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"Louis, Edward"
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Eliminating the universe : logical properties of natural language
\"This book synthesizes the author's work (1980s-2015) on the logical expressive power of natural language. It extends the tools and concepts of model theory as used in (higher order) predicate logic to the study of natural language semantics. It focuses on boolean structure, generalized quantification (separated from variable binding), covering some cases of anaphora. Different categories -- predicates, adjective, quantifiers -- are modeled by non-isomorphic boolean lattices. Of empirical linguistic interest is the expressibility of many natural classes of quantifiers defined in terms of their logical (automorphism invariant) properties. Some of these correlate with classes used syntactically in generative grammar. In other cases we find general (possibly universal) constraints on possible quantifier denotations in natural language. Also of novel logical interest are entailment paradigms that depend on relations between pairs or triples of generalized quantifier denoting expressions, ones that are in some cases inherently vague. In addition we note novel binary quantifiers that lie beyond the \"Frege boundary\" in that they are provably not identical to any iterated application of unary quantifiers. Of philosophical interest is the existence of models which make the same sentences true as standard models but which lack a universe and hence, seemingly, a notion of \"reference\". Moreover, these models generalize to ones in which we can represent (some) intensional expressions without the use of novel ontological objects, such as \"possible worlds\" or \"propositions\"-- Provided by publisher.
Book
Advances in Quantitative Trait Analysis in Yeast
Understanding the genetic mechanisms underlying complex traits is one of the next frontiers in biology. The budding yeast Saccharomyces cerevisiae has become an important model for elucidating the mechanisms that govern natural genetic and phenotypic variation. This success is partially due to its intrinsic biological features, such as the short sexual generation time, high meiotic recombination rate, and small genome size. Precise reverse genetics technologies allow the high throughput manipulation of genetic information with exquisite precision, offering the unique opportunity to experimentally measure the phenotypic effect of genetic variants. Population genomic and phenomic studies have revealed widespread variation between diverged populations, characteristic of man-made environments, as well as geographic clusters of wild strains along with naturally occurring recombinant strains (mosaics). Here, we review these recent studies and provide a perspective on how these previously unappreciated levels of variation can help to bridge our understanding of the genotype-phenotype gap, keeping budding yeast at the forefront of genetic studies. Not only are quantitative trait loci (QTL) being mapped with high resolution down to the nucleotide, for the first time QTLs of modest effect and complex interactions between these QTLs and between QTLs and the environment are being determined experimentally at unprecedented levels using next generation techniques of deep sequencing selected pools of individuals as well as multi-generational crosses.
Journal Article
Genome Diversity and Evolution in the Budding Yeasts (Saccharomycotina)
Considerable progress in our understanding of yeast genomes and their evolution has been made over the last decade with the sequencing, analysis, and comparisons of numerous species, strains, or isolates of diverse origins. The role played by yeasts in natural environments as well as in artificial manufactures, combined with the importance of some species as model experimental systems sustained this effort. At the same time, their enormous evolutionary diversity (there are yeast species in every subphylum of Dikarya) sparked curiosity but necessitated further efforts to obtain appropriate reference genomes. Today, yeast genomes have been very informative about basic mechanisms of evolution, speciation, hybridization, domestication, as well as about the molecular machineries underlying them. They are also irreplaceable to investigate in detail the complex relationship between genotypes and phenotypes with both theoretical and practical implications. This review examines these questions at two distinct levels offered by the broad evolutionary range of yeasts: inside the best-studied Saccharomyces species complex, and across the entire and diversified subphylum of Saccharomycotina. While obviously revealing evolutionary histories at different scales, data converge to a remarkably coherent picture in which one can estimate the relative importance of intrinsic genome dynamics, including gene birth and loss, vs. horizontal genetic accidents in the making of populations. The facility with which novel yeast genomes can now be studied, combined with the already numerous available reference genomes, offer privileged perspectives to further examine these fundamental biological questions using yeasts both as eukaryotic models and as fungi of practical importance.
Journal Article
Trait Variation in Yeast Is Defined by Population History
A fundamental goal in biology is to achieve a mechanistic understanding of how and to what extent ecological variation imposes selection for distinct traits and favors the fixation of specific genetic variants. Key to such an understanding is the detailed mapping of the natural genomic and phenomic space and a bridging of the gap that separates these worlds. Here we chart a high-resolution map of natural trait variation in one of the most important genetic model organisms, the budding yeast Saccharomyces cerevisiae, and its closest wild relatives and trace the genetic basis and timing of major phenotype changing events in its recent history. We show that natural trait variation in S. cerevisiae exceeds that of its relatives, despite limited genetic variation, and follows the population history rather than the source environment. In particular, the West African population is phenotypically unique, with an extreme abundance of low-performance alleles, notably a premature translational termination signal in GAL3 that cause inability to utilize galactose. Our observations suggest that many S. cerevisiae traits may be the consequence of genetic drift rather than selection, in line with the assumption that natural yeast lineages are remnants of recent population bottlenecks. Disconcertingly, the universal type strain S288C was found to be highly atypical, highlighting the danger of extrapolating gene-trait connections obtained in mosaic, lab-domesticated lineages to the species as a whole. Overall, this study represents a step towards an in-depth understanding of the causal relationship between co-variation in ecology, selection pressure, natural traits, molecular mechanism, and alleles in a key model organism.
Journal Article
Falmouth, Jamaica : architecture as history
Founded in 1769 as a new port town on JamaicaAEs north coast, Falmouth expanded dramatically in the decades around 1800 as it supported the rapidly expanding sugar production of Trelawney and neighboring parishes. Many of the surviving buildings in Falmouth are the townhouses and shops of the planters and merchants who benefitted from the wealth of sugar. That same community also built a major Anglican church and a courthouse, both of which still survive and remain in use. In those same years, the town hosted a growing free-black population and this community also left its mark on the historic town. In 1894, Falmouth received an extraordinary gift from the British crown in the form of the Albert George Market, at once a symbol of persistent colonialism, a shelter for the ancient Sunday markets, and a symbol of modernism in the form of its vast cast iron design. Monuments in the city from the twentieth century include an extraordinary round Catholic church and an impressively Modernist school wing. With little investment through the twentieth century, the town was entirely re-conceptualized in the opening years of the twenty-first century with the construction of a vast cruise ship terminal. Spanning from the foundation of the town in 1769 to the opening of the cruise ship terminal in 2008, this book explores the wide range of architecture built by Jamaicans and others in the making of this extraordinary town.
Book
Diversification of Angraecum (Orchidaceae, Vandeae) in Madagascar: Revised Phylogeny Reveals Species Accumulation through Time Rather than Rapid Radiation
Angraecum is the largest genus of subtribe Angraecinae (Orchidaceae) with about 221 species. Madagascar is the center of the diversity for the genus with ca. 142 species, of which 90% are endemic. The great morphological diversity associated with species diversification in the genus on the island of Madagascar offers valuable insights for macroevolutionary studies. Phylogenies of the Angraecinae have been published but a lack of taxon and character sampling and their limited taxonomic resolution limit their uses for macroevolutionary studies. We present a new phylogeny of Angraecum based on chloroplast sequence data (matk, rps16, trnL), nuclear ribosomal (ITS2) and 39 morphological characters from 194 Angraecinae species of which 69 were newly sampled. Using this phylogeny, we evaluated the monophyly of the sections of Angraecum as defined by Garay and investigated the patterns of species diversification within the genus. We used maximum parsimony and bayesian analyses to generate phylogenetic trees and dated divergence times of the phylogeny. We analyzed diversification patterns within Angraecinae and Angraecum with an emphasis on four floral characters (flower color, flower size, labellum position, spur length) using macroevolutionary models to evaluate which characters or character states are associated with speciation rates, and inferred ancestral states of these characters. The phylogenetic analysis showed the polyphyly of Angraecum sensu lato and of all Angraecum sections except sect. Hadrangis, and that morphology can be consistent with the phylogeny. It appeared that the characters (flower color, flower size, spur length) formerly used by many authors to delineate Angraecum groups were insufficient to do so. However, the newly described character, position of the labellum (uppermost and lowermost), was the main character delimiting clades within a monophyletic Angraecum sensu stricto. This character also appeared to be associated with speciation rates in Angraecum. The macroevolutionary model-based phylogeny failed to detect shifts in diversification that could be associated directly with morphological diversification. Diversification in Angraecum resulted from gradual species accumulation through time rather than from rapid radiation, a diversification pattern often encountered in tropical rain forests.
Journal Article
Impact of inter-species hybridisation on antifungal drug response in the Saccharomyces genus
Background
Antifungal drug resistance presents one of the major concerns for global public health, and hybridization allows the development of high fitness organisms that can better survive in restrictive conditions or in presence of antifungal agents. Hence, understanding how allelic variation can influence antifungal susceptibility in hybrid organisms is important for the development of targeted treatments. Here, we exploited recent advances in multigenerational breeding of
hemiascomycete
hybrids to study the impact of hybridisation on antifungal resistance and identify quantitative trait loci responsible for the phenotype.
Results
The offspring of
Saccharomyces cerevisiae
x
S. kudriavzevii
hybrids were screened in the presence of six antifungal drugs and revealed a broad phenotypic diversity across the progeny. QTL analysis was carried out comparing alleles between pools of high and low fitness offspring, identifying hybrid-specific genetic regions involved in resistance to fluconazole, micafungin and flucytosine. We found both drug specific and pleiotropic regions, including 41 blocks containing genes not previously associated with resistance phenotypes. We identified linked genes that influence the same trait, namely a hybrid specific ‘super’ QTL, and validated, via reciprocal hemizygosity analysis, two causal genes,
BCK2
and
DNF1
. The co-location of genes with similar phenotypic impact supports the notion of an adaption process that limits the segregation of advantageous alleles via recombination.
Conclusions
This study demonstrates the value of QTL studies to elucidate the hybrid-specific mechanisms of antifungal susceptibility. We also show that an inter-species hybrid model system in the
Saccharomyces
background, can help to decipher the trajectory of antifungal drug resistance in pathogenic hybrid lineages.
Journal Article
A High-Definition View of Functional Genetic Variation from Natural Yeast Genomes
The question of how genetic variation in a population influences phenotypic variation and evolution is of major importance in modern biology. Yet much is still unknown about the relative functional importance of different forms of genome variation and how they are shaped by evolutionary processes. Here we address these questions by population level sequencing of 42 strains from the budding yeast Saccharomyces cerevisiae and its closest relative S. paradoxus. We find that genome content variation, in the form of presence or absence as well as copy number of genetic material, is higher within S. cerevisiae than within S. paradoxus, despite genetic distances as measured in single-nucleotide polymorphisms being vastly smaller within the former species. This genome content variation, as well as loss-of-function variation in the form of premature stop codons and frameshifting indels, is heavily enriched in the subtelomeres, strongly reinforcing the relevance of these regions to functional evolution. Genes affected by these likely functional forms of variation are enriched for functions mediating interaction with the external environment (sugar transport and metabolism, flocculation, metal transport, and metabolism). Our results and analyses provide a comprehensive view of genomic diversity in budding yeast and expose surprising and pronounced differences between the variation within S. cerevisiae and that within S. paradoxus. We also believe that the sequence data and de novo assemblies will constitute a useful resource for further evolutionary and population genomics studies.
Journal Article