Biomedical subjects

A J Hope

Publications and source records attributed to A J Hope.

4 recordsLinked to original sources

PubMed2006

Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose-volume outcome relationships.

Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

Computer Simulation↗

PubMed1998

Switch in rod opsin gene expression in the European eel, Anguilla anguilla (L.).

The rod photoreceptors of the European eel, Anguilla anguilla (L.), alter their wavelength of maximum sensitivity (lambda max) from c.a. 523 nm to c.a. 482 nm at maturation, a switch involving the synthesis of a new visual pigment protein (opsin) that is inserted into the outer segments of existing rods. We artificially induced the switch in rod opsin production by the administration of hormones, and monitored the switch at the level of mRNA accumulation using radiolabelled oligonuleotides that hybridized differently to the two forms of eel rod opsin. The production of the deep-sea form of rod opsin was detected 6 h after the first hormone injection, and the switch in rod opsin expression was complete within four weeks, at which time only the mRNA for the deep-sea opsin was detectable in the retinal cells. It is suggested that this system could be used as a tractable model for studying the regulatory control of opsin gene expression.

Anguilla↗

PubMed1998

Functional coordination of microtubule-based and actin-based motility in melanophores.

The fish melanophore has been considered the exemplar of microtubule-based organelle transport. In this system, a radial array of uniformly polarized microtubules [1] provides a framework on which dynein-related and kinesin-related motors drive pigment granules toward the minus or plus ends, respectively [2-4]. Stimulation of minus-end motors accounts satisfactorily for aggregation of granules at the cell center. Rapid dispersion is clearly microtubule-dependent; however, the uniform distribution of granules throughout the cytoplasm is paradoxical because stimulation of plus-end motors is predicted to drive the granules to the cell margin. This paradox suggested that the transport system was incompletely understood. Here, we report the discovery of a microtubule-independent motility system in fish melanophores. The system is based on actin filaments and is required for achieving uniform distribution of pigment granules. When it is abrogated, granules accumulate at the cell's margin as predicted for microtubule plus-end motors acting alone. The results presented here demonstrate the functional coordination of microtubule and actin filament systems, a finding that may be of general significance for organelle motility in cytoplasm.

Actin Cytoskeleton↗

PubMed1997

Mechanisms of wavelength tuning in the rod opsins of deep-sea fishes.

The main object of this study was to investigate the molecular basis for changes in the spectral sensitivity of the visual pigments of deep-sea fishes. The four teleost species studied, Hoplostethus mediterraneus, Cataetyx laticeps, Gonostoma elongatum and Histiobranchus bathybius, are phylogenetically distant from each other and live at depths ranging from 500 to almost 5000 m. A single fragment of the intronless rod opsin gene was PCR-amplified from each fish and sequenced. The wavelength of peak sensitivity for the rod visual pigments of the four deep-sea species varies from 483 nm in H. mediterraneus and G. elongatum to 468 nm in C. laticeps. Six amino acids at sites on the inner face of the chromophore-binding pocket formed by the seven transmembrane a-helices are identified as candidates for spectral tuning. Substitutions at these sites involve either a change of charge, or a gain or loss of a hydroxyl group. Two of these, at positions 83 and 292, are consistently substituted in the visual pigments of all four species and are likely to be responsible for the shortwave sensitivity of the pigments. Shifts to wavelengths shorter than 480 nm may involve substitution at one or more of the remaining four sites. None of the modifications found in the derived sequences of these opsins suggest functional adaptations, such as increased content of hydroxyl-bearing or proline residues, to resist denaturation by the elevated hydrostatic pressures of the deep sea. Phylogenetic evidence for the duplication of the rod opsin gene in the Anguilliform lineage is presented.

Adaptation, Physiological↗