• Rumor and Gossip: The Social Psychology of Hearsay

      Rosnow, Ralph L.; Fine, Gary Alan (1976)
      Presents findings from a sociological and psychological study of rumor, gossip, and hearsay, showing that the distribution patterns of these communication forms closely parallel characteristics and rules of economic exchange, and that the consumption of rumor and gossip corresponds to the consumption of goods and services. Recommendations and guidelines for rumor control centers based on World War II clinics are presented.
    • People Studying People: Artifacts and Ethics in Behavioral Research

      Rosenthal, Robert, 1933-; Rosnow, Ralph L. (1977)
      This is a lively and engaging look at the factors, known as `artifacts', that can confound behavioural experiments. By describing key research studies in a narrative style, Rosnow and Rosenthal address the issues of scientific method and clarify the difficulties that behavioural researchers will encounter. Their final chapter addresses ethical issues, again through narrative use of examples.
    • The adaptive evolution database (TAED).

      Liberles, DA; Schreiber, DR; Govindarajan, S; Chamberlin, SG; Benner, SA; Liberles, David A|0000-0003-3487-8826 (2001-01-01)
      BACKGROUND: The Master Catalog is a collection of evolutionary families, including multiple sequence alignments, phylogenetic trees and reconstructed ancestral sequences, for all protein-sequence modules encoded by genes in GenBank. It can therefore support large-scale genomic surveys, of which we present here The Adaptive Evolution Database (TAED). In TAED, potential examples of positive adaptation are identified by high values for the normalized ratio of nonsynonymous to synonymous nucleotide substitution rates (KA/KS values) on branches of an evolutionary tree between nodes representing reconstructed ancestral sequences. RESULTS: Evolutionary trees and reconstructed ancestral sequences were extracted from the Master Catalog for every subtree containing proteins from the Chordata only or the Embryophyta only. Branches with high KA/KS values were identified. These represent candidate episodes in the history of the protein family when the protein may have undergone positive selection, where the mutant form conferred more fitness than the ancestral form. Such episodes are frequently associated with change in function. An unexpectedly large number of families (between 10% and 20% of those families examined) were found to have at least one branch with high KA/KS values above arbitrarily chosen cut-offs (1 and 0.6). Most of these survived a robustness test and were collected into TAED. CONCLUSIONS: TAED is a raw resource for bioinformaticists interested in data mining and for experimental evolutionists seeking candidate examples of adaptive evolution for further experimental study. It can be expanded to include other evolutionary information (for example changes in gene regulation or splicing) placed in a phylogenetic perspective.
    • A genomic timescale for the origin of eukaryotes

      Hedges, SB; Chen, H; Kumar, S; Wang, DYC; Thompson, AS; Watanabe, H; Kumar, Sudhir|0000-0002-9918-8212 (2001-09-12)
      Background: Genomic sequence analyses have shown that horizontal gene transfer occurred during the origin of eukaryotes as a consequence of symbiosis. However, details of the timing and number of symbiotic events are unclear. A timescale for the early evolution of eukaryotes would help to better understand the relationship between these biological events and changes in Earth's environment, such as the rise in oxygen. We used refined methods of sequence alignment, site selection, and time estimation to address these questions with protein sequences from complete genomes of prokaryotes and eukaryotes. Results: Eukaryotes were found to evolve faster than prokaryotes, with those eukaryotes derived from eubacteria evolving faster than those derived from archaebacteria. We found an early time of divergence (∼4 billion years ago, Ga) for archaebacteria and the archaebacterial genes in eukaryotes. Our analyses support at least two horizontal gene transfer events in the origin of eukaryotes, at 2.7 Ga and 1.8 Ga. Time estimates for the origin of cyanobacteria (2.6 Ga) and the divergence of an early-branching eukaryote that lacks mitochondria (Giardia) (2.2 Ga) fall between those two events. Conclusions: We find support for two symbiotic events in the origin of eukaryotes: one premitochondrial and a later mitochondrial event. The appearance of cyanobacteria immediately prior to the earliest undisputed evidence for the presence of oxygen (2.4-2.2 Ga) suggests that the innovation of oxygenic photosynthesis had a relatively rapid impact on the environment as it set the stage for further evolution of the eukaryotic cell. © 2001 Hedges et al; licensee BioMed Central Ltd.
    • Evolution enters the genomic era

      Liberles, DA; Liberles, David A|0000-0003-3487-8826 (2001-12-01)
      A report on the 18th Congress of the European Society for Evolutionary Biology (ESEB), Aarhus, Denmark, 20-25 August, 2001.
    • The Protein Trinity: Structure/Function Relationships That Include Intrinsic Disorder

      Dunker, A Keith; Brown, Celeste J; Lawson, Celeste J David; Iakoucheva-Sebat, Lilia M; Vucetic, Slobodan; Obradovic, Zoran (2002)
    • Proteomics in alcohol research

      Anni, H; Israel, Y (2002-01-01)
      The proteome is the complete set of proteins in an organism. It is considerably larger and more complex than the genome - the collection of genes that encodes these proteins. Proteomics deals with the qualitative and quantitative study of the proteome under physiological and pathological conditions (e.g., after exposure to alcohol, which causes major changes in numerous proteins of different cell types). To map large proteomes such as the human proteome, proteins from discrete tissues, cells, cell components, or biological fluids are first separated by high-resolution two-dimensional electrophoresis and multidimensional liquid chromatography. Then, individual proteins are identified by mass spectrometry. The huge amount of data acquired using these techniques is analyzed and assembled by fast computers and bioinformatics tools. Using these methods, as well as other technological advances, alcohol researchers can gain a better understanding of how alcohol globally influences protein structure and function, protein-protein interactions, and protein networks. This knowledge ultimately will assist in the early diagnosis and prognosis of alcoholism and the discovery of new drug targets and medications for treatment.
    • The evolutionary position of nematodes

      Blair, JE; Ikeo, K; Gojobori, T; Blair Hedges, S (2002-04-08)
      Background: The complete genomes of three animals have been sequenced by global research efforts: a nematode worm (Caenorhabditis elegans), an insect (Drosophila melanogaster), and a vertebrate (Homo sapiens). Remarkably, their relationships have yet to be clarified. The confusion concerns the enigmatic position of nematodes. Traditionally, nematodes have occupied a basal position, in part because they lack a true body cavity. However, the leading hypothesis now joins nematodes with arthropods in a molting clade, Ecdysozoa, based on data from several genes. Results: We tested the Ecdysozoa hypothesis with analyses of more than 100 nuclear protein alignments, under conditions that would expose biases, and found that it was not supported. Instead, we found significant support for the traditional hypothesis, Coelomata. Our result is robust to different rates of sequence change among genes and lineages, different numbers of taxa, and different species of nematodes. Conclusion: We conclude that insects (arthropods) are genetically and evolutionarily closer to humans than to nematode worms. © 2002 Blair et al; licensee BioMed Central Ltd.
    • Tracking adaptive evolutionary events in genomic sequences

      Liberles, DA; Wayne, ML; Liberles, David A|0000-0003-3487-8826 (2002-07-02)
      As more gene and genomic sequences from an increasing assortment of species become available, new pictures of evolution are emerging. Improved methods can pinpoint where positive and negative selection act in individual codons in specific genes on specific branches of phylogenetic trees. Positive selection appears to be important in the interaction between genotype, protein structure, function, and organismal phenotype.
    • Mouse ribonuclease III. cDNA structure, expression analysis, and chromosomal location

      Fortin, KR; Nicholson, RH; Nicholson, AW (2002-08-21)
      Background: Members of the ribonuclease III superfamily of double-stranded(ds)-RNA-specific endoribonucleases participate in diverse RNA maturation and decay pathways in eukaryotic and prokaryotic cells. A human RNase III orthologue has been implicated in ribosomal RNA maturation. To better understand the structure and mechanism of mammalian RNase III and its involvement in RNA metabolism we determined the cDNA structure, chromosomal location, and expression patterns of mouse RNase III. Results: The predicted mouse RNase III polypeptide contains 1373 amino acids (∼160 kDa). The polypeptide exhibits a single C-terminal dsRNA-binding motif (dsRBM), tandem catalytic domains, a proline-rich region (PRR) and an RS domain. Northern analysis and RT-PCR reveal that the transcript (4487 nt) is expressed in all tissues examined, including extraembryonic tissues and the midgestation embryo. Northern analysis indicates the presence of an additional, shorter form of the transcript in testicular tissue. Fluorescent in situ hybridization demonstrates that the mouse RNase III gene maps to chromosome 15, region B, and that the human RNase III gene maps to a syntenic location on chromosome 5p13-p14. Conclusions: The broad transcript expression pattern indicates a conserved cellular role(s) for mouse RNase III. The putative polypeptide is highly similar to human RNase III (99% amino acid sequence identity for the two catalytic domains and dsRBM), but is distinct from other eukaryotic orthologues, including Dicer, which is involved in RNA interference. The mouse RNase III gene has a chromosomal location distinct from the Dicer gene. © 2002 Fortin et al; licensee BioMed Central Ltd.
    • The retinoblastoma family: Twins or distant cousins?

      Claudio, PP; Tonini, T; Giordano, A; Giordano, Antonio|0000-0002-5959-016X (2002-09-23)
      The destiny of a cell - whether it undergoes division, differentiation or death - results from an intricate balance of many regulators, including oncoproteins, tumor-suppressor proteins and cell-cycle-associated proteins. One of the better-studied tumor suppressors is the retinoblastoma protein, known as pRb or p105. Two recently identified proteins, pRb2/p130 and p107, show structural and functional similarities to pRb, and these proteins and their orthologs make up the retinoblastoma (Rb) family. Members of the family have been found in animals and plants, and a related protein is known in the alga Chlamydomonas. Members of the Rb family are bound and inactivated by viral proteins and, in turn, bind cellular transcription factors and repress their function, and can also form complexes with cyclins and cyclin-dependent kinases and with histone deacetylases. The are found in the nucleus and their subnuclear localization depends on binding to the nuclear matrix. Members of the family form part of a signal-transduction pathway called the Rb pathway, which is important in cell-cycle regulation and have roles in growth suppression, differentiation and apoptosis in different organisms and cell types.
    • The salmon genome (and other issues in bioinformatics)

      Milchert, LEF; Liberles, DA; Elofsson, A; Liberles, David A|0000-0003-3487-8826 (2002-10-07)
      A report on the fourth annual conference of the Society for Bioinformatics in the Nordic Countries (SOCBIN), Bioinformatics 2002, Bergen, Norway, 4-7 April 2002.
    • Activation of the Syk tyrosine kinase is insufficient for downstream signal transduction in B lymphocytes.

      Hsueh, RC; Hammill, AM; Lee, JA; Uhr, JW; Scheuermann, RH (2002-12-06)
      BACKGROUND: Immature B lymphocytes and certain B cell lymphomas undergo apoptotic cell death following activation of the B cell antigen receptor (BCR) signal transduction pathway. Several biochemical changes occur in response to BCR engagement, including activation of the Syk tyrosine kinase. Although Syk activation appears to be necessary for some downstream biochemical and cellular responses, the signaling events that precede Syk activation remain ill defined. In addition, the requirements for complete activation of the Syk-dependent signaling step remain to be elucidated. RESULTS: A mutant form of Syk carrying a combination of a K395A substitution in the kinase domain and substitutions of three phenylalanines (3F) for the three C-terminal tyrosines was expressed in a murine B cell lymphoma cell line, BCL1.3B3 to interfere with normal Syk regulation as a means to examine the Syk activation step in BCR signaling. Introduction of this kinase-inactive mutant led to the constitutive activation of the endogenous wildtype Syk enzyme in the absence of receptor engagement through a 'dominant-positive' effect. Under these conditions, Syk kinase activation occurred in the absence of phosphorylation on Syk tyrosine residues. Although Syk appears to be required for BCR-induced apoptosis in several systems, no increase in spontaneous cell death was observed in these cells. Surprisingly, although the endogenous Syk kinase was enzymatically active, no enhancement in the phosphorylation of cytoplasmic proteins, including phospholipase Cgamma2 (PLCgamma2), a direct Syk target, was observed. CONCLUSION: These data indicate that activation of Syk kinase enzymatic activity is insufficient for Syk-dependent signal transduction. This observation suggests that other events are required for efficient signaling. We speculate that localization of the active enzyme to a receptor complex specifically assembled for signal transduction may be the missing event.
    • Comparison of mode estimation methods and application in molecular clock analysis

      Hedges, SB; Shah, P (2003-07-31)
      Background: Distributions of time estimates in molecular clock studies are sometimes skewed or contain outliers. In those cases, the mode is a better estimator of the overall time of divergence than the mean or median. However, different methods are available for estimating the mode. We compared these methods in simulations to determine their strengths and weaknesses and further assessed their performance when applied to real data sets from a molecular clock study. Results: We found that the half-range mode and robust parametric mode methods have a lower bias than other mode methods under a diversity of conditions. However, the half-range mode suffers from a relatively high variance and the robust parametric mode is more susceptible to bias by outliers. We determined that bootstrapping reduces the variance of both mode estimators. Application of the different methods to real data sets yielded results that were concordant with the simulations. Conclusion: Because the half-range mode is a simple and fast method, and produced less bias overall in our simulations, we recommend the bootstrapped version of it as a general-purpose mode estimator and suggest a bootstrap method for obtaining the standard error and 95% confidence interval of the mode. © 2003 Hedges and Shah; licensee BioMed Central Ltd.
    • Lorentz invariance relations among parton distributions revisited

      Goeke, K; Metz, A; Pobylitsa, PV; Polyakov, MV (2003-08-07)
      We revisit the derivation of the so-called Lorentz invariance relations between parton distributions. In the most important cases these relations involve twist-3 and transverse momentum dependent parton distributions. It is shown that these relations are violated if the path-ordered exponential is taken into account in the quark correlator. © 2003 Elsevier B.V. All rights reserved.
    • Collins fragmentation function from gluon rescattering

      Bacchetta, A; Metz, A; Yang, JJ (2003-11-13)
      We estimate the Collins fragmentation function by introducing the effect of gluon rescattering in a model calculation of the fragmentation process. We include all necessary diagrams to the one-loop level and compute the nontrivial phases giving rise to the Collins function. We compare our results to the ones obtained from pion rescattering. We conclude that three out of four one-loop diagrams give sizeable contributions to the Collins function, and that the effect of gluon rescattering has a magnitude comparable to that of pion rescattering, but has opposite sign. © 2003 Elsevier B.V. All rights reserved.
    • Methodology for detecting trace amounts of microchimeric DNA from peripheral murine white blood cells by real-time PCR

      Artlett, CM; Dito, CG; Christner, PJ (2003-12-01)
      Real-time PCR methodology can successfully quantitate microchimeric cell populations at a concentration of 100 microchimeric cells/100,000 host cells; however, it has not been successful in quantitating DNA from trace numbers of microchimeric white blood cells which we reported are present in murine peripheral blood at a concentration as low as 2/100,000 host cells. We report methodology using primers for a portion of the H2-kb murine histocompatibility sequence, specific for the C57BL/6J mouse. When these primers were used in the presence of 11,000 μM primer, a 20-fold increase in the median manufacturer's recommended concentration, the assay could be optimized to detect 34 pg of C57BL/6J DNA in a background of 2.5 μg of carrier BALB/cJ DNA (1/100,000). These conditions resulted in a detection limit half as sensitive as that found when no carrier DNA was present.
    • The colonization of land by animals: Molecular phylogeny and divergence times among arthropods

      Pisani, D; Poling, LL; Lyons-Weiler, M; Hedges, SB (2004-01-19)
      Background: The earliest fossil evidence of terrestrial animal activity is from the Ordovician, ∼450 million years ago (Ma). However, there are earlier animal fossils, and most molecular clocks suggest a deep origin of animal phyla in the Precambrian, leaving open the possibility that animals colonized land much earlier than the Ordovician. To further investigate the time of colonization of land by animals, we sequenced two nuclear genes, glyceraldehyde-3-phosphate dehydrogenase and enolase, in representative arthropods and conducted phylogenetic and molecular clock analyses of those and other available DNA and protein sequence data. To assess the robustness of animal molecular clocks, we estimated the deuterostome-arthropod divergence using the arthropod fossil record for calibration and tunicate instead of vertebrate sequences to represent Deuterostomia. Nine nuclear and 15 mitochondrial genes were used in phylogenetic analyses and 61 genes were used in molecular clock analyses. Results: Significant support was found for the unconventional pairing of myriapods (millipedes and centipedes) with chelicerates (spiders, scorpions, horseshoe crabs, etc.) using nuclear and mitochondrial genes. Our estimated time for the divergence of millipedes (Diplopoda) and centipedes (Chilopoda) was 442 ± 50 Ma, and the divergence of insects and crustaceans was estimated as 666 ± 58 Ma. Our results also agree with previous studies suggesting a deep divergence (∼1100 - 900 Ma) for arthropods and deuterostomes, considerably predating the Cambrian Explosion seen in the animal fossil record. Conclusions: The consistent support for a close relationship between myriapods and chelicerates, using mitochondrial and nuclear genes and different methods of analysis, suggests that this unexpected result is not an artefact of analysis. We propose the name Myriochelata for this group of animals, which includes many that immobilize prey with venom. Our molecular clock analyses using arthropod fossil calibrations support earlier studies using vertebrate calibrations in finding that deuterostomes and arthropods diverged hundreds of millions of years before the Cambrian explosion. However, our molecular time estimate for the divergence of millipedes and centipedes is close to the divergence time inferred from fossils. This suggests that arthropods may have adapted to the terrestrial environment relatively late in their evolutionary history. © 2004 Pisani et al; licensee BioMed Central Ltd.
    • A molecular timescale of eukaryote evolution and the rise of complex multicellular life

      Hedges, SB; Blair, JE; Venturi, ML; Shoe, JL (2004-01-28)
      Background: The pattern and timing of the rise in complex multicellular life during Earth's history has not been established. Great disparity persists between the pattern suggested by the fossil record and that estimated by molecular clocks, especially for plants, animals, fungi, and the deepest branches of the eukaryote tree. Here, we used all available protein sequence data and molecular clock methods to place constraints on the increase in complexity through time. Results: Our phylogenetic analyses revealed that (i) animals are more closely related to fungi than to plants, (ii) red algae are closer to plants than to animals or fungi, (iii) choanoflagellates are closer to animals than to fungi or plants, (iv) diplomonads, euglenozoans, and alveolates each are basal to plants+animals+fungi, and (v) diplomonads are basal to other eukaryotes (including alveolates and euglenozoans). Divergence times were estimated from global and local clock methods using 20-188 proteins per node, with data treated separately (multigene) and concatenated (supergene). Different time estimation methods yielded similar results (within 5%): vertebrate-arthropod (964 million years ago, Ma), Cnidaria-Bilateria (1,298 Ma), Porifera-Eumetozoa (1,351 Ma), Pyrenomycetes-Plectomycetes (551 Ma), Candida-Saccharomyces (723 Ma), Hemiascomycetes-filamentous Ascomycota (982 Ma), Basidiomycota-Ascomycota (968 Ma), Mucorales-Basidiomycota (947 Ma), Fungi-Animalia (1,513 Ma), mosses-vascular plants (707 Ma), Chlorophyta- Tracheophyta (968 Ma), Rhodophyta-Chlorophyta+Embryophyta (1,428 Ma), Plantae-Animalia (1,609 Ma), Alveolata-plants+animals+fungi (1,973 Ma), Euglenozoa-plants+animals+fungi (1,961 Ma), and Giardia-plants+animals+fungi (2,309 Ma). By extrapolation, mitochondria arose approximately 2300-1800 Ma and plastids arose 1600-1500 Ma. Estimates of the maximum number of cell types of common ancestors, combined with divergence times, showed an increase from two cell types at 2500 Ma to ∼10 types at 1500 Ma and 50 cell types at ∼1000 Ma. Conclusions: The results suggest that oxygen levels in the environment, and the ability of eukaryotes to extract energy from oxygen, as well as produce oxygen, were key factors in the rise of complex multicellular life. Mitochondria and organisms with more than 2-3 cell types appeared soon after the initial increase in oxygen levels at 2300 Ma. The addition of plastids at 1500 Ma, allowing eukaryotes to produce oxygen, preceded the major rise in complexity. © 2004 Hedges et al; licensee BioMed Central Ltd.