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.

Concept of Crossover point and its application on Threshold Voltage definition for Undoped-Body Transistors

As the conventional MOSFETs scaling is approaching the limit imposed by short channel effects, Double Gate (DG) MOS transistors are appearing as the most feasible andidate in terms of technology in sub-45nm technology nodes. As the short channel effect in DG transistor is controlled by the device geometry, undoped or lightly doped body, is used to sustain the channel. There exits a disparity in threshold voltage calculation criteria of undoped-body symmetric double gate transistors which uses two definitions, one is potential based and the another is charge based definition. In this paper, a novel concept of "crossover point" is introduced, which proves that the charge-based definition is more accurate than the potential based definition. The change in threshold voltage with body thickness variation for a fixed channel length is anomalous as predicted by, potential based definition while it is monotonous for change based definition. The threshold voltage is then extracted from drain currant versus gate voltage characteristics using linear extrapolation and "Third Derivative of Drain-Source Current" method or simply "TD" method. The trend of threshold voltage variation is found some in both the cases which support charge-based definition.

Long Wavelength Peristaltic Transport of Non-Newton Fluids

Solutions are obtained for the stream function and the pressure field for the flow of non-Newtonian fluids in a tube by long peristaltic waves of arbitrary shape. The axial velocity profiles and stress distributions on the wall are discussed for particular waves of some practical interest. The effect of non- Newtonian character of the fluid is examined.

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.

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.

Evaluation of growth and changes in body composition following neonatal diagnosis of cystic fibrosis

Early deficits in nutritional status that might require specific treatment and early response to nutritional therapy were studied longitudinally in 25 infants with cystic fibrosis (CF) diagnosed by neonatal screening, using anthropometric and research body composition methodology, and evaluation of pancreatic function. At the time of confirmed diagnosis (mean 5.4 weeks), body mass, length, total body fat (TBF), and total body potassium (TBK) were all significantly reduced. Following diagnosis and commencement of therapy there was a normalization of weight, length, and TBK by 6-12 months of age, indicating catch-up growth. But in some individuals the response was incomplete, and as a group, mean total body fat remained significantly lower than normal at 1 year of age. Seven of 25 (28%) were pancreatic sufficient at diagnosis, and all but one had evidence of declining pancreatic function requiring the institution of pancreatic enzyme therapy during the next 1-9 months. The median age of commencement of enzyme therapy was 10 weeks (range 5 weeks to 11 months). These longitudinal assessments emphasize the dynamic changes occurring in absorptive function, body composition, and nutritional status following neonatal diagnosis of cystic fibrosis and may reflect previously described abnormalities of energy metabolism in this age group. Abnormal body composition is evident in most CF infants following diagnosis by neonatal screening but pancreatic damage may still be evolving. We suggest that early active nutritional therapy and surveillance for changes in pancreatic function are warranted in CF infants diagnosed by neonatal screening.

Body composition studies in cystic fibrosis and myelomeningocele

One of the major considerations of improving the management of many chronic diseases has been the realisation of the importance of nutrition, and, in children, the maintenance of normal growth. Cystic Fibrosis (CF) and Myelomeningocele (MMC) are two such disease states in which nutritional status has a significant effect on morbidity.

Justifying threshold voltage definition for undoped body transistors through ``crossover point'' concept

Two different definitions, one is potential based and the other is charge based, are used in the literatures to define the threshold voltage of undoped body symmetric double gate transistors. This paper, by introducing a novel concept of crossover point, proves that the charge based definition is more accurate than the potential based definition. It is shown that for a given channel length the potential based definition predicts anomalous change in threshold voltage with body thickness variation while the charge based definition results in monotonous change. The threshold voltage is then extracted from drain current versus gate voltage characteristics using linear extrapolation, transconductance and match-point methods. In all the three cases it is found that trend of threshold voltage variation support the charge based definition.

Total body potassium in cystic fibrosis

To further evaluate the nature of malnutrition, define at-risk groups, and confirm the efficacy of nutritional supplementation on body composition in cystic fibrosis (CF), we have conducted longitudinal and cross-sectional studies of total body potassium (TBK) in 161 unselected CF subjects aged 1 month to 17 years. TBK was determined by measurement of40K in a whole body counter, reflecting body cell mass (BCM), the vital work-performing and growing cellular component of the body. Compared with normal TBK data for age and sex from pooled measurements of 1,629 healthy children aged 1 week to 17 years, CF infants (n = 12) diagnosed by newborn screening were depleted in TBK at diagnosis and showed catch-up with therapy by 1 year; CF children aged 2-17 years (n = 140) showed a tendency for inadequate accretion of TBK (and thus BCM) with increasing age, although the normal correlation between TBK and weight and height was maintained in the majority suggesting a pattern of nutritional stunting of growth; and malnourished CF children (n = 9) showed significant catchup in TBK with long-term nutritional rehabilitation (85-98% of TBK predicted for weight and height). These studies suggest that potentially serious, but possibly correctable deficits, in the growth of the body cell mass as measured by TBK occur commonly in CF. These deficits may be established very early in life and if not corrected lead to progressive nutritional growth retardation with increasing age. © 1989 Raven Press, Ltd., New York.

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.

Luce Irigaray's Philosophy of Feminine Being : Body, Desire and Wisdom

Luce Irigaray is a Belgian-born philosopher, psychoanalyst and linguist. Irigaray s concept of woman is crucial for understanding her own work but also for examining and developing the theoretical and methodological basis of feminist theory. This thesis argues that, ultimately, Irigaray s exploration of woman s being challenges our traditional notion of philosophy as a neutral discourse and the traditional notion of ourselves as philosophizing persons or human beings. However, despite its crucial role, Irigaray s idea of woman still lacks a comprehensive explication. This is because the discourse of sexual difference is blurred by the ideas of essentialism and biologism. --- Irigaray s concept of woman has been interpreted and criticized from the perspectives of metaphysical essentialism, strategic essentialism, realist essentialism and deconstructionism. This thesis argues that a reinterpretation is necessary to account for Irigaray s claims about the the traditional woman , mimesis, the specificity of the feminine body, feminine expression and sexual difference. Moreover, any reading should account for the differences between women and avoid giving a prescriptive function to the essence of woman. --- My thesis develops a new interpretation of Irigaray s concept of woman on the basis of the phenomenology of the body. It argues that Irigaray s discourse on woman can and must be understood by an idea of existential style. Existential style is embodied, affective and spiritual and it is constituted in relation to oneself, to others and to the world. It is temporal, it evolves and changes but preserves its open unity in its transformations. Stylistic unities, such as femininity or philosophy, are constituted in and by the singulars. -- This study discusses and analyses feminine existential style as a central theme and topic of Irigaray s works and shows how her work operates as a primary and paradigmatic example of the feminine style. These tasks are performed by studying the mimetic positions available for women and by explicating the phenomenological background of Irigaray s conceptions of the philosophical method, and the lived, expressive and affective body. The critical occupation and transformation of these mimetic positions, the inquiry into the first-person pre-discursive experience, and the cultivation of feminine expressivity open up the possibility of becoming a woman writer, a woman lover and a woman philosopher. The appearance of these new feminine figures is a precondition for the realization of sexual difference. So Irigaray opens up the possibility of sexual difference by instituting and constituting a feminine subject of love and wisdom, and by problematizing the idea of a neutral and absolute subject.