Tumour biology of a breast cancer at least partly reflects the biology of the tissue/epithelial cell of origin at the time of initiation - a hypothesis

A hypothesis is presented suggesting that initiation of breast epithelial cell freezes the cell at least partly according to the development/differention of cell at the time of initiation. Tumour biology will mimic the physiology of normal cell development at the time of initiation and this is preserved at least partly onwards. Also preferentially, tumours will develop from the cell type that is proliferating at the time of initiation. This may explain the overrepresentation of different types of histology in breast cancer in relation to age of the woman. The development of each tumour may follow at least partly a distinct pathway of evolution.     

Effects of sex, body size, temperature, and location on the antipredator tactics of free-ranging gartersnakes (Thamnophis sirtalis, Colubridae)

Gartersnakes (Thamnophis sirtalis parietalis) in southern Manitoba are subject to intense predation (primarily by crows) duringtheir spring breeding season. The huge numbers of snakes providea unique opportunity to quantify behavioral traits. We simulatedpredator attacks by "pecking" more than 500 free-ranging snakes,to explore the determinants of snake response. Snakes respondedto a human finger in the same way as they did to a more realisticstimulus (a model crow). A snake's response to attack dependedon several factors, which interacted in complex ways. The primaryinfluences on response were body temperature (warmer snakes tended to flee, whereas colder snakes remained cryptic or flattenedand/or gaped and struck) and sex (males were more likely toflee). Responses also depended on microhabitat (i.e., insidethe winter den versus in adjacent grassland) and on the snake'sprior activity (e.g., courting snakes often ignored our closeapproach). These factors interacted in significant ways; for example, snakes outside the den were smaller and warmer thanthose inside, male snakes were smaller and warmer than females,and mean body temperatures were higher in larger snakes withineach sex. Thus, a snake's body size and its location affectedits defensive response indirectly (via their influence on bodytemperature). Our results differ from those of previous studiesand suggest that antipredator responses in these animals dependin a flexible and complex way upon biotic and abiotic variables.Interactions among these variables also must be consideredbefore we can identify underlying causal processes.     

Increasing galactose consumption by Saccharomyces cerevisiae through metabolic engineering of the GAL gene regulatory network

Increasing the flux through central carbon metabolism is difficult because of rigidity in regulatory structures, at both the genetic and the enzymatic levels. Here we describe metabolic engineering of a regulatory network to obtain a balanced increase in the activity of all the enzymes in the pathway, and ultimately, increasing metabolic flux through the pathway of interest. By manipulating the GAL gene regulatory network of Saccharomyces cerevisiae, which is a tightly regulated system, we produced prototroph mutant strains, which increased the flux through the galactose utilization pathway by eliminating three known negative regulators of the GAL system: Gal6, Gal80, and Mig1. This led to a 41% increase in flux through the galactose utilization pathway compared with the wild-type strain. This is of significant interest within the field of biotechnology since galactose is present in many industrial media. The improved galactose consumption of the gal mutants did not favor biomass formation, but rather caused excessive respiro-fermentative metabolism, with the ethanol production rate increasing linearly with glycolytic flux.     

Psychometrics of odor quality discrimination: method for threshold determination

There is no natural physical continuum for odor quality along which an odor quality discrimination (OQD) threshold can be measured. In an attempt to overcome this problem, the substitution-reciprocity (SURE) method defines a framework for the measurement of an OQD threshold. More specifically, it (i) defines a threshold concept for OQD, including the quantification of qualitative change of the stimulus, and (ii) suggests how to avoid perceived intensity as an unwanted cue for discrimination. In doing this, the psychometric properties of odor quality in the case of eugenol and citral are investigated using both discrimination (experiment 1) and scaling (experiment 2). Based on discriminatory responses, a change of approximately one-third in stimulus content was needed to reach the OQD threshold for eugenol and citral.     

Cambial-region-specific expression of the Agrobacterium iaa genes in transgenic aspen visualized by a linked uidA reporter gene

The level of indole-3-acetic acid (IAA) was locally modified in cambial tissues of transgenic aspen (Populus tremula L. x Populus tremuloides Michx.). We also demonstrate the use of a linked reporter gene to visualize the expression of the iaa genes. The rate-limiting bacterial IAA-biosynthetic gene iaaM and the reporter gene for beta-glucuronidase (GUS), uidA, were each fused to the cambial-region-specific Agrobacterium rhizogenes rolC promoter and linked on the same T-DNA. In situ hybridization of the iaaM gene confirmed that histochemical analysis of GUS activity could be used to predict iaaM gene expression. Moreover, quantitative fluorometric analysis of GUS activity allowed estimation of the level of de novo production of IAA in transgenic lines carrying a single-copy insert of the iaaM, uidA T-DNA. Microscale analysis of the IAA concentration across the cambial region tissues showed an increase in IAA concentration of about 35% to 40% in the two transgenic lines, but no changes in the radial distribution pattern of IAA compared with wild-type plants. This increase did not result in any changes in the developmental pattern of cambial derivatives or the cambial growth rate, which emphasizes the importance of the radial distribution pattern of IAA in controlling the development of secondary xylem, and suggests that a moderate increase in IAA concentration does not necessarily stimulate growth.     

Neuronal expression of the ERM-like protein MIR in rat brain and its localization to human chromosome 6

The ERM proteins, ezrin, radixin, and moesin, regulate cell motility by linking cortical F-actin to the plasma membrane in different cell types. Myosin regulatory light chain interacting protein (MIR) is a recently cloned ERM-like protein which was shown to be involved in neurite outgrowth. Here we have studied the occurrence and expression of MIR in rats during brain development. As shown using Western blotting, MIR is present in different regions both in developing and adult brain. Immunohistochemistry and double labelling studies showed that MIR is localized especially to neurons in hippocampus and cerebellum. A search using the gene bank showed that the MIR gene localised to human chromosome 6 in the interval 6p22.3-23, the loss of which is characterized by mental retardation and different malformations in man. The presence of MIR in brain neurons during development together with its known effects on neurite outgrowth suggest an important function of the protein in the regulation of nerve cell motility and cytoskeletal interactions.     

Optimal Bayesian foraging policies and prey population dynamics-some comments on Rodriguez-Girones and Vasquez

In this paper we show the density-dependent harvest rates of optimal Bayesian foragers exploiting prey occurring with clumped spatial distribution. Rodríguez-Gironés and Vásquez (1997) recently treated the issue, but they used a patch-leaving rule (current value assessment rule) that is not optimal for the case described here. An optimal Bayesian forager exploiting prey whose distribution follows the negative binomial distribution should leave a patch when the potential (and not instantaneous) gain rate in that patch equals the best long-term gain rate in the environment (potential value assessment rule). It follows that the instantaneous gain rate at which the patches are abandoned is an increasing function of the time spent searching in the patch. It also follows that the proportion of prey harvested in a patch is an increasing sigmoidal function of the number of prey initially present. In this paper we vary several parameters of the model to evaluate the effects on the forager's intake rate, the proportion of prey harvested per patch, and the prey's average mortality rate in the environment. In each case, we study an intake rate maximizing forager's optimal response to the parameter changes. For the potential value assessment rule we find that at a higher average prey density in the environment, a lower proportion of the prey is taken in a patch with a given initial prey density. The proportion of prey taken in a patch of a given prey density also decreases when the variance of the prey density distribution is increased and if the travel time between patches is reduced. We also evaluate the effect of using predation minimization, rather than rate maximization, as the currency. Then a higher proportion of the prey is taken for each given initial prey density. This is related to the assumption that traveling between patches is the most risky activity. Compared to the optimal potential value assessment rule, the current value assessment rule performs worse, in terms of long-term intake rate achieved. The difference in performance is amplified when prey density is high or highly aggregated. These results pertain to the foraging patch spatial scale and may have consequences for the spatial distribution of prey in the environment.     

The role of metabolic engineering in the improvement of Saccharomyces cerevisiae: utilization of industrial media

Metabolic engineering has become a very important approach to strain improvement in parallel with classical strain development. Although Saccharomyces cerevisiae has been domesticated for ethanol and bread production, there are still some fundamental problems associated with its industrial use. The industrially used carbon sources often consist of a sugar mixture, and due to glucose repression these sugars are utilized sequentially, resulting in prolonged production time. In this article we discuss the application of metabolic engineering for construction of glucose-derepressed strains and specify advantages as well as difficulties associated with this approach.     

A Phosphothreonine Residue at the C-Terminal End of the Plasma Membrane H+-ATPase Is Protected by Fusicoccin-Induced 14–3–3 Binding

We have isolated the plasma membrane H⁺−ATPase in a phosphorylated form from spinach (Spinacia oleracea L.) leaf tissue incubated with fusicoccin, a fungal toxin that induces irreversible binding of 14–3–3 protein to the C terminus of the H⁺-ATPase, thus activating H⁺ pumping. We have identified threonine-948, the second residue from the C-terminal end of the H⁺-ATPase, as the phosphorylated amino acid. Turnover of the phosphate group of phosphothreonine-948 was inhibited by 14–3–3 binding, suggesting that this residue may form part of a binding motif for 14–3–3. This is the first identification to our knowledge of an in vivo phosphorylation site in the plant plasma membrane H⁺-ATPase.     

Growth of arbuscular mycorrhizal mycelium in calcareous dune sand and its interaction with other soil microorganisms as estimated by measurement of specific fatty acids

Fatty acid analysis was used for determining the extent of the development of the external mycelium of AM fungi (mixed inoculum from a sand dune) growing from roots of Festuca rubra and Plantago lanceolata in calcareous dune sand. The plants were raised in chambers specially designed to permit the growth of AM mycelium in root-free compartments. In two separate experiments, growth of external mycelium in the root-free compartments was detected and the amount of mycelium was estimated using the indicator of AM fungal biomass, phospholipid fatty acid (PLFA) 16:15. The results showed that the PLFA 16:15 was suitable for estimating the mycelium emerging from the mixed inoculum obtained from the field roots of F. rubra and P. lanceolata.The PLFA 16:15 showed external mycelium to become established in the root-free compartments within a period of 3 weeks and the amount of mycelium to continue to increase at 6 and 9 weeks. Increases in neutral lipid fatty acid (NLFA) 16:15 (indicator of storage lipids) over time were inconsistent between the two experiments, but appeared to follow patterns of sporulation in each experiment.In both experiments, the root-free compartment was colonised by saprophytic fungi to a greater extent in the case of non-mycorrhizal than of AM treatment, as indicated by an increase in PLFA 18:26,9 (indicator of saprophytic fungi). The absence of an increase in the case of AM treatment indicates that AM fungal mycelium can negatively affect the growth of saprophytic fungi in this soil type. This result was, however, only weakly supported by measurements of ergosterol content. The analysis of bacteria specific PLFAs showed that bacterial biomass was not affected by the AM mycelium.