Peroxisome proliferator-activated receptor alpha in the human breast cancer cell lines MCF-7 and MDA-MB-231

Peroxisome proliferator-activated receptor (PPAR) alpha is a ligand-activated transcription factor that has been linked with rodent hepatocarcinogenesis. It has been suggested that PPARalpha mRNA expression levels are an important determinant of rodent hepatic tumorigenicity. Previous work in rat mammary gland epithelial cells showed significantly increased PPARalpha mRNA expression in carcinomas, suggesting the possible role of this isoform in rodent mammary gland carcinogenesis. In this study we sought to determine whether PPARalpha is expressed and dynamically regulated in human breast cancer MCF-7 and MDA-MB-231 cells. Having established the presence of PPARalpha in both cell types, we then examined the consequence of PPARa activation, by its ligands Wy-14,643 and clofibrate, on proliferation. With real-time reverse transcriptase-polymerase chain reaction, we showed that PPARalpha mRNA was dynamically regulated in MDA-MB-231 cells and that PPARalpha activation significantly increased proliferation of the cell line. In contrast, PPARalpha expression in MCF-7 cells did not change with proliferation during culture and was present at significantly lower levels than in MDA-MB-231 cells. However, PPARalpha ligand activation still significantly increased the proliferation of MCF-7 cells. The promotion of proliferation in breast cancer cell lines following PPARalpha activation was in stark contrast to the effects of PPARgamma-activating ligands that decrease proliferation in human breast cancer cells. our results established the presence of PPARalpha in human breast cancer cell lines and showed for the first time that activation of PPARalpha in human breast cancer cells promoted proliferation. Hence, this pathway may be significant in mammary gland tumorigenesis. (C) 2002 Wiley-Liss, Inc.

Adjustment to chronic obstructive pulmonary disease: the importance of psychological factors

Research has indicated a weak relationship between the degree of physical problems and quality of life in patients with chronic obstructive pulmonary disease (COPD). The importance of adaptive psychological functioning to maintain optimum quality of life has long been recognized, but there is a lack of empirical evidence concerning the nature of psychological factors involved in adjustment to COPD. Ninety-two males completed questionnaires to determine their coping strategies, levels of self-efficacy of symptom management and social support. Adjustment was measured in terms of depression, anxiety and quality of life. Symptom severity, socioeconomic status, duration of disease and age, which have been demonstrated to be of consequence in COPD, were used as control variables in hierarchical multiple regression analyses. Higher levels of catastrophic withdrawal coping strategies and lower levels of self-efficacy of symptom management were associated with higher levels of depression, anxiety and a reduced quality of life. Higher levels of positive social support were linked to lower levels of depression and anxiety, while higher levels of negative social support were linked to higher levels of depression and anxiety. To maximize quality of life in patients with chronic obstructive pulmonary disease, psychological factors need to be carefully assessed and addressed.

Yield response of rice (Oryza sativa L.) genotypes to different types of drought under rainfed lowlands - Part 2. Selection of drought resistant genotypes

Drought frequently reduces grain yield of rainfed lowland rice. A series of experiments were conducted in drought-prone northeast Thailand to study the magnitude and consistency of yield responses of diverse, rainfed lowland rice genotypes to drought stress environments and to examine ways to identify genotypes that confer drought resistance. One hundred and twenty-eight genotypes were grown under non-stress and four different types of drought stress conditions. The relationship of genotypic variation in yield under drought conditions to genetic yield potential, flowering time and flowering delay, and to a drought response index (DRI) that removed the effect of potential yield and flowering time on yield under stress was examined. Drought stress that developed prior to flowering generally delayed the time of flowering of genotypes, and the delay in flowering was negatively associated with grain yield, fertile panicle percentage and filled grain percentage. Genotypes with a longer delay in flowering time had extracted more water during the early drought period, and as a consequence, had higher water deficits. They were consistently associated with a larger yield reduction under drought and in one experiment with a smaller DRI. Genotypes, however, responded differently to the different drought stress conditions and there was no consistency in the DRI estimates for the different genotypes across the drought stress experiments. The results indicate that with the use of irrigated-control and drought test environments, genotypes with drought resistance can be identified by using DRI or delay in flowering. However, selections will differ depending on the type of drought condition. The inconsistency of the estimates in DRI and flowering delay across different drought conditions reflects the nature of the large genotype-by-environment interactions observed for grain yield under various types of drought in rainfed lowland conditions. (C), 2002 Elsevier Science B.V. All rights reserved.

Predicting plant leaf area production: shoot assimilate accumulation and partitioning, and leaf area ratio, are stable for a wide range of sorghum population densities

Predicting plant leaf area production is required for modelling carbon balance and tiller dynamics in plant canopies. Plant leaf area production can be studied using a framework based on radiation intercepted, radiation use efficiency (RUE) and leaf area ratio (LAR) (ratio of leaf area to net above-ground biomass). The objective of this study was to test this framework for predicting leaf area production of sorghum during vegetative development by examining the stability of the contributing components over a large range of plant density. Four densities, varying from 2 to 16 plants m(-2), were implemented in a field experiment. Plants were either allowed to tiller or were maintained as uniculm by systematic tiller removal. In all cases, intercepted radiation was recorded daily and leaf area and shoot dry matter partitioning were quantified weekly at individual culm level. Up to anthesis, a unique relationship applied between fraction of intercepted radiation and leaf area index, and between shoot dry weight accumulation and amount of intercepted radiation, regardless of plant density. Partitioning of shoot assimilate between leaf, stem and head was also common across treatments up to anthesis, at both plant and culm levels. The relationship with thermal time (TT) from emergence of specific leaf area (SLA) and LAR of tillering plants did not change with plant density. In contrast, SLA of uniculm plants was appreciably lower under low-density conditions at any given TT from emergence. This was interpreted as a consequence of assimilate surplus arising from the inability of the plant to compensate by increasing the leaf area a culm could produce. It is argued that the stability of the extinction coefficient, RUE and plant LAR of tillering plants observed in these conditions provides a reliable way to predict leaf area production regardless of plant density. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

Gene complementation of airway epithelium in the cystic fibrosis mouse is necessary and sufficient to correct the pathogen clearance and inflammatory abnormalities

Increasingly, cystic fibrosis (CF) is regarded as an inflammatory disorder where the response of the lung to Pseudomonas aeruginosa is exaggerated as a consequence of processes mediated by the product of the CF gene, CFTR. Of importance to any gene-replacement strategy for treatment of CF is the identification of the cell type(s) within the lung milieu that need to be corrected and an indication whether this is sufficient to restore a normal inflammatory response and bacterial clearance. We generated G551D CF mice transgenically expressing the human CFTR gene in two tissue compartments previously demonstrated to mediate a CFTR-dependent inflammatory response: lung epithelium and alveolar macrophages. Following chronic pulmonary infection with P. aeruginosa, CF mice with epithelial-expressed but not macrophage-specific CFTR showed an improvement in pathogen clearance and inflammatory markers compared with control CF animals. Additionally, these data indicate the general role for epithelial cell-mediated events in the response of the lung to bacterial pathogens and the importance of CFTR in mediating these processes.

Adaptation of rainbow fish to lake and stream habitats

Fish occupy a range of hydrological habitats that exert different demands on locomotor performance. We examined replicate natural populations of the rainbow fishes Melanotaenia eachamensis and M. duboulayi to determine if colonization of low-velocity (lake) habitats by fish from high-velocity (stream) habitats resulted in adaptation of locomotor morphology and performance. Relative to stream conspecifics, lake fish had more posteriorly positioned first dorsal and pelvic fins, and shorter second dorsal fin bases. Habitat dimorphism observed between wild-caught fish was determined to be heritable as it was retained in M. eachamensis offspring raised in a common garden. Repeated evolution of the same heritable phenotype in independently derived populations indicated body shape divergence was a consequence of natural selection. Morphological divergence between hydrological habitats did not support a priori expectations of deeper bodies and caudal peduncles in lake fish. However, observed divergence in fin positioning was consistent with a family-wide association between habitat and morphology, and with empirical studies on other fish species. As predicted, decreased demand for sustained swimming in takes resulted in a reduction in caudal red muscle area of lake fish relative to their stream counterparts. Melanotaenia duboulayi lake fish also had slower sustained swimming speeds (U-crit) than stream conspecifics. In M. eachamensis, habitat affected U-crit of males and females differently. Specifically, females exhibited the pattern observed in M. duboulayi (lake fish had faster U-crit than stream fish), but the opposite association was observed in males (stream males had slower Ucrit than lake males). Stream M. eachamensis also exhibited a reversed pattern of sexual dimorphism in U-crit (males slower than females) relative to all other groups (males faster than females). We suggest that M. eachamensis males from streams responded to factors other than water velocity. Although replication of muscle and U,,it phenotypes across same habitat populations within and/or among species was suggestive of adaptation, the common garden experiment did not confirm a genetic basis to these associations. Kinematic studies should consider the effect of the position and base length of dorsal fins.

Genetic constraints on the evolution of mate recognition under natural selection

Field populations of Drosophila serrata display reproductive character displacement in cuticular hydrocarbons (CHCs) when sympatric with Drosophila birchii. We have previously shown that the naturally occurring pattern of reproductive character displacement can be experimentally replicated by exposing field allopatric populations of D. serrata to experimental sympatry with D. birchii. Here, we tested whether the repeated evolution of reproductive character displacement in natural and experimental populations was a consequence of genetic constraints on the evolution of CHCs. The genetic variance-covariance (G) matrices for CHCs were determined for populations of D. serrata that had evolved in either the presence or absence of D. birchii under field and experimental conditions. Natural selection on mate recognition under both field and experimental sympatric conditions increased the genetic variance in CHCs consistent with a response to selection based on rare alleles. A close association between G eigenstructure and the eigenstructure of the phenotypic divergence (D) matrix in natural and experimental populations suggested that G matrix eigenstructure may have determined the direction in which reproductive character displacement evolved during the reinforcement of mate recognition.

Dysarthria and dysphagia following treatment for a fourth ventricle choroid plexus papilloma

The present case report describes the presence of a persistent dysarthria and dysphagia as a consequence of surgical intervention for a choroid plexus papilloma (CPP). WM was a nine year ten month old male who at the time of the present study was seven years post-surgery. A comprehensive perceptual and instrumental test battery was used to document the nature of the dysarthria incorporating all components of speech production including respiration, phonation, resonance, articulation, and prosody. The nature of the dysphagia was evaluated through the use of videofluoroscopic evaluation of swallowing (VFS). Assessments confirmed the presence of a LMN dysarthria, marked by deficits in phonation, respiration, and prosody. Dysphagia assessment revealed deficits in oral preparatory, oral and pharyngeal stages of the swallow. The presence of persistent dysarthria and dysphagia in this case has a number of important implications for the management of children undergoing surgery for fourth ventricle CPPs, in particular the need for appropriate treatment, as well as counselling prior to surgery of the possible negative outcomes related to speech and swallowing. (C) 2003 Elsevier Science Ltd. All rights reserved.

Thermodynamic non-ideality as an alternative source of the effect of sucrose on the thrombin-catalyzed hydrolysis of peptide p-nitroanalide substrates

The inhibitory effect of sucrose on the kinetics of thrombin-catalyzed hydrolysis of the chromogenic substrate S-2238 (D-phenylalanyl-pipecolyl-arginoyl-p-nitroanilide) is re-examined as a possible consequence of thermodynamic non-ideality-an inhibition originally attributed to the increased viscosity of reaction mixtures. However, those published results may also be rationalized in terms of the suppression of a substrate-induced isomerization of thrombin to a slightly more expanded (or more asymmetric) transition state prior to the irreversible kinetic steps that lead to substrate hydrolysis. This reinterpretation of the kinetic results solely in terms of molecular crowding does not signify the lack of an effect of viscosity on any reaction step(s) subject to diffusion control. Instead, it highlights the need for development of analytical procedures that can accommodate the concomitant operation of thermodynamic non-ideality and viscosity effects.

Skolem-type difference sets for cycle systems

Cyclic m-cycle systems of order v are constructed for all m greater than or equal to 3, and all v = 1(mod 2m). This result has been settled previously by several authors. In this paper, we provide a different solution, as a consequence of a more general result, which handles all cases using similar methods and which also allows us to prove necessary and sufficient conditions for the existence of a cyclic m-cycle system of K-v - F for all m greater than or equal to 3, and all v = 2(mod 2m).

Electrolytic properties and nanostructural features in the La2O3-CeO2 system

Doped ceria (CeO2) compounds are fluorite-type oxides which show oxide ionic conductivity higher than yttria-stabilized zirconia in oxidizing atmosphere. As a consequence of this, considerable interest has been shown in applications of these materials for low or intermediate temperature operation of solid-oxide fuel cells (SOFCs). In this study, the effective index was suggested to maximize the ionic conductivity in La2O3-CeO2 based oxides. The index considers the fluorite structure, and combines the expected oxygen vacancy level with the ionic radius mismatch between host and dopant cations. Using this approach, the ionic conductivity of this system has been optimized and tested under operating conditions of SOFCs. LaxCe1-xO2-delta (x = 0.125, 0.15, 0.175, and 0.20), (LaxSr1-x)(0.175)Ce0.825O2-delta (x = 0.1, 0.2, and 0.4), and (La1-xSr0.2Bax)(0.175)Ce0.825O2-delta (x 5 0.03, 0.05, and 0.07) were prepared and characterized as the specimens with low, intermediate, and high index, respectively. The ionic conductivity was increased with increasing suggested index. The transmission electron microscopy analysis suggested that partial substitution of alkaline earth elements in place of La into Ce site contributes to a decrease of microdomain size and an improvement of conductivity. (La0.75Sr0.2Ba0.05)(0.175)Ce0.825O1.891 with high index and small microdomains exhibited the highest conductivity, wide ionic domain, and good performance in SOFCs. (C) 2003 The Electrochemical Society.

Asymmetric blasting: a rock mass dependent blast design method

Blasting has been the most frequently used method for rock breakage since black powder was first used to fragment rocks, more than two hundred years ago. This paper is an attempt to reassess standard design techniques used in blasting by providing an alternative approach to blast design. The new approach has been termed asymmetric blasting. Based on providing real time rock recognition through the capacity of measurement while drilling (MWD) techniques, asymmetric blasting is an approach to deal with rock properties as they occur in nature, i.e., randomly and asymmetrically spatially distributed. It is well accepted that performance of basic mining operations, such as excavation and crushing rely on a broken rock mass which has been pre conditioned by the blast. By pre-conditioned we mean well fragmented, sufficiently loose and with adequate muckpile profile. These muckpile characteristics affect loading and hauling [1]. The influence of blasting does not end there. Under the Mine to Mill paradigm, blasting has a significant leverage on downstream operations such as crushing and milling. There is a body of evidence that blasting affects mineral liberation [2]. Thus, the importance of blasting has increased from simply fragmenting and loosing the rock mass, to a broader role that encompasses many aspects of mining, which affects the cost of the end product. A new approach is proposed in this paper which facilitates this trend 'to treat non-homogeneous media (rock mass) in a non-homogeneous manner (an asymmetrical pattern) in order to achieve an optimal result (in terms of muckpile size distribution).' It is postulated there are no logical reasons (besides the current lack of means to infer rock mass properties in the blind zones of the bench and onsite precedents) for drilling a regular blast pattern over a rock mass that is inherently heterogeneous. Real and theoretical examples of such a method are presented.

Stability of planar flames as gasdynamic discontinuities

The stability of a steadily propagating planar premixed flame has been the subject of numerous studies since Darrieus and Landau showed that in their model flames are unstable to perturbations of any wavelength. Moreover, the instability was shown to persist even for very small wavelengths, i.e. there was no high-wavenumber cutoff of the instability. In addition to the Darrieus-Landau instability, which results from thermal expansion, analysis of the diffusional thermal model indicates that premixed flames may exhibit cellular and pulsating instabilities as a consequence of preferential diffusion. However, no previous theory captured all the instabilities including a high-wavenumber cutoff for each. In Class, Matkowsky & Klimenko (2003) a unified theory is proposed which, in appropriate limits and under appropriate assumptions, recovers all the relevant previous theories. It also includes additional new terms, not present in previous theories. In the present paper we consider the stability of a uniformly propagating planar flame as a solution of the unified model. The results are then compared to those based on the models of Darrieus-Landau, Sivashinsky and Matalon-Matkowsky. In particular, it is shown that the unified model is the only model to capture the Darrieus-Landau, cellular and pulsating instabilities including a high-wavenumber cutoff for each.

Diagnostic and management protocols for equine Cushing's syndrome

Equine Cushing's syndrome is a common problem in aged horses and ponies. It presents with a variable combination of clinical signs; hirsutism is characteristic of the disease, with laminitis frequently being the most devastating consequence. This article describes the diagnostic protocols available and, in view of the fact that complete resolution of the disease is not achievable, discusses how the condition might be managed appropriately to improve the quality of life of affected animals.

IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

Priming to Ag can inhibit subsequent induction of an immune response to a new epitope incorporated into that Ag, a phenomenon referred to as original antigenic sin. In this study, we show that prior immunity to a virus capsid can inhibit subsequent induction of the IFN-gamma effector T cell response to a novel CD8-restricted antigenic epitope associated with the virus capsid. Inhibition does not involve Ab to the virus capsid, as it is observed in animals lacking B cells. CD8-restricted virus-specific T cell responses are not required, as printing to virus without CTL induction is associated with inhibition. However, IL-10(-/-) mice, in contrast to IL-10(+/+) mice, generate CD8 T cell and Ab responses to novel epitopes incorporated into a virus capsid, even when priming to the capsid has resulted in high titer Ab to the capsid. Furthermore, capsid-primed mice, unable to mount a response to a novel epitope in the capsid protein, are nevertheless able to respond to the same novel epitope delivered independently of the capsid. Thus, inhibition of responsiveness to a novel epitope in a virus-primed animal is a consequence of secretion of IL-10 in response to presented Ag, which inhibits local generation of new CD8 IFN-gamma-secreting effector T cells. Induction of virus- or tumor Ag-specific CD8 effector T cells in the partially Ag-primed host may thus be facilitated by local neutralization of IL-10.