Phi-LOG: a domain specific language for solving phylogenetic inference problems.

Domain experts think and reason at a high level of abstraction when they solve problems in their domain of expertise. We present the design and motivation behind a domain specific language called Phi-LOG to enable biologists (domain experts) to program solutions to phylogenetic inference problems at a very high level of abstraction. The implementation infrastructure (interpreter, compiler, debugger) for the DSL is automatically obtained through a software engineering framework based on Denotational Semantics and Logic Programming.

Birth weight variation in the domestic pig: effects on offspring survival, weight gain and suckling behaviour.

In domestic pigs, litter-mates often vary considerably in birth weight. To examine whether this size variation influences piglet survival, weight gain and suckling behaviour, we experimentally manipulated the number and size distribution of litter-mates in 51 litters. Litters were small (eight or nine piglets) or large (11 or 12 piglets) compared to the herd mean of 10 piglets, and were made more or less variable in weight by using the largest and smallest quartiles of two combined litters (variable) or the middle two quartiles (uniform). Weights were measured on days 0, 3 and 21. Behavioural measures (percent of nursings missed, mean teat consistency score, per capita number of teat disputes before milk ejection, and percent time spent in teat disputes in the 20min after milk ejection) were recorded on days 1, 4, 10 and 17. Piglet weight variation (percent of coefficient of variation, CV) almost doubled over the 21 days in uniform litters and actually decreased in variable litters, but still remained higher in the variable litters. Overall, survival, percent of nursings missed, consistency in piglets' use of teats, number of teat disputes, percent time a piglet spent in teat disputes after milk ejection, and weight gain were unaffected by birth weight variation although there was a tendency (P=0.09) for more piglet deaths in variable litters. Behavioural measures of sibling competition were higher in large litters. The data provide little support for the hypotheses that high birth weight variation results in decreased survival, or that it permits rapid establishment of dominance, thereby reducing wasteful competitive behaviour in surviving piglets.

Magnitude of microelectrode refinement in pallidotomy and thalamotomy.

The relative accuracy of starting point algorithms in microelectrode-guided stereotactic pallidotomy and thalamotomy was evaluated using postoperative magnetic resonance imaging (MRI) data. Multiplanar reformations were performed to align postoperative MRI in anterior-posterior, dorsal-ventral and mediolateral planes. Three-dimensional distance and direction from the pallidal and thalamic stereotactic starting points to the respective radiofrequency lesions were measured. Similar magnitude of microelectrode refinement in pallidotomy and thalamotomy suggested similar accuracy of algorithms used to set the stereotactic starting point. Fewer microelectrode-recording tracts were required to identify optimal lesioning sites in thalamotomy compared to pallidotomy. Lesions were consistently localized anterior and superior to the starting point and a refined starting point algorithm may reduce the number of microelectrode recording tracts.

Long-distance seed dispersal in plant populations.

Long-distance seed dispersal influences many key aspects of the biology of plants, including spread of invasive species, metapopulation dynamics, and diversity and dynamics in plant communities. However, because long-distance seed dispersal is inherently hard to measure, there are few data sets that characterize the tails of seed dispersal curves. This paper is structured around two lines of argument. First, we argue that long-distance seed dispersal is of critical importance and, hence, that we must collect better data from the tails of seed dispersal curves. To make the case for the importance of long-distance seed dispersal, we review existing data and models of long-distance seed dispersal, focusing on situations in which seeds that travel long distances have a critical impact (colonization of islands, Holocene migrations, response to global change, metapopulation biology). Second, we argue that genetic methods provide a broadly applicable way to monitor long-distance seed dispersal; to place this argument in context, we review genetic estimates of plant migration rates. At present, several promising genetic approaches for estimating long-distance seed dispersal are under active development, including assignment methods, likelihood methods, genealogical methods, and genealogical/demographic methods. We close the paper by discussing important but as yet largely unexplored areas for future research.

Pallidotomy microelectrode targeting: neurophysiology-based target refinement.

OBJECTIVE: Microelectrode recording can refine targeting for stereotactic radiofrequency lesioning of the globus pallidus to treat Parkinson's disease. Multiple intraoperative microelectrode recording/stimulating tracks are searched and assessed for neuronal activity, presence of tremor cells, visual responses, and responses to kinesthetic input. These physiological data are then correlated with atlas-based anatomic data to approximate electrode location. On the basis of these physiological properties, one or more tracks are selected for lesioning. This study analyzes the track physiological factors that seem most significant in determining the microelectrode recording track(s) that will be chosen for pallidal lesioning. METHODS: Thirty-six patients with Parkinson's disease underwent microelectrode-guided pallidotomy. Between one and five microelectrode recording tracks were made per patient. Usually, one (n = 23) or two (n = 12) of these tracks were lesioned. Electrode positions in the x (mediolateral) and y (anteroposterior) axes were recorded and related to track neurophysiological findings and final lesion location. The stereotactic location and sequence of microelectrode tracks were recorded and plotted to illustrate individual search patterns. These patterns were then compared with those noted in other patients. Neurophysiological data obtained from recording tracks were analyzed. A retrospective analysis of track electrophysiology was performed to determine the track characteristics that seemed most important in the surgeon's choice of the track to lesion. Track physiological properties included general cell spike amplitude, tremor synchronous neuronal firing, kinesthetically responsive neuronal firing, and optic track responses (either phosphenes reported by the patient during track microstimulation or neuronal firing in response to light stimulus into the patient's eyes). Orthogonally corrected postoperative magnetic resonance images were used to confirm the anatomic lesion locations. RESULTS: In patients who had a single mapped track lesioned, specific track electrophysiological characteristics identified the track that would be lesioned most of the time (20 of 24 patients). Tracks that exhibited a combination of tremor synchronous firing, joint kinesthesia, and visual responsivity were lesioned 17 (85%) of 20 times. Analysis of intraoperative electrode movement in the x and y axes indicated a significant subset of moves but did not result in microelectrode positioning closer to the subsequently lesioned track. Accuracy of initial electrode movement in the x and y axes was most highly correlated with a measure of first-track electrophysiological activity. The number of microelectrode recording tracks did not correlate with clinical outcome. Anatomic analysis, using postoperative magnetic resonance imaging, revealed that all lesions were placed in the globus pallidus. Most patients (35 of 36) improved after surgery. CONCLUSION: The level of electrophysiological activity in the first track was the best predictive factor in determining whether the next microelectrode move would be closer to the ultimately lesioned track. The analysis of electrode track location and neurophysiological properties yields useful information regarding the effectiveness of microelectrode searching in the x and y axes. Within an institution, the application of this modeling method may increase the efficiency of the microelectrode refinement process.

Pollination biology in hybridizing Baptisia (Fabaceae) populations.

In their classic study, Alston and Turner (American Journal of Botany, vol. 50, 159-173, 1963) documented extensive hybridization among four morphologically distinct Baptisia species native to East Texas. While Alston and Turner found putative F1 hybrids in great numbers, they found no evidence of backcrossing. In this study prezygotic and postzygotic reproductive barriers between two of these species, B. leucophaea and B. sphaerocarpa, were investigated and found to be quite weak. Flowering times overlap and bumble bees were observed visiting both species and intermediate hybrids. While pollinator constancy in flights between B. leucophaea and B. sphaerocarpa was moderately strong, significant levels of constancy were not observed in flights involving hybrids and either parental species. Thus, backcrossing was not impeded by pollinator behavior. Further, hybrid pollen was highly stainable (93.5%) and able to effectively set seed in crossing experiments with both parental species. Pollinator behavior was compared in experimental populations with and without hybrid ramets and found to differ between these two treatments. Hybrids were found to facilitate pollinator movement between species. In total, these results suggest that reproductive isolation is not responsible for the rarity of backcrossing in naturally hybridizing B. leucophaea and B. sphaerocarpa populations.

Nuclear DNA-based markers for plant evolutionary biology.

While DNA-based markers can provide a wealth of information for the study of plant evolutionary biology, progress is limited by the lack of primers available for PCR. To overcome this limitation, we outline a protocol for developing oligonucleotide primers targeting regions of low copy-number nuclear genes. This protocol is intended to lead to universally useful primer sets. To test our approach, we designed eight primer sets and tested their abilities to amplify targets from representatives of each dicot and one monocot subclass. Five of the eight primer sets amplified targets from at least five of the seven taxa and thus exhibited broad taxonomic usefulness; the remaining primers were rather specific, however, and amplified targets from at most three taxa. In only one primer-taxon combination was a complex multiple-banded amplification produced. Overall, the protocol outlined proved quite useful at identifying broadly applicable primers targeted to low copy-number nuclear genes. Wider application of this approach should be effective at greatly increasing the amount of genetic information available for a diversity of plant nuclear genomes.

Contractile properties of obliquely striated muscle from the mantle of squid (Alloteuthis subulata) and cuttlefish (Sepia officinalis)

The mechanical properties of obliquely striated muscle fibres were investigated using thin slices of mantle from squid Alloteuthis subulata and cuttlefish Sepia officinalis. Brief tetani or twitch stimuli were used as this pattern is likely to occur during jetting of the intact animal. The length­active force relationship for twitches and tetani (0.1s, 50Hz) was similar to that of vertebrate cross-striated fibres. Passive force at the length giving maximum tetanic force was 0.13±0.05P0 (mean ± s.e.m., N=6, where P0 is maximum isometric tetanus force) and increased steeply at longer lengths. Peak force in a brief isometric tetanus (0.2s, 100­150Hz) was 262±16mNmm-2 cross-sectional area of wet tissue (N=6) for squid, and 226±19mNmm-2 (N=7) for cuttlefish. The force­velocity relationship for isotonic shortening during twitches of squid mantle slices was a 'double hyperbolic' relationship as described for cross-striated fibres by Edman. Fitting Edman's equation to the results gave: P*=1.18±0.07, Vmax=2.43±0.11Ltws-1 and 1/G=0.69±0.13 (N=8), where P* is the intercept on the force axis expressed relative to Ptw, peak isometric twitch force, Vmax is the intercept on the velocity axis, Ltw is the length at which Ptw is produced and G is the constant expressing curvature. The large values of 1/G indicate that the force­velocity relationship is not very curved. Maximum power was produced during shortening at 0.45±0.03Ptw (N=8). Maximum power during twitch contraction was 18.3±1.7mWg-1wetmass or, expressed in relative units, (V/Vmax)(P/Ptw), where V is the velocity during shortening and P is the force during shortening, was 0.16±0.01 (N=8), which is higher than that of many cross-striated locomotor muscles.

Different excitation-contraction coupling mechanisms exist in squid, cuttlefish and octopod mantle muscle

Excitation-contraction (EC) coupling was studied in central zone mantle muscle fibres of a squid (Alloteuthis subulata), a cuttlefish (Sepia officinalis) and an octopod (Eledone cirrhosa). Thin slices of muscle were used for twitch experiments and enzymatic isolation of single fibres for whole-cell patch-clamp studies. The current required for a supramaximal twitch response during direct stimulation of muscle slices was lower for squid than for cuttlefish. In squid, but not in cuttlefish, the current-response relationship was independent of slice thickness (range 0.1-0.5 mm). Twitches of squid and cuttlefish slices were reversibly abolished by removal of extracellular Ca2+. In squid, but not in cuttlefish, the current-response relationship was Na+-dependent, and in the absence of Na+ higher current strengths were required to generate a supramaximal response. In whole-cell voltage-clamp experiments on isolated muscle fibres from squid, cuttlefish and Eledone cirrhosa, a sustained inward current was recorded upon depolarisation. This current was blocked by 5 mmol l-1 Co2+ and suppressed by 10 micromol l-1 nifedipine. In squid, an additional inward fast-activating transient current was seen which was blocked by 2 micromol l-1 tetrodotoxin and depolarised holding potentials. The fast current represents a voltage-activated Na+ channel, and the slow currents represent L-type Ca2+ channels. We conclude that squid possess a specialised rapid EC coupling mechanism in central zone fibres that is absent in cuttlefish and Eledone cirrhosa.

Estimating long-term mating systems using DNA sequences.

Plant mating systems often involve a mixture of self fertilizations and outcross fertilizations. The degree of selfing has a large impact on the genetic composition of natural populations and on the evolution of the mating system itself in response to such factors as inbreeding depression. This paper describes a means of estimating the long-term rate of self-fertilization from samples of alleles taken from individuals in a population. Use is made of the genealogy of pairs of alleles at a locus within individuals and pairs between individuals. The degree of selfing is closely related to the extent to which the number of nucleotide sites differing within an individual is reduced relative to the number differing between individuals. Importantly, the estimate of long-term selfing is largely independent of population size and is not affected by historical fluctuations in population size; instead it responds directly to the mating system itself. The approach outlined here is most appropriate to evolutionary problems in which the long-term nature of the mating system is of interest, such as to determine the relationship between prior inbreeding and inbreeding depression.

Analysis of population genetic structure with RAPD markers.

Recent advances in the application of the polymerase chain reaction make it possible to score individuals at a large number of loci. The RAPD (random amplified polymorphic DNA) method is one such technique that has attracted widespread interest. The analysis of population structure with RAPD data is hampered by the lack of complete genotypic information resulting from dominance, since this enhances the sampling variance associated with single loci as well as induces bias in parameter estimation. We present estimators for several population-genetic parameters (gene and genotype frequencies, within- and between-population heterozygosities, degree of inbreeding and population subdivision, and degree of individual relatedness) along with expressions for their sampling variances. Although completely unbiased estimators do not appear to be possible with RAPDs, several steps are suggested that will insure that the bias in parameter estimates is negligible. To achieve the same degree of statistical power, on the order of 2 to 10 times more individuals need to be sampled per locus when dominant markers are relied upon, as compared to codominant (RFLP, isozyme) markers. Moreover, to avoid bias in parameter estimation, the marker alleles for most of these loci should be in relatively low frequency. Due to the need for pruning loci with low-frequency null alleles, more loci also need to be sampled with RAPDs than with more conventional markers, and some problems of bias cannot be completely eliminated.

Risk factors for suicide attempts among Navajo adolescents.

BACKGROUND: Rates of adolescent suicide in the United States are highest among Native Americans but little is known about risk factors for suicide attempts in this population. METHODS: To identify risk factors for self-reported suicide attempts by Navajo adolescents, we analyzed the 1988 Indian Health Service Adolescent Health Survey that was administered to 7,254 students in grades 6 through 12 on the Navajo reservation. The responses of students reporting a past suicide attempt were compared to others. RESULTS: Nearly 15 percent (N = 971) reported a previous suicide attempt; over half of those admitted to more than one attempt. Controlling for age, a logistic regression model revealed the following associations with suicide attempts: a history of mental health problems (OR = 3.2); alienation from family and community (OR = 3.2); having a friend who attempted suicide (OR = 2.8); weekly consumption of hard liquor (OR = 2.7); a family history of a suicide or attempt (OR = 2.3); poor self-perception of health (OR = 2.2); a history of physical abuse (OR = 1.9); female gender (OR = 1.7); and sexual abuse (OR = 1.5). CONCLUSIONS: Efforts to prevent adolescent suicide attempts in this population should target individuals with those risk factors of the highest risk and prevalence of exposure.

Dispersed repeats and structural reorganization in subclover chloroplast DNA.

The plastid genome from subclover, Trifolium subterraneum, is unusual in a variety of respects, compared with other land-plant chloroplast DNAs. Gene mapping of subclover chloroplast DNA reveals major structural reorganization of the genome. Ten clusters of genes are rearranged in both order and orientation. Eight large inversions are sufficient to explain this reorganization; however, the actual evolutionary changes may have been more complex. For example, a fine-scale analysis of a set of ribosomal protein genes reveals the occurrence of insertions, deletions, and transpositions. Associated with this unusually unstable genome are two structural features potentially involved in the rearrangements. A dispersed family of repeats, with each element about 1 kb in length, is present in at least six copies. A survey of a wide taxonomic range of species indicates that these elements are unique to the chloroplast DNAs of subclover and two closely related species. Several of the repeated elements are associated with genomic rearrangements, and one repeat is inserted within a normally highly conserved series of genes. This set of dispersed repeats may be the first family of transposable elements found in any organelle genome. In addition, the subclover genome is much larger than those in other closely related legumes, even when one takes into account the presence of the repeated elements. Some of the extra DNA has no sequence similarity to other chloroplast genomes and may represent insertion of DNA from another genome. These unusual features are not found in the structurally stable chloroplast genomes of other vascular plants and may, therefore, be implicated in the rapid and major reorganization of the chloroplast DNA in subclover.

Invasion and coexistence of two phenotypically variable species.

The effect of ecological polymorphism on the coexistence of species has not previously been studied. Using a model of competitive interactions within and among species I investigate invasion of both monomorphic and polymorphic species. Three comparisons are considered which place previous work in a broader context and extend it to cover the situations characterized by polymorphism. First, I examine invasion of a monomorphic species into the range of another monomorphic species. This is done in a manner which allows for generalization to the following more complex cases. Second, I examine invasion of a monomorphic species into the range of a polymorphic species. Finally, I examine invasion and coexistence of a polymorphic species in the range of another polymorphic species. This sequence of comparisons produces some simple generalizations concerning invasion and coexistence of species in a variety of ecological situations. Furthermore, it emphasizes polymorphism as a potentially important factor in shaping ecological communities.

Fourth goal of perinatal medicine.

Reduction in maternal mortality, infant mortality, and infant morbidity have been successively the goals of perinatal medicine. The fourth is to reduce bonding failure. In July 1978 a preventive service was started in the John Radcliffe Maternity Hospital. A twice-weekly round is made. Midwives refer families who cause them concern. In the first year the referral rate ws 20.5 per 1000 liveborn babies. The referred sample differed from the hospital population in terms of maternal psychiatric history, marital state and babies' admission to special care. The main reasons for referral were: doubt about parenting ability (27%), psychiatric history (15%), disturbed behaviour in hospital (14%), and diffuse social and medical problems (17%). Long-term care was needed for only 14% of families. At their first birthdays, six babies were placed away from their natural parents; the sample had had a slightly higher than expected admission rate to hospital; the distribution of weights did not differ from the expected; doctors and health visitors were still concerned about one-quarter of the families. Seven cases of screening failure were found among those not referred to our service, but only one was seriously abused. No child referred in the first year has been seriously neglected or abused.

The photodecomposition of tryptophan peptides.

Aqueous solutions of the four tryptophan peptides, Ala-Trp-Val, Val-Trp-Ala, Ala-Ala-Trp-Val and Ala-Gly-Trp-Leu, have been irradiated with the light of wavelength greater than 295 nm. The major changes were destruction of the tryptophan residue, liberation of ammonia and the formation of photoproducts of increased molecular weight. Up to 40% of Ala-Ala-Trp-Val and Ala-Gly-Trp-Leu were converted to products with molecular weights ranging from two to four times those of the original tetrapeptides. Most of the yellow material formed during irradiation in air was present in the high molecular weight fractions. Irradiation of Ala-Gly-[14C]Trp-Leu gave the following identifiable photoproducts: Ala-Gly-Asp-Leu, Ala-Gly-(N'formyl)Kyn-Leu, Ala-Gly-Oia-Leu, and ammonia, where Kyn means kynurenine and Oia, beta-(3-oxindolyl)alanine.

The complete enzymic hydrolysis of crosslinked proteins.

Procedures used for the complete enzymic hydrolysis of proteins are reviewed. The successful application of complete enzymic hydrolysis in the detection of naturally occurring isopeptide crosslinks and various other types of chemically introduced crosslinks is described. The method may fail if the level of crosslinking is too high, or if crosslinking is accompanied by racemization. Although it is usual to cleave disulphide crosslinks prior to enzymic digestion, the necessity for this in all cases is questioned.