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Biomedical subjects

S J Goodman

Publications and source records attributed to S J Goodman.

At least 19 recordsLinked to original sources

Selection and recombination drive the evolution of MHC class II DRB diversity in ungulates.

Major histocompatibility complex (MHC) antigen-presenting genes are the most variable loci in vertebrate genomes. Host-parasite co-evolution is assumed to maintain the excessive polymorphism in the MHC loci. However, the molecular mechanisms underlying the striking diversity in the MHC remain contentious. The extent to which recombination contributes to the diversity at MHC loci in natural populations is still controversial, and there have been only few comparative studies that make quantitative estimates of recombination rates. In this study, we performed a comparative analysis for 15 different ungulates species to estimate the population recombination rate, and to quantify levels of selection. As expected for all species, we observed signatures of strong positive selection, and identified individual residues experiencing selection that were congruent with those constituting the peptide-binding region of the human DRB gene. However, in addition for each species, we also observed recombination rates that were significantly different from zero on the basis of likelihood-permutation tests, and in other non-quantitative analyses. Patterns of synonymous and non-synonymous sequence diversity were consistent with differing demographic histories between species, but recent simulation studies by other authors suggest inference of selection and recombination is likely to be robust to such deviations from standard models. If high rates of recombination are common in MHC genes of other taxa, re-evaluation of many inference-based phylogenetic analyses of MHC loci, such as estimates of the divergence time of alleles and trans-specific polymorphism, may be required.

Alleles↗

Resonant coupling between bulk waves and guided modes in a dielectric slab with a thick holographic grating.

What we believe to be a new type of resonant coupling of an incident bulk wave into guided modes of a slab with a thick holographic grating is shown to occur in the presence of strong frequency detunings of the Bragg condition. This happens through the reflection of the strongly noneigen +1 diffracted order with the slab-grating boundaries, the resultant reflected waves forming a guided slab mode. Rigorous coupled-wave analysis is used for the numerical analysis of the predicted resonant effects. Possible applications include enhanced options for the design of multiplexing and demultiplexing systems, optical signal-processing devices, optical sensors, and measurement techniques.

Journal Article↗

Fossil-calibrated molecular phylogenies reveal that leaf-mining moths radiated millions of years after their host plants.

Coevolution has been hypothesized as the main driving force for the remarkable diversity of insect-plant associations. Dating of insect and plant phylogenies allows us to test coevolutionary hypotheses and distinguish between the contemporaneous radiation of interacting lineages vs. insect 'host tracking' of previously diversified plants. Here, we used nuclear DNA to reconstruct a molecular phylogeny for 100 species of Phyllonorycter leaf-mining moths and 36 outgroup taxa. Ages for nodes in the moth phylogeny were estimated using a combination of a penalized likelihood method and a Bayesian approach, which takes into account phylogenetic uncertainty. To convert the relative ages of the moths into dates, we used an absolute calibration point from the fossil record. The age estimates of (a selection of) moth clades were then compared with fossil-based age estimates of their host plants. Our results show that the principal radiation of Phyllonorycter leaf-mining moths occurred well after the main radiation of their host plants and may represent the dominant associational mode in the fossil record.

Animals↗

Bottlenecks, drift and differentiation: the population structure and demographic history of sika deer (Cervus nippon) in the Japanese archipelago.

We assessed genetic differentiation and diversity in 14 populations of sika deer (Cervus nippon) from Japan and four populations of sika deer introduced to the UK, using nine microsatellite loci. We observed extreme levels of differentiation and significant differences in diversity between populations. Our results do not support morphological subspecies designations, but are consistent with previous mitochondrial DNA analyses which suggest the existence of two genetically distinct lineages of sika deer in Japan. The source of sika introduced to the UK was identified as Kyushu. The underlying structure of Japanese populations probably derives from drift in separate glacial refugia and male dispersal limited by distance. This structure has been perturbed by bottlenecks and habitat fragmentation, resulting from human activity from the mid-nineteenth century. Most current genetic differentiation and differences in diversity among populations probably result from recent drift. Coalescent model analysis suggests sika on each of the main Japanese islands have experienced different recent population histories. Hokkaido, which has large areas of continuous habitat, has maintained high levels of gene flow. In Honshu the population is highly fragmented and is likely to have been evolving by drift alone. In Kyushu there has been a balance between gene flow and drift but all the populations have experienced high levels of drift. Habitat fragment size was not significantly associated with genetic diversity in populations but there was a significant correlation between habitat fragment size and effective population size.

Alleles↗

Introgression through rare hybridization: A genetic study of a hybrid zone between red and sika deer (genus Cervus) in Argyll, Scotland.

In this article we describe the structure of a hybrid zone in Argyll, Scotland, between native red deer (Cervus elaphus) and introduced Japanese sika deer (Cervus nippon), on the basis of a genetic analysis using 11 microsatellite markers and mitochondrial DNA. In contrast to the findings of a previous study of the same population, we conclude that the deer fall into two distinct genetic classes, corresponding to either a sika-like or red-like phenotype. Introgression is rare at any one locus, but where the taxa overlap up to 40% of deer carry apparently introgressed alleles. While most putative hybrids are heterozygous at only one locus, there are rare multiple heterozygotes, reflecting significant linkage disequilibrium within both sika- and red-like populations. The rate of backcrossing into the sika population is estimated as H = 0.002 per generation and into red, H = 0.001 per generation. On the basis of historical evidence that red deer entered Kintyre only recently, a diffusion model evaluated by maximum likelihood shows that sika have increased at approximately 9.2% yr-1 from low frequency and disperse at a rate of approximately 3.7 km yr-1. Introgression into the red-like population is greater in the south, while introgression into sika varies little along the transect. For both sika- and red-like populations, the degree of introgression is 30-40% of that predicted from the rates of current hybridization inferred from linkage disequilibria; however, in neither case is this statistically significant evidence for selection against introgression.

Alleles↗

Bovine microsatellite loci are highly conserved in red deer (Cervus elaphus), sika deer (Cervus nippon) and Soay sheep (Ovis aries).

We tested 174 bovine microsatellite primer pairs for use in a primitive breed of sheep and two species of deer. Of 173 markers, 127 (73.4%) gave a product in Soay sheep (Ovis aries) of which 54 (42.5%) were polymorphic. One hundred and twenty-nine of 174 (74.1%) markers gave a product in red deer (Cervus elaphus) of which 72 (55.8%) were polymorphic. In sika deer (Cervus nippon) 126 of 171 (73.7%) microsatellite primers gave a product with 47 (37.3%) polymorphic. The proportion of bovine microsatellite loci conserved across artiodactyl species was significantly greater in this study than previously reported. Reasons for this high degree of microsatellite conservation are discussed. We suggest that a high resolution comparative map of the artiodactyls can be constructed using microsatellites.

Alleles↗

Patterns of extensive genetic differentiation and variation among European harbor seals (Phoca vitulina vitulina) revealed using microsatellite DNA polymorphisms.

The harbor seal (Phoca vitulina) has the most extensive distribution of any phocid seal species. An analysis of population structure in this species across its European range was made using 7 phocid derived microsatellites in a sample of 1,029 individuals from 12 separate geographic areas. Despite the species potential for long-distance movement, significant genetic differentiation between areas was observed using an unbiased estimator of RST. Six distinct population units were identified: Ireland-Scotland, English east coast, Waddensea, western Scandinavia (Norway-Kattegat-Skagerrak-west Baltic), east Baltic, and Iceland. Little local substructuring is present along coastlines with a continuous distribution of breeding animals, but differentiation does increase with geographic distance. The degree of differentiation is greater over equivalent distances where the distribution is discontinuous, such as along coasts where breeding colonies are separated by large distances or by stretches of open sea. Patterns of population differentiation derived from microsatellites are very similar to those obtained from previous mitochondrial DNA analysis and suggest that philopatry in harbor seals operates over 300-500 km. In Europe, harbor seals have experienced a complex demographic history and patterns of population structure are likely to have been affected by natural environmental influences such as Pleistocene glaciations and epizootics. Comparison of Nm values from an unbiased estimator of RST, GST, and theta are consistent and, in some cases, may indicate populations where conditions deviate from the expectations of the RST model.

Animals↗

Triple-helical DNA as a reversible block of the branch point in a partially symmetrical DNA four-arm junction.

DNA branch migration is a fundamental process in genetic recombination. A new model system has been developed for studying branch migration in a small synthetic four-arm junction. A mathematical method for describing branch-point movement by discrete steps in such junctions is also presented. The key to our experimental system is the ability to fix the location of the branch point during the assembly of the junction with a reversible block. The block is provided by a short oligonucleotide that forms triplex DNA adjacent to the initial location branch point at low pH. Raising the pH causes the triplex strand to dissociate, making the branch point free to migrate. Once mobile, the branch point can run off the end of the junction. The time-course for this runoff is consistent with a random walk of the branch point. If it is assumed that one migration step moves the branch point one base-pair, the time-course gives a rate constant for one step of 1.4 second-1 at 37 degrees C in 10 mM MgCl2, 50 mM NaCl. These values are consistent with other measurements of non-enzymatic branch migration. We have also monitored the spread of the branch points directly with T4 endonuclease VII. Using EcoRI restriction endonuclease, we have shown that the binding of this protein to the arms of the junction essentially blocks branch migration through the binding site. In these experiments Ca2+ replaces Mg2+, and the enzyme does not cleave the DNA. In vivo there must be a special process to get branch points to migrate past bound proteins.

DNA↗

Interspecific microsatellite markers for the study of pinniped populations.

Microsatellites have rapidly become the marker of choice for a wide variety of population genetic studies. Here we describe 20 pinniped microsatellite markers which have been tested across 18 pinniped species. The majority of these markers have broad utility in all pinnipeds and provide a strong base for detailed population genetic studies in the Pinnipedia.

Animals↗

Head position signals used by parietal neurons to encode locations of visual stimuli.

The mechanism for object location in the environment, and the perception of the external world as stable when eyes, head and body are moved, have long been thought to be centred on the posterior parietal cortex. However, head position signals, and their integration with visual and eye position signals to form a representation of space referenced to the body, have never been examined in any area of the cortex. Here we show that the visual and saccadic activities of parietal neurons are strongly affected by head position. The eye and head position effects are equivalent for individual neurons, indicating that the modulation is a function of gaze direction, regardless of whether the eyes or head are used to direct gaze. These data are consistent with the idea that the posterior parietal cortex contains a distributed representation of space in body-centred coordinates.

Animals↗

Postoperative utilization of critical care services by cardiac surgery: a multicenter study in the Canadian healthcare system.

OBJECTIVES: To describe patterns of critical care services used after cardiac surgery and to evaluate whether variations in the process of care influence outcome. DESIGN: Multicenter, prospective study. SETTING: A convenience sample of four cardiac surgical units: three in university-affiliated (teaching) hospitals and one in a nonteaching regional referral center. PATIENTS: A "consecutive sample" of 335 patients after cardiac surgery in four hospitals. INTERVENTIONS: Data were collected regarding all cardiac surgery patients admitted to the critical care units in the four test hospitals. MEASUREMENTS AND MAIN RESULTS: The critical care unit and hospital lengths of stay and survival were followed. The Therapeutic Intervention Scoring System (TISS) was used to assess the intensive care unit (ICU) interventions used during the first 24 hrs in the ICU and for the final 24 hrs before discharge from the ICU. The severity of illness on admission was assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) scoring system. For patients having similar procedures (e.g., aortocoronary bypass and nonaortocoronary bypass procedures) and with similar outcome (mortality/total hospital length of stay), we found significant differences in the pattern of ICU resource utilization among hospitals. Significant (p < .05) differences in unit length of stay were related to varying factors in different hospitals. In hospital unit A, the type of procedure and preoperative chronic health status influenced unit length of stay (aortocoronary bypass 2.8 +/- 1.7 days; nonaortocoronary bypass 8.7 +/- 8.9 days) because length of stay was different for differing procedure groups. In hospital unit B, the critical care management system and lack of step-down (intermediate care) unit availability resulted in an increased unit length of stay for aortocoronary bypass patients (5.1 +/- 4.5 days) as compared with the other units (mean ICU lengths of stay of 2.8, 2.3, and 3.0 days, respectively). Unit B kept patients for monitoring purposes and had a reduced need for critical care nursing on the day of discharge (TISS = 7.5 +/- 5.5) as compared with the other units (mean TISS scores of 27.4, 23.2, and 21.5). CONCLUSIONS: Significant differences exist among hospitals in the same healthcare system in the utilization of critical care services for cardiac surgery. In spite of these differences, for similar patient "input," the outcome (mortality and hospital lengths of stay) appeared similar. Assessments of utilization of critical care must focus on more detailed specific issues than unit length of stay, and must include factors such as availability of intermediate care areas, the unit management system, chronic health status, and the operative procedures performed, if a utilization management process is to effect improved resource use in critical care.

Canada↗

Social support networks of adults with mental retardation who live at home.

The social support networks of 418 adults with mental retardation who live at home were found to be large, durable, active, and diverse in their composition. Family members predominated as members of these support networks. Differences were found in many network characteristics based on the gender and level of mental retardation of the adults. Males and those with the most severe mental retardation were found to be at risk for social isolation. Contrasts with the social support networks of adults in nonfamily settings were discussed.

Adolescent↗

Is outcome worse in a small volume Canadian trauma centre?

The minimum number of seriously injured patients required to maintain clinical competence and achieve acceptable clinical competence in a single trauma centre is unknown. It has been suggested that the probability of survival is improved in hospitals treating greater than 200 trauma patients annually. We sought to determine if probability of survival was lower in our small volume centre. Between 1986 and 1989, 752 (522 male, 230 female; average age, 36 years) trauma patients were admitted to our institution. The major mechanism of injury was blunt (89%). All patients underwent trauma severity scoring. Trauma Score, Injury Severity Score, and a Revised Trauma Score were used to derived the probability of survival by the TRISS method. The mean Injury Severity Score was 23.3 and the mean Trauma Score was 13.2. The overall mortality rate was 15.8%. The Z statistic demonstrated no significant difference between actual and predicted deaths for the 4-year period or for any individual year (range, -1.05 to 1.26, p greater than 0.05). The M statistic was 0.753. We conclude that, despite fewer trauma patient admissions (less than 200 per year), comparable clinical results can be achieved by surgeons dedicated to trauma management.

Adult↗

Elevation of pain threshold to tooth shock by brain stimulation in primates.

Electrical stimulation of the brain (ESB) for modulation of pain has been previously demonstrated in primates, but many of the sites which yield stimulation-produced analgesia (SPA) also elicit aversive side effects. In order to examine the aversive as well as analgesic effects of brain stimulation, nine rhesus monkeys (Macaca mulatta) were first trained to press a lever to escape or titrate noxious tooth shock. Stimulating electrodes were placed under the frontal cortex in 4 monkeys and were implanted in the diencephalon, brain stem, and cerebellum of five remaining monkeys. Diencephalic stimulation sites resulted in marked elevations of tooth shock threshold at ESB intensities which did not elicit aversive behaviors. The analgesic effects lasted up to 2 h past ESB offset. Moderate elevations of tooth shock threshold were also observed with orbital cortex stimulation. The midbrain central gray and the nucleus raphe magnus, however, did not greatly alter tooth shock level and typically resulted in aversive reactions. The diencephalic sites which elicited SPA also led to self-stimulation behavior, whereas stimulation of the brain stem or cerebellum usually resulted in escape responses. These findings thus indicate that, in primates, more effective relief of pain can be achieved with electrical activation of the medial diencephalon than with brain stem stimulation.

Animals↗