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Multivariate survival trees: a maximum likelihood approach based on frailty models.

A method of constructing trees for correlated failure times is put forward. It adopts the backfitting idea of classification and regression trees (CART) (Breiman et al., 1984, in Classification and Regression Trees). The tree method is developed based on the maximized likelihoods associated with the gamma frailty model and standard likelihood-related techniques are incorporated. The proposed method is assessed through simulations conducted under a variety of model configurations and illustrated using the chronic granulomatous disease (CGD) study data.

Biometry↗

Cloning and characterization of cellulose synthase-like gene, PtrCSLD2 from developing xylem of aspen trees.

Genetic improvement of cell wall polymer synthesis in forest trees is one of the major goals of forest biotechnology that could possibly impact their end product utilization. Identification of genes involved in cell wall polymer biogenesis is essential for achieving this goal. Among various candidate cell wall-related genes, cellulose synthase-like D (CSLD) genes are intriguing due to their hitherto unknown functions in cell wall polymer synthesis but strong structural similarity with cellulose synthases (CesAs) involved in cellulose deposition. Little is known about CSLD genes from trees. In the present article PtrCSLD2, a first CSLD gene from an economically important tree, aspen (Populus tremuloides) is reported. PtrCSLD2 cDNA was isolated from an aspen xylem cDNA library and encodes a protein that shares 90% similarity with Arabidopsis AtCSLD3 protein involved in root hair tip growth. It is possible that xylem fibers that also grow by intrusive tip growth may need expression of PtrCSLD2 for controlling the length of xylem fibers, a wood quality trait of great economical importance. PtrCSLD2 protein has a N-terminal cysteine-rich putative zinc-binding domain; eight transmembrane domains; alternating conserved and hypervariable domains; and a processive glycosyltransferases signature, D, D, D, QXXRW; all similar to aspen CesA proteins. However, PtrCSLD2 shares only 43-48% overall identity with the known aspen CesAs suggesting its distinct functional role in cell wall polymer synthesis perhaps other than cellulose biosynthesis. Based on Southern analysis, the aspen CSLD gene family consists of at least three genes and this gene copy estimate is supported by phylogenetic analysis of available CSLDs from plants. Moreover, gene expression studies using RT-PCR and in situ mRNA hybridization showed that PtrCSLD2 is expressed at a low level in all aspen tissues examined with a slightly higher expression level in secondary cell wall-enriched aspen xylem as compared to primary cell wall enriched tissues. Together, these observations suggest that PtrCSLD2 gene may be involved in the synthesis of matrix polysaccharides that are dominant in secondary cell walls of poplar xylem. Future molecular genetic analyses will clarify the functional significance of CSLD genes in the development of woody trees.

Journal Article↗

Chemical classification of cattle. 2. Phylogenetic tree and specific status of the Zebu.

Phylogenetic trees for the ten major breed groups of cattle were constructed by Farris's (1972) maximum parsimony method, or Fitch & Margoliash's (1967) method, which averages ou the deviation over the entire assemblage. Both techniques yield essentially identical trees. The phylogenetic tree for the ten major cattle breed groups can be superimposed on a map of Europe and western Asia, the root of the tree being close to the 'fertile crescent' in Asia Minor, believed to be a primary centre of bovine domestication. For some but not all protein variants there is a cline of gene frequencies as one proceeds from the British Isles and northwest Europe towards southeast Europe and Asia Minor, with the most extreme gene frequencies in the Zebu breeds of India. It is not clear to what extent the observed clines are primary or secondary, i.e., consequent to the initial migrations of cattle towards the end of the Pleistocene or consequent to the many migrations of man with his domesticated cattle. Such clines as exist are not in themselves sufficient to prove either selection versus genetic drift or to establish taxonomic ranking. Contrary to some suggestions in the literature, the biochemical evidence supports Linnaeus's original conclusions: Bos taurus and Bos indicus are distinct species.

Animals↗

Morphometric study of the development of Purkinje cell dendritic trees in the mouse using vertex analysis.

Vertices are the points in an arborescence which interconnect segments and comprise terminal or pendant vertices (Vp), nodal or branching points and the root point. Branching points may be dichotomous (Vd) or trichomtomous (Vt), etc., and are subdivided into distinct two-dimensional topological entities according to the number of terminal vertices they drain, i.e. Vds comprise primary vertices (Va), connecting two Vps; secondary vertices (Vb), connecting one Vp and one Vd or one Vt; and tertiary vertices (Vc), connecting either two Vds, two Vts or one Vt and one Vd. The four types of Vt (Va', Vb', Vc', Vd') similarly connect three, two, one and zero Vps respectively. Each Vt may be transformed into two Vds thus, Va' = Va + Vb; Vb' = Va/3 + 4Vb/3 + Vc/3; Vc' = Vb + Vc and Vd' = 2Vc. Analysis proceeds by transforming mixed trees containing varying proportions of Vds and Vts into entirely dichotomous branching structures. The topology is then defined by the Va/Vb ratio which has a unique value according to the mode of growth and the frequency of Vts. Vertices are ordered by a centrifugal technique. The frequency distribution of vertices of different order allow the changes in growth characteristics and in remodelling to be detected within particular regions of the tree. Metrical parameters are readily incorporated into the analysis since all vertices are interconnected by segments of finite length and are given the same order magnitude as the vertex they drain. The analytical capabilities of the method are exemplified by its application to the study of growth and plasticity in the dendritic trees of Purkinje cells in the mouse. Growth is defined in metrical and topological terms and sites of reorganization within the mature tree are identified.

Aging↗

The construction of a 'topic tree': a way of familiarizing a teaching staff to problem-oriented learning in a master's programme in public health.

At the planning stage of a community-oriented and problem-based learning master's programme in public health it is indispensable to build a network of teachers, experts in specific fields, willing to guide the students in acquiring new competencies and ready to facilitate the experimental learning process. We discuss in this paper the construction and the utilisation of the 'topic tree'. In addition we show how the teaching staff get acquainted with that educational methodology by experimenting with it themselves (prior to the students). About 10 experts, each one a specialist in a given field, have conceptualized their approach in building a topic tree (concept tree); such a tree makes it possible to schematize the topics to be understood in order to solve a given problem and the relationship existing between actions to be undertaken. The experiment, meant to initiate the teaching staff in experimental learning procedures, was appreciated by all the experts, who considered it a creative and stimulating method. It also permitted the construction of a bibliography including key documents concerning each identified priority health problem. We discuss the utility and the relevance of our approach in the perspective of initiating teachers in experiential learning based on problem-solving.

Algorithms↗

Physiological girdling of pine trees via phloem chilling: proof of concept.

Quantifying below-ground carbon (C) allocation is particularly difficult as methods usually disturb the root-mycorrhizal-soil continuum. We reduced C allocation below ground of loblolly pine trees by: (1) physically girdling trees and (2) physiologically girdling pine trees by chilling the phloem. Chilling reduced cambium temperatures by approximately 18 degrees C. Both methods rapidly reduced soil CO2 efflux, and after approximately 10 days decreased net photosynthesis (P(n)), the latter indicating feedback inhibition. Chilling decreased soil-soluble C, indicating that decreased soil CO2 efflux may have been mediated by a decrease in root C exudation that was rapidly respired by microbes. These effects were only observed in late summer/early autumn when above-ground growth was minimal, and not in the spring when above-ground growth was rapid. All of the effects were rapidly reversed when chilling was ceased. In fertilized plots, both chilling and physical girdling methods reduced soil CO2 efflux by approximately 8%. Physical girdling reduced soil CO2 efflux by 26% in non-fertilized plots. This work demonstrates that phloem chilling provides a non-destructive alternative to reducing the movement of recent photosynthate below the point of chilling to estimate C allocation below ground on large trees.

Carbon Dioxide↗

Phylogenomics reveal a robust fungal tree of life.

Our understanding of the tree of life (TOL) is still fragmentary. Until recently, molecular phylogeneticists have built trees based on ribosomal RNA sequences and selected protein sequences, which, however, usually suffered from lack of support for the deeper branches and inconsistencies probably due to limited subsampling of the entire genome. Now, phylogenetic hypotheses can be based on the analysis of full genomes. We used available complete genome data as well as the eukaryote orthologous group (KOG) proteins to reconstruct with confidence basal branches of the fungal TOL. Phylogenetic analysis of a core of 531 KOGs shared among 21 fungal genomes, three animal genomes and one plant genome showed a single tree with high support resulting from four different methods of phylogenetic reconstruction. The single tree that we inferred from our dataset showed excellent nodal support for each branch, suggesting that it reflects the true phylogenetic relationships of the species involved.

Evolution, Molecular↗

Genetic diversity and fitness in peripheral and central populations of the European tree frog Hyla arborea.

Genetic diversity is expected to decrease in small and isolated populations as a consequence of founder effects, bottlenecks, inbreeding and genetic drift. In this study we analyse temporal and spatial effects on genetic variation and progeny viability of the European tree frog (Hyla arborea) at two scales. First, the Swedish distribution has been isolated from the continental distribution for more than 8000 thousand years, and secondly, within Sweden, recent habitat alterations that have taken place during this century have increased isolation between local populations. Genetic variation and progeny survival in relation to isolation was studied within the entire Swedish distribution of the tree frog. Allozyme electrophoresis analysis of froglets, sampled across the Swedish distribution, revealed a low overall genetic variation (1.06 alleles/locus) at the protein level in comparison with continental populations (1.54-1.68 alleles/locus). However, egg hatchability (97%) and early larval survival (95%) were not lower than in other parts of the tree frog distribution or in other anuran species. Within the Swedish distribution, early larval survival was lower in isolated breeding ponds than in more central ones. However, no differences in genetic variation were found in relation to isolation. Polymorphism was detected only at a single locus, and was restricted geographically to the eastern part of the Swedish distribution. Bottlenecks due to climatic changes and fragmentation of suitable habitat (primarily natural pastures with ponds) are suggested as possible causes of the low genetic diversity of the Swedish tree frog population.

Animals↗

High density lipoproteins and prevention of experimental atherosclerosis with special reference to tree shrews.

According to data obtained from epidemiological and experimental survey, serum HDL level is known to be correlated conversely with the incidence of atherosclerosis. Experimental data collected in this article explained part of its mechanism, which is described in four parts as follows: 1. The result of 3 successive experiments on experimental atherosclerosis in tree shrews (total of 96 animals available including 40 as the controls) showed that the serum HDL level had been kept persistantly to 69-88% of the total serum lipoproteins even after a high cholesterol intake for 32 weeks. The incidence of atheromatous lesions developed was only 0-9%, but the incidence of gall stone was very high, 48-84% by gross examination by the end of these experiments. 2. HDL are also capable of (1) promotion of monocyte migration activity; (2) enhancement of cholesterol clearance rate of aortic smooth muscle cells originally isolated from either rabbits or tree shrews; (3) inhibition of 20% of LDL degradation but with no inhibitory effect obtained on Ac-LDL degradation in the endothelial cells; (4) presence of specific binding sites for apo E free HDL on the surface of aortic smooth muscle cells from either rabbits or tree shrews which recognizes apo A1 as a ligand. 3. Data from 2 successive experiments in rabbits showed that HDL lipoproteins (mainly apo A1) possess an inhibitory effect on the development of atheromatous plaques, but not a very strong one. 4. The colesterol clearance effect of smooth muscle cells was markedly enhanced by apo A1/phospholipid liposomes (the apo A1 used was isolated from either rabbit's or tree shrew's serum) in vitro.

Animals↗

Staged growth of optimized arterial model trees.

There is a marked difference in the structure of the arterial tree between epi- and endocardial layers of the human heart. To model these structural variations, we developed an extension to the computational method of constrained constructive optimization (CCO). Within the framework of CCO, a model tree is represented as a dichotomously branching network of straight cylindrical tubes, with flow conditions governed by Poiseuille's law. The tree is grown by successively adding new terminal segments from randomly selected points within the perfusion volume while optimizing the geometric location and topological site of each new connection with respect to minimum intravascular volume. The proposed method of "staged growth" guides the generation of new terminal sites by means of an additional time-dependent boundary condition, thereby inducing a sequence of domains of vascular growth within the given perfusion volume. Model trees generated in this way are very similar to reality in their visual appearance and predict diameter ratios of parent and daughter segments, the distribution of symmetry, the transmural distribution of flow, the volume of large arteries, as well as the ratio of small arterial volume in subendocardial and subepicardial layers in good agreement with experimental data. From this study we conclude that the method of CCO combined with staged growth reproduces many characteristics of the different arterial branching patterns in the subendocardium and the subepicardium, which could not be obtained by applying the principle of minimum volume alone.

Algorithms↗

Phylogenetic MCMC algorithms are misleading on mixtures of trees.

Markov chain Monte Carlo (MCMC) algorithms play a critical role in the Bayesian approach to phylogenetic inference. We present a theoretical analysis of the rate of convergence of many of the widely used Markov chains. For N characters generated from a uniform mixture of two trees, we prove that the Markov chains take an exponentially long (in N) number of iterations to converge to the posterior distribution. Nevertheless, the likelihood plots for sample runs of the Markov chains deceivingly suggest that the chains converge rapidly to a unique tree. Our results rely on novel mathematical understanding of the log-likelihood function on the space of phylogenetic trees. The practical implications of our work are that Bayesian MCMC methods can be misleading when the data are generated from a mixture of trees. Thus, in cases of data containing potentially conflicting phylogenetic signals, phylogenetic reconstruction should be performed separately on each signal.

Algorithms↗

Gene trees and the origins of inbred strains of mice.

Extensive data on genetic divergence among 24 inbred strains of mice provide an opportunity to examine the concordance of gene trees and species trees, especially whether structured subsamples of loci give congruent estimates of phylogenetic relationships. Phylogenetic analyses of 144 separate loci reproduce almost exactly the known genealogical relationships among these 24 strains. Partitioning these loci into structured subsets representing loci coding for proteins, the immune system and endogenous viruses give incongruent phylogenetic results. The gene tree based on protein loci provides an accurate picture of the genealogical relationships among strains; however, gene trees based upon immune and viral data show significant deviations from known genealogical affinities.

Algorithms↗

Mongolian Tree Rings and 20th-Century Warming

A 450-year tree-ring width chronology of Siberian pine (Pinus sibirica Du Tour) growing at timberline (2450 meters) in the Tarvagatay Mountains in west central Mongolia shows wide annual growth rings for the recent century. Ecological site observations and comparisons with instrumental temperature records indicate that the ring widths of these trees are sensitive to annual temperature variations. Low-frequency variations in the Tarvagatay tree-ring record are similar to those in a reconstruction of Arctic annual temperatures, which is based on 20 tree-ring width series from northern North America, Scandinavia, and western Russia. The results indicate that recent warming is unusual relative to temperatures of the past 450 years.

Journal Article↗

Phylogenetic classification and the universal tree.

From comparative analyses of the nucleotide sequences of genes encoding ribosomal RNAs and several proteins, molecular phylogeneticists have constructed a "universal tree of life," taking it as the basis for a "natural" hierarchical classification of all living things. Although confidence in some of the tree's early branches has recently been shaken, new approaches could still resolve many methodological uncertainties. More challenging is evidence that most archaeal and bacterial genomes (and the inferred ancestral eukaryotic nuclear genome) contain genes from multiple sources. If "chimerism" or "lateral gene transfer" cannot be dismissed as trivial in extent or limited to special categories of genes, then no hierarchical universal classification can be taken as natural. Molecular phylogeneticists will have failed to find the "true tree," not because their methods are inadequate or because they have chosen the wrong genes, but because the history of life cannot properly be represented as a tree. However, taxonomies based on molecular sequences will remain indispensable, and understanding of the evolutionary process will ultimately be enriched, not impoverished.

Animals↗

Classification tree method for bacterial source tracking with antibiotic resistance analysis data.

Various statistical classification methods, including discriminant analysis, logistic regression, and cluster analysis, have been used with antibiotic resistance analysis (ARA) data to construct models for bacterial source tracking (BST). We applied the statistical method known as classification trees to build a model for BST for the Anacostia Watershed in Maryland. Classification trees have more flexibility than other statistical classification approaches based on standard statistical methods to accommodate complex interactions among ARA variables. This article describes the use of classification trees for BST and includes discussion of its principal parameters and features. Anacostia Watershed ARA data are used to illustrate the application of classification trees, and we report the BST results for the watershed.

Animals↗

Characterization of the complete genome of the Tupaia (tree shrew) adenovirus.

The members of the family Adenoviridae are widely spread among vertebrate host species and normally cause acute but innocuous infections. Special attention is focused on adenoviruses because of their ability to transform host cells, their possible application in vector technology, and their phylogeny. The primary structure of the genome of Tupaia adenovirus (TAV), which infects Tupaia spp. (tree shrew) was determined. Tree shrews are taxonomically assumed to be at the base of the phylogenetic tree of mammals and are frequently used as laboratory animals in neurological and behavior research. The TAV genome is 33,501 bp in length with a G+C content of 49.96% and has 166-bp inverted terminal repeats. Analysis of the complete nucleotide sequence resulted in the identification of 109 open reading frames (ORFs) with a coding capacity of at least 40 amino acid residues. Thirty-eight of them are predicted to encode viral proteins based on the presence of transcription and translation signals and sequence and positional conservation. Thirty viral ORFs were found to show significant similarities to known adenoviral genes, arranged into discrete early and late genome regions as they are known from mastadenoviruses. Analysis of the nucleotide content of the TAV genome revealed a significant CG dinucleotide depletion at the genome ends that suggests methylation of these genomic regions during the viral life cycle. Phylogenetic analysis of the viral gene products, including penton and hexon proteins, viral protease, terminal protein, protein VIII, DNA polymerase, protein IVa2, and 100,000-molecular-weight protein, revealed that the evolutionary lineage of TAV forms a separate branch within the phylogenetic tree of the Mastadenovirus genus.

Adenoviridae↗

Ancestral maximum likelihood of evolutionary trees is hard.

Maximum likelihood (ML) (Neyman, 1971) is an increasingly popular optimality criterion for selecting evolutionary trees. Finding optimal ML trees appears to be a very hard computational task--in particular, algorithms and heuristics for ML take longer to run than algorithms and heuristics for maximum parsimony (MP). However, while MP has been known to be NP-complete for over 20 years, no such hardness result has been obtained so far for ML. In this work we make a first step in this direction by proving that ancestral maximum likelihood (AML) is NP-complete. The input to this problem is a set of aligned sequences of equal length and the goal is to find a tree and an assignment of ancestral sequences for all of that tree's internal vertices such that the likelihood of generating both the ancestral and contemporary sequences is maximized. Our NP-hardness proof follows that for MP given in (Day, Johnson and Sankoff, 1986) in that we use the same reduction from Vertex Cover; however, the proof of correctness for this reduction relative to AML is different and substantially more involved.

Algorithms↗

A dimensionless fit measure for phylogenetic distance trees.

We present a dimensionless fit index for phylogenetic trees that have been constructed from distance matrices. It is designed to measure the quality of the fit of the data to a tree in absolute terms, independent of linear transformations on the distance matrix. The index can be used as an absolute measure to evaluate how well a set of data fits to a tree, or as a relative measure to compare different methods that are expected to produce the same tree. The usefulness of the index is demonstrated in three examples.

Algorithms↗