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Crystallization of the oxygen-evolving reaction centre of photosystem II in nine different detergent mixtures.

Oxygen-evolving photosystem II reaction centres (RCII) isolated from both spinach and pea have been crystallized. A single crystal form grew from RCII monomers in the presence of nine different three-component mixtures of non-ionic detergents and heptane-1,2, 3-triol. The crystals grew as hexagonal rods with dimensions of up to 1 x 0.3 x 0.3 mm. The crystals diffracted to a maximum resolution of 6.5 A and belong to a hexagonal space group with unit-cell parameters a = 495, b = 495, c = 115 A, alpha = beta = 90, gamma = 120 degrees. The growth of a single crystal form in the presence of such a large variety of detergents suggests a very limited range of crystal lattice formation sites in the RCII complex.

Crystallization↗

HyperOncology: demonstration of an evolving comprehensive hypermedia-based workstation for the radiation oncologist.

HyperOncology is a prototype hypermedia-based workstation designed for the practicing radiation oncologist. Individual patient records consist of linked demographic, clinical history, presentation, staging, course, laboratory and treatment data. Searching and sorting capabilities, navigational aids, information printing and archiving, plotting capability, and graphics and updating tools are available. Upon integration with an evolving knowledge base, HyperOncology will eventually become a comprehensive clinical database and information retrieval system in the specialty of radiation oncology.

Information Storage and Retrieval↗

Healthcare technology, economics, and policy: an evolving balance.

Economic and policy issues increasingly influence healthcare technology solutions as we wrestle with keeping healthcare quality high while keeping costs under control. The healthcare system is also undergoing rapid change brought about by managed care, shifting care to team providers in an outpatient or home environment. The development of health technologies under new market arrangements needs to be examined so that quality of care and cost are not at cross roads. As these issues continue to evolve in the public forum, it is critical for engineers and contributors to technology in healthcare to understand the dynamics that influence technology need and and adoption in the healthcare market. We hope that this special issue will provide a basis for initial understanding of these issues and stimulate further involvement by the bioengineering community at large, for the improvement of healthcare across all of society.

Biomedical Engineering↗

Evolvable social agents for bacterial systems modeling.

We present two approaches to the individual-based modeling (IbM) of bacterial ecologies and evolution using computational tools. The IbM approach is introduced, and its important complementary role to biosystems modeling is discussed. A fine-grained model of bacterial evolution is then presented that is based on networks of interactivity between computational objects representing genes and proteins. This is followed by a coarser grained agent-based model, which is designed to explore the evolvability of adaptive behavioral strategies in artificial bacteria represented by learning classifier systems. The structure and implementation of the two proposed individual-based bacterial models are discussed, and some results from simulation experiments are presented, illustrating their adaptive properties.

Adaptation, Physiological↗

The Evolving Tree--analysis and applications.

In this paper, we enhance and analyze the Evolving Tree (ETree) data analysis algorithm. The suggested improvements aim to make the system perform better while still maintaining the simple nature of the basic algorithm. We also examine the system's behavior with many different kinds of tests, measurements and visualizations. We compare the ETree's performance against classical data analysis methods and very similar modern systems. We find that the ETree is a suitable method for unsupervised analysis of huge data sets.

Algorithms↗

The folding landscape of Streptomyces griseus protease B reveals the energetic costs and benefits associated with evolving kinetic stability.

Like most extracellular bacterial proteases, Streptomyces griseus protease B (SGPB) and alpha-lytic protease (alphaLP) are synthesized with covalently attached pro regions necessary for their folding. In this article, we characterize the folding free energy landscape of SGPB and compare it to the folding landscapes of alphaLP and trypsin, a mammalian homolog that folds independently of its zymogen peptide. In contrast to the thermodynamically stable native state of trypsin, SGPB and alphaLP fold to native states that are thermodynamically marginally stable or unstable, respectively. Instead, their apparent stability arises kinetically, from unfolding free energy barriers that are both large and highly cooperative. The unique unfolding transitions of SGPB and alphaLP extend their functional lifetimes under highly degradatory conditions beyond that seen for trypsin; however, the penalty for evolving kinetic stability is remarkably large in that each factor of 2.4-8 in protease resistance is accompanied by a cost of ~10(5) in the spontaneous folding rate and ~5-9 kcal/mole in thermodynamic stability. These penalties have been overcome by the coevolution of increasingly effective pro regions to facilitate folding. Despite these costs, kinetic stability appears to be a potent mechanism for developing native-state properties that maximize protease longevity.

Amino Acid Sequence↗

Grazing optimization, nutrient cycling, and spatial heterogeneity of plant-herbivore interactions: should a palatable plant evolve?

Can the evolution of plant defense lead to an optimal primary production? In a general theoretical model, Loreau (1995) and de Mazancourt et al. (1998, 1999) have shown that herbivory could increase primary production up to a moderate rate of grazing intensity through recycling of a limiting nutrient, provided several conditions are fulfilled. In the present paper, we assume: (1) grazing intensity is controlled by plants through their level of palatability; and (2) plant fitness is determined by its productivity. We explore the conditions under which such an optimal production may be reached through natural selection. We model two competing plant types that differ only in palatability and are distributed in a patchy landscape determined by the plant-herbivore interaction. Patch size is determined by herbivore behavior: herbivores recycle nutrient homogeneously within patches, but recycle nutrient proportionally to consumption between patches. The model shows that a strategy of intermediate palatability can be adaptive in response to a small herbivore that lives on and recycles nutrient around one or a few individual plants. For moderately small herbivores, plant palatability may evolve towards one of two local convergent strategies, depending on the initial conditions. For medium- to large-sized herbivores, the nonpalatable strategy is always selected. We discuss the functional and evolutionary implications of these results, and suggest that the traditional dichotomy describing antagonistic and mutualistic interactions may be misleading.

Adaptation, Physiological↗

Does viviparity evolve in cold climate reptiles because pregnant females maintain stable (not high) body temperatures?

Viviparity (live bearing) has evolved from egg laying (oviparity) in many lineages of lizards and snakes, apparently in response to occupancy of cold climates. Explanations for this pattern have focused on the idea that behaviorally thermoregulating (sun-basking) pregnant female reptiles can maintain higher incubation temperatures for their embryos than would be available in nests under the soil surface. This is certainly true at very high elevations, where only viviparous species occur. However, comparisons of nest and lizard temperatures at sites close to the upper elevational limit for oviparous reptiles (presumably, the selective environment where the transition from oviparity to viviparity actually occurs) suggest that reproductive mode has less effect on mean incubation temperatures than on the diel distribution of those temperatures. Nests of the oviparous scincid lizard Bassiana duperreyi showed smooth diel cycles of heating and cooling. In contrast, body temperatures of the viviparous scincid Eulamprus heatwolei rose abruptly in the morning, were high and stable during daylight hours, and fell abruptly at night. Laboratory incubation experiments mimicking these patterns showed that developmental rates of eggs and phenotypic traits of hatchling B. duperreyi were sensitive to this type of thermal variance as well as to mean temperature. Hence, diel distributions as well as mean incubation temperatures may have played an important role in the selective forces for viviparity. More generally, variances as well as mean values of abiotic factors may constitute significant selective forces on life-history evolution.

Animals↗

Abciximab treatment for obstructive prosthetic aortic and mitral valve thrombosis in the presence of large thrombi, cardiogenic shock, and acute evolving embolic stroke.

Obstructive thrombosis of left-sided mechanical prosthetic valves is a life-threatening complication. Intravenous thrombolytic therapy is contraindicated due to risk of clot embolization and surgical treatment is often required for hemodynamically unstable patients. We report for the first time the successful use of abciximab in the management of a patient in cardiogenic shock with multiple prosthetic valve obstructive thrombosis and evolving embolic stroke. Serial Doppler echocardiography and cinefluoroscopy demonstrated resolution of thrombi, improvements in transvalvular gradients and improvement in leaflet motion. This observation suggests abciximab should be considered as a therapeutic option in the treatment of obstructed prosthetic heart valves.

Abciximab↗

Sweet's syndrome evolved from recurrent erythema nodosum in a patient with myelodysplastic syndrome.

A 63-year-old man had painful nodules on his lower legs. Microscopic examination showed septal and lobular panniculitis composed of lympho-histiocytic infiltrates. Based on the clinical and histopathological findings, the diagnosis of erythema nodosum (EN) was made. Nonsteroidal anti-inflammatory drugs were temporarily effective, but the eruptions had repeated to the present, and 16 months later, myelodysplastic syndrome (MDS) was diagnosed. Then, 6 months later, he developed a high fever and edematous fresh red-colored nodules on his neck, arm and upper trunk. Histopathologically, a diffuse, dense, dermal infiltrate of neutrophils was seen, and Sweet's syndrome (SS) was diagnosed. SS is known to develop in patients with MDS, and EN is one of the dermatoses that occur in conjunction with hematoproliferative disorders. Furthermore, SS evolving from recurrent EN and the simultaneous occurrence of SS and EN have been reported in some patients. In our case, we suggest that some mediators such as cytokines associated with MDS might have first induced EN, and then, as the MDS developed, they were replaced by others that caused SS.

Biopsy, Needle↗

B-prolymphocytic leukaemia with t(11;14) revisited: a splenomegalic form of mantle cell lymphoma evolving with leukaemia.

We reviewed eight cases that were diagnosed before 1995 with B-prolymphocytic leukaemia (B-PLL) harbouring t(11;14)(q13;q32) and/or cyclin D1 staining. Thirteen B-PLL patients without t(11;14) were selected as controls. Peripheral blood, bone marrow and histological sections were re-examined without cytogenetic information. Final diagnosis was made using morphology, cytogenetics, immunophenotype and immunohistochemistry. Clinical characteristics were similar for both groups except for younger age, male predominance and extranodal involvement in cases with t(11;14). CD5 was more frequently positive in the t(11;14)+ group (80%) than in the t(11;14)- group (31%). Surface membrane immunoglobulin was strongly expressed by all t(11;14)+ cases, but only 45% of t(11;14)- cases. Histopathological and cytological review of cases with t(11;14) showed an infiltrate with a mixture of cells, some resembling prolymphocytes and others with mantle cell lymphoma (MCL) morphology. Blood films of cases with t(11;14) showed features suggestive of B-PLL in three, and in others, a mixture of cells resembling MCL and nucleolated ones; none corresponded to the blastoid form of MCL. We suggest that 'B-PLL' with t(11;14) may represent a splenomegalic form of MCL evolving with leukaemia. These cases illustrate the importance of tissue diagnosis with cyclin D1 staining and fluorescence in situ hybridization analysis in B-cell leukaemia with prolymphocytic features.

Aged↗

Keratinocyte expression of intercellular adhesion molecule 1 (ICAM-1) correlated with infiltration of lymphocyte function associated antigen 1 (LFA-1) positive cells in evolving allergic contact dermatitis reactions.

Adhesion molecules are considered to have an important role in inflammatory reactions. We investigated the kinetics of ICAM-1 expression on keratinocytes and correlated this with the numbers of lymphocytes expressing LFA-1 in the dermis and epidermis of evolving allergic contact dermatitis reactions. In nickel-sensitive individuals, after application of a nickel patch, increased expression of ICAM-1 on keratinocytes was observed as early as 3 h and reached a maximum at 48 h. The number of lymphocytes expressing LFA-1 in the dermis and epidermis was greatest at 48 h. The LFA-1 cells were observed to be in close proximity to keratinocytes expressing ICAM-1, thus supporting the hypothesis that T-lymphocytes attach to keratinocytes via LFA-1/ICAM-1 molecules.

Cell Adhesion Molecules↗

Novel genetic basis of field-evolved resistance to Bt toxins in Plutella xylostella.

Insecticidal toxins from Bacillus thuringiensis (Bt) are widely used to control pest insects, but evolution of resistance threatens their continued efficacy. The most common type of Bt resistance ('Mode 1') is characterized by recessive inheritance, > 500-fold resistance to at least one Cry1A toxin, negligible cross-resistance to Cry1C, and reduced binding of Bt toxins to midgut membrane target sites. Mutations affecting a Cry1A-binding midgut cadherin protein are linked to laboratory-selected Mode 1 resistance in Heliothis virescens and Pectinophora gossypiella. Here we show that field-evolved Mode 1 resistance in the diamondback moth, Plutella xylostella, has a different genetic basis, indicating that screening for resistance in the field should not be restricted to a previously proposed DNA-based search for cadherin mutations.

Animals↗

Women's mid-life experience: an evolving consciousness of self and children.

This paper describes a hermeneutical and phenomenological research study of the mid-life spiritual experience of 10 women who are members of the United Church of Canada. Based on in-depth, face-to-face interviews, the paper describes the first of two simultaneous and interrelated experiences: an evolving consciousness of self and children. The five invariant themes that emerge point to a need for an expanded framework of human development that takes fuller account of women's experience and spirituality.

Adult↗

The evolving role of community nurses for people with learning disabilities: changes over an 11-year period.

AIMS AND OBJECTIVES: To provide an overview of the changes in the caseload and working practices of community nurses for people with learning disabilities (CNLDs) over an 11-year period within one region of the UK. BACKGROUND: Recent reviews of government policy within the UK and internationally have highlighted the need to promote inclusion and health facilitation for people with learning disabilities (intellectual disabilities). The CNLDs have been highlighted as having an integral role in achieving these objectives. However, little is known about the current role of community nurses and how this has evolved over the past decade. DESIGNS AND METHODS: A survey design was used in which the total population of CNLDs within one region of the UK were asked to complete a postal questionnaire. RESULTS: Forty community nurses in Northern Ireland completed questionnaires. This provided information about 1559 people with learning disabilities on their current caseloads. Results showed less involvement with children, more focus on adults with physical and mental health needs and nurses often appeared to have a monitoring rather than an active clinical role. Data also identified an increasing caseload size and a pattern of referral largely from within learning disability services. CONCLUSIONS: The role of CNLDs has altered in Northern Ireland over the past 11 years with some evidence of a reorientation towards a more health-oriented focus. Further consideration needs to be given to how well this will meet the changing needs of people with learning disabilities and their families in light of the increasing emphasis on the provision of inclusive services. RELEVANCE TO CLINICAL PRACTICE: Community nurses need to review their current role, caseload management and links to primary and acute care if the policy objectives of inclusive services and health facilitation are to be achieved. It will also be necessary to revise their education preparation in light of the changing role of CNLDs.

Adult↗

How species evolve collectively: implications of gene flow and selection for the spread of advantageous alleles.

The traditional view that species are held together through gene flow has been challenged by observations that migration is too restricted among populations of many species to prevent local divergence. However, only very low levels of gene flow are necessary to permit the spread of highly advantageous alleles, providing an alternative means by which low-migration species might be held together. We re-evaluate these arguments given the recent and wide availability of indirect estimates of gene flow. Our literature review of F(ST) values for a broad range of taxa suggests that gene flow in many taxa is considerably greater than suspected from earlier studies and often is sufficiently high to homogenize even neutral alleles. However, there are numerous species from essentially all organismal groups that lack sufficient gene flow to prevent divergence. Crude estimates on the strength of selection on phenotypic traits and effect sizes of quantitative trait loci (QTL) suggest that selection coefficients for leading QTL underlying phenotypic traits may be high enough to permit their rapid spread across populations. Thus, species may evolve collectively at major loci through the spread of favourable alleles, while simultaneously differentiating at other loci due to drift and local selection.

Adaptation, Biological↗

Screening for rapidly evolving genes in the ectomycorrhizal fungus Paxillus involutus using cDNA microarrays.

We have examined the variations in gene content and sequence divergence that could be associated with symbiotic adaptations in the ectomycorrhizal fungus Paxillus involutus and the closely related species Paxillus filamentosus. Strains with various abilities to form mycorrhizae were analysed by comparative genomic hybridizations using a cDNA microarray containing 1076 putative unique genes of P. involutus. To screen for genes diverging at an enhanced and presumably non-neutral rate, we implemented a simple rate test using information from both the variations in hybridizations signal and data on sequence divergence of the arrayed genes relative to the genome of Coprinus cinereus. C. cinereus is a free-living saprophyte and is the closest evolutionary relative to P. involutus that has been fully sequenced. Approximately 17% of the genes investigated were detected as rapidly diverging within Paxillus. Furthermore, 6% of the genes varied in copy numbers between the analysed strains. Genome rearrangements associated with this variation including duplications and deletions may also play a role in adaptive evolution. The cohort of divergent and duplicated genes showed an over-representation of either orphans, genes whose products are located at membranes, or genes encoding for components of stress/defence reactions. Some of the identified genomic changes may be associated with the variation in host specificity of ectomycorrhizal fungi. The proposed procedure could be generally applicable to screen for rapidly evolving genes in closely related strains or species where at least one has been sequenced or characterized by expressed sequence tag analysis.

Analysis of Variance↗

Mosaic pbpX genes of major clones of penicillin-resistant Streptococcus pneumoniae have evolved from pbpX genes of a penicillin-sensitive Streptococcus oralis.

Penicillin-resistant clinical isolates of Streptococcus pneumoniae contain mosaic penicillin-binding protein (PBP) genes that encode PBPs with decreased affinity for beta-lactam antibiotics. The mosaic blocks are believed to be the result of gene transfer of homologous PBP genes from related penicillin-resistant species. We have now identified a gene homologous to the pneumococcal PBP2x gene (pbpX) in a penicillin-sensitive Streptococcus oralis isolate M3 from South Africa that diverged by almost 20% from pbpX of penicillin-sensitive pneumococci, and a central sequence block of a mosaic pbpX gene of Streptococcus mitis strain NCTC 10712. In contrast, it differed by only 2-4% of the 1 to 1.5 kb mosaic block in pbpX genes of three genetically unrelated penicillin-resistant S. pneumoniae isolates, two of them representing clones of serotype 6B and 23F, which are prevalent in Spain and are also already found in other countries. With low concentrations of cefotaxime, transformants of the sensitive S. pneumoniae R6 strain could be selected containing pbpX genes from either S. mitis NCTC 10712 or S. oralis M3, demonstrating that genetic exchange can already occur between beta-lactam-sensitive species. These data are in agreement with the assumption that PBPs as penicillin-resistance determinants have evolved by the accumulation of point mutations in genes of sensitive commensal species.

Amino Acid Sequence↗