Confidence Intervals for the Mean of a Poisson Distribution: A Review

The paper provides a comprehensive review of methodology for setting confidence intervals for the parameter of a Poisson distribution. The results are illustrated by a numerical example.     

Doubled Haploids for Estimating Mean and Variance of Recombination Values

In a diallel cross analysis using doubled haploids, both additive and additive x additive genetic variances can be estimated. In addition, mean and variance of recombination values can also be estimated. Linkage affects the covariance between half-sibs the most, the covariance between grandparent and grand offspring to an intermediate degree and the covariance between full sibs the least. The covariance of parent and offspring is not affected by linkage.     

A Semiempirical Transition State Structure for the First Step in the Alkaline Hydrolysis of Cocaine. Comparison between the Transition State Structure,the Phosphonate Monoester Transition State Analog,and a Newly Designed Thiophosphonate Transition State Analog

Semiempirical molecular orbital calculations have been performed for the first step in the alkaline hydrolysis of the neutral benzoylester of cocaine. Successes, failures, and limitations of these calculations are reviewed. A PM3 calculated transition state structure is compared with the PM3 calculated structure for the hapten used to induce catalytic antibodies for the hydrolysis of cocaine. Implications of these calculations for the computer–aided design of transition state analogs for the induction of catalytic antibodies are discussed.Supplementary material to this paper is available in electronic form at http://dx.doi.org/10.1007/s0089460020062     

Greedy Selection of Species for Ancestral State Reconstruction on Phylogenies: Elimination Is Better than Insertion

Accurate reconstruction of ancestral character states on a phylogeny is crucial in many genomics studies. We study how to select species to achieve the best reconstruction of ancestral character states on a phylogeny. We first show that the marginal maximum likelihood has the monotonicity property that more taxa give better reconstruction, but the Fitch method does not have it even on an ultrametric phylogeny. We further validate a greedy approach for species selection using simulation. The validation tests indicate that backward greedy selection outperforms forward greedy selection. In addition, by applying our selection strategy, we obtain a set of the ten most informative species for the reconstruction of the genomic sequence of the so-called boreoeutherian ancestor of placental mammals. This study has broad relevance in comparative genomics and paleogenomics since limited research resources do not allow researchers to sequence the large number of descendant species required to reconstruct an ancestral sequence.     

Ancestral transfer of symbionts between cockroaches and termites: an unlikely scenario.

Thorne's (Proc. R. Soc. Lond. B 241, 37 (1990] studies of the laboratory behaviour of extant woodroaches (Cryptocercus) and termites (Zootermopsis) suggest that transfaunation of hindgut protozoans potentially could occur by aggression and consumption in the field. However, existing literature suggests no overlap in protozoan species composition for these two taxa. Furthermore, it is doubtful that transfaunation would occur in the solitary ancestral 'termitoid' and 'roachoid' lines proposed by Thorne: not only is it unlikely that such insects would encounter each other, but it is doubtful that they would show the degree of aggression exhibited by the termite soldiers in her study. Inheritance from an ancestor common to Cryptocercus and the lower termites remains the most logical explanation for the presence of the unique cellulolytic oxymonad, trichomonad and hypermastigote flagellates in these two groups.     

Ancestral transfer of symbionts between cockroaches and termites: an alternative hypothesis.

Closely related cellulolytic protozoa reside in the hindguts of extant woodroaches (Cryptocercidae) and termites (Isoptera). The evolutionary origin of these symbiotic relationships in the two lineages is uncertain. Transfer of protozoa between ancestors of modern Cryptocercus and termites remains a valid alternative theory to the established hypothesis of symbiont inheritance from a common ancestor. Nalepa's (Proc. R. Soc. Lond. B 246, 185 (1991] concerns regarding the protozoan transfer hypothesis focus on the biology of modern species, and neglect to consider the evolutionary framework of an ancestral dynamic postulated to occur among Palaeozoic insects. Legitimacy of the symbiont transfer theory removes the constraint of interpreting presence of cellulolytic protozoa as a synapomorphy between Cryptocercidae and Isoptera, with potential impact on objective resolution of dictyopteran phylogeny.     

Evolutionary History of Assassin Bugs (Insecta: Hemiptera: Reduviidae): Insights from Divergence Dating and Ancestral State Reconstruction

Assassin bugs are one of the most successful clades of predatory animals based on their species numbers (∼6,800 spp.) and wide distribution in terrestrial ecosystems. Various novel prey capture strategies and remarkable prey specializations contribute to their appeal as a model to study evolutionary pathways involved in predation. Here, we reconstruct the most comprehensive reduviid phylogeny (178 taxa, 18 subfamilies) to date based on molecular data (5 markers). This phylogeny tests current hypotheses on reduviid relationships emphasizing the polyphyletic Reduviinae and the blood-feeding, disease-vectoring Triatominae, and allows us, for the first time in assassin bugs, to reconstruct ancestral states of prey associations and microhabitats. Using a fossil-calibrated molecular tree, we estimated divergence times for key events in the evolutionary history of Reduviidae. Our results indicate that the polyphyletic Reduviinae fall into 11–14 separate clades. Triatominae are paraphyletic with respect to the reduviine genus Opisthacidius in the maximum likelihood analyses; this result is in contrast to prior hypotheses that found Triatominae to be monophyletic or polyphyletic and may be due to the more comprehensive taxon and character sampling in this study. The evolution of blood-feeding may thus have occurred once or twice independently among predatory assassin bugs. All prey specialists evolved from generalist ancestors, with multiple evolutionary origins of termite and ant specializations. A bark-associated life style on tree trunks is ancestral for most of the lineages of Higher Reduviidae; living on foliage has evolved at least six times independently. Reduviidae originated in the Middle Jurassic (178 Ma), but significant lineage diversification only began in the Late Cretaceous (97 Ma). The integration of molecular phylogenetics with fossil and life history data as presented in this paper provides insights into the evolutionary history of reduviids and clears the way for in-depth evolutionary hypothesis testing in one of the most speciose clades of predators.     

Titration Properties and Thermodynamics of the Transition State for Folding: Comparison of Two-state and Multi-state Folding Pathways

CI2 folds and unfolds as a single cooperative unit by simple two-state kinetics, which enables the properties of the transition state to be measured from both the forward and backward rate constants. We have examined how the free energy of the transition state for the folding of chymotrypsin inhibitor 2 (CI2) changes with pH and temperature. In addition to the standard thermodynamic quantities, we have measured the overall acid-titration properties of the transition state and its heat capacity relative to both the denatured and native states. We were able to determine the latter by a method analogous to a well-established procedure for measuring the change in heat capacity for equilibrium unfolding: the enthalpy of activation of unfolding at different values of acid pH were plotted against the average temperature of each determination. Our results show that the transition state of CI2 has lost most of the electrostatic and van der Waals' interactions that are found in the native state, but it remains compact and this prevents water molecules from entering some parts of the hydrophobic core. The properties of the transition state of CI2 are then compared with the major folding transition state of the larger protein barnase, which folds by a multi-state mechanism, with the accumulation of a partly structured intermediate (D^physor I). CI2 folds from a largely unstructured denatured state under physiological conditionsviaa transition state which is compact but relatively uniformly unstructured, with tertiary and secondary structure being formed in parallel. We term this an expanded pathway. Conversely, barnase folds from a largely structured denatured state in which elements of structure are well formed through a transition state that has islands of folded elements of structure. We term this a compact pathway. These two pathways may correspond to the two extreme ends of a continuous spectrum of protein folding mechanisms. Although the properties of the two transition states are very different, the activation barrier for folding (D^phys→3 ) is very similar for both proteins.     

Nodes in phylogenetic trees: the relation between imbalance and number of descendent species

The imbalance of a node in a phylogenetic tree can be defined in terms of the relative numbers of species (or higher taxa) on the branches that originate at the node. Empirically, imbalance also turns out to depend on the absolute total number of species on the branches: in a sample of large trees, nodes with more descendent species tend to be more unbalanced. Subsidiary analyses suggest that this pattern is not a result of errors in tree estimation. Instead, the increase in imbalance with species is consistent with a cumulative effect of differences in diversification rates between branches. [Equal-rates Markov model; imbalance; phylogeny shape; proportional-to-distinguishable-arrangements model.].     

Molecular Phylogenetics of Finches and Sparrows: Consequences of Character State Removal in CytochromebSequences

The complete mitochondrial cytochromebgenes of 53 genera of oscine passerine birds representing the major groups of finches and some allies were compared. Phylogenetic trees resulting from three levels of character partition removal (no data removed, transitions at third positions of codons removed, and all transitions removed [transversion parsimony]) were generally concordant, and all supported several basic statements regarding relationships of finches and finch-like birds, including: (1) larks (Alaudidae) show no close relationship to any finch group; (2)Peucedramus(olive warbler) is phylogenetically far removed from true wood warblers; (3) a clade consisting of fringillids, passerids, motacillids, and emberizids is supported, and this clade is characterized by evolution of a vestigial 10th wing primary; and (4) Hawaiian honeycreepers are derived from within the cardueline finches. Excluding transition substitutions at third positions of codons resulted in phylogenetic trees similar to, but with greater bootstrap nodal support than, trees derived using either all data (equally weighted) or transversion parsimony. Relative to the shortest trees obtained using all data, the topologies obtained after elimination of third-position transitions showed only slight increases in realized treelength and homoplasy. These increases were negligable compared to increases in overall nodal support; therefore, this partition removal scheme may enhance recovery of deep phylogenetic signal in protein-coding DNA datasets.     

Emotionally Triggered Asthma: A Review of Research Literature and Some Hypotheses for Self-Regulation Therapies

Asthma is a common disease whose morbidity and mortality are rapidly increasing. Panic disorder is common in asthma. Panic, other negative emotions, and a passive coping orientation may affect asthma by producing hyperventilation, increased general autonomic lability, a specific pattern of autonomic arousal that may cause bronchoconstriction, and/or detrimental effects on health care behaviors. Generalized panic is a risk factor for increased asthma morbidity. A repressive coping style also appears to be a risk factor for asthma morbidity because it is accompanied by an impaired ability to perceive symptoms, a necessary prerequisite for taking appropriate remediation. Several self-regulation strategies are hypothesized to be useful adjuncts to asthma treatment. Preliminary research has been done on relaxation therapy, EMG biofeedback, biofeedback for improved sensitivity in perceiving respiratory sensations, and biofeedback training for increasing respiratory sinus arrhythmia. It is hypothesized that finger temperature biofeedback also may be a promising treatment method, and that relaxation-oriented methods will have their greatest effect among asthmatics who experience panic symptoms, while improved perceptual sensitivity will be helpful both for patients who panic and those with repressive coping styles.     

Interaction of Brain-Type Creatine Kinase with its Transition State Analog: Kinetics of Inhibition and Conformational Changes

Abstract

The effects of components of the transition state analog (creatine, MgADP, planar anion) on the kinetics and conformation of creatine kinase isozyme BB from monkey brain was studied. From analysis of the reaction time course using the pH stat assay, it was shown that during accumulation of the reaction products (ADP and creatine phosphate), among several anions added, nitrate proved the most effective in inhibiting catalytic activity. Maximum inhibition (77%) was achieved with 50 mM nitrate. The K_m for ATP was 0.48 mM and in the presence of 2.5 mM nitrate, 2.2 mM; for ATP in the presence of the dead-end complex, creatine and ADP, the apparent Km was 2.0 mM and theK wasO.16mM; in the presence of the transition state analog, MgADP + NO₃” + creatine, the K was estimated to be 0.04 mM.

Ultraviolet difference spectra of creatine kinase revealed significant differences only in the presence of the complete mixture of the components of the transition state analog. Comparison of gel nitration elution profiles for creatine kinase in the absence and presence of the complete mixture of components of the transition state analog did not reveal any differences in elution volume. Addition of components of the transition state analog to creatine kinase resulted in only a marginal change in intrinsic fluorescence. The presence of the components of the transition state analog increased the rate of reactivity of the enzyme with trinitrobenzenesulfonic acid from k = 6.06 ±0.05M^?1min to 6.96 ± 0.11 M^?1min^?1.

This study provides evidence that, like the muscle isozyme of creatine kinase, the brain form is effectively inhibited by the transition state analog. However, the inhibition is accompanied by small changes in the overall conformation of the protein. This adds to the evidence that the functional differences of the isozymic forms of creatine kinase cannot be attributed to differences in kinetic properties.     

Variance of Neutral Genetic Variances within and between Populations for a Quantitative Character

The variances of genetic variances within and between finite populations were systematically studied using a general multiple allele model with mutation in terms of identity by descent measures. We partitioned the genetic variances into components corresponding to genetic variances and covariances within and between loci. We also analyzed the sampling variance. Both transient and equilibrium results were derived exactly and the results can be used in diverse applications. For the genetic variance within populations, sigma 2 omega, the coefficient of variation can be very well approximated as [formula: see text] for a normal distribution of allelic effects, ignoring recurrent mutation in the absence of linkage, where m is the number of loci, N is the effective population size, theta 1(0) is the initial identity by descent measure of two genes within populations and t is the generation number. The first term is due to genic variance, the second due to linkage disequilibrium, and third due to sampling. In the short term, the variation is predominantly due to linkage disequilibrium and sampling; but in the long term it can be largely due to genic variance. At equilibrium with mutation [formula: see text] where u is the mutation rate. The genetic variance between populations is a parameter. Variance arises only among sample estimates due to finite sampling of populations and individuals. The coefficient of variation for sample gentic variance between populations, sigma 2b, can be generally approximated as [formula: see text] when the number of loci is large where S is the number of sampling populations.     

A Comparison of Experimental and Computational Methods for Mapping the Interactions Present in the Transition State for Folding of FKBP12

The folding pathway of FKBP12, a 107 residue / protein, has been characterised in detail using a combination of experimental and computational techniques. FKBP12 follows a two-state model of folding in which only the denatured and native states are significantly populated; no intermediate states are detected. The refolding rate constant in water is 4 s^-1 at 25 °C. Two different experimental strategies were employed for studying the transition state for folding. In the first case, a non-mutagenic approach was used and the unfolding and refolding of the wild-type protein measured as a function of experimental conditions such as temperature, denaturant, ligand and trifluoroethanol (TFE) concentration. These data suggest a compact transition state relative to the unfolded state with some 70% of the surface area buried. The ligand-binding site, whichis mainly formed by two long loops, is largely unstructured in the transition state. TFE experiments suggest that the -helix may be formed in the transition state. The second experimental approach involved using protein engineering techniques with -value analysis. Residue-specific information on the structure and energetics of the transition state can be obtained by this method. 34 mutations were made at sites throughout the protein to probe the extent of secondary and tertiary structure in the transition state. In contrast to some other proteins of this size, no element of structure is fully formed in the transition state, instead, the transition state is similar to that found for smaller, single-domain proteins, such as chymotrypsin inhibitor 2 and the SH3 domainfrom -spectrin. For FKBP12, the central three strands of the -sheet (2, 4 and 5), comprise the most structured region of the transition state. In particular Val 101, which is one of the most highly buried residues and located in the middle of the central -strand,makes approximately 60% of its native interactions. The outer -strands, and the ends of the central -strands are formed to a lesser degree. The short -helix is largely unstructured in the transition state as are the loops. The data are consistent with a nucleation-condensation model of folding, the nucleus of which is formed by side chains within -strands 2, 4 and 5 and the C-terminus of the -helix. These residues are distant in the primary sequence, demonstrating the importance of tertiary interactions in the transition state. High-temperature molecular dynamic simulations on the unfoldingpathway of FKBP12 are in good agreement with the experimental results.     

Ancestral variation and the potential for genetic accommodation in larval amphibians: implications for the evolution of novel feeding strategies

SUMMARY Few studies provide empirical evidence for phenotypic plasticity's role in the evolution of novel traits. One way to do so is to test whether latent plasticity is present in an ancestor that can be refined, enhanced, or diminished by selection in derived taxa (through "genetic accommodation"), thereby producing novel traits. Here, we evaluated whether gut plasticity preceded and promoted the evolution of a novel feeding strategy in spadefoot toad tadpoles. We studied Scaphiopus couchii , whose tadpoles develop an elongate gut and consume only detritus, and two derived species, Spea multiplicata and Sp. bombifrons , whose tadpoles also express a novel, short-gut phenotype in response to a novel resource (anostracan shrimp). Consistent with the expectations of plasticity-mediated trait evolution, we found that shrimp induced a range of phenotypes in Scaphiopus that were not produced with detritus. This plasticity was either suppressed or exaggerated in Spea depending on whether the induced phenotypes were adaptive. Moreover, in contrast to its effects on morphology, shrimp induced little or no functional plasticity, as assessed by gut cell proliferation, in Scaphiopus . Shrimp did, however, induce substantial proliferation in Sp. bombifrons , the species that consumes the most shrimp and that produces the short-gut phenotype the most frequently. Thus, if Spea had ancestral morphological plasticity in response to a novel diet, their shrimp-induced short-gut morphology may have undergone subsequent genetic accommodation that improved its functionality. Hence, diet-induced phenotypic plasticity may have preceded and even promoted the evolution of a novel phenotype.     

Growth Respiration of a Flood-Tolerant and a Flood-Intolerant Senecio Species: Correlation between Calculated and Experimental Values

Root growth respiration of Senecio aquaticus Hill (flood-tolerant) and Senecio jacobaea L. (flood-sensitive) was calculated, assuming different P: O ratios. The growth respiration values were calculated on the basis of the chemical composition of root and shoot dry matter, in combination with published data on the energy costs of biosynthetic and transport processes. The comparison between calculated and experimental values suggests a relatively low efficiency of ATP utilization in the roots of the flood-tolerant species. Root growth respiration of S. congestus (R.Br.)DC., which is also flood-tolerant, and Plantago lanceolata L. were also determined. The data showed that not all the flood-tolerant species investigated had high root growth respiration values. An “overflow model’ is proposed to explain observed differences in root growth respiration between species.     

A Conserved Behavioral State Barrier Impedes Transitions between Anesthetic-Induced Unconsciousness and Wakefulness: Evidence for Neural Inertia

One major unanswered question in neuroscience is how the brain transitions between conscious and unconscious states. General anesthetics offer a controllable means to study these transitions. Induction of anesthesia is commonly attributed to drug-induced global modulation of neuronal function, while emergence from anesthesia has been thought to occur passively, paralleling elimination of the anesthetic from its sites in the central nervous system (CNS). If this were true, then CNS anesthetic concentrations on induction and emergence would be indistinguishable. By generating anesthetic dose-response data in both insects and mammals, we demonstrate that the forward and reverse paths through which anesthetic-induced unconsciousness arises and dissipates are not identical. Instead they exhibit hysteresis that is not fully explained by pharmacokinetics as previously thought. Single gene mutations that affect sleep-wake states are shown to collapse or widen anesthetic hysteresis without obvious confounding effects on volatile anesthetic uptake, distribution, or metabolism. We propose a fundamental and biologically conserved concept of neural inertia, a tendency of the CNS to resist behavioral state transitions between conscious and unconscious states. We demonstrate that such a barrier separates wakeful and anesthetized states for multiple anesthetics in both flies and mice, and argue that it contributes to the hysteresis observed when the brain transitions between conscious and unconscious states.