Investigation of multifilament MgB2 superconducting joint technique for development of MRI magnets.

This study presents the investigation of superconducting joints fabricated using multifilament magnesium diboride (MgB2) wires for the development of persistent-current mode magnetic resonance imaging (MRI) magnets. The critical current of the jointed samples decreased with increasing cutting angle because the smaller cutting angle allowed greater exposure of the MgB2 filament, thereby increasing the contact area for the wire-bulk-wire connection. In addition, an appropriate pressing pressure (300 MPa) was necessary to establish the multifilament MgB2 joint without significant degradation of superconducting properties. The resistance of the optimal MgB2 joint, measured using the field-decay technique, was <1.5 × 10-14 Ω. Therefore, the proposed joint technique can be employed for developing multifilament MgB2 MRI magnets operating in the persistent-current mode.

Note: Progress on the use of MgB2 superconducting joint technique for the development of MgB2 magnets for magnetic resonance imaging (MRI).

This note presents a superconducting joint technique for the development of MgB2 magnetic resonance imaging (MRI) magnets. The MgB2 superconducting joint was fabricated by a powder processing method using Mg and B powders to establish a wire-bulk-wire connection. The joint resistance measured using a field-decay method was <10-14 Ω, demonstrating that the proposed joint technique could be employed for developing "next-generation" MgB2 MRI magnets operating in the persistent current mode.

ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells.

The ability of breast cancer cells to resist anoikis, apoptosis caused by detachment of the non-malignant epithelial cells from the extracellular matrix (ECM), is thought to be critical for breast tumor growth, invasion and metastasis. ErbB2, an oncoprotein that is often overproduced in breast tumors, can block breast cancer cell anoikis via mechanisms that are understood only in part. In an effort to understand them better we found that detachment of the non-malignant human breast epithelial cells from the ECM upregulates a protein Perp in these cells. Perp is a component of the desmosomes, multiprotein complexes involved in cell-to-cell adhesion. Perp can cause apoptosis via unknown mechanisms. We demonstrated that Perp upregulation by cell detachment is driven by detachment-induced loss of epidermal growth factor receptor (EGFR). We also found that Perp knockdown by RNA interference (RNAi) rescues detached cells from death which indicates that Perp contributes to their anoikis. We observed that ErbB2, when overexpressed in detached breast epithelial cells, causes Perp downregulation. Furthermore, ErbB2-directed RNAi or treatment with lapatinib, an ErbB2/EGFR small-molecule inhibitor used for breast cancer therapy, upregulated Perp in ErbB2-positive human breast and ovarian carcinoma cells. We established that ErbB2 downregulates Perp by activating an ErbB2 effector protein kinase Mek that blocks detachment-induced EGFR loss in a manner that requires the presence of a signaling protein Sprouty-2. Finally, we observed that restoration of the wild-type Perp levels in ErbB2-overproducing breast epithelial cells increases their anoikis susceptibility and blocks their clonogenicity in the absence of adhesion to the ECM. In summary, we have identified a novel mechanism of ErbB2-mediated mechanism of anoikis resistance of ErbB2-overproducing breast epithelial cells. This mechanism allows such cells to grow without adhesion to the ECM and is driven by ErbB2-induced activation of Mek, subsequent EGFR upregulation and further EGFR-dependent Perp loss.

Anoikis of colon carcinoma cells triggered by ß-catenin loss can be enhanced by tumor necrosis factor receptor 1 antagonists.

Detachment of non-malignant epithelial cells from the extracellular matrix causes their apoptosis, a phenomenon called anoikis. By contrast, carcinoma cells are anoikis-resistant, and this resistance is thought to be critical for tumor progression. Many oncogenes trigger not only anti- but also pr-apoptotic signals. The proapoptotic events represent an aspect of a phenomenon called oncogenic stress, which acts as a safeguard mechanism blocking tumor initiation. In cells that become malignant, oncogene-induced antiapoptotic signals outbalance the proapoptotic ones. It is now thought that treatments blocking the antiapoptotic events but preserving the proapoptotic signals can be particularly effective in killing tumor cells. Whether or not oncogenes induce any proanoikis signals that can be used for enhancing the efficiency of approaches aimed at triggering anoikis of cancer cells has never been explored. ß-Catenin is a major oncoprotein that is often activated in colorectal cancer and promotes tumor progression via mechanisms that are understood only in part. We found here that ß-catenin triggers both anti- and proanoikis signals in colon cancer cells. We observed that the antianoikis signals prevail and the cells become anoikis-resistant. We further established that one proanoikis signal in these cells is triggered by ß-catenin-induced downregulation of an apoptosis inhibitor tumor necrosis factor receptor 1 (TNFR1) and subsequent reduction of the activity of a transcription factor NF-κB (nuclear factor-κB), a mediator of TNFR1 signaling. We also found that the effect of ß-catenin on TNFR1 requires the presence of transcription factor TCF1, a ß-catenin effector. We demonstrated that ablation of ß-catenin in colon cancer cells triggers their anoikis and that this anoikis is enhanced even further if low TNFR1 or NF-κB activity is artificially preserved in the ß-catenin-deprived cells. Thus, inhibition of TNFR1 or NF-κB activity can be expected to enhance the efficiency of approaches aimed at blocking ß-catenin-driven anoikis resistance of colon carcinoma cells.

Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells.

Detachment of normal epithelial cells from the extracellular matrix triggers apoptosis, a phenomenon called anoikis. Conversely, carcinoma cells tend to be relatively more anoikis-resistant than their normal counterparts, and this increased resistance represents a critical feature of the malignant phenotype. Mechanisms that control susceptibility and resistance to anoikis are not fully understood. It is now known that detachment of non-malignant epithelial cells triggers both pro- and antiapoptotic signals, and it is the balance between these signals and the duration of detachment that determine further fate of the cells. Detachment-induced antiapoptotic events delay anoikis and if cells reattach relatively soon after detachment they survive. Direct regulators of apoptosis responsible for this delay of anoikis are unknown. We found that detachment of non-malignant intestinal epithelial cells triggers upregulation of inhibitors of apoptosis protein (IAP) family, such as X-chromosome-linked inhibitor of apoptosis protein and cellular inhibitor of apoptosis-2 (cIAP2). We demonstrated that this upregulation requires detachment-dependent activation of the transcription factor nuclear factor-kappaB. We further observed that various IAP antagonists accelerate anoikis, indicating that upregulation of the IAPs delays detachment-triggered apoptosis. We conclude that the IAPs are important regulators of the balance between detachment-triggered life and death signals. Perhaps, not by coincidence, these proteins are often upregulated in carcinomas, tumors composed of cells that tend to be anoikis-resistant.

Investigation of jewelry powders radiating far-infrared rays and the biological effects on human skin.

Far-infrared rays have certain kinds of effects on the human body, especially on skin, blood circulation, and skin cell vitalizing. Some jewelry powders radiate far-infrared rays. Jade has powerful far-infrared ray radiation, and tourmaline has pyroelectric and piezoelectric properties and radiated far-infrared rays. The jewelry powders (fine powdered jade and tourmaline powders) were screened by far-infrared rays for radiation properties and tested for the effects of far-infrared rays on the human skin by temperature observation using an infrared thermal analyzer.

Effects of Shikunshito-Kamiho on fecal enzymes and formation of aberrant crypt foci induced by 1,2-dimethylhydrazine.

Shikunshito-Kamiho (SKTK) is a traditional Chinese medicine composed of eight crude drugs (Ginseng Radix, Hoelen, Atractylodis Rhizoma, Glycyrrhizae Radix, Prunellae Spica, Ostreae Testa, Laminaria Thallus, Sargassum). We investigated the effects of SKTK on pH, ammonia, fecal enzymes such as beta-glucuronidase, tryptophanase, urease, and formation aberrant crypt foci in the colon carcinogenesis model induced by 1,2-dimethylhydrazine (DMH). Water extract of SKTK was administered orally for 5 weeks to DMH-treated mice as 0.5% and 1.5% of the diet. Beta-glucuronidase, pH and tryptophanase were significantly inhibited after treatment of 0.5% and 1.5% SKTK, while urease was significantly reduced only during and after treatment of 1.5% SKTK as compared with control data. However, the ammonia concentration wasn't different in SKTK treated groups from control group. The incidence number of aberrant crypts foci (ACF) and aberrant crypts/focus in colon was significantly decreased by 0.5% and 1.5% SKTK mixed diets compared with that in rats treated with DMH alone. These results suggest that SKTK exterts anticarcinogenic activity on experimental murine colorectal cancer.

Glibenclamide induces apoptosis through inhibition of cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels and intracellular Ca(2+) release in HepG2 human hepatoblastoma cells.

Glibenclamide, an inhibitor of cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels, induced apoptosis in a dose- and time-dependent manner in HepG2 human hepatoblastoma cells. Glibenclamide increased intracellular Ca(2+) concentration, which was significantly inhibited by Ca(2+) release blockers dantrolene and TMB-8. BAPTA/AM, an intracellular Ca(2+) chelator, and the Ca(2+) release blockers significantly inhibited glibenclamide-induced apoptosis. Glibanclamide also increased intracellular Cl(-) concentration, which was significantly blocked by CFTR Cl(-) channel activators levamisole and bromotetramisole. These activators also significantly inhibited both intracellular Ca(2+) release and apoptosis induced by glibenclamide. The expression of CFTR protein in the cells was confirmed by Western blot analysis. These results suggest that glibenclamide induced apoptosis through inhibition of CFTR Cl(-) channels and intracellular Ca(2+) release and that this protein may be a good target for treatment of human hepatomas.

MKP-1 induced in rat brain after electroconvulsive shock is independent of regulation of 42- and 44-kDa MAPK activity.

Electroconvulsive shock (ECS) activates MAPKs in rat brain and also induces immediate early genes. We investigated whether ECS induces MKP-1, a specific MAPK phosphatase and an immediate early gene, for feedback regulation of MAPK activity. ECS induced MKP-1 in the cortex, but MAPK activity returned to its basal level before MKP-1 protein increased, within 10 min of ECS. MKP-1 protein amount peaked 1 hr after ECS. MKP-1 induced did not lower the basal level of MAPK activity or attenuate MAPK activation by second ECS. MAPK activation in cerebellum was very weak, but the MKP-1 induction was faster and more prominent than in the cortex. These results suggest that ECS induces MKP-1 in various rat brain regions, however, the induction may not be related to the activation of MAPK and the MKP-1 induced may be independent of the regulation of MAPK activity after ECS.

Association of the major histocompatibility complex with avian leukosis virus infection in chickens.

1. Association of the B blood group, the major histocompatibility complex (MHC) in chickens, with avian leukosis virus (ALV) infection shown by shedding of group-specific (gs) antigen was studied in an Australorp line selected for short oviposition interval to improve egg production. Three haplotypes (B8a, B9a and B21) were segregating in this line at frequencies of 66.7, 15.6 and 17.8%, respectively, averaged over three generations. 2. The relative risk (odds ratio) of a hen becoming a gs-antigen shedder was calculated for progenies of the dams shedding gs-antigen and those of non-shedding dams separately and pooled over three generations. In the progenies of shedding dams, the relative risk was not significantly different from 1.0 for the three haplotypes. In contrast, in the progenies of non-shedding dams, the relative risk was 0.67, 0.48 and 2.53 for B8a, B9a and B21, respectively, with the last two ratios being significantly different from 1.0. 3. The average effect of haplotype substitution on probability of shedding was estimated from a linear logistic model. The estimates (relative to zero for B8a) for B9a and B21, respectively, were -0.26 and 0.03 among the progenies of shedding dams, and -0.16 and 0.87 among the progenies of non-shedding dams. The last estimate only was highly significant. 4. These results suggest that the three haplotypes were similar in susceptibility to congenital infection through hatching eggs, but differed in susceptibility to post-hatching infection from other infected birds.

Heterozygosity at protein loci in inbred and outbred lines of chickens.

Levels of heterozygosity at six polymorphic protein marker loci were determined by electrophoresis in 24 lines of poultry, encompassing 17 White Leghorn inbred lines (WLI) (with inbreeding coefficients, F, ranging from .946 to .988), five Australorp inbred lines (AusI) (with F values ranging from .924 to .961), and two randombred lines (one White Leghorn and one Australorp). Fixation was observed at one locus in WLI lines, and at two loci in the AusI lines. Segregation at the other loci was observed in the inbred lines of the two breeds. Observed heterozygosity in the inbred lines markedly exceeded the expectations under inbreeding theory. In White Leghorns, reproductive fitnesses for heterozygotes were superior to homozygotes in the inbred lines, but not in the control. Consequently, natural selection operating through associative overdominance appears to be responsible for the higher than expected heterozygosities in the inbred lines.

Genetic susceptibility of chicken macrophages to in vitro infection with infectious laryngotracheitis virus.

Chicken macrophages are susceptible to infection with infectious laryngotracheitis virus (ILTV), the level of infection being dependent, in part, on the genotype of the host cell. Following infection in vitro a greater proportion of macrophages from the ILTV-resistant J1(B113/113) and N1(B114/114) inbred lines of chickens were found to be positive for ILTV antigens, than macrophages from the ILTV-susceptible M1(B15/15) chickens. The proportion of ILTV-positive macrophages was found to be genetically regulated, in part by the chicken major histocompatibility complex (MHC), although alloantisera to class I and class II MHC antigens did not reduce the number of macrophages infected. Similarly, the phagocytic activity of the cultured macrophages from chickens of different MHC genotype did not correlate with their susceptibility to infection with ILTV.

Genetic resistance to infectious laryngotracheitis in inbred lines of White Leghorn chickens.

The susceptibility of inbred lines of chickens to graded levels of infection with a virulent isolate (wild-strain) of infectious laryngotracheitis virus (ILTV) was investigated. An association was found between the level of resistance to ILTV and the line of inbred chickens, with chickens from the J1 inbred line being more resistant to clinical ILTV than M1 and N1 inbred chickens. The N1 chickens, however, became susceptible with higher doses of ILTV, while J1 chickens remained relatively resistant to clinical disease. Studies using other inbred lines of chicken which had the same major histocompatibility complex (MHC) antigens showed similar levels of resistance or susceptibility, suggesting a possible association of the chicken MHC with resistance or susceptibility to ILTV.

Avian leukosis virus and selection on oviposition interval in Australorp lines.

1. Shedding of group-specific antigen of avian leukosis virus (ALV) into egg albumen was determined in three Australorp lines: AS line that had been selected primarily for short oviposition interval, ASS line that had been derived from the AS line and developed as a commercial dam line for egg laying, and AC line that had been kept as a randombred control. 2. The proportion of shedders was 13.1 to 16.7% in the AS line in 1984-88, 16.3% in the ASS line in 1984 (before culling of the shedders), and 6.1% and 6.6% in the AC line in 1984 and 1988, respectively. 3. In the AS line, shedders were 1.8% lower in rate of lay to 300 d of age, 1.3 g lower in average egg weight at 34 weeks of age, 5.6% lower in hatchability of fertile eggs and 0.24 h shorter in oviposition interval than non-shedders. In the ASS line (1984 only), the differences between shedders and non-shedders were in the same direction, but in magnitude greater for rate of lay and smaller for oviposition interval. 4. The shedders were favoured by the artificial selection because of their shorter oviposition interval and this appeared to be responsible for the higher levels of ALV shedding in the selection lines.

Reproductive fitness and artificial selection in animal breeding: culling on fitness prevents a decline in reproductive fitness in lines of Drosophila melanogaster selected for increased inebriation time.

The maintenance of reproductive fitness in lines subjected to artificial selection is one of the major problems in animal breeding. The decline in reproductive performance has neither been predictable from heritabilities and genetic correlations, nor have conventional selection indices been adequate to avoid the problem. Gowe (1983) has suggested that the heritabilities of reproductive traits are non-linear, with heritabilities being higher on the lower fitness side. Consequently, he has predicted that culling on reproductive fitness in artificial selection lines will be effective in preventing the usual declines in fitness. An experimental evaluation of Gowe's prediction has been carried out by comparing fitnesses of replicated lines of three treatments: selection for increased inebriation time without culling on fitness (HO), selection for inebriation time with culling of 20% (4/20) of selected females on reproductive fitness (HS), and unselected controls (C). Response to selection for inebriation time in the two selection treatments was similar. After 25 generations, the competitive index, a measure of reproductive fitness, was significantly lower in the HO treatment than the HS treatment, while the HS treatment did not differ from the control lines or the base population. These results demonstrate for the first time that culling on reproductive fitness in selection lines can be used to prevent the usual decline in reproductive performance.

Comparisons of time intervals and plasma LH concentrations during the ovulatory cycle of broiler breeder hens maintained under either a 24 h light:dark cycle or continuous light.

The possibility that egg production in broiler breeder hens may be increased by selection for reduced oviposition interval under continuous light was investigated by comparing the pattern of pre-ovulatory releases of plasma luteinising hormone (LH) and the associated ovipositions in the same broiler hens maintained under normal cycles (15.25 h light/d) or continuous light. The lighting conditions had no effect on plasma concentrations of LH before and at the pre-ovulatory LH peak in first, mid-sequence or terminal ovulatory cycles. Plasma LH concentrations were similar during first, mid-sequence and terminal ovulatory cycles. Mid-sequence oviposition intervals and the interval between a mid-sequence LH peak and its associated oviposition were longer under continuous light than under normal lighting. Pre-ovulatory releases of LH occurred during a restricted period of day in both lighting conditions. Under continuous lighting they were probably entrained by the daily pattern of restricted feeding. Any selection programme for reduced oviposition interval under continuous lighting in broiler breeder hens should take into account the entraining effects of the daily pattern of feeding.

Analyses of oviposition times and intervals in a wide range of layer flocks under normal and continuous lighting regimes.

Distributions of oviposition times and intra-clutch oviposition intervals in continuous light (CL) and normal light (NL) environments were studied in 39 populations of 27 different genotypes. The populations showed a range of mean intervals from 23.1 to 27.6 h in CL, arising from the history of selection directly on interval in some populations. The data were analysed to infer empirical relations of descriptive statistics of the distribution to each other and to rate of lay to 301 d of age (PRL). In NL, as the mean intra-clutch interval decreased, more intervals tended to accumulate against the barrier of 24 h imposed by the light-dark cycle and the variability of intervals declined rapidly. Similar, but less striking, relations were found in CL above a mean interval of about 24 h. Under CL, the mean intra-clutch interval (CIM) decreased beneath 24 h and the variability of intervals tended to show a steep increase. The rate of lay to 301 d of age increased linearly at a rate of 6.3% for each hour by which CIM decreased to about 24 h, but no further below that level. Oviposition time in NL was advanced with a decrease in CIM, apparently in two linear phases of differing slopes, perhaps reflecting different physiological bases of the change. The degree of entrainment in NL, measured by the proportion of eggs laid in the model 8 h, increased with reduction of CIM. The distribution of oviposition times in CL showed a great deal of variation among the populations and departed significantly (P less than 0.05) from the uniform rectangular distribution, in all but three populations. The proportion of eggs laid in the modal 8 h of the day, suggested as an indicator of sensitivity to uncontrolled timing cues in CL, was positively correlated with CIM. Free-running periods were estimated for individual pullets from sequences of oviposition times in CL. The mean period for a population declined linearly with CIM, but only when CIM had decreased below about 25.75 h, suggesting that the period of endogenous circadian rhythm might have been altered in some populations with low CIM's. The proportion of eggs laid in the modal 8 h of the free-running period, perhaps an indicator for regularity of the circadian rhythm, was negatively correlated with CIM.

Plasma concentrations of luteinising hormone during the ovulatory cycle in hens selected for reduced oviposition interval and maintained in continuous light or a 24 h light:dark cycle.

Plasma luteinising hormone (LH) concentrations were measured during the ovulatory cycle in lines of Australorps and White Leghorns selected for reduced oviposition interval and maintained under continuous light and noise. Selection significantly increased plasma LH concentrations in mid-sequence ovulatory cycles of Australorps but not in the White Leg-horns. Selection in the Australorps apparently increased the rate of ovarian follicular maturation, resulting in more frequent LH peaks. The effect of selection on plasma LH concentrations is a function of the lighting condition to which the hens are exposed.