Acute susceptibility of aged mice to infection with Candida albicans

The effect of aging on host resistance to systemic candidosis was assessed by monitoring the course of infection in 16-month-old CBA/CaH mice (aged non-immune) and in a comparable group that had been infected with a sublethal dose of Candida albicans at 6 weeks of age (aged immune). Aged non-immune mice showed rapid progression of the disease, with a marked increase in the number of mycelia in the brain and kidney, and early morbidity, Foci of myocardial necrosis were evident, but inflammatory cells were sparse. The histological picture in the aged immune mice was similar to that in the aged non-immune group, although fewer mycelial aggregates were seen. Both groups of aged mice showed a significantly lower fungal burden in the brain on day 1 of infection, but on day 4, colony counts increased significantly in the aged non-immune mice, Comparison of cytokine gene expression in the infected brains showed that the relative amount of interferon-gamma and tumour necrosis factor-alpha cDNA were similar in all three groups. Interleukin-6 was elevated in both infected non-immune and uninfected aged mice. Aged immune mice showed no morbidity after challenge, and both colonisation and tissue damage were reduced in comparison with the aged non-immune animals.

Expression of the estrogen receptor-associated immunophilins, cyclophilin 40 and FKBP52, in breast cancer

The estrogen receptor alpha (ER alpha) is implicated in the development of breast cancer. The immunophilins, cyclophilin 40 (CyP40) and FKBP52, are associated with ER alpha and other steroid receptors in mutually exclusive heterocomplexes and may differentially modulate receptor activity. Since previous studies have not assessed the levels of these immunophilins in breast cancer, we examined 10 breast cancer cell lines for mRNA and protein expression of CyP40 and FKBP52 and for amplification of the CyP40 gene. In addition, 26 breast carcinomas, including seven with matched normal breast tissue, were examined for mRNA expression of both immunophilins. CyP40 and FKBP52 were ubiquitously expressed in breast cancer cell lines, but there were significant differences in their pattern of expression. FKBP52 protein levels were generally an order of magnitude greater than those for CyP40. FKBP52 mRNA expression correlated strongly with protein expression and was significantly higher in ER alpha-positive compared with ER alpha-negative cell lines. However, CyP40 mRNA expression did not correlate with protein expression, nor did expression of this immunophilin correlate with ER alpha status. Relatively high expression of CyP40 in one cell line (BT-20) could be attributed to amplification of the CyP40 gene. Both immunophilins were also ubiquitously expressed in breast carcinomas, and we demonstrate for the first time that both CyP40 and FKBP52 mRNA are overexpressed in breast tumors compared to matched normal breast controls. The overexpression of CyP40 and FKBP52, coupled with relative differences in their expression in tumors, may have important functional implications for ER alpha and other steroid receptors in breast cancer.

Regulation of the Hsp90-binding immunophilin, cyclophilin 40, is mediated by multiple sites for CA-binding protein (GABP)

Within steroid receptor heterocomplexes the large tetraticopeptide repeat-containing immunophilins, cyclophilin 40 (CyP40), FKBP51, and FKBP52, target a common interaction site in heat shock protein 90 (HspSO) and act coordinately with HspSO to modulate receptor activity. The reversible nature of the interaction between the immunophilins and HspSO suggests that relative cellular abundance might be a key determinant of the immunophilin component within steroid receptor complexes. To investigate CyP40 gene regulation, we have isolated a fi-kilobase (kb) 5 ' -flanking region of the human gene and demonstrated that a similar to 50 base pair (bp) sequence adjacent to the transcription start site is essential for CyP40 basal expression. Three tandemly arranged Ets sites within this critical region were identified as binding elements for the multimeric Ets-related transcription factor, GA binding protein (GABP). Functional studies of this proximal promoter sequence, in combination with mutational analysis, confirmed these sites to be crucial for basal promoter function. Furthermore, overexpression of both GABP alpha and GABP beta subunits in Cos1 cells resulted in increased endogenous CyP40 mRNA levels. Significantly, a parallel increase in FKBP52 mRNA expression was not observed, highlighting an important difference in the mode of regulation of the CyP40 and FKBP52 genes. Our results identify GABP as a key regulator of CyP40 expression. GAFF is a common target of mitogen and stress-activated pathways and may integrate these diverse extracellular signals to regulate CyP40 gene expression.

Estradiol-regulated expression of the immunophilins cyclophilin 40 and FKBP52 in MCF-7 breast cancer cells

The immunophilins, cyclophilin 40 (CyP40) and FKBP52, are associated with the unactivated estrogen receptor in mutually exclusive heterocomplexes and may differentially modulate receptor activity, We have recently shown that CyP40 and FKBP52 mRNA's are differentially elevated in breast carcinomas compared with normal breast tissue. Other studies suggest that such alterations ill the ratio of immunophilins might potentially influence steroid receptor function. Studies were therefore initiated to investigate the influence of estradiol on CyP40 and FKBP52 expression in MCF-7 breast cancer cells. Over a 24-h-treatment period with estradiol, CyP40 and FKBP52 mRNA expression was increased approximately five- and 14-fold, respectively. The corresponding protein levels were also elevated in comparison to controls. The antiestrogen, ICI 182,780, was an antagonist for CyP40 and FKBP52 mRNA induction. Cycloheximide treatment did not inhibit this increased immunophilin expression, suggesting that estradiol-mediated activation is independent off de novo protein synthesis. Treatment of MCF-7 cells with estradiol resulted in an increased half-life of both CyP40 and FKBP52 mRNA, as determined by actinomycin D studies. These results suggest that estradiol regulates CyP40 and FKBP52 mRNA expression through both transcriptional and posttranscriptional mechanisms. (C) 2001 Academic Press.

The aesthetic turn in international political theory

This essay explores the nature and significance of aesthetic approaches to international political theory. More specifically, it contrasts aesthetic with mimetic forms of representation. The latter, which have dominated the study of international relations, seek to represent politics as realistically and authentically as possible, aiming at capturing world politics as it really is. An aesthetic approach, by contrast, assumes that there is always a gap between a form of representation and what is represented therewith. Rather than ignoring or seeking to narrow this gap, as mimetic approaches do, aesthetic insight recognises that the inevitable difference between the represented and its representation is the very location of politics. The essay, thus, argues for the need to reclaim the political value of the aesthetic; not to replace social science or technological reason, but to broaden our abilities to comprehend and deal with the key dilemmas of world politics. The ensuing model of thought facilitates productive interactions across different faculties, including sensibility, imagination and reason, without any of them annihilating the unique position and insight of the other.

Special issue: Selected papers from the sixth IFIP 2.6 working conference on visual database systems: Guest editors' introduction

While multimedia data, image data in particular, is an integral part of most websites and web documents, our quest for information so far is still restricted to text based search. To explore the World Wide Web more effectively, especially its rich repository of truly multimedia information, we are facing a number of challenging problems. Firstly, we face the ambiguous and highly subjective nature of defining image semantics and similarity. Secondly, multimedia data could come from highly diversified sources, as a result of automatic image capturing and generation processes. Finally, multimedia information exists in decentralised sources over the Web, making it difficult to use conventional content-based image retrieval (CBIR) techniques for effective and efficient search. In this special issue, we present a collection of five papers on visual and multimedia information management and retrieval topics, addressing some aspects of these challenges. These papers have been selected from the conference proceedings (Kluwer Academic Publishers, ISBN: 1-4020- 7060-8) of the Sixth IFIP 2.6 Working Conference on Visual Database Systems (VDB6), held in Brisbane, Australia, on 29–31 May 2002.

Potential triggers for akinete differentiation in an Australian strain of the cyanobacterium Cylindrospermopsis raciborskii (AWT 205/1)

Understanding the triggers for some cyanobacteria of the Nostocales and Stigonematales orders to produce specialised reproductive cells termed akinetes, is very important to gain further insights into their ecology. By improving our understanding of their life cycle, appropriate management options may be devised to control the formation of these cells, and therefore the potential bloom inoculum which they are thought to provide, may be reduced. This study investigated the effect of chemical (phosphorus limitation), and environmental variables (temperature shock) on akinete differentiation in the freshwater cyanobacterium Cylindrospermopsis raciborskii (AWT 205/1). From the preliminary results, it is suggested that the availability of phosphorus and changes in temperature were a necessary requirement for the formation of akinetes in this particular strain of C. raciborskii. In the four phosphorus treatments investigated (0, 3, 38 and 75 mug l(-1) P), only the two higher treatments produced akinetes (approximately 220 ml(-1)). When the first akinetes were observed in the 38 and 75 mug l(-1) P treatments, filterable reactive phosphorus (FRP) concentrations in the medium were approximately 22 and 52 mug l(-1) P, respectively, indicating that there was no phosphorus limitation. In the temperature shock experiment, akinetes were observed in the 15 and 20degreesC treatments. However, akinetes were degraded (pale yellow colour, limited swelling and shrivelled edges) and in much lower concentrations, which was thought to be a result of the daily temperature shock. We suggest that the formation of akinetes in C. raciborskii (AWT 205/1) can be triggered by an initial temperature shock and that phosphorus is a necessary requirement to allow further growth and full development of akinetes.

Aquisition and extinction of two characteristics consistent with fear relevance

Fear relevance, the potential of a stimulus to become quickly associated with fear, is a characteristic assumed to have an evolutionary basis and to result in preferential processing. Previous research has shown that fear relevant stimuli share a number of characteristics, negative valence and preferential identification in a visual search task, for instance. The present research examined whether these two characteristics can be acquired by non-fear relevant stimuli (geometric shapes) as a result of Pavlovian fear conditioning. Two experiments employed an aversive learning paradigm with geometric shape CSs and a shock US, with stimulus ratings, affective priming and visual search performance assessed before and after acquisition and after extinction. Differential electrodermal responses, larger during CS1 than CS, were present during acquisition but not during extinction. Affective priming results suggest that the CS1 acquired negative valence during acquisition, which was lost during extinction. However, negative valence as indexed by more negative ratings for CS1 than for CS shapes seemed to survive extinction. Preferential attentional processing as indexed by faster detection of CS1 among CS shapes than vice versa on the visual search task also remained. The current research confirmed that characteristics of fear relevant stimuli can be acquired in an aversive learning episode and that they may be extinguished. This supports the proposal that fear relevance may be malleable through learning.

Extinction of affective learning: No evidence for dual process accounts of human learning

The acquisition and extinction of affective valence to neutral geometrical shape conditional stimuli was investigated in three experiments. Experiment 1 employed a differential conditioning procedure with aversive shock USs. Differential electrodermal responding was evident during acquisition and lost during extinction. As indexed by verbal ratings, the CS1 acquired negative valence during acquisition,which was reduced after extinction. Affective priming, a reaction time based demand free measure of stimulus valence, failed to provide evidence for affective learning. Experiment 2 employed pictures of happy and angry faces as USs.Valence ratings after acquisitionweremore positive for theCS paired with happy faces (CS-H) and less positive for the CS paired with angry faces (CS-A) than during baseline. Extinction training reduced the extent of acquired valence significantly for both CSs, however, ratings of the CS-A remained different from baseline. Affective priming confirmed these results yielding differences between CS-A and CS-H after acquisition for pleasant and unpleasant targets, but for pleasant targets only after extinction. Experiment 3 replicated the design of Experiment 2, but presented the US pictures backwardly masked. Neither rating nor affective priming measures yielded any evidence for affective learning. The present results confirm across two different experimental procedures that, contrary to predictions from dual process accounts of human learning, affective learning is subject to extinction.

Changes in inflammatory mediators following eccentric exercise of the elbow flexors

The aims of this study were to examine the plasma concentrations of inflammatory mediators including cytokines induced by a single bout of eccentric exercise and again 4 weeks later by a second bout of eccentric exercise of the same muscle group. Ten untrained male subjects performed two bouts of the eccentric exercise involving the elbow flexors (6 sets of 5 repetitions) separated by four weeks. Changes in muscle soreness, swelling, and function following exercise were compared between the bouts. Blood was sampled before, immediately after, 1 h, 3 h, 6 h, 24 h (1 d), 48 h (2 d), 72 h (3 d), 96 h (4 d) following exercise bout to measure plasma creatine kinase (CK) activity, plasma concentrations of myoglobin (Mb), interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1ra), IL-4, IL-6, IL-8, IL-10, IL-12p40, tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), myeloperoxidase (MPO), prostaglandin E-2 (PGE(2)), heat shock protein (HSP) 60 and 70. After the first bout, muscle soreness increased significantly, and there was also significant increase in upper arm circumference; muscle function decreased and plasma CK activity and Mb concentration increased significantly. These changes were significantly smaller after the second bout compared to the first bout, indicating muscle adaptation to the repeated bouts of the eccentric exercise. Despite the evidence of greater muscle damage after the first bout, the changes in cytokines and other inflammatory mediators were quite minor, and considerably smaller than that following endurance exercise. These results suggest that eccentric exercise-induced muscle damage is not associated with the significant release of cytokines into the systemic circulation. After the first bout, plasma G-CSF concentration showed a small but significant increase, whereas TNF-alpha and IL-8 showed significant decreases compared to the pre-exercise values. After the second bout, there was a significant increase in IL-10, and a significant decrease in IL-8. In conclusion, although there was evidence of severe muscle damage after the eccentric exercise, this muscle damage was not accompanied by any large changes in plasma cytokine concentrations. The minor changes in systemic cytokine concentration found in this study might reflect more rapid clearance from the circulation, or a lack of any significant metabolic or oxidative demands during this particular mode of exercise. In relation to the adaptation to the muscle damage, the anti-inflammatory cytokine IL-10 might work as one of the underlying mechanisms of action.

Searching behaviour and diet of Oystercatcher Haematopus ostralegus pairs feeding in their territories

Search path, searching behaviour and diet of pairs of Oystercatchers feeding in mudflat territories were studied during spring. females ate Nereis, Mya, small unidentified prey, probably Corophium, and a few Macoma, whereas males primarily ate Macoma. Even when female and male foraged in the same site, they often caught different prey. The combination of 'The Search-rate/Detection Model' (Gendron & Staddon 1983) and 'The Harvestable Prey Model' (Zwarts & Wanink 1993) provide the theoretical framework in which to explain these differences in diet. Macoma are thought to be more cryptic than Nereis, Mya and Corophium. Therefore females, while searching at a faster rate than their respective mates, caught far fewer cryptic prey, but a greater number of more conspicuous prey than their mates. On the basis of distances moved before and after capturing prey, males exhibited area-restricted searching for Macoma and Corophium. In contrast, females did not exhibit any area-restricted searching. it is suggested that the distribution of Macoma and Corophium available to males searching slowly was more clumped than that of these two prey species available to females searching more quickly.

Fuel stagnation temperature effects on mixing with supersonic combustion flows

An experimental study of the effect of fuel stagnation temperature on mixing in a supersonic hydrogen-air flame is described, The combustor consisted of a constant-area rectangular duct with a centrally located fuel-injection strut that spanned the width. A high-enthalpy stream of air was supplied by a free-piston shock tunnel, and heated hydrogen fuel, supplied by a gun-tunnel, was injected into the freestream as a coflowing planar jet. The freestream total enthalpies were 5.6, 6.5, and 9 MJ/kg, and fuel stagnation temperatures were 300, 450, and 700 K, Raising the fuel stagnation temperature increased the fuel velocity to be near that of the airstream and resulted in a decrease in the mixing rate, Even as the fuel and air velocities became equal, significant mixing still occurred because of a large difference in density, Increasing the freestream enthalpy reduced the difference between the initial air temperature and the adiabatic flame temperature, which in turn reduced the heat addition, and subsequently, the amount of pressure rise in the duct.

The effect of unconditional stimulus modality and intensity on blink startle and electrodermal responses

Attentional accounts of blink facilitation during Pavlovian conditioning predict enhanced reflexes if reflex and unconditional stimuli (US) are from the same modality. Emotional accounts emphasize the importance of US intensity. In Experiment 1, we crossed US modality (tone vs, shock) and intensity in a 2 X 2 between-subjects design. US intensity but not US modality affected blink facilitation. Tn Experiment 2, we demonstrated that the results from Experiment 1 were not due to the motor task requirements employed. In Experiment 3, we used a within-subjects design to investigate the effects of US modality and intensity. Contrary to predictions derived from an attentional account, blink facilitation was larger during conditional stimuli that preceded shock than during those that preceded tones. The present results are not consistent with an attentional account of blink facilitation during Pavlovian conditioning in humans.

On the dynamics of mechanical milling in a vibratory mill

The dynamics of mechanical milling in a vibratory mill have been studied by means of mechanical vibration, shock measurements, computer simulation and microstructural evolution measurements. Two distinct modes of ball motion during milling, periodic and chaotic vibration, were observed. Mill operation in the regime of periodic vibration, in which each collision provides a constant energy input to milled powders, enabled a quantitative description of the effect of process parameters on system dynamics. An investigation of the effect of process parameters on microstructural development in an austenitic stainless steel showed that the impact force associated with collision events is an important process parameter for characterizing microstructural evolution. (C) 1997 Elsevier Science S.A.