It has been proposed that tissue-specific estrogenic and/or antiestrogenic actions of certain xenoestrogens may be associated
with alterations in the tertiary structure of estrogen receptor (ER) α ...and/or ERβ following ligand binding; changes which
are sensed by cellular factors (coactivators) required for normal gene expression. However, it is still unclear whether xenoestrogens
affect the normal behavior of ERα and/or ERβ subsequent to receptor binding. In view of the wide range of structural forms
now recognized to mimic the actions of the natural estrogens, we have assessed the ability of ERα and ERβ to recruit TIF2
and SRC-1a in the presence of 17β-estradiol, genistein, diethylstilbestrol, 4- tert -octylphenol, 2â²,3â²,4â²,5â²-tetrachlorobiphenyl-ol, and bisphenol A. We show that ligand-dependent differences exist in the
ability of ERα and ERβ to bind coactivator proteins in vitro , despite the similarity in binding affinity of the various ligands for both ER subtypes. The enhanced ability of ERβ (over
ERα) to recruit coactivators in the presence of xenoestrogens was consistent with a greater ability of ERβ to potentiate reporter
gene activity in transiently transfected HeLa cells expressing SRC-1e and TIF2. We conclude that ligand-dependent differences
in the ability of ERα and ERβ to recruit coactivator proteins may contribute to the complex tissue-dependent agonistic/antagonistic
responses observed with certain xenoestrogens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rainbow trout Oncorhynchus mykiss fry were reared at four densities ranging from 10,800 to 43,926 fish/m3 (9.91 to 37.60 kg/m3) during an initial feeding period of 35 d. Each of the four initial ...density treatments were then split into high (3,780 fish/m3) and low (1,890 fish/m3) density groups and reared in outdoor raceways for an additional 74 d. A necropsy‐based general health and condition assessment indicated that hematocrit, plasma protein, and the thymus index were significantly elevated in the outdoor high density group. Changes in these variables were unrelated to the initial rearing density, except for plasma protein which decreased as the initial density increased at low densities. Other necropsy variables indicated normal, healthy fish. Agonistic behavior was assessed at 4, 9 and 13 wk of age by observing the number of aggressive chases in paired and group (five fish) trials. The number of chases generally increased with age, although the difference between 9 and 13 wk was variable. Feeding did not elicit more chases in this study except for 9‐wk‐old fry. Initial rearing density did not have any impact on the number of chases at 4 or 13 wk, but at 9 wk the number of chases increased with initial density for the group tests. Relative fin length measurements of all fins except the adipose indicated no combination of initial density and outdoor density was superior to another for reducing fin erosion. This study indicated that rainbow trout fry may be reared at initial densities approaching 44,000 fish/m3 (Piper density index of 1.1) without negatively affecting growth and fin condition or inducing higher levels of agonistic behavior later on.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This paper highlights how the School of Occupational Therapy and Physiotherapy at the University of East Anglia (UEA) has identified reflection as a major component of professional development within ...the undergraduate curriculum. It describes the evolution, development and implementation of a portfolio-based, reflective method of assessment. Discussion of this experience from both staff and student perspectives identifies several interesting issues. Consideration of this process points to a professional development of both members of faculty and students.
In the varied topography of professional practice, there is a high, hard, ground where practitioners can make effective use of research based theory and techniques, and there is a swampy lowland where situations are confusing 'messes' incapable of technical solution. (Schon, 1991, p. 42)
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We used the highly selective 5-HT
6 receptor radioligand
125ISB-258585 (4-iodo-
N-4-methoxy-3-(4-methylpiperazin-1-yl)phenylbenzene-sulfonamide) to perform autoradiographic binding studies on the ...rat brain. High levels of specific binding occurred in the corpus striatum, nucleus accumbens, Islands of Calleja and the olfactory tubercle. A high level of binding also appeared in the choroid plexus. Moderate levels occurred in several regions of the hippocampal formation and in certain regions of the cerebral cortex, thalamus, hypothalamus, and substantia nigra; and very low levels in the globus pallidus, cerebellum, other mesencephalic regions, and the rhombencephalon. Displacement of total binding with 10 μM unlabelled SB-214111 (4-bromo-
N-4-methoxy-3-(4-methylpiperazin-1-yl)phenylbenzene-sulfonamide), another selective 5-HT
6 receptor antagonist, or 10 μM unlabelled methiothepin, reduced binding to barely discernible levels. Some animals received unilateral injections of 6-hydroxydopamine (6-OHDA) into the median forebrain bundle to lesion the nigro-striatal pathway before autoradiographic examination. Effectiveness of the 6-OHDA lesions in the substantia nigra and striatum was confirmed with tyrosine hydroxylase immunohistochemistry. Such lesions resulted in no significant changes in
125ISB-SB258585 binding in any brain region examined, suggesting that 5-HT
6 receptors in the striatum are not located on dendritic, somatic or terminal elements of dopaminergic neurones. Thus, the striatal binding sites seen in this study may be on intrinsic GABAergic or cholinergic neurones, or on terminals of projection neurones from the thalamus or cerebral cortex. The 5-HT
6 receptor ligand binding seen here in the striatum, accumbens, olfactory tubercle, Islands of Calleja, cerebral cortex and hippocampus are in concordance with previous immunohistochemical studies, and suggest a possible involvement of 5-HT
6 receptors in locomotor control, cognition, memory, and control of affect. The high levels of binding observed in the choroid plexus in this study have not been reported before. This finding suggests that 5-HT
6 receptors could play a role in the control of cerebrospinal fluid dynamics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
495.
Drug acetylation in breast cancer WEBSTER, D. J. T; FLOOK, D; JENKINS, J ...
British journal of cancer,
08/1989, Volume:
60, Issue:
2
Journal Article
Peer reviewed
Open access
The acetylator phenotype was determined in 100 patients with breast cancer and 100 control female subjects using isoniazid. The proportion of fast acetylators in the breast cancer patients (43%) was ...not significantly different from the control group (43%). We conclude that acetylator phenotype is unlikely to be an important determinant of the risk of developing breast cancer.
We simulate the flux emitted from galaxy halos in order to quantify the brightness of the circumgalactic medium (CGM). We use dedicated zoom-in cosmological simulations with the hydrodynamical ...Adaptive Mesh Refinement code RAMSES, which are evolved down to z=0 and reach a maximum spatial resolution of 380 \(h^{-1}\)pc and a gas mass resolution up to 1.8\(\times 10^{5} h^{-1} \rm{M}_{\odot}\) in the densest regions. We compute the expected emission from the gas in the CGM using CLOUDY emissivity models for different lines (e.g. Ly\(\alpha\), CIV, OVI, CVI, OVIII) considering UV background fluorescence, gravitational cooling and continuum emission. In the case of Ly\(\alpha\) we additionally consider the scattering of continuum photons. We compare our predictions to current observations and find them to be in good agreement at any redshift after adjusting the Ly\(\alpha\) escape fraction. We combine our mock observations with instrument models for FIREBall-2 (UV balloon spectrograph) and HARMONI (visible and NIR IFU on the ELT) to predict CGM observations with either instrument and optimise target selections and observing strategies. Our results show that Ly\(\alpha\) emission from the CGM at a redshift of 0.7 will be observable with FIREBall-2 for bright galaxies (NUV\(\sim\)18 mag), while metal lines like OVI and CIV will remain challenging to detect. HARMONI is found to be well suited to study the CGM at different redshifts with various tracers.
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