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D Donnelly

Publications and source records attributed to D Donnelly.

36 records · Page 2Linked to original sources
PubMed1994

The prediction and orientation of alpha-helices from sequence alignments: the combined use of environment-dependent substitution tables, Fourier transform methods and helix capping rules.

Amino acid substitution tables are used to estimate the extent to which amino acids in families of homologous proteins are exposed to the solvent. The approach depends on the comparison of difference environment-dependent tables for solvent accessible/inaccessible residues with amino acid substitutions at each position in an aligned set of sequences. The periodicity in the predicted accessible/inaccessible residues is calculated using a Fourier transform procedure modified from that used to calculate hydrophobic moments. alpha-Helices are identified from the characteristic periodicities and the solvent accessible face of the helix is defined. The initial helix predictions are refined using rules for identifying the N- and C-termini of helices from sequence alignments. These rules have been defined from a study of protein structures. The combined method correctly predicts 79% of the residues in helices and incorrectly predicts only 12% of the nonhelical residues as helical. In addition, since the method is reliable at predicting the correct number of helices in the correct position in the sequence and since it also predicts the internal face of each helix, the results can be used to postulate 3-D arrangements of the secondary structure elements.

Amino Acid Sequence↗
PubMed1994

The evolution and structure of aminergic G protein-coupled receptors.

An analysis of aligned sequences of the seven transmembrane segments of 59 aminergic G protein-coupled receptors (GPCRs) shows that their classification into subclasses based upon the nature of their ligands is over-simplified. Sequences similarity dendrograms indicate that the evolution of these receptors occurs at two sites (the G protein-coupling regions and the ligand binding site) and this results in convergent as well as divergent evolution. Amino acid substitution patterns at each position in the alignment discriminate between the internal residues and those that face the lipid and the periodicity in these patterns matches that of the classical alpha-helix. The point at which the fifth transmembrane helix protrudes into the cytoplasm and the point at which the seventh transmembrane helix protrudes on the extracellular side of the bilayer are detected. The positions of charged residues on the external face of the remaining helices are used to determine the point at which they enter and leave the bilayer. These data are used to construct three-dimensional models of GPCRs, which are based on the recently determined arrangement of the helices of bovine rhodopsin rather than on the structure of bacteriorhodopsin.

Amino Acid Sequence↗
PubMed1993

Modeling alpha-helical transmembrane domains: the calculation and use of substitution tables for lipid-facing residues.

Amino acid substitution tables are calculated for residues in membrane proteins where the side chain is accessible to the lipid. The analysis is based upon the knowledge of the three-dimensional structures of two homologous bacterial photosynthetic reaction centers and alignments of their sequences with the sequences of related proteins. The patterns of residue substitutions show that the lipid-accessible residues are less conserved and have distinctly different substitution patterns from the inaccessible residues in water-soluble proteins. The observed substitutions obtained from sequence alignments of transmembrane regions (identified from, e.g., hydrophobicity analysis) can be compared with the patterns derived from the substitution tables to predict the accessibility of residues to the lipid. A Fourier transform method, similar to that used for the calculation of a hydrophobic moment, is used to detect periodicity in the predicted accessibility that is compatible with the presence of an alpha-helix. If the putative transmembrane region is identified as helical, then the buried and exposed faces can be discriminated. The presence of charged residues on the lipid-exposed face can help to identify the regions that are in contact with the polar environment on the borders of the bilayer, and the construction of a meaningful three-dimensional model is then possible. This method is tested on an alignment of bacteriorhodopsin and two related sequences for which there are structural data at near atomic resolution.

Amino Acid Sequence↗
PubMed1993

Predicting the point at which transmembrane helices protrude from the bilayer: a model of the antenna complexes from photosynthetic bacteria.

We describe a method for predicting the point at which a transmembrane helix leaves the bilayer and enters the more polar region of the aqueous exterior. This is achieved by comparing the relative directions of the hydrophobic and internal faces of the transmembrane helices which should be opposite for the regions within the bilayer but equivalent for the regions on the outside. This information provides a strong constraint in the process of modelling membrane proteins. We go on to use the approach to model the monomers of the bacterial light-harvesting antenna complexes. This information is then combined with some preliminary crystallographic data and biochemical results to produce a 3-D model of a tetramer.

Amino Acid Sequence↗
PubMed1992

Environment-specific amino acid substitution tables: tertiary templates and prediction of protein folds.

The local environment of an amino acid in a folded protein determines the acceptability of mutations at that position. In order to characterize and quantify these structural constraints, we have made a comparative analysis of families of homologous proteins. Residues in each structure are classified according to amino acid type, secondary structure, accessibility of the side chain, and existence of hydrogen bonds from the side chains. Analysis of the pattern of observed substitutions as a function of local environment shows that there are distinct patterns, especially for buried polar residues. The substitution data tables are available on diskette with Protein Science. Given the fold of a protein, one is able to predict sequences compatible with the fold (profiles or templates) and potentially to discriminate between a correctly folded and misfolded protein. Conversely, analysis of residue variation across a family of aligned sequences in terms of substitution profiles can allow prediction of secondary structure or tertiary environment.

Amino Acid Sequence↗
PubMed1991

Relative contributions of dietary sodium sources.

Information on the relative contributions of all dietary sodium (Na) sources is needed to assess the potential efficacy of manipulating the component parts in efforts to implement current recommendations to reduce Na intake in the population. The present study quantified the contributions of inherently food-borne, processing-added, table, cooking, and water sources in 62 adults who were regular users of discretionary salt to allow such an assessment. Seven-day dietary records, potable water collections, and preweighted salt shakers were used to estimate Na intake. Na added during processing contributed 77% of total intake, 11.6% was derived from Na inherent to food, and water was a trivial source. The observed table (6.2%) and cooking (5.1%) values may overestimate the contribution of these sources in the general population due to sample characteristics, yet they were still markedly lower than previously reported values. These findings, coupled with similar observations from other studies, indicate that reduction of discretionary salt will contribute little to moderation of total Na intake in the population.

Adult↗
PubMed1991

Sexual relations in later life: a national study of married persons.

Sexual behavior among married persons 60 years of age and older was examined using data from the National Survey of Families and Households. About 53 percent of the entire sample, and 24 percent of those 76 years of age and older, report having had sexual relations at least once within the past month. Persons who have been sexually active within the past month report having sex about four times during the month. While respondent's age is significantly related to sexual behavior, the monthly incidence and overall sexual frequency variables are not influenced by gender, race, or a Gender by Spouse's Health Status interaction term. While the NSFH variables included in our model are poor predictors of elderly persons' sexual behavior, analyses reveal that a person's sense of self-worth/competence and his/her partner's health status are significantly and positively related to the incidence of sex within the past month.

Aged↗
PubMed1989

An analysis of the periodicity of conserved residues in sequence alignments of G-protein coupled receptors. Implications for the three-dimensional structure.

Twenty-three sequences from the family of G-protein coupled receptors have been aligned according to the 'historical alignment' procedure of Feng and Doolittle. Fourier transform analysis of this reveals that parts of five of the seven putative membrane-spanning regions exhibit a periodicity of conserved/nonconserved residues which is compatible with the periodicity of the alpha-helix. This would place the conserved residues on one side of the helix, which may face the inside of the proposed seven membered helical bundle.

Amino Acid Sequence↗
PubMed1987

Instilling eyedrops: difficulties experienced by patients following cataract surgery.

It was hypothesized that patients instilling their own drops following cataract extraction would experience difficulties with this, due to age-related factors, the nature of the operation itself and the fact that studies in other areas have shown compliance to be less than predicted. Ten patients who intended to instil their own drops were each interviewed on the ward before discharge and again 2 weeks later at home. They were asked about previous experience of using drops, general health, knowledge of their treatment regime, practice received on the ward and their feelings about how they were coping. The majority had inappropriate expectations of what compliance with treatment would involve. Six had used drops before and this was the major factor influencing their decision on this occasion. Supervised practice emerged as the recommended method for teaching drop instillation but this was not carried out often enough on the wards. It was concluded that if more time was devoted to developing and improving the teaching of drop instillation this would result in increased compliance with treatment. However, it may not be possible to achieve all the goals of a teaching programme on the wards and the teaching role may need to be extended into the community.

Adaptation, Psychological↗
PubMed1984

A noncholinergic site-directed monoclonal antibody can impair agonist-induced ion flux in Torpedo californica acetylcholine receptor.

We have employed several monoclonal antibodies (mAbs) directed against several regions of the acetylcholine receptor (AcChoR) to assist in the determination of the antigenic structure of this multisubunit glycoprotein and to better understand molecular events involved in the impairment of neuromuscular transmission in the autoimmune disease myasthenia gravis. Among three mAbs shown to block agonist-induced ion fluxes, mAb 371A is a putative probe of an ion channel domain(s) of the AcChoR. It appears to bind to an antigenic determinant whose structure is maintained upon treatment with sodium dodecyl sulfate, the stoichiometry of binding being of one mAb per alpha-bungarotoxin binding site. Binding of mAb 371A to the AcChoR does not affect binding of cholinergic agonists or antagonists (carbamoylcholine and d-tubocurarine) or neurotoxins (alpha-bungarotoxin) or the ability of membrane-bound AcChoR to undergo reversible sensitization-desensitization affinity transitions. However, this mAb inhibits agonist-induced thallium (T1+) influx into AcChoR-rich membrane vesicles, as measured on a millisecond time scale by means of a rapid kinetics "stopped-flow/fluorescence quenching" technique. The stoichiometry of inhibition by bound mAb 371A coincides with that for maximal binding.

Animals↗
PubMedDate not supplied

The tie that binds. Nurturing the faith tradition.

Catholic healthcare leadership has changed dramatically. Even when sisters administer a system or facility, other executives often are not affiliated with canonical religious institutes. Yet lay and religious alike are responsible for ensuring that the faith which inspired the ministry is still the source of a healthcare organization's common vision and direction. Faith is best understood as "meaning making," which everyone does in the process of making sense out of our worlds. As we sort out meaning about ourselves and our relationships, we make statements that indicate where our faith is. Faith also involves the whole person: affective, behavioral, and cognitive. Catholic healthcare's task is more than to instruct about "content" of the faith tradition. The task is to nurture people to be in faith through faith development. Faith development is based on the conviction that faith changes, is dynamic, and is challenging. Faith development never stops. Faith formation is applying what we profess to believe to what we do.

Catholicism↗