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PubMed2003

Genome-wide studies of protein-protein interaction.

Recent large-scale studies of protein complexes in yeast have demonstrated that the wide majority of proteins exist in the cell as parts of multicomponent assemblies, mostly novel and of unknown function. The structural and functional analysis of these complexes should be a priority for structural biologists in coming years. In silico methods such as docking simulations, which may contribute to this analysis, are being tested in the CAPRI community-wide experiment, which assesses blind predictions of the structure of protein-protein complexes.

Algorithms↗
PubMed1993

Development of screening tests for aneuploidy induction by environmental pollutants.

When legally required mutagenicity testing of chemicals is undertaken, the important genetic end point of aneuploidy is not included because validated test methods are lacking. Therefore, the Commission of the European Communities (CEC) has funded a research program to develop and validate tests for aneuploidy induction. Ten chemicals, selected on the basis of their ability to interact with cell organelles relevant for aneuploidy induction, were tested in 11 laboratories. The assays ranged from in vitro tubulin assembly studies to in vivo germ-cell tests. The results allow several conclusions: a) Fungal aneuploidy tests are not capable of detecting inhibitors of mammalian tubulin polymerization such as colchicine and vinblastine. Therefore, they will not play a role in screening for aneuploidy but are of value for studying the relationship between induced aneuploidy and recombination. b) Chemicals that induce aneuploidy in mammalian germ cells are readily detected in the in vitro mammalian cell systems. Some chemicals such as thiabendazole and thimerosal induce aneuploidy in vitro but do not appear to be very effective in vivo. c) Cell division aberrations induced in mammalian cells in vitro seem to be predictive for aneuploidy induction in the same cell type. Likewise, c-mitotic effects and cell cycle delay in vivo in mitotic and meiotic cells correlate with aneuploidy induction in the respective tissue. A second CEC Aneuploidy Program has started recently to refine the most promising test protocols, to provide understanding of variety of mechanisms by which chemicals induce aneuploidy, and to establish a data base for aneugens among environmental pollutants.

Aneuploidy↗
PubMed2006

Annotating the human proteome: beyond establishing a parts list.

The completion of the human genome has shifted the attention from deciphering the sequence to the identification and characterisation of the functional components, including genes. Improved gene prediction algorithms, together with the existing transcript and protein information, have enabled the identification of most exons in a genome. Availability of the 'parts list' has fostered the development of experimental approaches to systematically interrogate gene function on the genome, transcriptome and proteome level. Studying gene function at the protein level is vital to the understanding of how cells perform their functions as variations in protein isoforms and protein quantity which may underlie a change in phenotype can often not be deduced from sequence or transcript level genomics experiments alone. Recent advancements in proteomics have afforded technologies capable of measuring protein expression, post-translational modifications of these proteins, their subcellular localisation and assembly into complexes and pathways. Although an enormous amount of data already exists on the function of many human proteins, much of it is scattered over multiple resources. Public domain databases are therefore required to manage and collate this information and present it to the user community in both a human and machine readable manner. Of special importance here is the integration of heterogeneous data to facilitate the creation of resources that go beyond a mere parts list.

Humans↗
PubMed2004

Molecular phylogeography and systematics of the arid-zone members of the Egernia whitii (Lacertilia: Scincidae) species group.

We assembled a molecular phylogeny for the arid-zone members of the Egernia whitii species group to test Pianka's [Zoogeography and speciation of Australian desert lizards: an ecological perspective, Copeia (1972) 127-145] hypothesis that habitat specificity to the three major arid-zone vegetation communities is the primary cause of lizard speciation within the arid interior of Australia. This hypothesis predicts that species should exhibit phylogeographic structuring concordant with the major arid-zone vegetation types. Sequence data were obtained from four of the five arid-zone members of the E. whitii species group, and from across the ranges of the ecologically generalized E. inornata and E. multiscutata and the more specialized E. striata. We targeted a fragment (696 base pair (bp)) of the mitochondrial genome comprising the 3' half of the ND4 gene. We analysed the data using parsimony, maximum likelihood and Bayesian methods. Our phylogeny confirms the monophyly of the arid-zone members of the species group, although the phylogenetic relationships among species were not fully resolved. Although our topology does not support the recognition of the existing subspecies within E. multiscutata, there is a substantial phylogeographic break between South Australian/Victorian (Clade 1) and Western Australian (Clade 2) populations. We found considerable phylogeographic structure within E. inornata, with six major clades identified. However, these clades were not concordant with the distribution of habitat types in the arid-zone. Phylogeographic structure was also observed in the more specialized E. striata, although our analysis revealed close phylogenetic affinities between the sympatric species E. striata and E. kintorei. Shimodaira-Hasegawa topology tests were equivocal in regard to whether the phylogeographic structure within E. striata was in accordance with Pianka's predictions. Although our data failed to provide strong support for the suggestion that ecological and habitat factors are responsible for the diversification of arid-zone lizards, most E. inornata and E. striata populations had similar habitats, indicating that adaptation to particular habitats may have some role in the speciation of lizards in the Australian arid-zone.

Animals↗
PubMed2006

The role of ring external fixation in Charcot foot arthropathy.

These two morbidly obese patients with severe Charcot foot arthropathy were treated successfully with percutaneous correction of their deformity followed by a stepwise application of a pre-assembled neutrally aligned multiplane ring external fixator. This technique transfers well to the trauma environment in which alignment can be maintained without further violation within the zone of injury. The application of the fine wire ring external fixation has been used for many years to accomplished leg lengthening and correction of deformity. Historically it has required a great deal of experience to apply to complex frames and implement the required daily adjustments. The patient experience often has been an unpleasant ordeal with a high potential for associated morbidity. This negative exposure has prompted practicing orthopedic surgeons to avoid this technique, feeling that it best be left to those in tertiary care setting who are equipped to handle the morbidity and complications. Taking this technology from the domain of the deformity surgeon to the general orthopedic community will require the suppression of bad memories from residency. Using the device solely as a method of maintaining alignment eliminates many of the dynamic attributes that contributes to pain and morbidity. The bone and soft tissues are not stretched, eliminating much of the pain and decreasing the rate of traction-associated pin tract morbidity. Because there is no dynamic of the treatment, the simplified frame can be pre-assembled and have no adjustable components. The experience derived from this application has the potential of expanding the role of ring external fixation. Where the ring has been used previously as method of both obtaining and maintaining alignment, this application uses a simplified neutral version of a complex device to simply maintain alignment in a high risk patient population. Correction of deformity and achieving alignment/reduction of fractures is well within the domain of practicing orthopedic surgeon. Once that correction has been achieved, this application simply maintains that correction. It helps avoid extensive surgical dissection in a poor host and eliminates the need for bone that is mechanically capable of holding internal fixation devices during the bony and soft tissue healing period.

Adult↗
PubMedDate not supplied

Culturally attuned recruitment, retention, and adherence in Alzheimer disease and associated disorders: a best practices working model.

This analysis presents a recruitment, retention, and (treatment and/or research) adherence (RRA) best practices model for targeting Alzheimer disease and associated dementias (ADAD) impacting ethnically diverse populations. RRA practice involves many more factors beyond cultural considerations to be highlighted here. However, it is the cultural dimension where much is at stake, where there is the least comprehensive framework, and where the most ambiguity exists relative to RRA practice. The discussion proceeds on three premises. First, a composite, culturally attuned RRA working model can be assembled from the current literature. Second, culturally speaking, recruitment, retention, and adherence are essentially linked processes. Although each of the components of RRA practice has its own unique set of tasks, culture permeates them all. Third, any RRA practice model that emerges must be tailored to the communities, the specific target populations, and the programmatic circumstances to which the effort is attached.

Biomedical Research↗
PubMed2005

Genome cluster database. A sequence family analysis platform for Arabidopsis and rice.

The genome-wide protein sequences from Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) spp. japonica were clustered into families using sequence similarity and domain-based clustering. The two fundamentally different methods resulted in separate cluster sets with complementary properties to compensate the limitations for accurate family analysis. Functional names for the identified families were assigned with an efficient computational approach that uses the description of the most common molecular function gene ontology node within each cluster. Subsequently, multiple alignments and phylogenetic trees were calculated for the assembled families. All clustering results and their underlying sequences were organized in the Web-accessible Genome Cluster Database (http://bioinfo.ucr.edu/projects/GCD) with rich interactive and user-friendly sequence family mining tools to facilitate the analysis of any given family of interest for the plant science community. An automated clustering pipeline ensures current information for future updates in the annotations of the two genomes and clustering improvements. The analysis allowed the first systematic identification of family and singlet proteins present in both organisms as well as those restricted to one of them. In addition, the established Web resources for mining these data provide a road map for future studies of the composition and structure of protein families between the two species.

Algorithms↗
PubMed1981

A correspondence course for the further education of French dietitians -- a pilot experiment run by Nancy University.

A further education scheme French dietitians began in 1975 at the request of the Association of French Dietitians. Because the dietitians were widely scattered, a correspondence course was chosen. The three-year course comprises 18 booklets including pathology, physiology, organisation and administration, community law and hygiene, and pedagogy. At the end of each booklet the candidates write a paper, on a given aspect of the subject concerned, which is returned to the training centre for correction by the writer of the booklet. Each year the dietitians and teaching staff assemble for a five-day seminar at which the subjects are further elaborated. Candidates completing 12 written papers and attending all three seminars are eligible to sit the examination. Over the past five years, 679 dietitians have taken part in this course and 126 candidates have passed Nancy University's advanced dietetics examination. The original feature of this scheme is that dietitians are able to study for higher qualifications whilst continuing their regular professional duties.

Curriculum↗
PubMed2001

Demographic and health issues in rural aging: a global perspective.

The world is witnessing unprecedented changes in population structure, so that both the absolute number and proportion of older people are increasing worldwide. For many developing countries, rapid population aging and the phenomenon of a "double burden" of both infectious disease and emerging chronic diseases represent a major challenge. Many of those who will contribute to these extraordinary transitions will live in rural areas. Many countries, especially the poorest, still have a huge burden of infectious diseases, including increasing rates of HIV/AIDS along with a growing problem of chronic diseases. A number of critical policy considerations come to the fore in examining issues associated with rural aging, including: the need for rural development policies that take account of population aging and the needs of older people; improved coordination and integration of public health and care services in rural areas; support for nongovernmental organizations and community group efforts; and greater use of new technologies for communication. The year 1999 was pivotal for aging in terms of perceptions, attitudes, public action, better research and knowledge, and improved policy decisions that will benefit all of society into this new century. The Second United Nations World Assembly to be held in Madrid in April 2002 will provide further opportunity to build upon this progress and in the formulation of a new International Plan of Action on Aging to point the way for decisive action on positive policy and program initiatives for the future.

Aged↗
PubMed1995

[Legislation related to mental health: a review of various international experiences].

The main areas dealt with by current mental health legislation, worldwide, are reviewed. These areas concern mainly: (i) rights of the mentally ill (right to care and human rights), (ii) quality of care, (iii) the use of administrative and budget control measures, and (iv) consumer participation and involvement in the organization and management of mental health care services. The evolution of international legislation (particularly United Nations Declarations, Covenants and Resolutions) relative to people with mental disorders are described on the basis of up-to-date examples of legal models from different jurisdictions throughout the world. The main current trends are identified and alternatives are advanced for the respect of the human rights of these people and for the improvement of their care. The basis for these proposed alternatives is to be found in the recently approved United Nations General Assembly Resolution on "The protection of persons with mental illness and the improvement and the improvement of mental health care". This Resolution is described and discussed in some detail.

Community Participation↗
PubMed2004

A community-based breast cancer screening program for medically underserved women: its effect on disease stage at diagnosis and on hazard of death.

OBJECTIVE: Earlier studies by this research team found that medically underserved minority women in the Miami-Dade County area of the state of Florida, United States, were in need of breast cancer screening and that there were problems with availability, accessibility, and acceptability of services. In response, a community-based comprehensive breast cancer screening program called the Early Detection Program (EDP) was developed. The specific purpose of this study was to assess the effect that EDP participation had on stage at diagnosis and on hazard of death. METHODS: Existing data from the Florida Cancer Data System (FCDS), a statewide cancer registry, were linked with data from the EDP. In December 1998 we assembled a multiethnic (African-American, black Hispanic, white Hispanic, and white non-Hispanic) retrospective cohort with the following inclusion criteria: all women aged 40 and older with breast cancer diagnosed and staged at University of Miami/Jackson Memorial Medical Center (which is located in the city of Miami, Florida) from January 1987 through December 1997. EDP participants were medically underserved, that is, they resided in lower socioeconomic areas and/or had limited or no health insurance to cover medical costs. Subjects identified as EDP participants were compared to nonparticipants with respect to disease stage at diagnosis and hazard of death. Logistic regression and Cox regression models were used for analysis. RESULTS: EDP participants were 2.4 times as likely (95% confidence interval = 1.71 to 3.43) to present with a diagnosis of localized cancer as were nonparticipants, even after controlling for race and age at diagnosis. EDP participation was independently associated with both earlier diagnosis and reduced hazard of death. CONCLUSIONS: Participation in the EDP increases the likelihood of early detection of breast cancer and reduces the hazard of death for medically underserved women in the Miami-Dade County area of Florida. Interestingly, white Hispanics showed a better survival than did both African-Americans and white non-Hispanics. Our research also demonstrates the value of utilizing existing cancer registry data to evaluate a community-based program such as the EDP.

Adult↗
PubMed2004

BOD: a customizable bioinformatics on demand system accommodating multiple steps and parallel tasks.

The integration of bioinformatics resources worldwide is one of the major concerns of the biological community. We herein established the BOD (Bioinformatics on demand) system to use Grid computing technology to set up a virtual workbench via a web-based platform, to assist researchers performing customized comprehensive bioinformatics work. Users will be able to submit entire search queries and computation requests, e.g. from DNA assembly to gene prediction and finally protein folding, from their own office using the BOD end-user web interface. The BOD web portal parses the user's job requests into steps, each of which may contain multiple tasks in parallel. The BOD task scheduler takes an entire task, or splits it into multiple subtasks, and dispatches the task or subtasks proportionally to computation node(s) associated with the BOD portal server. A node may further split and distribute an assigned task to its sub-nodes using a similar strategy. In the end, the BOD portal server receives and collates all results and returns them to the user. BOD uses a pipeline model to describe the user's submitted data and stores the job requests/status/results in a relational database. In addition, an XML criterion is established to capture task computation program details.

Computational Biology↗
PubMed1991

[Mosquito caused death: the yellow fever epidemics in San Juan of Puerto Rico 1804-1805].

At the end of the eighteenth and beginning of the nineteenth centuries, yellow fever epidemics occurred frequently in America and Europe, in the vicinity of the Mediterranean, Atlantic, and Caribbean coasts. There is only brief information available on the 1804-5 epidemic in San Juan, but it shows that mortality in the city was inordinate. Nevertheless, the minutes of the meetings of the Municipal Assembly in this period make no mention of the epidemic, and allude to it only in veiled fashion. In spite of the accumulation of individual tragedies (for example, it is likely that the two daughters of governor Ramón de Castro were among the victims), the documents show little evidence of community reaction to the epidemic, which apparently ceased in mid-1805.

Aedes↗
PubMed2026

Elevated water levels drive greenhouse gas mitigation in the riparian zone profile.

Wetlands are critical for climate regulation, with their hyporheic zone serving as sensitive interfaces for groundwater-soil-atmosphere exchange. These zones are active hotspots for carbon-nitrogen cycling and greenhouse gas (GHG) emissions (CO2, CH4, N2O), yet the impact of water level fluctuations on these emissions and their microbial drivers in freshwater wetlands remains poorly understood. This study investigated the spatiotemporal dynamics of GHG emissions and carbon-nitrogen coupling processes along riparian soil profiles of Baiyangdian Lake during water level fluctuations. Employing static chamber measurements, microcosms, quantitative PCR, Metagenome-Assembled genome (MAG) analyses, and Structural Equation Modeling (SEM), we observed that GHG emissions were significantly affected by water level fluctuations. Specifically, CO2 and N2O fluxes, as well as CO2 production potential were significantly lower at high-water-level conditions. Water level also emerged as a key driver of microbial community structure, with Methylococcaceae and Methanosarcinaceae as key regulators of CH4 emission, and Anaeromyxobacteraceae as central to N2O dynamics. A high-quality Methylomirabilales-like MAG, possessing the complete pathway for coupled nitrate reduction and methane oxidation, was identified. Its abundance negatively correlated with water level, suggesting that these C-N coupling bacteria contribute to reducing GHG emissions. This study provides crucial theoretical insights and identifies microbial targets for mitigating wetland GHG emission through hydrological management.

Greenhouse Gases↗
PubMed1993

Criterion based audit in prosthetic dentistry.

A criterion based retrospective audit into the provision of complete dentures in an undergraduate teaching programme has been produced. This consisted of a series of questions related to the treatment of the patient and the satisfaction or otherwise expressed about the treatment. The audit revealed where treatment had been successful according to the established criteria. It has been found that an audit of this nature is demanding of clinicians' time but does show where improvements can be made in patient management which will result in better health care. Clinical audit is now recognized as forming an important part of health care. It is applicable to all areas of dentistry, ie general dental practice, the community dental services and the hospital services, and to all specialities eg prosthetics, orthodontics etc. An audit programme needs careful planning and a pilot study is worthwhile to indicate areas of difficulty. This audit has been used in an undergraduate training programme, however, the process by which the audit has been assembled is an example of how an audit could be established in any area of dentistry, provided that the criteria are modified to make them relevant to the clinical speciality.

Aged↗
PubMed2000

An optimized protocol for analysis of EST sequences.

The vast body of Expressed Sequence Tag (EST) data in the public databases provide an important resource for comparative and functional genomics studies and an invaluable tool for the annotation of genomic sequences. We have developed a rigorous protocol for reconstructing the sequences of transcribed genes from EST and gene sequence fragments. A key element in developing this protocol has been the evaluation of a number of sequence assembly programs to determine which most faithfully reproduce transcript sequences from EST data. The TIGR Gene Indices constructed using this protocol for human, mouse, rat and a variety of other plant and animal models have demonstrated their utility in a variety of applications and are freely available to the scientific research community.

Algorithms↗
PubMed2006

High-throughput trapping of secretory pathway genes in mouse embryonic stem cells.

High-throughput gene trapping is a random approach for inducing insertional mutations across the mouse genome. This approach uses gene trap vectors that simultaneously inactivate and report the expression of the trapped gene at the insertion site, and provide a DNA tag for the rapid identification of the disrupted gene. Gene trapping has been used by both public and private institutions to produce libraries of embryonic stem (ES) cells harboring mutations in single genes. Presently, approximately 66% of the protein coding genes in the mouse genome have been disrupted by gene trap insertions. Among these, however, genes encoding signal peptides or transmembrane domains (secretory genes) are underrepresented because they are not susceptible to conventional trapping methods. Here, we describe a high-throughput gene trapping strategy that effectively targets secretory genes. We used this strategy to assemble a library of ES cells harboring mutations in 716 unique secretory genes, of which 61% were not trapped by conventional trapping, indicating that the two strategies are complementary. The trapped ES cell lines, which can be ordered from the International Gene Trap Consortium (http://www.genetrap.org), are freely available to the scientific community.

Animals↗