Ciba Foundation symposium最新文献

Tuftelin is a novel acidic enamel protein thought to play a major role in enamel mineralization. Its identity and localization has been confirmed by amino acid composition, enzyme-linked immunosorbant assay, Western blots, indirect immunohistochemistry and high resolution protein-A gold immunocytochemistry. The deduced tuftelin protein (pI 5.2) contains 389 amino acids and has a calculated peptide molecular mass of 43,814 Da. Immunological studies suggest conservation of tuftelin structure between species throughout vertebrate evolution. The cDNA sequence encodes for several putative post-translation sites including one N-glycosylation consensus site, seven O-glycosylation sites and seven phosphorylation sites, as well as an EF-hand calcium-binding domain (with mismatch), localized towards the N-terminal region. At the C-terminal region (residues 252-345) tuftelin contains structurally relevant determinants for self assembly. We recently cloned and partially sequenced the human tuftelin gene (four exons have now been sequenced). These sequences include exon 1 and over 1000 bases of the putative promoter region. Employing fluorescent in situ hybridization, we mapped the human tuftelin gene to chromosome 1q 21-31. Localization of the human tuftelin gene to a well-defined cytogenetic region may be important in understanding the aetiology of autosomally inherited amelogenesis imperfecta, the most common enamel hereditary disease.

The biochemistry and genetics of antibiotic resistance are far better known than the equally important events underlying the selection of resistant populations. The hidden selection of low-level resistant variants may be a key process in the emergence of high-level antibiotic resistance. Different low-level resistant bacterial subpopulations may be specifically selected by different low antibiotic concentrations. The space in the environment (human body) where a given selective concentration exists represents the selective compartment. For pharmacokinetic reasons, low antibiotic concentrations occur in a larger selective compartment and persist longer than high antibiotic concentrations. The specific selection of low-level variants by low concentrations of antibiotic can be reproduced in experimental in vitro models using mixtures of susceptible and low-level resistant populations. We demonstrated this in Escherichia coli strains harbouring TEM-1, TEM-12 and TEM-10 beta-lactamases challenged by cefotaxime, and also Streptococcus pneumoniae strains with various levels of penicillin resistance challenged by amoxicillin or cefotaxime. In both cases, four hours of antibiotic challenge produced selective peaks of low-level resistant variant populations at low-level antibiotic concentrations. We conclude that variants with small decreases in antibiotic susceptibility may be fully selectable under in vivo circumstances; on the other hand, low-level antibiotic concentrations may have a considerable selective effect on the emergence of antibiotic resistance.

Animal information processing and decision making are often considered to be adaptations that allow individuals to behave optimally under particular ecological conditions. Numerous examples demonstrate how cues from the biotic and abiotic environments affect the ways in which animals process information and make decisions. Information gained from interactions with living organisms is the most complex because individuals have to respond to heterospecifics or conspecifics which may decide on what to do depending on the behaviour of a focal individual. Evolutionary conflicts of interest include: (i) interactions between hosts and parasites, predators and prey, and between competitors; (ii) sperm competition interactions between females, male mates and male non-mates, and (iii) interactions between mate-searching females and their potential mates. Brains may evolve particularly rapidly under the influence of evolutionary conflicts and they may enhance the importance of adapted psychologies in these contexts.

Precision agriculture is based on the concept of soil-specific management, which aims to adapt management within a field according to specific site conditions in order to maximize production and minimize environmental damage. This paper examines how the nature and sources of variation in soil moisture regimes affect our ability to simulate soil water behaviour within a field with adequate precision in order to advise optimal soil-specific management. Field examples of variation in soil moisture regimes are described to illustrate the difficulties involved. A discussion identifies three main points. First, it is recognized that the current modelling approaches to soil moisture regimes do not sufficiently account for local heterogeneities in soil and crop characteristics such as soil morphology and rooting patterns. Second, the estimation of within-field variation of soil hydraulic properties is difficult because of large short-range variation of the properties and general lack of observed data; one way to overcome this problem is to seek new measurement techniques or to find easy-to-measure auxiliary variables spatially correlated to the variables of interest. Last, as pollution impacts often become noticeable to society at scales larger than the scale of agricultural management, hydrological modelling can serve for linking both scales and advising agricultural practices that minimize undesirable pollution effects.

Accurate interpolation of soil and climate variables at fine spatial scales is necessary for precise field management. Interpolation is needed to produce the input variables necessary for crop modelling. It is also important when deciding on regulations to limit environmental impacts from processes such as nitrate leaching. Non-stationarity may arise due to many factors, including differences in soil type, or heterogeneity in chemical concentrations. Many geostatistical methods make stationarity assumptions. Substantial improvements in interpolation or in the estimation of standard errors may be obtained by using non-stationary models of spatial covariances. This paper presents recent methodological developments for an approach to modelling non-stationary spatial covariance structure through deformations of the geographic coordinate system. This approach was first introduced by Sampson & Guttorp, although the estimation approach is updated in more recent papers. They compute a deformation of the geographic plane so that the spatial covariance structure can be considered stationary in terms of a new spatial coordinate system. This provides a non-stationary model for the spatial covariances between sampled locations and prediction locations. In this paper, we present a cross-validation procedure to avoid over-fitting of the sample dispersions. Results concerning the variability of the spatial covariance estimates are also presented. An example of the modelling of the spatial correlation field of rainfall at small regional scale is presented. Other directions in methodological development, including modelling temporally varying spatial correlation, and approaches to model temporal and spatial correlation are mentioned. Future directions for methodological development are indicated, including the modelling of multivariate processes and the use of external spatially dense covariables. Such covariates are frequently available in precision agriculture.

Application of the theories of precision agriculture to the practicalities of broad-acre farming relies on successful handling of the ramifications of uncertainty in information, i.e. information pertaining to the spatial and temporal variation of those factors which determine yield components and/or environmental losses. This paper discusses the uncertainty of yield and related variables as measured by their spatial and temporal variance. The magnitude of these two components gives a suggestion as to the appropriate scale of management. Simultaneous reporting on spatial and temporal variation is rare and the theory of these types of process is still in its infancy. Some brief theory is presented, followed by several examples from the Rothamsted classic experiments, yield-monitoring experiments in Australia, a long-term barley trial in Denmark, and a soil moisture monitoring network. It is clear that annual temporal variation is much larger than the spatial variation within single fields. This leads to the conclusion that if precision agriculture is to have a sound scientific basis and ultimately a practical outcome then the null hypothesis that still remains to be seriously researched is: 'given the large temporal variation in yields relative to the scale of a single field, then the optimal risk aversion strategy is uniform management.'

The apatitic calcium phosphate crystals in dental enamel are too small for single crystal diffraction studies so the only possible direct structure determination must use whole-pattern-fitting Rietveld analysis of X-ray and neutron powder diffraction patterns. As a result, aspects of the structure are not known in detail. Further structural information can be obtained by consideration of published chemical analyses and infrared studies, taking into account studies of the crystal chemistry of synthetic apatitic analogues of enamel apatite. The apatitic constitutional water and total water content of enamel are particularly important, but there are difficulties in their determination. Making reasonable assumptions, a number of models of the unit cell can be derived. The weight per cent (including constitutional water) and density of the enamel apatite crystals for the most probable model are about 98 wt.% and 3.0 g cm-3, respectively. The apatite volume per cent calculated from these values is about 96%. The weight per cent and volume per cent of enamel apatite are higher than normally accepted values because of inclusion of constitutional water and use of a density for enamel apatite that takes into account its known lattice expansion over hydroxyapatite and probable lattice vacancies.

Methicillin-resistant Staphylococcus aureus (MRSA) is an intractable nosocomial pathogen. The chemotherapeutic intransigence of this organism stems from its predilection to antimicrobial resistance as a consequential response to selective pressures prevailing in the clinical environment. MRSA isolates are frequently resistant to all practicable antimicrobials except the glycopeptide, vancomycin. Although antimicrobial resistance sometimes arises via chromosomal mutation, the emergence of multiply-antibiotic-resistant staphylococci is primarily due to the acquisition of pre-existent resistance genes; such determinants can be encoded chromosomally or by plasmids and are often associated with transposons or insertion sequences. Clinical staphylococci commonly carry one or more plasmids, ranging from small replicons that are phenotypically cryptic or contain only a single resistance gene, to larger episomes that possess several such determinants and sometimes additionally encode systems that mediate their own conjugative transmission and the mobilization of other plasmids. The detection of closely related plasmids, elements and/or genes in other hosts, including coagulase-negative staphylococci and enterococci, attests to interspecific and intergeneric genetic exchange facilitated by mobile genetic elements and DNA transfer mechanisms. The extended genetic reservoir accessible to staphylococci afforded by such horizontal gene flux is fundamental to the acquisition, maintenance and dissemination of staphylococcal antimicrobial resistance in general, and multiresistance in particular.

The T cell hypothesis of asthma, particularly chronic asthma, is based around the concept that the disease is driven and maintained by the persistence of a specialized subset of chronically activated T memory cells sensitized against an array of allergenic, occupational or viral antigens which home to the lung after appropriate antigen exposure or viral infection. Allergens induce a CD4+ T helper (Th) cell response, whereas viruses recognize CD8+ T cytotoxic (Tc) cells. In the asthmatic airway there appears to be both CD4+ and CD8+ cells with a type 2 cytokine phenotype (i.e. Th2 and Tc2 type). These cells produce: interleukin (IL)-5, IL-3 and granulocyte macrophage colony-stimulating factor, which recruit, mobilize and activate eosinophils for subsequent mucosal tissue damage; and IL-4, an essential co-factor for local or generalized IgE production. This in turn leads to eosinophilic desquamative bronchitis, with epithelial shedding, mucus hypersecretion and bronchial smooth muscle contraction. Thus, although the eosinophil is largely responsible for airway symptoms, its function appears to be under T cell control. Support for this hypothesis includes: the observations that activated T cells and their products can be identified in biopsies from the major variants of the disease (atopic, nonatopic [intrinsic] and occupational asthma); the co-localization of mRNA for type 2 cytokines to CD4+ and CD8+ cells in atopic and non-atopic asthma; the presence of chronically activated cytokine-producing T cells in corticosteroid-resistant asthma; the association of disease severity with type 2 cytokines, especially IL-5; and the efficacy of cyclosporin A in chronic steroid-dependent disease. Inhibitors and/or antagonists directed against more precise T cell-associated molecular targets hold promise for the future treatment of chronic asthma.