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A relational database of protein structures designed for flexible enquiries about conformation.

A relational database of protein structure has been developed to enable rapid and flexible enquiries about the occurrence of many aspects of protein architecture. The coordinates of 294 proteins from the Brookhaven Data Bank have been processed by standard computer programs to generate many additional terms that quantify aspects of protein structure. These terms include solvent accessibility, main-chain and side-chain dihedral angles, and secondary structure. In a relational database, the information is stored in tables with columns holding the different terms and rows holding the different entries for the terms. The different relational base tables store the information about the protein coordinate set, the different chains in the protein, the amino acid residues and ligands, the atomic coordinates, the salt bridges, the hydrogen bonds, the disulphide bridges and the close tertiary contacts. The database was established under ORACLE management system. Enquiries are constructed in ORACLE using SQL (structured query language) which is simple to use and alleviates the need for extensive computer programs. A single table can be searched for entries that meet various criteria, e.g. all protein solved to better than a given resolution. The power of the database occurs when several tables, or the entries in a single table, are cross-correlated. For example the dihedral angles of proline in the fourth position in an alpha-helix in high resolution structures can be rapidly obtained. The structural database provides a powerful tool to obtain empirical rules about protein conformation. This database of protein structures is part of a joint project between Birkbeck College and Leeds University to establish an integrated data resource of protein sequences and structures (ISIS) that encodes the complex patterns of residues and coordinates that define protein conformation. The entire data resource (ISIS) will provide a system to guide all areas of protein modelling including structure prediction, site-directed mutagenesis and de novo protein design. The availability of ISIS is described in the paper.

Computer Simulation↗

Bioinformatics analyses of circular dichroism protein reference databases.

MOTIVATION: Circular dichroism (CD) spectroscopy has become established as a key method for determining the secondary structure contents of proteins which has had a significant impact on molecular biology. Many excellent mathematical protocols have been developed for this purpose and their quality is above question. However, reference database sets of proteins, with CD spectra matched to secondary structure components derived from X-ray structures, provide the key resource for this task. These databases were created many years ago, before most CD spectrophotometers became standardized and before it was commonplace to validate X-ray structures prior to publication. The analyses presented here were undertaken to investigate the overall quality of these reference databases in light of their extensive usage in determining protein secondary structure content from CD spectra. RESULTS: The analyses show that there are a number of significant problems associated with the CD reference database sets in current use. There are disparities between CD spectra for the same protein collected by different groups. These include differences in magnitudes, peak positions or both. However, many current reference sets are now amalgamations of spectra from these groups, introducing inconsistencies that can lead to inaccuracies in the determination of secondary structure components from the CD spectra. A number of the X-ray structures used fall short on the validation criteria now employed as standard for structure determination. Many have substantial percentages of residues in the disallowed regions of the Ramachandran plot. Hence their calculated secondary structure components, used as a foundation for the reference databases, are likely to be in error. Additionally, the coverage of secondary structure space in the reference datasets is poorly correlated to the secondary structure components found in the Protein Data Bank. A conclusion is that a new reference CD database with cross-correlated, machine-independent CD spectra and validated X-ray structures that cover more secondary structure components, including diverse protein folds, is now needed. However, that reasonably accurate values for the secondary structure content of proteins can be determined from spectra is a testament to CD spectroscopy being a very powerful technique.

Circular Dichroism↗

Confabulation following rupture of posterior communicating artery.

In this study we report a patient, MG, who following rupture of left posterior communicating artery exhibited an amnesic-confabulatory syndrome. Neuropsychological examination showed severe impairment on episodic memory tasks, which were marred by florid but plausible and semantically appropriate confabulation. Performance on tasks involving various kinds of semantic knowledge was normal or only mildly impaired. Performance on tasks traditionally considered sensitive to frontal dysfunction was severely impaired with the exception of Cognitive Estimates where MG's performance was completely normal. There was no evidence of structural (CT scan) or metabolic (SPECT) damage to the frontal lobe. It is argued that tasks traditionally considered sensitive to frontal dysfunction are not specifically implemented by cognitive resources based on frontal structures. MG's confabulation is discussed in terms of a possible disruption of cognitive functions involved in the control of the subjective experience of feeling of remembering.

Adult↗

Structural factors in HIV prevention: concepts, examples, and implications for research.

INTRODUCTION: HIV-prevention behavior is affected by the environment as well as by characteristics of individuals at risk. HIV-related structural factors are defined as barriers to, or facilitators of, an individual's HIV prevention behaviors; they may relate to economic, social, policy, organizational or other aspects of the environment. IMPACT OF STRUCTURAL INTERVENTIONS: A relatively small number of intervention studies demonstrates the potential of structural interventions to increase HIV prevention in the United States and internationally. The promise of structural interventions has also been shown in studies of interventions to prevent disease or promote public health in areas other than HIV. FRAMEWORK OF STRUCTURAL FACTORS: Frameworks help define and exemplify structural barriers and facilitators for HIV prevention. One framework developed at Centers for Disease Control and Prevention gives examples of structural facilitators in terms of the economic resources, policy supports, societal attitudes, and organizational structures and functions associated with governments, service organizations, businesses, workforce organizations, faith communities, justice systems, media organizations, educational systems, and healthcare systems. Frameworks should assist researchers and health officials to identify important areas for structural research and programming. CONCLUSIONS: A structural approach is timely and innovative. Despite limitations, including the challenge of a new perspective on prevention and the difficulty of evaluating their effects, researchers and public health officials are urged to pursue structural interventions to prevent HIV.

Condoms↗

RAG: RNA-As-Graphs web resource.

BACKGROUND: The proliferation of structural and functional studies of RNA has revealed an increasing range of RNA's structural repertoire. Toward the objective of systematic cataloguing of RNA's structural repertoire, we have recently described the basis of a graphical approach for organizing RNA secondary structures, including existing and hypothetical motifs. DESCRIPTION: We now present an RNA motif database based on graph theory, termed RAG for RNA-As-Graphs, to catalogue and rank all theoretically possible, including existing, candidate and hypothetical, RNA secondary motifs. The candidate motifs are predicted using a clustering algorithm that classifies RNA graphs into RNA-like and non-RNA groups. All RNA motifs are filed according to their graph vertex number (RNA length) and ranked by topological complexity. CONCLUSIONS: RAG's quantitative cataloguing allows facile retrieval of all classes of RNA secondary motifs, assists identification of structural and functional properties of user-supplied RNA sequences, and helps stimulate the search for novel RNAs based on predicted candidate motifs.

Computational Biology↗

FATCAT: a web server for flexible structure comparison and structure similarity searching.

Protein structure comparison, an important problem in structural biology, has two main applications: (i) comparing two protein structures in order to identify the similarities and differences between them, and (ii) searching for structures similar to a query structure. Many web-based resources for both applications are available, but all are based on rigid structural alignment algorithms. FATCAT server implements the recently developed flexible protein structure comparison algorithm FATCAT, which automatically identifies hinges and internal rearrangements in two protein structures. The server provides access to two algorithms: FATCAT-pairwise for pairwise flexible structure comparison and FATCAT-search for database searching for structurally similar proteins. Given two protein structures [in the Protein Data Bank (PDB) format], FATCAT-pairwise reports their structural alignment and the corresponding statistical significance of the similarity measured as a P-value. Users can view the superposition of the structures online in web browsers that support the Chime plug-in, or download the superimposed structures in PDB format. In FATCAT-search, users provide one query structure and the server returns a list of protein structures that are similar to the query, ordered by the P-values. In addition, FATCAT server can report the conformational changes of the query structure as compared to other proteins in the structure database. FATCAT server is available at http://fatcat.burnham.org.

Algorithms↗

[Comparative analysis of health systems: various methodologic aspects].

This paper discusses the comparative analysis of health systems, its relative low level of development, its great importance for training health sector leaders and some of the difficulties and limitations for implementing it transnationally. The appropriate understanding of the sociohistorical conditions and the economic and political context are of germane importance for comparative analyses. Moreover, analysis of the financial aspects of health systems, as well as that of the physical or technological infrastructure, of the human resources, or the organizational structure and also of the health levels bring about particular difficulties which need adequate methodological developments.

Health Resources↗

Conditional responses of organisms to habitat structure: an example from intertidal mudflats.

Habitat structure is often assumed to be a predictor of habitat function. However, habitat structure may be insufficient to predict the functional significance of a habitat if the level of resources in the habitat is a consequence of the interaction between the habitat structure and physical or biological factors. In this study, we investigated whether depressions in tidal flat sediments generated by stout razor clams, Tagelus plebeius, affect the spatial patterns of pit digging by deposit-feeding burrowing crabs, Chasmagnathus granulata. The pits dug by crabs while feeding overlapped with clam siphon holes at a frequency higher than expected at random, and measurements of pit-digging by crabs integrated over several days indicated a higher frequency of feeding in the sediment of depressions. The daily frequency of pit-digging by crabs in depressions was positively related to the organic matter content of their sediments, but was significantly higher than the frequency of pit-digging away from clam siphon holes only after events of high bedload sediment transport, when the organic matter in the sediments of these depressions peaked. This example demonstrates the conditional nature of the relationship between habitat structure and function by illustrating how a physical process--bedload sediment transport--may introduce variation in the function that depressions play as feeding sites for burrowing crabs. Published information suggests that such conditional responses of organisms to habitat structure: (1) occur in a variety of habitats; (2) involve a variety of structures either of biotic or abiotic origin; and (3) are the consequence of either physical or biological controls that vary in importance according to the general mechanism through which habitat structure affect resources. This broad experimental evidence suggests that the accuracy of predictive models linking habitat structure and function can be improved by incorporating a mechanistic perspective that allows recognition of the potential for conditional responses of organisms to habitat structure.

Analysis of Variance↗

Evidence-based medicine: applications in dietetic practice.

Evidence-based medicine has been defined as "the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients." Evidence-based practice requires the ability to apply knowledge of medical informatics (eg, efficiently searching the medical literature) and clinical epidemiology (eg, being able to critically appraise the literature) to the treatment of individual patients. Being able to apply the principles of evidence-based medicine in the dietetic practice adds to the credibility and value of dietetics professionals, is consistent with the dietetic code of ethics, and is empowering. This article provides an introduction to the history, philosophy, and methods of evidence-based medicine as applied to the dietetic practice. This article focuses on a 5-step process to finding the best evidence to answer clinical questions: (a) formulate the question, (b) search for answers, (c) appraise the evidence, (d) apply the results, and (e) assess the outcome. We describe the 4S methodology-a systematic approach to efficiently finding the best evidence to answer clinical questions involving the use of systems (comprehensive, evidence-based resources), synopses (compilations of structured abstracts of high-quality studies), syntheses (systematic reviews), and studies (original research articles). Particular emphasis is given to a method for critically appraising papers that emphasizes validity, importance, and clinical applicability. Resources (including Web sites) for further learning are provided. J Am Diet Assoc. 2002;102:1263-1272.

Data Interpretation, Statistical↗

Nurse practitioners: leadership behaviors and organizational climate.

The purpose of this article is to examine the relationships of individual nurse practitioners' perceptions of the leadership climate in their organizations and self-reported formal and informal leadership behaviors. The nine climate dimensions (Structure, Responsibility, Reward, Perceived Support of Risk Taking, Warmth, Support, Standard Setting, Conflict, and Identity) identified by Litwin and Stringer in 1968 were used to predict five leadership dimensions (Meeting Organizational Needs, Managing Resources, Leadership Competence, Task Accomplishment, and Communications). Demographic variables of age, educational level, and percent of time spent performing administrative functions were forced as a first step in each multiple regression analysis and used to explain a significant amount of variance in all but one analysis. All leadership dimensions were predicted by at least one organizational climate dimension: (1) Meeting Organizational Needs by Risk and Reward; (2) Managing Resources by Risk and Structure; (3) Leadership Competence by Risk and Standards; (4) Task Accomplishment by Structure, Risk, and Standards; and (5) Communication by Rewards.

Adult↗

The CATH domain structure database: new protocols and classification levels give a more comprehensive resource for exploring evolution.

We report the latest release (version 3.0) of the CATH protein domain database (http://www.cathdb.info). There has been a 20% increase in the number of structural domains classified in CATH, up to 86 151 domains. Release 3.0 comprises 1110 fold groups and 2147 homologous superfamilies. To cope with the increases in diverse structural homologues being determined by the structural genomics initiatives, more sensitive methods have been developed for identifying boundaries in multi-domain proteins and for recognising homologues. The CATH classification update is now being driven by an integrated pipeline that links these automated procedures with validation steps, that have been made easier by the provision of information rich web pages summarising comparison scores and relevant links to external sites for each domain being classified. An analysis of the population of domains in the CATH hierarchy and several domain characteristics are presented for version 3.0. We also report an update of the CATH Dictionary of homologous structures (CATH-DHS) which now contains multiple structural alignments, consensus information and functional annotations for 1459 well populated superfamilies in CATH. CATH is directly linked to the Gene3D database which is a projection of CATH structural data onto approximately 2 million sequences in completed genomes and UniProt.

Classification↗

Effects of decreased resource availability, protozoan grazing and viral impact on a structure of bacterioplankton assemblage in a canyon-shaped reservoir.

We conducted a transplant experiment to elucidate the effects of different levels of grazing pressure, nutrient availability, especially phosphorus, and the impact of viruses on the changes in the structure of bacterioplankton assemblage in a meso-eutrophic reservoir. A sample taken from the nutrient-rich inflow part of the reservoir was size-fractionated and incubated in dialysis bags in both inflow and dam area. The structure of bacterial assemblage was examined by fluorescence in situ hybridization using oligonucleotide probes with different levels of specificity. In terms of the relative proportions of different bacterial groups, we found very few significant changes in the bacterioplankton composition after transplanting the treatments to the nutrient-poor dam area. However, we observed marked shifts in morphology and biomass towards the development of filaments, flocs and "vibrio-like" morphotypes of selected probe-defined groups of bacteria induced by increased grazing pressure. Despite the very high abundances of viruses in all the treatments, their effects on bacterioplankton were rather negligible.

Animals↗

Community level factors and child maltreatment rates.

Using census and administrative agency data for 177 urban census tracts, variation in rates of officially reported child maltreatment is found to be related to structural determinants of community social organization: economic and family resources, residential instability, household and age structure, and geographic proximity of neighborhoods to concentrated poverty. Furthermore, child maltreatment rates are found to be intercorrelated with other indicators of the breakdown of community social control and organization. These other indicators are similarly affected by the structural dimensions of neighborhood context. Children who live in neighborhoods that are characterized by poverty, excessive numbers of children per adult resident, populations turnover, and the concentration of female-headed families are at highest risk of maltreatment. This analysis suggests that child maltreatment is but one manifestation of community social organization and that its occurrence is related to some of the same underlying macro-social conditions that foster other urban problems.

Adolescent↗

Neuropathological alterations in alcoholic brains. Studies arising from the New South Wales Tissue Resource Centre.

Alcohol dependence and abuse are among the most costly health problems in the world from both social and economic points of view. Patterns of drinking appear to be changing throughout the world with more women and young people drinking heavily. Excessive drinking can lead to impairment of cognitive function and structural brain changes--some permanent, some reversible. Patterns of damage appear to relate to lifetime alcohol consumption but, more importantly, to associated medical complications. The most significant of these is the alcohol-related vitamin deficient state, the Wernicke-Korsakoff syndrome (WKS), which is caused by thiamin deficiency but is seen most commonly in alcoholics. Careful selection and classification of alcoholic cases into those with and without these complications, together with detailed quantitative neuropathological analyses has provided data that gives clues to the most vulnerable regions and cells in the brain. Brain shrinkage is largely accounted for by loss of white matter. Some of this damage appears to be reversible. Alcohol-related neuronal loss has been documented in specific regions of the cerebral cortex (superior frontal association cortex), hypothalamus and cerebellum. No change is found in basal ganglia, nucleus basalis, or serotonergic raphe nuclei. Many of these regions which are normal in uncomplicated alcoholics are damaged in those with the WKS. Dendritic and synaptic changes have been documented in alcoholics and these, together with receptor and transmitter changes, may explain functional changes and cognitive deficits, which precede more severe structural neuronal changes. A resource to provide human brain tissues for these types of studies has been developed at the University of Sydney--the New South Wales Tissue Resource Centre. The aim of this facility is to provide research groups throughout the world with fresh and/or frozen tissues from well-characterized cases of alcohol-related brain damage and matched controls. The development of new technologies in pathology and molecular biology means that many more questions can be addressed using appropriately stored human brain tissues. Examples of the application of some of these techniques, involving neurochemical, neuropharmacological, neuroimaging and gene expression studies are included in this paper. Important public health outcomes have arisen from some of these studies including the enrichment of bread flour with thiamin for the whole of Australia. Researchers with an interest in alcohol studies can access tissues from this brain bank.

Alcoholism↗

On the determinants of population structure in antigenically diverse pathogens.

Many pathogens exhibit antigenic diversity and elicit strain-specific immune responses. This potential for cross-immunity structure in the host resource motivates the development of mathematical models, stressing competition for susceptible hosts in driving pathogen population dynamics and genetics. Here we establish that certain model formulations exhibit characteristics of prototype pattern-forming systems, with pathogen population structure emerging as three possible patterns: (i) incidence is steady and homogeneous; (ii) incidence is steady but heterogeneous; and (iii) incidence shows oscillatory dynamics, with travelling waves in strain-space. Results are robust to strain number, but sensitive to the mechanism of cumulative immunity.

Animals↗

Coping and self-image in patients with visual display terminal-related skin symptoms and perceived hypersensitivity to electricity.

OBJECTIVES: The aim of the present study was to measure coping resources and self-image in patients with visual display terminal (VDT)-related skin symptoms and hypersensitivity to electricity (HE). METHODS: From 1980 to 1998, 350 patients with electrical sensitivity were registered. The patients were subdivided into two groups: patients with skin symptoms evoked by VDTs, television screens, and fluorescent-light tubes and patients with so-called hypersensitivity to electricity with multiple symptoms evoked by exposure to different electrical environments. A questionnaire was sent to all patients and contained the coping resources inventory (CRI) and the structural analysis of social behaviour (SASB) in order for us to measure coping resources and self-image, respectively. The CRI and SASB scores were compared with those of control groups. Two hundred and fifty respondents (73%) returned the questionnaire, 200 (78.5% women) in the VDT group and 50 (62% women) in the HE group. RESULTS: The patient group rated high on the CRI spiritual/philosophical scale and high on the SASB spontaneous, positive and negative clusters but low on the controlled cluster. The female patients scored high on the CRI emotional scale. The VDT group rated lower than the controls on the SASB controlled cluster and higher on both the positive and negative cluster. The HE group scored higher than the control group on the SASB spontaneous and positive clusters. The women in the HE group scored higher on the CRI cognitive and CRI total scale than the VDT group and control group and higher on the CRI emotional scale than the controls. The women in the HE group rated higher than both the women in the VDT and control groups on the SASB spontaneous and positive clusters. CONCLUSIONS: The deviant self-image found in these patients, especially the female HE patients, support the view that VDT and HE symptoms can be stress related. In the clinic, a trustful alliance should be established with the patient in order for a more realistic view to be achieved of the capacity.

Adaptation, Psychological↗