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PubMed2005

The hangover gene defines a stress pathway required for ethanol tolerance development.

Repeated alcohol consumption leads to the development of tolerance, simply defined as an acquired resistance to the physiological and behavioural effects of the drug. This tolerance allows increased alcohol consumption, which over time leads to physical dependence and possibly addiction. Previous studies have shown that Drosophila develop ethanol tolerance, with kinetics of acquisition and dissipation that mimic those seen in mammals. This tolerance requires the catecholamine octopamine, the functional analogue of mammalian noradrenaline. Here we describe a new gene, hangover, which is required for normal development of ethanol tolerance. hangover flies are also defective in responses to environmental stressors, such as heat and the free-radical-generating agent paraquat. Using genetic epistasis tests, we show that ethanol tolerance in Drosophila relies on two distinct molecular pathways: a cellular stress pathway defined by hangover, and a parallel pathway requiring octopamine. hangover encodes a large nuclear zinc-finger protein, suggesting a role in nucleic acid binding. There is growing recognition that stress, at both the cellular and systemic levels, contributes to drug- and addiction-related behaviours in mammals. Our studies suggest that this role may be conserved across evolution.

Alcoholism↗

PubMed2000

Natural history of portal hypertensive gastropathy in patients with liver cirrhosis. The New Italian Endoscopic Club for the study and treatment of esophageal varices (NIEC).

BACKGROUND & AIMS: The clinical importance of portal hypertensive gastropathy (PHG) as a source of gastrointestinal bleeding in patients with cirrhosis is poorly defined. We investigated the natural history of this condition in a large series of patients. METHODS: All patients with cirrhosis seen at 7 hospitals during June and July 1992 were followed up with clinical and endoscopic examinations every 6 months for up to 3 years. Gastropathy was classified according to the classification of the New Italian Endoscopic Club. RESULTS: The prevalence of gastropathy was 80% and was correlated with the duration of disease, presence and size of esophagogastric varices, and a previous history of endoscopic variceal sclerotherapy. During 18+/-8 months of follow-up, gastropathy was stable in 29% of patients, deteriorated in 23%, improved in 23%, and fluctuated with time in 25%. The evolution of gastropathy with time was identical in patients with and without previous or current sclerotherapy. Acute bleeding from gastropathy occurred in 8 of 315 patients (2.5%). The bleeding-related mortality rate was 12.5%. Chronic bleeding occurred in 34 patients (10.8%). CONCLUSIONS: PHG is common in patients with cirrhosis, and its prevalence parallels the severity of portal hypertension. Gastropathy can progress from mild to severe and vice versa or even disappear completely. Bleeding from this lesion is relatively uncommon and rarely severe. Sclerotherapy of esophageal varices does not seem to influence the natural history of this condition.

Acute Disease↗

PubMed2002

gamma -Glutamyl carboxylation: An extracellular posttranslational modification that antedates the divergence of molluscs, arthropods, and chordates.

The posttranslational gamma-carboxylation of glutamate residues in secreted proteins to gamma-carboxyglutamate is carried out by the vitamin K-dependent enzyme gamma-glutamyl carboxylase. gamma-Carboxylation has long been thought to be a biochemical specialization of vertebrates, essential for blood clotting. Recently, a gamma-carboxylase was shown to be expressed in Drosophila, although its function remains undefined in this organism. We have characterized both cDNA and genomic clones for the gamma-glutamyl carboxylase from the marine mollusc, Conus, the only nonvertebrate organism for which gamma-carboxyglutamate-containing proteins have been biochemically and physiologically characterized. The predicted amino acid sequence has a high degree of sequence similarity to the Drosophila and vertebrate enzymes. Although gamma-carboxylases are highly conserved, the Conus and mammalian enzymes have divergent substrate specificity. There are striking parallels in the gene organization of Conus and human gamma-carboxylases. Of the 10 Conus introns identified, 8 are in precisely the same position as the corresponding introns in the human enzyme. This remarkable conservation of intron/exon boundaries reveals that an intron-rich gamma-carboxylase was present early in the evolution of the animal phyla; although specialized adaptations in mammals and molluscs that require this extracellular modification have been identified, the ancestral function(s) and wider biological roles of gamma-carboxylation still need to be defined. The data raise the possibility that most introns in the genes of both mammals and molluscs antedate the divergence of these phyla.

Amino Acid Sequence↗

PubMed2002

Topology of electronic charge density and energetics of planar faults in fcc metals.

Using ab initio calculations we have studied the energetics and the evolution of the electronic charge density with shear in three fcc metals exhibiting different deformation properties, aluminum, silver, and iridium. The charge redistribution described by the change in character of specific charge density critical points (cps), is ascertained from the values of the charge density, rho(0), and its three principal curvatures, rho( parallel parallel), rho(hh), and rho(vv), respectively. The change in character of cps correlates with the energetics. For all three metals, rho(hh) vanishes near the unstable stacking configuration. The symmetry or asymmetry of the charge redistribution, measured by rho(hh)/rho(vv), may be an important factor determining stacking fault energies.

Journal Article↗

PubMed2005

Role of kinetic effects on the polarization current around a magnetic island.

The polarization current due to a magnetic island rotating in a tokamak plasma is believed to play a central role in the initial evolution of the neoclassical tearing mode. Monte Carlo delta f simulations are performed which also cover a parameter range that is not amenable to analytic treatment but is relevant to experiments. It is shown that the polarization current can change sign when the island rotation frequency is of the order of the ion parallel streaming around the island. Moreover, the current is reduced when the island width is of the order of the ion banana width. Finally, the transition to the enhanced high-collisionality regime is shown to occur for collision frequencies higher than those typical of today's experiments.

Journal Article↗

PubMedDate not supplied

The evolutionary basis of some clinical disorders of the human foot: a comparative survey of the living primates.

The living primates are a highly diverse group of essentially arboreal animals whose feet are variously adapted for grasping, climbing, and leaping in trees. One of the most remarkable aspects of the anatomical variation in the feet of the extant primates is that this diversity can be arranged in a graduated sequence ranging from the primitive transtarsal-opposition type of grasping foot found in the lemurs, through the specialized transmetarsal-adduction type that characterizes the higher primates, to the unique nongrasping foot of humans. The comparative study of this graded series makes it possible, without recourse to the fossil record, to appreciate the adaptive and functional stages through which the human foot passed in its evolution. It is hypothesized that the initial stage of human erect posture was characterized by a foot which was adapted to both hallucial grasping and short distance bipedal walking. In many respects, the structure of the foot of this primitive human was probably similar to that of the living highland gorilla. When compared with the feet of our closest living relatives, the African apes, the human foot is characterized by two major evolutionary specializations: the longitudinal and transverse arches, and the parallel first and second metatarsals. These two morphological adaptations, together with several associated specializations, are the structural basis of the bipedal human foot. Reconstructing the evolutionary and adaptive history of these specializations creates a better understanding of some of the more common clinical podiatric disorders. The modern human foot is structurally so well adapted to prolonged bipedal walking and standing that even slight deviations from its evolutionarily established pattern will produce debilitating clinical manifestations. In most cases, successful treatment of such disorders involves restoration of the foot's basic adaptive configuration.

Adaptation, Biological↗

PubMed2001

Recent developments in the evolution of morphologies and controllers for physically simulated creatures.

Karl Sims' work on evolving body shapes and controllers for three-dimensional, physically simulated creatures generated wide interest on its publication in 1994. The purpose of this article is threefold: (a) to highlight a spate of recent work by a number of researchers in replicating, and in some cases extending, Sims' results using standard PCs (Sims' original work was done on a Connection Machine CM-5 parallel computer). In particular, a re-implementation of Sims' work by the authors will be described and discussed; (b) to illustrate how off-the-shelf physics engines can be used in this sort of work, and also to highlight some deficiencies of these engines and pitfalls when using them; and (c) to indicate how these recent studies stand in respect to Sims' original work.

Anatomy↗

PubMed1994

Molecular evolution of the major capsid protein VP1 of enterovirus 70.

Nucleotide sequences of the genome RNA encoding capsid protein VP1 (918 nucleotides) of 18 enterovirus 70 (EV70) isolates collected from various parts of the world in 1971 to 1981 were determined, and nucleotide substitutions among them were studied. The genetic distances between isolates were calculated by the pairwise comparison of nucleotide difference. Regression analysis of the genetic distances against time of isolation of the strains showed that the synonymous substitution rate was very high at 21.53 x 10(-3) substitution per nucleotide per year, while the nonsynonymous rate was extremely low at 0.32 x 10(-3) substitution per nucleotide per year. The rate estimated by the average value of synonymous and nonsynonymous substitutions (W.-H. Li, C.-C. Wu, and C.-C. Luo, Mol. Biol. Evol. 2:150-174, 1985) was 5.00 x 10(-3) substitution per nucleotide per year. Taking the average value of synonymous and nonsynonymous substitutions as genetic distances between isolates, the phylogenetic tree was inferred by the unweighted pairwise grouping method of arithmetic average and by the neighbor-joining method. The tree indicated that the virus had evolved from one focal place, and the time of emergence was estimated to be August 1967 +/- 15 months, 2 years before first recognition of the pandemic of acute hemorrhagic conjunctivitis. By superimposing every nucleotide substitution on the branches of the phylogenetic tree, we analyzed nucleotide substitution patterns of EV70 genome RNA. In synonymous substitutions, the proportion of transitions, i.e., C<==>U and G<==>A, was found to be extremely frequent in comparison with that reported on other viruses or pseudogenes. In addition, parallel substitutions (independent substitutions at the same nucleotide position on different branches, i.e., different isolates, of the tree) were frequently found in both synonymous and nonsynonymous substitutions. These frequent parallel substitutions and the low nonsynonymous substitution rate despite the very high synonymous substitution rate described above imply a strong restriction on nonsynonymous substitution sites of VP1, probably due to the requirement for maintaining the rigid icosahedral conformation of the virus.

Base Sequence↗

PubMed2003

Crystal structure of creatininase from Pseudomonas putida: a novel fold and a case of convergent evolution.

Creatinine amidohydrolase (creatininase; EC 3.5.2.10) from Pseudomonas putida, a homohexameric enzyme with a molecular mass of 28.4 kDa per subunit, is a cyclic amidohydrolase catalysing the reversible conversion of creatinine to creatine. The enzyme plays a key role in the bacterial degradation of creatinine. The three-dimensional structure of creatininase from P.putida was determined and refined to 2.1A. The structure shows the six subunits arranged as a trimer of dimers and definitely disproves previous reports that the enzyme has an octameric quaternary structure. Each monomer consists of a central, four-stranded, parallel beta-sheet flanked by two alpha-helices on both sides of the beta-sheet. This topology is unique within the superfamily of amidohydrolases. Moreover, creatininase possesses a novel fold with no close structural relatives within the Protein Data Bank. Each creatininase monomer contains a binuclear zinc centre near the C termini of the beta-strands and the N termini of the main alpha-helices. These zinc ions indicate the location of the active site unambiguously. The active site is entirely buried and is not accessible from the solution without movement of parts of the protein. The two zinc ions are bridged by a water molecule and by an aspartate residue, which acts as a bidentate ligand. They differ from each other in the number and the spatial arrangement of their ligands. One of them is tetrahedrally and the other trigonal-bipyramidally ligated. Using two water molecules of the first coordination sphere as anchor points, a creatinine-water adduct resembling the transition state of the hydrolysation reaction was modelled into the active site. The resulting complex in combination with structural comparisons with other amidohydrolases enabled us to identify the most probable candidate for the catalytic base and to suggest a putative reaction mechanism. Surprisingly these structural comparisons revealed a similarity in the active-site arrangement between creatininase and the hydantoinase-like cyclic amidohydrolases that was unexpected, given the completely unrelated primary and tertiary structures. In particular, the zinc-bridging aspartate residue of creatininase is a spatially and functionally analogue to a carboxylated lysine residue found in dihydroorotase and the hydantoinases. Hence, creatininase and the hydantoinase-like cyclic amidohydrolases represent a further example of convergent evolution within the enzyme class of hydrolases.

Amidohydrolases↗

PubMed1998

Recent advances in noninvasive techniques to monitor hormone-behavior interactions.

This paper reviews recent advances in field endocrinology, a focus as well as a method in primatology and behavioral ecology that permits the examination of social behavior and life history through hormonal investigations in natural settings. Endocrine data complements the traditional behavioral data collected by field scientists by providing quantitative measures for the examination of adaptive tradeoffs, costs of social strategies, and reproductive and social significance of mating events. Further, investigations of the physiological mechanisms of reproductive constraint provide tests of the adaptive significance of reproductive skew in cooperative and competitive breeders. Hormone data also can provide insights into the costs of competition and aggression and the role of temperament in individual reproductive success and the evolution of social systems. New, noninvasive methods for the collection of this information have augmented and expanded field endocrinology through the use of techniques that do not require potentially confounding physical or physiological manipulations. Specifically, urine and fecal samples can be collected from free-ranging animals and contain gonadal and adrenal hormones that parallel profiles of serum hormones. Sampling, preservation, extraction, and assay methods for the analysis of excreted steroids are reviewed along with the species and questions to which these methods have been applied.

Animals↗

PubMed1998

Body proportions of Australopithecus afarensis and A. africanus and the origin of the genus Homo.

New discoveries of A. africanus fossils from Member 4 Sterkfontein reveal a body form quite unlike earlier Australopithecus species. The new adult material consists of over 48 fore- and hindlimb specimens and includes an associated partial skeleton, Stw 431. The forelimbs and relatively large: the average size of their joints corresponds to a modern human with body mass of 53 kg. The hindlimbs are much smaller with an average size matching a modern human of only 33 kg. Analyses of the Stw 431 partial skeleton confirm these results. In contrast, A. afarensis and anamensis more closely approximate a human pattern of forelimb joint size. This is an unanticipated complication in our understanding of early human evolution. In general, craniodental morphology tracks time in species of Australopithecus: A. anamensis (3.5-4.1 Ma) is the the most primitive with a strongly sloping symphysis, large canine roots, etc., A. afarensis (3.0-3.6 Ma) is less primitive, and A. africanus (2.6-3.0 Ma) shares many derived characteristics with early Homo (e.g., expanded brain, reduced canine, bicuspid lower third premolar, reduced prognathism, greater flexion of the cranial base, deeper TMJ). the new postcranial material, however, reveals an apparently primitive morphology of relatively large forelimb and small hindlimb joints resembling more the pongid than the human pattern. More pongid-like proportions are also present in the two known associated partial skeletons of H. habilis (OH 62 KNM-ER 3735). This may imply either (1) that A. africanus and H. habilis evolved craniodental characters in parallel with the lineage leading to later Homo, or (2) that fore- to hindlimb proportions of A. afarensis (and perhaps A. anamensis) evolved independent of the lineage leading to Homo and does not imply a close phylogenetic link with Homo. Both of these explanations or any other phylogeny imply homoplasy.

Adult↗

PubMed1987

Quantitative genetic models of sexual selection: a review.

Quantitative genetic models of sexual selection have disproven some of the central tenets of both the handicap mechanism and the 'sexy son' hypothesis. These results suggest that the 'good genes' approach to sexual selection may often lead to erroneous results. Runaway sexual selection seems possible under a wide variety of circumstances. Quantitative genetic models have revealed runaway processes for sexually selected attributes expressed in both sexes and for attributes of parental care. Furthermore, the runaway could occur simultaneously in a series of populations that straddle an environmental gradient. While the models support the feasibility of runaway processes, empirical studies are needed to evaluate whether runaways actually happen. Estimates of critical genetic parameters are particularly needed, as well as measures of natural and sexual selection acting on the same population. The models also show that sexual selection has tremendous potential to produce population differentiation, particularly in epigamic traits. Differentiation is promoted by indeterminancy of evolutionary outcome, transient differences among populations during the final slow approach to equilibrium, sampling drift among equilibrium populations, and the tendency of sexual selection to amplify geographic variation arising from spatial differences in natural selection. Recent work with two- and three-locus models of sexual selection has produced results that parallel the results of the polygenic models (Kirkpatrick, 1982, 1985, 1986; Seger, 1985). Thus the feature of indeterminate equilibria (outcome dependent on initial conditions) is common to both types of model.

Animals↗

PubMed1992

Natural DNA sequences complementary in the same direction: evidence for parallel biosynthesis?

Based on both the occurrence of families of DNA sequences complementary in the same direction in different genomes and the physical possibility of DNA forming a parallel double helix, we postulate an unusual enzymatic synthesis of parallel DNA on a DNA template from its 5'-end. We discuss the assumed evolutionary aspects of this problem and suggest ways to check the hypothesis.

Amino Acid Sequence↗

PubMed1979

Primary and secondary electron donors in photosystem II of chloroplasts. Rates of electron transfer and location in the membrane.

Absorption changes at 820 or 515 nm after a short laser flash were studied comparatively in untreated chloroplasts and in chloroplasts in which oxygen evolution is inhibited. In chloroplasts pre-treated with Tris, the primary donor of Photosystem II (P-680) is oxidized by the flash it is re-reduced in a biphasic manner with half-times of 6 microseconds (major phase) and 22 microseconds. After the second flash, the 6 microseconds phase is nearly absent and P-680+ decays with half-times of 130 microseconds (major phase) and 22 microseconds. Exogenous electron donors (MnCl2 or reduced phenylenediamine) have no direct influence on the kinetics of P-680+. In untreated chloroplasts the 6 and 22 microseconds phases are of very small amplitude, either at the 1st, 2nd or 3rd flash given after dark-adaptation. They are observed, however, after incubation with 10 mM hydroxylamine. These results are interpreted in terms of multiple pathways for the reduction of P-680+: a rapid reduction (less than 1 microseconds) by the physiological donor D1; a slower reduction (6 and 22 microseconds) by donor D'1, operative when O2 evolution is inhibited; a back-reaction (130 microseconds) when D'1 is oxidized by the pre-illumination in inhibited chloroplasts. In Tris-treated chloroplasts the donor system to P-680+ has the capacity to deliver only one electron. The absorption change at 515 nm (electrochromic absorption shift) has been measured in parallel. It is shown that the change linked to Photosystem II activity has nearly the same magnitude in untreated chloroplasts or in chloroplasts treated with hydroxylamine or with Tris (first and subsequent flashes). Thus we conclude that all the donors (P-680, D1, D'1) are located at the internal side of the thylakoid membrane.

Absorption↗

PubMed1995

Evolution of hospital participation in the National Nosocomial Infections Surveillance System, 1986 to 1993.

OBJECTIVE: To study changes in the use of National Nosocomial Infections Surveillance System (NNIS) surveillance components since 1986 that could reflect an evolution in the way in which NNIS hospitals conduct surveillance of nosocomial infections. METHOD: We analyzed NNIS data from 1986 to 1993 collected at the 199 US hospitals that participated in the NNIS system during this period. RESULTS: The number of hospitals participating in the NNIS system increased threefold between 1986 and 1993. A parallel increase was noticed in the amount of surveillance data for all NNIS components except for the hospital-wide component. The percentage of all hospitals reporting at least 1 calendar month per year of data from the hospital-wide component decreased from 95% in 1986 to 37% in 1993. During this period, use of the hospital-wide component was greater among the hospitals whose first participation in the NNIS system occurred before 1987. CONCLUSION: Interest by NNIS hospitals in the hospital-wide component apparently decreased between 1987 and 1993. In contrast, the interest in NNIS components that allow calculation of risk-adjusted nosocomial infection rates (intensive care unit, high-risk nursery, and surgical patient components) increased dramatically after 1986. This increased interest in surveillance with NNIS components that allow risk adjustment and interhospital comparison of infection rates suggests that the feasibility of collection of and interest in such data are high.

Cross Infection↗

PubMed1993

Organization of cortical afferent input to orbitofrontal areas in the rhesus monkey.

Odorant signal processing takes place in a diverse group of primary olfactory areas which receive direct input from the olfactory bulb. Orbitofrontal cortices participate in olfactory functions, but the pathways through which they receive olfactory or other input have not been clearly defined. The retrograde tracers horseradish peroxidase and fluorescent dyes were injected in orbital cortices to study their afferent cortical connections. Labeled neurons in primary olfactory areas (prepiriform cortex, anterior olfactory nucleus and olfactory tubercle) were directed mainly to a posterior orbitofrontal region and to a lesser extent the neighboring caudal part of area 13. There was no evidence of direct projections from primary olfactory areas to the rostral parts of area 13, or to areas 12 or 11. Most labeled neurons in primary olfactory areas were directed to agranular cortices, fewer projected to dysgranular areas, and there was no evidence that any reached granular cortices. The areas which received the most robust olfactory projections showed the lowest degree of laminar organization among prefrontal cortices. Early processing in the olfactory system thus takes place in areas which differ sharply on structural grounds from "early" eulaminate post-Rolandic sensory cortices. In addition to olfactory cortical projections, numerous labeled neurons in transitional (limbic) cortices were directed to orbital areas, and fewer but still substantial numbers of afferent neurons were found in eulaminate cortices. Unlike post-Rolandic unimodal sensory areas, which seems to be committed to the processing of input from one sensory modality via sequential and/or parallel pathways, caudal orbital areas received highly distributed input from primary olfactory areas, and in addition, from gustatory, visual, auditory and somatosensory areas. The structural and connectional features of olfactory recipient orbital cortices thus differ markedly from those observed in other sensory association areas and suggest a mode of processing adapted early in cortical evolution.

Animals↗

PubMed2004

A molecular model for transcription in the RNA world based on the ribosome large subunit.

Examination of the tRNA binding sites in the ribosome suggests that it might once have been able to catalyse the polymerisation of RNA. Based on a viral RNA-dependant RNA polymerase, the geometry of a potential active site for this ribopolymerase was constructed. From examination of the active site geometry, along with other arguments, it is suggested that the ribopolymerase synthesised a parallel complementary strand. When combined into a dimeric polymerase, this strategy minimises the exposure of single-stranded RNA and prevents self-hybridisation: both previously difficult problems for the RNA world hypothesis.

Evolution, Molecular↗

PubMed2004

Parameters influencing the templated growth of colloidal crystals on chemically patterned surfaces.

The influence of various experimental parameters on the vertical deposition and structure formation of colloidal crystals on chemically patterned surfaces, with hydrophilic and hydrophobic areas, was investigated. The pattern dimensions range from about 4 to 400 microm, which is much larger than the individual particle size (255 nm), to control the microscopic crystal shape rather than influencing the crystal lattice geometry (as achieved in colloidal epitaxy). The deposition resolution and selectivity were tested by varying the particle concentration in the suspension, the substrate withdrawing speed, pattern size and orientation, and wetting contrast between the hydrophilic and hydrophobic regions. The evolution of colloidal crystal thickness with respect to the pattern dimensions and deposition parameters was further studied. Our results show that the pattern size has a rather strong influence on the deposited number of colloid layers and on the crystal quality. Better results are obtained when the lines of a stripe pattern are oriented parallel to the withdrawing direction rather than perpendicular. The deposition resolution (defined as the minimum feature size on which particles can be deposited) depends on the wetting contrast and increases with lower average hydrophobicity of the substrate.

Colloids↗