bluuebunny/crossref_metadata_2025 huggingface dataset:
Membrane targeting of cGMP-dependent protein kinase is required for cystic fibrosis transmembrane conductance regulator Cl
−
channel activation
Authors: Vaandrager Arie. B. , Smolenski Albert , Tilly Ben C. , Houtsmuller Adriaan B. , Ehlert Ehrich M. E. , Bot Alice G. M. , Edixhoven Marcel , Boomaars Wendy E. M. , Lohmann Suzanne M. , de Jonge Hugo R.
Published: July 2002

A recently cloned isoform of cGMP-dependent protein kinase (cGK), designated type II, was implicated as the mediator of cGMP-provoked intestinal Cl
−
secretion based on its localization in the apical membrane of enterocytes and on its capacity to activate cystic fibrosis transmembrane conductance regulator (CFTR) Cl
−
channels. In contrast, the soluble type I cGK was unable to activate CFTR in intact cells, although both cGK I and cGK II could phosphorylate CFTR
in vitro
. To investigate the molecular basis for the cGK II isotype specificity of CFTR channel gating, we expressed cGK II or cGK I mutants possessing different membrane binding properties by using adenoviral vectors in a CFTR-transfected intestinal cell line, and we examined the ability of cGMP to phosphorylate and activate the Cl
−
channel. Mutation of the cGK II N-terminal myristoylation site (Gly
2
→ Ala) reduced cGK II membrane binding and severely impaired cGK II activation of CFTR. Conversely, a chimeric protein, in which the N-terminal membrane-anchoring domain of cGK II was fused to the N terminus of cGK Iβ, acquired the ability to associate with the membrane and activate the CFTR Cl
−
channel. The potency order of cGK constructs for activation of CFTR (cGK II > membrane-bound cGK I chimer ≫ nonmyristoylated cGK II > cGK Iβ) correlated with the extent of
32
P incorporation into CFTR observed in parallel measurements. These results strongly support the concept that membrane targeting of cGK is a major determinant of CFTR Cl
−
channel activation in intact cells.
Immune regulation by the ST6Gal sialyltransferase
Authors: Hennet Thierry , Chui Daniel , Paulson James C. , Marth Jamey D.
Published: July 2002

The ST6Gal sialyltransferase controls production of the Siaα2-6Galβ1-4GlcNAc (Sia6LacNAc) trisaccharide, which is the ligand for the lectin CD22. Binding of CD22 to Sia6LacNAc is implicated in regulating lymphocyte adhesion and activation. We have investigated mice that lack ST6Gal and report that they are viable, yet exhibit hallmarks of severe immunosuppression unlike CD22-deficient mice. Notably, Sia6LacNAc-deficient mice display reduced serum IgM levels, impaired B cell proliferation in response to IgM and CD40 crosslinking, and attenuated antibody production to T-independent and T-dependent antigens. Deficiency of ST6Gal was further found to alter phosphotyrosine accumulation during signal transduction from the B lymphocyte antigen receptor. These studies reveal that the ST6Gal sialyltransferase and corresponding production of the Sia6LacNAc oligosaccharide are essential in promoting B lymphocyte activation and immune function.
Mechanisms of color constancy under nearly natural viewing
Authors: Kraft J. M. , Brainard D. H.
Published: July 2002

Color constancy is our ability to perceive constant surface colors despite changes in illumination. Although color constancy has been studied extensively, its mechanisms are still largely unknown. Three classic hypotheses are that constancy is mediated by local adaptation, by adaptation to the spatial mean of the image, or by adaptation to the most intense image region. We measure color constancy under nearly natural viewing conditions, by using a design that allows us to test these three hypotheses directly. By suitable stimulus manipulation, we are able to titrate the degree of constancy between 11% and 83%, indicating that we have achieved good laboratory control. Our results rule out all three classic hypotheses and thus suggest that there is more to constancy than can be easily explained by the action of simple visual mechanisms.
Transgenic plants for tropical regions: Some considerations about their development and their transfer to the small farmer
Authors: Herrera-Estrella Luis
Published: July 2002

Biotechnological applications, especially transgenic plants,
probably hold the most promise in augmenting agricultural production in
the first decades of the next millennium. However, the application of
these technologies to the agriculture of tropical regions where the
largest areas of low productivity are located, and where they are most
needed, remains a major challenge. In this paper, some of the important
issues that need to be considered to ensure that plant biotechnology is
effectively transferred to the developing world are discussed.
Expression pattern of the mouse ortholog of the Pendred’s syndrome gene (
Pds
) suggests a key role for pendrin in the inner ear
Authors: Everett Lorraine A. , Morsli Hakim , Wu Doris K. , Green Eric D.
Published: July 2002

Pendred’s syndrome is an autosomal-recessive disorder characterized by deafness and goiter. After our recent identification of the human gene mutated in Pendred’s syndrome (
PDS
), we sought to investigate in greater detail the expression of the gene and the function of its encoded protein (pendrin). Toward that end, we isolated the corresponding mouse ortholog (
Pds
) and performed RNA
in situ
hybridization on mouse inner ears (from 8 days postcoitum to postnatal day 5) to establish the expression pattern of
Pds
in the developing auditory and vestibular systems.
Pds
expression was detected throughout the endolymphatic duct and sac, in distinct areas of the utricle and saccule, and in the external sulcus region within the cochlea. This highly discrete expression pattern is unlike that of any other known gene and involves several regions thought to be important for endolymphatic fluid resorption in the inner ear, consistent with the putative functioning of pendrin as an anion transporter. These studies provide key first steps toward defining the precise role of pendrin in inner ear development and elucidating the pathogenic mechanism for the deafness seen in Pendred’s syndrome.
Androgens regulate bone resorption activity of isolated osteoclastsin vitro
Authors: Pederson Larry , Kremer Matthew , Judd Jeffrey , Pascoe David , Spelsberg Thomas C. , Riggs B. Lawrence , Oursler Merry Jo
Published: July 2002

For many years it has been recognized that sex steroids have profound effects on bone metabolism. The current perception is that estrogen decreases bone resorption and androgen increases bone deposition. To investigate the potential for androgens to directly modulate bone resorption, we have examined avian osteoclast and human and mouse osteoclast-like cells for androgen responsiveness. There was a dose-dependent decrease in resorption activity in response to α-dihydrotestosterone (α-DHT), β-DHT, testosterone, or the synthetic androgen RU1881. This decrease was blocked by cotreatment with the specific androgen antagonist hydroxyflutamide. Further examination of avian osteoclasts revealed that the cells exhibited specific and saturable nuclear binding of tritiated RU1881 and that α-DHT stimulated the activity of the androgen response element as measured by using a chloramphenicol acetyltransferase reporter plasmid. In addition, avian osteoclasts responded to androgen treatment with elevated production and secretion of transforming growth factor β, a well documented response to androgen exposure in other cell systems. Treatment with either α-DHT or β-DHT for 24 hours resulted in a significant dose-dependent decrease in secretion of cathepsin B and tartrate-resistant acid phosphatase. This response to β-DHT, a stereoisomer of α-DHT that is inactive in other androgen receptor-dependent systems, supports the hypothesis that the osteoclast androgen receptor has unusual ligand-binding properties. Taken together, these results confirm the presence of functional androgen receptors in these cells and support the conclusion that osteoclasts are able to respond directly to androgensin vitroand thus are potential androgen target cellsin vivo.
Sonic hedgehog protein signals not as a hydrolytic enzyme but as an apparent ligand for Patched
Authors: Fuse Naoyuki , Maiti Tapan , Wang Baolin , Porter Jeffery A. , Hall Traci M. Tanaka , Leahy Daniel J. , Beachy Philip A.
Published: July 2002

The amino-terminal signaling domain of the Sonic hedgehog secreted
protein (Shh-N), which derives from the Shh precursor through an
autoprocessing reaction mediated by the carboxyl-terminal domain,
executes multiple functions in embryonic tissue patterning, including
induction of ventral and suppression of dorsal cell types in the
developing neural tube. An apparent catalytic site within Shh-N is
suggested by structural homology to a bacterial carboxypeptidase. We
demonstrate here that alteration of residues presumed to be critical
for a hydrolytic activity does not cause a loss of inductive activity,
thus ruling out catalysis by Shh-N as a requirement for signaling. We
favor the alternative, that Shh-N functions primarily as a ligand for
the putative receptor Patched (Ptc). This possibility is supported by
new evidence for direct binding of Shh-N to Ptc and by a strong
correlation between the affinity of Ptc-binding and the signaling
potency of Shh-N protein variants carrying alterations of conserved
residues in a particular region of the protein surface. These results
together suggest that direct Shh-N binding to Ptc is a critical event
in transduction of the Shh-N signal.
D
2
dopamine receptors induce mitogen-activated protein kinase and cAMP response element-binding protein phosphorylation in neurons
Authors: Yan Zhen , Feng Jian , Fienberg Allen A. , Greengard Paul
Published: July 2002

Dopamine, by activating D
1
- and D
2
-class receptors, plays a significant role in regulating gene expression. Although much is known about D
1
receptor-regulated gene expression, there has been far less information on gene regulation mediated by D
2
receptors. In this study, we show that D
2
receptors can activate the mitogen-activated protein kinase (MAPK) and the cAMP response element-binding protein (CREB) in neurons. Treatment of brain slices with the D
2
receptor agonist quinpirole induced rapid phosphorylation of MAPK and CREB. The neuroleptic drug eticlopride, a highly selective D
2
receptor antagonist, blocked the quinpirole-induced phosphorylation of MAPK and CREB. D
2
receptor-induced MAPK phosphorylation depended on intracellular Ca
2+
elevation, protein kinase C activation, and MAPK kinase activation, but not on the protein tyrosine kinase Pyk2, even though quinpirole stimulated Pyk2 phosphorylation. D
2
receptor-induced CREB phosphorylation was mediated by activation of protein kinase C and Ca
2+
/calmodulin-dependent protein kinase, but not MAPK. The dopamine and cAMP-regulated phosphoprotein DARPP-32 also was required for the regulation of MAPK and CREB phosphorylation by D
2
receptors. Our results suggest that MAPK and CREB signaling cascades are involved in the regulation of gene expression and other long-term effects of D
2
receptor activation.
Progesterone receptors in the thymus are required for thymic involution during pregnancy and for normal fertility
Authors: Tibbetts Todd A. , DeMayo Franco , Rich Susan , Conneely Orla M. , O’Malley Bert W.
Published: July 2002

Thymocyte development is reported to be inhibited by pregnancy, although the impact of this effect on fertility is unknown. We demonstrate, using progesterone receptor null mutant mice, that the inhibitory effects of pregnancy hormones on T cell development require the presence of functional progesterone receptor (PR). A combination of hysterectomy, thymic immunohistochemistry, and transplant studies reveals that local expression of PR in thymic stromal cells is specifically required for thymic involution to occur. These cells, under the influence of progesterone, block T cell development at the early pre-T cell (CD3−CD44+CD25+) stage of development via a paracrine mechanism. In addition, age-related thymic involution is shown to occur by a separate PR-independent mechanism. Finally, pregnancy studies with thymic transplants from progesterone receptor null mutant mice to wild-type female recipients demonstrate that thymic stromal PR is required for normal fertility. Together, these observations provide evidence for a PR-dependent paracrine mechanism that blocks very early T cell lymphopoiesis during pregnancy and is essential for normal fertility.
Single-molecule fluorescence spectroscopy of enzyme conformational dynamics and cleavage mechanism
Authors: Ha Taekjip , Ting Alice Y. , Liang Joy , Caldwell W. Brett , Deniz Ashok A. , Chemla Daniel S. , Schultz Peter G. , Weiss Shimon
Published: July 2002

Fluorescence resonance energy transfer and fluorescence polarization anisotropy are used to investigate single molecules of the enzyme staphylococcal nuclease. Intramolecular fluorescence resonance energy transfer and fluorescence polarization anisotropy measurements of fluorescently labeled staphylococcal nuclease molecules reveal distinct patterns of fluctuations that may be attributed to protein conformational dynamics on the millisecond time scale. Intermolecular fluorescence resonance energy transfer measurements provide information about the dynamic interactions of staphylococcal nuclease with single substrate molecules. The experimental methods demonstrated here should prove generally useful in studies of protein folding and enzyme catalysis at single-molecule resolution.
Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: Increased duodenal expression of the iron transporter DMT1
Authors: Fleming Robert E. , Migas Mary C. , Zhou XiaoYan , Jiang Jinxing , Britton Robert S. , Brunt Elizabeth M. , Tomatsu Shunji , Waheed Abdul , Bacon Bruce R. , Sly William S.
Published: July 2002

Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by tissue iron deposition secondary to excessive dietary iron absorption. We recently reported that HFE, the protein defective in HH, was physically associated with the transferrin receptor (TfR) in duodenal crypt cells and proposed that mutations in HFE attenuate the uptake of transferrin-bound iron from plasma by duodenal crypt cells, leading to up-regulation of transporters for dietary iron. Here, we tested the hypothesis that HFE
−/−
mice have increased duodenal expression of the divalent metal transporter (DMT1). By 4 weeks of age, the HFE
−/−
mice demonstrated iron loading when compared with HFE
+/+
littermates, with elevated transferrin saturations (68.4% vs. 49.8%) and elevated liver iron concentrations (985 μg/g vs. 381 μg/g). By using Northern blot analyses, we quantitated duodenal expression of both classes of DMT1 transcripts: one containing an iron responsive element (IRE), called DMT1(IRE), and one containing no IRE, called DMT1(non-IRE). The positive control for DMT1 up-regulation was a murine model of dietary iron deficiency that demonstrated greatly increased levels of duodenal DMT1(IRE) mRNA. HFE
−/−
mice also demonstrated an increase in duodenal DMT1(IRE) mRNA (average 7.7-fold), despite their elevated transferrin saturation and hepatic iron content. Duodenal expression of DMT1(non-IRE) was not increased, nor was hepatic expression of DMT1 increased. These data support the model for HH in which HFE mutations lead to inappropriately low crypt cell iron, with resultant stabilization of DMT1(IRE) mRNA, up-regulation of DMT1, and increased absorption of dietary iron.
Horizontal gene transfer among genomes: The complexity hypothesis
Authors: Jain Ravi , Rivera Maria C. , Lake James A.
Published: July 2002

Increasingly, studies of genes and genomes are indicating that considerable horizontal transfer has occurred between prokaryotes. Extensive horizontal transfer has occurred for operational genes (those involved in housekeeping), whereas informational genes (those involved in transcription, translation, and related processes) are seldomly horizontally transferred. Through phylogenetic analysis of six complete prokaryotic genomes and the identification of 312 sets of orthologous genes present in all six genomes, we tested two theories describing the temporal flow of horizontal transfer. We show that operational genes have been horizontally transferred continuously since the divergence of the prokaryotes, rather than having been exchanged in one, or a few, massive events that occurred early in the evolution of prokaryotes. In agreement with earlier studies, we found that differences in rates of evolution between operational and informational genes are minimal, suggesting that factors other than rate of evolution are responsible for the observed differences in horizontal transfer. We propose that a major factor in the more frequent horizontal transfer of operational genes is that informational genes are typically members of large, complex systems, whereas operational genes are not, thereby making horizontal transfer of informational gene products less probable (the complexity hypothesis).
Noninvasive measurement of anatomic structure and intraluminal oxygenation in the gastrointestinal tract of living mice with spatial and spectral EPR imaging
Authors: He Guanglong , Shankar Ravi A. , Chzhan Michael , Samouilov Alexandre , Kuppusamy Periannan , Zweier Jay L.
Published: July 2002

EPR imaging has emerged as an important tool for noninvasive three-dimensional (3D) spatial mapping of free radicals in biological tissues. Spectral–spatial EPR imaging enables mapping of the spectral information at each spatial position, and, from the observed line width, the localized tissue oxygenation can be mapped. We report the development of EPR imaging instrumentation enabling 3D spatial and spectral–spatial EPR imaging of small animals. This instrumentation, along with the use of a biocompatible charcoal oximetry-probe suspension, enabled 3D spatial imaging of the gastrointestinal (GI) tract, along with mapping of oxygenation in living mice. By using these techniques, the oxygen tension was mapped at different levels of the GI tract from the stomach to the rectum. The results clearly show the presence of a marked oxygen gradient from the proximal to the distal GI tract, which decreases after respiratory arrest. This technique for
in vivo
mapping of oxygenation is a promising method, enabling the noninvasive imaging of oxygen within the normal GI tract. This method should be useful in determining the alterations in oxygenation associated with disease.
The middle way
Authors: Laughlin R. B. , Pines David , Schmalian Joerg , Stojković Branko P. , Wolynes Peter
Published: July 2002

Mesoscopic organization in soft, hard, and biological matter is examined in the context of our present understanding of the principles responsible for emergent organized behavior (crystallinity, ferromagnetism, superconductivity, etc.) at long wavelengths in very large aggregations of particles. Particular attention is paid to the possibility that as-yet-undiscovered organizing principles might be at work at the mesoscopic scale, intermediate between atomic and macroscopic dimensions, and the implications of their discovery for biology and the physical sciences. The search for the existence and universality of such rules, the proof or disproof of organizing principles appropriate to the mesoscopic domain, is called the middle way.
Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: Relation to hypercortisolism and corticotropin-releasing hormone
Authors: Wong Ma-Li , Kling Mitchel A. , Munson Peter J. , Listwak Samuel , Licinio Julio , Prolo Paolo , Karp Brian , McCutcheon Ian E. , Geracioti Thomas D. , DeBellis Michael D. , Rice Kenner C. , Goldstein David S. , Veldhuis Johannes D. , Chrousos George P. , Oldfield Edward H. , McCann Samuel M. , Gold Philip W.
Published: July 2002

Both stress-system activation and melancholic depression are characterized by fear, constricted affect, stereotyped thinking, and similar changes in autonomic and neuroendocrine function. Because norepinephrine (NE) and corticotropin-releasing hormone (CRH) can produce these physiological and behavioral changes, we measured the cerebrospinal fluid (CSF) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression. Plasma adrenocorticotropic hormone (ACTH) and cortisol levels were obtained every 30 min. Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock. Diurnal variations in CSF NE and plasma cortisol levels were virtually superimposable and positively correlated with each other in both patients and controls. Despite their hypercortisolism, depressed patients had normal levels of plasma ACTH and CSF CRH. However, plasma ACTH and CSF CRH levels in depressed patients were inappropriately high, considering the degree of their hypercortisolism. In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls, patients with depression showed no statistical relationship between these parameters. These data indicate that persistent stress-system dysfunction in melancholic depression is independent of the conscious stress of the disorder. These data also suggest mutually reinforcing bidirectional links between a central hypernoradrenergic state and the hyperfunctioning of specific central CRH pathways that each are driven and sustained by hypercortisolism. We postulate that Î±-noradrenergic blockade, CRH antagonists, and treatment with antiglucocorticoids may act at different loci, alone or in combination, in the treatment of major depression with melancholic features.
Identification and characterization of a p53 homologue in
Drosophila melanogaster
Authors: Jin Shengkan , Martinek Sebastian , Joo Woo S. , Wortman Jennifer R. , Mirkovic Nebojsa , Sali Andrej , Yandell Mark D. , Pavletich Nikola P. , Young Michael W. , Levine Arnold J.
Published: July 2002

The tumor suppressor gene
p53
in mammalian cells plays a critical role in safeguarding the integrity of genome. It functions as a sequence-specific transcription factor. Upon activation by a variety of cellular stresses, p53 transactivates downstream target genes, through which it regulates cell cycle and apoptosis. However, little is known about p53 in invertebrates. Here we report the identification and characterization of a
Drosophila
p53
homologue gene,
dp53
.
dp53
encodes a 385-amino acid protein with significant homology to human
p53
(
hp53
) in the region of the DNA-binding domain, and to a lesser extent the tetramerization domain. Purified
dp53
DNA-binding domain protein was shown to bind to the consensus hp53-binding site by gel mobility analysis. In transient transfection assays, expression of
dp53
in Schneider cells transcriptionally activated promoters that contained consensus hp53-responsive elements. Moreover, a mutant dp53 (Arg-155 to His-155), like its hp53 counterpart mutant, exerted a dominant-negative effect on transactivation. Ectopic expression of
dp53
in
Drosophila
eye disk caused cell death and led to a rough eye phenotype.
dp53
is expressed throughout the development of
Drosophila
with highest expression levels in early embryogenesis, which has a maternal component. Consistent with this,
dp53
RNA levels were high in the nurse cells of the ovary. It appears that p53 is structurally and functionally conserved from flies to mammals.
Drosophila
will provide a useful genetic system to the further study of the p53 network.
The NF-κB signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation
Authors: Hajra Leena , Evans Andrew I. , Chen Mian , Hyduk Sharon J. , Collins Tucker , Cybulsky Myron I.
Published: July 2002

Atherosclerotic lesions form at distinct sites in the arterial tree, suggesting that hemodynamic forces influence the initiation of atherogenesis. If NF-κB plays a role in atherogenesis, then the activation of this signal transduction pathway in arterial endothelium should show topographic variation. The expression of NF-κB/IκB components and NF-κB activation was evaluated by specific antibody staining,en faceconfocal microscopy, and image analysis of endothelium in regions of mouse proximal aorta with high and low probability (HP and LP) for atherosclerotic lesion development. In control C57BL/6 mice, expression levels of p65, IκBα, and IκBβ were 5- to 18-fold higher in the HP region, yet NF-κB was activated in a minority of endothelial cells. This suggested that NF-κB signal transduction was primed for activation in HP regions on encountering an activation stimulus. Lipopolysaccharide treatment or feeding low-density lipoprotein receptor knockout mice an atherogenic diet resulted in NF-κB activation and up-regulated expression of NF-κB-inducible genes predominantly in HP region endothelium. Preferential regional activation of endothelial NF-κB by systemic stimuli, including hypercholesterolemia, may contribute to the localization of atherosclerotic lesions at sites with high steady-state expression levels of NF-κB/IκB components.
A hippocampal interneuron associated with the mossy fiber system
Authors: Vida Imre , Frotscher Michael
Published: July 2002

Network properties of the hippocampus emerge from the interaction of principal cells and a heterogeneous population of interneurons expressing
γ
-aminobutyric acid (GABA). To understand these interactions, the synaptic connections of different types of interneurons need to be elucidated. Here we describe a type of inhibitory interneuron of the hippocampal CA3 region that has an axon coaligned with the mossy fibers. Whole-cell patch-clamp recordings, in combination with intracellular biocytin filling, were made from nonpyramidal cells of the stratum lucidum under visual control. Mossy fiber-associated (MFA) interneurons generated brief action potentials followed by a prominent after-hyperpolarization. Subsequent visualization revealed an extensive axonal arbor which was preferentially located in the stratum lucidum of CA3 and often invaded the hilus. The dendrites of MFA interneurons were mainly located in the strata radiatum and oriens, suggesting that these cells are primarily activated by associational and commissural fibers. Electron microscopic analysis showed that axon terminals of MFA interneurons established symmetric synaptic contacts predominantly on proximal apical dendritic shafts, and to a lesser degree, on somata of pyramidal cells. Synaptic contacts were also found on GABAergic interneurons of the CA3 region and putative mossy cells of the hilus. Inhibitory postsynaptic currents (IPSCs) elicited by MFA interneurons in simultaneously recorded pyramidal cells had fast kinetics (half duration, 3.6 ms) and were blocked by the GABA
A
receptor antagonist bicuculline. Thus, MFA interneurons are GABAergic cells in a position to selectively suppress the mossy fiber input, an important requirement for the recall of memory traces from the CA3 network.
The epidemiology of antibiotic resistance in hospitals: Paradoxes and prescriptions
Authors: Lipsitch Marc , Bergstrom Carl T. , Levin Bruce R.
Published: July 2002

A simple mathematical model of bacterial transmission within a hospital was used to study the effects of measures to control nosocomial transmission of bacteria and reduce antimicrobial resistance in nosocomial pathogens. The model predicts that: (
i
) Use of an antibiotic for which resistance is not yet present in a hospital will be positively associated at the individual level (odds ratio) with carriage of bacteria resistant to other antibiotics, but negatively associated at the population level (prevalence). Thus inferences from individual risk factors can yield misleading conclusions about the effect of antibiotic use on resistance to another antibiotic. (
ii
) Nonspecific interventions that reduce transmission of all bacteria within a hospital will disproportionately reduce the prevalence of colonization with resistant bacteria. (
iii
) Changes in the prevalence of resistance after a successful intervention will occur on a time scale of weeks to months, considerably faster than in community-acquired infections. Moreover, resistance can decline rapidly in a hospital even if it does not carry a fitness cost. The predictions of the model are compared with those of other models and published data. The implications for resistance control and study design are discussed, along with the limitations and assumptions of the model.
Québécois, Haitian, and Vietnamese Mothers' Report of Infant Temperament
Authors: Pomerleau Andrée , Sabatier Colette , Malcuit Gérard
Published: July 2002

Research has shown different temperamental attributes in infants of various cultural origins. Some authors have suggested that these temperamental attributes might be related to biological and genetic differences. In the present study, mothers' reports of infant temperament, using the Revised Infant Temperament Questionnaire (Carey & McDevitt, 1978), were compared among Québécois, Haitian, and Vietnamese groups living in Montréal. Results indicated patterns of differences across groups that essentially distinguished the Québécois from the other two groups. These two groups reported more difficult temperamental characteristics in their infants. The values and caretaking practices related to the specific cultural contexts, contrasted with the values expressed through a North‐American validated questionnaire, may explain the variations in infant temperament reports. Further studies should examine more thoroughly the relation between observed infant behaviours and maternal reports.
Analysing Power Relations in Partnerships: Is There a Role for Discourse Analysis?
Authors: Hastings Annette
Published: July 2002

The aim of this paper is to assess power relations between the participants involved in a newly formed, multi-sectoral, urban regeneration partnership. The paper examines the extent of 'transformation' during the progress of the partnership; focusing on identifying changes in partners' theories of the causes of the local regeneration 'problem'. It draws upon the theoretical framework and analytical tools provided by critical discourse analysis in order to explore how a focus on language use can contribute to identifying changes in assumptions and values. The overall purpose of the paper is to consider the practical usefulness of discourse theory and analysis in identifying instances of the exercise of power. It concludes that discourse analysis can help to detect ways in which power is being exercised which may not be apparent to or acknowledged by those involved in partnerships and can therefore be made to play a useful role in assessing power in partnership working.
Political Culture and National Symbols: Their Impact on the Belarusian Nation-Building Process
Authors: Sahm Astrid
Published: July 2002

The new states emerging from the break-up of the Soviet Union not only had to manage the task of political and economic reforms but were also forced to develop a suitable national state ideology in order to ensure their achieved independence. The existence of a national consensus is essential for the stability of every state and society, and during periods of transition the question how national identity is defined becomes especially important. Thus, on the one hand, the dominance of a concrete national state concept may facilitate the transformation process because people are ready to bear the social costs of economic reforms in the name of state sovereignty, as was the case in Lithuania. On the other hand, a continuing Soviet cultural hegemony can also block necessary modernization in the post-Soviet period.
No Good Surprises: Intending lecturers' preconceptions and initial experiences of further education
Authors: Wallace Sue
Published: July 2002

Abstract Current initiatives to promote lifelong learning and a broader inclusiveness in post‐16 education have focused attention on further education (FE). The article examines the experiences and reactions of 41 intending lecturers studying full‐time for a Postgraduate Certificate in Further Education and Training (PGCET), as they enter FE colleges on teaching practice and encounter FE students for the first time. It argues that the sector may have something to learn from the contrast between these intending lecturers' expectations and their subsequent experiences, and that attempts to address problems which are endemic within the current FE sector by initiatives to improve teacher competence, such as the Further Education National Training Organisation (FENTO)'s recently introduced FE teacher training standards, are inadequate and misdirected.
Can racial identity be promotive of academic efficacy?
Authors: Oyserman Daphna , Harrison Kathy , Bybee Deborah
Published: July 2002

We hypothesised a gender specific relationship between efficacy and three components of racial identity, feeling that achievement is part of being black, feeling connected to the black community, and sensitivity to, awareness of outgroup barriers and racism. Because male gender socialisation downplays relationality, the “connectedness” component of racial identity was posited to be particularly helpful for boys. Because female gender socialisation downplays independent achievement and agency, the “achievement” component of racial identity was posited to be particularly helpful for girls in buffering the negative effects of the “awareness of racism” component. Controlling for fall grades and academic efficacy, fall racial identity significantly predicted spring academic efficacy differentially for boys and girls (n = 91 African-American eighth graders), with the lack of the achievement component of racial identity being particularly detrimental to girls.
Change in Work Values and Norms among Dutch Young Adults: Ageing or Societal Trends?
Authors: van der Velde Mandy E.G. , Feij Jan A. , van Emmerik Hetty
Published: July 2002

In the present study, data were analysed longitudinally on the basis of lifespan developmental psychology to determine if work values and norms change as a result of ageing/maturation or societal trends (i.e. period effects between two measurement waves). Moreover, data were collected to determine if the younger participants showed more change than the older participants. Participants were three age groups, 18, 22, and 26 years old, respectively, in 1987 ( N 806). The participants completed a questionnaire in 1987 and 1991. Measures of work values and norms included Absolute Work Centrality, Relative Importance of Work, Obligation Work Norm, Emancipation Norm and Spare Time Norm, and Intrinsic, Extrinsic and Social Work Values. Using tests of differences in over time correlation coefficients, paired t-tests and analyses of variance, the results show that work, and especially intrinsic work values become more important by ageing than by societal trends and that younger participants indeed changed more than the older participants. These results underscore the plea of Schulenberg, Vondracek, and Kim (1993) for a combination of a developmental and individual difference perspective of work value change in career theory and practice.
The Impact of Maternal Schooling and Occupation on Child-rearing Attitudes and Behaviours in Low Income Neighbourhoods in Cairo, Egypt
Authors: von der Lippe Anna Louise
Published: July 2002

As a developing country, Egypt and especially Cairo, is in a transitional phase between a traditional and a modern, education-based society and between traditional child-rearing values of passivity and obedience and new demands for academic competence. Education is seen by present day parents as the major vehicle for the future success and happiness of children and much effort is expended toward this goal. Thirty Cairene mothers from low income neighbourhoods with similar housing standards and crowding, but with different levels of education and occupational status were interviewed (1994-95) about socialisation values and practices and observed with their children in order to evaluate how mothers prepare preschoolers for the cognitive demands of school. It was anticipated that educated working mothers would be less traditional and engage their children in more active competence training (mediation of learning experience, MLE, and authoritative child-raising style, AC-R) as a mediator to children’s cognitive competence. These expectations were supported.

The 30 mothers were generally found to emphasise a controlling, restricting, and protecting style of child rearing, with moral education, compliance, agreeableness, passivity, and loyalty as ideals. Observation revealed little verbal interaction or stimulation of children. Educated working mothers, however, expressed belief in earlier developmental timetables and endorsed the less traditional values of stimulating and interacting rather than controlling and expecting obedience of the child more than the remaining mothers. Educated working mothers were also more positively verbally interacting with their children during the interview than nonworking low-educated mothers. They scored higher on AC-R and on the MLE categories guiding and expanding in interactive play and these variables were related to the children’s cognitive competence (intelligence scores), also when the mothers’ intelligence was accounted for. Mothers’ educational and occupational levels did not predict children’s cognitive competence directly, suggesting that mothers’ child-rearing behaviours acted as mediators. Fathers’ educational level was not related to the children’s cognitive competence. The results point to the potential benefit of investing in girls’ (and future mothers’) education for the future of their children.
Regulation of Xenobiotic Metabolism by Orphan Nuclear Receptors
Authors: Miller Richard T. , Willson Timothy M.
Published: July 2002

Nuclear receptors control gene transcription by binding to specifi cpromoter regions of DNA in the presence of ligand. Orphan nuclear receptors are nuclear receptors for which the endogenous ligand(s) has yet to be identified. Systematic evaluation of orphan nuclear receptors can elucidate species differences in xenobiotic metabolism in addition to aiding in identification of endogenous ligands. The receptor-binding affinity and specifi city of various chemicals, with subsequent determination of the genes controlled by nuclear receptors, are goals of investigations into orphan nuclear receptor structure/function and can provide valuable tools in predicting drug interactions and toxicity.
Molecular Basis of Dioxin Actions: Evidence Supporting Chemoprotection
Authors: Greenlee William F. , Hushka Leslie J. , Hushka Dennet R.
Published: July 2002

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD or dioxin), a highly publicized environmental contaminant, was shown to be chemoprotective against breast cancer in both rats and mice in bioassays conducted in the late 1970s. This fi nding went largely unnoticed as investigators focused on animal tumors that were increased by dioxin. The position that dioxin causes human tumors remains a subject for debate; however, recent epidemiological studies of a population highly exposed to dioxin in 1976 as a result of an industrial accident suggest that women with higher dioxin body burdens may have a lower incidence of breast cancer. With the growth of new knowledge about the molecular basis of dioxin actions in humans and animals, it is clear that most of the responses produced by this agent are initiated by a specifi c recognition protein (designated the Ah receptor) found in almost all animal and human tissues and organs. The recognition event between the Ah receptor and environmental agents like dioxin is due to the formation of a complex. We have observed that in the presence of dioxin, the Ah receptor turns off proliferation in tumor cells and suppresses the ability of these cells to invade normal tissue. We believe that these fi ndings provide a molecular and biochemical basis for understanding the chemoprotective mechanisms suggested by the fi ndings of rodent bioassays and could lead to the development of novel therapeutic agents targeting the Ah receptor.
The Effect of Short Intermittent Light Exposures on the Melatonin Circadian Rhythm and NMU-Induced Breast Cancer in Female F344/N Rats
Authors: Travlos Gregory S. , Wilson Ralph E. , Murrell James A. , Chignell Colin F. , Boorman Gary A.
Published: July 2002

We investigated the effects of altered endogenous nighttime melatonin concentrations on mammary tumor production in an N-nitroso-N-methylurea (NMU)-induced breast cancer model in female Fischer 344 (F344)/N rats. Experiments were designed 1) to evaluate whether short-duration intermittent exposures to light at night would affect the nocturnal rise of melatonin, resulting in a decrease in nighttime serum melatonin concentrations, 2) to evaluate whether any suppression of nighttime serum melatonin concentrations could be maintained for a period of weeks, and 3) to determine the effects of suppressed serum melatonin concentrations on the incidence and progression of NMU-induced breast cancer. In vivo studies were used to assess serum melatonin concentrations after 1 day and 2 and 10 weeks of nightly administration of short-duration intermittent light exposure at night and incidence of NMU-induced tumors. Five 1-minute exposures to incandescent light every 2 hours after the start of the dark phase of the light: dark cycle decreased the magnitude of the nocturnal rise of serum melatonin concentrations in rats by approximately 65%. After 2 weeks of nightly intermittent light exposures, an average decrease of the peak nighttime serum melatonin concentrations of approximately 35% occurred. The amelioration continued and, at 10 weeks, peak nighttime serum melatonin concentrations were still decreased, by approximately 25%. Because peak endogenous nighttime serum melatonin values could be moderately suppressed for at least 10 weeks, a 26-week NMU mammary tumor study was conducted. Serum melatonin concentrations and incidence, multiplicity, and weight of NMU-induced mammary tumors were assessed. A group of pinealectomized (Px) animals was also included in the tumor study. No effect on the development of mammary tumors in an NMU-induced tumor model in rats occurred when endogenous nighttime serum melatonin concentrations were moderately suppressed by short-duration intermittent light exposures at night. At necropsy, there were no alterations in mammary tumor incidence (28/40 NMU controls, 28/40 NMU + light, 31/40 NMU + Px), multiplicity (2.18 tumors/tumor-bearing NMU control, 1.89 NMU + light, 2.39 NMU + Px), or average tumor weight (1.20 g NMU control, 1.19 g NMU + light, 0.74 g NMU + Px). Tumor burden had no effect on the serum melatonin cycle. At 26 weeks, however, animals exposed to intermittent light at night exhibited approximately 3-fold higher serum melatonin concentrations as compared with controls. Additionally, rats that had been pinealectomized at 4 weeks of age had serum melatonin concentrations that were markedly higher than the expected baseline concentrations for pinealectomized rats (<15 pg/ml), suggesting the reestablishment of a melatonin cycle. This finding was unexpected and suggests that melatonin can be produced by an organ or tissue other than the pineal gland.
Acute Changes in Lung Histopathology and Bronchoalveolar Lavage Parameters in Mice Exposed to the Choking Agent Gas Phosgene
Authors: Duniho Steven M. , Martin Jamie , Forster Jeffry S. , Cascio Matthew B. , Moran Ted S. , Carpin Laura B. , Sciuto Alfred M.
Published: July 2002

Phosgene (CG) is a highly irritant gas widely used industrially as a chemical intermediate for the production of dyes, pesticides, and plastics, and can cause life-threatening pulmonary edema within 24 hours of exposure. This study was designed to investigate acute changes in lung tissue histopathology and selected bronchoalveolar lavage fl uid (BALF) factors over time to determine early diagnostic indicators of exposure. Three groups of 40 male mice each were exposed to 32 mg/m 3 (8 ppm) CG for 20 minutes, and 3 groups of 40 control male mice were exposed to fi ltered room air for 20 minutes, both exposures were followed by room air washout for 5 minutes. At 1, 4, 8, 12, 24, 48, and 72 hours after exposure each group of mice was euthanized and processed for histopathology, bronchoalveolar lavage or gravimetric measurements, respectively. Over time, the histopathological lesions were characterized by acute changes consisting of alveolar and interstitial edema, fi brin and hemorrhage, followed by signifi cant alveolar and interstitial fl ooding with infl ammatory cell infi ltrates and scattered bronchiolar and terminal airway epithelial degeneration and necrosis. From 48 to 72 hours, there was partial resolution of the edema and degenerative changes, followed by epithelial and fi broblastic regeneration centered on the terminal bronchiolar areas. Bronchoalveolar lavage was processed for cell differential counts, LDH, and protein determination. Comparative analysis revealed signifi cant increases in both postexposure lung wet/dry weight ratios, and early elevations of BALF LDH and protein, and later elevations in leukocytes. This article describes the use of histopathology to chronicle the temporal pulmonary changes subsequent to whole body exposure to phosgene, and correlate these changes with BALF ingredients and postexposure lung wet weights in an effort to characterize toxic gas-induced acute lung injury and identify early markers of phosgene exposure.
Supporting Rural Labour Markets
Authors: Monk Sarah , Hodge Ian , Dunn Jessica
Published: July 2002

Deprivation and disadvantage in rural areas is often thought to be “hidden” from official statistics largely because people in rural areas are dispersed into small, scattered settlements. This paper draws on research undertaken in two contrasting rural areas to explore one aspect of disadvantage, the labour market, an d goes on to consider possible policy mechanisms which might be able to address rural deprivation . In particular, it examines the potential for more flexible policies, which appear to have been successful in urban con texts, but which are targeted at areas with high concentrations of deprivation so that rural areas do not qualify.
Alcohol harm reduction education in schools: planning an efficacy study in Australia
Authors: MCBRIDE NYANDA T. , MDFORD RICHARD , FARRINGDON FIONA H.
Published: July 2002

The School Health and Alcohol Harm Reduction Project (SHAHRP) is a 4‐year, quasi‐experimental, evidence‐based intervention research study designed to explore the effects of a student‐focused, secondary school, alcohol education intervention in reducing alcohol‐related harm experienced by school students. The SHAHRP study is unusual in that it has a primary aim of harm minimization rather than non‐use or delayed use. The SHAHRP intervention aims to reduce harm by enhancing students' abilities to identify and deal with high‐risk drinking situations particularly likely to be encountered by young people. The intervention involves eight lessons in the first year with five booster lessons in the subsequent year. The SHAHRP research will follow individual students exposed to both the alcohol and health promotion interventions over 3 successive years taking measures in: knowledge; attitudes; patterns of use; context of use; alcohol‐related harm associated with the student' own use; alcohol‐related harm associated with other people's use of alcohol. This paper describes the evidence‐based conceptual components and design of the study by providing a review of the health and drug education literature particularly related to components that have the potential of influencing behaviour.
Pigs and Ferrets as Models in Toxicology and Biological Safety Assessment
Authors: Gad Shayne C.
Published: July 2002

Both the pig and the ferret are used as animal models in toxicology and drug development, with the pig having been subject to a significant increase in usage (particularly in Europe) over the last 5 years. These two species are quite different from primates and dogs, the “standard” nonrodent models. This article seeks to both survey the rationales for and extent of use of the pig and ferret, and to highlight consideration and key factors in their use in studies.