Philosophical Transactions of The Royal Society B Biological Sciences

Published by Royal Society, The
Online ISSN: 1471-2970
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Article
Two major types of environment provide habitats for the most xerophilic organisms known: foods preserved by some form of dehydration or enhanced sugar levels, and hypersaline sites where water availability is limited by a high concentration of salts (usually NaCl). These environments are essentially microbial habitats, with high-sugar foods being dominated by xerophilic (sometimes called osmophilic) filamentous fungi and yeasts, some of which are capable of growth at a water activity (a(w)) of 0.61, the lowest a(w) value for growth recorded to date. By contrast, high-salt environments are almost exclusively populated by prokaryotes, notably the haloarchaea, capable of growing in saturated NaCl (a(w) 0.75). Different strategies are employed for combating the osmotic stress imposed by high levels of solutes in the environment. Eukaryotes and most prokaryotes synthesize or accumulate organic so-called 'compatible solutes' (osmolytes) that have counterbalancing osmotic potential. A restricted range of bacteria and the haloarchaea counterbalance osmotic stress imposed by NaCl by accumulating equivalent amounts of KCl. Haloarchaea become entrapped and survive for long periods inside halite (NaCl) crystals. They are also found in ancient subterranean halite (NaCl) deposits, leading to speculation about survival over geological time periods.
 
Article
In natural ecosystems, microbial activity is often associated with the presence of a surface, particularly in low-nutrient environments. The chemostat allows the study of such low-nutrient environments together with the precise control of other growth parameters. By using this system, enrichment cultures with inocula from two different river sources have been made. A more diverse community attached itself to surfaces placed in the chemostat when the cultures were carbon-limited than when the limiting nutrient was nitrogen. Further studies on a pseudomonad isolated from the carbon-limited enrichment cultures have shown that surface-associated organisms grow at approximately twice the rate of the same organism in the free surrounding medium. A hypothesis to explain this phenomenon based on the chemiosmotic theory is discussed.
 
Attendees at the Kavli satellite meeting. 
Article
The meeting 'Human evolution, migration and history revealed by genetics, immunity and infection', along with the follow-on satellite meeting at the Kavli Centre over the subsequent two days, brought together diverse talents. The aim was to see if new insights could be gained by bringing together those who have interests in the past 50-100 000 years of human history, overlaying the perspectives of palaeogeneticists, anthropologists, human geneticists, pathogen geneticists, immunologists, disease modellers, linguists, immunogeneticists, historians and archaeologists. It rapidly became clear that while all may agree on the broad brush-strokes including 'out-of-Africa' and the general approximations of timelines, diverse approaches may often suggest somewhat different ways of telling the story.
 
Article
Two novel reductive dehalogenases (RDases) that are highly similar to each other but catalyse distinct dechlorination reactions were identified from Dehalobacter-containing mixed cultures. These two RDases were partially purified from crude protein extracts of anaerobic dechlorinating enrichment cultures using blue native polyacrylamide gel electrophoresis. Gel slices were assayed for dechlorinating activity, and associated proteins were identified using liquid chromatography tandem mass spectrometry with the metagenome of the parent culture as the reference database. The two RDases identified, annotated as CfrA and DcrA, share an amino acid identity of 95.2 per cent, but use different substrates: CfrA dechlorinates chloroform (CF) and 1,1,1-trichloroethane (1,1,1-TCA), but not 1,1-dichloroethane; DcrA dechlorinates 1,1-dichloroethane, but not CF or 1,1,1-TCA. These two novel RDases share no more than 40 per cent amino acid identity to any other known or putative RDases, but both have a twin-arginine motif and two iron-sulfur binding motifs conserved in most RDases. Peptides specific to two putative membrane anchor proteins, annotated as CfrB and DcrB, were also detected in gel slices.
 
Evaluation of biochemical and metabolomic parameters in P. pavonaceae cells growing exponentially on MMY medium containing either 30 mM D-glucose or citrate (i.e. glycolytic and gluconeogenic metabolic regimes) under control conditions (nil) and in the presence of 0.5 mM 1,3-dichloroprop-1-ene (1,3-DCP). (a) In vitro quantification of the specific (Sp) D-glucose-6-P dehydrogenase activity. Note that the superoxide-generating naphtoquinone menadione was added at 0.15 mM to some cultures to impose oxidative stress conditions. (b) Determination of the intracellular D-glucose-6-P concentration. Appropriate aliquots of clarified cellfree extracts were boiled and centrifuged, and supernatants were spectrophotometrically analysed for D-glucose-6-P as detailed in §2. Each bar represents the mean value of the corresponding parameter + s.d. of duplicate measurements from at least three independent experiments. In both cases, the asterisk marks denote significant differences in the corresponding parameter at either the 95% level (single asterisk) or the 99% level (double asterisks) when compared with the control culture (without additives), as evaluated with ANOVA. 
Article
Chlorinated pollutants are hardly biodegradable under oxic conditions, but they can often be metabolized by anaerobic bacteria through organohalide respiration reactions. In an attempt to identify bottlenecks limiting aerobic catabolism of 1,3-dichloroprop-1-ene (1,3-DCP; a widely used organohalide) in Pseudomonas pavonaceae, the possible physiological restrictions for this process were surveyed. Flow cytometry and a bioluminescence reporter of metabolic state revealed that cells treated with 1,3-DCP experienced an intense stress that could be traced to the endogenous production of reactive oxygen species (ROS) during the metabolism of the compound. Cells exposed to 1,3-DCP also manifested increased levels of d-glucose-6-P 1-dehydrogenase activity (G6PDH, an enzyme key to the synthesis of reduced NADPH), observed under both glycolytic and gluconeogenic growth regimes. The increase in G6PDH activity, as well as cellular hydroperoxide levels, correlated with the generation of ROS. Additionally, the high G6PDH activity was paralleled by the accumulation of d-glucose-6-P, suggesting a metabolic flux shift that favours the production of NADPH. Thus, G6PDH and its cognate substrate seem to play an important role in P. pavonaceae under redox stress caused by 1,3-DCP, probably by increasing the rate of NADPH turnover. The data suggest that oxidative stress associated with the biodegradation of 1,3-DCP reflects a significant barrier for the evolution of aerobic pathways for chlorinated compounds, thereby allowing for the emergence of anaerobic counterparts.
 
Article
The paper describes the arrangement of the atoms within rhombohedral crystals of 2Zn pig insulin as seen in electron density maps calculated from X-ray data extending to 1.5 A (1 A = 10(-10) m = 10(-1) nm) at room temperature and refined to R = 0.153. The unit cell contains 2 zinc ions, 6 insulin molecules and about 3 x 283 water molecules. The atoms in the protein molecules appear well defined, 7 of the 102 side chains in the asymmetric unit have been assigned alternative disordered positions. The electron density over the water molecules has been interpreted in terms of 349 sites, 217 weighted 1.0, 126 weighted 0.5, 5 at 0.33 and 1 at 0.25 giving ca. 282 molecules. The positions and contacts of all the residues belonging to the two A and B chains of the asymmetric unit are shown first and then details of their arrangement in the two insulin molecules, 1 and 2, which are different. The formation from these molecules of a compact dimer and the further aggregation of three dimers to form a hexamer around two zinc ions, follows. It appears that in the packing of the hexamers in the crystal there are conflicting influences; too-close contacts between histidine B5 residues in neighbouring hexamers are probably responsible for movements of atoms at the beginning of the A chain of one of the two molecules of the dimer that initiate movements in other parts, particularly near the end of the B chain. At every stage of the building of the protein structure, residues to chains of definite conformation, molecules, dimers, hexamers and crystals, we can trace the effect of the packing of like groups to like, aliphatic groups together, aromatic groups together, hydrogen-bonded structures, positive and negative ions. Between the protein molecules, the water is distributed in cavities and channels that are continuous throughout the crystals. More than half the water molecules appear directly hydrogen bonded to protein atoms. These are generally in contact with other water molecules in chains and rings of increasing disorder, corresponding with their movement through the crystals. Within the established crystal structure we survey next the distribution of hydrogen bonds within the protein molecules and between water and protein and water and water; all but eight of the active atoms in the protein form at least one hydrogen bond.(ABSTRACT TRUNCATED AT 400 WORDS)
 
Article
Magnetic resonance imaging (MRI) has rapidly become an important tool in clinical medicine and biological research. Its functional variant (functional magnetic resonance imaging; fMRI) is currently the most widely used method for brain mapping and studying the neural basis of human cognition. While the method is widespread, there is insufficient knowledge of the physiological basis of the fMRI signal to interpret the data confidently with respect to neural activity. This paper reviews the basic principles of MRI and fMRI, and subsequently discusses in some detail the relationship between the blood-oxygen-level-dependent (BOLD) fMRI signal and the neural activity elicited during sensory stimulation. To examine this relationship, we conducted the first simultaneous intracortical recordings of neural signals and BOLD responses. Depending on the temporal characteristics of the stimulus, a moderate to strong correlation was found between the neural activity measured with microelectrodes and the BOLD signal averaged over a small area around the microelectrode tips. However, the BOLD signal had significantly higher variability than the neural activity, indicating that human fMRI combined with traditional statistical methods underestimates the reliability of the neuronal activity. To understand the relative contribution of several types of neuronal signals to the haemodynamic response, we compared local field potentials (LFPs), single- and multi-unit activity (MUA) with high spatio-temporal fMRI responses recorded simultaneously in monkey visual cortex. At recording sites characterized by transient responses, only the LFP signal was significantly correlated with the haemodynamic response. Furthermore, the LFPs had the largest magnitude signal and linear systems analysis showed that the LFPs were better than the MUAs at predicting the fMRI responses. These findings, together with an analysis of the neural signals, indicate that the BOLD signal primarily measures the input and processing of neuronal information within a region and not the output signal transmitted to other brain regions.
 
Richness and percentage complementarity of spider faunas along an elevational gradient in Bolivia (Coddington et al. 1991; J. A. Coddington L. H. Young, unpublished data) (Sequential sites are separated by about 110 km Matrix entries: percentage complementarity (number of species in common).) 
Article
Both the magnitude and the urgency of the task of assessing global biodiversity require that we make the most of what we know through the use of estimation and extrapolation. Likewise, future biodiversity inventories need to be designed around the use of effective sampling and estimation procedures, especially for 'hyperdiverse' groups of terrestrial organisms, such as arthropods, nematodes, fungi, and microorganisms. The challenge of estimating patterns of species richness from samples can be separated into (i) the problem of estimating local species richness, and (ii) the problem of estimating the distinctness, or complementarity, of species assemblages. These concepts apply on a wide range of spatial, temporal, and functional scales. Local richness can be estimated by extrapolating species accumulation curves, fitting parametric distributions of relative abundance, or using non-parametric techniques based on the distribution of individuals among species or of species among samples. We present several of these methods and examine their effectiveness for an example data set. We present a simple measure of complementarity, with some biogeographic examples, and outline the difficult problem of estimating complementarity from samples. Finally, we discuss the importance of using 'reference' sites (or sub-sites) to assess the true richness and composition of species assemblages, to measure ecologically significant ratios between unrelated taxa, to measure taxon/sub-taxon (hierarchical) ratios, and to 'calibrate' standardized sampling methods. This information can then be applied to the rapid, approximate assessment of species richness and faunal or floral composition at 'comparative' sites.
 
Shuiyousphaeridium macroreticulatum from the Mesoproterozoic Ruyang Group, China. (a) Light microphotograph showing specimen with numerous regularly spaced cylindrical processes that flare outward; (b, c, e-f ) SEM images showing (b) whole specimen, with inset showing details of process morphology, (c) outer wall surface covered with ridges that delimit granular polygonal fields, (e) wall reticulation and ( f ) inner wall surface of closely packed, beveled hexagonal plates; (d ) TEM image showing the two appressed walls of a single specimen-note multilayered wall comprising a thick electron-dense homogeneous layer of organic plates (ii) between an outer layer of debris and processes-note base of process at bottom left of centre (iii) and a thin electron-tenuous layer (i) that lines the inner side of plates. Scale bar in aZ57 mm for a, 50 mm for b (20 mm for inset), 1.2 mm for c and e, 0.5 mm for d and 2.5 mm for f.
Diversity of Late Palaeoproterozoic to Early Mesoproterozoic eukaryotic fossils. (a) Tappania plana, from the Early Mesoproterozoic Roper Group, Australia; (b) Horodyskia moniliformis, from the Mesoproterozoic Bangemall Group, Western Australia; (c, f ) Satka favosa, from the Roper Group, (c) showing the wall construction of hexagonal plates, shown under SEM in ( f ); (d, e) Valeria lophopstriata, showing ornamentation of closely spaced parallel ridges on the inner wall surface in SEM (d ) and light microscopic (e) view; (g, h) Leiosphaeridia sp., an unornamented spheroidal acritarch, with a complex wall composed of two electron-dense, homogeneous layers (i) that sandwich a thick central layer with electron-dense, porous texture (ii) visible in TEM cross-section (h); Grypania spiralis, a coiled macrofossil compression from the Mesoproterozoic Gaoyuzhuang Formation, China (courtesy of M. Walter). Scale barZ40 mm for (a), 7.8 mm for (b), 35 mm for (c), 4 mm for (d ), 15 mm for (e), 7.5 mm for f, 1 mm for (h), and 3 mm for (i ).
Late Mesoproterozoic and Neoproterozoic eukaryotic fossils: (a, b) 'Tappania plana' from the Neoproterozoic Wynniatt Formation, arctic Canada, a complex form with septate, anastomosing processes, shown in detail in (b); (c) Bangiomorpha pubescens, from the Late Mesoproterozoic Hunting Formation, arctic Canada, showing radial division of cells within a discrete zone of uniseriate filaments; (d ) Konglingiphyton erecta, a macroscopic, dichotomously branched alga from the Ediacaran Doushantou Formation, China; (e) Eosaccharomyces ramosa from the Late Mesoproterozoic Lakhanda succession, Siberia, showing net-like distribution on a bedding surface, with cells aligned along strands; ( f ) Segmentothallus asperus from the Lakhanda succession, a large uniseriate filament; (g) Appendisphaera grandis, a large acritarch with numerous, symmetrically arranged processes, from the Ediacaran Khamaka Formation, Siberia; (h) Kildinosphaera verrucata, an ornamented acritarch from the Neoproterozoic Miroyedikha Formation, Siberia; (i ) Bonniea dacruchares, a vase-shaped protistan test from the Neoproterozoic Kwagunt Formation, Grand Canyon, USA; ( j ) preserved cast and mould of vase-shaped protist in silicified carbonates of the Neoproterozoic Ryssö Formation, Svalbard. Scale barZ100 mm in (a), 12 mm in (b), 40 mm in (c) 4 mm in (d ) 150 mm in (e), 500 mm in ( f ), 70 mm in ( g), 25 mm in (h), 43 mm in (i ), and 75 mm in ( j ).
(Caption opposite.)
Article
The geological record of protists begins well before the Ediacaran and Cambrian diversification of animals, but the antiquity of that history, its reliability as a chronicle of evolution and the causal inferences that can be drawn from it remain subjects of debate. Well-preserved protists are known from a relatively small number of Proterozoic formations, but taphonomic considerations suggest that they capture at least broad aspects of early eukaryotic evolution. A modest diversity of problematic, possibly stem group protists occurs in ca 1800-1300 Myr old rocks. 1300-720 Myr fossils document the divergence of major eukaryotic clades, but only with the Ediacaran-Cambrian radiation of animals did diversity increase within most clades with fossilizable members. While taxonomic placement of many Proterozoic eukaryotes may be arguable, the presence of characters used for that placement is not. Focus on character evolution permits inferences about the innovations in cell biology and development that underpin the taxonomic and morphological diversification of eukaryotic organisms.
 
Article
The elucidation of the complex machinery used by the human brain to segregate and integrate information while performing high cognitive functions is a subject of imminent future consequences. The most significant contributions to date in this field, known as cognitive neuroscience, have been achieved by using innovative neuroimaging techniques, such as electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI), which measure variations in both the time and the space of some interpretable physical magnitudes. Extraordinary maps of cerebral activation involving function-restricted brain areas, as well as graphs of the functional connectivity between them, have been obtained from EEG and fMRI data by solving some spatio-temporal inverse problems, which constitutes a top-down approach. However, in many cases, a natural bridge between these maps/graphs and the causal physiological processes is lacking, leading to some misunderstandings in their interpretation. Recent advances in the comprehension of the underlying physiological mechanisms associated with different cerebral scales have provided researchers with an excellent scenario to develop sophisticated biophysical models that permit an integration of these neuroimage modalities, which must share a common aetiology. This paper proposes a bottom-up approach, involving physiological parameters in a specific mesoscopic dynamic equations system. Further observation equations encapsulating the relationship between the mesostates and the EEG/fMRI data are obtained on the basis of the physical foundations of these techniques. A methodology for the estimation of parameters from fused EEG/fMRI data is also presented. In this context, the concepts of activation and effective connectivity are carefully revised. This new approach permits us to examine and discuss some future prospects for the integration of multimodal neuroimages.
 
Article
This paper focuses on what electrical and magnetic recordings of human brain activity reveal about spoken language understanding. Based on the high temporal resolution of these recordings, a fine-grained temporal profile of different aspects of spoken language comprehension can be obtained. Crucial aspects of speech comprehension are lexical access, selection and semantic integration. Results show that for words spoken in context, there is no 'magic moment' when lexical selection ends and semantic integration begins. Irrespective of whether words have early or late recognition points, semantic integration processing is initiated before words can be identified on the basis of the acoustic information alone. Moreover, for one particular event-related brain potential (ERP) component (the N400), equivalent impact of sentence- and discourse-semantic contexts is observed. This indicates that in comprehension, a spoken word is immediately evaluated relative to the widest interpretive domain available. In addition, this happens very quickly. Findings are discussed that show that often an unfolding word can be mapped onto discourse-level representations well before the end of the word. Overall, the time course of the ERP effects is compatible with the view that the different information types (lexical, syntactic, phonological, pragmatic) are processed in parallel and influence the interpretation process incrementally, that is as soon as the relevant pieces of information are available. This is referred to as the immediacy principle.
 
Expanded polyglutamine protein causes degeneration of the Drosophila eye. ( a ) Eye of a normal £y, showing highly ordered precise neurocrystalline lattice, and red pigmentation. ( b ) Eye of a £y expressing the control protein, MJDtr-Q27. The eye morphology is identical to that of a normal £y. Fly of genotype w ; gmr-GAL4 / UAS-MJDtr- Q27 . ( c ) Eye of a £y expressing the expanded polyglutamine protein, MJDtr-Q78. The eye shows severe degeneration compared to the normal eye. Externally, pigmentation is lost (seen here as a light coloured eye), internally (see Warrick et al . 1998) the eye shows complete loss of the photoreceptor neurons. ( d ) Developing eye disc of a larva expressing the MJDtr-Q27 protein. The protein is being expressed from the start of di¡erentiation at the furrow (arrow), and shows a di¡use cytoplasmic expression pattern. Larva of genotype w ; gmr-GAL4 / UAS-MJDtr-Q27 . ( e ) Developing eye disc of a larva expressing the MJDtr-Q78 protein. The protein is being expressed from the start of di¡erentiation at the furrow (arrow). The protein shows eventual concentration into brightly £uorescing nuclear inclusions. Older cells are to the left. Larva of genotype w ; gmr-GAL4 / UAS-MJDtr-Q78 . 
Article
To apply genetics to the problem of human polyglutamine-repeat disease, we recreated polyglutamine-repeat disease in Drosophila melanogaster. To do this, we expressed forms of the human gene encoding spinocerebellar ataxia type 3, also called Machado-Joseph disease (SCA-3/MJD). This gene is responsible for the most common form of human ataxia worldwide. Expression of a normal form of the MJD protein with 27 polyglutamines (MJDtr-Q27) had no phenotype. However, expression of a form of the protein with an expanded run of 78 glutamines (MJDtr-Q78) caused late onset progressive degeneration. In addition, the MJDtr-Q78 formed abnormal protein aggregates, or nuclear inclusions (NIs), whereas the control protein was cytoplasmic. These data indicate that the mechanisms of human polyglutamine-repeat disease are conserved to Drosophila. We are currently using this model to address potential mechanisms by which the mutant disease protein causes neural degeneration, as well as to define genes that can prevent polyglutamine-induced degeneration. By applying the power of Drosophila genetics to the problem of human polyglutamine-induced neural degeneration, we hope to identify ways to prevent and treat these diseases in humans.
 
Multiplicative gene action for a quantitative trait exhibiting inbreeding depression results in an expected loglinear decline (a) with increasing genome homozygosity (F). Epistasis can cause a curvilinear response, either concave up (diminishing epistasis, d) or concave down (reinforcing epistasis, r).
The North Carolina 3 breeding design. Inbred lines are crossed to form genetically uniform F 1 hybrids. F 1 hybrids are selfed to form segregating F 2 progeny. F 2 sires are used in backcrosses to the parental inbred lines.  
Graphical representation (after Fu & Ritland 1994a) of expected segregation ratios (the frequency of the marker heterozygote) and the less common homozygote ( p11) based on seven different models of allele interaction: overdominance (o), fully recessive (r), partly recessive (pr), additive (a), part dominance (pd), dominance (d) and underdominance (u). This model assumes unknown linkage between the marker and viability locus. Note the areas of overlap between the different types of allele interaction.  
Article
Predictions for the evolution of mating systems and genetic load vary, depending on the genetic basis of inbreeding depression (dominance versus overdominance, epistasis and the relative frequencies of genes of large and small effect). A distinction between the dominance and overdominance hypotheses is that deleterious recessive mutations should be purged in inbreeding populations. Comparative studies of populations differing in their level of inbreeding and experimental approaches that allow selection among inbred lines support this prediction. More direct biometric approaches provide strong support for the importance of partly recessive deleterious alleles. Investigators using molecular markers to study quantitative trait loci (QTL) often find support for overdominance, though pseudo-overdominance (deleterious alleles linked in repulsion) may bias this perception. QTL and biometric studies of inbred lines often find evidence for epistasis, which may also contribute to the perception of overdominance, though this may be because of the divergent lines initially crossed in QTL studies. Studies of marker segregation distortion commonly uncover genes of major effect on viability, but these have only minor contributions to inbreeding depression. Although considerable progress has been made in understanding the genetic basis of inbreeding depression, we feel that all three aspects merit more study in natural plant populations.
 
The Vanuatu archipelago showing locations sampled. Numbers refer to locations in table 1. Zosterops lateralis were not found on Maewo and Aneityum. Inset shows the position of Vanuatu (circled) in the southwest Pacific. Scale bar, 100 km.  
Distribution of microsatellite genetic clusters from STRUCTURE and estimates of migration rates from BAYESASS among islands for (a) Z. lateralis: five genetic clusters. In text, cluster 1, red; 2, yellow; 3, green; 4, purple; 5, blue. (b) Zosterops lateralis migration rates; (c) dark plumage group Z. flavifrons clusters; (d) dark plumage group Z. flavifrons migration rates; and (e) yellow plumage group Z. flavifrons genetic clusters. Note that STRUCTURE analysis was conducted for each group separately and pie colours do not relate to across-group comparisons. STRUCTURE data for Z. flavifrons taken from Phillimore et al. (2008b). Solid lines show migration rates more than 0.1, dashed lines 0.03 –0.1 and dotted lines 0.02 –0.03.  
Regression of three diversity measures (allelic richness, expected heterozygosity (H E ) and modal F values from 2MOD analysis) with island area (square kilometres) and distance to nearest inhabited island (kilometres) (of the same colour morph in the case of Z. flavifrons). Zosterops lateralis: open circles, solid line; dark plumage Z. flavifrons: black circles, dashed line; yellow plumage Z. flavifrons: black triangles (no regression shown). Zosterops flavifrons from Aneityum (indicated by an asterisk) was not included in regressions because of its paraphyletic status.  
Isolation by distance relationships for Zosterops. (a) Zosterops lateralis: pairwise comparisons among all islands (solid line shows the reduced major axis (RMA) regression line when all points (open and closed circles) are included), and pairwise comparison among northern islands only (from Epi northwards to Vanua Lava, open circles only, dashed RMA line regression line). (b) Zosterops flavifrons: pairwise comparisons among all island populations. (c) Z. flavifrons: pairwise comparisons within yellow (open circles, dashed RMA regression line) and dark (closed circles, solid RMA regression line) plumage groups.  
Article
Colonization of an archipelago sets the stage for adaptive radiation. However, some archipelagos are home to spectacular radiations, while others have much lower levels of diversification. The amount of gene flow among allopatric populations is one factor proposed to contribute to this variation. In island colonizing birds, selection for reduced dispersal ability is predicted to produce changing patterns of regional population genetic structure as gene flow-dominated systems give way to drift-mediated divergence. If this transition is important in facilitating phenotypic divergence, levels of genetic and phenotypic divergence should be associated. We consider population genetic structure and phenotypic divergence among two co-distributed, congeneric (Genus: Zosterops) bird species inhabiting the Vanuatu archipelago. The more recent colonist, Z. lateralis, exhibits genetic patterns consistent with a strong influence of distance-mediated gene flow. However, complex patterns of asymmetrical gene flow indicate variation in dispersal ability or inclination among populations. The endemic species, Z. flavifrons, shows only a partial transition towards a drift-mediated system, despite a long evolutionary history on the archipelago. We find no strong evidence that gene flow constrains phenotypic divergence in either species, suggesting that levels of inter-island gene flow do not explain the absence of a radiation across this archipelago.
 
Article
The field biology of the platypus, Ornithorhynchus anatinus, was first studied by a number of expatriate biologists who visited the Australian colonies to collect specimens in the 1800s. Their work was followed in the early to mid-1900s by a group of resident natural historians and later by an increasing number of academic biologists. All of these workers contributed significantly to the current understanding of the field biology of this unique Australian species. The platypus occupies much the same general distribution as it did prior to European occupation of Australia, except for its loss from the state of South Australia. However, local changes and fragmentation of distribution due to human modification of its habitat are documented. The species currently inhabits eastern Australia from around Cooktown in the north to Tasmania in the south. Although not found in the west-flowing rivers of northern Queensland, it inhabits the upper reaches of rivers flowing to the west and north of the dividing ranges in the south of the state and in New South Wales and Victoria. Its current and historical abundance, however, is less well known and it has probably declined in numbers, although still being considered as common over most of its current range. The species was extensively hunted for its fur until around this turn of this century. The platypus is mostly nocturnal in its foraging activities, being predominantly an opportunistic carnivore of benthic invertebrates. The species is homeothermic, maintaining its low body temperature (32 degrees C), even while foraging for hours in water below 5 degrees C. Its major habitat requirements include both riverine and riparian features which maintain a supply of benthic prey species and consolidated banks into which resting and nesting burrows can be excavated. The species exhibits a single breeding season, with mating occurring in late winter or spring and young first emerging into the water after 3-4 months of nurture by the lactating females in the nesting burrows. Natural history observations, mark and recapture studies and preliminary investigations of population genetics indicate the possibility of resident and transient members of populations and suggest a polygynous mating system. Recent field studies have largely confirmed and extended the work of the early biologists and natural historians.
 
Article
Many studies indicate that recognition memory involves at least two separable processes, familiarity discrimination and recollection. Aspects of what is known of potential neuronal substrates of familiarity discrimination are reviewed. Lesion studies have established that familiarity discrimination for individual visual stimuli is effected by a system centred on the perirhinal cortex of the temporal lobe. The fundamental change that encodes prior occurrence of such stimuli appears to be a reduction in the response of neurons in anterior inferior temporal (including perirhinal) cortex when a stimulus is repeated. The neuronal responses rapidly signal the presence of a novel stimulus, and are evidence of long-lasting learning after a single exposure. Computational modelling indicates that a neuronal network based on such a change in responsiveness is potentially highly efficient in information theoretic terms. Processes that occur in long-term depression within the perirhinal cortex provide candidate synaptic plastic mechanisms for that underlying the change, but such linkage remains to be experimentally established.
 
Effect of maternal age, natal diet and adult diet on offspring size variability in the soil mite, S. berlesei (data from Plaistow et al. 2007). Data are divided into adult food treatments ((a) high, (b) medium and (c) low), and divided within each adult treatment into rearing food treatments (circles and solid line, high; pluses and dashed line, medium; and crosses and dotted line, low). 
Summary of results from case studies. 
Schematic showing the effect of increasing offspring size variability on the mean size of offspring that mothers produce. Panels show relationship between mean offspring size and maternal fitness (as indicated by the dotted curves) and distribution of offspring sizes that mothers produce (as indicated by the normal distributions). Relationship between mean offspring size and maternal fitness taken from Marshall et al. (2006). Predicted size distribution of eggs that mothers should produce in order to maximize their own fitness based on D. Marshall & L. Bussiere 2005, unpublished analyses. (a) Mothers produce only a small range of offspring sizes; hence, the mean offspring size they produce is close to both the minimum offspring size threshold for survival and the optimum offspring size for that environment (as indicated by the vertical dashed line). (b) Mothers produce a larger range of offspring sizes; hence, the mean offspring size they produce must be further from both the minimum size threshold for survival and the optimum offspring size. 
Article
Mothers in a range of taxa manipulate the phenotype of their offspring in response to environmental change in order to maximize their own fitness. Most studies have focused on changes in the mean phenotype of offspring. Focusing on mean offspring phenotypes is appropriate for species in which mothers are likely to successfully predict the environment their offspring will experience, but what happens when the offspring's environment is unpredictable? Theory suggests that when mothers face uncertainty regarding their offspring's environment, they should increase within-clutch variation in the offspring phenotype (i.e. they should bet hedge). While comparative analyses support the idea that mothers do bet hedge in response to environmental unpredictability, empirical tests are very rare and it remains unclear whether mothers adaptively adjust variance in offspring traits (a phenomenon we call dynamic bet hedging). As a first step towards examining dynamic bet hedging, we reanalysed data from five previously published studies. These studies were across a range of taxa, but all manipulated the maternal environment/phenotype and then examined changes in mean offspring size. We found some support for the theoretical predictions that mothers should increase within-clutch offspring size variation when faced with unpredictable environments. We predict that dynamic bet hedging is more common than previously anticipated and suggest that it has some interesting implications for the studies that focus on shifts in mean offspring traits alone. Hence, future studies should examine maternal effects on both the mean and the variance of offspring traits.
 
Concordant laterality of epithalamic and heart asymmetries in zebrafish and medaka. 
(a) Zebrafish and (b) medaka share an overall pattern of molecular and morphological epithalamic asymmetry. ((i),(ii)) Asymmetric expression of components of the nodal signalling pathway in the presumptive epithalamus. mRNA expression of orthologue genes was detected by whole-mount in situ hybridization (arrows) at (i) normalized STU 35 (Dr-lefty1, Ol-lefty) and (ii) 43 (Dr-pitx2c, Ol-pitx2c) (table 2). The lateral flexure of the third ventricle is indicated by arrowheads. (iii) Left-sided positioning and efferent projection of the parapineal organ. Expression of GFP was detected in medaka Tg( fRx2::GFP ) and zebrafish Tg(FoxD3::GFP ) and pseudo-coloured in blue and green to label pineal and parapineal organs, respectively. The red arrowhead points to the terminal dandelion seed-head-shaped domain of parapineal efferent connectivity. (iv) Asymmetric organization of neuropil in the habenulae. Arrows indicate the regions of neuropil, which exhibit dissimilar growth between the left and right habenulae, as detected by immunostaining against acetylated a-tubulin. The red arrowhead points to a neuropil domain that is detected exclusively in the left habenula of medaka. (v) Asymmetric organization of neuronal cell bodies in the habenulae. Asterisks indicate equivalent regions of the left and right habenulae. The red arrowhead points to a domain devoid of fluorescent Nissl staining that is detected exclusively in the left habenula of medaka. ((vi),(vii)) Dorsoventral segregation of left-right habenular efferents in the IPN. Left and right habenular projections were labelled with DiD (red) and DiO (green), respectively. Images correspond to ((i)-(vi)) dorsal and (vii) lateral views with anterior and dorsal to the top, respectively. Stages of development correspond to 120 HPF (zebrafish, at 268C) and Iwamatsu's stage 39 (medaka), unless otherwise stated. ((iii)-(vii)) Three-dimensional projections from confocal z-stacks. L, left; R, right; Lh, left habenula; Rh, right habenula; hc, habenular commissure; Lfr, left fasciculus retroflexus; Rfr, right fasciculus retroflexus; dIPN, dorsal domain of the IPN; vIPN, ventral domain of the IPN. Scale bars, ((i)-(v)) 20 mm, ((vi),(vii)) 30 mm. 
Comparison of sequence, relative timing and duration of developmental events during the establishment of epithalamic asymmetry in zebrafish and medaka. The diagrams show the temporal occurrence of key steps of asymmetric brain morphogenesis in zebrafish and medaka, expressed in (a) absolute and (b) normalized times. To provide a contextual view, the timing of main embryonic events is also included. The colour codes shown at the bottom of the figure indicate different developmental events (lines) and periods ( boxes or bars) analysed in the temporal plots of (a,b). For clarity, equivalent events in medaka and zebrafish are joined. Diagrams of developmental stages were obtained from the literature (Kimmel et al. 1995; Iwamatsu 2004). Schematic of epithalamic asymmetry events (bottom right) correspond, from top to bottom, to: a frontal view of the epithalamus depicting left-sided asymmetric nodal expression, a dorsal view of the pineal complex showing the initiation of left-sided parapineal axonal projection and a dorsal view of the IPN (white circle) revealing habenular efferent connectivity reaching dorsal and ventral regions of the IPN. The scale was maintained in (a,b) to emphasize the effect of time normalization. Zebrafish and medaka show a conserved sequence of developmental events of epithalamic asymmetry although they exhibit distinct relative timing ( heterochrony). 
Developmental models of heterotopic parapineal efferent connectivity. (a) Zebrafish: asymmetries of the parapineal organ and habenulae interact in three consecutive steps during development. (i) Initial left-right biases in the presumptive habenular region guide parapineal migration to the left side. (ii) Subsequent left-sided positioning of the parapineal organ is involved in the induction/propagation of a distinct spatial pattern of habenular differentiation. (iii) Finally, the topology of subdomains arising after habenular differentiation determines the position of habenular neurons receiving parapineal efferent connectivity. (b) Medaka (model 1): heterotopic parapineal efferent connectivity arises from a different topological organization of habenular subdomains. In this model, spatial differences in the location of the parapineal organ at the time of habenular differentiation and/or underlying differences in habenular (i) pre-patterning lead to (ii) distinct topological programmes of habenular subdomain differentiation and (iii) subsequent positioning of parapineal target cells. (c) Medaka (model 2): heterotopic parapineal efferent connectivity arises from different selection of parapineal target cells within the habenulae. In this model, parapineal migration and habenular differentiation are equivalent in both species. However, parapineal projections reach different target neurons in the habenula of both species owing to the differences in axon guidance cues. (i) Shaded green regions depict molecular left-right biases within the presumptive habenulae. The movement of the parapineal organ from the midline to the left side (arrows) is represented as partially overlapping drawings of parapineal outlines. (ii) White and red regions illustrate putative subdomains of the habenulae. Arrows illustrate the direction of the inductive properties of the parapineal organ. (iii) The topological pattern of parapineal efferent connectivity (black) and the location of parapineal target cells within the habenula (colours) are shown (see also figure 2). Colours represent equivalent cellular identities. All diagrams correspond to dorsal views, with anterior to the top. For clarity, only the left habenula is illustrated, and the right habenula is depicted with dotted lines. L, left; R, right; Lh, left habenula; Rh, right habenula; hc, habenular commissure. 
Article
Comparison between related species is a successful approach to uncover conserved and divergent principles of development. Here, we studied the pattern of epithalamic asymmetry in zebrafish (Danio rerio) and medaka (Oryzias latipes), two related teleost species with 115-200 Myr of independent evolution. We found that these species share a strikingly conserved overall pattern of asymmetry in the parapineal-habenular-interpeduncular system. Nodal signalling exhibits comparable spatial and temporal asymmetric expressions in the presumptive epithalamus preceding the development of morphological asymmetries. Neuroanatomical asymmetries consist of left-sided asymmetric positioning and connectivity of the parapineal organ, enlargement of neuropil in the left habenula compared with the right habenula and segregation of left-right habenular efferents along the dorsoventral axis of the interpeduncular nucleus. Despite the overall conservation of asymmetry, we observed heterotopic changes in the topology of parapineal efferent connectivity, heterochronic shifts in the timing of developmental events underlying the establishment of asymmetry and divergent degrees of canalization of embryo laterality. We offer new tools for developmental time comparison among species and propose, for each of these transformations, novel hypotheses of ontogenic mechanisms that explain interspecies variations that can be tested experimentally. Together, these findings highlight the usefulness of zebrafish and medaka as comparative models to study the developmental mechanisms of epithalamic asymmetry in vertebrates.
 
Article
At The Royal Society Discussion Meeting, Origins of HIV and the AIDS epidemic, which this issue records, Edward Hooper added two new 'smoking guns' to the accusations published previously in The river. These were proposed as conclusive evidence for the hypothesis that simian immunodeficiency virus-contaminated CHAT polio vaccine caused the HIV-1 group M epidemic. We have investigated the facts in relation to these 'smoking guns'.
 
Article
Organismal phylogeny depends on cell division, stasis, mutational divergence, cell mergers (by sex or symbiogenesis), lateral gene transfer and death. The tree of life is a useful metaphor for organismal genealogical history provided we recognize that branches sometimes fuse. Hennigian cladistics emphasizes only lineage splitting, ignoring most other major phylogenetic processes. Though methodologically useful it has been conceptually confusing and harmed taxonomy, especially in mistakenly opposing ancestral (paraphyletic) taxa. The history of life involved about 10 really major innovations in cell structure. In membrane topology, there were five successive kinds of cell: (i) negibacteria, with two bounding membranes, (ii) unibacteria, with one bounding and no internal membranes, (iii) eukaryotes with endomembranes and mitochondria, (iv) plants with chloroplasts and (v) finally, chromists with plastids inside the rough endoplasmic reticulum. Membrane chemistry divides negibacteria into the more advanced Glycobacteria (e.g. Cyanobacteria and Proteobacteria) with outer membrane lipolysaccharide and primitive Eobacteria without lipopolysaccharide (deserving intenser study). It also divides unibacteria into posibacteria, ancestors of eukaryotes, and archaebacteria-the sisters (not ancestors) of eukaryotes and the youngest bacterial phylum. Anaerobic eobacteria, oxygenic cyanobacteria, desiccation-resistant posibacteria and finally neomura (eukaryotes plus archaebacteria) successively transformed Earth. Accidents and organizational constraints are as important as adaptiveness in body plan evolution.
 
Article
Faster than ever, neuroscience is generating vast amounts of data that await cross-referencing, comparison, integration and interpretation in the endeavour to unravel the mechanisms of the brain. The complex, diverse and distributed nature of these data requires the development of advanced neuroinformatics methodologies for databases and associated tools that are now beginning to emerge. This paper presents an overview of current issues in the representation, integration and analysis of neuroscience data from molecular to brain systems levels, including issues of implementation, standardization, management, quality control, copyright, confidentiality and acceptance. Particular emphasis is given to integrative neuroinformatics approaches for exploring structure-function relationships in the brain.
 
Article
The ecological and evolutionary opportunities of apomixis in the short and the long term are considered, based on two closely related apomictic genera: Taraxacum (dandelion) and Chondrilla (skeleton weed). In both genera apomicts have a wider geographical distribution than sexuals, illustrating the short–term ecological success of apomixis. Allozymes and DNA markers indicate that apomictic populations are highly polyclonal. In Taraxacum , clonal diversity can be generated by rare hybridization between sexuals and apomicts, the latter acting as pollen donors. Less extensive clonal diversity is generated by mutations within clonal lineages. Clonal diversity may be maintained by frequency–dependent selection, caused by biological interactions (e.g. competitors and pathogens). Some clones are geographically widespread and probably represent phenotypically plastic ‘general–purpose genotypes’. The long–term evolutionary success of apomictic clones may be limited by lack of adaptive potential and the accumulation of deleterious mutations. Although apomictic clones may be considered as ‘evolutionary dead ends’, the genes controlling apomixis can escape from degeneration and extinction via pollen in crosses between sexuals and apomicts. In this way, apomixis genes are transferred to a new genetic background, potentially adaptive and cleansed from linked deleterious mutations. Consequently, apomixis genes can be much older than the clones they are currently contained in. The close phylogenetic relationship between Taraxacum and Chondrilla and the similarity of their apomixis mechanisms suggest that apomixis in these two genera could be of common ancestry.
 
Article
In the language of mathematics, one needs minimally two interacting variables (two dimensions) to describe repeatable periodic behaviour, and in the language of density dependence, one needs delayed, not immediate, density dependence to produce cyclicity. Neither language specifies the causal mechanism. There are two major potential mechanisms: exogenous mechanisms involving species interactions as in predator-prey or host-parasite, and endogenous mechanisms such as maternal effects where population growth results from the cross-generational transmission of individual quality. The species interactions view stemming from a major observation of Elton and a simultaneous independent theory by Lotka and Volterra is currently dominant. Most ecologists, when faced with cyclic phenomena, automatically look for an interacting species one step below or above in a food chain in order to find an explanation. Maternal effects hypothesis, verbally suggested in the 1950s, had only found its theoretical implementation in the 1990 s. In a relatively short time, the degree of acceptance of this view grew to the level of a 'minority opinion' as evidenced by the widely used textbook of Begon et al. This short review attempts to describe the arguments for and against this internal two-dimensional approach.
 
Article
The plant pathogen Agrobacterium tumefaciens induces the formation of crown gall tumours at wound sites on host plants by directly transforming plant cells. This disease strategy benefits the bacteria as the infected plant tissue produces novel nutrients, called opines, that the colonizing bacteria can use as nutrients. Almost all of the genes that are required for virulence, and all of the opine uptake and utilization genes, are carried on large tumour-inducing (Ti) plasmids. The observation more than 25 years ago that specific opines are required for Ti plasmid conjugal transfer led to the discovery of a cell-cell signalling system on these plasmids that is similar to the LuxR-LuxI system first described in Vibrio fischeri. All Ti plasmids that have been described to date carry a functional LuxI-type N-acylhomoserine lactone synthase (TraI), and a LuxR-type signal receptor and transcriptional regulator called TraR. The traR genes are expressed only in the presence of specific opines called conjugal opines. The TraR-TraI system provides an important model for LuxR-LuxI-type systems, especially those found in the agriculturally important Rhizobiaceae family. In this review, we discuss current advances in the biochemistry and structural biology of the TraR-TraI system.
 
Proportions of antagonistic QTLs for various categories of organisms and traits in crosses involving wild species and tests for significant deviations from neutrality. 
ANOVA of the effects of kingdom, population type, cross type, mating system and trait type on the total number of QTLs per trait. 
Logistic analysis of whether or not each trait had at least one antagonistic QTL as a function of kingdom, popu- lation type, cross type, mating system, trait type and the total number of QTLs per trait. 
Article
Segregating hybrids often exhibit phenotypes that are extreme or novel relative to the parental lines. This phenomenon is referred to as transgressive segregation, and it provides a mechanism by which hybridization might contribute to adaptive evolution. Genetic studies indicate that transgressive segregation typically results from recombination between parental taxa that possess quantitative trait loci (QTLs) with antagonistic effects (i.e. QTLs with effects that are in the opposite direction to parental differences for those traits). To assess whether this genetic architecture is common, we tabulated the direction of allelic effects for 3252 QTLs from 749 traits and 96 studies. Most traits (63.6%) had at least one antagonistic QTL, indicating that the genetic substrate for transgressive segregation is common. Plants had significantly more antagonistic QTLs than animals, which agrees with previous reports that transgressive segregation is more common in plants than in animals. Likewise, antagonistic QTLs were more frequent in intra- than in interspecific crosses and in morphological than in physiological traits. These results indicate that transgressive segregation provides a general mechanism for the production of extreme phenotypes at both above and below the species level and testify to the possible creative part of hybridization in adaptive evolution and speciation.
 
A schematic illustration of the cytoarchitectonic division of (a) the hand and (b) the foot somatosensory cortices. The shadowed areas indicate areas where currents can generate MEG signals outside the head.
Article
Magnetoencephalography (MEG) is a totally non-invasive research method which provides information about cortical dynamics on a millisecond time-scale. Whole-scalp magnetic field patterns following stimulation of different peripheral nerves indicate activation of an extensive cortical network. At the SI cortex, the responses reflect mainly the activity of area 3b, with clearly somatotopical representations of different body parts. The SII cortex is activated bilaterally and it also receives, besides tactile input, nociceptive afference. Somatically evoked MEG signals may also be detected from the posterior parietal cortex, central mesial cortex and the frontal lobe. The serial versus parallel processing in the cortical somatosensory network is still under debate.
 
Article
Allopolyploidy, the joining of two parental genomes in a polyploid organism with diploid meiosis, is an important mechanism of reticulate evolution. While many successful long-established allopolyploids are known, those formed recently undergo an instability phase whose basis is now being characterized. We describe observations made with the Arabidopsis system that include phenotypic instability, gene silencing and activation, and methylation changes. We present a model based on the epigenetic destabilization of genomic repeats, which in the parents are heterochromatinized and suppressed. We hypothesize that loss of epigenetic suppression of these sequences, here defined as the heterome, results in genomic instability including silencing of single-copy genes.
 
Article
Despite striking advances in functional brain imaging, the cellular and molecular mechanisms that underlie the signals detected by these techniques are still largely unknown. The basic physiological principle of functional imaging is represented by the tight coupling existing between neuronal activity and the associated local increase in both blood flow and energy metabolism. Positron emission tomography (PET) signals detect blood flow, oxygen consumption and glucose use associated with neuronal activity; the degree of blood oxygenation is currently thought to contribute to the signal detected with functional magnetic resonance imaging, while magnetic resonance spectroscopy (MRS) identifies the spatio-temporal pattern of the activity-dependent appearance of certain metabolic intermediates such as glucose or lactate. Recent studies, including those of neurotransmitter-regulated metabolic fluxes in purified preparations and analyses of the cellular localization of enzymes and transporters involved in energy metabolism, as well as in vivo microdialysis and MRS approaches have identified the neurotransmitter glutamate and astrocytes, a specific type of glial cell, as pivotal elements in the coupling of synaptic activity with energy metabolism. Astrocytes are ideally positioned to sense increases in synaptic activity and to couple them with energy metabolism. Indeed they possess specialized processes that cover the surface of intraparenchymal capillaries, suggesting that astrocytes may be a likely site of prevalent glucose uptake. Other astrocyte processes are wrapped around synaptic contacts which possess receptors and reuptake sites for neurotransmitters. Glutamate stimulates glucose uptake into astrocytes. This effect is mediated by specific glutamate transporters present on these cells. The activity of these transporters, which is tightly coupled to the synaptic release of glutamate and operates the clearance of glutamate from the extracellular space, is driven by the electrochemical gradient of Na+. This Na(+)-dependent uptake of glutamate into astrocytes triggers a cascade of molecular events involving the Na+/K(+)-ATPase leading to the glycolytic processing of glucose and the release of lactate by astrocytes. The stoichiometry of this process is such that for one glutamate molecule taken up with three Na+ ions, one glucose molecule enters an astrocyte, two ATP molecules are produced through aerobic glycolysis and two lactate molecules are released. Within the astrocyte, one ATP molecule fuels one 'turn of the pump' while the other provides the energy needed to convert glutamate to glutamine by glutamine synthase. Evidence has been accumulated from structural as well as functional studies indicating that, under aerobic conditions, lactate may be the preferred energy substrate of activated neurons. Indeed, in the presence of oxygen, lactate is converted to pyruvate, which can be processed through the tricarboxylic acid cycle and the associated oxidative phosphorylation, to yield 17 ATP molecules per lactate molecule. These data suggest that during activation the brain may transiently resort to aerobic glycolysis occurring in astrocytes, followed by the oxidation of lactate by neurons. The proposed model provides a direct mechanism to couple synaptic activity with glucose use and is consistent with the notion that the signals detected during physiological activation with 18F-deoxyglucose (DG)-PET may reflect predominantly uptake of the tracer into astrocytes. This conclusion does not question the validity of the 2-DG-based techniques, rather it provides a cellular and molecular basis for these functional brain imaging techniques.
 
Individual male fertilities {l k } of individuals in a population of Chamaelirium luteum estimated by ML paternity analysis. 
Nonlinear regression coefficients estimated for each plot -year combination using the model lnl ik = gd ik 1 af ik . 
Expected relative male reproductive success {l k } according to a negative exponential model of pollen dispersal (equation (2.2)) with different values for the distance effect parameter g. 
Observed counts of transgenic progeny over the hexagonal grid for each plot-year combination: (a) plot 1, 1999; (b) plot 2, 1999; (c) plot 1, 2000; (d ) plot 2, 2000. 
Predicted counts of transgenic progeny over the hexagonal grid (see table 2 for nonlinear regression coefficients) for each plot-year combination: (a) plot 1, 1999; (b) plot 2, 1999; (c) plot 1, 2000; (d ) plot 2, 2000. 
Article
One element of the current public debate about genetically modified crops is that gene flow from transgenic cultivars into surrounding weed populations will lead to more problematic weeds, particularly for traits such as herbicide resistance. Evolutionary biologists can inform this debate by providing accurate estimates of gene flow potential and subsequent ecological performance of resulting hybrids. We develop a model for gene flow incorporating exponential distance and directional effects to be applied to windpollinated species. This model is applied to previously published data on gene flow in experimental plots of Agrostis stolonifera L. (creeping bentgrass), which assessed gene flow from transgenic plants resistant to the herbicide glufosinate to surrounding non-transgenic plants. Our results show that although pollen dispersal can be limited in some sites, it may be extensive in others, depending on local conditions such as exposure to wind. Thus, hybridization under field conditions is likely to occur. Given the nature of the herbicide resistance trait, we regard this trait as unlikely to persist in the absence of herbicide, and suggest that the ecological consequences of such gene flow are likely to be minimal.
 
Article
Plant evolutionary biologists' view of gene flow and hybridization has undergone a revolution. Twenty-five years ago, both were considered rare and largely inconsequential. Now gene flow and hybridization are known to be idiosyncratic, varying with the specific populations involved. Gene flow typically occurs at evolutionarily significant rates and at significant distances. Spontaneous hybridization occasionally has important applied consequences, such as stimulating the evolution of more aggressive invasives and increasing the extinction risk for rare species. The same problems have occurred for spontaneous hybridization between crops and their wild relatives. These new data have implications for transgenic crops: (i) for most crops, gene flow can act to introduce engineered genes into wild populations; (ii) depending on the specific engineered gene(s) and populations involved, gene flow may have the same negative impacts as those observed for traditionally improved crops; (iii) gene flow's idiosyncratic nature may frustrate management and monitoring attempts; and (iv) intercrop transgene flow, although rarely discussed, is equally worthy of study.
 
Article
In this article we review recent studies, primarily from our laboratory, using 13C NMR (nuclear magnetic resonance) to non-invasively measure the rate of the glutamate-glutamine neurotransmitter cycle in the cortex of rats and humans. In the glutamate-glutamine cycle, glutamate released from nerve terminals is taken up by surrounding glial cells and returned to the nerve terminals as glutamine. 13C NMR studies have shown that the rate of the glutamate-glutamine cycle is extremely high in both the rat and human cortex, and that it increases with brain activity in an approximately 1:1 molar ratio with oxidative glucose metabolism. The measured ratio, in combination with proposals based on isolated cell studies by P. J. Magistretti and co-workers, has led to the development of a model in which the majority of brain glucose oxidation is mechanistically coupled to the glutamate-glutamine cycle. This model provides the first testable mechanistic relationship between cortical glucose metabolism and a specific neuronal activity. We review here the experimental evidence for this model as well as implications for blood oxygenation level dependent magnetic resonance imaging and positron emission tomography functional imaging studies of brain function.
 
Trends in central tendency and variability of incubation periods at varying dose. (a) Box-whisker plot of incubation period as a function of relative dose (di¡erence from ID 50 ). Relative dose is a logarithmic measure so a one unit increase represents a tenfold rise in the concentration of infectious material in the inoculum. As dose increases, median incubation period decreases in a linear fashion. (b) Detailed distribution of incubation periods at relative doses 4, 2 and 0. (c) Box-whisker plot of the di¡erence of each mouse's incubation period from the average for its group (i.e. all infected mice at that dose in that experiment). Mice in groups where only one animal was infected are excluded. This treatment of the data removes betweenexperiment variability and is therefore a better method for investigating trends in the variability of incubation period with dose. Between the ID 50 and four logs above, each tenfold increase in dose leads to a seven-day reduction in the interquartile range for the incubation period. (d ) Detail of the distributions of di¡erence from mean incubation period at relative doses 4, 2 and 0. These curves show that it would be reasonable to assume a normal distribution of the incubation period within an experimental group. (e) Box-whisker plot of incubation periods as a function of relative dose for the 16 experiments that used ME7 in C57 mice. ( f ) Box-whisker plot of incubation periods as a function of relative dose for the 22 experiments that used 22A in VM mice. 
Article
An analysis of 117 titration experiments in the murine scrapie model is presented. The experiments encompass 30 years' work and a wide range of experimental conditions. To check that the experimental designs were reasonably consistent over time, comparisons were made of size, duration, source of inoculum, etc., in each experiment. These comparisons revealed no systematic trends that would render invalid comparisons across experiments. For 114 of the experiments it was possible to calculate the dose at which half of the challenged animals were infected (the ID50). These 114 experiments were then combined on the basis of relative dose (i.e. tenfold dilution relative to the ID50). This created a data set in which over 4000 animals were challenged with doses of scrapie ranging from four orders of magnitude below to five orders of magnitude above the ID50. Analysis of this data reveals that mean incubation periods rise linearly with logarithmic decreases in dose. A one unit increase in relative dose (i.e. a tenfold increase in actual dose) will, on average, decrease the incubation period by 25 days. At ID50 the average incubation period in this data set is 300 days. Within a single dose, in a single experimental model, incubation periods have a distribution close to normal. Variability in incubation period also rises linearly as dose decreases. There is no age or sex effect upon the probability of infection, but female mice have incubation periods that are, on average, nine days shorter than their male counterparts and young mice have incubation periods that are longer by seven days. Although many of these patterns are apparent in the results of single titration curves, they can be more rigorously investigated by considering the outcome for thousands of mice.
 
Article
As a neurotransmitter, serotonin (5-HT) is widely used throughout the brain and known to play a role in many processes including emotion and brain development. Of the 15 subtypes of 5-HT receptors, the 1A receptor (5-HT(1A)) has been implicated in depression and suicide. Using the [carbonyl-(11)C]WAY100635 ([(11)C]WAY) ligand and positron emission tomography, we have studied the 5-HT(1A) receptor, first in a group of healthy controls, then in two separate groups of subjects with major depressive disorder (MDD) (antidepressant exposed and not recently medicated), and, lastly, in a group of subjects remitted from MDD. All MDD subjects were medication-free at the time of scan. We found higher 5-HT(1A) binding potential (BP(F)) in MDD subjects not recently exposed to an antidepressant compared with controls and recently medicated MDD subjects; and higher BP(F) in subjects with the C(-1019)G promoter polymorphism. We replicated these findings in a novel cohort and reconciled our discrepant findings with other groups using alternate quantification techniques. We also reported higher BP(F) in subjects remitted from a major depressive episode than in controls. From this work, we proposed a temporal model in which 5-HT(1A) BP(F) may be a trait abnormality of MDD. To further explore the genetic components of MDD and utility of 5-HT(1A) imaging as a potential tool for biomarker or treatment response prediction, these findings should be replicated in a larger cohort using the [(11)C]CUMI-101 agonist tracer.
 
Epifluorescence image of the surface of a rock from an intertidal pool on the South Devon coast.The sample was taken in December 2004 and was stained with SYBR Green I and viewed with a Bio-Rad 1024 confocal laser microscope. The bacteria are stained green and the red fluorescence is due to the autofluorescence of chloroplasts within microalgae. 
The relationship between the density of bacteria (Vibrio anguillarum) in a biofilm and the number of zoospores that attach to the biofilm. The response of the wild-type (C), which produces three AHL molecules (C6-HSL, 3-hydroxyHSL and 3-oxo-C10-HSL) is compared with a vanIM mutant (,) that produces no AHLs.
Attraction of zoospores to biofilm surface roughness. ( a ) Transmission image of zoospores settled on a filamentous actinobacteria biofilm (scale bar, 25 m m). Zoospore settlement on biofilms of ( b ) a filamentous actinobacteria is compared with ( c ) an AHL-producing strain. Treating the biofilms with UV (1 h) or antibiotics (5 units ml K 1 penicillin, 30 min) caused no significant 
Exposure to 3-oxo-C12-HSL induces a calcium influx in Ulva zoospores. (a) False colour image of an Ulva zoospore loaded with the fluorescent calcium indicator dye, calcium orange AM, and viewed by confocal laser microscopy. Calcium influx was determined by the manganese quench technique. Ulva zoospores were exposed to 175 mmol l K1 3-oxo-C12-HSL after prior incubation in seawater containing 100 mmol l K1 MnCl 2 for 5 min. Fluorescence was imaged following excitation at 568 nm, using a Bio-Rad 1024 confocal laser microscope. Only zoospores that had not undergone settlement and retained flagella throughout the time-course were measured. (b) Mean cellular fluorescence in Ulva zoospores expressed as a percentage of initial fluorescence on addition of 3-oxo-C12-HSL (nZ9, control nZ5). Scale bar is 5 mm.
Article
The green seaweed Ulva has been shown to detect signal molecules produced by bacteria. Biofilms that release N-acylhomoserine lactones (AHLs) attract zoospores--the motile reproductive stages of Ulva. The evidence for AHL involvement is based on several independent lines of evidence, including the observation that zoospores are attracted to wild-type bacteria that produce AHLs but are not attracted to mutants that do not produce signal molecules. Synthetic AHL also attracts zoospores and the attraction is lost in the presence of autoinducer inactivation (AiiA) protein. The mechanism of attraction is not chemotactic but involves chemokinesis. When zoospores detect AHLs, the swimming rate is reduced and this results in accumulation of cells at the source of the AHL. It has been demonstrated that the detection of AHLs results in calcium influx into the zoospore. This is the first example of a calcium signalling event in a eukaryote in response to bacterial quorum sensing molecules. The role of AHLs in the ecology of Ulva is discussed. It is probable that AHLs act as cues for the settlement of zoospores, rather than being directly involved as a signalling mechanism.
 
Article
A central issue in evolutionary quantitative genetics is to understand how genetic variation for quantitative traits is maintained in natural populations. Estimates of genetic variation and of genetic correlations and pleiotropy among multiple traits, inbreeding depression, mutation rates for fitness and quantitative traits and of the strength and nature of selection are all required to evaluate theoretical models of the maintenance of genetic variation. Studies in Drosophila melanogaster have shown that a substantial fraction of segregating variation for fitness-related traits in Drosophila is due to rare deleterious alleles maintained by mutation-selection balance, with a smaller but significant fraction attributable to intermediate frequency alleles maintained by alleles with antagonistic pleiotropic effects, and late-age-specific effects. However, the nature of segregating variation for traits under stabilizing selection is less clear and requires more detailed knowledge of the loci, mutation rates, allelic effects and frequencies of molecular polymorphisms affecting variation in suites of pleiotropically connected traits. Recent studies in D. melanogaster have revealed unexpectedly complex genetic architectures of many quantitative traits, with large numbers of pleiotropic genes and alleles with sex-, environment- and genetic background-specific effects. Future genome wide association analyses of many quantitative traits on a common panel of fully sequenced Drosophila strains will provide much needed empirical data on the molecular genetic basis of quantitative traits.
 
Appetite suppressing effects of leptin. The figure illustrates the powerful inhibitory effect of leptin on food intake in ob/ob mice, which lack the functional hormone. Mice were injected with vehicle from days K4 to 0 and then with recombinant leptin (1.25 mg g K1 body wt, twice daily) from days 0 to 7; they were then returned to vehicle injections. Adapted from Mercer et al. (1997).  
Schematic view of the integrated signalling effect of leptin on appetite through the central hypothalamic neuroendocrine pathways. AgRP, agouti-related peptide; CART, cocaine-and amphetamine-regulated transcript; CRH, corticotrophin releasing hormone; MCH, melanin concentrating hormone; NPY, neuropeptide Y; POMC, pro- opiomelanocortin.  
Leptin and putative appetite signals from white adipose tissue. IL, interleukin; TNFa, tumour necrosis factor-a.  
Article
Interest in the biology of white adipose tissue has risen markedly with the recent surge in obesity and its associated disorders. The tissue is no longer viewed simply as a vehicle for lipid storage; instead, it is recognized as a major endocrine and secretory organ. White adipocytes release a multiplicity of protein hormones, signals and factors, termed adipokines, with an extensive range of physiological actions. Foremost among these various adipokines is the cytokine-like hormone, leptin, which is synthesized predominantly in white fat. Leptin plays a critical role in the control of appetite and energy balance, with mutations in the genes encoding the hormone or its receptor leading to profound obesity in both rodents and man. Leptin regulates appetite primarily through an interaction with hypothalamic neuroendocrine pathways, inhibiting orexigenic peptides such as neuropeptide Y and orexin A, and stimulating anorexigenic peptides such as proopiomelanocortin. White fat also secretes several putative appetite-related adipokines, which include interleukin-6 and adiponectin, but whether these are indeed significant signals in the regulation of food intake has not been established. Through leptin and the other adipokines it is evident that adipose tissue communicates extensively with other organs and plays a pervasive role in metabolic homeostasis.
 
Article
There is a difference in viewpoint of developmental and evo-devo geneticists versus breeders and students of quantitative evolution. The former are interested in understanding the developmental process; the emphasis is on identifying genes and studying their action and interaction. Typically, the genes have individually large effects and usually show substantial dominance and epistasis. The latter group are interested in quantitative phenotypes rather than individual genes. Quantitative traits are typically determined by many genes, usually with little dominance or epistasis. Furthermore, epistatic variance has minimum effect, since the selected population soon arrives at a state in which the rate of change is given by the additive variance or covariance. Thus, the breeder's custom of ignoring epistasis usually gives a more accurate prediction than if epistatic variance were included in the formulae.
 
Article
Reef fishes present the observer with the most diverse and stunning assemblage of animal colours anywhere on earth. The functions of some of these colours and their combinations are examined using new non-subjective spectrophotometric measurements of the colours of fishes and their habitat. Conclusions reached are as follows: (i) the spectra of colours in high spatial frequency patterns are often well designed to be very conspicuous to a colour vision system at close range but well camouflaged at a distance; (ii) blue and yellow, the most frequently used colours in reef fishes, may be good for camouflage or communication depending on the background they are viewed against; and (iii) reef fishes use a combination of colour and behaviour to regulate their conspicuousness and crypsis.
 
Article
Several sex differences in eating, their control by gonadal steroid hormones and their peripheral and central mediating mechanisms are reviewed. Adult female rats and mice as well as women eat less during the peri-ovulatory phase of the ovarian cycle (estrus in rats and mice) than other phases, an effect under the control of cyclic changes in estradiol secretion. Women also appear to eat more sweets during the luteal phase of the cycle than other phases, possibly due to simultaneous increases in estradiol and progesterone. In rats and mice, gonadectomy reveals further sex differences: orchiectomy decreases food intake by decreasing meal frequency and ovariectomy increases food intake by increasing meal size. These changes are reversed by testosterone and estradiol treatment, respectively. A variety of peripheral feedback controls of eating, including ghrelin, cholecystokinin (CCK), glucagon, hepatic fatty acid oxidation, insulin and leptin, has been shown to be estradiol-sensitive under at least some conditions and may mediate the estrogenic inhibition of eating. Of these, most progress has been made in the case of CCK. Neurons expressing estrogen receptor-alpha in the nucleus tractus solitarius of the brainstem appear to increase their sensitivity to CCK-induced vagal afferent input so as to lead to an increase in the satiating potency of CCK, and consequently decreased food intake, during the peri-ovulatory period in rats. Central serotonergic mechanisms also appear to be part of the effect of estradiol on eating. The physiological roles of other peripheral feedback controls of eating and their central mediators remain to be established.
 
Article
Fishes have evolved a diversity of sound-generating organs and acoustic signals of various temporal and spectral content. Additionally, representatives of many teleost families such as otophysines, anabantoids, mormyrids and holocentrids possess accessory structures that enhance hearing abilities by acoustically coupling air-filled cavities to the inner ear. Contrary to the accessory hearing structures such as Weberian ossicles in otophysines and suprabranchial chambers in anabantoids, sonic organs do not occur in all members of these taxa. Comparison of audiograms among nine representatives of seven otophysan families from four orders revealed major differences in auditory sensitivity, especially at higher frequencies (> 1 kHz) where thresholds differed by up to 50 dB. These differences showed no apparent correspondence to the ability to produce sounds (vocal versus non-vocal species) or to the spectral content of species-specific sounds. In anabantoids, the lowest auditory thresholds were found in the blue gourami Trichogaster trichopterus, a species not thought to be vocal. Dominant frequencies of sounds corresponded with optimal hearing bandwidth in two out of three vocalizing species. Based on these results, it is concluded that the selective pressures involved in the evolution of accessory hearing structures and in the design of vocal signals were other than those serving to optimize acoustic communication.
 
Article
Various mutations in the prion protein (PrP) gene are associated with Creutzfeldt-Jakob disease (CJD), a transmissible fatal neurodegenerative disorder. Among Libyan Jews, CJD is a familial disease with an incidence about 100 times higher than the worldwide population. CJD in this community segregates with a point mutation at codon 200 of the PrP gene which causes the substitution of lysine for glutamate. This mutation was found in all definitely affected individuals and yields a maximum lod score of 4.85. Some healthy elderly mutation carries above 65 years of age were identified, suggesting partial penetrance. Homozygous patients have the same disease pattern and age of onset as heterozygous patients, which argues that CJD associated with the codon 200 lysine mutation is a true dominant disorder. In the caucasian population, Palmer et al. (1991) reported an association between homozygosity in a polymorphic site at codon 129 of the PrP gene, coding for either valine or methionine, with a tendency to acquire the sporadic or iatrogenic forms of CJD, as well as with disease age of appearance in the genetic type. The incidence of the polymorphism at codon 129 in the control Libyan population is similar to the one found in the caucasian population. In the Libyan CJD patients, the codon 200 mutation is within a Met129-encoding allele. The incidence of the Met allele is significantly higher in the affected pedigrees than in the control Libyan population; however, no difference was detected between CJD patients, codon 200 healthy carriers, and their normal family members.(ABSTRACT TRUNCATED AT 250 WORDS)
 
Article
Beta-Epimerization in the corrinoid system has recently emerged as a complicating factor in the latter stages of the total synthesis of vitamin B12 (Eschenmoser 1971; Woodward 1973). It has also found some application in biosynthetic studies on the origin of the methyl groups in ring C (Scott, Townsend & Cushley 1973; Scott, this Discussion p. 303). This paper sets out to review briefly the beta-epimerization of corrinoid polyamides, with particular reference to our work on the neo-series which provided the first established example of this phenomenon.
 
Article
Neural stimuli associated with traumatic events can readily become conditioned so as to reinstate the memory of the original trauma. These conditioned fear responses can last a lifetime and may be especially resistant to extinction. A large amount of data from many different laboratories indicate that the amygdala plays a crucial role in conditioned fear. The amygdala receives information from all sensory modalities and projects to a variety of hypothalamic and brainstem target areas known to be critically involved in specific signs that are used to define fear and anxiety. Electrical stimulation of the amygdala elicits a pattern of behaviours that mimic natural or conditioned states of fear. Lesions of the amygdala block innate or conditioned fear and local infusion of drugs into the amygdala have anxiolytic effects in several behavioural tests. Excitatory amino acid receptors in the amygdala are critical for the acquisition, expression and extinction of conditioned fear.
 
Article
The effective population size (Ne) is an important parameter in ecology, evolutionary biology and conservation biology. It is, however, notoriously difficult to estimate, mainly because of the highly stochastic nature of the processes of inbreeding and genetic drift for which Ne is usually defined and measured, and because of the many factors (such as time and spatial scales, systematic forces) confounding such processes. Many methods have been developed in the past three decades to estimate the current, past and ancient effective population sizes using different information extracted from some genetic markers in a sample of individuals. This paper reviews the methodologies proposed for estimating Ne from genetic data using information on heterozygosity excess, linkage disequilibrium, temporal changes in allele frequency, and pattern and amount of genetic variation within and between populations. For each methodology, I describe mainly the logic and genetic model on which it is based, the data required and information used, the interpretation of the estimate obtained, some results from applications to simulated or empirical datasets and future developments that are needed.
 
Article
There are, in the broadest sense, two mechanisms by which gene expression can be extinguished in vertebrates. The first of these is based on mass action effects of positive and negative regulatory factors and is termed activation and repression; the second is independent of positive regulatory factors but is based on the history of the affected gene and is termed silencing. It can be said, again in the broadest sense, that imprinted genes, genes subject to X inactivation, and transposon promoters are subject to silencing, while the promoters of tissue-specific genes in non-expressing tissues are controlled by activation and repression. The escape of imprinted genes from silencing through unknown mechanisms can cause developmental abnormalities and can predispose to the formation of embryonal tumours. One developmental disorder caused by loss of imprinting of genes on chromosome 11p15.5 is Beckwith-Wiedemann syndrome (BWS). This syndrome has long been known to be inexplicably common in monozygotic twins; the twins are nearly always discordant for BWS, and nearly all twins are female. A loss of imprinting model based on stochastic errors in the nucleocytoplasmic trafficking of the DNA methyltransferase DNMT1, or a paternally expressed function that opposes maintenance methylation of maternally repressed growth-enhancing genes, is proposed to explain the perplexing genetics of BWS in monozygotic twins.
 
Article
The posterior parietal cortex has long been considered an 'association' area that combines information from different sensory modalities to form a cognitive representation of space. However, until recently little has been known about the neural mechanisms responsible for this important cognitive process. Recent experiments from the author's laboratory indicate that visual, somatosensory, auditory and vestibular signals are combined in areas LIP and 7a of the posterior parietal cortex. The integration of these signals can represent the locations of stimuli with respect to the observer and within the environment. Area MSTd combines visual motion signals, similar to those generated during an observer's movement through the environment, with eye-movement and vestibular signals. This integration appears to play a role in specifying the path on which the observer is moving. All three cortical areas combine different modalities into common spatial frames by using a gain-field mechanism. The spatial representations in areas LIP and 7a appear to be important for specifying the locations of targets for actions such as eye movements or reaching; the spatial representation within area MSTd appears to be important for navigation and the perceptual stability of motion signals.
 
Article
Does movement of the eyes in one or another direction function as an automatic attentional cue to a location of interest? Two experiments explored the directional movement of the eyes in a full face for speed of detection of an aftercoming location target in young people with autism and in control participants. Our aim was to investigate whether a low-level perceptual impairment underlies the delay in gaze following characteristic of autism. The participants' task was to detect a target appearing on the left or right of the screen either 100 ms or 800 ms after a face cue appeared with eyes averting to the left or right. Despite instructions to ignore eye-movement in the face cue, people with autism and control adolescents were quicker to detect targets that had been preceded by an eye movement cue congruent with target location compared with targets preceded by an incongruent eye movement cue. The attention shifts are thought to be reflexive because the cue was to be ignored, and because the effect was found even when cue-target duration was short (100 ms). Because (experiment two) the effect persisted even when the face was inverted, it would seem that the direction of movement of eyes can provide a powerful (involuntary) cue to a location.
 
Putative Ediacaran metazoans. (a) Natural cast on bed base of Kimberella resting trace (asterisk) and Radulichnus radular feeding trace fans (arrows); scale bar, 1 cm. (b)Parvancorina minchami; scale bar, 1 cm. (c) Spriggina floundersi; scale bar, 10 mm. ( d ) Marywadea ovata; scale bar, 10 mm. ( e ) Dickinsonia costata; scale bar, 2 cm.  
Article
Unravelling the timing of the metazoan radiation is crucial for elucidating the macroevolutionary processes associated with the Cambrian explosion. Because estimates of metazoan divergence times derived from molecular clocks range from quite shallow (Ediacaran) to very deep (Mesoproterozoic), it has been difficult to ascertain whether there is concordance or quite dramatic discordance between the genetic and geological fossil records. Here, we show using a range of molecular clock methods that the major pulse of metazoan divergence times was during the Ediacaran, which is consistent with a synoptic reading of the Ediacaran macrobiota. These estimates are robust to changes in priors, and are returned with or without the inclusion of a palaeontologically derived maximal calibration point. Therefore, the two historical records of life both suggest that although the cradle of Metazoa lies in the Cryogenian, and despite the explosion of ecology that occurs in the Cambrian, it is the emergence of bilaterian taxa in the Ediacaran that sets the tempo and mode of macroevolution for the remainder of geological time.
 
Article
The lateral frontal cortex is involved in various aspects of executive processing within short- and long-term memory. It is argued that the different parts of the lateral frontal cortex make distinct contributions to memory that differ in terms of the level of executive processing that is carried out in interaction with posterior cortical systems. According to this hypothesis, the mid-dorsolateral frontal cortex (areas 46 and 9) is a specialized system for the monitoring and manipulation of information within working memory, whereas the mid-ventrolateral frontal cortex (areas 47/12 and 45) is involved in the active retrieval of information from the posterior cortical association areas. Data are presented which support this two-level hypothesis that posits two distinct levels of interaction of the lateral frontal cortex with posterior cortical association areas. Functional activation studies with normal human subjects have demonstrated specific activity within the mid-dorsolateral region of the frontal cortex during the performance of tasks requiring monitoring of self-generated and externally generated sequences of responses. In the monkey, lesions restricted to this region of the frontal cortex yield a severe impairment in performance of the above tasks, this impairment appearing against a background of normal performance on several basic mnemonic tasks. By contrast, a more severe impairment follows damage to the mid-ventrolateral frontal region and functional activation studies have demonstrated specific changes in activity in this region in relation to the active retrieval of information from memory.
 
Schematic overview of model for genomic medicine based on integration of gene expression profiles with clinical and other data. Based in part on Nevins et al. (2003). 
Integrated translational process for genomic medicine. 
Article
Advances in genome technology and other fruits of the Human Genome Project are playing a growing role in the delivery of health care. With the development of new technologies and opportunities for large-scale analysis of the genome, transcriptome, proteome and metabolome, the genome sciences are poised to have a profound impact on clinical medicine. Cancer prognostics will be among the first major test cases for a genomic medicine paradigm, given that all cancer is caused by genomic instability, and microarrays allow assessment of patients' entire expressed genomes. Analysis of breast cancer patients' expression patterns can already be highly correlated with recurrence risks. By integrating clinical data with gene expression profiles, imaging, metabolomic profiles and proteomic data, the prospect for developing truly individualized care becomes ever more real. Notwithstanding these promises, daunting challenges remain for genomic medicine. Success will require planning robust prospective trials, analysing health care economic and outcome data, assuaging insurance and privacy concerns, developing health delivery models that are commercially viable and scaling up to meet the needs of the whole population.
 
Top-cited authors
Morton Barlaz
  • North Carolina State University
Charles James Moore
  • Algalita Marine Research and Education
François Galgani
  • Institut Français de Recherche pour l'Exploitation de la Mer
Shanna H Swan
  • Icahn School of Medicine at Mount Sinai
Frederick vom Saal
  • University of Missouri