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PubMed2005

MAVisto: a tool for the exploration of network motifs.

UNLABELLED: MAVisto is a tool for the exploration of motifs in biological networks. It provides a flexible motif search algorithm and different views for the analysis and visualization of network motifs. These views help to explore interesting motifs: the frequency of motif occurrences can be compared with randomized networks, a list of motifs along with information about structure and number of occurrences depending on the reuse of network elements shows potentially interesting motifs, a motif fingerprint reveals the overall distribution of motifs of a given size and the distribution of a particular motif in the network can be visualized using an advanced layout algorithm. AVAILABILITY: MAVisto is platform independent and available free of charge as a Java webstart application at http://mavisto.ipk-gatersleben.de/ CONTACT: schwoebb@ipk-gatersleben.de SUPPLEMENTARY INFORMATION: Can be found at http://mavisto.ipk-gatersleben.de/

Computer Simulation↗

PubMed2004

Audism: exploring the metaphysics of oppression.

This article traces the development of the concept of "audism" from its inception in the mid-1970s by exploring three distinct dimensions of oppression: individual, institutional, and metaphysical. Although the first two aspects of audism have been identified, there is a deeply rooted belief system regarding language and human identity that is yet to be explored within the context of audism. This article attempts to expose how our particular historical and philosophical constructions of language and being have created what French philosopher Jacques Derrida calls phonocentrism. Although Derrida does not discuss audism, his deconstruction of the Western notion of language provides a lens through which we can better see the orientation that has provided fertile ground out of which individual and institutional audism has flourished.

Deafness↗

PubMed1999

"I was always on guard"--an exploration of woman abuse in a group of women with musculoskeletal pain.

OBJECTIVES: We aimed to explore experiences of abuse of women, and the way it was described and hinted at, in a group of women suffering from biomedically undefined long-term musculo-skeletal pain (UMSD). METHOD: Twenty women patients participated. Data were gained through repeated semi-structured interviews conducted over 2 years and qualitatively analysed according to grounded theory. RESULTS: Eleven participants had experienced abuse. Abuse was difficult to disclose due to shame, fear of the listener's preconceptions and fear of the abuser. In the interviews it was diminished, 'sugar-coated' and renamed. However, the women gave hints of abuse before avowing it. 'An understanding listener', who was expected to apprehend the hints, ask about abuse and confirm that it was valid to talk about it, was described as a precondition for disclosure. CONCLUSION: This study suggests that it is important to explore woman abuse when investigating and treating UMSD. When there are hints of abuse, one should avoid blaming, stand by, be patient and ask about abuse even if the woman has once negated it. Fear of the abuser permeated the narratives and it is therefore suggested that doctors must consider carefully the danger involved.

Adult↗

PubMed2001

An exploration of help-seeking behaviour in older people with unmet needs.

BACKGROUND: Despite decades of research showing high rates of unmet need in older people, there currently is little understanding of why these needs remain unmet. This study was performed as part of a larger feasibility study of a multidisciplinary needs assessment tool in primary care. OBJECTIVE: The aim of the present study was to explore patients' and carers' help-seeking behaviour and perceived barriers to meeting unmet needs. METHOD: Four general practices were selected purposefully in inner city and suburban London A random sample of 1 in 20 people aged 75 years and over registered with each practice was selected for a multidisciplinary needs assessment using the 'Camberwell Assessment of Need for the Elderly' (CANE) schedule and unmet needs identified by patients and their informal carers. For each unmet need, a further semi-structured interview was used to explore the help-seeking behaviour and perceived barriers to meeting their needs. Responses were recorded verbatim contemporaneously and a thematic analysis performed on perceived barriers following completion of all interviews. RESULTS: A total of 55/84 (65.5%) of patients and 15/17 (88%) of carers completed the initial needs assessment. For 104 unmet needs identified by 31 patients and 11 carers, a further interview was completed on the barriers to meeting that need. Help had been sought for only 25/104 (24%) of unmet needs and it had been offered in only 19/104 (18%). In those not seeking help, withdrawal, resignation and low expectations were dominant themes. In those that had sought help, there were issues of perceived failure of service delivery and rationing, with themes of resignation and withdrawal again emerging in those declining help offered. CONCLUSION: The majority of older people and their carers do not appear to seek help for their unmet needs for a range of complex reasons, often involving issues of withdrawal, resignation and low expectations. This complexity has implications for the commissioning of services for older people.

Activities of Daily Living↗

PubMed1999

An exploration of oral health beliefs and attitudes of Chinese in West Yorkshire: a qualitative investigation.

This qualitative study explores oral health beliefs and attitudes among Chinese resident in West Yorkshire using six focus groups differentiated by age and gender. Focus group discussions took place in community settings led by trained Chinese facilitators. All groups believed that they were susceptible to dental disease, and that bleeding gums and total tooth loss were 'normal'; apart from the elderly, tooth loss was seen as undesirable. The elderly and adult groups believed in traditional remedies and claimed that preventive oral health measures were ineffective. These groups lacked faith in dentists, and for them cost, language difficulties and lack of awareness were the main reported barriers to accessing dental services. Traditional Chinese oral health beliefs remain influential for the elderly and adult UK Chinese. In contrast, teenagers thought that toothbrushing and sugar restriction would help to prevent dental diseases. The appropriateness of the focus group and interview methods for exploring oral health beliefs for the Chinese are discussed, as are implications of the reported intergenerational differences for oral health promotion strategy in the UK.

Adolescent↗

PubMed2000

The microarray explorer tool for data mining of cDNA microarrays: application for the mammary gland.

The Microarray Explorer (MAExplorer) is a versatile Java-based data mining bioinformatic tool for analyzing quantitative cDNA expression profiles across multiple microarray platforms and DNA labeling systems. It may be run as either a stand-alone application or as a Web browser applet over the Internet. With this program it is possible to (i) analyze the expression of individual genes, (ii) analyze the expression of gene families and clusters, (iii) compare expression patterns and (iv) directly access other genomic databases for clones of interest. Data may be downloaded as required from a Web server or in the case of the stand-alone version, reside on the user's computer. Analyses are performed in real-time and may be viewed and directly manipulated in images, reports, scatter plots, histograms, expression profile plots and cluster analyses plots. A key feature is the clone data filter for constraining a working set of clones to those passing a variety of user-specified logical and statistical tests. Reports may be generated with hypertext Web access to UniGene, GenBank and other Internet databases for sets of clones found to be of interest. Users may save their explorations on the Web server or local computer and later recall or share them with other scientists in this groupware Web environment. The emphasis on direct manipulation of clones and sets of clones in graphics and tables provides a high level of interaction with the data, making it easier for investigators to test ideas when looking for patterns. We have used the MAExplorer to profile gene expression patterns of 1500 duplicated genes isolated from mouse mammary tissue. We have identified genes that are preferentially expressed during pregnancy and during lactation. One gene we identified, carbonic anhydrase III, is highly expressed in mammary tissue from virgin and pregnant mice and in gene knock-out mice with underdeveloped mammary epithelium. Other genes, which include those encoding milk proteins, are preferentially expressed during lactation.

Animals↗

PubMed2002

SYSTERS, GeneNest, SpliceNest: exploring sequence space from genome to protein.

We have integrated the protein families from SYSTERS and the expressed sequence tag (EST) clusters from our database GeneNest with SpliceNest, a new database mapping EST contigs into genomic DNA. The SYSTERS protein sequence cluster set provides an automatically generated classification of all sequences of the SWISS-PROT, TrEMBL and PIR databases into disjoint protein family and superfamily clusters. GeneNest is a database and software package for producing and visualizing gene indices from ESTs and mRNAs. Currently, the database comprises gene indices of human, mouse, Arabidopsis thaliana and zebrafish. SpliceNest is a web-based graphical tool to explore gene structure, including alternative splicing, based on a mapping of the EST consensus sequences from GeneNest to the complete human genome. The integration of SYSTERS, GeneNest and SpliceNest into one framework now permits an overall exploration of the whole sequence space covering protein, mRNA and EST sequences, as well as genomic DNA. The databases are available for querying and browsing at http://cmb.molgen.mpg.de.

Alternative Splicing↗

PubMed2003

Target Explorer: An automated tool for the identification of new target genes for a specified set of transcription factors.

With the increasing number of eukaryotic genomes available, high-throughput automated tools for identification of regulatory DNA sequences are becoming increasingly feasible. Several computational approaches for the prediction of regulatory elements were recently developed. Here we combine the prediction of clusters of binding sites for transcription factors with context information taken from genome annotations. Target Explorer automates the entire process from the creation of a customized library of binding sites for known transcription factors through the prediction and annotation of putative target genes that are potentially regulated by these factors. It was specifically designed for the well-annotated Drosophila melanogaster genome, but most options can be used for sequences from other genomes as well. Target Explorer is available at http://trantor.bioc.columbia.edu/Target_Explorer/

Animals↗

PubMed2004

PDA: a pipeline to explore and estimate polymorphism in large DNA databases.

Polymorphism studies are one of the main research areas of this genomic era. To date, however, no available web server or software package has been designed to automate the process of exploring and estimating nucleotide polymorphism in large DNA databases. Here, we introduce a novel software, PDA, Pipeline Diversity Analysis, that automatically can (i) search for polymorphic sequences in large databases, and (ii) estimate their genetic diversity. PDA is a collection of modules, mainly written in Perl, which works sequentially as follows: unaligned sequence retrieved from a DNA database are automatically classified by organism and gene, and aligned using the ClustalW algorithm. Sequence sets are regrouped depending on their similarity scores. Main diversity parameters, including polymorphism, synonymous and non-synonymous substitutions, linkage disequilibrium and codon bias are estimated both for the full length of the sequences and for specific functional regions. Program output includes a database with all sequences and estimations, and HTML pages with summary statistics, the performed alignments and a histogram maker tool. PDA is an essential tool to explore polymorphism in large DNA databases for sequences from different genes, populations or species. It has already been successfully applied to create a secondary database. PDA is available on the web at http://pda.uab.es/.

Databases, Nucleic Acid↗

PubMed2005

GoPubMed: exploring PubMed with the Gene Ontology.

The biomedical literature grows at a tremendous rate and PubMed comprises already over 15 000 000 abstracts. Finding relevant literature is an important and difficult problem. We introduce GoPubMed, a web server which allows users to explore PubMed search results with the Gene Ontology (GO), a hierarchically structured vocabulary for molecular biology. GoPubMed provides the following benefits: first, it gives an overview of the literature abstracts by categorizing abstracts according to the GO and thus allowing users to quickly navigate through the abstracts by category. Second, it automatically shows general ontology terms related to the original query, which often do not even appear directly in the abstract. Third, it enables users to verify its classification because GO terms are highlighted in the abstracts and as each term is labelled with an accuracy percentage. Fourth, exploring PubMed abstracts with GoPubMed is useful as it shows definitions of GO terms without the need for further look up. GoPubMed is online at www.gopubmed.org. Querying is currently limited to 100 papers per query.

Abstracting and Indexing↗

PubMed2005

WebGestalt: an integrated system for exploring gene sets in various biological contexts.

High-throughput technologies have led to the rapid generation of large-scale datasets about genes and gene products. These technologies have also shifted our research focus from 'single genes' to 'gene sets'. We have developed a web-based integrated data mining system, WebGestalt (http://genereg.ornl.gov/webgestalt/), to help biologists in exploring large sets of genes. WebGestalt is composed of four modules: gene set management, information retrieval, organization/visualization, and statistics. The management module uploads, saves, retrieves and deletes gene sets, as well as performs Boolean operations to generate the unions, intersections or differences between different gene sets. The information retrieval module currently retrieves information for up to 20 attributes for all genes in a gene set. The organization/visualization module organizes and visualizes gene sets in various biological contexts, including Gene Ontology, tissue expression pattern, chromosome distribution, metabolic and signaling pathways, protein domain information and publications. The statistics module recommends and performs statistical tests to suggest biological areas that are important to a gene set and warrant further investigation. In order to demonstrate the use of WebGestalt, we have generated 48 gene sets with genes over-represented in various human tissue types. Exploration of all the 48 gene sets using WebGestalt is available for the public at http://genereg.ornl.gov/webgestalt/wg_enrich.php.

Computer Graphics↗

PubMed2006

CrossLink: visualization and exploration of sequence relationships between (micro) RNAs.

CrossLink is a versatile tool for the exploration of relationships between RNA sequences. After a parametrization phase, CrossLink delegates the determination of sequence relationships to established tools (BLAST, Vmatch and RNAhybrid) and then constructs a network. Each node in this network represents a sequence and each link represents a match or a set of matches. Match attributes are reflected by graphical attributes of the links and corresponding alignments are displayed on a mouse-click. The distributions of match attributes such as E-value, match length and proportion of identical nucleotides are displayed as histograms. Sequence sets can be highlighted and visibility of designated matches can be suppressed by real-time adjustable thresholds for attribute combinations. Powerful network layout operations (such as spring-embedding algorithms) and navigation capabilities complete the exploration features of this tool. CrossLink can be especially useful in a microRNA context since Vmatch and RNAhybrid are suitable tools for determining the antisense and hybridization relationships, which are decisive for the interaction between microRNAs and their targets. CrossLink is available both online and as a standalone version at http://www-ab.informatik.uni-tuebingen.de/software.

Computer Graphics↗

PubMed2000

[(99m)Tc]-sestamibi parathyroid scintigraphy in chronic haemodialysis patients: static and dynamic explorations.

BACKGROUND: The place of parathyroid gland imaging by [(99m)Tc](technetium)-sestamibi scintigraphy in uraemic patients with secondary hyperparathyroidism remains a matter of debate. The purpose of the present study was (i) to assess its value with respect to plasma intact parathyroid hormone (iPTH) levels and to surgical parathyroidectomy (PTx), and (ii) to explore the possibility of suppressing parathyroid [(99m)Tc]-sestamibi uptake by calcitriol. METHODS: In a first cross-sectional, static study 52 chronic haemodialysis (HD) patients with plasma iPTH levels between 14 and 2791 pg/ml (normal, 10-65 pg/ml) had a [(99m)Tc]-sestamibi scan, and 21 of them underwent surgical PTx. In a second longitudinal, dynamic study 14 chronic HD patients with advanced secondary hyperparathyroidism received short-term calcitriol treatment in an attempt to suppress [(99m)Tc]-sestamibi imaging of parathyroid glands. Calcitriol was given intravenously for 2 weeks, 2 microg after each haemodialysis session. Scintigraphy was carried out before and at the end of this inhibition test. RESULTS: [(99m)Tc]-Sestamibi scan led to imaging of one or more (maximum three) parathyroid glands in most, but not all, HD patients with plasma iPTH values >600 pg/ml. Based on surgical findings, overall sensitivity of [(99m)Tc]-sestamibi scan in correctly locating parathyroid glands was only 50%, whereas specificity was 100%. In contrast, its sensitivity was 100% in locating single glands in the subgroup of five patients with recurrent hyperparathyroidism. The calcitriol inhibition test showed suppression of [(99m)Tc]-sestamibi uptake by at least one parathyroid gland in eight patients (57%), with complete suppression in five of them (36%). Basal plasma iPTH or decrease of plasma iPTH in response to calcitriol was not predictive of suppressible [(99m)Tc]-sestamibi uptake in the individual case, although mean iPTH was markedly higher in patients with non-suppressible parathyroid glands. CONCLUSION: Because of its relatively low sensitivity the [(99m)Tc]-sestamibi scan is of limited help in the exploration of uraemic patients with severe secondary hyperparathyroidism before a first surgical PTx. However, it is very useful in locating the remaining parathyroid gland(s) in case of reoperation. The novel calcitriol inhibition test of [(99m)Tc]-sestamibi uptake could help to better distinguish parathyroid glands with non-suppressible, autonomous activity from glands whose activity might be amenable to long-term suppression.

Calcitriol↗

PubMed2004

Combinatorial exploration of the catalytic site of a drug-resistant dihydrofolate reductase: creating alternative functional configurations.

We have applied a global approach to enzyme active site exploration, where multiple mutations were introduced combinatorially at the active site of Type II R67 dihydrofolate reductase (R67 DHFR), creating numerous new active site environments within a constant framework. By this approach, we combinatorially modified all 16 principal amino acids that constitute the active site of this enzyme. This approach is fundamentally different from active site point mutation in that the native active site context is no longer accounted for. Among the 1536 combinatorially mutated active site variants of R67 DHFR we created, we selected and kinetically characterized three variants with highly altered active site compositions. We determined that they are of high fitness, as defined by a complex function consisting jointly of catalytic activity and resistance to trimethoprim. The k(cat) and K(M) values were similar to those for the native enzyme. The favourable Delta(DeltaG) values obtained (ranging from -0.72 to -1.08 kcal/mol) suggest that, despite their complex mutational pattern, no fundamental change in the catalytic mechanism has occurred. We illustrate that combinatorial active site mutagenesis can allow for the creation of compensatory mutations that could not be predicted and thus provides a route for more extensive exploration of functional sequence space than is allowed by point mutation.

Amino Acids↗

PubMed2003

Exploring the reciprocal relationship between immunity and inflammation in chronic inflammatory arthritis.

Experimental models seeking to explore how susceptible individuals develop rheumatoid arthritis (RA) propose that genetic and environmental factors shape a complex series of molecular and cellular interactions leading to a chronic inflammatory response. T lymphocytes and MHC class II genes have featured prominently in these models. More recent studies have suggested that perpetuation of inflammation in a disease-susceptible host might occur through failure to down-regulate the inflammatory process. One prediction from this model is that effective mechanisms of immunoregulation might be most easily investigated in non-susceptible individuals. However, this has been difficult to study in man. Based on the observation that extended MHC haplotypes are strongly associated with RA in different ethnic groups, I have explored the function of human MHC-encoded genes in transgenic mice using two different experimental approaches. First, by comparing the molecular interactions between disease-associated or non-associated HLA-DR4 molecules and CD4+ T lymphocytes, it has been possible to gain insight into how immune responses in non-susceptible individuals might differ from T-cell responses observed in a susceptible host. This has been achieved using transgenic mice expressing RA disease-associated and non-associated human HLA class II molecules. Secondly, the effects of prolonged exposure of T cells to the proinflammatory cytokine tumour necrosis factor alpha (TNF) have been studied in vitro and in vivo, focusing on T-cell receptor (TCR) signalling and effector responses. In studies of HLA class II transgenic mice, the major differences between disease-associated and non-associated alleles in terms of T-cell responses occur at the level of presentation of antigenic peptides, and the sustained expression of inflammatory cytokines such as TNF. Chronic exposure of T cells to inflammatory cytokines such as TNF induces a phenotype which resembles RA synovial T cells, including the induction of non-deletional and reversible hyporesponsiveness to TCR ligation and uncoupling of proximal TCR signal transduction pathways. The experimental findings are consistent with a model in which HLA class II-driven inflammatory cytokine expression uncouples TCR signalling pathways in the susceptible host in such a way as to profoundly suppress proliferative and immunoregulatory cytokine responses, while at the same time promoting cell survival and effector responses.

Animals↗

PubMed2005

Implications of the space radiation environment for human exploration in deep space.

Human exploration of the solar system beyond Earth's orbit will entail many risks for the crew on these deep space missions. One of the most significant health risks is exposure to the harsh space radiation environment beyond the protection provided by the Earth's intrinsic magnetic field. Crew on exploration missions will be exposed to a complex mixture of very energetic particles. Chronic exposures to the ever-present background galactic cosmic ray (GCR) spectrum consisting of all naturally occurring chemical elements are combined with sporadic, possibly acute exposures to large fluxes of solar energetic particles, mainly protons and alpha particles. The background GCR environment is mainly a matter of concern for stochastic effects, such as the induction of cancer with subsequent mortality in many cases, and late deterministic effects, such as cataracts and possible damage to the central nervous system. Unfortunately, the actual risks of cancer induction and mortality owing to the very important high-energy heavy ion component of the GCR spectrum are essentially unknown. The sporadic occurrence of extremely large solar energetic particle events (SPE), usually associated with intense solar activity, is also a major concern for the possible manifestation of acute effects from the accompanying high doses of such radiations, especially acute radiation syndrome effects such as nausea, emesis, haemorrhaging or, possibly, even death. In this presentation, an overview of the space radiation environment, estimates of the associated body organ doses and equivalent doses and the potential biological effects on crew in deep space are presented. Possible methods of mitigating these radiations, thereby reducing the associated risks to crew are also described.

Astronauts↗

PubMed2006

Medication adherence in schizophrenia: exploring patients', carers' and professionals' views.

One of the major clinical problems in the treatment of people with schizophrenia is suboptimal medication adherence. Most research focusing on determinants of nonadherence use quantitative research methods. These studies have some important limitations in exploring the decision-making process of patients concerning medication. In this study we explore factors influencing medication adherence behavior in people with schizophrenia using concept mapping. Concept mapping is a structured qualitative method and was performed in 4 European countries. Participants were 27 patients with schizophrenia, 29 carers, and 28 professionals of patients with schizophrenia. Five clinically relevant themes were identified that affect adherence: medication efficacy, external factors (such as patient support and therapeutic alliance), insight, side effects, and attitudes toward medication. Importance ratings of these factors differed significantly between professionals and carers and patients. Professionals, carers, and patients do not have a shared understanding of which factors are important in patients' medication adherence behavior. Adherence may be positively influenced if professionals focus on the positive aspects of medication, on enhancing insight, and on fostering a positive therapeutic relationship with patients and carers.

Adult↗

PubMed2003

From 1960s Evans County Georgia to present-day Jackson, Mississippi: an exploration of the evolution of cardiovascular disease in African Americans.

Cardiovascular disease (CVD) is the No. 1 cause of mortality in the United States and it disproportionately affects African Americans. However, there are earlier reports that African Americans had significantly less CVD than whites. This racial discrepancy in CVD rates was noticed primarily for coronary heart disease (CHD). This issue was examined in the Evans County (Georgia) Cardiovascular Disease Study conducted in the 1960s. It showed that African American men had significantly lower rates of CHD than white men. Over the last couple of decades, the rates of CVD have been declining. However, the rate of decline of CVD in African Americans has not been equal to that seen in whites, such that African Americans now have a disproportionate share of CVD in the United States. In the 1990s, the Jackson Heart Study was designed to explore the reasons for the current racial discrepancy. This articles reviews the findings of the Evans County Study and explores various hypotheses for why CVD in African Americans has evolved from a disease from which African Americans may have been "protected" to one in which they shoulder a disproportionate burden.

Black or African American↗