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The optical design and performance of the recently opened 13A biological small-angle X-ray scattering (SAXS) beamline at the 3.0â GeV Taiwan Photon Source of the National Synchrotron Radiation Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4â m IU24 undulator of the beamline provides high-flux X-rays in the energy range 4.0-23.0â keV. MoB4C double-multilayer and Si(111) double-crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high-flux beam of â¼4 × 1014â photonsâ s-1 to a high-energy-resolution beam of ΔE/E ≃ 1.5 × 10-4; both modes share a constant beam exit. With a set of Kirkpatrick-Baez (KB) mirrors, the X-ray beam is focused to the farthest SAXS detector position, 52â m from the source. A downstream four-bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra-SAXS with a minimum scattering vector q down to 0.0004â Å-1, which allows resolving ordered d-spacing up to 1â µm. A microbeam, of 10-50â µm beam size, is tailored by a combined set of high-heat-load slits followed by micrometre-precision slits situated at the front-end 15.5â m position. The second set of KB mirrors then focus the beam to the 40â m sample position, with a demagnification ratio of â¼1.5. A detecting system comprising two in-vacuum X-ray pixel detectors is installed to perform synchronized small- and wide-angle X-ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra-SAXS in one beamline.
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Fotones , Sincrotrones , Dispersión del Ángulo Pequeño , Taiwán , Difracción de Rayos X , Rayos XRESUMEN
BACKGROUND AND PURPOSE: Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia-associated genes can provide new avenues for stroke prognostic applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia-induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA-messenger RNA (mRNA) biomarkers in addition to using traditional risk factors. METHODS: After the integration analysis of small RNA sequencing and mRNA polymerase chain reaction array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischaemic stroke patients. Receiver operator characteristic analysis was used to determine the performance of mRNA and miRNA expression. RESULTS: The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. In addition, Fas gene level was significantly higher in patients with an unfavorable outcome when compared with patients with a favorable outcome. The expression of Fas and miRNA hsa-let-7b-5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among patients with an unfavorable outcome, suggesting Fas signal transporting through exosome in the circulation system. CONCLUSIONS: Combined analyses of Fas and has-let-7b-5p expression in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in ischaemic stroke patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia-induced stroke outcomes.
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Isquemia Encefálica , Hiperglucemia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Biomarcadores , Isquemia Encefálica/complicaciones , Isquemia Encefálica/genética , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/genética , ARN Largo no Codificante , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/genética , Receptor fasRESUMEN
Objective: To provide scientific basis for the prevention and control of pneumoconiosis and the formulation of relevant policies, this paper discusses the loss of health life and economic loss caused by coal worker's pneumoconiosis in a mining group. Methods: From March to October 2017, 1262 cases of coal worker's pneumoconiosis were diagnosed in a mining group from 1972 to 2013. The direct and indirect economic losses are calculated by the step-by-step model method. Direct economic losses include medical expenses, one-time disability allowance, disability allowance, funeral allowance, one-time work death allowance, living and nursing expenses, food allowance, pension for supporting relatives and transportation expenses, etc. Indirect economic losses includes loss of social productivity, additional training fee for new employees, transportation fee for accompanying family members, loss of social productivity of accompanying family members, loss of production suspension and production reduction, etc. Life table method was used to calculate the loss of social productivity caused by coal worker's pneumoconiosis. Results: All 1262 coal worker's pneumoconiosis patients were male. In the stage of pneumoconiosis, 95.40% (1204/1262) of the first stage of pneumoconiosis and 42.62% (538/1262) of the seventh stage of disability. The age of diagnosis (22.02-71.33) was 47.38 years on average. 1262 coal worker's pneumoconiosis patients caused a total of 9068.54 years of health life loss, of which YLD accounted for 93.56% (8484.69/9068.54) . The loss of YLD (0.06-33.30) years in 1262 coal worker's pneumoconiosis patients was 6.70 years per capita. The total economic loss of 1262 coal workers with pneumoconiosis was 2842185447.70 yuan, with a per capita of 2252127.93 yuan. The direct economic loss accounted for 81.59% (2318990168.46/2842185447.70) , which was 4.42 times of the indirect economic loss. Among the direct economic loss per capita, medical expenses accounted for a large proportion of 50.04% (919510.84/1837551.64) . The per capita indirect economic loss is 414576.29 yuan. The loss of social productivity accounted for 56.18% (232908.95/414576.29) . Conclusion: Coal worker's pneumoconiosis causes heavy economic burden and serious loss of social productivity.
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Antracosis/epidemiología , Minas de Carbón , Personas con Discapacidad , Antracosis/economía , Costo de Enfermedad , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The NF-kB (nuclear factor kB) pathway is involved in the proliferation of many cell types. To explore the mechanism of the NF-kB signaling pathway underlying the oval cell proliferation during rat liver regeneration, the Rat Genome 230 2.0 Array was used to detect expression changes of NF-kB signaling pathway-related genes in oval cells. The results revealed that the expression levels of many genes in the NF-kB pathway were significantly changed. This included 48 known genes and 16 homologous genes, as well as 370 genes and 85 homologous genes related to cell proliferation. To further understand the biological significance of these changes, an expression profile function was used to analyze the potential biological processes. The results showed that the NF-kB pathway promoted oval cell proliferation mainly through three signaling branches; the tumor necrosis factor alpha branch (TNF-a pathway), the growth factor branch, and the chemokine branch. An integrated statistics method was used to define the key genes in the NF-kB pathway. Seven genes were identified to play vital roles in the NF-kB pathway. To confirm these results, the protein content, including two key genes (TNF and FGF11) and two non-key genes (CCL2 and TNFRSF12A), were analyzed using two-dimensional gel electrophoresis and MALDI-TOF/TOF mass spectrometry. The results were generally consistent with those of the array data. To conclude, three branches and seven key genes were involved in the NF-kB signaling pathway that regulates oval cell proliferation during rat liver regeneration.
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Proliferación Celular , Regeneración Hepática , Hígado/metabolismo , FN-kappa B/metabolismo , Transducción de Señal , Animales , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Hígado/citología , Hígado/fisiología , FN-kappa B/genética , Ratas , Receptores del Factor de Necrosis Tumoral/genética , Receptores del Factor de Necrosis Tumoral/metabolismo , Receptor de TWEAK , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Serine peptidase inhibitor, Kazal type 3 (SPINK3) is a trypsin inhibitor, and also a growth factor that has an identical structure to epidermal growth factor (EGF), which could combine with epidermal growth factor receptor (EGFR) to promote cell proliferation. To shed light on the role and regulation mechanism of SPINK3 in rat liver regeneration (LR), Rat Genome 230 2.0 assay was used to detect the expression profiles of LR genes after partial hepatectomy (PH). The results showed that Spink3 was significantly up-regulated at 2-24 h and 72-168 h after PH. In the present study, RT-PCR and immunoblotting were used to validate the assay results. Ingenuity Pathway Analysis 9.0 (IPA) software was used to build the SPINK3 signaling regulating LR and analyze the possible mechanism. And then the expression of cell proliferation-associated gene Ccna2 was examined by RT-PCR in normal rat liver cell line BRL-3A in which Spink3 was overexpressed. The results showed that Ccna2 was significantly up-regulated in BRL-3A in which Spink3 was over-expressed. SPINK3 combining with EGFR accelerated cell proliferation during rat liver regeneration via P38, PKC, JAK-STAT and AKT pathways. Thus, SPINK3 was likely to promote hepatocytes proliferation in LR through P38, PKC, JAK-STAT and AKT.
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Proteínas Portadoras/metabolismo , Ciclina A2/genética , Receptores ErbB/genética , Redes Reguladoras de Genes , Hepatectomía , Regeneración Hepática/genética , Inhibidores de Serina Proteinasa/genética , Animales , Línea Celular , Proliferación Celular/genética , Ciclina A2/metabolismo , Receptores ErbB/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Hepatocitos/citología , Hepatocitos/metabolismo , Quinasas Janus/genética , Quinasas Janus/metabolismo , Hígado/metabolismo , Hígado/cirugía , Proteína Quinasa C/genética , Proteína Quinasa C/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Inhibidores de Serina Proteinasa/metabolismo , Transducción de Señal , Inhibidor de Tripsina Pancreática de Kazal , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Objective: To investigate the effect of occupational lead exposure on blood pressure and pro-vide supportive evidence of health protection on lead - exposed workers. Methods: 612 workers (452 lead - ex-posed workers, 160 workers as control) were recruited in the battery factory. The blood lead concentration and blood pressure were detected by occupational health examination and biological monitoring. The relationship of blood lead concentration and blood pressure wasanalyzed. Results: The blood lead concentration in the exposed group (249.84±137.74) µg/L was higher than that of the control group (117.25±70.15) µg/L, and the differ-ence was statistically significant (P<0.01) . The difference of abnormal blood pressure and diastolic pressure among the exposed and the control group was statistically significant (P<0.05) . The abnormal blood pressure rate, systolic pressure rate and diastolic pressure rate in the 400~726 µg/L group was higher than that of the 6~199 µg/L and 200~399 µg/L group, and the difference was statistically significant (P<0.01) . Multiple lin-ear regression analysis showed that the influencing factors of the systolic pressure followed by sex, age, length of service and blood lead concentration, diastolic pressure followed by sex, age, smoke and blood lead concen-tration. Conclusion: These findings suggest that long - term occupational lead exposure may result in the in-crease of blood lead concentration.
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Presión Sanguínea/efectos de los fármacos , Plomo/sangre , Exposición Profesional , Estudios de Casos y Controles , Suministros de Energía Eléctrica , Monitoreo del Ambiente , Humanos , Plomo/toxicidad , Análisis Multivariante , Análisis de RegresiónRESUMEN
We examined the gene expression profiles of the 5-hydroxytryptamine signaling pathway in the regenerating liver and 8 types of liver cells during rat liver regeneration, and explored expression differences in 5-hydroxytryptamine signaling pathway genes at the level of tissues and cells, as well as the role of the pathway on liver regeneration. Eight types of rat regenerating liver cells were isolated using Percoll density-gradient centrifugation and immunomagnetic bead methods. Rat Genome 230 2.0 Array was used to detect expression changes in 5-hydroxytryptamine signaling pathway genes. The results showed that 26, 47, 8, 21, 16, 19, 22, 27, and 20 genes changed significantly in hepatocytes, biliary epithelial cells, hepatic stellate cells, oval cells, sinusoidal endothelial cells, Kupffer cells, pit cells, dendritic cells, and the regenerating liver, respectively. Synthetic effects of 5-hydroxytryptamine signaling pathway genes in 8 types of liver cells showed that 26 genes were expressed significantly; the expression trends of 10 genes were the same in the regenerating liver, while others were different. Based on the gene expression profiles of the 8 types of liver cells, 5-hydroxytryptamine promoted hepatocyte proliferation through the RAS and STAT3 signaling pathways, proliferation and differentiation of sinusoidal endothelial cells through the STAT3 signaling pathway, and proliferation and apoptosis of pit cells through the AKT3 signaling pathway. There were large differences in genes involved in 5-hydroxytryptamine signaling at the tissue and cellular levels; thus, liver regeneration should be studied in-depth at the cellular level to reveal the molecular mechanism of liver regeneration.
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Hepatocitos/metabolismo , Regeneración Hepática , Serotonina/fisiología , Transcriptoma , Animales , Células Cultivadas , Femenino , Perfilación de la Expresión Génica , Hígado/citología , Hígado/metabolismo , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
Previous studies have demonstrated that the nuclear factor κB (NF-κB) pathway is involved in promoting cell proliferation. To further explore the regulatory branches and their sequence in the NF-κB pathway in the promotion of hepatocyte proliferation at the transcriptional level during rat liver regeneration, Rat Genome 230 2.0 array was used to detect the expression changes of the isolated hepatocytes. We found that many genes involved in the NF-κB pathway (including 73 known genes and 19 homologous genes) and cell proliferation (including 484 genes and 104 homologous genes) were associated with liver regeneration. Expression profile function (Ep) was used to analyze the biological processes. It was revealed that the NF-κB pathway promoted hepatocyte proliferation through three branches. Several methods of integrated statistics were applied to extract and screen key genes in liver regeneration, and it indicated that eight genes may play a vital role in rat liver regeneration. To confirm the above predicted results, Ccnd1, Jun and Myc were analyzed using qRT-PCR, and the results were generally consistent with that of microarray data. It is concluded that 3 branches and 8 key genes involved in the NF-κB pathway regulate hepatocyte proliferation during rat liver regeneration.
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Hepatocitos/citología , Hepatocitos/metabolismo , Regeneración Hepática/genética , FN-kappa B/metabolismo , Transducción de Señal/genética , Animales , Proliferación Celular , Regulación de la Expresión Génica , Modelos Biológicos , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
As the oldest known magnetic material, magnetite (Fe3O4) has fascinated mankind for millennia. As the first oxide in which a relationship between electrical conductivity and fluctuating/localized electronic order was shown, magnetite represents a model system for understanding correlated oxides in general. Nevertheless, the exact mechanism of the insulator-metal, or Verwey, transition has long remained inaccessible. Recently, three-Fe-site lattice distortions called trimerons were identified as the characteristic building blocks of the low-temperature insulating electronically ordered phase. Here we investigate the Verwey transition with pump-probe X-ray diffraction and optical reflectivity techniques, and show how trimerons become mobile across the insulator-metal transition. We find this to be a two-step process. After an initial 300 fs destruction of individual trimerons, phase separation occurs on a 1.5±0.2 ps timescale to yield residual insulating and metallic regions. This work establishes the speed limit for switching in future oxide electronics.
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OBJECTIVE: Primary cilia are present in almost every cell type including chondrocytes. Studies have shown that defects in primary cilia result in skeletal dysplasia. The purpose of this study was to understand how loss of primary cilia affects articular cartilage. DESIGN: Ift88 encodes a protein that is required for intraflagellar transport and formation of primary cilia. In this study, we used Col2aCre;Ift88(fl/fl) transgenic mice in which primary cilia were deleted in chondrocytes. Col2aCre;Ift88(fl/fl) articular cartilage was characterized by histological staining, real time RT-PCR, and microindentation. Hedgehog (Hh) signaling was measured by expression of Ptch1 and Gli1 mRNA. The levels of Gli3 proteins were determined by western blot. RESULTS: Col2aCre;Ift88(fl/fl) articular cartilage was thicker and had increased cell density, likely due to decreased apoptosis during cartilage remodeling. Mutant articular cartilage also showed increased expression of osteoarthritis (OA) markers including Mmp13, Adamts5, ColX, and Runx2. OA was also evident by reduced stiffness in mutant cartilage as measured by microindentation. Up-regulation of Hh signaling, which has been associated with OA, was present in mutant articular cartilage as measured by expression of Ptch1 and Gli1. Col2aCre;Ift88(fl/fl) cartilage also demonstrated reduced Gli3 repressor to activator ratio. CONCLUSION: Our results indicate that primary cilia are required for normal development and maintenance of articular cartilage. It was shown that primary cilia are required for processing full length Gli3 to the truncated repressor form. We propose that OA symptoms in Col2aCre;Ift88(fl/fl) cartilage are due to reduced Hh signal repression by Gli3.
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Artritis Experimental/patología , Cartílago Articular/ultraestructura , Condrocitos/ultraestructura , Cilios/patología , Osteoartritis/patología , Animales , Artritis Experimental/metabolismo , Artritis Experimental/fisiopatología , Biomarcadores/metabolismo , Cartílago Articular/metabolismo , Cartílago Articular/fisiopatología , Cilios/fisiología , Proteínas Hedgehog/metabolismo , Factores de Transcripción de Tipo Kruppel/biosíntesis , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones , Ratones Transgénicos , Proteínas del Tejido Nervioso/metabolismo , Osteoartritis/metabolismo , Osteoartritis/fisiopatología , Receptores Patched , Receptor Patched-1 , ARN Mensajero/genética , Receptores de Superficie Celular/biosíntesis , Receptores de Superficie Celular/genética , Transducción de Señal/fisiología , Estrés Mecánico , Regulación hacia Arriba , Proteína con Dedos de Zinc GLI1 , Proteína Gli3 con Dedos de ZincRESUMEN
We studied the symmetry of the Fe 3d wave function in magnetite below the Verwey temperature T(V) with resonant soft-x-ray diffraction. Although the lattice structure of the low-temperature phase of Fe(3)O(4) is well described by the pseudo-orthorhombic Pmca with a slight monoclinic P2/c distortion, we find that the 3d wave function does not reflect the Pmca symmetry, and its distortion toward monoclinic symmetry is by far larger than that of the lattice. The result supports a scenario in which the Verwey transition involves the ordering of t(2g) orbitals with complex-number coefficients.
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Recent developments in the instrumentation and data analysis of synchrotron small-angle X-ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0â GeV Taiwan Photon Source for biological small- and wide-angle X-ray scattering (SAXS-WAXS or SWAXS). The endstation features an in-vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size-exclusion chromatography system incorporating several optical probes including a UV-Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS-WAXS data collection and data reduction for high-throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal-model fittings to the data in the q range â¼0.005-2.0â Å-1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration-dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.
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OBJECTIVE: To examine rubella seroepidemiology, and estimate rates of catch-up immunisation and persistence of antibody titers in pregnant women in Taiwan after mass immunisation. DESIGN: A retrospective study. SETTING: Two medical centres and four regional hospitals specialising in obstetric care. SAMPLE: A total of 43,640 prenatal rubella test results for pregnant women from 2001 to 2008. METHODS: Rubella immunoglobulin G (IgG) antibody assay. MAIN OUTCOME MEASURES: Seronegativity, rate of catch-up immunization, and antibody decline. RESULTS: The seronegativity was 10.9% in all pregnant women. Immigrant women had higher seronegativity than indigenous women (OR 2.86; 95% CI 2.65, 3.01). Indigenous women born prior to implementation of the vaccination programmes were more susceptible (20.1%) to rubella infection than were women born thereafter (6.7%). Rates of seropositive conversion were low in both Taiwanese-born and foreign-born women (11.5 and 30.7%, respectively). The rubella antibody titers for vaccinated Taiwanese women in the 1971-1976 and after-1976 birth cohorts declined by 0.6 and 2.3% per year, respectively. CONCLUSIONS: This study demonstrates high seronegativity of older indigenous and immigrant women, a low catch-up immunisation rate, and the persistence of rubella antibodies in Taiwan after mass vaccination. Our study suggests that a single dose of rubella vaccine in teenagers effectively increased rubella seropositivity during their childbearing years. This finding is useful for countries that lack the resources necessary for a two-dose regimen. We recommend free rubella antibody tests to women of childbearing age and free vaccination as required. All postpartum women testing negative for rubella antibodies should be vaccinated before they leave hospital.
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Anticuerpos Antivirales/sangre , Complicaciones Infecciosas del Embarazo/epidemiología , Vacuna contra la Rubéola , Rubéola (Sarampión Alemán)/epidemiología , Emigrantes e Inmigrantes , Femenino , Humanos , Vacunación Masiva/estadística & datos numéricos , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/prevención & control , Rubéola (Sarampión Alemán)/inmunología , Rubéola (Sarampión Alemán)/prevención & control , Síndrome de Rubéola Congénita/epidemiología , Síndrome de Rubéola Congénita/inmunología , Síndrome de Rubéola Congénita/prevención & control , Estudios Seroepidemiológicos , Taiwán/epidemiología , Taiwán/etnologíaRESUMEN
BACKGROUND AND OBJECTIVE: Individuals with p phenotype lack P1, P(k) and P antigens on red blood cells, presumably as a result of deficiency in the enzyme α(1,4)galactosyltransferase (A4GALT). The aim of this study was to explore the molecular background of a Taiwanese family with p phenotype. MATERIALS AND METHODS: Blood samples from two p siblings and seven family members were investigated. The coding region of the A4GALT gene was analysed by polymerase chain reaction and direct sequencing. The wild- and mutant-complementary DNAs (cDNAs) of A4GALT were cloned into an expression vector and transfected to Chinese hamster ovary (CHO) cells. P(k) expression on the transfected cells was analysed by flow cytometry and the activities of A4GALT were measured by high-performance liquid chromatography. RESULTS: The two individuals with p phenotype were homozygous for the complex mutation, which was caused by a combined deletion and insertion between nt 418 and 428. No expression of P(k) and no enzyme activity were observed in cells transfected with the mutant construct. CONCLUSION: The first case of p phenotype in Taiwan was caused by a non-functional allele resulting from a homozygous complex mutation of A4GALT gene.
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Galactosiltransferasas/genética , Sistema del Grupo Sanguíneo P/genética , Alelos , Animales , Células CHO , Cricetinae , Cricetulus , Análisis Mutacional de ADN , ADN Complementario/genética , Femenino , Galactosiltransferasas/deficiencia , Humanos , Masculino , Mutagénesis Insercional , Linaje , Fenotipo , Eliminación de Secuencia , Taiwán , TransfecciónRESUMEN
Liver cancer (LC) is generally characterized by malignant cell proliferation and growth; it normally develops in stages that progress from non-specific injury of the liver to liver fibrosis, liver cirrhosis, dysplasia nodules, and liver carcinoma. We used a rat model of diethylnitrosamine (DENA)-induced LC; a Rat Genome 230 2.0 Array was used to detect gene expression profile of liver tissues from male rats 5, 8, 12, 16, and 18 weeks following the beginning of DENA-induced LC. We found 909 known genes, including 637 up-regulated, 270 down-regulated, and two up/down-regulated genes, that were significantly changed in expression. Among them, 108 genes were expressed at the 5th, 213 at the 8th, 516 at the 12th, 698 at the 16th, and 506 at the 18th week of DENA-induced LC. Methods in bioinformatics and systems biology were applied to explore the correlation between the gene expression profile of rat liver tissue and liver cancer occurrence at the transcriptional level; 23 physiological activities were found to be associated with LC. Among these, eight physiological activities, including stimulus response, inflammation and immune response, oxidative reduction, cell proliferation, differentiation, migration, adhesion, and angiogenesis were increased, implying that they could play important roles in the occurrence and development of LC. In addition, carbohydrate, lipid, and organic acid metabolism were decreased, suggesting that liver injury induced by a carcinogenic agent has a negative effect on the metabolism of fundamental substances.
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Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Hígado/metabolismo , Hígado/patología , Animales , Dietilnitrosamina , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Hígado/fisiopatología , Neoplasias Hepáticas/fisiopatología , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los ResultadosRESUMEN
Hepatic pit cells are a population of large granular lymphocytes that substantially contribute to hepatic immunity. Studies have proven that pit cells have a role in liver regeneration, but the details of the relationship between pit cells and liver regeneration is not clear at present. We subjected rats to a two-third hepatectomy; pit cells with high purity were obtained with Percoll density centrifugation and immunomagnetic bead methods, and the changes in mRNA levels in pit cells from the regenerating liver were monitored up to 168 h using a Rat Genome 230 2.0 Array composed of 25,020 distinct rat liver cDNA clones. Of the 25,020 genes analyzed, 612 known and 358 unknown genes were identified to be associated with liver regeneration. The 612 known genes are classified into up-regulation and down-regulation patterns based on the expression levels; they primarily participate in at least 23 biological activities based on gene ontology analysis. Together with gene function enrichment analysis, cytokines and a growth factor-mediated pathway in pit cells were activated at an early phase of liver regeneration; pit cell proliferation occurred from 24-72 h after liver hepatectomy; the machinery of pit cell differentiation commenced early and came into play late; an immune/inflammatory response was enhanced late. Expression pattern analysis of functionally classified genes in pit cells can give insights into the relationship between pit cells and liver regeneration.
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Regulación de la Expresión Génica , Células Asesinas Naturales , Regeneración Hepática , Hígado/fisiología , Animales , ADN Complementario , Perfilación de la Expresión Génica , Hepatectomía , Inmunidad Innata , Células Asesinas Naturales/citología , Células Asesinas Naturales/inmunología , Hígado/citología , Análisis por Micromatrices , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , ARN Mensajero/genética , Ratas , Ratas Sprague-DawleyRESUMEN
The JC virus (JCV) may infect human oligodendrocytes and consequently cause progressive multifocal leukoencephalopathy (PML) in patients with immune deficiency. In addition, the virus has also been detected in other human tissues, including kidney, B lymphocytes, and gastrointestinal tissue. The recombinant major structural protein, VP1, of JCV is able to self-assemble to form a virus-like particle (VLP). It has been shown that the VLP is capable of packaging and delivering exogenous DNA into human cells for gene expression. However, gene transfer is not efficient when using in vitro DNA packaging methods with VLPs. In this study, a novel in vivo DNA packaging method using the JCV VLP was used to obtain high efficiency gene transfer. A reporter gene, the green fluorescence protein, and a suicide gene, the herpes simplex virus thymidine kinase (tk), were encapsidated into VLPs in Escherichia coli. The VLP was used to specifically target human colon carcinoma (COLO-320 HSR) cells in a nude mouse model. Intraperitoneal administration of ganciclovir in the tk-VLP-treated mice greatly reduced tumor volume. These findings suggest that it will be possible to develop the JCV VLP as a gene delivery vector for human colon cancer therapy in the future.
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Adenocarcinoma/terapia , Neoplasias del Colon/terapia , Terapia Genética/métodos , Virus JC/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Animales , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Escherichia coli/genética , Ganciclovir/uso terapéutico , Técnicas de Transferencia de Gen , Vectores Genéticos , Proteínas Fluorescentes Verdes/análisis , Humanos , Ratones , Ratones Desnudos , Transducción Genética , Células Tumorales Cultivadas , Virión/genéticaRESUMEN
We have successfully grown centimeter-sized layered [Formula: see text] single crystals under high oxygen pressures of 120-150 bar by the floating zone technique. This enabled us to perform neutron scattering experiments where we observe close to quarter-integer magnetic peaks below [Formula: see text] that are accompanied by steep upwards dispersing spin excitations. Within the high-frequency Ni-O bond stretching phonon dispersion, a softening at the propagation vector for a checkerboard modulation can be observed. We were able to simulate the magnetic excitation spectra using a model that includes two essential ingredients, namely checkerboard charge disproportionation and nano phase separation. The results thus suggest that charge disproportionation is preferred instead of a Jahn-Teller distortion even for this layered [Formula: see text] system.
RESUMEN
We investigated the magnetoresistance (MR) of a single crystal of magnetite, Fe3O4. In an effort to distinguish between different contributions to the MR the samples were prepared in two different initial magnetic states, i.e. by either zero-field or by field cooling from room temperature. The different magnetic structures in this sample have a dramatic effect on the magnetoresistance: for initially zero-field-cooled conditions a negative MR of about -20% is observed just below the Verwey transition at [Formula: see text] K. For decreasing temperature the MR increases, changes sign at â¼78 K and reaches a record positive value of â¼45% at around 50 K. This behavior is completely absent in the field-cooled sample. Magnetization measurements corroborate an alignment of the easy magnetization direction in applied magnetic fields below [Formula: see text] as a cause of the strong effects observed in both, magnetization and MR. Our results point to a complex interplay of structural and magnetocrystalline effects taking place upon cooling Fe3O4 through [Formula: see text].
RESUMEN
Amino acids (AA) are components of protein and precursors of many important biological molecules. To address effects of the genes associated with metabolism and transport of AA and their derivatives during rat liver regeneration (LR), we firstly obtained the above genes by collecting databases data and retrieving related thesis, and then analyzed their expression profiles during LR using Rat Genome 230 2.0 array. The LR-associated genes were identified by comparing the gene expression difference between partial hepatectomy (PH) and sham-operation (SO) rat livers. It was approved that 134 genes associated with metabolism of AA and their derivatives and 26 genes involved in transport of them were LR-associated. The initially and totally expressing number of these genes occurring in initial phase of LR (0.5-4 h after PH), G0/G1 (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and structure-function reconstruction of liver tissue (72-168 h after PH) were respectively 76, 17, 79, 5 and 162, 89, 564, 195, illustrating that these LR-associated genes were initially expressed mainly in initial stage, and functioned in different phases. Frequencies of up-regulation and down-regulation of them being separately 564 and 357 demonstrated that genes up-regulated outnumbered those down-regulated. Categorization of their expression patterns into 22 types implied the diversity of cell physiological and biochemical activities. According to expression changes and patterns of the above-mentioned genes in LR, it was presumed that histidine biosynthesis in the metaphase and anaphase, valine metabolism in the anaphase, and metabolism of glutamate, glutamine, asparate, asparagine, methionine, alanine, leucine and aromatic amino acid almost were enhanced in the whole LR; as for amino acid derivatives, transport of neutral amino acids, urea, gamma-aminobutyric acid, betaine and taurine, metabolism of dopamine, heme, S-adenosylmethionine, thyroxine, and biosynthesis of hydroxyproline, nitric oxide, orinithine, polyamine, carnitine, selenocysteine were augmented during the entire liver restoration. Above results showed that metabolism and transport of AA and their derivates were necessary in liver regeneration.