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PubMed2000

[Management of Mauritanian children with cariomyopathies: cooperative experience with non-government organization].

In the field of a convention between Mauritania and the organisation "Earth of man" we install a cooperation between cardiologists and pediatricians of Nouakchott and medica part of this non governmental organisation. With this cooperation, 62 children all Mauritanians aged from 1 to 15 years and affected by cardiopathies have been oriented to the canton hospital of Geneva for diagnostic therapeutic and surgical problems. Evolution is favorable in 85.5% of cases but we observe 9 deaths 5 in Switzerland and 4 in Mauritania after 1 to 2 years of follow-up.

Adolescent↗
PubMed1983

Chronic myelodysplastic syndrome: short survival with or without evolution to acute leukaemia.

The myelodysplastic syndromes represent a prognostically diverse group of disorders. Their study has recently been facilitated by the classification proposed by the French-American-British (FAB) Cooperative Group. Using this scheme it is now possible to define more precisely their natural history and clinical relationship to acute leukaemia. Using the longitudinal case control technique, we reviewed the clinical data and morphology of 69 patients (all elderly males) with chronic irreversible haematological cytopenia and dysplasia. Applying FAB criteria we found: refractory anaemia (RA) in 43%; sideroblastic anaemia (RA-S) in 33%; refractory anaemia with excess blasts (RAEB) in 13%; RAEB in transformation (RAEB-T) in 9% and chronic myelomonocytic leukaemia (CMML) in 1%. The median survival for the entire group was 27 months (RA, 52; RA-S, 29; RAEB, 12; RAEB-T 11; and CMML, 2 months). Short survival was predicted by transfusion requirement and other manifestations of severe cytopenia, as well as by myeloid immaturity. The presence or absence of sideroblastosis did not correlate with survival. Acute leukaemia developed in only eight patients (12%), six of whom initially had RA. Leukaemic transformation was not predicted by progressive cytological immaturity. This study demonstrates that even in the absence of leukaemic transformation, chronic myelodysplasia is a lethal haematological disorder.

Adult↗
PubMed2004

Development and the Baldwin effect.

Baldwin's classic hypothesis states that behavioral plasticity can speed evolution by (a) smoothing the fitness landscape and (b) indirect genetic assimilation of acquired characteristics. This latter phase demands a strong correlation between genotype and phenotype space. But the natural world shows signs of this correlation at only a very coarse level, since the intervening developmental process greatly complicates the mapping from genetics to physiology and ethology. Hence, development appears to preclude a strong Baldwin effect. However, by adding a simple developmental mechanism to Hinton and Nowlan's classic model of the Baldwin effect, and by allowing evolution to determine the proper balance between direct and indirect mapping of genome to phenotype, this research reveals several different effects of development on the Baldwin effect, some promoting and others inhibiting. Perhaps the most interesting result is an evolved cooperation between direct blueprints and indirect developmental recipes in searching for unstructured and partially structured target patterns in large, needle-in-the-haystack fitness landscapes.

Adaptation, Physiological↗
PubMed2005

Species choice for comparative genomics: being greedy works.

Several projects investigating genetic function and evolution through sequencing and comparison of multiple genomes are now underway. These projects consume many resources, and appropriate planning should be devoted to choosing which species to sequence, potentially involving cooperation among different sequencing centres. A widely discussed criterion for species choice is the maximisation of evolutionary divergence. Our mathematical formalization of this problem surprisingly shows that the best long-term cooperative strategy coincides with the seemingly short-term "greedy" strategy of always choosing the next best single species. Other criteria influencing species choice, such as medical relevance or sequencing costs, can also be accommodated in our approach, suggesting our results' broad relevance in scientific policy decisions.

Algorithms↗
PubMed2004

TOR action in mammalian cells and in Caenorhabditis elegans.

The p70 S6 kinase (p70 S6K) was the first signaling element in mammalian cells shown to be inhibited by rapamycin. The activity of the p70 S6K in mammalian cell is upregulated by extracellular amino acids (especially leucine) and by signals from receptor tyrosine kinases (RTKs), primarily through activation of the type 1A PI-3 kinase. The amino acid-/rapamycin-sensitive input and the PI-3 kinase input are co-dominant but largely independent, in that deletion of the amino-terminal and carboxy-terminal noncatalytic sequences flanking the p70 S6K catalytic domain renders the kinase insensitive to inhibition by both rapamycin and by withdrawal of amino acids, whereas this p70 S6K mutant remains responsive to activation by RTKs and to inhibition by wortmannin. At a molecular level, this dual control of p70 S6K activity is attributable to phosphorylation of the two p70 S6K sites: The Ptd Ins 3,4,5P3-dependent kinasel (PDK1) phosphorylates p70 S6K at a Thr on the activation loop, whereas mTOR phosphorylates a Thr located in a hydrophobic motif carboxyterminal to the catalytic domain. Together these two phosphorylations engender a strong, positively cooperative activation of p70 S6K, so that each is indispensable for physiologic regulation. Like RTKs, the p70 S6K appears early in metazoan evolution and comes to represent an important site at which the more ancient, nutrient-responsive TOR pathway converges with the RTK/PI-3 kinase pathway in the control of cell growth. Dual regulation of p70 S6K is seen in Drosophila; however, this convergence is not yet evident in Caenorhabditis elegans, wherein nutrient activation of the insulin receptor (InsR) pathway negatively regulates dauer development and longevity, whereas the TOR pathway regulates overall mRNA translation through effectors distinct from p70 S6K, as in yeast. The C. elegans TOR and InsR pathways show none of the cross- or convergent regulation seen in mammalian cells. The nature of the elements that couple nutrient sufficiency to TOR activity remain to be discovered, and the mechanisms by which RTKs influence TOR activity in mammalian cells require further study. One pathway for RTK control involves the tuberous sclerosis complex, which is absent in C. elegans, but of major importance in Drosophila and higher metazoans.

Animals↗
PubMed1998

Abiotic nitrogen reduction on the early Earth.

The production of organic precursors to life depends critically on the form of the reactants. In particular, an environment dominated by N2 is far less efficient in synthesizing nitrogen-bearing organics than a reducing environment rich in ammonia. Relatively reducing lithospheric conditions on the early Earth have been presumed to favour the generation of an ammonia-rich atmosphere, but this hypothesis has not been studied experimentally. Here we demonstrate mineral-catalysed reduction of N2, NO2- and NO3- to ammonia at temperatures between 300 and 800 degrees C and pressures of 0.1-0.4 GPa-conditions typical of crustal and oceanic hydrothermal systems. We also show that only N2 is stable above 800 degrees C, thus precluding significant atmospheric ammonia formation during hot accretion. We conclude that mineral-catalysed N2 reduction might have provided a significant source of ammonia to the Hadean ocean. These results also suggest that, whereas nitrogen in the Earth's early atmosphere was present predominantly as N2, exchange with oceanic, hydrothermally derived ammonia could have provided a significant amount of the atmospheric ammonia necessary to resolve the early-faint-Sun paradox.

Ammonia↗
PubMed2004

Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey.

Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans (jawless fish) and of immunoglobulin gene segments in gnathostomes (jawed vertebrates).

Adaptation, Physiological↗
PubMed2001

Reward and punishment.

Minigames capturing the essence of Public Goods experiments show that even in the absence of rationality assumptions, both punishment and reward will fail to bring about prosocial behavior. This result holds in particular for the well-known Ultimatum Game, which emerges as a special case. But reputation can induce fairness and cooperation in populations adapting through learning or imitation. Indeed, the inclusion of reputation effects in the corresponding dynamical models leads to the evolution of economically productive behavior, with agents contributing to the public good and either punishing those who do not or rewarding those who do. Reward and punishment correspond to two types of bifurcation with intriguing complementarity. The analysis suggests that reputation is essential for fostering social behavior among selfish agents, and that it is considerably more effective with punishment than with reward.

Behavior↗
PubMed2000

A Transactional Theory of Within-Group Conflict.

Transactional models of social evolution emphasize that dominant members of the society can be favored to donate parcels of reproduction to subordinate members in return for cooperation. I construct a formal theory of intragroup conflict within the framework of transactional models by determining the maximum extent to which colony members can be selfish without destabilizing the group. The difference between the maximum value of the subordinate's fraction of group reproduction that the dominant can tolerate before ejecting the subordinate and the minimum value required by the subordinate to stay and cooperate peacefully in the group defines the "window of selfishness," which in turn predicts the frequency of within-group conflict. The window of selfishness tends to increase with increasing group reproductive output, increasingly harsh ecological constraints on solitary breeding, and, counterintuitively, increasing relatedness between subordinate and dominant. Increasing fighting ability of the subordinate can either widen or narrow the window of selfishness, the latter being most likely when ecological constraints on group living are strong. Although increasing relatedness is predicted to increase the rate of within-group aggression, the mean intensity of an aggressive act should decline, as predicted by the general theory of honest signaling between relatives and the tug-of-war models of within-group selfishness. In the bidding game, in which multiple dominants bid for the services of a subordinate, the window of selfishness is predicted to have zero width. A zero-width window of selfishness and low conflict also are predicted for saturated N-person groups, that is, groups whose total output is a concave function of group size and in which the dominant is not favored to admit additional subordinates. The model's predictions are compared to empirical evidence and to predictions of alternative models of intragroup aggression, including the value-aggression model and the pure tug-of-war model.

aggression↗
PubMed1995

Postglacial expansion and genome subdivision in the European grasshopper Chorthippus parallelus.

A noncoding nuclear DNA marker sequence (Cpn1-1) was used to investigate subdivision in the grasshopper Chorthippus parallelus and deduce postglacial expansion patterns across its species range in Europe. Investigation of the spatial distribution of 71 Cpn1-1 haplotypes and estimation of levels of genetic differentiation (KST values) between populations and geographic regions provided evidence for subdivision of C. parallelus into at least five major geographic regions and indicated that the French form of C. parallelus originated after range expansion from a Balkan refugium. Further evidence for subdivision of C. parallelus between Italy and northern Europe suggests that the Alps may have formed a significant barrier to gene flow in this grasshopper.

Animals↗
PubMed1996

Life with 6000 genes.

The genome of the yeast Saccharomyces cerevisiae has been completely sequenced through a worldwide collaboration. The sequence of 12,068 kilobases defines 5885 potential protein-encoding genes, approximately 140 genes specifying ribosomal RNA, 40 genes for small nuclear RNA molecules, and 275 transfer RNA genes. In addition, the complete sequence provides information about the higher order organization of yeast's 16 chromosomes and allows some insight into their evolutionary history. The genome shows a considerable amount of apparent genetic redundancy, and one of the major problems to be tackled during the next stage of the yeast genome project is to elucidate the biological functions of all of these genes.

Amino Acid Sequence↗
PubMed2005

Evolutionary genetics of the accessory gene regulator (agr) locus in Staphylococcus aureus.

The accessory gene regulator (agr) locus influences the expression of many virulence genes in the human pathogen Staphylococcus aureus. Four allelic groups of agr, which generally inhibit the regulatory activity of each other, have been identified within the species. Interference in virulence gene expression caused by different agr groups has been suggested to be a mechanism for isolating bacterial populations and a fundamental basis for subdividing the species. To test the hypothesis that the species is phylogenetically structured according to agr groups, we mapped agr groups onto a clone phylogeny inferred from partial sequences of 14 genes from 27 genetically diverse strains. Shimodaira-Hasegawa and parametric bootstrap tests rejected the hypotheses that the species is subdivided into three or five monophyletic agr groups but failed to reject the hypothesis that the species is subdivided into two groups that each consist of multiple clonal complexes and multiple agr groups. Additional evidence for agr recombination is found from clustered polymorphisms in complete agr sequences. However, agr recombination has not occurred frequently or randomly through time, because the topology and branch lengths of the clone phylogeny are reflected within each agr group. To account for these observations, we propose a new evolutionary model that involves a genetically polymorphic ancestral population of S. aureus that horizontally transferred agr groups between two subspecies groups near the time that these subspecies groups diverged.

Bacterial Proteins↗
PubMed2006

Fertility cycle patterns in motives for sexual behavior.

Three studies examined the relationship between fertility, as indexed by day in cycle or salivary estradiol levels, and reported motives for sexual intercourse. Data from university and community samples in both cross-sectional and repeated-measures designs showed that sex-for-intimacy motives are endorsed significantly less by women who are relatively more fertile or show higher salivary estrogen levels. Sex for enhancement, self-affirmation, and partner approval also declined, although the data were less consistent. The remaining motives (coping and power) showed no consistent patterns across fertility status. Results suggest that sexual motives are rooted partly in woman's biology and are discussed in terms of plausible evolutionary mechanisms that might promote female "choosiness" at midcycle.

Adult↗
PubMed2002

The retina of Spalax ehrenbergi: novel histologic features supportive of a modified photosensory role.

PURPOSE: The retina of the blind mole rat Spalax ehrenbergi was compared with other vertebrate photosensitive organs in an attempt to correlate its histologic organization with a presumptive nonvisual photoreceptor role. METHODS: The eyes of eight adult animals were analyzed by light and electron microscopy, using conventional staining and immunolabeling with antibodies against phototransduction proteins and calretinin. RESULTS: Rods accounted for most of the photoreceptor cells in the Spalax retina, although their morphology is dissimilar to that of sighted mammals, in that they contained only rudimentary outer segments. The latter showed strong rod-opsin and transducin immunoreactions. The phagosomes in the retinal pigmentary epithelium were also rod-opsin positive. Synapses were evident at the photoreceptor cells pedicles. Occasionally, several synaptic active sites were present, suggesting cone cell origin; however, cone-opsin was not immunodetected in the study samples. Synaptic ribbon fields, sometimes distant to the active sites, resembled those found in the vertebrate pineal. The other retinal layers were somewhat less organized than in sighted mammals. Some cells were displaced and the calretinin-positive inner plexiform layer had no sublayers. Calretinin immunolabeling was found in horizontal, amacrine, and ganglion cells. Folding of the retina produced rosette-like images similar to those reported before in the retina of nocturnal mammals and in the avian pineal gland. CONCLUSIONS: These data suggest that the retina of the mole rat has undergone evolutionary restructuring to a photoreceptive pineal-like organization. This supports the thesis that the photoreceptor cells of this unique organ have been reprogrammed during the subterranean adaptation of Spalax, from their original visual function to mediating photoperiodic regulation.

Animals↗