E-cadherin homophilic ligation directly signals through Rac and phosphatidylinositol 3-kinase to regulate adhesive contacts

Classical cadherins mediate cell recognition and cohesion in many tissues of the body. It is increasingly apparent that dynamic cadherin contacts play key roles during morphogenesis and that a range of cell signals are activated as cells form contacts with one another. It has been difficult, however, to determine whether these signals represent direct downstream consequences of cadherin ligation or are juxtacrine signals that are activated when cadherin adhesion brings cell surfaces together but are not direct downstream targets of cadherin signaling. In this study, we used a functional cadherin ligand (hE/Fc) to directly test whether E-cadherin ligation regulates phosphatidylinositol 3-kinase (PI 3-kinase) and Rac signaling. We report that homophilic cadherin ligation recruits Rae to nascent adhesive contacts and specifically stimulates Rae signaling. Adhesion to hE/Fc also recruits PI 3-kinase to the cadherin complex, leading to the production of phosphatidylinositol 3,4,5-trisphosphate in nascent cadherin contacts. Rae activation involved an early phase, which was PI 3-kinase-independent, and a later amplification phase, which was inhibited by wortmannin. PI 3-kinase and Rae activity were necessary for productive adhesive contacts to form following initial homophilic ligation. We conclude that E-cadherin is a cellular receptor that is activated upon homophilic ligation to signal through PI 3-kinase and Rae. We propose that a key function of these cadherin-activated signals is to control adhesive contacts, probably via regulation of the actin cytoskeleton, which ultimately serves to mediate adhesive cell-cell recognition.

Metformin & lifestyle intervention prevent Type 2 diabetes: lifestyle intervention has the greater effect

Diabetes mellitus is now occurring in epidemic proportions in many countries. Owing to the limited effectiveness of drug prophylaxis of diabetic complications after diabetes has developed, it may be more appropriate to investigate ways to prevent the onset of diabetes. A recent trial published by the Diabetes Prevention Programme Research Group investigated whether lifestyle changes or metformin were effective in delaying the onset of diabetes in subjects with impaired glucose tolerance. The goals of the intensive lifestyle intervention were to achieve and maintain a weight reduction of 7% through a low-calorie, low-fat diet and to engage in physical activity of moderate intensity, such as brisk walking, for at least 150 min/week. The effectiveness of the intensive lifestyle intervention on body weight was initially quite good but decreased over time. Metformin caused some weight loss but to a lesser extent than the intensive lifestyle intervention. Both therapies decreased the fasting plasma glucose levels to a similar extent initially. The intensive lifestyle intervention decreased plasma glycosylated haemoglobin levels to a greater extent than metformin. Both intensive lifestyle intervention and metformin reduced the incidence of diabetes, with the lifestyle intervention having the greater effect.

Transcriptional regulation of the sodium-sulfate cotransporter NaSi-1 gene

Inorganic sulfate is one of the most abundant anions in mammalian plasma and is essential for proper cell growth and development, as well as detoxification and activation of many biological compounds. To date, little is understood how physiological levels of sulfate are maintained in the body. Our studies, and of others, have identified the NAS(i)-1 protein to be a functional sulfate transporter in the kidney and intestine, and due to this localization, constitutes a strong candidate gene for maintaining body sulfate homeostasis. Several factors, including hormones and metabolic conditions, have been shown to alter NAS(i)-1 mRNA and protein levels in vivo. In this study, we describe the transcriptional regulation of NaSi-1, with a focus on the mouse NaSi-1 gene (Nas1) that was recently cloned in our laboratory. Vitamin D (1,25-(OH)(2)D-3) and thyroid hormone (T-3) led to an increase in Nas1 promoter activity in OK cells. Mutational analysis of the Nas1 promoter resulted in identification of a direct repeat 6-type vitamin-D-responsive element (DR6 VDRE) at -525 to -508 and an imperfect inverted repeat 0-type T-3 responsive element (IRO T3RE) at -426 to -425 which conferred 1,25-(OH)(2)D-3 and T-3 responsiveness respectively. These findings suggest for vitamin D and thyroid hormone regulation of NaSi-1, may provide important clues to the physiological control of sulfate homeostasis.

Species richness in agamid lizards: chance, body size, sexual selection or ecology?

Why does species richness vary so greatly across lineages? Traditionally, variation in species richness has been attributed to deterministic processes, although it is equally plausible that it may result from purely stochastic processes. We show that, based on the best available phylogenetic hypothesis, the pattern of cladogenesis among agamid lizards is not consistent with a random model, with some lineages having more species, and others fewer species, than expected by chance. We then use phylogenetic comparative methods to test six types of deterministic explanation for variation in species richness: body size, life history, sexual selection, ecological generalism, range size and latitude. Of eight variables we tested, only sexual size dimorphism and sexual dichromatism predicted species richness. Increases in species richness are associated with increases in sexual dichromatism but reductions in sexual size dimorphism. Consistent with recent comparative studies, we find no evidence that species richness is associated with small body size or high fecundity. Equally, we find no evidence that species richness covaries with ecological generalism, latitude or range size.

Segmenting the market of West Australian senior tourists using an artificial neural network

Measuring perceptions of customers can be a major problem for marketers of tourism and travel services. Much of the problem is to determine which attributes carry most weight in the purchasing decision. Older travellers weigh many travel features before making their travel decisions. This paper presents a descriptive analysis of neural network methodology and provides a research technique that assesses the weighting of different attributes and uses an unsupervised neural network model to describe a consumer-product relationship. The development of this rich class of models was inspired by the neural architecture of the human brain. These models mathematically emulate the neurophysical structure and decision making of the human brain, and, from a statistical perspective, are closely related to generalised linear models. Artificial neural networks or neural networks are, however, nonlinear and do not require the same restrictive assumptions about the relationship between the independent variables and dependent variables. Using neural networks is one way to determine what trade-offs older travellers make as they decide their travel plans. The sample of this study is from a syndicated data source of 200 valid cases from Western Australia. From senior groups, active learner, relaxed family body, careful participants and elementary vacation were identified and discussed. (C) 2003 Published by Elsevier Science Ltd.

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.

Heritability of adult body height: A comparative study of twin cohorts in eight countries

A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men.

Trichostome ciliates from Australian marsupials. III. Megavestibulum gen. nov. (Litostomatea : Macropodiniidae)

A new macropodiniid ciliate genus, Megavestibulum, is described which is endocommensal in the stomach of macropodid marsupials. Two new species, M. morganorum and M. kuhri, are described from Macropus dorsalis and Wallabia, bicolor respectively. Megavestibulum is holotrichous, the somatic ciliation arranged into meridional, curving kineties between broad ridges. The interkinetal ridges are lined apically by thick-walled vacuoles similar to those lining the longitudinal grooves of Macropodinium. The conical vestibulum is apical and very large, occupying up to 1/3 of the cell volume. The vestibular lip appears closable and has a cleft which may allow distention of the vestibullum to ingest large food items. The vestibular ultrastructure is similar to that of Macropodinium including the presence of vestibular vacuoles and the hemispherical differentiation of the distribution of small nematodesmata. Many specimens contained ingested whole ciliates of the genera Amylovorax and Polycosta. The structure of the vestibulum suggests that Megavestibulum is adapted for life as an active predator of other stomach ciliates as well as sweeping in small particulates. The morphology of Megavestibulum suggests that it represents the plesiomorphic body plan within the family Macropodiniidae.

Induction of metallothionein in human skin by routine exposure to sunlight: Evidence for a systemic response and enhanced induction at certain body sites

Expression of metallothionein, an antioxidant induced by a variety of stimuli including ultraviolet light, was quantitated by immunohistochemistry in the skin of males aged over 50 who had known short- and long-term exposures to sunlight. Skin punch biopsies were taken from two sites in each subject: the hand in all subjects and a range of other sites matched to patients with a previously excised primary melanoma. Metallothionein expression (strongest in the basal layers of the epidermis and primarily nuclear) was associated with both short- and long-term exposure to sunlight. A plateau of staining intensity was reached after 3 h sun exposure, within the previous 3 d before biopsy. Expression was also elevated in the nonexposed skin sites of subjects who had recent sun exposure, indicating a systemic response to exposure of remote sites. Using the skin of the hand to normalize responses to chronic exposure between individuals, the systemically modulated response to sunlight was significantly greater on the unexposed back than on other sites. The possibility of ultraviolet-induced cytokines selectively modifying the response of skin on a site-specific basis was investigated. The circulating leukocytes, but not lymphocytes, of two individuals exposed to 1 minimal erythema dose whole-body solar-simulated ultraviolet showed increased interleukin-6 mRNA 4 h after exposure. Interleukin-6 was not directly induced in these cell populations 4 h after ultraviolet A or ultraviolet B irradiation ex vivo . Leukocytes may therefore contribute to and amplify the systemic effects of ultraviolet-induced interleukin-6 and metallothionein expression.

Body proportions in three Nigerian tribes

Prediction equations of body composition based on measurements of whole-body bioelectrical impedance analysis (BIA) have been found to be population-specific. It was hypothesised that this may be, in part, due to differences in proportional limb lengths between ethnic or racial groups. As a preliminary to a survey of body composition in urban Nigerians using BIA, the relative limb lengths of the three major tribal groups (Hausa, Yoruba and Ibo) were determined. We found small (5-9%) but significantly longer limb lengths in Nigerians compared to a Caucasian population, but no significant differences between tribes. This implies that BIA prediction equations generated in a Caucasian population are inappropriate for use in a Nigerian population.