-23027746

RESUMEN

TarI is a ribitol-5-phosphate cytidylyltransferase that catalyzes the formation of CDP-ribitol, which is involved in the biosynthesis of wall teichoic acids, from CTP and ribitol 5-phosphate. TarI from Bacillus subtilis (BsTarI) was purified and crystallized using the sitting-drop vapour-diffusion method. The crystals diffracted to a resolution of 1.78 Šand belonged to the monoclinic space group C2, with unit-cell parameters a = 103.74, b = 60.97, c = 91.80 Å, ß = 113.48°. The initial structural model indicated that the crystals of BsTarI contained a dimer in the asymmetric unit.


Asunto(s)
Bacillus subtilis/enzimología , Nucleotidiltransferasas/química , Cristalización , Cristalografía por Rayos X , Expresión Génica , Modelos Moleculares , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/aislamiento & purificación , Estructura Terciaria de Proteína
16.
Artículo en Inglés | MEDLINE | ID: mdl-22750871

RESUMEN

The D-alanyl lipoteichoic acids (D-alanyl LTAs) present in the cell walls of Gram-positive bacteria play crucial roles in autolysis, cation homeostasis and biofilm formation. The alanylation of LTAs requires the D-alanyl carrier protein DltC to transfer D-Ala onto a membrane-associated LTA. Here, DltC from Staphylococcus epidermidis (SeDltC) was purified and crystallized using the sitting-drop vapour-diffusion method. The crystals diffracted to a resolution of 1.83 Šand belonged to space group P2, with unit-cell parameters a = 66.26, b = 53.28, c = 88.05 Å, ß = 98.22°. The results give a preliminary crystallographic analysis of SeDltC and shed light on the functional role of DltC in the alanylation of LTAs.


Asunto(s)
Proteínas Bacterianas/química , Proteínas Portadoras/química , Staphylococcus epidermidis/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/aislamiento & purificación , Proteínas Portadoras/genética , Proteínas Portadoras/aislamiento & purificación , Cristalización , Cristalografía por Rayos X , Expresión Génica
17.
FEBS Lett ; 586(16): 2260-6, 2012 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-22684010

RESUMEN

In nucleus, eIF4E regulates the nucleus export of specific mRNA. In this study, altered 4E-BP3 (eIF4E-binding protein 3) expression resulted in profoundly affected cyclin D1 protein levels, partially due to changes in the cytoplasmic cyclin D1 mRNA levels in both U2OS and MCF7 cells, whereas altered 4E-BP1 expression did not affect eIF4E-mediated cyclin D1 mRNA export. 4E-BP3 also affected a subset of growth promoting mRNAs exported in an eIF4-dependent manner. Furthermore, 4E-BP3 interacted with dephosphorylated RPA2 (replication protein A2). The results indicated 4E-BP3 acts as an inhibitor of eIF4E-mediated mRNA export in the examined cells, and 4E-BP3 inhibition of eIF4E-mediated mRNA export is regulated by the phosphorylation state of RPA2.


Asunto(s)
Núcleo Celular/metabolismo , Factor 4E Eucariótico de Iniciación/fisiología , Regulación Neoplásica de la Expresión Génica , Regulación de la Expresión Génica , Proteína de Replicación A/metabolismo , Transporte Activo de Núcleo Celular , Línea Celular Tumoral , Ciclina D1/metabolismo , Citoplasma/metabolismo , Daño del ADN , Replicación del ADN , Factor 4E Eucariótico de Iniciación/metabolismo , Humanos , Modelos Biológicos , Fosforilación , Estructura Terciaria de Proteína , ARN Mensajero/metabolismo , Distribución Tisular
18.
J Immunol ; 188(4): 1981-91, 2012 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-22238453

RESUMEN

IL-20 is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about its role in breast cancer. We explored the function of IL-20 in tumor growth and metastasis, as well as in clinical outcome. Tumor expression of IL-20 was assessed by immunohistochemical staining among 198 patients with invasive ductal carcinoma of the breast, using available clinical and survival data. IL-20 expression was associated with advanced tumor stage, greater tumor metastasis, and worse survival. Reverse transcription quantitative polymerase chain reaction showed that clinical breast tumor tissue expressed higher levels of IL-20 and its receptors than did nontumorous breast tissue. IL-20 was also highly expressed in breast cancer bone-metastasis tissue. In vitro, IL-20 upregulated matrix metalloproteinase-9, matrix metalloproteinase-12, cathepsin K, and cathepsin G, and enhanced proliferation and migration of breast cancer cells, which were inhibited by anti-IL-20 mAb 7E. In vivo, we generated murine models to evaluate the therapeutic potential of 7E, using luminescence intensity, radiological scans, and micro-computed tomography. 7E reduced tumor growth, suppressed bone colonization, diminished tumor-mediated osteolysis, and lessened bone density decrement in mice injected with breast cancer cells. In conclusion, our results suggest that IL-20 plays pivotal roles in the tumor progression of breast cancer. IL-20 expression in breast cancer tissue is associated with a poor clinical outcome. Anti-IL-20 mAb 7E suppressed bone colonization and decreased osteolytic bone lesions. Therefore, IL-20 may be a novel target in treating breast tumor-induced osteolysis.


Asunto(s)
Anticuerpos Monoclonales , Neoplasias de la Mama/inmunología , Carcinoma Ductal de Mama/inmunología , Interleucinas/biosíntesis , Interleucinas/inmunología , Osteólisis , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Huesos/patología , Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/metabolismo , Catepsina G/biosíntesis , Catepsina K/biosíntesis , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/inmunología , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Femenino , Humanos , Interleucinas/farmacología , Metaloproteinasa 12 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/biosíntesis , Ratones , Ratones Endogámicos BALB C , Metástasis de la Neoplasia , Osteólisis/tratamiento farmacológico , Osteólisis/inmunología , Osteólisis/patología
19.
J Struct Biol ; 174(3): 485-93, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21397029

RESUMEN

A NADPH-dependent blue fluorescent protein from Vibrio vulnificus CKM-1 (BFPvv) emits blue fluorescence under UV-exposure. Previously, the BFPvvD7 mutant generated by directed evolution displayed a fourfold enhancement in fluorescent intensity. Herein, a further increase in fluorescence in the new BFPvvD8 mutant, with three additional mutations from BFPvvD7, was made. To understand the underlying mechanism of the increased fluorescent intensity of BFPvv, we solved the BFPvvD8-NADPH complex structure. Accompanied with lifetime detection, we proposed that the enhanced intensity is related to the conformational change caused by a glycine residue (Gly176) mutated to other non-glycine residues at a turn close to the NADPH binding site. We also observed the Förster resonance energy transfer (FRET) from our BFPvvD8 to each of the GFP-like fluorescent proteins, mTFP1 and EGFP, joined by an eight-residue linker between the N-terminal of BFPvvD8 and the C-terminal of GFPs. Taken together, with the newly solved BFPvvD8 structure, our results not only provide new considerations within the rational-based protein engineering of this NADPH-dependent BFP, but also suggest that BFPvvD8 could be a potential candidate in FRET-based biosensor techniques.


Asunto(s)
Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Glicina/química , Proteínas Luminiscentes/química , Proteínas Luminiscentes/genética , NADP/química , Conformación Proteica , Secuencia de Aminoácidos , Técnicas Biosensibles , Dominio Catalítico , Color , Fluorescencia , Transferencia Resonante de Energía de Fluorescencia/métodos , Modelos Moleculares , Datos de Secuencia Molecular , Alineación de Secuencia , Vibrio vulnificus/química , Difracción de Rayos X
20.
Microbiology (Reading) ; 155(Pt 7): 2365-2374, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19389759

RESUMEN

Salmonella enterica serovar Choleraesuis (SC) is an important enteric pathogen that causes serious systemic infections in swine and humans. To identify the genes required for resistance to antimicrobial peptides, we constructed a bank of SC transposon mutants and screened them for hypersensitivity to the cationic peptide polymyxin B. Here we report one isolated polymyxin B-susceptible mutant that also exhibited increased sensitivity toward human neutrophil peptide alpha-defensin 1 (HNP-1) and hydrophobic antibiotics including erythromycin and novobiocin. The mutant had a mutation in an ORF identified as outer membrane beta-barrel protein gene omb. The purified recombinant Omb protein was characterized as a ferrous iron-binding protein. The constructed omb isogenic mutant grew more slowly in iron-limiting conditions than the wild-type (WT) parent strain. In addition, compared with the WT strain, the omb mutant exhibited an increase in net negative charge upon the cell surface and was more easily killed by polymyxin B, HNP-1 and hydrophobic antibiotics. The omb gene was transcribed, regardless of the iron content within the growth medium, and the Omb protein appeared exclusively in the outer membrane fraction. Infection experiments demonstrated virulence attenuation when the mutant was administered orally or intraperitoneally to mice. This study indicates that Omb is a previously unrecognized ferrous iron-binding protein. In vivo, Omb may be involved in the acquisition of ferrous iron during the initial stages of SC infection and appears to be an important virulence factor for SC in mice.


Asunto(s)
Antibacterianos/farmacología , Proteínas de la Membrana Bacteriana Externa/metabolismo , Farmacorresistencia Bacteriana/genética , Hierro/metabolismo , Salmonella enterica , Animales , Proteínas de la Membrana Bacteriana Externa/genética , Eritromicina/farmacología , Humanos , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Novobiocina/farmacología , Polimixina B/farmacología , Salmonella enterica/efectos de los fármacos , Salmonella enterica/metabolismo , Salmonella enterica/patogenicidad , Virulencia , alfa-Defensinas/farmacología
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