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Biomedical subjects

Paul Kearney

Publications and source records attributed to Paul Kearney.

6 recordsLinked to original sources

The use of functional domains to improve transmembrane protein topology prediction.

Transmembrane proteins affect vital cellular functions and pathogenesis, and are a focus of drug design. It is difficult to obtain diffraction quality crystals to study transmembrane protein structure. Computational tools for transmembrane protein topology prediction fill in the gap between the abundance of transmembrane proteins and the scarcity of known membrane protein structures. Their prediction accuracy is still inadequate: TMHMM, the current state-of-the-art method, has less than 52% accuracy in topology prediction on one set of transmembrane proteins of known topology. Based on the observation that there are functional domains that occur preferentially internal or external to the membrane, we have extended the model of TMHMM to incorporate functional domains, using a probabilistic approach originally developed for computational gene finding. Our extension is better than TMHMM in predicting the topology of transmembrane proteins. As prediction of functional domain improves, our system's prediction accuracy will likely improve as well.

Computational Biology↗

Organ messenger ribonucleic acid and plasma proteome changes in the adjuvant-induced arthritis model: responses to disease induction and therapy with the estrogen receptor-beta selective agonist ERB-041.

Two receptors [estrogen receptor (ER)alpha and ERbeta] mediate the manifold effects of estrogens throughout the body. Although a clear role has been established for ERalpha in the classical effects of estrogen activity, the physiological role of ERbeta is less well understood. A small-molecule ERbeta selective agonist, ERB-041, has potent antiinflammatory activity in the Lewis rat model of adjuvant-induced arthritis. To characterize the response of target organs and pathways responsible for this antiinflammatory effect, mRNA expression profiling of the spleen, lymph node, and liver was performed, in conjunction with a global analysis of the plasma proteome. We find that the expression of a large number of genes and proteins are altered in the disease model and the majority of these are partially or fully reversed by ERB-041 treatment. Regulated pathways include the acute-phase response, eicosanoid synthesis, fatty acid metabolism, and iron metabolism. In addition, many of the regulated genes and proteins are known to be dysregulated in human rheumatoid arthritis, providing further evidence that the manifestations of the Lewis rat adjuvant-induced arthritis model bear similarity to the human disease.

Animals↗

Novel spanish translators for acute care nurses and physicians: usefulness and effect on practitioners' stress.

BACKGROUND: Language barriers are significant impediments to providing quality health care, and increased stress levels among nurses and physicians are associated with these barriers. However, little evidence supports the usefulness of a translation tool specific to health care. OBJECTIVES: To evaluate the effectiveness of a novel English-Spanish translator designed specifically for nurses and physicians. The hypothesis was that the translator would be useful and that use of the translator would decrease stress levels among nurses and physicians caring for Spanish-speaking patients. METHODS: Novel English-Spanish translators were developed entirely on the basis of input from critical care nurses and physicians. After 7 months of use, users completed surveys. Usefulness of the translator and stress levels among users were reported. RESULTS: A total of 60% of nurses (n=32) and 71% (n=25) of physicians responded to the survey. A total of 96% of physicians and 97% of nurses considered the language barrier an impediment to delivering quality care. Nurses reported significantly more stress reduction than did physicians (P=.01). Most nurses and physicians had used the translator during the survey period. Overall, 91% of nurses and 72% of physicians found that the translator met their needs at the bedside some, most, or all of the time. All nurses thought that they most likely would use the translator in the future. CONCLUSIONS: The translator was useful for most critical care nurses and physicians surveyed. Health care providers, especially nurses, experienced decreased stress levels when they used the translator.

Communication Barriers↗

Probabilistic analysis indicates discordant gene trees in chloroplast evolution.

Analyses of whole-genome data often reveal that some genes have evolutionary histories that diverge from the majority phylogeny estimated for the entire genome. We present a probabilistic model that deals with heterogeneity among gene trees, implement it via the Gibbs sampler, and apply it to the plastid genome. Plastids and their genomes are transmitted as a single block without recombination, hence homogeneity among gene trees within this genome is expected. Nevertheless, previous work has revealed clear heterogeneity among plastid genes (e.g., Delwiche and Palmer 1996). Other studies, using whole plastid genomes of various algae and land plants, found little additional heterogeneity (Martin et al. 1998; Adachi et al. 2000). We augment the earlier studies by using a data set of 14 taxa: 6 land plants, 2 green algae, a diatom, 2 red algae and a cryptophyte, the cyanelle of the glaucocystophyte Cyanophora, and the blue-green alga Synechocystis as an outgroup. Contrary to the earlier analyses, we cannot find even a single, dominant consensus tree. Therefore, we formulate a probabilistic model that divides the genes into two sets: those that follow the consensus tree and those that have independent gene trees. No particular tree is supported by more than three-fourths of the genes. But the set of genes that follows a certain tree is fairly independent of data processing and the method of analysis. With one possible exception, we find no evidence for collinear or functionally related genes to follow similar trees. The phylogenetic pattern also seems independent of bias in amino acid composition. Among possible explanations for the observed phenomenon, the hypothesis that different genes have different covarion structures is difficult to assess. But gene duplication may be possible through the inverted or direct repeat regions, while horizontal gene transfer seems less likely. In contrast to green algae and land plants, inverted repeat regions in red algae and in Cyanophora show abundant differences among the copies. Thus, genes may get duplicated when they are recruited into the inverted repeat region and one of the two copies may be lost after leaving the inverted repeat region.

Chloroplasts↗

Organelle proteomics: looking at less to see more.

The recent finding that the human genome comprises between 21000 and 39000 genes, a number much lower than expected, has in no way simplified the complexity associated with the understanding of how cells perform their functions. Elucidation of the molecular mechanisms underlying cell functions will require a global knowledge of the expressed proteins, including splice variant products, their post-translational modifications, their subcellular localizations and their assembly into molecular machines as deduced from protein-protein interactions, at any given time during the life of the cell or under any cellular conditions. Current and expected advances in mass spectrometry and bioinformatics might help the realization of these goals in a shorter time than is currently predicted.

Animals↗

Impact of language barrier on acute care medical professionals is dependent upon role.

Communication with patients is essential to providing quality medical care. The study was conducted to evaluate the effects of language barriers on health care professionals. It is hypothesized that these language barriers are commonly perceived by health care professionals and they are a source of workplace stress in acute care environments. We designed and distributed a survey tool of staff experiences and attitudes regarding the English-Spanish language barrier among patients in an acute care surgical environment of a tertiary medical center. Responses were anonymous, stratified by professional role and comparisons made using paired t tests. Sixty-one nurses and 36 physicians responded to the survey. Overall, 95% of nurses reported that the language barrier was an impediment to quality care, whereas 88% of physicians responded similarly (P = .0004). More nurses than physicians report experiencing stress (97% vs. 78%) and the degree of stress appears to be greater for nurses (P < .0001). The basis of stress was unique between the two groups. This study demonstrates that acute care hospital medical professionals perceive language barriers as an impediment to quality care delivery and as a source of workplace stress. Nurse and physician perceptions differ; therefore, strategies to address these language barriers should be specific to those professional roles. These barriers create a void in health care quality and safety that has effects on health care professionals.

Academic Medical Centers↗