ABSTRACT
OBJECTIVE: This study analyzes interactions of body condition score (BCS) with other factors and the effect of BCS on estimates of genetic paremeters of conception rate (CR) in Japanese Black cows. METHODS: Factors affecting CR were analyzed through the linear mixed model, and genetic parameters of CR were estimated through the threshold animal model. RESULTS: The interactions between BCS and each season and the number of artificial inseminations (AI) was significant (p<0.05), but that between BCS and parity showed no significance for CR. High CR was observed with BCS 3 in autumn (0.56±0.01) and BCS 4 in summer (0.56±0.02). The highest CR with BCS 3 (0.56±0.02) and BCS 4 (0.55±0.01) was observed at first AI. With BCS 5, however, the highest CR (0.55±0.08) was observed at second AI. CONCLUSION: The model with BCS was notably conducive to the estimation of genetic parameters because of a low deviance information criterion of heritability that, nevertheless, was slightly lower than the model without BCS.
ABSTRACT
BACKGROUND: We previously reported that Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal (Kampo) medicine used for the treatment of postoperative ileus (POI), has characteristic potent anti-inflammatory activity. This effect may be partly mediated by the activation of α7 nicotinic acetylcholine receptor (nAChR). In this study, we identified the specific herbs in DKT that induce anti-inflammatory action. METHODS: The herbal components of DKT were individually administered orally to each mouse four times before and after intestinal manipulation (IM) was carried out on the distal ileum. The anti-inflammatory activity of each crude drug was subsequently evaluated using immunohistochemical analyses of relevant molecules. KEY RESULTS: Treatment with Zingiberis Siccatum Rhizoma (ZSR) but not the other components inhibited the infiltration of cluster of differentiation 68 (CD68)-positive macrophages as effectively as DKT treatment. Selective α7nAChR antagonists, such as methyllycaconitine citrate, or transient receptor potential ankyrin 1 (TRPA1) antagonists, such as HC-030031, significantly inhibited the amelioration of macrophage infiltration by ZSR. The inhibition of macrophage infiltration by ZSR was abolished in both α7nAChR and 5-hydroxytryptamine 4 receptor (5-HT4 R) knockout mice. CONCLUSIONS & INFERENCES: Daikenchuto-induced anti-inflammatory activity, which was mediated by inhibiting macrophage infiltration in POI, is dependent on the effects of ZSR. Zingiberis Siccatum Rhizoma activates TRPA1 channels possibly in enterochromaffin (EC) cells to release 5-HT, which stimulates 5-HT4 R in the myenteric plexus neurons to release ACh, which in turn activates α7nAChR on macrophages to inhibit inflammation in POI.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Macrophages/drug effects , Plant Extracts/pharmacology , Zingiberales , alpha7 Nicotinic Acetylcholine Receptor/drug effects , Animals , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Gastrointestinal Transit/drug effects , Ileus , Male , Medicine, Kampo , Mice , Mice, Inbred C57BL , Mice, Knockout , Panax , Plant Extracts/chemistry , Postoperative Complications , Rhizome , Zanthoxylum , Zingiberaceae , alpha7 Nicotinic Acetylcholine Receptor/metabolismABSTRACT
Accelerated release of potassium (K), magnesium (Mg) and phosphorus (P) from surplus activated sludge (SAS) was investigated to develop a new system for the recovery of the elements. Anaerobic cultivation of SAS during 24 h released 78% of K and about 50% of Mg and P from SAS more effectively compared to aerobic cultivation (K: 40%, Mg: 15%, P: 15%). Furthermore, the addition of sodium acetate as an organic carbon source remarkably accelerated the release of K, Mg and P from SAS under anaerobic condition. However, no increase in the maximum release efficiencies was observed. The elements released from SAS could be transferred to separate liquid with the existing mechanical thickener and be recovered as MgKPO4 by some additional process. Furthermore, the removal of the elements from SAS would inhibit the formation of struvite causing the blockage of sludge transport pipe after anaerobic digestion process of thickened sludge.
Subject(s)
Magnesium/chemistry , Phosphorus/chemistry , Potassium/chemistry , Sewage/chemistry , Struvite/chemistry , Waste Disposal, Fluid/methods , Anaerobiosis , WastewaterABSTRACT
Onset of the cancer mesenchymal program is closely associated with cancer malignancy and drug resistance. Among the different epithelial-mesenchymal transition (EMT)-associated transcriptional factors, ZEB1 has a key role in inducing the mesenchymal phenotypes and stem cell-like properties of different breast cancer cells. ARF6 and its effector AMAP1 are frequently overexpressed in breast cancer cells, and promote invasion, metastasis and drug resistance. EPB41L5 is induced during EMT, and mediates the disruption of E-cadherin-based cell-cell adhesion and the promotion of focal adhesion dynamics. Here we show that EPB41L5 is an integral component of the ARF6-based pathway, which is induced by ZEB1. We found that EPB41L5 is expressed at high levels in malignant breast cancer cells and binds to AMAP1. ZEB1 induced EPB41L5 both in cancer cells and normal cells. This relationship was recaptured with The Cancer Genome Atlas RNASeq data set, and correlated with the poor outcome of the patients. In contrast, diversified events, such as tumor growth factor ß1 stimulation, expression of SNAI1 and TP53 mutation, can each cause the induction of ZEB1 and EPB41L5, depending on the cellular context. Our results demonstrated that the ZEB1-EPB41L5 axis is at the core of the cancer mesenchymal program that drives ARF6-based invasion, metastasis and drug resistance of significant populations of primary breast cancers, and is tightly correlated with the poor outcomes of patients.
ABSTRACT
To reduce labor for superovulation treatment by twice-daily intramuscular (im) administration of FSH for more than 3 to 4 days, we investigated the superovulatory responses of Japanese Black cows to porcine FSH (pFSH) used as a single subcutaneous (sc) administration at two different doses in two different volumes of saline. In experiment 1, 20 Armour units (AU) of pFSH dissolved in either 10 mL (treatment A; n = 14) or 50 mL (treatment B; n = 14) of saline was administered subcutaneously in the neck region. In experiment 2, 30 AU of pFSH dissolved in either 10 mL (treatment C; n = 15) or 50 mL (treatment D; n = 15) of saline was administered subcutaneously in the neck region. The control animals in experiment 1 (n = 14) and experiment 2 (n = 15) received 20 AU of pFSH administered intramuscularly twice daily in decreasing doses for more than 3 days. In experiment 1, mean (±SEM) numbers of CL (15.4 ± 2.5, 18.1 ± 3.4, and 17.2 ± 2.6), total number of ova and embryos (12.9 ± 1.4, 15.9 ± 3.5, and 16.2 ± 2.8), and transferable embryos (7.5 ± 2.0, 10.4 ± 2.8, and 8.0 ± 2.1) did not differ among treatments A, B, and control. In experiment 2, mean (±SEM) numbers of CL (20.5 ± 4.3, 20.4 ± 2.7, and 20.1 ± 3.4), total number of ova and embryos (21.7 ± 4.2, 17.3 ± 3.4, and 16.5 ± 3.2), and transferable embryos (8.1 ± 1.6, 9.3 ± 2.2, and 9.5 ± 1.9) did not differ among treatments C, D, and control. Although there were no differences in serum pFSH concentrations among the three treatments at each of the time points in experiment 1, in experiment 2, the serum pFSH concentration at 6 and 8 hours after pFSH administration in treatment C (3.1 ± 0.8, 2.7 ± 0.5 ng/mL, mean ± SEM) was significantly greater (P < 0.05) than in the control (0.7 ± 0.1, 1.1 ± 0.2 ng/mL). At 10 hours after administration, the pFSH concentration had decreased and there were no differences among the three treatments at subsequent time points. These results suggest that increasing the volume of saline or the dose of pFSH does not affect the absorption pattern of pFSH administered as a single sc administration. In conclusions, single sc administration of pFSH at a dose of 20 or 30 AU dissolved in 10 or 50 mL of saline is able to induce a superovulatory response comparable with that obtained by twice-daily im administration in Japanese Black cows.
Subject(s)
Cattle/physiology , Follicle Stimulating Hormone/pharmacology , Superovulation/drug effects , Animals , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follicle Stimulating Hormone/administration & dosage , Injections, Intramuscular , Injections, SubcutaneousABSTRACT
Our objective was to evaluate the temporal evolution of mercury exposure in two riverside communities, Barreiras and São Luiz do Tapajós, downstream of gold mining areas in the Tapajós basin, Brazilian Amazon. The quantification of mercury in hair sample was made by atomic absorption spectrophotometry in the period between 1994 and 2010. In São Luiz do Tapajós the mercury exposure varied, in log units, from the peak of 1.21 ± 0.03 µg/g in 1996 to 1.16 ± 0.07 µg/g in 2007. Mercury exposure in Barreiras varied, in log units, from 1.25 ± 0.04 µg/g in 1994 to 1 ± 0.03 µg/g in 2010, peaking in 1995 at 1.25 ± 0.06 µg/g. Total mercury concentration found in both communities had no statistical differences across the years (p > 0.05) and they were higher than non-mercury exposed communities in Brazil and in South America. We concluded that the mercury exposure in the Tapajós basin is more than regulatory levels or higher than the general population.
Subject(s)
Environmental Exposure/statistics & numerical data , Hair/metabolism , Mercury/metabolism , Water Pollutants, Chemical/metabolism , Adult , Brazil , Female , Food Contamination/statistics & numerical data , Hair/chemistry , Humans , Male , Mercury/analysis , Middle Aged , Mining , Residence Characteristics , Rivers/chemistry , Water Pollutants, Chemical/analysisABSTRACT
Radioresistance, which is a major cause of failure of radiotherapy (RT), is proposed as one of the intrinsic characteristics of cancer stem cells (CSCs) whose unique DNA damage response (DDR), efficient DNA repair and resistance to apoptosis are thought to confer the phenotype. We have isolated surviving CSCs by exposure to long-term fractionated radiation for 82 days from HepG2 and A172 cells (82FR-31NR cells). 82FR-31NR cells exhibited CSC properties, such as high expression of CSC marker CD133 and the ABC transporters (MDR1 and BCRP1), and high tumorigenic potential after transplantation into nude mice. The advantage of our isolated CSCs is that they can proliferate in as the same growth medium as that of parental cells without loss of CSC properties. Therefore, we can analyze DDR of non-stem cells and CSCs without any influences caused by different culture conditions. 82FR-31NR cells showed efficient DNA repair of radiation-induced DNA damage and radioresistance with activation of the AKT/cyclin D1 survival signaling pathway. In contrast, DNA damage persisted for a long time after irradiation in parental cells compared with isolated CSCs. Persisted DNA damage induced apoptosis in parental cells without activation of the AKT/cyclin D1 pathway. Therefore, inhibition of the AKT/cyclin D1 pathway by an AKT inhibitor, API-2, or cyclin D1 siRNA resulted in a loss of efficient DNA repair and radiosensitization of 82FR-31NR cells. Furthermore, knockdown of Cdk4 by its siRNA or a Cdk4 inhibitor was sufficient to suppress radioresistance of CSCs. In this study, we present a newly discovered DDR regarding the AKT/cyclin D1/Cdk4 pathway in response to radiation in CSCs. Combination of fractionated RT and reagents targeting the AKT/cyclin D1/Cdk4 pathway to eradicate CSCs would be effective therapeutic modality.
ABSTRACT
ZnO with additions of Fe2O3 or In2O3 shows characteristic inversion domain structures. ZnO domains are separated by two types of inversion domain boundaries (IDBs): basal b-IDBs parallel to (0001) planes, and complementary pairs of three possible variants of pyramidal p-IDBs parallel to {2115} lattice planes. The structure and composition of IDBs were investigated in a sophisticated aberration-corrected scanning transmission electron microscope (probe-corrected TEM/STEM). It is shown that Fe and In additions are essentially located in monolayers within the IDBs, and EELS electron spectroscopic imaging (ESI) as well as EDS spectroscopic imaging by X-rays (SIX) are capable of rapidly mapping the element distribution. With solid solubility of trivalent dopant species well below 1at.% within ZnO domains, the lateral spacings of b-IDBs are inversely proportional to the dopant concentration. Quantification of data acquired by ESI and SIX from well defined sample regions in STEM both confirm the assumption of one full monolayer of dopants per IDB. Atom columns of cations are well resolved in HAADF STEM imaging; experimental contrast intensities are approximately proportional to Z¹·6. Furthermore, annular bright-field (ABF)-STEM imaging is capable of resolving oxygen columns even in thick sample regions, thus providing highly localized information on atom positions and lattice distortions, and enables the construction of more reliable structure models of IDBs in doped ZnO.
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Radiotherapy is a well-established treatment for cancer. However, the existence of radioresistant cells is one of the major obstacles in radiotherapy. In order to understand the mechanism of cellular radioresistance and develop more effective radiotherapy, we have established clinically relevant radioresistant (CRR) cell lines, which continue to proliferate under daily exposure to 2 Gray (Gy) of X-rays for >30 days. X-ray irradiation significantly induced autophagic cells in parental cells, which was exiguous in CRR cells, suggesting that autophagic cell death is involved in cellular radiosensitivity. An autophagy inducer, rapamycin sensitized CRR cells to the level of parental cells and suppressed cell growth. An autophagy inhibitor, 3-methyladenine induced radioresistance of parental cells. Furthermore, inhibition of autophagy by knockdown of Beclin-1 made parental cells radioresistant to acute radiation. These suggest that the suppression of autophagic cell death but not apoptosis is mainly involved in cellular radioresistance. Therefore, the enhancement of autophagy may have a considerable impact on the treatment of radioresistant tumor.
Subject(s)
Autophagy/drug effects , Neoplasms/drug therapy , Neoplasms/radiotherapy , Radiation Tolerance/drug effects , Adenine/analogs & derivatives , Adenine/pharmacology , Adenine/therapeutic use , Cell Death/drug effects , Cell Survival/drug effects , Humans , Neoplasms/pathology , Tumor Cells, Cultured , X-RaysABSTRACT
Perillae Herba (a leaf of Perilla frutescens) has been prescribed as one of the component herbs in certain Kampo (Japanese herbal) medicines that are used clinically for the improvement of depressive mood. l-Perillaldehyde (PAH) is a major component in the essential oil containing in Perillae Herba, but its antidepressant-like effect has not been reported. To clarify the antidepressant-like effect of PAH, the inhaled effect of PAH on stress-induced depression-like model mice prepared by subjection to a combination of forced swimming and chronic mild stresses was investigated. The degree of the depression-like state was measured by the animal's duration of immobility using a forced swimming test. Inhalation of PAH (0.0965 and 0.965 mg/mouse/day, 9 days) significantly shortened the duration of immobility of the depression-like model mice and did not affect locomotor activity. However, another odor substance, cinnamaldehyde containing in Cinnamomi Cortex, exhibited no reduction in the immobility. The reduction in the immobility induced by the inhalation of PAH was prevented on anosmia-induced mice prepared by intranasal irrigation with zinc sulfate. These results suggest that the inhalation of PAH shows antidepressant-like activity through the olfactory nervous function.
ABSTRACT
Ostwald ripening has been broadly studied because it plays a determinant role in the evolution of cluster size during both chemical and physical synthesis of nanoparticles. This thermoactivated process causes large particles to grow, drawing material from the smaller particles, which shrink. However, this phenomenon becomes more complex when considering the coarsening of metallic alloy clusters. The present experimental and theoretical investigations show that the relative composition of CoPt nanoparticles can be strongly modified during high temperature annealing and displays a size-dependent behavior. This compositional change originates from the higher evaporation rate of Co atoms from the nanoparticles. More importantly, this effect is expected in all alloy clusters containing species with different mobilities.
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AIMS: To determine the sensitivity and specificity of the photopic negative response (PhNR) of the focal electroretinograms (ERG; focal PhNR) to detect glaucomatous eyes with different degrees of visual field defects. METHODS: One-hundred and fourteen eyes of 114 patients with open angle glaucoma and 42 eyes of 42 normal controls were studied. The focal ERGs were elicited by a 15 degrees stimulus spot centred on the macula, and on the supero-temporal and on the infero-temporal areas of the macula. The receiver operating characteristic curves were determined to obtain optimal cut-off values. Eyes were classified as being glaucomatous when their focal PhNRs were less than the cut-off values in either retinal area (combined criterion). RESULTS: The focal PhNR amplitudes were significantly reduced with an advance in the stage of glaucoma. In early glaucoma, the sensitivities of the PhNR measured for each retinal area ranged from 58.1% to 80.7%. The sensitivities were significantly increased to 90.6% and 96.9% for the focal PhNR amplitude and the focal PhNR/b-wave amplitude ratio, respectively, when the combined criterion was employed. The specificity was >90%. CONCLUSIONS: Focal PhNRs have diagnostic ability in detecting early glaucoma with high sensitivity and specificity, especially when the combined criterion is used.
Subject(s)
Glaucoma, Open-Angle/diagnosis , Adult , Aged , Aged, 80 and over , Aging/physiology , Early Diagnosis , Electroretinography/methods , Glaucoma, Open-Angle/physiopathology , Humans , Middle Aged , Sensitivity and Specificity , Severity of Illness Index , Signal Processing, Computer-Assisted , Visual Field Tests , Visual Fields/physiologyABSTRACT
The objective of this study was to find optimal traits for inclusion in selection criteria by estimating genetic parameters for direct genetic, maternal genetic, and common environmental effects for growth traits before 60 d of age and for the number of teats under an open breeding population, and to evaluate genetic relationships for traits at 60 d of age. Records of 2,344 male and 2,204 female purebred Berkshire pigs were analyzed. For BW at 14 d of age and for weaning weight, the heritabilities of a direct genetic effect were greater than those of a maternal genetic effect. This result is contrary to previous results showing a gradual decrease in the maternal genetic effect and an increase in the direct genetic effect up to weaning. The positive genetic correlations between direct and maternal genetic effects for BW at 14 d of age and weaning weight are clearly contrary to other reports. This phenomenon seems to be caused by creep feeding begun just after the birth of the piglets and maintained throughout the preweaning period in this Berkshire population.
Subject(s)
Swine/genetics , Animal Feed , Animals , Animals, Suckling/genetics , Animals, Suckling/growth & development , Birth Weight/genetics , Breeding/methods , Environment , Female , Male , Models, Genetic , Quantitative Trait, Heritable , Swine/growth & development , Weaning , Weight Gain/geneticsABSTRACT
Chemically ordered bimetallic nanoparticles are promising candidates for magnetic-storage applications. However, the use of sub-10 nm nanomagnets requires further study of possible size effects on their physical properties. Here, the effects of size and morphology on the order-disorder phase transition temperature of CoPt nanoparticles (T(C)(NP)) have been investigated experimentally, using transmission electron microscopy, and theoretically, with canonical Monte Carlo simulations. For 2.4-3-nm particles, T(C)(NP) is found to be 325-175 degrees C lower than the bulk material transition temperature, consistent with our Monte Carlo simulations. Furthermore, we establish that T(C)(NP) is also sensitive to the shape of the nanoparticles, because only one dimension of the particle (that is, in-plane size or thickness) smaller than 3 nm is sufficient to induce a considerable depression of T(C)(NP). This work emphasizes the necessity of taking into account the three-dimensional morphology of nano-objects to understand and control their structural properties.
ABSTRACT
Nanoparticles' morphology is a key parameter in the understanding of their thermodynamical, optical, magnetic and catalytic properties. In general, nanoparticles, observed in transmission electron microscopy (TEM), are viewed in projection so that the determination of their thickness (along the projection direction) with respect to their projected lateral size is highly questionable. To date, the widely used methods to measure nanoparticles thickness in a transmission electron microscope are to use cross-section images or focal series in high-resolution transmission electron microscopy imaging (HRTEM "slicing"). In this paper, we compare the focal series method with the electron tomography method to show that both techniques yield similar particle thickness in a range of size from 1 to 5 nm, but the electron tomography method provides better statistics since more particles can be analyzed at one time. For this purpose, we have compared, on the same samples, the nanoparticles thickness measurements obtained from focal series with the ones determined from cross-section profiles of tomograms (tomogram slicing) perpendicular to the plane of the substrate supporting the nanoparticles. The methodology is finally applied to the comparison of CoPt nanoparticles annealed ex situ at two different temperatures to illustrate the accuracy of the techniques in detecting small particle thickness changes.
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The objective of this study was to estimate genetic parameters for growth and body composition traits at 60 d of age and at finish in a population of Berkshire pigs and to evaluate the effectiveness of selection at 60 d of age for meat productivity. A total of 4,548 purebred Berkshire (2,344 males and 2,204 females) pigs born between December 1994 and January 2005 were used in this study. The traits analyzed were BW at 60 d of age; daily BW gain from birth to finish, from weaning to 60 d, from weaning to finish, and from 60 d to finish; age at finish; backfat thickness at 60 d of age and at finish; loin eye area at 60 d of age (LEA60) and at finish; and the number of teats. The heritability estimates for BW at 60 d of age, daily BW gain from weaning to 60 d, backfat thickness at 60 d of age, and LEA60 were 0.22, 0.25, 0.49, and 0.22, respectively. The estimated common environmental effect for BW at 60 d of age, daily BW gain from weaning to 60 d, backfat thickness at 60 d of age, and LEA60 were 0.12, 0.13, 0.18, and 0.21, respectively. Therefore, the common environmental effect should be included in the model to analyze traits at 60 d of age. The positive genetic correlation between LEA60 and loin eye area at finish and the negative genetic correlation between LEA60 and backfat thickness at finish indicated that improvement of the ultrasonic loin eye area at 60 d of age may result in favorable correlated responses to the traits at finish, an increase in loin eye area, and a decrease in backfat thickness. In addition, genetic correlations of backfat thickness at 60 d of age with backfat thickness at finish and loin eye area at finish were found to be favorable, indicating that improvement of ultrasonic backfat thickness at 60 d of age may result in greater correlated responses to the traits at finish: an increase in loin eye area and a decrease in backfat thickness. Therefore, constructing a selection scheme that includes body composition traits at 60 d and traits at finish is practical for gaining a greater selection response.
Subject(s)
Breeding , Meat/standards , Swine/growth & development , Swine/genetics , Weaning , Adipose Tissue/physiology , Animals , Body Composition/genetics , Environment , Female , Male , Selection, Genetic , Time FactorsABSTRACT
Records on 514 bulls from the sire population born from 1978 to 2004, and on 22,099 of their field progeny born from 1997 to 2003 with available pedigree information (total number = 124,458) were used to estimate genetic parameters for feed intake and energy efficiency traits of bulls and their relationships with carcass traits of field progeny. Feed intake and energetic efficiency traits were daily feed intake, TDN intake, feed conversion ratio (FCR), TDN conversion ratio (TDNCR), residual feed intake (RFI), partial efficiency of growth, relative growth rate, and Kleiber ratio. Progeny carcass traits were carcass weight (CWT), yield estimate, ribeye area, rib thickness, subcutaneous fat thickness (SFT), marbling score (MSR), meat color standard (MCS), fat color standard (FCS), and meat quality grade. All measures of feed intake and energetic efficiency were moderately heritable (ranged from 0.24 to 0.49), except for partial efficiency of growth and relative growth rate, which were high (0.58) and low (0.14), respectively. The phenotypic and genetic correlations between FCR and TDNCR were >or=0.93. Selection for Kleiber ratio will improve all of the energetic efficiency traits with no effect on feed intake measures (daily feed intake and TDN intake). The genetic correlations of FCR, TDNCR, and RFI of bulls with most of the carcass traits of their field progeny were favorable (ranged from -0.24 to -0.72), except with fat color standard (no correlation), MCS, and SFT. Positive (unfavorable) genetic correlations of MCS with FCR, TDNCR, and RFI (0.79, 0.70, and 0.51, respectively) were found. The SFT was negatively genetically correlated with FCR and TDNCR (-0.32 and -0.20, respectively); however, the genetic correlation between RFI and SFT was not significantly different from zero (r(g) = -0.08 +/- 0.12). Favorable correlated responses in CWT, yield estimate, ribeye area, rib thickness, MSR, and meat quality grade would be predicted for selection against any measure of energetic efficiency. The correlated responses in CWT and MSR of progeny were greater for selection against RFI than for selection against any other energetic efficiency trait. Results of this study indicate that RFI should be preferred over other measures of energetic efficiency to include in selection programs.
Subject(s)
Cattle/genetics , Cattle/metabolism , Energy Metabolism/genetics , Meat/standards , Phenotype , Animals , Breeding , Eating/genetics , Female , Genetic Variation , Japan , MaleABSTRACT
The Wnt signaling pathway is involved in normal embryonic development and controls the homeostatic self-renewal of stem cells in adult tissues. Constitutive activation of Wnt signaling contributes to cancer development and progression. We identified a CXXC4 homozygous deletion at 4q24 in an aggressive renal cell carcinoma (RCC) using single-nucleotide polymorphism (SNP) arrays. CXXC4 encodes Idax, which negatively regulates Wnt signaling by binding to the PDZ domain of Dishevelled. CXXC4 mRNA levels in tumor samples were significantly lower in patients with metastases compared with those without (P=0.0016). Patients whose tumors had lower CXXC4 expression than normal kidney showed a poorer cause-specific survival outcome than those with higher expression (P=0.0095). Decreased expression of CXXC4 also correlated with cytoplasmic staining of beta-catenin. Knockdown of CXXC4 induced the nuclear translocation of beta-catenin and altered expression of a set of genes involved in cell proliferation, invasion and survival. Furthermore, reduced expression of CXXC4 by small interfering RNAs promoted cell proliferation and inhibited apoptosis after 5-FU and doxorubicin treatment in RCC cells. These data suggest that CXXC4 plays a critical role in tumor progression of RCC through Wnt signaling. Wnt signaling could thus be a potential molecular target in RCC indicating decreased CXXC4 expression.
Subject(s)
Carcinoma, Renal Cell/genetics , Cell Transformation, Neoplastic/genetics , DNA-Binding Proteins/physiology , Kidney Neoplasms/genetics , Neoplasm Proteins/physiology , Sequence Deletion , Transcription Factors/physiology , Wnt Proteins/physiology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Cell Division/genetics , Chromosomes, Human, Pair 4/genetics , DNA, Neoplasm/genetics , DNA-Binding Proteins/genetics , Drug Resistance, Neoplasm/genetics , Gene Dosage , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Proteins/genetics , RNA, Small Interfering/pharmacology , Signal Transduction , Survival Analysis , Transcription Factors/genetics , beta Catenin/metabolismABSTRACT
Motional Stark effect (MSE) diagnostics in JT-60U works as polarimeter to measure the pitch angle of magnetic field as well as beam-emission-spectroscopy (BES) monochromator simultaneously at 30 spatial channels. Fluctuation in the BES signal using MSE optics (MSE/BES) contains fluctuations in not only the density but also the pitch angle (or the magnetic field). Correlation analysis of the magnetic fluctuation between two spatial channels is applied to high-beta plasma with a magnetohydrodynamic activity at frequency of about 0.9 kHz. It has been found that the magnetic fluctuation measured by the MSE/BES is spatially localized near the magnetic flux surface having safety factor and that the phase of the fluctuation is inverted at about the surface, suggesting magnetic island structure by tearing mode. The phase of the magnetic fluctuation measured by the MSE/BES at outside of the q=2 surface is consistent with that by the pickup coil placed outside the plasma.
ABSTRACT
A decrease in orexin-A (OX-A) levels has been reported to be associated with depression. It is also well known that stress and depression can disrupt neurogenesis in the dentate gyrus of the hippocampus; however, it is unclear how OX-A is involved in depression and/or neurogenesis. In the present study, we investigated the effect of i.c.v. administration of OX-A on the forced swimming test (FST), an accepted behavioral screen of antidepressant-like activity, and on the cell proliferation with bromodeoxyuridine (BrdU) in the dentate gyrus at 4 days after i.c.v. administration of OX-A. OX-A administration (140 pmol/mouse) led to a significant reduction in animal immobility in the FST, without affecting spontaneous locomotor activities or serum corticosterone levels. In addition, the number of BrdU-positive cells in the dentate gyrus was significantly increased in OX-A-treated mice in vivo; however, OX-A did not affect the percentage of doublecortin-positive cells in the dentate gyrus. The proliferation of neural progenitor cells derived from rat fetal brain was not affected by OX-A treatment in vitro, and the orexin receptor 1 (OXR1) protein was not expressed in these cells. Treatment with the OXR1 antagonist SB-334867 (30 mg/kg, i.p.) blocked both the OX-A-induced decrease in the immobility of FST and increase in BrdU-positive. Moreover, the OX-A-induced increase in neuropeptide Y (NPY)-positive cells in the hilus of the dentate gyrus was blocked by SB-334867. These results suggest that OX-A induces an antidepressive-like effect, at least in part, via the enhancement of cell proliferation in the dentate gyrus. These effects of OX-A also may be partly relevant to the regulation of the NPY system in the hilus of the dentate gyrus.