The corporate regulation of sexual harassment in Japan

Book Title in Japanese: 雇用・社会保障とジェンダー Chapter Title in Japanese: セクシャル・ハラスメント規制の企業化と男女平等政策への示唆

Influence of lanthanum doping on the dielectric, ferroelectric and relaxor behaviour of barium bismuth titanate ceramics

Barium lanthanum bismuth titanate (Ba1−(3/2)xLaxBi4Ti4O15, x = 0–0.4) ceramics were fabricated using the powders synthesized via the solid-state reaction route. X-ray powder diffraction analysis confirmed the above compositions to be monophasic and belonged to the m = 4 member of the Aurivillius family of oxides. The effect of the partial presence of La3+ on Ba2+ sites on the microstructure, dielectric and relaxor behaviour of BaBi4Ti4O15 (BBT) ceramics was investigated. For the compositions pertaining to x ≤ 0.1, the dielectric constant at both room temperature and in the vicinity of the temperature of the dielectric maximum (Tm) of the parent phase (BBT) increased significantly with an increase in x while Tm remained almost constant. Tm shifted towards lower temperatures accompanied by a decrease in the magnitude of the dielectric maximum (εm) with an increase in the lanthanum content (0.1 < x ≤ 0.4). The dielectric relaxation was modelled using the Vogel–Fulcher relation and a decrease in the activation energy for frequency dispersion with increasing x was observed. The frequency dispersion of Tm was found to decrease with an increase in lanthanum doping, and for compositions corresponding to x ≥ 0.3, Tm was frequency independent. Well-developed P(polarization)–E(electric field) hysteresis loops were observed at 150 °C for all the samples and the remanent polarization (2Pr) was improved from 6.3 µC cm−2 for pure BBT to 13.4 µC cm−2 for Ba0.7La0.2Bi4Ti4O15 ceramics. Dc conductivities and associated activation energies were evaluated using impedance spectroscopy.

Structural basis for the function of anti-idiotypic antibody in immune memory

We had earlier proposed a hypothesis to explain the mechanism of perpetuation of immunological memory based on the operation of idiotypic network in the complete absence of antigen. Experimental evidences were provided for memory maintenance through anti-idiotypic antibody (Ab2) carrying the internal image of the antigen. In the present work, we describe a structural basis for such memory perpetuation by molecular modeling and structural analysis studies. A three-dimensional model of Ab2 was generated and the structure of the antigenic site on the hemagglutinin protein H of Rinderpest virus was modeled using the structural template of hemagglutinin protein of Measles virus. Our results show that a large portion of heavy chain containing the CDR regions of Ab2 resembles the domain of the hemagglutinin housing the epitope regions. The similarity demonstrates that an internal image of the H antigen is formed in Ab2, which provides a structural basis for functional mimicry demonstrated earlier. This work brings out the importance of the structural similarity between a domain of hemagglutinin protein to that of its corresponding Ab2. It provides evidence that Ab2 is indeed capable of functioning as surrogate antigen and provides support to earlier proposed relay hypothesis which has provided a mechanism for the maintenance of immunological memory.

Influence of cobalt doping on superconducting transition in as-grown YBCO single crystals

The role of a charge buffer layer in the superconductivity of high-T-c materials is best studied by cationic substitutions. In this work, the chain copper in YBCO single crystals is substituted by Co3+ ion and consequent effect on superconducting transition temperature (T-c) studied. The T-c is measured using non-resonant Microwave Absorption technique, which is a highly sensitive and contactless method. It is seen that T-c of as-grown crystals is considerably enhanced by cobalt doping in low concentration regime. In contrast, higher T-c is achieved in undoped crystals only after extended oxygen anneal. When dopant concentration increases beyond an optimal value, T-c decreases and the system does not show superconductivity when cobalt content is high (x > 0.5 in YBa2Cu3-xCOxO7+/-delta). This behaviour consequent to cobalt substitution is discussed with reference to the apical oxygen model. Optimal cobalt doping can be thought of as an alternative to extended oxygen anneal in as-grown crystals of YBCO.

Oestrogenic regulation and differential expression of WNT4 in the bonnet monkey and rodent epididymis

A role for oestrogen in regulating fluid reabsorption in the monkey epididymis was recently demonstrated. Here, these Studies are extended to identify potential oestrogen-regulated proteins in the cauda region of monkey epididymis treated with vehicle and oestrogen receptor antagonist (ICI 182780). Two-dimensional electrophoretic analysis was used to identify the proteins. The results indicated down-regulation of WNT4 in the ICI-182780-treated monkey cauda. In addition. the Wnt4f mRNA concentration was also reduced in the caput regions of ICI-182780-treated rats and oestrogen receptor knockout mice. WNT4 is a key regulator of gonadal differentiation in humans and mice and plays a pivotal role in early mouse embryogenesis. The results of the present Study establish the presence of WNT4 in the monkey epididymis and its regulation by oestrogen, and Suggest a role for WNT4 in maintaining epididymal homeostasis.

Unusual effect of tellurium doping on the electrical-properties of bulk amorphous selenium

Abstract is not available.

The Effects of Nicotine on the Regulation of Neuronal Alpha7 Nicotinic Acetylcholine Receptors and Intracellular Signalling Pathways

Nicotine, the addictive compound of tobacco products, exerts its effects in the brain by binding to neuronal acetylcholine nicotinic receptors (nAChRs). The aim of the present study was to increase the knowledge of nicotine s complex effects, the focus being on homomeric alpha7-nAChRs that are widely expressed in the brain. Nicotinic regulation of differential signalling molecules including transcriptional regulators was also studied. We found that the number of alpha7-nAChRs is increased in specific brain regions in mice, in a time-dependent manner after chronic oral nicotine administration. Our results suggest that in addition to alpha4beta2-nAChRs, the other major nAChR subtype expressed in the brain, the number of alpha7-nAChRs is affected by chronic presence of nicotine. We suggest that when studying the long-term effects of nicotine, the duration on administration is of great importance. Next, we observed that nicotine exposure induces accumulation of cAMP in cell cultures expressing nAChRs. Furthermore, nicotine-induced alpha7-nAChR upregulation was potentiated by treatments enhancing cAMP-signalling, suggesting a role for cAMP in the upregulation process. Protein kinase C (PKC) was found essential for the basal regulation of alpha7-nAChR number. The nicotine-evoked alpha7-nAChR upregulation could be further increased by PKC overexpression. Thirdly, the effects of nicotine on dopamine and cAMP regulated phosphoprotein (DARPP-32) were characterised in rat brain. The results show that DARPP-32 is regulated by both acute and long-term nicotine treatment in the striatal subdivisions. The effect of acute nicotine is dose-dependent and the three striatal regions display differential sensitivities to nicotine. Chronic nicotine is also able to regulate DARPP-32 signalling with prominent effect seen in the nucleus accumbens (NAc), suggesting a role for DARPP-32 in the mediation of long-term effects of nicotine. Finally, the regulation of transcription factors Elk-1 and FosB/deltaFosB by nicotine was investigated. We found that Elk-1 is activated by acute nicotine selectively in the NAc core and hippocampal area CA1, whereas acute nicotine does not affect FosB/deltaFosB. Long-term intermittent or continuous nicotine increases the level of total Elk-1 in the same brain regions as acute nicotine. FosB/deltaFosB is also affected by chronic nicotine. Thus, similarly to other drugs of abuse, nicotine regulates transcriptional regulators Elk-1 and FosB/deltaFosB. These results bring further support for a common mechanism underlying the development of addiction. Nicotine s positive effects on learning and memory might involve the transcription factor Elk-1 based on the changes seen in the hippocampus, the key area in cognitive functions.

Structural basis for the function of anti-idiotypic antibody in immune memory

We had earlier proposed a hypothesis to explain the mechanism of perpetuation of immunological memory based on the operation of idiotypic network in the complete absence of antigen. Experimental evidences were provided for memory maintenance through anti-idiotypic antibody (Ab(2)) carrying the internal image of the antigen. In the present work, we describe a structural basis for such memory perpetuation by molecular modeling and structural analysis studies. A three-dimensional model of Ab(2) was generated and the structure of the antigenic site on the hemagglutinin protein H of Rinderpest virus was modeled using the structural template of hemagglutinin protein of Measles virus. Our results show that a large portion of heavy chain containing the CDR regions of Ab(2) resembles the domain of the hemagglutinin housing the epitope regions. The similarity demonstrates that an internal image of the H antigen is formed in Ab(2), which provides a structural basis for functional mimicry demonstrated earlier. This work brings out the importance of the structural similarity between a domain of hemagglutinin protein to that of its corresponding Ab(2). It provides evidence that Ab(2) is indeed capable of functioning as surrogate antigen and provides support to earlier proposed relay hypothesis which has provided a mechanism for the maintenance of immunological memory.

A genetic variant of MDM4 influences regulation by multiple microRNAs in prostate cancer

The oncogene MDM4, also known as MDMX or HDMX, contributes to cancer susceptibility and progression through its capacity to negatively regulate a range of genes with tumour-suppressive functions. As part of a recent genome-wide association study it was determined that the A-allele of the rs4245739 SNP (A>C), located in the 3'-UTR of MDM4, is associated with an increased risk of prostate cancer. Computational predictions revealed that the rs4245739 SNP is located within a predicted binding site for three microRNAs (miRNAs): miR-191-5p, miR-887 and miR-3669. Herein, we show using reporter gene assays and endogenous MDM4 expression analyses that miR-191-5p and miR-887 have a specific affinity for the rs4245739 SNP C-allele in prostate cancer. These miRNAs do not affect MDM4 mRNA levels, rather they inhibit its translation in C-allele-containing PC3 cells but not in LNCaP cells homozygous for the A-allele. By analysing gene expression datasets from patient cohorts, we found that MDM4 is associated with metastasis and prostate cancer progression and that targeting this gene with miR-191-5p or miR-887 decreases in PC3 cell viability. This study is the first, to our knowledge, to demonstrate regulation of the MDM4 rs4245739 SNP C-allele by two miRNAs in prostate cancer, and thereby to identify a mechanism by which the MDM4 rs4245739 SNP A-allele may be associated with an increased risk for prostate cancer.

Transcriptional regulation of a pineapple polyphenol oxidase gene and its relationship to blackheart.

Two genes encoding polyphenol oxidase (PPO) were isolated from pineapple (Ananas comosus[L.] Merr. cv. Smooth Cayenne). Sequence analyses showed that both contained a single intron and encoded typical chloroplast-localized PPO proteins, the sequences of which corresponded to two pineapple PPO cDNAs, PINPPO1 and PINPPO2, recently described by Stewart et al. (2001). Southern blot analyses suggested that pineapple contained only two PPO genes. Analysis of expression of PINPPO1 promoter GUS fusion constructs showed this promoter had a low basal activity and was cold- and wound-inducible, consistent with known mRNA expression profiles. Striking homologies to gibberellin response complexes (GARC) were observed in sequences of both the PINPPO1 and PINPPO2 promoters. Transient assays in mature pineapple fruit and stable expression in transgenic tobacco showed that PINPPO1 promoter-GUS fusions were indeed gibberellin (GA) responsive. A role for the element within the putative GARCs in mediating GA-responsiveness of the PINPPO1 promoter was confirmed by mutational analysis. PINPPO2 was also shown to be GA-responsive by RT-PCR analysis. Mutant PINPPO1 promoter-GUS fusion constructs, which were no longer GA-inducible, showed a delayed response to cold induction in pineapple fruit in transient assays, suggesting a role for GA in blackheart development. This was supported by observations that exogenous GA3 treatment induced blackheart in the absence of chilling. Sequences showing homology to GARCs are also present in some PPO promoters in tomato, suggesting that GA regulates PPO expression in diverse species.

Regulation of Gonadotropin-Releasing Hormone (GnRH)-Receptor Gene Expression in Tilapia: Effect of GnRH and Dopamine

The present work was designed to study certain aspects of the endocrine regulation of gonadotropin-releasing hormone receptor (GnRH-R) in the pituitary of the teleost fish tilapia. A GnRH-R was cloned from the pituitary of hybrid tilapia (taGnRH-R) and was identified as a typical seven-transmembrane receptor. Northern blot analysis revealed a single GnRH-R transcript in the pituitary of approximately 2.3 kilobases. The taGnRH-R mRNA levels were significantly higher in females than in males. Injection of the salmon GnRH analog (sGnRHa; 5–50 μg/kg) increased the steady-state levels of taGnRH-R mRNA, with the highest response recorded at 25 μg/kg and at 36 h. At the higher dose of sGnRHa (50 μg/kg), taGnRH-R transcript appeared to be down-regulated. Exposure of tilapia pituitary cells in culture to graded doses (0.1–100 nM) of seabream (sbGnRH = GnRH I), chicken II (cGnRH II), or salmon GnRH (sGnRH = GnRH III) resulted in a significant increase in taGnRH-R mRNA levels. The highest levels of both LH release and taGnRH-R mRNA levels were recorded after exposure to cGnRH II and the lowest after exposure to sbGnRH. The dopamine-agonist quinpirole suppressed LH release and mRNA levels of taGnRH-R, indicating an inhibitory effect on GnRH-R synthesis. Collectively, these data provide evidence that GnRH in tilapia can up- regulate, whereas dopamine down-regulates, taGnRH-R mRNA levels.

Timing the Emergence of Resistance to Anti-HIV Drugs with Large Genetic Barriers

New antiretroviral drugs that offer large genetic barriers to resistance, such as the recently approved inhibitors of HIV-1 protease, tipranavir and darunavir, present promising weapons to avert the failure of current therapies for HIV infection. Optimal treatment strategies with the new drugs, however, are yet to be established. A key limitation is the poor understanding of the process by which HIV surmounts large genetic barriers to resistance. Extant models of HIV dynamics are predicated on the predominance of deterministic forces underlying the emergence of resistant genomes. In contrast, stochastic forces may dominate, especially when the genetic barrier is large, and delay the emergence of resistant genomes. We develop a mathematical model of HIV dynamics under the influence of an antiretroviral drug to predict the waiting time for the emergence of genomes that carry the requisite mutations to overcome the genetic barrier of the drug. We apply our model to describe the development of resistance to tipranavir in in vitro serial passage experiments. Model predictions of the times of emergence of different mutant genomes with increasing resistance to tipranavir are in quantitative agreement with experiments, indicating that our model captures the dynamics of the development of resistance to antiretroviral drugs accurately. Further, model predictions provide insights into the influence of underlying evolutionary processes such as recombination on the development of resistance, and suggest guidelines for drug design: drugs that offer large genetic barriers to resistance with resistance sites tightly localized on the viral genome and exhibiting positive epistatic interactions maximally inhibit the emergence of resistant genomes.

Glucosinolate composition and anti-cancer potential of daikon and radish sprouts

Daikon and radish sprouts contain high levels of glucoraphenin, a glucosinolate which hydrolyses to form sulphoraphene. Sulphoraphene, like sulphoraphane from broccoli, is a potent inducer of phase 2 detoxification enzymes and consequently has potential anti-cancer action. Unlike broccoli however, daikon and radish do not possess epithiospecifier protein, a protein that inhibits conversion of glucosinolates to isothiocyanates, and consequently they may represent more suitable sources of phyto-chemicals with anti-cancer potential. Concentrations of glucoraphenin were highest in the seed, declining exponentially with sprout development. The rate of decline was observed to vary considerably between varieties of daikon and radish, with some varieties maintaining significantly high levels of glucoraphenin. Varieties maintaining a high level of glucoraphenin included 'Cherry Belle' and 'French Breakfast'.