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Sample records for evolutionary molecular engineering

  1. EVOLUTIONARY FOUNDATIONS FOR MOLECULAR MEDICINE

    PubMed Central

    Nesse, Randolph M.; Ganten, Detlev; Gregory, T. Ryan; Omenn, Gilbert S.

    2015-01-01

    Evolution has long provided a foundation for population genetics, but many major advances in evolutionary biology from the 20th century are only now being applied in molecular medicine. They include the distinction between proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are further transforming evolutionary biology and creating yet more opportunities for progress at the interface of evolution with genetics, medicine, and public health. This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and others to speed the development of evolutionary molecular medicine. PMID:22544168

  2. Evolutionary engineering for industrial microbiology.

    PubMed

    Vanee, Niti; Fisher, Adam B; Fong, Stephen S

    2012-01-01

    Superficially, evolutionary engineering is a paradoxical field that balances competing interests. In natural settings, evolution iteratively selects and enriches subpopulations that are best adapted to a particular ecological niche using random processes such as genetic mutation. In engineering desired approaches utilize rational prospective design to address targeted problems. When considering details of evolutionary and engineering processes, more commonality can be found. Engineering relies on detailed knowledge of the problem parameters and design properties in order to predict design outcomes that would be an optimized solution. When detailed knowledge of a system is lacking, engineers often employ algorithmic search strategies to identify empirical solutions. Evolution epitomizes this iterative optimization by continuously diversifying design options from a parental design, and then selecting the progeny designs that represent satisfactory solutions. In this chapter, the technique of applying the natural principles of evolution to engineer microbes for industrial applications is discussed to highlight the challenges and principles of evolutionary engineering.

  3. Lectin engineering, a molecular evolutionary approach to expanding the lectin utilities.

    PubMed

    Hu, Dan; Tateno, Hiroaki; Hirabayashi, Jun

    2015-04-27

    In the post genomic era, glycomics--the systematic study of all glycan structures of a given cell or organism--has emerged as an indispensable technology in various fields of biology and medicine. Lectins are regarded as "decipherers of glycans", being useful reagents for their structural analysis, and have been widely used in glycomic studies. However, the inconsistent activity and availability associated with the plant-derived lectins that comprise most of the commercially available lectins, and the limit in the range of glycan structures covered, have necessitated the development of innovative tools via engineering of lectins on existing scaffolds. This review will summarize the current state of the art of lectin engineering and highlight recent technological advances in this field. The key issues associated with the strategy of lectin engineering including selection of template lectin, construction of a mutagenesis library, and high-throughput screening methods are discussed.

  4. Molecular phylogenetics: testing evolutionary hypotheses.

    PubMed

    Walsh, David A; Sharma, Adrian K

    2009-01-01

    A common approach for investigating evolutionary relationships between genes and organisms is to compare extant DNA or protein sequences and infer an evolutionary tree. This methodology is known as molecular phylogenetics and may be the most informative means for exploring phage evolution, since there are few morphological features that can be used to differentiate between these tiny biological entities. In addition, phage genomes can be mosaic, meaning different genes or genomic regions can exhibit conflicting evolutionary histories due to lateral gene transfer or homologous recombination between different phage genomes. Molecular phylogenetics can be used to identify and study such genome mosaicism. This chapter provides a general introduction to the theory and methodology used to reconstruct phylogenetic relationships from molecular data. Also included is a discussion on how the evolutionary history of different genes within the same set of genomes can be compared, using a collection of T4-type phage genomes as an example. A compilation of programs and packages that are available for conducting phylogenetic analyses is supplied as an accompanying appendix.

  5. Integrating evolutionary and molecular genetics of aging.

    PubMed

    Flatt, Thomas; Schmidt, Paul S

    2009-10-01

    Aging or senescence is an age-dependent decline in physiological function, demographically manifest as decreased survival and fecundity with increasing age. Since aging is disadvantageous it should not evolve by natural selection. So why do organisms age and die? In the 1940s and 1950s evolutionary geneticists resolved this paradox by positing that aging evolves because selection is inefficient at maintaining function late in life. By the 1980s and 1990s this evolutionary theory of aging had received firm empirical support, but little was known about the mechanisms of aging. Around the same time biologists began to apply the tools of molecular genetics to aging and successfully identified mutations that affect longevity. Today, the molecular genetics of aging is a burgeoning field, but progress in evolutionary genetics of aging has largely stalled. Here we argue that some of the most exciting and unresolved questions about aging require an integration of molecular and evolutionary approaches. Is aging a universal process? Why do species age at different rates? Are the mechanisms of aging conserved or lineage-specific? Are longevity genes identified in the laboratory under selection in natural populations? What is the genetic basis of plasticity in aging in response to environmental cues and is this plasticity adaptive? What are the mechanisms underlying trade-offs between early fitness traits and life span? To answer these questions evolutionary biologists must adopt the tools of molecular biology, while molecular biologists must put their experiments into an evolutionary framework. The time is ripe for a synthesis of molecular biogerontology and the evolutionary biology of aging.

  6. The evolutionary ecology of molecular replicators.

    PubMed

    Nee, Sean

    2016-08-01

    By reasonable criteria, life on the Earth consists mainly of molecular replicators. These include viruses, transposons, transpovirons, coviruses and many more, with continuous new discoveries like Sputnik Virophage. Their study is inherently multidisciplinary, spanning microbiology, genetics, immunology and evolutionary theory, and the current view is that taking a unified approach has great power and promise. We support this with a new, unified, model of their evolutionary ecology, using contemporary evolutionary theory coupling the Price equation with game theory, studying the consequences of the molecular replicators' promiscuous use of each others' gene products for their natural history and evolutionary ecology. Even at this simple expository level, we can make a firm prediction of a new class of replicators exploiting viruses such as lentiviruses like SIVs, a family which includes HIV: these have been explicitly stated in the primary literature to be non-existent. Closely connected to this departure is the view that multicellular organism immunology is more about the management of chronic infections rather than the elimination of acute ones and new understandings emerging are changing our view of the kind of theatre we ourselves provide for the evolutionary play of molecular replicators. This study adds molecular replicators to bacteria in the emerging field of sociomicrobiology.

  7. The evolutionary ecology of molecular replicators

    PubMed Central

    2016-01-01

    By reasonable criteria, life on the Earth consists mainly of molecular replicators. These include viruses, transposons, transpovirons, coviruses and many more, with continuous new discoveries like Sputnik Virophage. Their study is inherently multidisciplinary, spanning microbiology, genetics, immunology and evolutionary theory, and the current view is that taking a unified approach has great power and promise. We support this with a new, unified, model of their evolutionary ecology, using contemporary evolutionary theory coupling the Price equation with game theory, studying the consequences of the molecular replicators' promiscuous use of each others' gene products for their natural history and evolutionary ecology. Even at this simple expository level, we can make a firm prediction of a new class of replicators exploiting viruses such as lentiviruses like SIVs, a family which includes HIV: these have been explicitly stated in the primary literature to be non-existent. Closely connected to this departure is the view that multicellular organism immunology is more about the management of chronic infections rather than the elimination of acute ones and new understandings emerging are changing our view of the kind of theatre we ourselves provide for the evolutionary play of molecular replicators. This study adds molecular replicators to bacteria in the emerging field of sociomicrobiology. PMID:27853598

  8. Evolutionary engineering by genome shuffling.

    PubMed

    Biot-Pelletier, Damien; Martin, Vincent J J

    2014-05-01

    An upsurge in the bioeconomy drives the need for engineering microorganisms with increasingly complex phenotypes. Gains in productivity of industrial microbes depend on the development of improved strains. Classical strain improvement programmes for the generation, screening and isolation of such mutant strains have existed for several decades. An alternative to traditional strain improvement methods, genome shuffling, allows the directed evolution of whole organisms via recursive recombination at the genome level. This review deals chiefly with the technical aspects of genome shuffling. It first presents the diversity of organisms and phenotypes typically evolved using this technology and then reviews available sources of genetic diversity and recombination methodologies. Analysis of the literature reveals that genome shuffling has so far been restricted to microorganisms, both prokaryotes and eukaryotes, with an overepresentation of antibiotics- and biofuel-producing microbes. Mutagenesis is the main source of genetic diversity, with few studies adopting alternative strategies. Recombination is usually done by protoplast fusion or sexual recombination, again with few exceptions. For both diversity and recombination, prospective methods that have not yet been used are also presented. Finally, the potential of genome shuffling for gaining insight into the genetic basis of complex phenotypes is also discussed.

  9. Molecular selection in a unified evolutionary sequence

    NASA Technical Reports Server (NTRS)

    Fox, S. W.

    1986-01-01

    With guidance from experiments and observations that indicate internally limited phenomena, an outline of unified evolutionary sequence is inferred. Such unification is not visible for a context of random matrix and random mutation. The sequence proceeds from Big Bang through prebiotic matter, protocells, through the evolving cell via molecular and natural selection, to mind, behavior, and society.

  10. Engineering molecular machines

    NASA Astrophysics Data System (ADS)

    Erman, Burak

    2016-04-01

    Biological molecular motors use chemical energy, mostly in the form of ATP hydrolysis, and convert it to mechanical energy. Correlated thermal fluctuations are essential for the function of a molecular machine and it is the hydrolysis of ATP that modifies the correlated fluctuations of the system. Correlations are consequences of the molecular architecture of the protein. The idea that synthetic molecular machines may be constructed by designing the proper molecular architecture is challenging. In their paper, Sarkar et al (2016 New J. Phys. 18 043006) propose a synthetic molecular motor based on the coarse grained elastic network model of proteins and show by numerical simulations that motor function is realized, ranging from deterministic to thermal, depending on temperature. This work opens up a new range of possibilities of molecular architecture based engine design.

  11. Evolutionary Forecast Engines for Solar Meteorology

    NASA Astrophysics Data System (ADS)

    Coimbra, C. F.

    2012-12-01

    A detailed comparison of non-stationary regression and stochastic learning methods based on k-Nearest Neighbor (kNN), Artificial Neural Networks (ANN) and Genetic Algorithm (GA) approaches is carried out in order to develop high-fidelity solar forecast engines for several time horizons of interest. A hybrid GA/ANN method emerges as the most robust stochastic learning candidate. The GA/ANN approach In general the following decisions need to be made when creating an ANN-based solar forecast model: the ANN architecture: number of layers, numbers of neurons per layer; the preprocessing scheme; the fraction and distribution between training and testing data, and the meteorological and radiometric inputs. ANNs are very well suited to handle multivariate forecasting models due to their overall flexibility and nonlinear pattern recognition abilities. However, the forecasting skill of ANNs depends on a new set of parameters to be optimized within the context of the forecast model, which is the selection of input variables that most directly impact the fidelity of the forecasts. In a data rich scenario where irradiation, meteorological, and cloud cover data are available, it is not always evident which variables to include in the model a priori. New variables can also arise from data preprocessing such as smoothing or spectral decomposition. One way to avoid time-consuming trial-and-error approaches that have limited chance to result in optimal ANN topology and input selection is to couple the ANN with some optimization algorithm that scans the solution space and "evolves" the ANN structure. Genetic Algorithms (GAs) are well suited for this task. Results and Discussion The models built upon the historical data of 2009 and 2010 are applied to the 2011 data without modifications or retraining. We consider 3 solar variability seasons or periods, which are subsets of the total error evaluation data set. The 3 periods are defined based on the solar variability study as: - a high

  12. Reverse engineering molecular hypergraphs.

    PubMed

    Rahman, Ahsanur; Poirel, Christopher L; Badger, David J; Estep, Craig; Murali, T M

    2013-01-01

    Analysis of molecular interaction networks is pervasive in systems biology. This research relies almost entirely on graphs for modeling interactions. However, edges in graphs cannot represent multiway interactions among molecules, which occur very often within cells. Hypergraphs may be better representations for networks having such interactions, since hyperedges can naturally represent relationships among multiple molecules. Here, we propose using hypergraphs to capture the uncertainty inherent in reverse engineering gene-gene networks. Some subsets of nodes may induce highly varying subgraphs across an ensemble of networks inferred by a reverse engineering algorithm. We provide a novel formulation of hyperedges to capture this uncertainty in network topology. We propose a clustering-based approach to discover hyperedges. We show that our approach can recover hyperedges planted in synthetic data sets with high precision and recall, even for moderate amount of noise. We apply our techniques to a data set of pathways inferred from genetic interaction data in S. cerevisiae related to the unfolded protein response. Our approach discovers several hyperedges that capture the uncertain connectivity of genes in relevant protein complexes, suggesting that further experiments may be required to precisely discern their interaction patterns. We also show that these complexes are not discovered by an algorithm that computes frequent and dense subgraphs.

  13. Replaying the evolutionary tape: biomimetic reverse engineering of gene networks.

    PubMed

    Marbach, Daniel; Mattiussi, Claudio; Floreano, Dario

    2009-03-01

    In this paper, we suggest a new approach for reverse engineering gene regulatory networks, which consists of using a reconstruction process that is similar to the evolutionary process that created these networks. The aim is to integrate prior knowledge into the reverse-engineering procedure, thus biasing the search toward biologically plausible solutions. To this end, we propose an evolutionary method that abstracts and mimics the natural evolution of gene regulatory networks. Our method can be used with a wide range of nonlinear dynamical models. This allows us to explore novel model types such as the log-sigmoid model introduced here. We apply the biomimetic method to a gold-standard dataset from an in vivo gene network. The obtained results won a reverse engineering competition of the second DREAM conference (Dialogue on Reverse Engineering Assessments and Methods 2007, New York, NY).

  14. Engineering reduced evolutionary potential for synthetic biology.

    PubMed

    Renda, Brian A; Hammerling, Michael J; Barrick, Jeffrey E

    2014-07-01

    The field of synthetic biology seeks to engineer reliable and predictable behaviors in organisms from collections of standardized genetic parts. However, unlike other types of machines, genetically encoded biological systems are prone to changes in their designed sequences due to mutations in their DNA sequences after these devices are constructed and deployed. Thus, biological engineering efforts can be confounded by undesired evolution that rapidly breaks the functions of parts and systems, particularly when they are costly to the host cell to maintain. Here, we explain the fundamental properties that determine the evolvability of biological systems. Then, we use this framework to review current efforts to engineer the DNA sequences that encode synthetic biology devices and the genomes of their microbial hosts to reduce their ability to evolve and therefore increase their genetic reliability so that they maintain their intended functions over longer timescales.

  15. Transitions, transversions, and the molecular evolutionary clock.

    PubMed

    Jukes, T H

    1987-01-01

    Nucleotide substitutions in the form of transitions (purine-purine or pyrimidine-pyrimidine interchanges) and transversions (purine-pyrimidine interchanges) occur during evolution and may be compiled by aligning the sequences of homologous genes. Referring to the genetic code tables, silent transitions take place in third positions of codons in family boxes and two-codon sets. Silent transversions in third positions occur only in family boxes, except for A = C transversions between AGR and CGR arginine codons (R = A or G). Comparisons of several protein genes have been made, and various subclasses of transitional and transversional nucleotide substitutions have been compiled. Considerable variations occur among the relative proportions of transitions and transversions. Such variations could possibly be caused by mutator genes, favoring either transitions or, conversely, transversions, during DNA replication. At earlier stages of evolutionary divergence, transitions are usually more frequent, but there are exceptions. No indication was found that transversions usually originate from multiple substitutions in transitions.

  16. Molecular imaging with engineered physiology

    PubMed Central

    Desai, Mitul; Slusarczyk, Adrian L.; Chapin, Ashley; Barch, Mariya; Jasanoff, Alan

    2016-01-01

    In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging. CGRP-based agents induce effects at nanomolar concentrations in deep tissue and can be engineered into switchable analyte-dependent forms and genetically encoded reporters suitable for molecular imaging or cell tracking. Such artificially engineered physiological changes, therefore, provide a highly versatile means for sensitive analysis of molecular events in living organisms. PMID:27910951

  17. Molecular imaging with engineered physiology.

    PubMed

    Desai, Mitul; Slusarczyk, Adrian L; Chapin, Ashley; Barch, Mariya; Jasanoff, Alan

    2016-12-02

    In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging. CGRP-based agents induce effects at nanomolar concentrations in deep tissue and can be engineered into switchable analyte-dependent forms and genetically encoded reporters suitable for molecular imaging or cell tracking. Such artificially engineered physiological changes, therefore, provide a highly versatile means for sensitive analysis of molecular events in living organisms.

  18. Automatic Molecular Design using Evolutionary Techniques

    NASA Technical Reports Server (NTRS)

    Globus, Al; Lawton, John; Wipke, Todd; Saini, Subhash (Technical Monitor)

    1998-01-01

    Molecular nanotechnology is the precise, three-dimensional control of materials and devices at the atomic scale. An important part of nanotechnology is the design of molecules for specific purposes. This paper describes early results using genetic software techniques to automatically design molecules under the control of a fitness function. The fitness function must be capable of determining which of two arbitrary molecules is better for a specific task. The software begins by generating a population of random molecules. The population is then evolved towards greater fitness by randomly combining parts of the better individuals to create new molecules. These new molecules then replace some of the worst molecules in the population. The unique aspect of our approach is that we apply genetic crossover to molecules represented by graphs, i.e., sets of atoms and the bonds that connect them. We present evidence suggesting that crossover alone, operating on graphs, can evolve any possible molecule given an appropriate fitness function and a population containing both rings and chains. Prior work evolved strings or trees that were subsequently processed to generate molecular graphs. In principle, genetic graph software should be able to evolve other graph representable systems such as circuits, transportation networks, metabolic pathways, computer networks, etc.

  19. Molecular evolutionary analyses of insect societies.

    PubMed

    Fischman, Brielle J; Woodard, S Hollis; Robinson, Gene E

    2011-06-28

    The social insects live in extraordinarily complex and cohesive societies, where many individuals sacrifice their personal reproduction to become helpers in the colony. Identifying adaptive molecular changes involved in eusocial evolution in insects is important for understanding the mechanisms underlying transitions from solitary to social living, as well as the maintenance and elaboration of social life. Here, we review recent advances made in this area of research in several insect groups: the ants, bees, wasps, and termites. Drawing from whole-genome comparisons, candidate gene approaches, and a genome-scale comparative analysis of protein-coding sequence, we highlight novel insights gained for five major biological processes: chemical signaling, brain development and function, immunity, reproduction, and metabolism and nutrition. Lastly, we make comparisons across these diverse approaches and social insect lineages and discuss potential common themes of eusocial evolution, as well as challenges and prospects for future research in the field.

  20. Molecular evolutionary analyses of insect societies

    PubMed Central

    Fischman, Brielle J.; Woodard, S. Hollis; Robinson, Gene E.

    2011-01-01

    The social insects live in extraordinarily complex and cohesive societies, where many individuals sacrifice their personal reproduction to become helpers in the colony. Identifying adaptive molecular changes involved in eusocial evolution in insects is important for understanding the mechanisms underlying transitions from solitary to social living, as well as the maintenance and elaboration of social life. Here, we review recent advances made in this area of research in several insect groups: the ants, bees, wasps, and termites. Drawing from whole-genome comparisons, candidate gene approaches, and a genome-scale comparative analysis of protein-coding sequence, we highlight novel insights gained for five major biological processes: chemical signaling, brain development and function, immunity, reproduction, and metabolism and nutrition. Lastly, we make comparisons across these diverse approaches and social insect lineages and discuss potential common themes of eusocial evolution, as well as challenges and prospects for future research in the field. PMID:21690385

  1. Molecular Evolutionary Consequences of Island Colonization

    PubMed Central

    James, Jennifer E.; Lanfear, Robert; Eyre-Walker, Adam

    2016-01-01

    Island endemics are expected to have low effective population sizes (Ne), first because some may experience population bottlenecks when they are founded, and second because they have restricted ranges. Therefore, we expect island species to have reduced genetic diversity, inefficient selection, and reduced adaptive potential compared with their mainland counterparts. We used both polymorphism and substitution data to address these predictions, improving on the approach of recent studies that only used substitution data. This allowed us to directly test the assumption that island species have small values of Ne. We found that island species had significantly less genetic diversity than mainland species; however, this pattern could be attributed to a subset of island species that appeared to have undergone a recent population bottleneck. When these species were excluded from the analysis, island and mainland species had similar levels of genetic diversity, despite island species occupying considerably smaller areas than their mainland counterparts. We also found no overall difference between island and mainland species in terms of the effectiveness of selection or the mutation rate. Our evidence suggests that island colonization has no lasting impact on molecular evolution. This surprising result highlights gaps in our knowledge of the relationship between census and effective population size. PMID:27358424

  2. Molecular Evolutionary Consequences of Island Colonization.

    PubMed

    James, Jennifer E; Lanfear, Robert; Eyre-Walker, Adam

    2016-07-02

    Island endemics are expected to have low effective population sizes (Ne), first because some may experience population bottlenecks when they are founded, and second because they have restricted ranges. Therefore, we expect island species to have reduced genetic diversity, inefficient selection, and reduced adaptive potential compared with their mainland counterparts. We used both polymorphism and substitution data to address these predictions, improving on the approach of recent studies that only used substitution data. This allowed us to directly test the assumption that island species have small values of Ne We found that island species had significantly less genetic diversity than mainland species; however, this pattern could be attributed to a subset of island species that appeared to have undergone a recent population bottleneck. When these species were excluded from the analysis, island and mainland species had similar levels of genetic diversity, despite island species occupying considerably smaller areas than their mainland counterparts. We also found no overall difference between island and mainland species in terms of the effectiveness of selection or the mutation rate. Our evidence suggests that island colonization has no lasting impact on molecular evolution. This surprising result highlights gaps in our knowledge of the relationship between census and effective population size.

  3. Molecular dating, evolutionary rates, and the age of the grasses.

    PubMed

    Christin, Pascal-Antoine; Spriggs, Elizabeth; Osborne, Colin P; Strömberg, Caroline A E; Salamin, Nicolas; Edwards, Erika J

    2014-03-01

    Many questions in evolutionary biology require an estimate of divergence times but, for groups with a sparse fossil record, such estimates rely heavily on molecular dating methods. The accuracy of these methods depends on both an adequate underlying model and the appropriate implementation of fossil evidence as calibration points. We explore the effect of these in Poaceae (grasses), a diverse plant lineage with a very limited fossil record, focusing particularly on dating the early divergences in the group. We show that molecular dating based on a data set of plastid markers is strongly dependent on the model assumptions. In particular, an acceleration of evolutionary rates at the base of Poaceae followed by a deceleration in the descendants strongly biases methods that assume an autocorrelation of rates. This problem can be circumvented by using markers that have lower rate variation, and we show that phylogenetic markers extracted from complete nuclear genomes can be a useful complement to the more commonly used plastid markers. However, estimates of divergence times remain strongly affected by different implementations of fossil calibration points. Analyses calibrated with only macrofossils lead to estimates for the age of core Poaceae ∼51-55 Ma, but the inclusion of microfossil evidence pushes this age to 74-82 Ma and leads to lower estimated evolutionary rates in grasses. These results emphasize the importance of considering markers from multiple genomes and alternative fossil placements when addressing evolutionary issues that depend on ages estimated for important groups.

  4. Multiobjective Optimization of Rocket Engine Pumps Using Evolutionary Algorithm

    NASA Technical Reports Server (NTRS)

    Oyama, Akira; Liou, Meng-Sing

    2001-01-01

    A design optimization method for turbopumps of cryogenic rocket engines has been developed. Multiobjective Evolutionary Algorithm (MOEA) is used for multiobjective pump design optimizations. Performances of design candidates are evaluated by using the meanline pump flow modeling method based on the Euler turbine equation coupled with empirical correlations for rotor efficiency. To demonstrate the feasibility of the present approach, a single stage centrifugal pump design and multistage pump design optimizations are presented. In both cases, the present method obtains very reasonable Pareto-optimal solutions that include some designs outperforming the original design in total head while reducing input power by one percent. Detailed observation of the design results also reveals some important design criteria for turbopumps in cryogenic rocket engines. These results demonstrate the feasibility of the EA-based design optimization method in this field.

  5. Comparative approaches in evolutionary psychology: molecular neuroscience meets the mind.

    PubMed

    Panksepp, Jaak; Moskal, Joseph R; Panksepp, Jules B; Kroes, Roger A

    2002-12-01

    Evolutionary psychologists often overlook a wealth of information existing between the proximate genotypic level and the ultimate phenotypic level. This commonly ignored level of biological organization is the ongoing activity of neurobiological systems. In this paper, we extend our previous arguments concerning strategic weaknesses of evolutionary psychology by advocating a foundational view that focuses on similarities in brain, behavior, and various basic psychological features across mammalian species. Such an approach offers the potential to link the emerging discipline of evolutionary psychology to its parent scientific disciplines such as biochemistry, physiology, molecular genetics, developmental biology and the neuroscientific analysis of animal behavior. We detail an example of this through our impending work using gene microarray technology to characterize gene expression patterns in rats during aggressive and playful social interactions. Through a focus on functional homologies and the experimental analysis of conserved, subcortical emotional and motivational brain systems, neuroevolutionary psychobiology can reveal ancient features of the human mind that are still shared with other animals. Claims regarding evolved, uniquely human, psychological constructs should be constrained by the rigorous evidentiary standards that are routine in other sciences.

  6. The molecular evolutionary tree of lizards, snakes, and amphisbaenians.

    PubMed

    Vidal, Nicolas; Hedges, S Blair

    2009-01-01

    Squamate reptiles (lizards, snakes, amphisbaenians) number approximately 8200 living species and are a major component of the world's terrestrial vertebrate diversity. Recent molecular phylogenies based on protein-coding nuclear genes have challenged the classical, morphology-based concept of squamate relationships, requiring new classifications, and drawing new evolutionary and biogeographic hypotheses. Even the key and long-held concept of a dichotomy between iguanians (approximately 1470 sp.) and scleroglossans (all other squamates) has been refuted because molecular trees place iguanians in a highly nested position. Together with snakes and anguimorphs, iguanians form a clade--Toxicofera--characterized by the presence of toxin secreting oral glands and demonstrating a single early origin of venom in squamates. Consequently, neither the varanid lizards nor burrowing lineages such as amphisbaenians or dibamid lizards are the closest relative of snakes. The squamate timetree shows that most major groups diversified in the Jurassic and Cretaceous, 200-66 million years (Myr) ago. In contrast, five of the six families of amphisbaenians arose during the early Cenozoic, approximately 60-40 Myr ago, and oceanic dispersal on floating islands apparently played a significant role in their distribution on both sides of the Atlantic Ocean. Among snakes, molecular data support the basic division between the small fossorial scolecophidians (approximately 370 sp.) and the alethinophidians (all other snakes, approximately 2700 sp.). They show that the alethinophidians were primitively macrostomatan and that this condition was secondarily lost by burrowing lineages. The diversification of alethinophidians resulted from a mid-Cretaceous vicariant event, the separation of South America from Africa, giving rise to Amerophidia (aniliids and tropidophiids) and Afrophidia (all other alethinophidians). Finally, molecular phylogenies have made it possible to draw a detailed evolutionary

  7. Evolutionary molecular cytogenetics of catarrhine primates: past, present and future.

    PubMed

    Stanyon, R; Rocchi, M; Bigoni, F; Archidiacono, N

    2012-01-01

    The catarrhine primates were the first group of species studied with comparative molecular cytogenetics. Many of the fundamental techniques and principles of analysis were initially applied to comparisons in these primates, including interspecific chromosome painting, reciprocal chromosome painting and the extensive use of cloned DNA probes for evolutionary analysis. The definition and importance of chromosome syntenies and associations for a correct cladistics analysis of phylogenomic relationships were first applied to catarrhines. These early chromosome painting studies vividly illustrated a striking conservation of the genome between humans and macaques. Contemporarily, it also revealed profound differences between humans and gibbons, a group of species more closely related to humans, making it clear that chromosome evolution did not follow a molecular clock. Chromosome painting has now been applied to more that 60 primate species and the translocation history has been mapped onto the major taxonomic divisions in the tree of primate evolution. In situ hybridization of cloned DNA probes, primarily BAC-FISH, also made it possible to more precisely map breakpoints with spanning and flanking BACs. These studies established marker order and disclosed intrachromosomal rearrangements. When applied comparatively to a range of primate species, they led to the discovery of evolutionary new centromeres as an important new category of chromosome evolution. BAC-FISH studies are intimately connected to genome sequencing, and probes can usually be assigned to a precise location in the genome assembly. This connection ties molecular cytogenetics securely to genome sequencing, assuring that molecular cytogenetics will continue to have a productive future in the multidisciplinary science of phylogenomics.

  8. Process Engineering with the Evolutionary Spiral Process Model. Version 01.00.06

    DTIC Science & Technology

    1994-01-01

    AD-A2 7 5 398 DIDTICJ. SFEB~ v. PROCESS ENGINEERING WITH THE EVOLUTIONARY SPIRAL PROCESS MODEL SPC-93098-CMC VERSION 01.00.06 JANUARY 1994 S... %-94...34" " , 4":42-" 9442004212 94 2 0.7 0,56 PROCESS ENGINEERING WITH THE EVOLUTIONARY SPIRAL PROCESS MODEL F 7o For DTIC QUALMY NTIS CRA&I M1 LNVPZMZ1¶g) 8...3. EXTENDING THE EVOLUTIONARY SPIRAL PROCESS MODEL TO PROCESS ENGINEERING ........................................... 3-1 3.1 Overview

  9. The Molecular Apgar Score: A Key to Unlocking Evolutionary Principles

    PubMed Central

    Torday, John S.; Nielsen, Heber C.

    2017-01-01

    Apgar Score. As such, these molecular elements can be examined using a Molecular Apgar evaluation of keystone evolutionary events that predict successful evolutionary adaptation of physiologic functions necessary for neonatal transition and survival. PMID:28373969

  10. Control of quantum phenomena through evolutionary engineering: let the system do the thinking

    NASA Astrophysics Data System (ADS)

    Rabitz, Herschel H.; Bosacchi, Bruno

    2002-12-01

    We discuss a successful application of evolutionary algorithms and femtosecond pulse-shaping technology to the coherent control of quantum phenomena. After a brief review of the field of quantum control, we show how evolutionary algorithms provide an effective and, so far, the only general solution to the problem of managing the complex interplay of interference effects which characterize quantum phenomena. A representative list of experimental results is presented, and some directions for future developments are discussed. The success of evolutionary algorithms in quantum control is seen as a significant step in the evolution of computational intelligence, from evolutionary algorithms, to evolutionary programming, to evolutionary engineering, whereby a hardware system organizes itself and evolves on line to achieve a desired result.

  11. Engineering microbial systems to explore ecological and evolutionary dynamics.

    PubMed

    Tanouchi, Yu; Smith, Robert P; You, Lingchong

    2012-10-01

    A major goal of biological research is to provide a mechanistic understanding of diverse biological processes. To this end, synthetic biology offers a powerful approach, whereby biological questions can be addressed in a well-defined framework. By constructing simple gene circuits, such studies have generated new insights into the design principles of gene regulatory networks. Recently, this strategy has been applied to analyze ecological and evolutionary questions, where population-level interactions are critical. Here, we highlight recent development of such systems and discuss how they were used to address problems in ecology and evolutionary biology. As illustrated by these examples, synthetic ecosystems provide a unique platform to study ecological and evolutionary phenomena that are challenging to study in their natural contexts.

  12. Process Engineering with the Evolutionary Spiral Process Model. Version 01.00.01

    DTIC Science & Technology

    1992-12-01

    Appicv7c tcd 9N1 • ~92 12 28 13 PROCESS ENGINEERING WITH THE EVOLUTIONARY SPIRAL PROCESS MODEL DTI0QUA£T’•tN•L2•TEED 5/ SPC-92079-CMC r - -, - VERSION...Synthesis Process Model ............................................. 6 2.2.2 Process Activities...14 2.4 Sum m ary .................................................................... 15 3. EVOLUTIONARY SPIRAL PROCESS MODEL CONCEPTS

  13. Comment on “The Molecular Evolutionary Patterns of the Insulin/FOXO Signaling Pathway”

    PubMed Central

    Alvarez-Ponce, David; Aguadé, Montserrat; Rozas, Julio

    2013-01-01

    Letter to the Editor on Wang M, Wang Q, Wang Z, Zhang X, Pan Y. The molecular evolutionary patterns of the insulin/FOXO signaling pathway. Evol Bioinform. 2013;9:1–16. doi: 10.4137/EBO.S10539. PMID:23818748

  14. Molecular cytogenetics of the california condor: evolutionary and conservation implications.

    PubMed

    Modi, W S; Romanov, M; Green, E D; Ryder, O

    2009-01-01

    Evolutionary cytogenetic comparisons involved 5 species of birds (California condor, chicken, zebra finch, collared flycatcher and black stork) belonging to divergent taxonomic orders. Seventy-four clones from a condor BAC library containing 80 genes were mapped to condor chromosomes using FISH, and 15 clones containing 16 genes were mapped to the stork Z chromosome. Maps for chicken and finch were derived from genome sequence databases, and that for flycatcher from the published literature. Gene content and gene order were highly conserved when individual condor, chicken, and zebra finch autosomes were compared, confirming that these species largely retain karyotypes close to the ancestral condition for neognathous birds. However, several differences were noted: zebra finch chromosomes 1 and 1A are homologous to condor and chicken chromosomes 1, the CHUNK1 gene appears to have transposed on condor chromosome 1, condor chromosomes 4 and 9 and zebra finch chromosomes 4 and 4A are homologous to chicken chromosome arms 4q and 4p, and novel inversions on chromosomes 4, 12 and 13 were found. Condor and stork Z chromosome gene orders are collinear and differentiated by a series of inversions/transpositions when compared to chicken, zebra finch, or flycatcher; phylogenetic analyses suggest independent rearrangement along the chicken, finch, and flycatcher lineages.

  15. Bird-pollinated flowers in an evolutionary and molecular context.

    PubMed

    Cronk, Quentin; Ojeda, Isidro

    2008-01-01

    Evolutionary shifts to bird pollination (ornithophily) have occurred independently in many lineages of flowering plants. This shift affects many floral features, particularly those responsible for the attraction of birds, deterrence of illegitimate flower visitors (particularly bees), protection from vigorous foraging by birds, and accurate placement of pollen on bird's bodies. Red coloration appears to play a major role in both bee-deterrence and bird-attraction. Other mechanisms of bird-attraction include the production of abundant dilute nectar and the provision of secondary perches (for non-hovering birds). As a result of selection for similar phenotypic traits in unrelated bird-pollinated species, a floral syndrome of ornithophily can be recognized, and this review surveys the component floral traits. The strong convergent evolution evident in bird-pollinated flowers raises a question about the nature of the genetic mechanisms underlying such transitions and whether the same gene systems are involved in most cases. As yet there is too little information to answer this question. However, some promising model systems have been developed that include closely related bee and bird-pollinated flowers, such as Ipomoea, Mimulus, and Lotus. Recent studies of floral developmental genetics have identified numerous genes important in the development of the floral phenotype, which are also potential candidates for involvement in shifts between bee-pollination and bird pollination. As more whole-genome information becomes available, progress should be rapid.

  16. Molecular Biological Methods in Environmental Engineering.

    PubMed

    Zhang, Guocai; Wei, Li; Chang, Chein-Chi; Zhang, Yuhua; Wei, Dong

    2016-10-01

    Bacteria, acting as catalysts, perform the function of degrading pollutants. Molecular biological techniques play an important role in research on the community analysis, the composition and the functions of complex microbial communities. The development of secondary high-throughput pyrosequencing techiniques enhances the understanding of the composition of the microbial community. The literatures of 2015 indicated that 16S rDNA gene as genetic tag is still the important method for bacteria identification and classification. 454 high throughput sequencing and Illumina MiSeq sequencing have been the primary and widely recognized methods to analyze the microbial. This review will provide environmental engineers and microbiologists an overview of important advancements in molecular techniques and highlight the application of these methods in diverse environments.

  17. Interferons and viruses: an evolutionary arms race of molecular interactions

    PubMed Central

    Hoffmann, Hans-Heinrich; Schneider, William M.; Rice, Charles M.

    2015-01-01

    Over half a century has passed since interferons (IFNs) were discovered and shown to inhibit virus infection in cultured cells. Since then, researchers have steadily brought to light the molecular details of IFN signaling, catalogued their pleiotropic effects on cells, and harnessed their therapeutic potential for a variety of maladies. While advances have been plentiful, several fundamental questions have yet to be answered and much complexity remains to be unraveled. We explore the current knowledge surrounding four main questions: are type I IFN subtypes differentially produced in response to distinct pathogens? How are IFN subtypes distinguished by cells? What are the mechanisms and consequences of viral antagonism? Lastly, how can the IFN response be harnessed to improve vaccine efficacy? PMID:25704559

  18. Inspection planning development: An evolutionary approach using reliability engineering as a tool

    NASA Technical Reports Server (NTRS)

    Graf, David A.; Huang, Zhaofeng

    1994-01-01

    This paper proposes an evolutionary approach for inspection planning which introduces various reliability engineering tools into the process and assess system trade-offs among reliability, engineering requirement, manufacturing capability and inspection cost to establish an optimal inspection plan. The examples presented in the paper illustrate some advantages and benefits of the new approach. Through the analysis, reliability and engineering impacts due to manufacturing process capability and inspection uncertainty are clearly understood; the most cost effective and efficient inspection plan can be established and associated risks are well controlled; some inspection reductions and relaxations are well justified; and design feedbacks and changes may be initiated from the analysis conclusion to further enhance reliability and reduce cost. The approach is particularly promising as global competitions and customer quality improvement expectations are rapidly increasing.

  19. Sequence diversity and molecular evolutionary rates between buffalo and cattle.

    PubMed

    Moaeen-ud-Din, M; Bilal, G

    2015-02-01

    Identification of genes of importance regarding production traits in buffalo is impaired by a paucity of genomic resources. Choice to fill this gap is to exploit data available for cow. The cross-species application of comparative genomics tools is potential gear to investigate the buffalo genome. However, this is dependent on nucleotide sequences similarity. In this study, gene diversity between buffalo and cattle was determined using 86 gene orthologues. There was approximately 3% difference in all genes in terms of nucleotide diversity and 0.267 ± 0.134 in amino acids, indicating the possibility for successfully using cross-species strategies for genomic studies. There were significantly higher non-synonymous substitutions both in cattle and buffalo; however, there was similar difference in terms of dN- dS (4.414 versus 4.745) in buffalo and cattle, respectively. Higher rate of non-synonymous substitutions at similar level in buffalo and cattle indicated a similar positive selection pressure. Results for relative rate test were assessed with the chi-squared test. There was no significance difference on unique mutations between cattle and buffalo lineages at synonymous sites. However, there was a significance difference on unique mutations for non-synonymous sites, indicating ongoing mutagenic process that generates substitutional mutation at approximately the same rate at silent sites. Moreover, despite of common ancestry, our results indicate a different divergent time among genes of cattle and buffalo. This is the first demonstration that variable rates of molecular evolution may be present within the family Bovidae.

  20. Relationship between the column density distribution and evolutionary class of molecular clouds as viewed by ATLASGAL

    NASA Astrophysics Data System (ADS)

    Abreu-Vicente, J.; Kainulainen, J.; Stutz, A.; Henning, Th.; Beuther, H.

    2015-09-01

    We present the first study of the relationship between the column density distribution of molecular clouds within nearby Galactic spiral arms and their evolutionary status as measured from their stellar content. We analyze a sample of 195 molecular clouds located at distances below 5.5 kpc, identified from the ATLASGAL 870 μm data. We define three evolutionary classes within this sample: starless clumps, star-forming clouds with associated young stellar objects, and clouds associated with H ii regions. We find that the N(H2) probability density functions (N-PDFs) of these three classes of objects are clearly different: the N-PDFs of starless clumps are narrowest and close to log-normal in shape, while star-forming clouds and H ii regions exhibit a power-law shape over a wide range of column densities and log-normal-like components only at low column densities. We use the N-PDFs to estimate the evolutionary time-scales of the three classes of objects based on a simple analytic model from literature. Finally, we show that the integral of the N-PDFs, the dense gas mass fraction, depends on the total mass of the regions as measured by ATLASGAL: more massive clouds contain greater relative amounts of dense gas across all evolutionary classes. Appendices are available in electronic form at http://www.aanda.org

  1. Combining geometric morphometrics, molecular phylogeny, and micropaleontology to assess evolutionary patterns in Mallomonas (Synurophyceae: Heterokontophyta).

    PubMed

    Siver, P A; Wolfe, A P; Rohlf, F J; Shin, W; Jo, B Y

    2013-03-01

    Synurophytes, also known as scaled chrysophytes, are ecologically important algae that produce an array of siliceous structures upon which their taxonomy is based. Despite occupying a key position within the photosynthetic heterokonts, the evolutionary history of synurophytes remains poorly constrained. Here, modern and Middle Eocene siliceous scales of the morphotaxon Mallomonas insignis are used as a model to investigate synurophyte evolutionary patterns. Structural details of scale morphology were examined comparatively with scanning electron microscopy and scored for geometric morphometric analyses to assess the stability of shape characters. Although consistent size differences exist (modern scales are larger than Eocene counterparts), the populations cannot be differentiated on the basis of shape or microstructural detail, implying considerable evolutionary stasis in scale morphology. A time-calibrated relaxed molecular clock analysis using a three-gene concatenated data set (27 strains) suggests that the M. insignis lineage predates the available fossil record, having diverged from closest congeneric taxa in the Cretaceous (≥94 Ma). However, the molecular analysis also implies that considerable genetic variability is present within several morphotaxa of Mallomonas, implying that substantial genetic variability has arisen despite the retention of uniform scale morphologies, and resulting in the widespread occurrence of cryptic taxa. Results from the synurophyte lineage are consistent with the notion of protracted ghost ranges (>10 Ma) implied by the molecular phylogenies of other algal groups, together pointing to the paucity of the fossil record of these organisms on these timescales.

  2. The Design and Transformation of Biofundamentals: A Nonsurvey Introductory Evolutionary and Molecular Biology Course

    PubMed Central

    Klymkowsky, Michael W.; Rentsch, Jeremy D.; Begovic, Emina; Cooper, Melanie M.

    2016-01-01

    Many introductory biology courses amount to superficial surveys of disconnected topics. Often, foundational observations and the concepts derived from them and students’ ability to use these ideas appropriately are overlooked, leading to unrealistic expectations and unrecognized learning obstacles. The result can be a focus on memorization at the expense of the development of a meaningful framework within which to consider biological phenomena. About a decade ago, we began a reconsideration of what an introductory course should present to students and the skills they need to master. The original Web-based course’s design presaged many of the recommendations of the Vision and Change report; in particular, a focus on social evolutionary mechanisms, stochastic (evolutionary and molecular) processes, and core ideas (cellular continuity, evolutionary homology, molecular interactions, coupled chemical reactions, and molecular machines). Inspired by insights from the Chemistry, Life, the Universe & Everything general chemistry project, we transformed the original Web version into a (freely available) book with a more unified narrative flow and a set of formative assessments delivered through the beSocratic system. We outline how student responses to course materials are guiding future course modifications, in particular a more concerted effort at helping students to construct logical, empirically based arguments, explanations, and models. PMID:27909020

  3. The Design and Transformation of Biofundamentals: A Nonsurvey Introductory Evolutionary and Molecular Biology Course.

    PubMed

    Klymkowsky, Michael W; Rentsch, Jeremy D; Begovic, Emina; Cooper, Melanie M

    2016-01-01

    Many introductory biology courses amount to superficial surveys of disconnected topics. Often, foundational observations and the concepts derived from them and students' ability to use these ideas appropriately are overlooked, leading to unrealistic expectations and unrecognized learning obstacles. The result can be a focus on memorization at the expense of the development of a meaningful framework within which to consider biological phenomena. About a decade ago, we began a reconsideration of what an introductory course should present to students and the skills they need to master. The original Web-based course's design presaged many of the recommendations of the Vision and Change report; in particular, a focus on social evolutionary mechanisms, stochastic (evolutionary and molecular) processes, and core ideas (cellular continuity, evolutionary homology, molecular interactions, coupled chemical reactions, and molecular machines). Inspired by insights from the Chemistry, Life, the Universe & Everything general chemistry project, we transformed the original Web version into a (freely available) book with a more unified narrative flow and a set of formative assessments delivered through the beSocratic system. We outline how student responses to course materials are guiding future course modifications, in particular a more concerted effort at helping students to construct logical, empirically based arguments, explanations, and models.

  4. Engineering crystals by the strategy of molecular tectonics.

    PubMed

    Wuest, James D

    2005-12-21

    Detailed structures of molecular crystals cannot yet be predicted with consistent accuracy, but the strategy of molecular tectonics offers crystal engineers a powerful tool for designing molecules that are predisposed to form crystals with particular structural features and properties.

  5. Molecular systematics, zoogeography, and evolutionary ecology of the atlantic parrotfish genus Sparisoma.

    PubMed

    Bernardi, G; Robertson, D R; Clifton, K E; Azzurro, E

    2000-05-01

    Parrotfishes of the genus Sparisoma (Scaridae) are ecologically important tropical reef fishes restricted to the Atlantic Ocean. We investigated phylogenetic relationships among the eight extant species within this genus using mitochondrially encoded 12S and 16S ribosomal genes. Our molecular data support the view that (i) Sparisoma originated approximately 14-35 million years ago (mya), probably in the tropical western Atlantic, off Brazil; (ii) there have been at least four discrete bouts of cladogenesis within the genus, with the most recent one ( approximately 2.8-5.6 mya) involving four events in both the east and the west Atlantic and across the Atlantic; and (iii) the genus invaded the eastern Atlantic on two different occasions, probably by at least two different routes. The data also offer support for Bellwood's ideas concerning the evolutionary changes in adult feeding patterns and habitat use within Scarids. Specifically, they support the evolutionary position of the ecological traits of Sparisoma as intermediate within the family.

  6. Molecular trafficking in tissue engineered cartilage constructs

    NASA Astrophysics Data System (ADS)

    de Rosa, Enrica

    2005-03-01

    Tissue processing in vitro requires an effective trafficking of biologically active agents within three-dimensional constructs for induction of appropriate and enhanced cellular growth, biosynthesis and tissue remodeling. Moreover, nutrients and waste products need to move freely through the cellular constructs to minimize the presence of regions with necrotic and/or apoptotic cells. In tissue-engineered cartilage, for example, during the time of culture, cells seeded within the three-dimensional constructs lay-down their own extracellular matrix and this may lead to a heterogeneous distribution of transport properties both in time and space. In this work the diffusion coefficient of BSA and 500kDa dextran has been measured with FRAP thecnique in agarose gel chondrocytes constructs at different position and time during the culture. The diffusion coefficient of both molecular probes within the developing tissue well correlated with the ECM production and assembly. Moreover the comparision between BSA and dextran transport parameters revealed a selective hindrance effect of the neo tissue on high interacting molecules.

  7. Molecular phylogenetic relationships reveal contrasting evolutionary patterns in Gorgoniidae (Octocorallia) in the Eastern Pacific.

    PubMed

    Soler-Hurtado, M M; López-González, P J; Machordom, A

    2017-03-24

    The description and delimitation of species in an evolutionary framework is essential for understanding patterns of biodiversity and distribution, and in the assessment of conservation strategies for natural resources. This study seeks to clarify the evolutionary history and genetic variation within and between closely related octocoral species that are fundamental to benthic marine ecosystems for harbouring a high diversity of associated fauna. For our study system, we focused on members of the Gorgoniidae family in the Eastern Pacific, particularly of the Ecuadorian littoral, a less studied marine ecosystem. According to our results, the diagnosis of the genus Pacifigorgia is here amended to include species previously considered in the genus Leptogorgia. The genera Leptogorgia and Eugorgia are included within a single clade, and neither are recovered as monophyletic. In this case, according to the priority rule of the International Code of Zoological Nomenclature (ICZN), our proposal is to include the species considered in these two genera in Leptogorgia. In addition, we found evidence of interesting speciation patterns: morphological differentiation with no apparent genetic differentiation (in Pacifigorgia), and inconsistencies between mitochondrial and nuclear data that suggest a hybridisation phenomenon (in Leptogorgia). In the first case, recent radiation, ancient hybridisation, sympatric speciation, and in the second, reticulate evolution may have contributed to the evolutionary history of the studied taxa. Therefore, incongruences observed between morphological and molecular evidences in these octocorals, and in corals in general, may reveal the types of events/patterns that have influenced their evolution.

  8. Novel evolutionary engineering approach for accelerated utilization of glucose, xylose, and arabinose mixtures by engineered Saccharomyces cerevisiae strains.

    PubMed

    Wisselink, H Wouter; Toirkens, Maurice J; Wu, Qixiang; Pronk, Jack T; van Maris, Antonius J A

    2009-02-01

    Lignocellulosic feedstocks are thought to have great economic and environmental significance for future biotechnological production processes. For cost-effective and efficient industrial processes, complete and fast conversion of all sugars derived from these feedstocks is required. Hence, simultaneous or fast sequential fermentation of sugars would greatly contribute to the efficiency of production processes. One of the main challenges emerging from the use of lignocellulosics for the production of ethanol by the yeast Saccharomyces cerevisiae is efficient fermentation of D-xylose and L-arabinose, as these sugars cannot be used by natural S. cerevisiae strains. In this study, we describe the first engineered S. cerevisiae strain (strain IMS0003) capable of fermenting mixtures of glucose, xylose, and arabinose with a high ethanol yield (0.43 g g(-1) of total sugar) without formation of the side products xylitol and arabinitol. The kinetics of anaerobic fermentation of glucose-xylose-arabinose mixtures were greatly improved by using a novel evolutionary engineering strategy. This strategy included a regimen consisting of repeated batch cultivation with repeated cycles of consecutive growth in three media with different compositions (glucose, xylose, and arabinose; xylose and arabinose; and only arabinose) and allowed rapid selection of an evolved strain (IMS0010) exhibiting improved specific rates of consumption of xylose and arabinose. This evolution strategy resulted in a 40% reduction in the time required to completely ferment a mixture containing 30 g liter(-1) glucose, 15 g liter(-1) xylose, and 15 g liter(-1) arabinose.

  9. Molecular engineering of industrial enzymes: recent advances and future prospects.

    PubMed

    Yang, Haiquan; Li, Jianghua; Shin, Hyun-Dong; Du, Guocheng; Liu, Long; Chen, Jian

    2014-01-01

    Many enzymes are efficiently produced by microbes. However, the use of natural enzymes as biocatalysts has limitations such as low catalytic efficiency, low activity, and low stability, especially under industrial conditions. Many protein engineering technologies have been developed to modify natural enzymes and eliminate these limitations. Commonly used protein engineering strategies include directed evolution, site-directed mutagenesis, truncation, and terminal fusion. This review summarizes recent advances in the molecular engineering of industrial enzymes and discusses future prospects in this field. We expect this review to increase interest in and advance the molecular engineering of industrial enzymes.

  10. An evolutionary metabolic engineering approach for enhancing lipogenesis in Yarrowia lipolytica.

    PubMed

    Liu, Leqian; Pan, Anny; Spofford, Caitlin; Zhou, Nijia; Alper, Hal S

    2015-05-01

    Lipogenic organisms provide an ideal platform for biodiesel and oleochemical production. Through our previous rational metabolic engineering efforts, lipogenesis titers in Yarrowia lipolytica were significantly enhanced. However, the resulting strain still suffered from decreased biomass generation rates. Here, we employ a rapid evolutionary metabolic engineering approach linked with a floating cell enrichment process to improve lipogenesis rates, titers, and yields. Through this iterative process, we were able to ultimately improve yields from our prior strain by 55% to achieve production titers of 39.1g/L with upwards of 76% of the theoretical maximum yield of conversation. Isolated cells were saturated with up to 87% lipid content. An average specific productivity of 0.56g/L/h was achieved with a maximum instantaneous specific productivity of 0.89g/L/h during the lipid production phase in fermentation. Genomic sequencing of the evolved strains revealed a link between a decrease/loss of function mutation of succinate semialdehyde dehydrogenase, uga2, suggesting the importance of gamma-aminobutyric acid assimilation in lipogenesis. This linkage was validated through gene deletion experiments. This work presents an improved host strain that can serve as a platform for efficient oleochemical production.

  11. Phenotypic engineering of sperm-production rate confirms evolutionary predictions of sperm competition theory

    PubMed Central

    Sekii, Kiyono; Vizoso, Dita B.; Kuales, Georg; De Mulder, Katrien; Ladurner, Peter; Schärer, Lukas

    2013-01-01

    Sperm production is a key male reproductive trait and an important parameter in sperm competition theory. Under sperm competition, paternity success is predicted to depend strongly on male allocation to sperm production. Furthermore, because sperm production is inherently costly, individuals should economize in sperm expenditure, and conditional adjustment of the copulation frequency according to their sperm availability may be expected. However, experimental studies showing effects of sperm production on mating behaviour and paternity success have so far been scarce, mainly because sperm production is difficult to manipulate directly in animals. Here, we used phenotypic engineering to manipulate sperm-production rate, by employing dose-dependent RNA interference (RNAi) of a spermatogenesis-specific gene, macbol1, in the free-living flatworm Macrostomum lignano. We demonstrate (i) that our novel dose-dependent RNAi approach allows us to induce high variability in sperm-production rate; (ii) that a reduced sperm-production rate is associated with a decreased copulation frequency, suggesting conditional adjustment of mating behaviour; and (iii) that both sperm production and copulation frequency are important determinants of paternity success in a competitive situation, as predicted by sperm competition theory. Our study clearly documents the potential of phenotypic engineering via dose-dependent RNAi to test quantitative predictions of evolutionary theory. PMID:23446521

  12. 70% efficiency of bistate molecular machines explained by information theory, high dimensional geometry and evolutionary convergence

    PubMed Central

    Schneider, Thomas D.

    2010-01-01

    The relationship between information and energy is key to understanding biological systems. We can display the information in DNA sequences specifically bound by proteins by using sequence logos, and we can measure the corresponding binding energy. These can be compared by noting that one of the forms of the second law of thermodynamics defines the minimum energy dissipation required to gain one bit of information. Under the isothermal conditions that molecular machines function this is joules per bit ( is Boltzmann's constant and T is the absolute temperature). Then an efficiency of binding can be computed by dividing the information in a logo by the free energy of binding after it has been converted to bits. The isothermal efficiencies of not only genetic control systems, but also visual pigments are near 70%. From information and coding theory, the theoretical efficiency limit for bistate molecular machines is ln 2 = 0.6931. Evolutionary convergence to maximum efficiency is limited by the constraint that molecular states must be distinct from each other. The result indicates that natural molecular machines operate close to their information processing maximum (the channel capacity), and implies that nanotechnology can attain this goal. PMID:20562221

  13. Evolutionary dynamics of molecular markers during local adaptation: a case study in Drosophila subobscura

    PubMed Central

    2008-01-01

    Background Natural selection and genetic drift are major forces responsible for temporal genetic changes in populations. Furthermore, these evolutionary forces may interact with each other. Here we study the impact of an ongoing adaptive process at the molecular genetic level by analyzing the temporal genetic changes throughout 40 generations of adaptation to a common laboratory environment. Specifically, genetic variability, population differentiation and demographic structure were compared in two replicated groups of Drosophila subobscura populations recently sampled from different wild sources. Results We found evidence for a decline in genetic variability through time, along with an increase in genetic differentiation between all populations studied. The observed decline in genetic variability was higher during the first 14 generations of laboratory adaptation. The two groups of replicated populations showed overall similarity in variability patterns. Our results also revealed changing demographic structure of the populations during laboratory evolution, with lower effective population sizes in the early phase of the adaptive process. One of the ten microsatellites analyzed showed a clearly distinct temporal pattern of allele frequency change, suggesting the occurrence of positive selection affecting the region around that particular locus. Conclusion Genetic drift was responsible for most of the divergence and loss of variability between and within replicates, with most changes occurring during the first generations of laboratory adaptation. We also found evidence suggesting a selective sweep, despite the low number of molecular markers analyzed. Overall, there was a similarity of evolutionary dynamics at the molecular level in our laboratory populations, despite distinct genetic backgrounds and some differences in phenotypic evolution. PMID:18302790

  14. An engine for global plant diversity: highest evolutionary turnover and emigration in the American tropics

    PubMed Central

    Antonelli, Alexandre; Zizka, Alexander; Silvestro, Daniele; Scharn, Ruud; Cascales-Miñana, Borja; Bacon, Christine D.

    2015-01-01

    Understanding the processes that have generated the latitudinal biodiversity gradient and the continental differences in tropical biodiversity remains a major goal of evolutionary biology. Here we estimate the timing and direction of range shifts of extant flowering plants (angiosperms) between tropical and non-tropical zones, and into and out of the major tropical regions of the world. We then calculate rates of speciation and extinction taking into account incomplete taxonomic sampling. We use a recently published fossil calibrated phylogeny and apply novel bioinformatic tools to code species into user-defined polygons. We reconstruct biogeographic history using stochastic character mapping to compute relative numbers of range shifts in proportion to the number of available lineages through time. Our results, based on the analysis of c. 22,600 species and c. 20 million geo-referenced occurrence records, show no significant differences between the speciation and extinction of tropical and non-tropical angiosperms. This suggests that at least in plants, the latitudinal biodiversity gradient primarily derives from other factors than differential rates of diversification. In contrast, the outstanding species richness found today in the American tropics (the Neotropics), as compared to tropical Africa and tropical Asia, is associated with significantly higher speciation and extinction rates. This suggests an exceedingly rapid evolutionary turnover, i.e., Neotropical species being formed and replaced by one another at unparalleled rates. In addition, tropical America stands out from other continents by having “pumped out” more species than it received through most of the last 66 million years. These results imply that the Neotropics have acted as an engine for global plant diversity. PMID:25904934

  15. An engine for global plant diversity: highest evolutionary turnover and emigration in the American tropics.

    PubMed

    Antonelli, Alexandre; Zizka, Alexander; Silvestro, Daniele; Scharn, Ruud; Cascales-Miñana, Borja; Bacon, Christine D

    2015-01-01

    Understanding the processes that have generated the latitudinal biodiversity gradient and the continental differences in tropical biodiversity remains a major goal of evolutionary biology. Here we estimate the timing and direction of range shifts of extant flowering plants (angiosperms) between tropical and non-tropical zones, and into and out of the major tropical regions of the world. We then calculate rates of speciation and extinction taking into account incomplete taxonomic sampling. We use a recently published fossil calibrated phylogeny and apply novel bioinformatic tools to code species into user-defined polygons. We reconstruct biogeographic history using stochastic character mapping to compute relative numbers of range shifts in proportion to the number of available lineages through time. Our results, based on the analysis of c. 22,600 species and c. 20 million geo-referenced occurrence records, show no significant differences between the speciation and extinction of tropical and non-tropical angiosperms. This suggests that at least in plants, the latitudinal biodiversity gradient primarily derives from other factors than differential rates of diversification. In contrast, the outstanding species richness found today in the American tropics (the Neotropics), as compared to tropical Africa and tropical Asia, is associated with significantly higher speciation and extinction rates. This suggests an exceedingly rapid evolutionary turnover, i.e., Neotropical species being formed and replaced by one another at unparalleled rates. In addition, tropical America stands out from other continents by having "pumped out" more species than it received through most of the last 66 million years. These results imply that the Neotropics have acted as an engine for global plant diversity.

  16. Evolutionary and molecular analysis of Dof transcription factors identified a conserved motif for intercellular protein trafficking.

    PubMed

    Chen, Huan; Ahmad, Munawar; Rim, Yeonggil; Lucas, William J; Kim, Jae-Yean

    2013-06-01

    · Cell-to-cell trafficking of transcription factors (TFs) has been shown to play an important role in the regulation of plant developmental events, but the evolutionary relationship between cell-autonomous and noncell-autonomous (NCA) TFs remains elusive. · AtDof4.1, named INTERCELLULAR TRAFFICKING DOF 1 (ITD1), was chosen as a representative NCA member to explore this evolutionary relationship. Using domain structure-function analyses and swapping studies, we examined the cell-to-cell trafficking of plant-specific Dof TF family members across Arabidopsis and other species. · We identified a conserved intercellular trafficking motif (ITM) that is necessary and sufficient for selective cell-to-cell trafficking and can impart gain-of-function cell-to-cell movement capacity to an otherwise cell-autonomous TF. The functionality of related motifs from Dof members across the plant kingdom extended, surprisingly, to a unicellular alga that lacked plasmodesmata. By contrast, the algal homeodomain related to the NCA KNOX homeodomain was either inefficient or unable to impart such cell-to-cell movement function. · The Dof ITM appears to predate the evolution of selective plasmodesmal trafficking in the plant kingdom, which may well have acted as a molecular template for the evolution of Dof proteins as NCA TFs. However, the ability to efficiently traffic for KNOX homeodomain (HD) proteins may have been acquired during the evolution of early nonvascular plants.

  17. Molecular systematics and evolutionary history of the genus Carabus (Col. Carabidae).

    PubMed

    Deuve, Thierry; Cruaud, Astrid; Genson, Gwenaëlle; Rasplus, Jean-Yves

    2012-10-01

    Despite the number of evolutionary, ecological and conservation studies that are conducted on Carabus, the global evolutionary history of the genus remains poorly understood. Here, we analysed 7.5 kilobases of DNA sequence data (six mitochondrial and four nuclear genes) from a worldwide sample of 45% of the known subgenera (99 species and 14 subspecies). We compared the nuclear and mitochondrial phylogenies obtained from Maximum likelihood and Bayesian analyses through topological tests of congruence and dating analyses. Our results mostly corroborate the monophyly of the morphological subgroups of Carabus. However, current morphological and molecular data appear unable to accurately infer the deep branchings within the genus. We show that Carabus originated ca. 16.7-25.1 Ma, approximately 25 Myr later than previously estimated. Major groups of Carabus are subdivided into clades that diverged from each other in a relatively short period of time around 10 Ma (6.6-14.8). This time frame suggests that the present-day distribution of Carabus subgroups may be explained by isolation resulting from Eurasian forest fragmentation brought on by Miocene climate changes and by mountain orogenesis. Finally, we highlight several conflicts between mitochondrial and nuclear topologies that may be explained by mitochondrial introgression.

  18. B13+: Photodriven Molecular Wankel Engine

    SciTech Connect

    Zhang, Jin; Sergeeva, Alina P.; Sparta, Manuel; Alexandrova, Anastassia N.

    2012-07-09

    Synthetic molecular motors that are capable of delivering controlled movement upon energy input are one of the key building blocks in nanomachinery. The major energy sources of molecular motors are from chemical reactions, photon beams, or electric current, which are converted into mechanical forces through the excitation of the electronic states of the molecule. The energy scale of the electronic excitation is normally two orders of magnitude larger than the molecular vibrational frequencies. To reduce the heat dissipation and increase the energy utilization efficiency, a motor running purely on the electronic ground-state (GS) potential energy surfaces is highly desirable.

  19. Evolutionary traces decode molecular mechanism behind fast pace of myosin XI

    PubMed Central

    2011-01-01

    Background Cytoplasmic class XI myosins are the fastest processive motors known. This class functions in high-velocity cytoplasmic streaming in various plant cells from algae to angiosperms. The velocities at which they process are ten times faster than its closest class V homologues. Results To provide sequence determinants and structural rationale for the molecular mechanism of this fast pace myosin, we have compared the sequences from myosin class V and XI through Evolutionary Trace (ET) analysis. The current study identifies class-specific residues of myosin XI spread over the actin binding site, ATP binding site and light chain binding neck region. Sequences for ET analysis were accumulated from six plant genomes, using literature based text search and sequence searches, followed by triple validation viz. CDD search, string-based searches and phylogenetic clustering. We have identified nine myosin XI genes in sorghum and seven in grape by sequence searches. Both the plants possess one gene product each belonging to myosin type VIII as well. During this process, we have re-defined the gene boundaries for three sorghum myosin XI genes using fgenesh program. Conclusion Molecular modelling and subsequent analysis of putative interactions involving these class-specific residues suggest a structural basis for the molecular mechanism behind high velocity of plant myosin XI. We propose a model of a more flexible switch I region that contributes to faster ADP release leading to high velocity movement of the algal myosin XI. PMID:21942950

  20. Molecular phylogeny of the Indian Ocean Terpsiphone paradise flycatchers: undetected evolutionary diversity revealed amongst island populations.

    PubMed

    Bristol, Rachel M; Fabre, Pierre-Henri; Irestedt, Martin; Jønsson, Knud A; Shah, Nirmal J; Tatayah, Vikash; Warren, Ben H; Groombridge, Jim J

    2013-05-01

    We construct a molecular phylogeny of Terpsiphone flycatchers of the Indian Ocean and use this to investigate their evolutionary relationships. A total of 4.4 kb of mitochondrial (cyt-b, ND3, ND2, control region) and nuclear (G3PDH, MC1R) sequence data were obtained from all species, sub-species and island populations of the region. Colonisation of the western Indian Ocean has been within the last two million years and greatly postdates the formation of the older islands of the region. A minimum of two independent continent-island colonisation events must have taken place in order to explain the current distribution and phylogenetic placement of Terpsiphone in this region. While five well-diverged Indian Ocean clades are detected, the relationship between them is unclear. Short intermodal branches are indicative of rapid range expansion across the region, masking exact routes and chronology of colonisation. The Indian Ocean Terpsiphone taxa fall into five well supported clades, two of which (the Seychelles paradise flycatcher and the Mascarene paradise flycatcher) correspond with currently recognised species, whilst a further three (within the Madagascar paradise flycatcher) are not entirely predicted by taxonomy, and are neither consistent with distance-based nor island age-based models of colonisation. We identify the four non-Mascarene clades as Evolutionarily Significant Units (ESUs), while the Mascarene paradise flycatcher contains two ESUs corresponding to the Mauritius and Réunion subspecies. All six ESUs are sufficiently diverged to be worthy of management as if they were separate species. This phylogenetic reconstruction highlights the importance of sub-specific molecular phylogenetic reconstructions in complex island archipelago settings in clarifying phylogenetic history and ESUs that may otherwise be overlooked and inadvertently lost. Our phylogenetic reconstruction has identified hidden pockets of evolutionary distinctiveness, which provide a valuable

  1. Evolutionary Engineering Improves Tolerance for Replacement Jet Fuels in Saccharomyces cerevisiae

    PubMed Central

    Brennan, Timothy C. R.; Williams, Thomas C.; Schulz, Benjamin L.; Palfreyman, Robin W.; Nielsen, Lars K.

    2015-01-01

    Monoterpenes are liquid hydrocarbons with applications ranging from flavor and fragrance to replacement jet fuel. Their toxicity, however, presents a major challenge for microbial synthesis. Here we evolved limonene-tolerant Saccharomyces cerevisiae strains and sequenced six strains across the 200-generation evolutionary time course. Mutations were found in the tricalbin proteins Tcb2p and Tcb3p. Genomic reconstruction in the parent strain showed that truncation of a single protein (tTcb3p1-989), but not its complete deletion, was sufficient to recover the evolved phenotype improving limonene fitness 9-fold. tTcb3p1-989 increased tolerance toward two other monoterpenes (β-pinene and myrcene) 11- and 8-fold, respectively, and tolerance toward the biojet fuel blend AMJ-700t (10% cymene, 50% limonene, 40% farnesene) 4-fold. tTcb3p1-989 is the first example of successful engineering of phase tolerance and creates opportunities for production of the highly toxic C10 alkenes in yeast. PMID:25746998

  2. Molecular biomimetics: nanotechnology and bionanotechnology using genetically engineered peptides.

    PubMed

    Tamerler, Candan; Sarikaya, Mehmet

    2009-05-13

    Nature provides inspiration for designing materials and systems that derive their functions from highly organized structures. Biological hard tissues are hybrid materials having inorganics within a complex organic matrix, the molecular scaffold controlling the inorganic structures. Biocomposites incorporate both biomacromolecules such as proteins, lipids and polysaccharides, and inorganic materials, such as hydroxyapatite, silica, magnetite and calcite. The ordered organization of hierarchical structures in organisms begins via the molecular recognition of inorganics by proteins that control interactions and is followed by the highly efficient self-assembly across scales. Following the molecular biological principle, proteins could also be used in controlling materials formation in practical engineering via self-assembled, hybrid, functional materials structures. In molecular biomimetics, material-specific peptides could be the key in the molecular engineering of biology-inspired materials. With the recent developments of nanoscale engineering in physical sciences and the advances in molecular biology, we now combine genetic tools with synthetic nanoscale constructs to create a novel methodology. We first genetically select and/or design peptides with specific binding to functional solids, tailor their binding and assembly characteristics, develop bifunctional peptide/protein genetic constructs with both material binding and biological activity, and use these as molecular synthesizers, erectors and assemblers. Here, we give an overview of solid-binding peptides as novel molecular agents coupling bio- and nanotechnology.

  3. Engineering molecular crystals with abnormally weak cohesion.

    PubMed

    Maly, Kenneth E; Gagnon, Eric; Wuest, James D

    2011-05-14

    Adding astutely placed methyl groups to hexaphenylbenzene increases molecular weight but simultaneously weakens key C-H···π interactions, thereby leading to decreased enthalpies of sublimation and showing that materials with abnormally weak cohesion can be made by identifying and then obstructing interactions that help control association.

  4. Evolutionary animation: How do molecular phylogenies compare to Mayr's reconstruction of speciation patterns in the sea?

    PubMed Central

    Palumbi, Stephen R.; Lessios, H. A.

    2005-01-01

    Ernst Mayr used the geography of closely related species in various stages of increasing divergence to “animate” the process of geographic, or allopatric, speciation. This approach was applied to a wide set of taxa, and a seminal paper by Mayr used it to explore speciation patterns in tropical sea urchins. Since then, taxonomic information in several of these genera has been augmented by detailed molecular phylogenies. We compare Mayr's animation with the phylogenies of eight sea urchin genera placed by Mayr into four speciation groups. True to Mayr's predictions, early-stage genera have on average lower species divergence and more polytypic species than genera in later stages. For six of these genera, we also have information about the evolution of the gamete recognition protein bindin, which is critical to reproductive isolation. These comparisons show that later-stage genera with many sympatric species tend to be those with rapid bindin evolution. By contrast, early-stage genera with few sympatric species are not necessarily earlier in the divergence process; they happen to be those with slow rates of bindin evolution. These results show that the rate of speciation in sea urchins does not only depend on the steady accumulation of genome divergence over time, but also on the rate of evolution of gamete recognition proteins. The animation method used by Mayr is generally supported by molecular phylogenies. However, the existence of multiple rates in the acquisition of reproductive isolation complicates placement of different genera in an evolutionary series. PMID:15851681

  5. Unraveling the evolutionary radiation of the families of the Zingiberales using morphological and molecular evidence.

    PubMed

    Kress, W J; Prince, L M; Hahn, W J; Zimmer, E A

    2001-01-01

    The Zingiberales are a tropical group of monocotyledons that includes bananas, gingers, and their relatives. The phylogenetic relationships among the eight families currently recognized are investigated here by using parsimony and maximum likelihood analyses of four character sets: morphological features (1), and sequence data of the (2) chloroplast rbcL gene, (3) chloroplast atpB gene, and (4) nuclear 18S rDNA gene. Outgroups for the analyses include the closely related Commelinaceae + Philydraceae + Haemodoraceae + Pontederiaceae + Hanguanaceae as well as seven more distantly related monocots and paleoherbs. Only slightly different estimates of evolutionary relationships result from the analysis of each character set. The morphological data yield a single fully resolved most-parsimonious tree. None of the molecular datasets alone completely resolves interfamilial relationships. The analyses of the combined molecular dataset provide more resolution than do those of individual genes, and the addition of the morphological data provides a well-supported estimate of phylogenetic relationships: (Musaceae ((Strelitziaceae, Lowiaceae) (Heliconiaceae ((Zingiberaceae, Costaceae) (Cannaceae, Marantaceae))))). Evidence from branch lengths in the parsimony analyses and from the fossil record suggests that the Zingiberales originated in the Early Cretaceous and underwent a rapid radiation in the mid-Cretaceous, by which time most extant family lineages had diverged.

  6. Molecular phylogeny of echiuran worms (Phylum: Annelida) reveals evolutionary pattern of feeding mode and sexual dimorphism.

    PubMed

    Goto, Ryutaro; Okamoto, Tomoko; Ishikawa, Hiroshi; Hamamura, Yoichi; Kato, Makoto

    2013-01-01

    The Echiura, or spoon worms, are a group of marine worms, most of which live in burrows in soft sediments. This annelid-like animal group was once considered as a separate phylum because of the absence of segmentation, although recent molecular analyses have placed it within the annelids. In this study, we elucidate the interfamily relationships of echiuran worms and their evolutionary pattern of feeding mode and sexual dimorphism, by performing molecular phylogenetic analyses using four genes (18S, 28S, H3, and COI) of representatives of all extant echiuran families. Our results suggest that Echiura is monophyletic and comprises two unexpected groups: [Echiuridae+Urechidae+Thalassematidae] and [Bonelliidae+Ikedidae]. This grouping agrees with the presence/absence of marked sexual dimorphism involving dwarf males and the paired/non-paired configuration of the gonoducts (genital sacs). Furthermore, the data supports the sister group relationship of Echiuridae and Urechidae. These two families share the character of having anal chaetae rings around the posterior trunk as a synapomorphy. The analyses also suggest that deposit feeding is a basal feeding mode in echiurans and that filter feeding originated once in the common ancestor of Urechidae. Overall, our results contradict the currently accepted order-level classification, especially in that Echiuroinea is polyphyletic, and provide novel insights into the evolution of echiuran worms.

  7. Molecular engineering of antibodies for therapeutic and diagnostic purposes

    PubMed Central

    Ducancel, Frédéric; Muller, Bruno H.

    2012-01-01

    During the past ten years, monoclonal antibodies (mAbs) have taken center stage in the field of targeted therapy and diagnosis. This increased interest in mAbs is due to their binding accuracy (affinity and specificity) together with the original molecular and structural rules that govern interactions with their cognate antigen. In addition, the effector properties of antibodies constitute a second major advantage associated with their clinical use. The development of molecular and structural engineering and more recently of in vitro evolution of antibodies has opened up new perspectives in the de novo design of antibodies more adapted to clinical and diagnostic use. Thus, efforts are regularly made by researchers to improve or modulate antibody recognition properties, to adapt their pharmacokinetics, engineer their stability, and control their immunogenicity. This review presents the latest molecular engineering results on mAbs with therapeutic and diagnostic applications. PMID:22684311

  8. Molecular phylogeny and evolutionary dynamics of influenza A nonstructural (NS) gene.

    PubMed

    Xu, Jianpeng; Zhong, Haizhen A; Madrahimov, Alex; Helikar, Tomáš; Lu, Guoqing

    2014-03-01

    While the nonstructural gene (NS) of the influenza A virus plays a crucial role in viral virulence and replication, the complete understanding of its molecular phylogeny and evolutionary dynamics remains lacking. In this study, the phylogenetic analysis of 7581 NS sequences revealed ten distinct lineages within alleles A and B: three host-specific (human, classical swine and equine), two reassortment-originated (A(H1N1)pdm09 and triple reassortment swine), one transmission-originated (Eurasian swine), and two geographically isolated avian (Eurasian/Oceanian and North American) for allele A and two geographically isolated avian (Eurasian/Oceanian and North American) for allele B. The average nucleotide substitution rates of the lineages range from 1.24×10(-3) (equine) to 4.34×10(-3) (A(H1N1)pdm09) substitutions per site per year. The selection pressure analysis demonstrated that the dN/dS ratio of the NS gene in A(H1N1)pdm09 lineage was higher than its closely related triple reassortant swine, which could be attributed to the adaptation to the new host and/or intensive surveillance after the inter-species transmission from swine to human. The positive selection sites were found in all lineages except the equine lineage and mostly in the NS1 region. The positive selection sites 22, 26, 226, 227 and 230 of the human lineage are significant because these residues participate in either forming the dimerization of the two RNA binding domain (RBD) monomers or blocking the replication of host genes. Residues at position 171 provide hydrophobic interactions with hydrophobic residues at p85β and thus induce viral cell growth. The lineages and evolutionary dynamics of influenza A NS gene obtained in this study, along with the studies of other gene segments, are expected to improve the early detection of new viruses and thus have the potential to enhance influenza surveillance.

  9. Molecular engineering of semiconductor surfaces and devices.

    PubMed

    Ashkenasy, Gonen; Cahen, David; Cohen, Rami; Shanzer, Abraham; Vilan, Ayelet

    2002-02-01

    Grafting organic molecules onto solid surfaces can transfer molecular properties to the solid. We describe how modifications of semiconductor or metal surfaces by molecules with systematically varying properties can lead to corresponding trends in the (electronic) properties of the resulting hybrid (molecule + solid) materials and devices made with them. Examples include molecule-controlled diodes and sensors, where the electrons need not to go through the molecules (action at a distance), suggesting a new approach to molecule-based electronics.

  10. Cell Engineering and Molecular Pharming for Biopharmaceuticals

    PubMed Central

    Abdullah, M.A; Rahmah, Anisa ur; Sinskey, A.J; Rha, C.K

    2008-01-01

    Biopharmaceuticals are often produced by recombinant E. coli or mammalian cell lines. This is usually achieved by the introduction of a gene or cDNA coding for the protein of interest into a well-characterized strain of producer cells. Naturally, each recombinant production system has its own unique advantages and disadvantages. This paper examines the current practices, developments, and future trends in the production of biopharmaceuticals. Platform technologies for rapid screening and analyses of biosystems are reviewed. Strategies to improve productivity via metabolic and integrated engineering are also highlighted. PMID:19662143

  11. Mesoscopic Fluorescence Molecular Tomography for Evaluating Engineered Tissues

    PubMed Central

    Ozturk, Mehmet S.; Chen, Chao-Wei; Ji, Robin; Zhao, Lingling; Nguyen, Bao-Ngoc B.; Fisher, John P.; Chen, Yu; Intes, Xavier

    2015-01-01

    Optimization of regenerative medicine strategies includes the design of biomaterials, development of cell-seeding methods, and control of cell-biomaterial interactions within the engineered tissues. Among these steps, one paramount challenge is to non-destructively image the engineered tissues in their entirety to assess structure, function, and molecular expression. It is especially important to be able to enable cell phenotyping and monitor the distribution and migration of cells throughout the bulk scaffold. Advanced fluorescence microscopic techniques are commonly employed to perform such tasks; however, they are limited to superficial examination of tissue constructs. Therefore, the field of tissue engineering and regenerative medicine would greatly benefit from the development of molecular imaging techniques which are capable of non-destructive imaging of three-dimensional cellular distribution and maturation within a tissue-engineered scaffold beyond the limited depth of current microscopic techniques. In this review, we focus on an emerging depth-resolved optical mesoscopic imaging technique, termed Laminar Optical Tomography (LOT) or Mesoscopic Fluorescence Molecular Tomography (MFMT), which enables longitudinal imaging of cellular distribution in thick tissue engineering constructs at depths of a few millimeters and with relatively high resolution. The physical principle, image formation, and instrumentation of LOT/MFMT systems are introduced. Representative applications in tissue engineering include imaging the distribution of human mesenchymal stem cells (hMSCs) embedded in hydrogels, imaging of bio-printed tissues, and in vivo applications. PMID:26645079

  12. A molecular phylogeny of nephilid spiders: evolutionary history of a model lineage.

    PubMed

    Kuntner, Matjaž; Arnedo, Miquel A; Trontelj, Peter; Lokovšek, Tjaša; Agnarsson, Ingi

    2013-12-01

    The pantropical orb web spider family Nephilidae is known for the most extreme sexual size dimorphism among terrestrial animals. Numerous studies have made Nephilidae, particularly Nephila, a model lineage in evolutionary research. However, a poorly understood phylogeny of this lineage, relying only on morphology, has prevented thorough evolutionary syntheses of nephilid biology. We here use three nuclear and five mitochondrial genes for 28 out of 40 nephilid species to provide a more robust nephilid phylogeny and infer clade ages in a fossil-calibrated Bayesian framework. We complement the molecular analyses with total evidence analysis including morphology. All analyses find strong support for nephilid monophyly and exclusivity and the monophyly of the genera Herennia and Clitaetra. The inferred phylogenetic structure within Nephilidae is novel and conflicts with morphological phylogeny and traditional taxonomy. Nephilengys species fall into two clades, one with Australasian species (true Nephilengys) as sister to Herennia, and another with Afrotropical species (Nephilingis Kuntner new genus) as sister to a clade containing Clitaetra plus most currently described Nephila. Surprisingly, Nephila is also diphyletic, with true Nephila containing N. pilipes+N. constricta, and the second clade with all other species sister to Clitaetra; this "Nephila" clade is further split into an Australasian clade that also contains the South American N. sexpunctata and the Eurasian N. clavata, and an African clade that also contains the Panamerican N. clavipes. An approximately unbiased test constraining the monophyly of Nephilengys, Nephila, and Nephilinae (Nephila, Nephilengys, Herennia), respectively, rejected Nephilengys monophyly, but not that of Nephila and Nephilinae. Further data are therefore necessary to robustly test these two new, but inconclusive findings, and also to further test the precise placement of Nephilidae within the Araneoidea. For divergence date estimation

  13. Molecular recognition in myxobacterial outer membrane exchange: Functional, social and evolutionary implications

    PubMed Central

    Wall, Daniel

    2014-01-01

    Summary Through cooperative interactions, bacteria can build multicellular communities. To ensure that productive interactions occur, bacteria must recognize their neighbors and respond accordingly. Molecular recognition between cells is thus a fundamental behavior, and in bacteria important discoveries have been made. This MicroReview focuses on a recently described recognition system in myxobacteria that is governed by a polymorphic cell surface receptor called TraA. TraA regulates outer membrane exchange (OME), whereby myxobacterial cells transiently fuse their OMs to efficiently transfer proteins and lipids between cells. Unlike other transport systems, OME is rather indiscriminate in what OM goods are transferred. In contrast, the recognition of partnering cells is discriminatory and only occurs between cells that bear identical or closely related TraA proteins. Therefore TraA functions in kin recognition and, in turn, OME helps regulate social interactions between myxobacteria. Here, I discuss and speculate on the social and evolutionary implications of OME and suggest it helps to guide their transition from free-living cells into coherent and functional populations. PMID:24261719

  14. Molecular, genetic and evolutionary analysis of a paracentric inversion in Arabidopsis thaliana.

    PubMed

    Fransz, Paul; Linc, Gabriella; Lee, Cheng-Ruei; Aflitos, Saulo Alves; Lasky, Jesse R; Toomajian, Christopher; Ali, Hoda; Peters, Janny; van Dam, Peter; Ji, Xianwen; Kuzak, Mateusz; Gerats, Tom; Schubert, Ingo; Schneeberger, Korbinian; Colot, Vincent; Martienssen, Rob; Koornneef, Maarten; Nordborg, Magnus; Juenger, Thomas E; de Jong, Hans; Schranz, Michael E

    2016-10-01

    Chromosomal inversions can provide windows onto the cytogenetic, molecular, evolutionary and demographic histories of a species. Here we investigate a paracentric 1.17-Mb inversion on chromosome 4 of Arabidopsis thaliana with nucleotide precision of its borders. The inversion is created by Vandal transposon activity, splitting an F-box and relocating a pericentric heterochromatin segment in juxtaposition with euchromatin without affecting the epigenetic landscape. Examination of the RegMap panel and the 1001 Arabidopsis genomes revealed more than 170 inversion accessions in Europe and North America. The SNP patterns revealed historical recombinations from which we infer diverse haplotype patterns, ancient introgression events and phylogenetic relationships. We find a robust association between the inversion and fecundity under drought. We also find linkage disequilibrium between the inverted region and the early flowering Col-FRIGIDA allele. Finally, SNP analysis elucidates the origin of the inversion to South-Eastern Europe approximately 5000 years ago and the FRI-Col allele to North-West Europe, and reveals the spreading of a single haplotype to North America during the 17th to 19th century. The 'American haplotype' was identified from several European localities, potentially due to return migration.

  15. Molecular phylogenetics and evolutionary history of ariid catfishes revisited: a comprehensive sampling

    PubMed Central

    Betancur-R, Ricardo

    2009-01-01

    Background Ariids or sea catfishes are one of the two otophysan fish families (out of about 67 families in four orders) that inhabit mainly marine and brackish waters (although some species occur strictly in fresh waters). The group includes over 150 species placed in ~29 genera and two subfamilies (Galeichthyinae and Ariinae). Despite their global distribution, ariids are largely restricted to the continental shelves due in part to their specialized reproductive behavior (i.e., oral incubation). Thus, among marine fishes, ariids offer an excellent opportunity for inferring historical biogeographic scenarios. Phylogenetic hypotheses available for ariids have focused on restricted geographic areas and comprehensive phylogenies are still missing. This study inferred phylogenetic hypotheses for 123 ariid species in 28 genera from different biogeographic provinces using both mitochondrial and nuclear sequences (up to ~4 kb). Results While the topologies obtained support the monophyly of basal groups, up to ten genera validated in previous morphological studies were incongruent with the molecular topologies. New World ariines were recovered as paraphyletic and Old World ariines were grouped into a well-supported clade that was further divided into subclades mainly restricted to major Gondwanan landmasses. A general area cladogram derived from the area cladograms of ariines and three other fish groups was largely congruent with the geological area cladogram of Gondwana. Nonetheless, molecular clock estimations provided variable results on the timing of ariine diversification (~105-41 mya). Conclusion This study provides the most comprehensive phylogeny of sea catfishes to date and highlights the need for re-assessment of their classification. While from a topological standpoint the evolutionary history of ariines is mostly congruent with vicariance associated with the sequence of events during Gondwanan fragmentation, ambiguous divergence time estimations hinders

  16. Beyond fossil calibrations: realities of molecular clock practices in evolutionary biology

    PubMed Central

    Hipsley, Christy A.; Müller, Johannes

    2014-01-01

    Molecular-based divergence dating methods, or molecular clocks, are the primary neontological tool for estimating the temporal origins of clades. While the appropriate use of vertebrate fossils as external clock calibrations has stimulated heated discussions in the paleontological community, less attention has been given to the quality and implementation of other calibration types. In lieu of appropriate fossils, many studies rely on alternative sources of age constraints based on geological events, substitution rates and heterochronous sampling, as well as dates secondarily derived from previous analyses. To illustrate the breadth and frequency of calibration types currently employed, we conducted a literature survey of over 600 articles published from 2007 to 2013. Over half of all analyses implemented one or more fossil dates as constraints, followed by geological events and secondary calibrations (15% each). Vertebrate taxa were subjects in nearly half of all studies, while invertebrates and plants together accounted for 43%, followed by viruses, protists and fungi (3% each). Current patterns in calibration practices were disproportionate to the number of discussions on their proper use, particularly regarding plants and secondarily derived dates, which are both relatively neglected in methodological evaluations. Based on our survey, we provide a comprehensive overview of the latest approaches in clock calibration, and outline strengths and weaknesses associated with each. This critique should serve as a call to action for researchers across multiple communities, particularly those working on clades for which fossil records are poor, to develop their own guidelines regarding selection and implementation of alternative calibration types. This issue is particularly relevant now, as time-calibrated phylogenies are used for more than dating evolutionary origins, but often serve as the backbone of investigations into biogeography, diversity dynamics and rates of

  17. Beyond fossil calibrations: realities of molecular clock practices in evolutionary biology.

    PubMed

    Hipsley, Christy A; Müller, Johannes

    2014-01-01

    Molecular-based divergence dating methods, or molecular clocks, are the primary neontological tool for estimating the temporal origins of clades. While the appropriate use of vertebrate fossils as external clock calibrations has stimulated heated discussions in the paleontological community, less attention has been given to the quality and implementation of other calibration types. In lieu of appropriate fossils, many studies rely on alternative sources of age constraints based on geological events, substitution rates and heterochronous sampling, as well as dates secondarily derived from previous analyses. To illustrate the breadth and frequency of calibration types currently employed, we conducted a literature survey of over 600 articles published from 2007 to 2013. Over half of all analyses implemented one or more fossil dates as constraints, followed by geological events and secondary calibrations (15% each). Vertebrate taxa were subjects in nearly half of all studies, while invertebrates and plants together accounted for 43%, followed by viruses, protists and fungi (3% each). Current patterns in calibration practices were disproportionate to the number of discussions on their proper use, particularly regarding plants and secondarily derived dates, which are both relatively neglected in methodological evaluations. Based on our survey, we provide a comprehensive overview of the latest approaches in clock calibration, and outline strengths and weaknesses associated with each. This critique should serve as a call to action for researchers across multiple communities, particularly those working on clades for which fossil records are poor, to develop their own guidelines regarding selection and implementation of alternative calibration types. This issue is particularly relevant now, as time-calibrated phylogenies are used for more than dating evolutionary origins, but often serve as the backbone of investigations into biogeography, diversity dynamics and rates of

  18. Traditional Taxonomic Groupings Mask Evolutionary History: A Molecular Phylogeny and New Classification of the Chromodorid Nudibranchs

    PubMed Central

    Johnson, Rebecca Fay; Gosliner, Terrence M.

    2012-01-01

    Chromodorid nudibranchs (16 genera, 300+ species) are beautiful, brightly colored sea slugs found primarily in tropical coral reef habitats and subtropical coastal waters. The chromodorids are the most speciose family of opisthobranchs and one of the most diverse heterobranch clades. Chromodorids have the potential to be a model group with which to study diversification, color pattern evolution, are important source organisms in natural products chemistry and represent a stunning and widely compelling example of marine biodiversity. Here, we present the most complete molecular phylogeny of the chromodorid nudibranchs to date, with a broad sample of 244 specimens (142 new), representing 157 (106 new) chromodorid species, four actinocylcid species and four additional dorid species utilizing two mitochondrial markers (16s and COI). We confirmed the monophyly of the Chromodorididae and its sister group relationship with the Actinocyclidae. We were also able to, for the first time, test generic monophyly by including more than one member of all 14 of the non-monotypic chromodorid genera. Every one of these 14 traditional chromodorid genera are either non-monophyletic, or render another genus paraphyletic. Additionally, both the monotypic genera Verconia and Diversidoris are nested within clades. Based on data shown here, there are three individual species and five clades limited to the eastern Pacific and Atlantic Oceans (or just one of these ocean regions), while the majority of chromodorid clades and species are strictly Indo-Pacific in distribution. We present a new classification of the chromodorid nudibranchs. We use molecular data to untangle evolutionary relationships and retain a historical connection to traditional systematics by using generic names attached to type species as clade names. PMID:22506002

  19. Plant synthetic biology for molecular engineering of signalling and development

    PubMed Central

    Nemhauser, Jennifer L.; Torii, Keiko U.

    2016-01-01

    Molecular genetic studies of model plants in the past few decades have identified many key genes and pathways controlling development, metabolism and environmental responses. Recent technological and informatics advances have led to unprecedented volumes of data that may uncover underlying principles of plants as biological systems. The newly emerged discipline of synthetic biology and related molecular engineering approaches is built on this strong foundation. Today, plant regulatory pathways can be reconstituted in heterologous organisms to identify and manipulate parameters influencing signalling outputs. Moreover, regulatory circuits that include receptors, ligands, signal transduction components, epigenetic machinery and molecular motors can be engineered and introduced into plants to create novel traits in a predictive manner. Here, we provide a brief history of plant synthetic biology and significant recent examples of this approach, focusing on how knowledge generated by the reference plant Arabidopsis thaliana has contributed to the rapid rise of this new discipline, and discuss potential future directions. PMID:27249346

  20. Merging molecular mechanism and evolution: theory and computation at the interface of biophysics and evolutionary population genetics

    PubMed Central

    Serohijos, Adrian W.R.; Shakhnovich, Eugene I.

    2014-01-01

    The variation among sequences and structures in nature is both determined by physical laws and by evolutionary history. However, these two factors are traditionally investigated by disciplines with different emphasis and philosophy—molecular biophysics on one hand and evolutionary population genetics in another. Here, we review recent theoretical and computational approaches that address the critical need to integrate these two disciplines. We first articulate the elements of these integrated approaches. Then, we survey their contribution to our mechanistic understanding of molecular evolution, the polymorphisms in coding region, the distribution of fitness effects (DFE) of mutations, the observed folding stability of proteins in nature, and the distribution of protein folds in genomes. PMID:24952216

  1. Engineering imaging probes and molecular machines for nanomedicine.

    PubMed

    Tong, Sheng; Cradick, Thomas J; Ma, Yan; Dai, Zhifei; Bao, Gang

    2012-10-01

    Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, life sciences and medicine; it is expected to produce major breakthroughs in medical diagnostics and therapeutics. Due to the size-compatibility of nano-scale structures and devices with proteins and nucleic acids, the design, synthesis and application of nanoprobes, nanocarriers and nanomachines provide unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention. Recent advances in nanomedicine include the development of functional nanoparticle based molecular imaging probes, nano-structured materials as drug/gene carriers for in vivo delivery, and engineered molecular machines for treating single-gene disorders. This review focuses on the development of molecular imaging probes and engineered nucleases for nanomedicine, including quantum dot bioconjugates, quantum dot-fluorescent protein FRET probes, molecular beacons, magnetic and gold nanoparticle based imaging contrast agents, and the design and validation of zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) for gene targeting. The challenges in translating nanomedicine approaches to clinical applications are discussed.

  2. Engineering controllable bidirectional molecular motors based on myosin.

    PubMed

    Chen, Lu; Nakamura, Muneaki; Schindler, Tony D; Parker, David; Bryant, Zev

    2012-02-19

    Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells and have potential applications in molecular detection and diagnostic devices. Engineering molecular motors with controllable properties will allow selective perturbation of mechanical processes in living cells and provide optimized device components for tasks such as molecular sorting and directed assembly. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions and other signals. Here, we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies and guided by a structural model for the redirected power stroke of myosin VI, we have constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should make it possible to achieve spatiotemporal control over a range of motor properties including processivity, stride size and branchpoint turning.

  3. Molecular Diversity and Evolutionary Relationships of Tn1546-Like Elements in Enterococci from Humans and Animals

    PubMed Central

    Willems, Rob J. L.; Top, Janetta; van den Braak, Nicole; van Belkum, Alex; Mevius, Dik J.; Hendriks, Giel; van Santen-Verheuvel, Marga; van Embden, Jan D. A.

    1999-01-01

    We report on a detailed study on the molecular diversity and evolutionary relationships of Tn1546-like elements in vancomycin-resistant enterococci (VRE) from humans and animals. Restriction fragment length polymorphism (RFLP) analysis of the VanA transposon of 97 VRE revealed seven different Tn1546 types. Subsequent sequencing of the complete VanA transposons of 13 VRE isolates representing the seven RFLP types followed by sequencing of the identified polymorphic regions in 84 other VanA transposons resulted in the identification of 22 different Tn1546 derivatives. Differences between the Tn1546 types included point mutations in orf1, vanS, vanA, vanX, and vanY. Moreover, insertions of an IS1216V-IS3-like element in orf1, of IS1251 in the vanS-vanH intergenic region, and of IS1216V in the vanX-vanY intergenic region were found. The presence of insertion sequence elements was often associated with deletions in Tn1546. Identical Tn1546 types were found among isolates from humans and farm animals in The Netherlands, suggesting the sharing of a common vancomycin resistance gene pool. Application of the genetic analysis of Tn1546 to VRE isolates causing infections in hospitals in Oxford, United Kingdom, and Chicago, Ill., suggested the possibility of the horizontal transmission of the vancomycin resistance transposon. The genetic diversity in Tn1546 combined with epidemiological data suggest that the DNA polymorphism among Tn1546 variants can successfully be exploited for the tracing of the routes of transmission of vancomycin resistance genes. PMID:10049255

  4. Molecular Cloning, Functional Characterization, and Evolutionary Analysis of Vitamin D Receptors Isolated from Basal Vertebrates

    PubMed Central

    Kollitz, Erin M.; Zhang, Guozhu; Hawkins, Mary Beth; Whitfield, G. Kerr; Reif, David M.; Kullman, Seth W.

    2015-01-01

    The vertebrate genome is a result of two rapid and successive rounds of whole genome duplication, referred to as 1R and 2R. Furthermore, teleost fish have undergone a third whole genome duplication (3R) specific to their lineage, resulting in the retention of multiple gene paralogs. The more recent 3R event in teleosts provides a unique opportunity to gain insight into how genes evolve through specific evolutionary processes. In this study we compare molecular activities of vitamin D receptors (VDR) from basal species that diverged at key points in vertebrate evolution in order to infer derived and ancestral VDR functions of teleost paralogs. Species include the sea lamprey (Petromyzon marinus), a 1R jawless fish; the little skate (Leucoraja erinacea), a cartilaginous fish that diverged after the 2R event; and the Senegal bichir (Polypterus senegalus), a primitive 2R ray-finned fish. Saturation binding assays and gel mobility shift assays demonstrate high affinity ligand binding and classic DNA binding characteristics of VDR has been conserved across vertebrate evolution. Concentration response curves in transient transfection assays reveal EC50 values in the low nanomolar range, however maximum transactivational efficacy varies significantly between receptor orthologs. Protein-protein interactions were investigated using co-transfection, mammalian 2-hybrid assays, and mutations of coregulator activation domains. We then combined these results with our previous study of VDR paralogs from 3R teleosts into a bioinformatics analysis. Our results suggest that 1, 25D3 acts as a partial agonist in basal species. Furthermore, our bioinformatics analysis suggests that functional differences between VDR orthologs and paralogs are influenced by differential protein interactions with essential coregulator proteins. We speculate that we may be observing a change in the pharmacodynamics relationship between VDR and 1, 25D3 throughout vertebrate evolution that may have been

  5. Distinct Molecular Evolutionary Mechanisms Underlie the Functional Diversification of the Wnt and TGFβ Signaling Pathways

    PubMed Central

    Konikoff, Charlotte E.; Wisotzkey, Robert G.; Stinchfield, Michael J.

    2010-01-01

    The canonical Wnt pathway is one of the oldest and most functionally diverse of animal intercellular signaling pathways. Though much is known about loss-of-function phenotypes for Wnt pathway components in several model organisms, the question of how this pathway achieved its current repertoire of functions has not been addressed. Our phylogenetic analyses of 11 multigene families from five species belonging to distinct phyla, as well as additional analyses employing the 12 Drosophila genomes, suggest frequent gene duplications affecting ligands and receptors as well as co-evolution of new ligand–receptor pairs likely facilitated the expansion of this pathway’s capabilities. Further, several examples of recent gene loss are visible in Drosophila when compared to family members in other phyla. By comparison the TGFβ signaling pathway is characterized by ancient gene duplications of ligands, receptors, and signal transducers with recent duplication events restricted to the vertebrate lineage. Overall, the data suggest that two distinct molecular evolutionary mechanisms can create a functionally diverse developmental signaling pathway. These are the recent dynamic generation of new genes and ligand–receptor interactions as seen in the Wnt pathway and the conservative adaptation of ancient pre-existing genes to new roles as seen in the TGFβ pathway. From a practical perspective, the former mechanism limits the investigator’s ability to transfer knowledge of specific pathway functions across species while the latter facilitates knowledge transfer. Electronic supplementary material The online version of this article (doi:10.1007/s00239-010-9337-z) contains supplementary material, which is available to authorized users. PMID:20339843

  6. Current review of genetics of human obesity: from molecular mechanisms to an evolutionary perspective.

    PubMed

    Albuquerque, David; Stice, Eric; Rodríguez-López, Raquel; Manco, Licíno; Nóbrega, Clévio

    2015-08-01

    It is well-known that obesity is a complex multifactorial and heterogeneous condition with an important genetic component. Recently, major advances in obesity research emerged concerning the molecular mechanisms contributing to the obese condition. This review outlines several studies and data concerning the genetics and other important factors in the susceptibility risk to develop obesity. Based in the genetic etiology three main categories of obesity are considered: monogenic, syndromic, and common obesity. For the monogenic forms of obesity, the gene causing the phenotype is clearly identified, whereas for the common obesity the loci architecture underlying the phenotype is still being characterized. Given that, in this review we focus mainly in this obesity form, reviewing loci found until now by genome-wide association studies related with the susceptibility risk to develop obesity. Moreover, we also detail the obesity-related loci identified in children and in different ethnic groups, trying to highlight the complexity of the genetics underlying the common obese phenotype. Importantly, we also focus in the evolutionary hypotheses that have been proposed trying to explain how natural selection favored the spread of genes that increase the risk for an obese phenotype and how this predisposition to obesity evolved. Other factors are important in the obesity condition, and thus, we also discuss the epigenetic mechanisms involved in the susceptibility and development of obesity. Covering all these topics we expect to provide a complete and recent perspective about the underlying mechanisms involved in the development and origin of obesity. Only with a full understanding of the factors and mechanisms contributing to obesity, it will be possible to provide and allow the development of new therapeutic approaches to this condition.

  7. A Molecular and Co-Evolutionary Context for Grazer Induced Toxin Production in Alexandrium tamarense

    PubMed Central

    Wohlrab, Sylke; Iversen, Morten H.; John, Uwe

    2010-01-01

    Marine dinoflagellates of the genus Alexandrium are the proximal source of neurotoxins associated with Paralytic Shellfish Poisoning. The production of these toxins, the toxin biosynthesis and, thus, the cellular toxicity can be influenced by abiotic and biotic factors. There is, however, a lack of substantial evidence concerning the toxins' ecological function such as grazing defense. Waterborne cues from copepods have been previously found to induce a species-specific increase in toxin content in Alexandrium minutum. However, it remains speculative in which context these species-specific responses evolved and if it occurs in other Alexandrium species as well. In this study we exposed Alexandrium tamarense to three copepod species (Calanus helgolandicus, Acartia clausii, and Oithona similis) and their corresponding cues. We show that the species-specific response towards copepod-cues is not restricted to one Alexandrium species and that co-evolutionary processes might be involved in these responses, thus giving additional evidence for the defensive role of phycotoxins. Through a functional genomic approach we gained insights into the underlying molecular processes which could trigger the different outcomes of these species-specific responses and consequently lead to increased toxin content in Alexandrium tamarense. We propose that the regulation of serine/threonine kinase signaling pathways has a major influence in directing the external stimuli i.e. copepod-cues, into different intracellular cascades and networks in A. tamarense. Our results show that A. tamarense can sense potential predating copepods and respond to the received information by increasing its toxin production. Furthermore, we demonstrate how a functional genomic approach can be used to investigate species interactions within the plankton community. PMID:21124775

  8. A molecular and co-evolutionary context for grazer induced toxin production in Alexandrium tamarense.

    PubMed

    Wohlrab, Sylke; Iversen, Morten H; John, Uwe

    2010-11-29

    Marine dinoflagellates of the genus Alexandrium are the proximal source of neurotoxins associated with Paralytic Shellfish Poisoning. The production of these toxins, the toxin biosynthesis and, thus, the cellular toxicity can be influenced by abiotic and biotic factors. There is, however, a lack of substantial evidence concerning the toxins' ecological function such as grazing defense. Waterborne cues from copepods have been previously found to induce a species-specific increase in toxin content in Alexandrium minutum. However, it remains speculative in which context these species-specific responses evolved and if it occurs in other Alexandrium species as well. In this study we exposed Alexandrium tamarense to three copepod species (Calanus helgolandicus, Acartia clausii, and Oithona similis) and their corresponding cues. We show that the species-specific response towards copepod-cues is not restricted to one Alexandrium species and that co-evolutionary processes might be involved in these responses, thus giving additional evidence for the defensive role of phycotoxins. Through a functional genomic approach we gained insights into the underlying molecular processes which could trigger the different outcomes of these species-specific responses and consequently lead to increased toxin content in Alexandrium tamarense. We propose that the regulation of serine/threonine kinase signaling pathways has a major influence in directing the external stimuli i.e. copepod-cues, into different intracellular cascades and networks in A. tamarense. Our results show that A. tamarense can sense potential predating copepods and respond to the received information by increasing its toxin production. Furthermore, we demonstrate how a functional genomic approach can be used to investigate species interactions within the plankton community.

  9. Molecular characterization and evolutionary origins of farinin genes in Brachypodium distachyon L.

    PubMed

    Subburaj, Saminathan; Luo, Nana; Lu, Xiaobing; Li, Xiaohui; Cao, Hui; Hu, Yingkao; Li, Jiarui; Yan, Yueming

    2016-08-01

    Farinins are one of the oldest members of the gluten family in wheat and Aegilops species, and they influence dough properties. Here, we performed the first detailed molecular genetic study on farinin genes in Brachypodium distachyon L., the model species for Triticum aestivum. A total of 51 b-type farinin genes were cloned and characterized, including 27 functional and 24 non-functional pseudogenes from 14 different B. distachyon accessions. All genes were highly similar to those previously reported from wheat and Aegilops species. The identification of deduced amino acid sequences showed that b-type farinins across Triticeae genomes could be classified as b1-, b2-, b3-, and b4-type farinins; however, B. distachyon had only b3- and b4-type farinins. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) revealed that farinin genes are transcribed into mRNA in B. distachyon at much lower levels than in Triticeae, despite the presence of cis-acting elements in promoter regions. Phylogenetic analysis suggested that Brachypodium farinins may have closer relationships with common wheat and further confirmed four different types of b-type farinins in Triticeae and Brachypodium genomes, corresponding to b1, b2, b3 (group 1), and b4 (group 2). A putative evolutionary origin model of farinin genes in Brachypodium, Triticum, and the related species suggests that all b-type farinins diverged from their common ancestor ~3.2 million years ago (MYA). The b3 and b4 types could be considered older in the farinin family. The results explain the loss of b1- and b2-type farinin alleles in Brachypodium.

  10. Evolutionary Design of Low Molecular Weight Organic Anolyte Materials for Applications in Nonaqueous Redox Flow Batteries.

    PubMed

    Sevov, Christo S; Brooner, Rachel E M; Chénard, Etienne; Assary, Rajeev S; Moore, Jeffrey S; Rodríguez-López, Joaquín; Sanford, Melanie S

    2015-11-18

    The integration of renewable energy sources into the electric grid requires low-cost energy storage systems that mediate the variable and intermittent flux of energy associated with most renewables. Nonaqueous redox-flow batteries have emerged as a promising technology for grid-scale energy storage applications. Because the cost of the system scales with mass, the electroactive materials must have a low equivalent weight (ideally 150 g/(mol·e(-)) or less), and must function with low molecular weight supporting electrolytes such as LiBF4. However, soluble anolyte materials that undergo reversible redox processes in the presence of Li-ion supports are rare. We report the evolutionary design of a series of pyridine-based anolyte materials that exhibit up to two reversible redox couples at low potentials in the presence of Li-ion supporting electrolytes. A combination of cyclic voltammetry of anolyte candidates and independent synthesis of their corresponding charged-states was performed to rapidly screen for the most promising candidates. Results of this workflow provided evidence for possible decomposition pathways of first-generation materials and guided synthetic modifications to improve the stability of anolyte materials under the targeted conditions. This iterative process led to the identification of a promising anolyte material, N-methyl 4-acetylpyridinium tetrafluoroborate. This compound is soluble in nonaqueous solvents, is prepared in a single synthetic step, has a low equivalent weight of 111 g/(mol·e(-)), and undergoes two reversible 1e(-) reductions in the presence of LiBF4 to form reduced products that are stable over days in solution.

  11. Molecular and chemical engineering of bacteriophages for potential medical applications.

    PubMed

    Hodyra, Katarzyna; Dąbrowska, Krystyna

    2015-04-01

    Recent progress in molecular engineering has contributed to the great progress of medicine. However, there are still difficult problems constituting a challenge for molecular biology and biotechnology, e.g. new generation of anticancer agents, alternative biosensors or vaccines. As a biotechnological tool, bacteriophages (phages) offer a promising alternative to traditional approaches. They can be applied as anticancer agents, novel platforms in vaccine design, or as target carriers in drug discovery. Phages also offer solutions for modern cell imaging, biosensor construction or food pathogen detection. Here we present a review of bacteriophage research as a dynamically developing field with promising prospects for further development of medicine and biotechnology.

  12. Molecular phylogeny and evolutionary history of the Eurasiatic orchid genus Himantoglossum s.l. (Orchidaceae)

    PubMed Central

    Sramkó, Gábor; Attila, Molnár V.; Hawkins, Julie A.; Bateman, Richard M.

    2014-01-01

    Background and Aims Lizard orchids of the genus Himantoglossum include many of Eurasia's most spectacular orchids, producing substantial spikes of showy flowers. However, until recently the genus had received only limited, and entirely traditional, systematic study. The aim of the current work was to provide a more robust molecular phylogeny in order to better understand the evolutionary relationships among species of particular conservation concern. Methods All putative species of Himantoglossum s.l. were sampled across its geographical range. A large subsample of the 153 populations studied contributed to an initial survey of nuclear ribosomal internal transcribed spacer (nrITS) ribotypes. Smaller subsets were then sequenced for four plastid regions and the first intron of the low-copy-number nuclear gene LEAFY. Rooted using Steveniella as outgroup, phylogenetic trees were generated using parsimony and Bayesian methods from each of the three datasets, supplemented with a ribotype network. Key Results The resulting trees collectively determined the order of branching of the early divergent taxa as Himantoglossum comperianum > H. robertianum group > H. formosum, events that also involved significant morphological divergence. Relaxed molecular clock dating suggested that these divergences preceded the Pleistocene glaciations (the origin of the H. robertianum group may have coincided with the Messinian salinity crisis) and occurred in Asia Minor and/or the Caucasus. Among more controversial taxa of the H. hircinum-jankae clade, which are only subtly morphologically divergent, topological resolution was poorer and topological incongruence between datasets was consequently greater. Conclusions Plastid sequence divergence is broadly consistent with prior, morphologically circumscribed taxa and indicates a division between H. hircinum–adriaticum to the west of the Carpathians and H. jankae–caprinum (plus local endemics) to the east, a distinction also suggested by nr

  13. Reverse engineering chemical structures from molecular descriptors : how many solutions?

    SciTech Connect

    Brown, William Michael; Martin, Shawn Bryan; Faulon, Jean-Loup Michel

    2005-06-01

    Physical, chemical and biological properties are the ultimate information of interest for chemical compounds. Molecular descriptors that map structural information to activities and properties are obvious candidates for information sharing. In this paper, we consider the feasibility of using molecular descriptors to safely exchange chemical information in such a way that the original chemical structures cannot be reverse engineered. To investigate the safety of sharing such descriptors, we compute the degeneracy (the number of structure matching a descriptor value) of several 2D descriptors, and use various methods to search for and reverse engineer structures. We examine degeneracy in the entire chemical space taking descriptors values from the alkane isomer series and the PubChem database. We further use a stochastic search to retrieve structures matching specific topological index values. Finally, we investigate the safety of exchanging of fragmental descriptors using deterministic enumeration.

  14. Molecular biology and genetic engineering in nitrogen fixation.

    PubMed

    Dos Santos, Patricia C

    2011-01-01

    Biological nitrogen fixation is a complex and tightly regulated process limited to a group of prokaryotic species known as diazotrophs. Among well-studied diazotrophs, Azotobacter vinelandii is the best studied for its convenience of aerobic growth, its high levels of nitrogenase expression, and its genetic tractability. This chapter includes protocols and strategies in the molecular biology and genetic engineering of A. vinelandii that have been used as valuable tools for advancing studies on the biosynthesis, mechanism, and regulation of nitrogen fixation.

  15. Simulational nanoengineering: Molecular dynamics implementation of an atomistic Stirling engine.

    PubMed

    Rapaport, D C

    2009-04-01

    A nanoscale-sized Stirling engine with an atomistic working fluid has been modeled using molecular dynamics simulation. The design includes heat exchangers based on thermostats, pistons attached to a flywheel under load, and a regenerator. Key aspects of the behavior, including the time-dependent flows, are described. The model is shown to be capable of stable operation while producing net work at a moderate level of efficiency.

  16. Designing a Pedagogical Model for Web Engineering Education: An Evolutionary Perspective

    ERIC Educational Resources Information Center

    Hadjerrouit, Said

    2005-01-01

    In contrast to software engineering, which relies on relatively well established development approaches, there is a lack of a proven methodology that guides Web engineers in building reliable and effective Web-based systems. Currently, Web engineering lacks process models, architectures, suitable techniques and methods, quality assurance, and a…

  17. Molecular engineering of glycosaminoglycan chemistry for biomolecule delivery

    PubMed Central

    Miller, Tobias; Goude, Melissa C.; McDevitt, Todd C.

    2013-01-01

    Glycosaminoglycans (GAGs) are linear, negatively charged polysaccharid es that interact with a variety of positively-charged growth factors. In this review article, the effects of engineering GAG chemistry for molecular delivery applications in regenerative medicine are presented. Three major areas of focus at the structure-function-property interface are discussed: 1) macromolecular properties of GAGs, 2) effects of chemical modifications on protein binding, and 3) degradation mechanisms of GAGs. GAG-protein interactions can be based on 1) GAG sulfation pattern, 2) GAG carbohydrate conformation, and 3) GAG polyelectrolyte behavior. Chemical modifications of GAGs, which are commonly performed to engineer molecular delivery systems, affect protein binding and are highly dependent on the site of modification on the GAG molecules. The rate and mode of degradation can determine the release of molecules as well as the length of GAG fragments to which the cargo is electrostatically coupled and eventually released from the delivery system. Overall, GAG-based polymers are a versatile biomaterial platform offering novel means to engineer molecular delivery systems with a high degree of control in order to better treat a range of degenerate or injured tissues. PMID:24121191

  18. Xylose isomerase overexpression along with engineering of the pentose phosphate pathway and evolutionary engineering enable rapid xylose utilization and ethanol production by Saccharomyces cerevisiae.

    PubMed

    Zhou, Hang; Cheng, Jing-Sheng; Wang, Benjamin L; Fink, Gerald R; Stephanopoulos, Gregory

    2012-11-01

    Xylose is the main pentose and second most abundant sugar in lignocellulosic feedstocks. To improve xylose utilization, necessary for the cost-effective bioconversion of lignocellulose, several metabolic engineering approaches have been employed in the yeast Saccharomyces cerevisiae. In this study, we describe the rational metabolic engineering of a S. cerevisiae strain, including overexpression of the Piromyces xylose isomerase gene (XYLA), Pichia stipitis xylulose kinase (XYL3) and genes of the non-oxidative pentose phosphate pathway (PPP). This engineered strain (H131-A3) was used to initialize a three-stage process of evolutionary engineering, through first aerobic and anaerobic sequential batch cultivation followed by growth in a xylose-limited chemostat. The evolved strain H131-A3-AL(CS) displayed significantly increased anaerobic growth rate (0.203±0.006 h⁻¹) and xylose consumption rate (1.866 g g⁻¹ h⁻¹) along with high ethanol conversion yield (0.41 g/g). These figures exceed by a significant margin any other performance metrics on xylose utilization and ethanol production by S. cerevisiae reported to-date. Further inverse metabolic engineering based on functional complementation suggested that efficient xylose assimilation is attributed, in part, to the elevated expression level of xylose isomerase, which was accomplished through the multiple-copy integration of XYLA in the chromosome of the evolved strain.

  19. SHARP's systems engineering challenge: rectifying integrated product team requirements with performance issues in an evolutionary spiral development acquisition

    NASA Astrophysics Data System (ADS)

    Kuehl, C. Stephen

    2003-08-01

    Completing its final development and early deployment on the Navy's multi-role aircraft, the F/A-18 E/F Super Hornet, the SHAred Reconnaissance Pod (SHARP) provides the war fighter with the latest digital tactical reconnaissance (TAC Recce) Electro-Optical/Infrared (EO/IR) sensor system. The SHARP program is an evolutionary acquisition that used a spiral development process across a prototype development phase tightly coupled into overlapping Engineering and Manufacturing Development (EMD) and Low Rate Initial Production (LRIP) phases. Under a tight budget environment with a highly compressed schedule, SHARP challenged traditional acquisition strategies and systems engineering (SE) processes. Adopting tailored state-of-the-art systems engineering process models allowd the SHARP program to overcome the technical knowledge transition challenges imposed by a compressed program schedule. The program's original goal was the deployment of digital TAC Recce mission capabilities to the fleet customer by summer of 2003. Hardware and software integration technical challenges resulted from requirements definition and analysis activities performed across a government-industry led Integrated Product Team (IPT) involving Navy engineering and test sites, Boeing, and RTSC-EPS (with its subcontracted hardware and government furnished equipment vendors). Requirements development from a bottoms-up approach was adopted using an electronic requirements capture environment to clarify and establish the SHARP EMD product baseline specifications as relevant technical data became available. Applying Earned-Value Management (EVM) against an Integrated Master Schedule (IMS) resulted in efficiently managing SE task assignments and product deliveries in a dynamically evolving customer requirements environment. Application of Six Sigma improvement methodologies resulted in the uncovering of root causes of errors in wiring interconnectivity drawings, pod manufacturing processes, and avionics

  20. Simultaneously improving xylose fermentation and tolerance to lignocellulosic inhibitors through evolutionary engineering of recombinant Saccharomyces cerevisiae harbouring xylose isomerase

    PubMed Central

    2014-01-01

    Background Yeasts tolerant to toxic inhibitors from steam-pretreated lignocellulose with xylose co-fermentation capability represent an appealing approach for 2nd generation ethanol production. Whereas rational engineering, mutagenesis and evolutionary engineering are established techniques for either improved xylose utilisation or enhancing yeast tolerance, this report focuses on the simultaneous enhancement of these attributes through mutagenesis and evolutionary engineering of Saccharomyces cerevisiae harbouring xylose isomerase in anoxic chemostat culture using non-detoxified pretreatment liquor from triticale straw. Results Following ethyl methanesulfonate (EMS) mutagenesis, Saccharomyces cerevisiae strain D5A+ (ATCC 200062 strain platform), harbouring the xylose isomerase (XI) gene for pentose co-fermentation was grown in anoxic chemostat culture for 100 generations at a dilution rate of 0.10 h-1 in a medium consisting of 60% (v/v) non-detoxified hydrolysate liquor from steam-pretreated triticale straw, supplemented with 20 g/L xylose as carbon source. In semi-aerobic batch cultures in the same medium, the isolated strain D5A+H exhibited a slightly lower maximum specific growth rate (μmax = 0.12 ± 0.01 h-1) than strain TMB3400, with no ethanol production observed by the latter strain. Strain D5A+H also exhibited a shorter lag phase (4 h vs. 30 h) and complete removal of HMF, furfural and acetic acid from the fermentation broth within 24 h, reaching an ethanol concentration of 1.54 g/L at a yield (Yp/s) of 0.06 g/g xylose and a specific productivity of 2.08 g/gh. Evolutionary engineering profoundly affected the yeast metabolism, given that parental strain D5A+ exhibited an oxidative metabolism on xylose prior to strain development. Conclusions Physiological adaptations confirm improvements in the resistance to and conversion of inhibitors from pretreatment liquor with simultaneous enhancement of xylose to ethanol fermentation. These data

  1. The current status of REH theory. [Random Evolutionary Hits in biological molecular evolution

    NASA Technical Reports Server (NTRS)

    Holmquist, R.; Jukes, T. H.

    1981-01-01

    A response is made to the evaluation of Fitch (1980) of REH (random evolutionary hits) theory for the evolutionary divergence of proteins and nucleic acids. Correct calculations for the beta hemoglobin mRNAs of the human, mouse and rabbit in the absence and presence of selective constraints are summarized, and it is shown that the alternative evolutionary analysis of Fitch underestimates the total fixed mutations. It is further shown that the model used by Fitch to test for the completeness of the count of total base substitutions is in fact a variant of REH theory. Considerations of the variance inherent in evolutionary estimations are also presented which show the REH model to produce no more variance than other evolutionary models. In the reply, it is argued that, despite the objections raised, REH theory applied to proteins gives inaccurate estimates of total gene substitutions. It is further contended that REH theory developed for nucleic sequences suffers from problems relating to the frequency of nucleotide substitutions, the identity of the codons accepting silent and amino acid-changing substitutions, and estimate uncertainties.

  2. Controlling the conductance of molecular wires by defect engineering

    NASA Astrophysics Data System (ADS)

    Nozaki, D.; Pastawski, H. M.; Cuniberti, G.

    2010-06-01

    Understanding the charge transport mechanisms in nanoscale structures is essential for the development of molecular electronic devices. Charge transport through one-dimensional (1D) molecular systems connected between two contacts is influenced by several parameters, such as the electronic structure of the molecule and the presence of disorder and defects. In this work, we have modeled 1D molecular wires connected between electrodes and systematically investigated the influence of both soliton formation and the presence of defects on properties such as conductance and the density of states. Our numerical calculations have shown that the transport properties are highly sensitive to the positions of both the solitons and the defects. Interestingly, the introduction of a single defect in the molecular wire that divides it into two fragments, both consisting of an odd number of sites, creates a new conduction channel at the center of the band gap, resulting in higher zero-bias conductance than for defect-free systems. This phenomenon suggests alternative routes for the engineering of molecular wires with enhanced conductance.

  3. Energetics of a heat engine: a molecular dynamics simulation study

    NASA Astrophysics Data System (ADS)

    Tadele, Kumneger; Tatek, Yergou B.; Bekele, Mulugeta

    2016-11-01

    We perform a classical molecular dynamics simulation study of a heat engine operating between two heat reservoirs and performing a Carnot-like cycle in a finite time over a wide range of process rates. The working substance of the heat engine is made of highly concentrated interacting Lennard-Jones particles with the aim to simulate a real gas. The piston speed and temperature ratio of the cold and hot heat reservoirs are used as control parameters whereas efficiency and power output per cycle are the physical quantities of interest. The variation of these quantities as a function of the independent parameters is studied with the objective to investigate the validity of relevant theoretical predictions. For instance, for small process rates, the linear dependence of the heat engine efficiency with temperature ratio, in agreement with theory, has been demonstrated. Finally, a unified optimization criterion is applied to determine optimum operation conditions of the engine that make the best trade-off between efficiency and power output.

  4. Methods of Genome Engineering: a New Era of Molecular Biology.

    PubMed

    Chugunova, A A; Dontsova, O A; Sergiev, P V

    2016-07-01

    Genome sequencing now progressing much faster than our understanding of the majority of gene functions. Studies of physiological functions of various genes would not be possible without the ability to manipulate the genome. Methods of genome engineering can now be used to inactivate a gene to study consequences, introduce heterologous genes into the genome for scientific and biotechnology applications, create genes coding for fusion proteins to study gene expression, protein localization, and molecular interactions, and to develop animal models of human diseases to find appropriate treatment. Finally, genome engineering might present the possibility to cure hereditary diseases. In this review, we discuss and compare the most important methods for gene inactivation and editing, as well as methods for incorporation of heterologous genes into the genome.

  5. Remembering the Forest While Viewing the Trees: Evolutionary Thinking in the Teaching of Molecular Biology

    ERIC Educational Resources Information Center

    Saraswati, Sitaraman; Sitaraman, Ramakrishnan

    2014-01-01

    Given the centrality of evolutionary theory to the study of biology, we present a strategy for reinforcing its importance by appropriately recontextualizing classic and well-known experiments that are not explicitly linked with evolution in conventional texts. This exercise gives students an appreciation of the applicability of the theory of…

  6. Remembering the forest while viewing the trees: evolutionary thinking in the teaching of molecular biology.

    PubMed

    Saraswati, Sitaraman; Sitaraman, Ramakrishnan

    2014-01-01

    Given the centrality of evolutionary theory to the study of biology, we present a strategy for reinforcing its importance by appropriately recontextualizing classic and well-known experiments that are not explicitly linked with evolution in conventional texts. This exercise gives students an appreciation of the applicability of the theory of evolution in diverse contexts, including those where it is not explicitly mentioned.

  7. Molecular engineering of polymer actuators for biomedical and industrial use

    NASA Astrophysics Data System (ADS)

    Banister, Mark; Eichorst, Rebecca; Gurr, Amy; Schweitzer, Georgette; Geronov, Yordan; Rao, Pavalli; McGrath, Dominic

    2012-04-01

    Five key materials engineering components and how each component impacted the working performance of a polymer actuator material are investigated. In our research we investigated the change of actuation performance that occurred with each change we made to the material. We investigated polymer crosslink density, polymer chain length, polymer gelation, type and density of reactive units, as well as the addition of binders to the polymer matrix. All five play a significant role and need to be addressed at the molecular level to optimize a polymer gel for use as a practical actuator material for biomedical and industrial use.

  8. Nanoindentation in crystal engineering: quantifying mechanical properties of molecular crystals.

    PubMed

    Varughese, Sunil; Kiran, M S R N; Ramamurty, Upadrasta; Desiraju, Gautam R

    2013-03-04

    Nanoindentation is a technique for measuring the elastic modulus and hardness of small amounts of materials. This method, which has been used extensively for characterizing metallic and inorganic solids, is now being applied to organic and metal-organic crystals, and has also become relevant to the subject of crystal engineering, which is concerned with the design of molecular solids with desired properties and functions. Through nanoindentation it is possible to correlate molecular-level properties such as crystal packing, interaction characteristics, and the inherent anisotropy with micro/macroscopic events such as desolvation, domain coexistence, layer migration, polymorphism, and solid-state reactivity. Recent developments and exciting opportunities in this area are highlighted in this Minireview.

  9. Structural and Molecular Evolutionary Analysis of Agouti and Agouti-Related Proteins

    PubMed Central

    Jackson, Pilgrim J.; Douglas, Nick R.; Chai, Biaoxin; Binkley, Jonathan; Sidow, Arend; Barsh, Gregory S.; Millhauser, Glenn L.

    2010-01-01

    Summary Agouti (ASIP) and Agouti-related protein (AgRP) are endogenous antagonists of melanocortin receptors that play critical roles in the regulation of pigmentation and energy balance, respectively, and which arose from a common ancestral gene early in vertebrate evolution. The N-terminal domain of ASIP facilitates antagonism by binding to an accessory receptor, but here we show that the N-terminal domain of AgRP has the opposite effect and acts as a prodomain that negatively regulates antagonist function. Computational analysis reveals similar patterns of evolutionary constraint in the ASIP and AgRP C-terminal domains, but fundamental differences between the N-terminal domains. These studies shed light on the relationships between regulation of pigmentation and body weight, and they illustrate how evolutionary structure function analysis can reveal both unique and common mechanisms of action for paralogous gene products. PMID:17185225

  10. Molecular Evolutionary Constraints that Determine the Avirulence State of Clostridium botulinum C2 Toxin.

    PubMed

    Prisilla, A; Prathiviraj, R; Chellapandi, P

    2017-04-05

    Clostridium botulinum (group-III) is an anaerobic bacterium producing C2 toxin along with botulinum neurotoxins. C2 toxin is belonged to binary toxin A family in bacterial ADP-ribosylation superfamily. A structural and functional diversity of binary toxin A family was inferred from different evolutionary constraints to determine the avirulence state of C2 toxin. Evolutionary genetic analyses revealed evidence of C2 toxin cluster evolution through horizontal gene transfer from the phage or plasmid origins, site-specific insertion by gene divergence, and homologous recombination event. It has also described that residue in conserved NAD-binding core, family-specific domain structure, and functional motifs found to predetermine its virulence state. Any mutational changes in these residues destabilized its structure-function relationship. Avirulent mutants of C2 toxin were screened and selected from a crucial site required for catalytic function of C2I and pore-forming function of C2II. We found coevolved amino acid pairs contributing an essential role in stabilization of its local structural environment. Avirulent toxins selected in this study were evaluated by detecting evolutionary constraints in stability of protein backbone structure, folding and conformational dynamic space, and antigenic peptides. We found 4 avirulent mutants of C2I and 5 mutants of C2II showing more stability in their local structural environment and backbone structure with rapid fold rate, and low conformational flexibility at mutated sites. Since, evolutionary constraints-free mutants with lack of catalytic and pore-forming function suggested as potential immunogenic candidates for treating C. botulinum infected poultry and veterinary animals. Single amino acid substitution in C2 toxin thus provides a major importance to understand its structure-function link, not only of a molecule but also of the pathogenesis.

  11. Molecular evolutionary analysis of the high-affinity K+ transporter gene family in angiosperms.

    PubMed

    Yang, P; Hua, C; Zhou, F; Zhang, B-J; Cai, X-N; Chen, Q-Z; Wang, R-L

    2016-07-15

    The high-affinity K(+) transporter (HKT) family comprises a group of multifunctional cation transporters widely distributed in organisms ranging from Bacteria to Eukarya. In angiosperms, the HKT family consists primarily of nine types, whose evolutionary relationships are not fully understood. The available sequences from 31 plant species were used to perform a comprehensive evolutionary analysis, including an examination of selection pressure and estimating phylogenetic tree and gene duplication events. Our results show that a gene duplication in the HKT1;5/HKT1;4 cluster might have led to the divergence of the HKT1;5 and HKT1;4 subfamilies. Additionally, maximum likelihood analysis revealed that the HKT family has undergone a strong purifying selection. An analysis of the amino acids provided strong statistical evidence for a functional divergence between subfamilies 1 and 2. Our study was the first to provide evidence of this functional divergence between these two subfamilies. Analysis of co-evolution in HKT identified 25 co-evolved groups. These findings expanded our understanding of the evolutionary mechanisms driving functional diversification of HKT proteins.

  12. Carotenoid biosynthetic pathway: molecular phylogenies and evolutionary behavior of crt genes in eubacteria.

    PubMed

    Phadwal, Kanchan

    2005-01-17

    Phylogenetic analysis of carotenoid biosynthetic pathway genes and their evolutionary rate variations were studied among eubacterial taxa. The gene sequences for the enzymes involved in this pathway were obtained for major phylogenetic groups of eubacteria (green sulfur bacteria, green nonsulphur bacteria, Gram-positive bacteria, proteobacteria, flavobacteria, cyanobacteria) and archeabacteria. These gene datasets were distributed under five major steps of carotenoid biosynthesis in eubacteria; isoprenoid precursor biosynthesis, phytoene synthesis, dehydrogenation of phytoene, lycopene cyclization, formation of acyclic xanthophylls, formation of cyclic xanthophylls and carotenoid biosynthesis regulation. The NJ algorithm was used on protein coding DNA sequences to deduce the evolutionary relationship for the respective crt genes among different eubacterial lineages. The rate of nonsynonymous nucleotide substitutions per nonsynonymous site (d(N)) and synonymous nucleotide substitutions per synonymous site (d(S)) were calculated for different clades of the respective phylogenetic tree for specific crt genes. The phylogenetic analysis suggests that evolutionary pattern of crt genes in eubacteria is characterized by lateral gene transfer and gene duplication events. The d(N) values indicate that carotenoid biosynthetic genes are more conserved in proteobacteria than in any other eubacterial phyla. Furthermore, of the genes involved in carotenoid biosynthesis pathway, structural genes evolve slowly than the regulatory genes in eubacteria.

  13. A molecular phylogeny of Dorylus army ants provides evidence for multiple evolutionary transitions in foraging niche

    PubMed Central

    Kronauer, Daniel JC; Schöning, Caspar; Vilhelmsen, Lars B; Boomsma, Jacobus J

    2007-01-01

    Background Army ants are the prime arthropod predators in tropical forests, with huge colonies and an evolutionary derived nomadic life style. Five of the six recognized subgenera of Old World Dorylus army ants forage in the soil, whereas some species of the sixth subgenus (Anomma) forage in the leaf-litter and some as conspicuous swarm raiders on the forest floor and in the lower vegetation (the infamous driver ants). Here we use a combination of nuclear and mitochondrial DNA sequences to reconstruct the phylogeny of the Dorylus s.l. army ants and to infer the evolutionary transitions in foraging niche and associated morphological adaptations. Results Underground foraging is basal and gave rise to leaf-litter foraging. Leaf-litter foraging in turn gave rise to two derived conditions: true surface foraging (the driver ants) and a reversal to subterranean foraging (a clade with most of the extant Dorylus s.s. species). This means that neither the subgenus Anomma nor Dorylus s.s. is monophyletic, and that one of the Dorylus s.s. lineages adopted subterranean foraging secondarily. We show that this latter group evolved a series of morphological adaptations to underground foraging that are remarkably convergent to the basal state. Conclusion The evolutionary transitions in foraging niche were more complex than previously thought, but our comparative analysis of worker morphology lends strong support to the contention that particular foraging niches have selected for very specific worker morphologies. The surprising reversal to underground foraging is therefore a striking example of convergent morphological evolution. PMID:17408491

  14. Evolutionary mechanics: new engineering principles for the emergence of flexibility in a dynamic and uncertain world.

    PubMed

    Whitacre, James M; Rohlfshagen, Philipp; Bender, Axel; Yao, Xin

    2012-09-01

    Engineered systems are designed to deftly operate under predetermined conditions yet are notoriously fragile when unexpected perturbations arise. In contrast, biological systems operate in a highly flexible manner; learn quickly adequate responses to novel conditions, and evolve new routines and traits to remain competitive under persistent environmental change. A recent theory on the origins of biological flexibility has proposed that degeneracy-the existence of multi-functional components with partially overlapping functions-is a primary determinant of the robustness and adaptability found in evolved systems. While degeneracy's contribution to biological flexibility is well documented, there has been little investigation of degeneracy design principles for achieving flexibility in systems engineering. Actually, the conditions that can lead to degeneracy are routinely eliminated in engineering design. With the planning of transportation vehicle fleets taken as a case study, this article reports evidence that degeneracy improves the robustness and adaptability of a simulated fleet towards unpredicted changes in task requirements without incurring costs to fleet efficiency. We find that degeneracy supports faster rates of design adaptation and ultimately leads to better fleet designs. In investigating the limitations of degeneracy as a design principle, we consider decision-making difficulties that arise from degeneracy's influence on fleet complexity. While global decision-making becomes more challenging, we also find degeneracy accommodates rapid distributed decision-making leading to (near-optimal) robust system performance. Given the range of conditions where favorable short-term and long-term performance outcomes are observed, we propose that degeneracy may fundamentally alter the propensity for adaptation and is useful within different engineering and planning contexts.

  15. Using PEBBLE for the evolutionary analysis of serially sampled molecular sequences.

    PubMed

    Goode, Matthew; Rodrigo, Allen G

    2004-05-01

    The PEBBLE (Phylogenetics, Evolutionary Biology, and Bioinformatics in a moduLar Environment) application is a relative newcomer to the field of phylogenetic applications. Although designed as a customizable generalist application, PEBBLE was initially developed to implement procedures for the analysis of sequences associated with different sampling times, e.g., rapidly evolving viral genes sampled over the course of infection, or ancient DNA sequences. The basic protocol describes the use of PEBBLE to infer a phylogenetic tree using the sUPGMA algorithm, and the inference of substitution rate parameters using maximum likelihood. The alternate and support protocols describe the simulation capabilities of PEBBLE, and general use of the PEBBLE application, respectively.

  16. Rational and evolutionary engineering approaches uncover a small set of genetic changes efficient for rapid xylose fermentation in Saccharomyces cerevisiae.

    PubMed

    Kim, Soo Rin; Skerker, Jeffrey M; Kang, Wei; Lesmana, Anastashia; Wei, Na; Arkin, Adam P; Jin, Yong-Su

    2013-01-01

    Economic bioconversion of plant cell wall hydrolysates into fuels and chemicals has been hampered mainly due to the inability of microorganisms to efficiently co-ferment pentose and hexose sugars, especially glucose and xylose, which are the most abundant sugars in cellulosic hydrolysates. Saccharomyces cerevisiae cannot metabolize xylose due to a lack of xylose-metabolizing enzymes. We developed a rapid and efficient xylose-fermenting S. cerevisiae through rational and inverse metabolic engineering strategies, comprising the optimization of a heterologous xylose-assimilating pathway and evolutionary engineering. Strong and balanced expression levels of the XYL1, XYL2, and XYL3 genes constituting the xylose-assimilating pathway increased ethanol yields and the xylose consumption rates from a mixture of glucose and xylose with little xylitol accumulation. The engineered strain, however, still exhibited a long lag time when metabolizing xylose above 10 g/l as a sole carbon source, defined here as xylose toxicity. Through serial-subcultures on xylose, we isolated evolved strains which exhibited a shorter lag time and improved xylose-fermenting capabilities than the parental strain. Genome sequencing of the evolved strains revealed that mutations in PHO13 causing loss of the Pho13p function are associated with the improved phenotypes of the evolved strains. Crude extracts of a PHO13-overexpressing strain showed a higher phosphatase activity on xylulose-5-phosphate (X-5-P), suggesting that the dephosphorylation of X-5-P by Pho13p might generate a futile cycle with xylulokinase overexpression. While xylose consumption rates by the evolved strains improved substantially as compared to the parental strain, xylose metabolism was interrupted by accumulated acetate. Deletion of ALD6 coding for acetaldehyde dehydrogenase not only prevented acetate accumulation, but also enabled complete and efficient fermentation of xylose as well as a mixture of glucose and xylose by the

  17. Molecular engineering of porous silica using aryl templates

    DOEpatents

    Loy, D.A.; Shea, K.J.

    1994-06-14

    A process is described for manipulating the porosity of silica using a series of organic template groups covalently incorporated into the silicate matrix. The templates in the bridged polysilsesquioxanes are selectively removed from the material by oxidation with oxygen plasma or other means, leaving engineered voids or pores. The size of these pores is dependent upon the length or size of the template or spacer. The size of the templates is measured in terms of Si-Si distances which range from about 0.67 nm to 1.08 nm. Changes introduced by the loss of the templates result in a narrow range of micropores (i.e. <2 nm). Both aryl and alkyl template groups are used as spacers. Novel microporous silica materials useful as molecular sieves, desiccants, and catalyst supports are produced. 3 figs.

  18. Molecular engineering of porous silica using aryl templates

    DOEpatents

    Loy, Douglas A.; Shea, Kenneth J.

    1994-01-01

    A process for manipulating the porosity of silica using a series of organic template groups covalently incorporated into the silicate matrix. The templates in the bridged polysilsesquioxanes are selectively removed from the material by oxidation with oxygen plasma or other means, leaving engineered voids or pores. The size of these pores is dependent upon the length or size of the template or spacer. The size of the templates is measured in terms of Si-Si distances which range from about 0.67 nm to 1.08 nm. Changes introduced by the loss of the templates result in a narrow range of micropores (i.e. <2 nm). Both aryl and alkyl template groups are used as spacers. Novel microporous silica materials useful as molecular seives, dessicants, and catalyst supports are produced.

  19. RNA polymerase active center: the molecular engine of transcription.

    PubMed

    Nudler, Evgeny

    2009-01-01

    RNA polymerase (RNAP) is a complex molecular machine that governs gene expression and its regulation in all cellular organisms. To accomplish its function of accurately producing a full-length RNA copy of a gene, RNAP performs a plethora of chemical reactions and undergoes multiple conformational changes in response to cellular conditions. At the heart of this machine is the active center, the engine, which is composed of distinct fixed and moving parts that serve as the ultimate acceptor of regulatory signals and as the target of inhibitory drugs. Recent advances in the structural and biochemical characterization of RNAP explain the active center at the atomic level and enable new approaches to understanding the entire transcription mechanism, its exceptional fidelity and control.

  20. DNA Aptamer Based Nanodrugs: Molecular Engineering for Efficiency

    PubMed Central

    Cansiz, Sena; Zhang, Liqin; Wu, Cuichen; Wu, Yuan; Teng, I-Ting; Hou, Weijia; Wang, Yanyue; Wan, Shuo; Cai, Ren; Jin, Chen; Liu, Qiaoling; Tan, Weihong

    2015-01-01

    In the past two decades, the study of cancer therapy has gradually advanced to the “Nano” era. Numerous novel nanomaterials armed with unique physical properties have been introduced into biomedical research. At the same time, functional nucleic acid molecules, especially aptamers, have aroused broad attention from the biomedical community. Benefiting from the advancement of molecular engineering strategies, it is now feasible to combine the cancer specific recognition capability of aptamers with various other special functions of nanomaterials to develop cancer specific drugs at the nanoscale. Nanodrugs are now offering an unprecedented opportunity to achieve the goal of efficient targeted delivery as well as controlled release. This review highlights some achievements of multiple aptamer-based nanodrug systems which have emerged in recent years, including studies in the infant stage of “proof-of-concept”. PMID:26177853

  1. Molecular basis of glyphosate resistance: Different approaches through protein engineering

    PubMed Central

    Pollegioni, Loredano; Schonbrunn, Ernst; Siehl, Daniel

    2011-01-01

    Glyphosate (N-phosphonomethyl-glycine) is the most-used herbicide in the world: glyphosate-based formulations exhibit broad-spectrum herbicidal activity with minimal human and environmental toxicity. The extraordinary success of this simple small molecule is mainly due to the high specificity of glyphosate towards the plant enzyme enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway leading to biosynthesis of aromatic amino acids. Starting in 1996, transgenic glyphosate-resistant plants were introduced thus allowing the application of the herbicide to the crop (post-emergence) to remove emerged weeds without crop damage. This review focuses on the evolution of mechanisms of resistance to glyphosate as obtained through natural diversity, the gene shuffling approach to molecular evolution, and a rational, structure-based approach to protein engineering. In addition, we offer rationale for the means by which the modifications made have had their intended effect. PMID:21668647

  2. Brief Communication: Quantitative- and molecular-genetic differentiation in humans and chimpanzees: implications for the evolutionary processes underlying cranial diversification.

    PubMed

    Weaver, Timothy D

    2014-08-01

    Estimates of the amount of genetic differentiation in humans among major geographic regions (e.g., Eastern Asia vs. Europe) from quantitative-genetic analyses of cranial measurements closely match those from classical- and molecular-genetic markers. Typically, among-region differences account for ∼10% of the total variation. This correspondence is generally interpreted as evidence for the importance of neutral evolutionary processes (e.g., genetic drift) in generating among-region differences in human cranial form, but it was initially surprising because human cranial diversity was frequently assumed to show a strong signature of natural selection. Is the human degree of similarity of cranial and DNA-sequence estimates of among-region genetic differentiation unusual? How do comparisons with other taxa illuminate the evolutionary processes underlying cranial diversification? Chimpanzees provide a useful starting point for placing the human results in a broader comparative context, because common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the extant species most closely related to humans. To address these questions, I used 27 cranial measurements collected on a sample of 861 humans and 263 chimpanzees to estimate the amount of genetic differentiation between pairs of groups (between regions for humans and between species or subspecies for chimpanzees). Consistent with previous results, the human cranial estimates are quite similar to published DNA-sequence estimates. In contrast, the chimpanzee cranial estimates are much smaller than published DNA-sequence estimates. It appears that cranial differentiation has been limited in chimpanzees relative to humans.

  3. Statistical and molecular analyses of evolutionary significance of red-green color vision and color blindness in vertebrates.

    PubMed

    Yokoyama, Shozo; Takenaka, Naomi

    2005-04-01

    Red-green color vision is strongly suspected to enhance the survival of its possessors. Despite being red-green color blind, however, many species have successfully competed in nature, which brings into question the evolutionary advantage of achieving red-green color vision. Here, we propose a new method of identifying positive selection at individual amino acid sites with the premise that if positive Darwinian selection has driven the evolution of the protein under consideration, then it should be found mostly at the branches in the phylogenetic tree where its function had changed. The statistical and molecular methods have been applied to 29 visual pigments with the wavelengths of maximal absorption at approximately 510-540 nm (green- or middle wavelength-sensitive [MWS] pigments) and at approximately 560 nm (red- or long wavelength-sensitive [LWS] pigments), which are sampled from a diverse range of vertebrate species. The results show that the MWS pigments are positively selected through amino acid replacements S180A, Y277F, and T285A and that the LWS pigments have been subjected to strong evolutionary conservation. The fact that these positively selected M/LWS pigments are found not only in animals with red-green color vision but also in those with red-green color blindness strongly suggests that both red-green color vision and color blindness have undergone adaptive evolution independently in different species.

  4. Evolutionary decay and the prospects for long-term disease intervention using engineered insect vectors

    PubMed Central

    2015-01-01

    After a long history of applying the sterile insect technique to suppress populations of disease vectors and agricultural pests, there is growing interest in using genetic engineering both to improve old methods and to enable new methods. The two goals of interventions are to suppress populations, possibly eradicating a species altogether, or to abolish the vector’s competence to transmit a parasite. New methods enabled by genetic engineering include the use of selfish genes toward either goal as well as a variety of killer-rescue systems that could be used for vector competence reduction. This article reviews old and new methods with an emphasis on the potential for evolution of resistance to these strategies. Established methods of population suppression did not obviously face a problem from resistance evolution, but newer technologies might. Resistance to these newer interventions will often be mechanism-specific, and while it is too early to know where resistance evolution will become a problem, it is at least possible to propose properties of interventions that will be more or less effective in blocking resistance evolution. PMID:26160736

  5. Molecularly Engineered Energy Materials, an Energy Frontier Research Center

    SciTech Connect

    Ozolins, Vidvuds

    2016-09-28

    Molecularly Engineered Energy Materials (MEEM) was established as an interdisciplinary cutting-edge UCLA-based research center uniquely equipped to attack the challenge of rationally designing, synthesizing and testing revolutionary new energy materials. Our mission was to achieve transformational improvements in the performance of materials via controlling the nano-and mesoscale structure using selectively designed, earth-abundant, inexpensive molecular building blocks. MEEM has focused on materials that are inherently abundant, can be easily assembled from intelligently designed building blocks (molecules, nanoparticles), and have the potential to deliver transformative economic benefits in comparison with the current crystalline-and polycrystalline-based energy technologies. MEEM addressed basic science issues related to the fundamental mechanisms of carrier generation, energy conversion, as well as transport and storage of charge and mass in tunable, architectonically complex materials. Fundamental understanding of these processes will enable rational design, efficient synthesis and effective deployment of novel three-dimensional material architectures for energy applications. Three interrelated research directions were initially identified where these novel architectures hold great promise for high-reward research: solar energy generation, electrochemical energy storage, and materials for CO2 capture. Of these, the first two remained throughout the project performance period, while carbon capture was been phased out in consultation and with approval from BES program manager.

  6. Molecular engineering and characterization of self-assembled biorecognition surfaces

    NASA Astrophysics Data System (ADS)

    Pan, Sheng

    The development of molecular engineering techniques for the fabrication of biomaterial surfaces is of importance in the field of biomaterials. It offers opportunities for better understanding of biological processes on material surfaces and rational design of contemporary biomaterials. Our work in this area aims to develop novel engineering strategies to design biorecognition surfaces via self-assembly and surface derivatization. Fundamental issues regarding self-assembled monolayer (SAM) structure, formation kinetics, and chemical derivatization were investigated systematically using electron spectroscopy for chemical analysis (ESCA), time-of-flight secondary ion mass spectrometry (TOF-SIMS), infrared reflection absorption spectroscopy (IRAS), atomic force microscopy (AFM), and contact angle measurements. Novel engineering concepts based on multifunctionality and statistical pattern matching were introduced and applied to develop biomimetic surfaces. Our study illustrated that molecules underwent structural transition and orientation development during self-assembly formation, from a disordered, low-density, more liquid-like structure to a highly ordered, closed-packed crystalline-like structure. Surface properties, such as wettability and the reactivity of outermost functional groups can be related to film structure, packing density, as well as molecular orientation. Given the order and organization of SAMs, the accessibility and reactivity of the outermost functional groups, reaction kinetics, stoichiometry, and SAMs stability were studied systematically by surface derivatization of trifluoroacetic anhydride (TFAA). The TFAA derivatization reactions exhibited rapid kinetics on the hydroxyl-terminated SAMs. The data from complementary surface analytical techniques consistently indicated a nearly complete surface reaction. Biomimetic surfaces were made by random immobilization of amino acid of arginine (R), glycine (G), and aspartic acid (D) on well-defined SAMs

  7. A computational kinematics and evolutionary approach to model molecular flexibility for bionanotechnology

    NASA Astrophysics Data System (ADS)

    Brintaki, Athina N.

    Modeling molecular structures is critical for understanding the principles that govern the behavior of molecules and for facilitating the exploration of potential pharmaceutical drugs and nanoscale designs. Biological molecules are flexible bodies that can adopt many different shapes (or conformations) until they reach a stable molecular state that is usually described by the minimum internal energy. A major challenge in modeling flexible molecules is the exponential explosion in computational complexity as the molecular size increases and many degrees of freedom are considered to represent the molecules' flexibility. This research work proposes a novel generic computational geometric approach called enhanced BioGeoFilter (g.eBGF) that geometrically interprets inter-atomic interactions to impose geometric constraints during molecular conformational search to reduce the time for identifying chemically-feasible conformations. Two new methods called Kinematics-Based Differential Evolution ( kDE) and Biological Differential Evolution ( BioDE) are also introduced to direct the molecular conformational search towards low energy (stable) conformations. The proposed kDE method kinematically describes a molecule's deformation mechanism while it uses differential evolution to minimize the intra-molecular energy. On the other hand, the proposed BioDE utilizes our developed g.eBGF data structure as a surrogate approximation model to reduce the number of exact evaluations and to speed the molecular conformational search. This research work will be extremely useful in enabling the modeling of flexible molecules and in facilitating the exploration of nanoscale designs through the virtual assembly of molecules. Our research work can also be used in areas such as molecular docking, protein folding, and nanoscale computer-aided design where rapid collision detection scheme for highly deformable objects is essential.

  8. Molecular phylogeny of Myriapoda provides insights into evolutionary patterns of the mode in post-embryonic development.

    PubMed

    Miyazawa, Hideyuki; Ueda, Chiaki; Yahata, Kensuke; Su, Zhi-Hui

    2014-02-18

    Myriapoda, a subphylum of Arthropoda, comprises four classes, Chilopoda, Diplopoda, Pauropoda, and Symphyla. While recent molecular evidence has shown that Myriapoda is monophyletic, the internal phylogeny, which is pivotal for understanding the evolutionary history of myriapods, remains unresolved. Here we report the results of phylogenetic analyses and estimations of divergence time and ancestral state of myriapods. Phylogenetic analyses were performed based on three nuclear protein-coding genes determined from 19 myriapods representing the four classes (17 orders) and 11 outgroup species. The results revealed that Symphyla whose phylogenetic position has long been debated is the sister lineage to all other myriapods, and that the interordinal relationships within classes were consistent with traditional classifications. Ancestral state estimation based on the tree topology suggests that myriapods evolved from an ancestral state that was characterized by a hemianamorphic mode of post-embryonic development and had a relatively low number of body segments and legs.

  9. Phylogeny of Eutardigrada: new molecular data and their morphological support lead to the identification of new evolutionary lineages.

    PubMed

    Bertolani, Roberto; Guidetti, Roberto; Marchioro, Trevor; Altiero, Tiziana; Rebecchi, Lorena; Cesari, Michele

    2014-07-01

    An extensive study of the phylogeny of Eutardigrada, the largest class of Tardigrada, has been performed analyzing one hundred and forty sequences (eighty of which newly obtained) representative of one hundred and twenty-nine specimens belonging to all families (except Necopinatidae) of this class. The molecular (18S and 28S rRNA) results were compared with new and previous morphological data, allowing us to find new phylogenetic relationships, to identify new phylogenetic lineages, to erect new taxa for some lineages, and to find several morphological synapomorphies supporting the identified clusters. The class Eutardigrada has been confirmed and, within it, the orders Apochela and Parachela, the superfamilies Macrobiotoidea, Hypsibioidea, Isohypsibioidea, and Eohypsibioidea, and all the families and subfamilies considered, although with emended diagnoses in several cases. In addition, new taxa have been erected: the new subfamily Pilatobiinae (Hypsibiidae) with the new genus Pilatobius, as well as an upgrading of Diphascon and Adropion to genus level, previously considered subgenera of Diphascon. Our results demonstrate that while molecular analysis is an important tool for understanding phylogeny, an integrative and comparative approach using both molecular and morphological data is necessary to better elucidate evolutionary relationships.

  10. Evolutionary diversification of retinoic acid receptor ligand-binding pocket structure by molecular tinkering

    PubMed Central

    Gutierrez-Mazariegos, Juliana; Nadendla, Eswar Kumar; Studer, Romain A.; Alvarez, Susana; de Lera, Angel R.; Kuraku, Shigehiro; Bourguet, William; Laudet, Vincent

    2016-01-01

    Whole genome duplications (WGDs) have been classically associated with the origin of evolutionary novelties and the so-called duplication–degeneration–complementation model describes the possible fates of genes after duplication. However, how sequence divergence effectively allows functional changes between gene duplicates is still unclear. In the vertebrate lineage, two rounds of WGDs took place, giving rise to paralogous gene copies observed for many gene families. For the retinoic acid receptors (RARs), for example, which are members of the nuclear hormone receptor (NR) superfamily, a unique ancestral gene has been duplicated resulting in three vertebrate paralogues: RARα, RARβ and RARγ. It has previously been shown that this single ancestral RAR was neofunctionalized to give rise to a larger substrate specificity range in the RARs of extant jawed vertebrates (also called gnathostomes). To understand RAR diversification, the members of the cyclostomes (lamprey and hagfish), jawless vertebrates representing the extant sister group of gnathostomes, provide an intermediate situation and thus allow the characterization of the evolutionary steps that shaped RAR ligand-binding properties following the WGDs. In this study, we assessed the ligand-binding specificity of cyclostome RARs and found that their ligand-binding pockets resemble those of gnathostome RARα and RARβ. In contrast, none of the cyclostome receptors studied showed any RARγ-like specificity. Together, our results suggest that cyclostome RARs cover only a portion of the specificity repertoire of the ancestral gnathostome RARs and indicate that the establishment of ligand-binding specificity was a stepwise event. This iterative process thus provides a rare example for the diversification of receptor–ligand interactions of NRs following WGDs. PMID:27069642

  11. Evolutionary engineering of Saccharomyces cerevisiae for enhanced tolerance to hydrolysates of lignocellulosic biomass.

    PubMed

    Almario, María P; Reyes, Luis H; Kao, Katy C

    2013-10-01

    Lignocellulosic biomass has become an important feedstock to mitigate current ethical and economical concerns related to the bio-based production of fuels and chemicals. During the pre-treatment and hydrolysis of the lignocellulosic biomass, a complex mixture of sugars and inhibitors are formed. The inhibitors interfere with microbial growth and product yields. This study uses an adaptive laboratory evolution method called visualizing evolution in real-time (VERT) to uncover the molecular mechanisms associated with tolerance to hydrolysates of lignocellulosic biomass in Saccharomyces cerevisiae. VERT enables a more rational scheme for isolating adaptive mutants for characterization and molecular analyses. Subsequent growth kinetic analyses of the mutants in individual and combinations of common inhibitors present in hydrolysates (acetic acid, furfural, and hydroxymethylfurfural) showed differential levels of resistance to different inhibitors, with enhanced growth rates up to 57%, 12%, 22%, and 24% in hydrolysates, acetic acid, HMF and furfural, respectively. Interestingly, some of the adaptive mutants exhibited reduced fitness in the presence of individual inhibitors, but showed enhanced fitness in the presence of combinations of inhibitors compared to the parental strains. Transcriptomic analysis revealed different mechanisms for resistance to hydrolysates and a potential cross adaptation between oxidative stress and hydrolysates tolerance in several of the mutants.

  12. Incorporating Molecular and Cellular Biology into a Chemical Engineering Degree Program

    ERIC Educational Resources Information Center

    O'Connor, Kim C.

    2005-01-01

    There is a growing need for a workforce that can apply engineering principles to molecular based discovery and product development in the biological sciences. To this end, Tulane University established a degree program that incorporates molecular and cellular biology into the chemical engineering curriculum. In celebration of the tenth anniversary…

  13. Activation of glycerol metabolic pathway by evolutionary engineering of Rhizopus oryzae to strengthen the fumaric acid biosynthesis from crude glycerol.

    PubMed

    Huang, Di; Wang, Ru; Du, Wenjie; Wang, Guanyi; Xia, Menglei

    2015-11-01

    Rhizopus oryzae is strictly inhibited by biodiesel-based by-product crude glycerol, which results in low fumaric acid production. In this study, evolutionary engineering was employed to activate the glycerol utilization pathway for fumaric acid production. An evolved strain G80 was selected, which could tolerate and utilize high concentrations of crude glycerol to produce 14.9g/L fumaric acid with a yield of 0.248g/g glycerol. Key enzymes activity analysis revealed that the evolved strain displayed a significant upregulation in glycerol dissimilation, pyruvate consumption and reductive tricarboxylic acid pathways, compared with the parent strain. Subsequently, intracellular metabolic profiling analysis showed that amino acid biosynthesis, tricarboxylic acid cycle, fatty acid and stress response metabolites accounted for metabolic difference between two strains. Moreover, a glycerol fed-batch strategy was optimized to obtain the highest fumaric acid production of 25.5g/L, significantly increased by 20.9-fold than that of the parent strain of 1.2g/L.

  14. Evolutionary engineered Saccharomyces cerevisiae wine yeast strains with increased in vivo flux through the pentose phosphate pathway.

    PubMed

    Cadière, Axelle; Ortiz-Julien, Anne; Camarasa, Carole; Dequin, Sylvie

    2011-05-01

    Amplification of the flux toward the pentose phosphate (PP) pathway might be of interest for various S. cerevisiae based industrial applications. We report an evolutionary engineering strategy based on a long-term batch culture on gluconate, a substrate that is poorly assimilated by S. cerevisiae cells and is metabolized by the PP pathway. After adaptation for various periods of time, we selected strains that had evolved a greater consumption capacity for gluconate. (13)C metabolic flux analysis on glucose revealed a redirection of carbon flux from glycolysis towards the PP pathway and a greater synthesis of lipids. The relative flux into the PP pathway was 17% for the evolved strain (ECA5) versus 11% for the parental strain (EC1118). During wine fermentation, the evolved strains displayed major metabolic changes, such as lower levels of acetate production, higher fermentation rates and enhanced production of aroma compounds. These represent a combination of novel traits, which are of great interest in the context of modern winemaking.

  15. History of Molecular Beam Research: Personal Reminiscences of the Important Evolutionary Period 1919-1933

    ERIC Educational Resources Information Center

    Estermann, Immanuel

    1975-01-01

    Describes the early historical period of the molecular beam method, including the Stern-Gerlach experiment, the work of Davisson and Germer, and the magnetic moment determinations for the proton, neutron, and deuteron. Contains some amusing historical sidelights on the research personalities that dominated that period. (MLH)

  16. Molecular Signatures for the PVC Clade (Planctomycetes, Verrucomicrobia, Chlamydiae, and Lentisphaerae) of Bacteria Provide Insights into Their Evolutionary Relationships.

    PubMed

    Gupta, Radhey S; Bhandari, Vaibhav; Naushad, Hafiz Sohail

    2012-01-01

    The PVC superphylum is an amalgamation of species from the phyla Planctomycetes, Verrucomicrobia, and Chlamydiae, along with the Lentisphaerae, Poribacteria, and two other candidate divisions. The diverse species of this superphylum lack any significant marker that differentiates them from other bacteria. Recently, genome sequences for 37 species covering all of the main PVC groups of bacteria have become available. We have used these sequences to construct a phylogenetic tree based upon concatenated sequences for 16 proteins and identify molecular signatures in protein sequences that are specific for the species from these phyla or those providing molecular links among them. Of the useful molecular markers identified in the present work, six conserved signature indels (CSIs) in the proteins Cyt c oxidase, UvrD helicase, urease, and a helicase-domain containing protein are specific for the species from the Verrucomicrobia phylum; three other CSIs in an ABC transporter protein, cobyrinic acid ac-diamide synthase, and SpoVG protein are specific for the Planctomycetes species. Additionally, a 3 aa insert in the RpoB protein is uniquely present in all sequenced Chlamydiae, Verrucomicrobia, and Lentisphaerae species, providing evidence for the shared ancestry of the species from these three phyla. Lastly, we have also identified a conserved protein of unknown function that is exclusively found in all sequenced species from the phyla Chlamydiae, Verrucomicrobia, Lentisphaerae, and Planctomycetes suggesting a specific linkage among them. The absence of this protein in Poribacteria, which branches separately from other members of the PVC clade, indicates that it is not specifically related to the PVC clade of bacteria. The molecular markers described here in addition to clarifying the evolutionary relationships among the PVC clade of bacteria also provide novel tools for their identification and for genetic and biochemical studies on these organisms.

  17. Molecular Signatures for the PVC Clade (Planctomycetes, Verrucomicrobia, Chlamydiae, and Lentisphaerae) of Bacteria Provide Insights into Their Evolutionary Relationships

    PubMed Central

    Gupta, Radhey S.; Bhandari, Vaibhav; Naushad, Hafiz Sohail

    2012-01-01

    The PVC superphylum is an amalgamation of species from the phyla Planctomycetes, Verrucomicrobia, and Chlamydiae, along with the Lentisphaerae, Poribacteria, and two other candidate divisions. The diverse species of this superphylum lack any significant marker that differentiates them from other bacteria. Recently, genome sequences for 37 species covering all of the main PVC groups of bacteria have become available. We have used these sequences to construct a phylogenetic tree based upon concatenated sequences for 16 proteins and identify molecular signatures in protein sequences that are specific for the species from these phyla or those providing molecular links among them. Of the useful molecular markers identified in the present work, six conserved signature indels (CSIs) in the proteins Cyt c oxidase, UvrD helicase, urease, and a helicase-domain containing protein are specific for the species from the Verrucomicrobia phylum; three other CSIs in an ABC transporter protein, cobyrinic acid ac-diamide synthase, and SpoVG protein are specific for the Planctomycetes species. Additionally, a 3 aa insert in the RpoB protein is uniquely present in all sequenced Chlamydiae, Verrucomicrobia, and Lentisphaerae species, providing evidence for the shared ancestry of the species from these three phyla. Lastly, we have also identified a conserved protein of unknown function that is exclusively found in all sequenced species from the phyla Chlamydiae, Verrucomicrobia, Lentisphaerae, and Planctomycetes suggesting a specific linkage among them. The absence of this protein in Poribacteria, which branches separately from other members of the PVC clade, indicates that it is not specifically related to the PVC clade of bacteria. The molecular markers described here in addition to clarifying the evolutionary relationships among the PVC clade of bacteria also provide novel tools for their identification and for genetic and biochemical studies on these organisms. PMID:23060863

  18. Evolutionary Computing

    SciTech Connect

    Patton, Robert M; Cui, Xiaohui; Jiao, Yu; Potok, Thomas E

    2008-01-01

    The rate at which information overwhelms humans is significantly more than the rate at which humans have learned to process, analyze, and leverage this information. To overcome this challenge, new methods of computing must be formulated, and scientist and engineers have looked to nature for inspiration in developing these new methods. Consequently, evolutionary computing has emerged as new paradigm for computing, and has rapidly demonstrated its ability to solve real-world problems where traditional techniques have failed. This field of work has now become quite broad and encompasses areas ranging from artificial life to neural networks. This chapter focuses specifically on two sub-areas of nature-inspired computing: Evolutionary Algorithms and Swarm Intelligence.

  19. Molecular Engineering for Mechanically Resilient and Stretchable Electronic Polymers and Composites

    DTIC Science & Technology

    2016-06-08

    AFRL-AFOSR-VA-TR-2016-0231 Molecular Engineering for Mechanically Resilient and Stretchable Electronic Polymers and Composites Darren Lipomi...04-2013 to 31-03-2016 4. TITLE AND SUBTITLE Molecular Engineering for Mechanically Resilient and Stretchable Electronic Polymers and Composites 5a...conjugated polymers and composites by analysis of the structural determinants of the mechanical properties. We developed coarse-grained molecular

  20. The evolutionary diversity of insect retinal mosaics: Common design principles and emerging molecular logic

    PubMed Central

    Wernet, Mathias F.; Perry, Michael W.; Desplan, Claude

    2015-01-01

    Independent evolution has resulted in a vast diversity of eyes. Despite the lack of a common Bauplan or ancestral structure, similar developmental strategies are used. For instance, different classes of photoreceptor cells (PRs) are distributed stochastically and/or localized in different regions of the retina. Here we focus on recent progress made towards understanding the molecular principles behind patterning retinal mosaics of insects, one of the most diverse groups of animals adapted to life on land, in the air, under water, or on the water surface. Morphological, physiological, and behavioral studies from many species provide detailed descriptions of the vast variation in retinal design and function. By integrating this knowledge with recent progress in the characterization of insect Rhodopsins as well as insight from the model organism Drosophila melanogaster, we seek to identify the molecular logic behind the adaptation of retinal mosaics to an animal’s habitat and way of life. PMID:26025917

  1. A broad molecular phylogeny of ciliates: identification of major evolutionary trends and radiations within the phylum.

    PubMed Central

    Baroin-Tourancheau, A; Delgado, P; Perasso, R; Adoutte, A

    1992-01-01

    The cellular architecture of ciliates is one of the most complex known within eukaryotes. Detailed systematic schemes have thus been constructed through extensive comparative morphological and ultrastructural analysis of the ciliature and of its internal cytoskeletal derivatives (the infraciliature), as well as of the architecture of the oral apparatus. In recent years, a consensus was reached in which the phylum was divided in eight classes as defined by Lynn and Corliss [Lynn, D. H. & Corliss, J. O. (1991) in Microscopic Anatomy of Invertebrates: Protozoa (Wiley-Liss, New York), Vol. 1, pp. 333-467]. By comparing partial sequences of the large subunit rRNA molecule, and by using both distance-matrix and maximum-parsimony-tree construction methods (checked by boot-strapping), we examine the phylogenetic relationships of 22 species belonging to seven of these eight classes. At low taxonomic levels, the traditional grouping of the species is generally confirmed. At higher taxonomic levels, the branching pattern of these seven classes is resolved in several deeply separated major branches. Surprisingly, the first emerging one contains the heterotrichs and is strongly associated with a karyorelictid but deeply separated from hypotrichs. The litostomes, the oligohymenophorans, and the hypotrichs separate later in a bush-like topology hindering the resolution of their order of diversification. These results show a much more ancient origin of heterotrichs than was classically assumed, indicating that asymmetric, abundantly ciliated oral apparatuses do not correspond to "highly evolved" traits as previously thought. They also suggest the occurrence of a major radiative explosion in the evolutionary history of the ciliates, yielding five of the eight classes of the phylum. These classes appear to differ essentially according to the cytoskeletal architecture used to shape and sustain the cellular cortex (a process of essential adaptative and morphogenetic importance in

  2. Molecular phylogenetics and evolutionary history of sect. Quinquefoliae (Pinus): implications for Northern Hemisphere biogeography.

    PubMed

    Hao, Zhen-Zhen; Liu, Yan-Yan; Nazaire, Mare; Wei, Xiao-Xin; Wang, Xiao-Quan

    2015-06-01

    Climatic changes and tectonic events in the Cenozoic have greatly influenced the evolution and geographic distribution of the temperate flora. Such consequences should be most evident in plant groups that are ancient, widespread, and diverse. As one of the most widespread genera of trees, Pinus provides a good model for investigating the history of species diversification and biogeographic disjunction in the Northern Hemisphere. In this study, we reconstructed the phylogeny and investigated the evolutionary and biogeographic history of sect. Quinquefoliae (Pinus), a species-rich lineage disjunctly distributed in Asia, Europe and North America, based on complete taxon sampling and by using nine DNA fragments from chloroplast (cp), mitochondrial (mt) and nuclear genomes. The monophyly of the three subsections, Krempfianae, Gerardianae, and Strobus, is well-supported by cpDNA and nuclear gene phylogenies. However, neither subsect. Gerardianae nor subsect. Strobus forms a monophyletic group in the mtDNA phylogeny, in which sect. Quinquefoliae was divided into two major clades, one consisting of the North American and northeastern Asian species as well as the European P. peuce of subsect. Strobus, and the other comprising the remaining Eurasian species belonging to three subsections. The significant topological incongruence among the gene trees, in conjunction with divergence time estimation and ancestral area reconstruction, indicates that both ancient and relatively recent introgressive hybridization events occurred in the evolution of sect. Quinquefoliae, particularly in northeastern Asia and northwestern North America. In addition, the phylogenetic analysis suggests that the species of subsect. Strobus from subtropical eastern Asia and neighboring areas may have a single origin, although species non-monophyly is very widespread in the nuclear gene trees. Moreover, our study seems to support a Tethyan origin of sect. Quinquefoliae given the distributions and

  3. Monolithic integration of microelectronics and photonics using molecularly engineered materials

    NASA Astrophysics Data System (ADS)

    Kubacki, Ronald M.

    2005-03-01

    The monolithic integration of CMOS microelectronics with photonics is inevitable and benefits both technologies. Photonic integration to microelectronics provides such solutions as overcoming microprocessor communication roadblocks through the use of optical interconnection. Microelectronic integration can provide benefits to photonic structures by optimizing electronic signals generated by photonic biosensors for example. Photonic integration must complement, build on, and enhance the existing state of CMOS microelectronic technology. Photonic approaches that ignore the realities of CMOS architectures (such as power and thermal limitations), provide little benefit to the CMOS device performance, are incompatible with CMOS silicon manufacturing processes, or are incapable of achieving levels of long term reliability already well demonstrated by microelectronic devices, give little reason for photonic/microelectronic integration. Practical implementation of photonics on chip, monolithically with CMOS type microelectronic devices, remains in the laboratory. This work presents architectures to integrate photonics and microelectronics that address CMOS fabrication realities, increase performance of both the electronic and optical functions, and retain current levels of reliability. Fabricating these structures with the limited CMOS material set and/or typical photonic materials requires materials to be molecularly engineered to provide required properties. Materials have been investigated that enable economic fabrication of photonic structures for monolithic integration. Low loss self assembled silicon nanocomposite VIPIR waveguide structures are combined with long term stable non-linear poled polymers for fabrication of electro-optic active devices. Materials are fabricated using low temperature plasma enhanced chemical vapor deposition (PECVD).

  4. Evolutionary screening and adsorption behavior of engineered M13 bacteriophage and derived dodecapeptide for selective decoration of gold interfaces.

    PubMed

    Causa, F; Della Moglie, R; Iaccino, E; Mimmi, S; Marasco, D; Scognamiglio, P L; Battista, E; Palmieri, C; Cosenza, C; Sanguigno, L; Quinto, I; Scala, G; Netti, P A

    2013-01-01

    There is a growing interest in identifying biomacromolecules such as proteins and peptides to functionalize metallic surfaces through noncovalent binding. One method for functionalizing materials without fundamentally changing their inherent structure is using biorecognition moieties. Here, we proved a general route to select a biomolecule adhesive motif for surface functionalization by comprehensively screening phage displayed peptides. In particular, we selected a genetically engineered M13 bacteriophage and a linear dodecapeptide derived from its pIII domain for recognizing gold surfaces in a specific and selective manner. In the phage context, we demonstrated the adhesive motif was capable to adsorb on gold in a preferential way with a morphological and viscoelastic signature of the adsorbed layer as evidenced by QCM-D and AFM investigations. Out of the phage context, the linear dodecapeptide is reproducibly found to adhere to the gold surface, and by quantitative SPR measurements, high affinity constants (K(eq)~10(6)M(-1), binding energy ~-8 kcal/mol) were determined. We proved that the interactions occurring at gold interface were mainly hydrophobic as a consequence of high frequency of hydrophobic residues in the peptide sequence. Moreover, by CD, molecular dynamics and steered molecular dynamics, we demonstrated that the molecular flexibility only played a minor role in the peptide adsorption. Such noncovalent but specific modification of inorganic surfaces through high affinity biomolecule adsorption represents a general strategy to modulate the functionality of multipurpose metallic surfaces.

  5. Molecular signature of the D-loop in the brown pencilfish Nannostomus eques (Characiformes, Lebiasinidae) reveals at least two evolutionary units in the Rio Negro basin, Brazil.

    PubMed

    Terencio, M L; Schneider, C H; Porto, J I R

    2012-07-01

    The genetic variability of the brown pencilfish Nannostomus eques was studied, based on an analysis of sequences from the control region (1084 bp) of mitochondrial (mt)DNA in 125 individuals collected from eight tributaries along the upper (Açaituba, Miuá, Jaradi and Arixanã), middle (Demini), and lower (Jacundá, Maguari and Catalão) Rio Negro (Brazil). Phylogenetic inferences using mtDNA data from N. eques revealed two evolutionary units. Genetic distance between them ranged from 5.5 to 8.3% and differed by 8.5-11.8% from the sister species pencilfish Nannostomus unifasciatus. The time of divergence between the two evolutionary units was estimated to be the Middle Pliocene (c. 2.99 million years before present). Population genetic analysis (DNA polymorphism, AMOVA and Mantel test) showed high haplotype diversity (HD, >0.90) in each evolutionary unit, a strong population genetic structure in the Demini River that formed a monophyletic group and a correlation between genetic divergence and geographical distance in only one of these units (evolutionary unit 1). On the basis of molecular data, the rapids and waterfalls near São Gabriel da Cachoeira (Upper Rio Negro) were the main barriers to gene flow within evolutionary unit 1 in some localities. The emergences of the Branco River and the Anavilhanas Archipelago were apparently responsible for the discrepancy in distribution of the two evolutionary units, except at Jacundá, where the evolutionary units were sympatric. In view of the differences between the evolutionary units, N. eques cannot be treated as a single stock in the Rio Negro basin. These results may have important implications for the fishery management of this ornamental fish.

  6. The Interstellar Bullet Engine IRAS05506+2414: A Molecular-Line Study

    NASA Astrophysics Data System (ADS)

    Sahai, Raghvendra; Patel, N.; Claussen, M. J.; Sanchez Contreras, C.; Morris, M. R.

    2012-01-01

    High-mass stars play a decisive role in the evolution of galaxies. An exciting recent development in the understanding of those early evolutionary stages, based on a new study of the Orion BN/KL region, is that the disruption of a massive young stellar system can lead to an explosive event producing a wide-angle outflow. This is an entirely different phenomenon from the classical bipolar flows driven by YSO accretion disks. We report here preliminary results from a molecular-line study of a serendipitously discovered object, IRAS05506+2414, which most likely is only the second known example of this phenomenon in our Galaxy. Our HST images show a fan-like spray of high-velocity (up to 350 km/s) elongated knots which appear to emanate from a bright compact central source. The physical properties (opening angle, outflow speeds, knot masses, Herbig-Haro-object like optical line emission) of the IRAS05506 wide-angle outflow are very similar to the one in Orion. A second jet engine, similar to those which drive the classical accretion-driven jets seen in low-mass YSOs, also appears to be operating simultaneously in IRAS05506. This is indicated by an optical jet-like feature aligned with a high-velocity (>100 km/s) molecular outflow which appears to be bipolar and nearly perpendicular to the average direction of the knot spray. Our molecular-line study includes (a) single-dish observations at 1.1-1.3 and 2.6-3 mm of high-density tracers such as HCO+, CS and SO, and mapping of the ambient molecular cloud in CO and 13CO using the ARO's 10- and 12-m dishes, and (b) interferometric observations at 2.6 and 1.3 mm with OVRO and the SMA of CO, 13CO, SO and SiO lines and the dust continuum. Preliminary results on the mass, density and temperature of the outflow and ambient cloud using simple excitation/radiative transfer models will be presented.

  7. Molecular and evolutionary insights into the structural organization of cation chloride cotransporters

    PubMed Central

    Hartmann, Anna-Maria; Nothwang, Hans Gerd

    2015-01-01

    Cation chloride cotransporters (CCC) play an essential role for neuronal chloride homeostasis. K+-Cl− cotransporter (KCC2), is the principal Cl−-extruder, whereas Na+-K+-Cl− cotransporter (NKCC1), is the major Cl−-uptake mechanism in many neurons. As a consequence, the action of the inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine strongly depend on the activity of these two transporters. Knowledge of the mechanisms involved in ion transport and regulation is thus of great importance to better understand normal and disturbed brain function. Although no overall 3-dimensional crystal structures are yet available, recent molecular and phylogenetic studies and modeling have provided new and exciting insights into structure-function relationships of CCC. Here, we will summarize our current knowledge of the gross structural organization of the proteins, their functional domains, ion binding and translocation sites, and the established role of individual amino acids (aa). A major focus will be laid on the delineation of shared and distinct organizational principles between KCC2 and NKCC1. Exploiting the richness of recently generated genome data across the tree of life, we will also explore the molecular evolution of these features. PMID:25653592

  8. Evolutionary relationships of Metazoa within the eukaryotes based on molecular data from Porifera.

    PubMed Central

    Schütze, J; Krasko, A; Custodio, M R; Efremova, S M; Müller, I M; Müller, W E

    1999-01-01

    Recent molecular data provide strong support for the view that all metazoan phyla, including Porifera, are of monophyletic origin. The relationship of Metazoa, including the Porifera, to Plantae, Fungi and unicellular eukaryotes has only rarely been studied by using cDNAs coding for proteins. Sequence data from rDNA suggested a relationship of Porifera to unicellular eukaryotes (choanoflagellates). However, ultrastructural studies of choanocytes did not support these findings. In the present study, we compared amino acid sequences that are found in a variety of metazoans (including sponges) with those of Plantae, Fungi and unicellular eukaryotes, to obtain an answer to this question. We used the four sequences from 70 kDa heat-shock proteins, the serine-threonine kinase domain found in protein kinases, beta-tubulin and calmodulin. The latter two sequences were deduced from cDNAs, isolated from the sponge Geodia cydonium for the phylogenetic analyses presented. These revealed that the sponge molecules were grouped into the same branch as the Metazoa, which is statistically (significantly) separated from those branches that comprise the sequences from Fungi, Plantae and unicellular eukaryotes. From our molecular data it seems evident that the unicellular eukaryotes existed at an earlier stage of evolution, and the Plantae and especially the Fungi and the Metazoa only appeared later. PMID:10081159

  9. Molecular clocks provide new insights into the evolutionary history of Galeichthyine sea catfishes.

    PubMed

    Betancur-R, Ricardo; Armbruster, Jonathan W

    2009-05-01

    Intercontinental distributions in the southern hemisphere can either be the result of Gondwanan vicariance or more recent transoceanic dispersal. Transoceanic dispersal has come into vogue for explaining many intercontinental distributions; however, it has been used mainly for organisms that can float or raft between the continents. Despite their name, the Sea Catfishes (Ariidae) have limited dispersal ability, and there are no examples of nearshore ariid genera with a transoceanic distribution except for Galeichthys where three species occur in southern Africa and one in the Peruvian coast. A previous study suggested that the group originated in Gondwana, and that the species arrived at their current range after the breakup of the supercontinent in the Early Cretaceous. To test this hypothesis, we infer molecular phylogenies (mitochondrial cytochrome b, ATP synthase 8/6, 12S, and 16S; nuclear rag2; total approximately 4 kb) and estimate intercontinental divergence via molecular clocks (penalized-likelihood, Bayesian relaxed clock, and universal clock rates in fishes). Age ranges for cladogenesis of African and South American lineages are 15.4-2.5 my, far more recent than would be suggested by Gondwanan vicariance; thus, the distribution of galeichthyines must be explained by dispersal or more recent vicariant events. The nested position of the Peruvian species (Galeichthys peruvianus) within the African taxa is robust, suggesting that the direction of the dispersal was from Africa to South America. The progenitor of the Peruvian species likely arrived at its current distribution with the aid of ocean currents, and several scenarios are discussed.

  10. Molecular evolutionary rates predict both extinction and speciation in temperate angiosperm lineages

    PubMed Central

    2010-01-01

    Background A positive relationship between diversification (i.e., speciation) and nucleotide substitution rates is commonly reported for angiosperm clades. However, the underlying cause of this relationship is often unknown because multiple intrinsic and extrinsic factors can affect the relationship, and these have confounded previous attempts infer causation. Determining which factor drives this oft-reported correlation can lend insight into the macroevolutionary process. Results Using a new database of 13 time-calibrated angiosperm phylogenies based on internal transcribed spacer (ITS) sequences, and controlling for extrinsic variables of life history and habitat, I evaluated several potential intrinsic causes of this correlation. Speciation rates (λ) and relative extinction rates (ε) were positively correlated with mean substitution rates, but were uncorrelated with substitution rate heterogeneity. It is unlikely that the positive diversification-substitution correlation is due to accelerated molecular evolution during speciation (e.g., via enhanced selection or drift), because punctuated increases in ITS rate (i.e., greater mean and variation in ITS rate for rapidly speciating clades) were not observed. Instead, fast molecular evolution likely increases speciation rate (via increased mutational variation as a substrate for selection and reproductive isolation) but also increases extinction (via mutational genetic load). Conclusions In general, these results predict that clades with higher background substitution rates may undergo successful diversification under new conditions while clades with lower substitution rates may experience decreased extinction during environmental stasis. PMID:20515493

  11. Fault diagnosis engineering in molecular signaling networks: an overview and applications in target discovery.

    PubMed

    Abdi, Ali; Emamian, Effat S

    2010-05-01

    Fault diagnosis engineering is a key component of modern industrial facilities and complex systems, and has gone through considerable developments in the past few decades. In this paper, the principles and concepts of molecular fault diagnosis engineering are reviewed. In this area, molecular intracellular networks are considered as complex systems that may fail to function, due to the presence of some faulty molecules. Dysfunction of the system due to the presence of a single or multiple molecules can ultimately lead to the transition from the normal state to the disease state. It is the goal of molecular fault diagnosis engineering to identify the critical components of molecular networks, i.e., those whose dysfunction can interrupt the function of the entire network. The results of the fault analysis of several signaling networks are discussed, and possible connections of the findings with some complex human diseases are examined. Implications of molecular fault diagnosis engineering for target discovery and drug development are outlined as well.

  12. Evolutionary history of tall fescue morphotypes inferred from molecular phylogenetics of the Lolium-Festuca species complex

    PubMed Central

    2010-01-01

    Background The agriculturally important pasture grass tall fescue (Festuca arundinacea Schreb. syn. Lolium arundinaceum (Schreb.) Darbysh.) is an outbreeding allohexaploid, that may be more accurately described as a species complex consisting of three major (Continental, Mediterranean and rhizomatous) morphotypes. Observation of hybrid infertility in some crossing combinations between morphotypes suggests the possibility of independent origins from different diploid progenitors. This study aims to clarify the evolutionary relationships between each tall fescue morphotype through phylogenetic analysis using two low-copy nuclear genes (encoding plastid acetyl-CoA carboxylase [Acc1] and centroradialis [CEN]), the nuclear ribosomal DNA internal transcribed spacer (rDNA ITS) and the chloroplast DNA (cpDNA) genome-located matK gene. Other taxa within the closely related Lolium-Festuca species complex were also included in the study, to increase understanding of evolutionary processes in a taxonomic group characterised by multiple inter-specific hybridisation events. Results Putative homoeologous sequences from both nuclear genes were obtained from each polyploid species and compared to counterparts from 15 diploid taxa. Phylogenetic reconstruction confirmed F. pratensis and F. arundinacea var. glaucescens as probable progenitors to Continental tall fescue, and these species are also likely to be ancestral to the rhizomatous morphotype. However, these two morphotypes are sufficiently distinct to be located in separate clades based on the ITS-derived data set. All four of the generated data sets suggest independent evolution of the Mediterranean and Continental morphotypes, with minimal affinity between cognate sequence haplotypes. No obvious candidate progenitor species for Mediterranean tall fescues were identified, and only two putative sub-genome-specific haplotypes were identified for this morphotype. Conclusions This study describes the first phylogenetic analysis of

  13. Housing helpful invaders: the evolutionary and molecular architecture underlying plant root-mutualist microbe interactions

    PubMed Central

    Lagunas, B.; Schäfer, P.; Gifford, M. L.

    2015-01-01

    Plant root rhizosphere interactions with mutualistic microbes are diverse and numerous, having evolved over time in response to selective pressures on plants to attain anchorage and nutrients. These relationships can be considered to be formed through a combination of architectural connections: molecular architecture interactions that control root–microbe perception and regulate the balance between host and symbiont and developmental architecture interactions that enable the microbes to be ‘housed’ in the root and enable the exchange of compounds. Recent findings that help to understand the common architecture that exists between nodulation and mycorrhizal interactions, and how this architecture could be re-tuned to develop new symbioses, are discussed here. PMID:25743160

  14. Molecular and evolutionary history of melanism in North American gray wolves.

    PubMed

    Anderson, Tovi M; vonHoldt, Bridgett M; Candille, Sophie I; Musiani, Marco; Greco, Claudia; Stahler, Daniel R; Smith, Douglas W; Padhukasahasram, Badri; Randi, Ettore; Leonard, Jennifer A; Bustamante, Carlos D; Ostrander, Elaine A; Tang, Hua; Wayne, Robert K; Barsh, Gregory S

    2009-03-06

    Morphological diversity within closely related species is an essential aspect of evolution and adaptation. Mutations in the Melanocortin 1 receptor (Mc1r) gene contribute to pigmentary diversity in natural populations of fish, birds, and many mammals. However, melanism in the gray wolf, Canis lupus, is caused by a different melanocortin pathway component, the K locus, that encodes a beta-defensin protein that acts as an alternative ligand for Mc1r. We show that the melanistic K locus mutation in North American wolves derives from past hybridization with domestic dogs, has risen to high frequency in forested habitats, and exhibits a molecular signature of positive selection. The same mutation also causes melanism in the coyote, Canis latrans, and in Italian gray wolves, and hence our results demonstrate how traits selected in domesticated species can influence the morphological diversity of their wild relatives.

  15. Molecular insights into the evolutionary pathway of Vibrio cholerae O1 atypical El Tor variants.

    PubMed

    Kim, Eun Jin; Lee, Dokyung; Moon, Se Hoon; Lee, Chan Hee; Kim, Sang Jun; Lee, Jae Hyun; Kim, Jae Ouk; Song, Manki; Das, Bhabatosh; Clemens, John D; Pape, Jean William; Nair, G Balakrish; Kim, Dong Wook

    2014-09-01

    Pandemic V. cholerae strains in the O1 serogroup have 2 biotypes: classical and El Tor. The classical biotype strains of the sixth pandemic, which encode the classical type cholera toxin (CT), have been replaced by El Tor biotype strains of the seventh pandemic. The prototype El Tor strains that produce biotype-specific cholera toxin are being replaced by atypical El Tor variants that harbor classical cholera toxin. Atypical El Tor strains are categorized into 2 groups, Wave 2 and Wave 3 strains, based on genomic variations and the CTX phage that they harbor. Whole-genome analysis of V. cholerae strains in the seventh cholera pandemic has demonstrated gradual changes in the genome of prototype and atypical El Tor strains, indicating that atypical strains arose from the prototype strains by replacing the CTX phages. We examined the molecular mechanisms that effected the emergence of El Tor strains with classical cholera toxin-carrying phage. We isolated an intermediary V. cholerae strain that carried two different CTX phages that encode El Tor and classical cholera toxin, respectively. We show here that the intermediary strain can be converted into various Wave 2 strains and can act as the source of the novel mosaic CTX phages. These results imply that the Wave 2 and Wave 3 strains may have been generated from such intermediary strains in nature. Prototype El Tor strains can become Wave 3 strains by excision of CTX-1 and re-equipping with the new CTX phages. Our data suggest that inter-chromosomal recombination between 2 types of CTX phages is possible when a host bacterial cell is infected by multiple CTX phages. Our study also provides molecular insights into population changes in V. cholerae in the absence of significant changes to the genome but by replacement of the CTX prophage that they harbor.

  16. Evolutionary Description of Giant Molecular Cloud Mass Functions on Galactic Disks

    NASA Astrophysics Data System (ADS)

    Kobayashi, Masato I. N.; Inutsuka, Shu-ichiro; Kobayashi, Hiroshi; Hasegawa, Kenji

    2017-02-01

    Recent radio observations show that giant molecular cloud (GMC) mass functions noticeably vary across galactic disks. High-resolution magnetohydrodynamics simulations show that multiple episodes of compression are required for creating a molecular cloud in the magnetized interstellar medium. In this article, we formulate the evolution equation for the GMC mass function to reproduce the observed profiles, for which multiple compressions are driven by a network of expanding shells due to H ii regions and supernova remnants. We introduce the cloud–cloud collision (CCC) terms in the evolution equation in contrast to previous work (Inutsuka et al.). The computed time evolution suggests that the GMC mass function slope is governed by the ratio of GMC formation timescale to its dispersal timescale, and that the CCC effect is limited only in the massive end of the mass function. In addition, we identify a gas resurrection channel that allows the gas dispersed by massive stars to regenerate GMC populations or to accrete onto pre-existing GMCs. Our results show that almost all of the dispersed gas contributes to the mass growth of pre-existing GMCs in arm regions whereas less than 60% contributes in inter-arm regions. Our results also predict that GMC mass functions have a single power-law exponent in the mass range <105.5 {M}ȯ (where {M}ȯ represents the solar mass), which is well characterized by GMC self-growth and dispersal timescales. Measurement of the GMC mass function slope provides a powerful method to constrain those GMC timescales and the gas resurrecting factor in various environments across galactic disks.

  17. Novel molecular, structural and evolutionary characteristics of the phosphoketolases from bifidobacteria and Coriobacteriales

    PubMed Central

    Nanda, Anish; Khadka, Bijendra

    2017-01-01

    Members from the order Bifidobacteriales, which include many species exhibiting health promoting effects, differ from all other organisms in using a unique pathway for carbohydrate metabolism, known as the “bifid shunt”, which utilizes the enzyme phosphoketolase (PK) to carry out the phosphorolysis of both fructose-6-phosphate (F6P) and xylulose-5-phosphate (X5P). In contrast to bifidobacteria, the PKs found in other organisms (referred to XPK) are able to metabolize primarily X5P and show very little activity towards F6P. Presently, very little is known about the molecular or biochemical basis of the differences in the two forms of PKs. Comparative analyses of PK sequences from different organisms reported here have identified multiple high-specific sequence features in the forms of conserved signature inserts and deletions (CSIs) in the PK sequences that clearly distinguish the X5P/F6P phosphoketolases (XFPK) of bifidobacteria from the XPK homologs found in most other organisms. Interestingly, most of the molecular signatures that are specific for the XFPK from bifidobacteria are also shared by the PK homologs from the Coriobacteriales order of Actinobacteria. Similarly to the Bifidobacteriales, the order Coriobacteriales is also made up of commensal organisms, that are saccharolytic and able to metabolize wide variety of carbohydrates, producing lactate and other metabolites. Phylogenetic studies provide evidence that the XFPK from bifidobacteria are specifically related to those found in the Coriobacteriales and suggest that the gene for PK (XFPK) was horizontally transferred between these two groups. A number of the identified CSIs in the XFPK sequence, which serve to distinguish the XFPK homologs from XPK homologs, are located at the subunit interface in the structure of the XFPK dimer protein. The results of protein modelling and subunit docking studies indicate that these CSIs are involved in the formation/stabilization of the protein dimer. The

  18. Molecular systematics of Serrasalmidae: Deciphering the identities of piranha species and unraveling their evolutionary histories

    USGS Publications Warehouse

    Freeman, B.; Nico, L.G.; Osentoski, M.; Jelks, H.L.; Collins, T.M.

    2007-01-01

    Piranhas and their relatives have proven to be a challenging group from a systematic perspective, with difficulties in identification of species, linking of juveniles to adults, diagnosis of genera, and recognition of higher-level clades. In this study we add new molecular data consisting of three mitochondrial regions for museum vouchered and photo-documented representatives of the Serrasalmidae. These are combined with existing serrasalmid sequences in GenBank to address species and higher-level questions within the piranhas using parsimony and Bayesian methods. We found robust support for the monophyly of Serrasalmus manueli, but not for Serrasalmus gouldingi when GenBank specimens identified as S. gouldingi were included in the analysis. "Serrasalmus gouldingi" sequences in GenBank may, however, be misidentified. Linking of juveniles to adults of the same species was greatly facilitated by the addition of sequence data. Based on our sampling and identifications, our data robustly reject the monophyly of the genera Serrasalmus and Pristobrycon. We found evidence for a well-supported clade comprised of Serrasalmus, Pygocentrus, and Pristobrycon (in part). This clade was robustly supported in separate and combined analyses of gene regions, and was also supported by a unique molecular character, the loss of a tandem repeat in the control region. Analysis of specimens and a literature review suggest this clade is also characterized by the presence of a pre-anal spine and ectopterygoid teeth. A persistent polytomy at the base of this clade was dated using an independent calibration as 1.8 million years old, corresponding to the beginning of the Pleistocene Epoch, and suggesting an origin for this clade more recent than dates cited in the recent literature. The sister group to this clade is also robustly supported, and consists of Catoprion, Pygopristis, and Pristobrycon striolatus. If the term piranha is to refer to a monophyletic clade, it should be restricted to

  19. The dynamical evolution of molecular clouds near the Galactic Centre - I. Orbital structure and evolutionary timeline

    NASA Astrophysics Data System (ADS)

    Kruijssen, J. M. Diederik; Dale, James E.; Longmore, Steven N.

    2015-02-01

    We recently proposed that the star-forming potential of dense molecular clouds in the Central Molecular Zone (CMZ, i.e. the central few 100 pc) of the Milky Way is intimately linked to their orbital dynamics, potentially giving rise to an absolute-time sequence of star-forming clouds. In this paper, we present an orbital model for the gas stream(s) observed in the CMZ. The model is obtained by integrating orbits in the empirically constrained gravitational potential and represents a good fit (χ _red^2=2.0) to the observed position-velocity distribution of dense (n > several 103 cm-3) gas, reproducing all of its key properties. The orbit is also consistent with observational constraints not included in the fitting process, such as the 3D space velocities of Sgr B2 and the Arches and Quintuplet clusters. It differs from previous, parametric models in several respects: (1) the orbit is open rather than closed due to the extended mass distribution in the CMZ, (2) its orbital velocity (100-200 km s-1) is twice as high as in previous models, and (3) Sgr A* coincides with the focus of the (eccentric) orbit rather than being offset. Our orbital solution supports the recently proposed scenario in which the dust ridge between G0.253+0.016 (`the Brick') and Sgr B2 represents an absolute-time sequence of star-forming clouds, of which the condensation was triggered by the tidal compression during their most recent pericentre passage. We position the clouds on a common timeline and find that their pericentre passages occurred 0.30-0.74 Myr ago. Given their short free-fall times (tff ˜ 0.34 Myr), the quiescent cloud G0.253+0.016 and the vigorously star-forming complex Sgr B2 are separated by a single free-fall time of evolution, implying that star formation proceeds rapidly once collapse has been initiated. We provide the complete orbital solution, as well as several quantitative predictions of our model (e.g. proper motions and the positions of star formation `hotspots'). The

  20. Novel molecular, structural and evolutionary characteristics of the phosphoketolases from bifidobacteria and Coriobacteriales.

    PubMed

    Gupta, Radhey S; Nanda, Anish; Khadka, Bijendra

    2017-01-01

    Members from the order Bifidobacteriales, which include many species exhibiting health promoting effects, differ from all other organisms in using a unique pathway for carbohydrate metabolism, known as the "bifid shunt", which utilizes the enzyme phosphoketolase (PK) to carry out the phosphorolysis of both fructose-6-phosphate (F6P) and xylulose-5-phosphate (X5P). In contrast to bifidobacteria, the PKs found in other organisms (referred to XPK) are able to metabolize primarily X5P and show very little activity towards F6P. Presently, very little is known about the molecular or biochemical basis of the differences in the two forms of PKs. Comparative analyses of PK sequences from different organisms reported here have identified multiple high-specific sequence features in the forms of conserved signature inserts and deletions (CSIs) in the PK sequences that clearly distinguish the X5P/F6P phosphoketolases (XFPK) of bifidobacteria from the XPK homologs found in most other organisms. Interestingly, most of the molecular signatures that are specific for the XFPK from bifidobacteria are also shared by the PK homologs from the Coriobacteriales order of Actinobacteria. Similarly to the Bifidobacteriales, the order Coriobacteriales is also made up of commensal organisms, that are saccharolytic and able to metabolize wide variety of carbohydrates, producing lactate and other metabolites. Phylogenetic studies provide evidence that the XFPK from bifidobacteria are specifically related to those found in the Coriobacteriales and suggest that the gene for PK (XFPK) was horizontally transferred between these two groups. A number of the identified CSIs in the XFPK sequence, which serve to distinguish the XFPK homologs from XPK homologs, are located at the subunit interface in the structure of the XFPK dimer protein. The results of protein modelling and subunit docking studies indicate that these CSIs are involved in the formation/stabilization of the protein dimer. The

  1. Evolutionary adaptation of plant annexins has diversified their molecular structures, interactions and functional roles.

    PubMed

    Clark, Greg B; Morgan, Reginald O; Fernandez, Maria-Pilar; Roux, Stanley J

    2012-11-01

    Annexins are an homologous, structurally related superfamily of proteins known to associate with membrane lipid and cytoskeletal components. Their involvement in membrane organization, vesicle trafficking and signaling is fundamental to cellular processes such as growth, differentiation, secretion and repair. Annexins exist in some prokaryotes and all eukaryotic phyla within which plant annexins represent a monophyletic clade of homologs descended from green algae. Genomic, proteomic and transcriptomic approaches have provided data on the diversity, cellular localization and expression patterns of different plant annexins. The availability of 35 complete plant genomes has enabled systematic comparative analysis to determine phylogenetic relationships, characterize structures and observe functional specificity between and within individual subfamilies. Short amino termini and selective erosion of the canonical type 2 calcium coordinating sites in domains 2 and 3 are typical of plant annexins. The convergent evolution of alternate functional motifs such as 'KGD', redox-sensitive Cys and hydrophobic Trp/Phe residues argues for their functional relevance and contribution to mechanistic diversity in plant annexins. This review examines recent findings and advances in plant annexin research with special focus on their structural diversity, cellular and molecular interactions and their potential integrated functions in the broader context of physiological responses.

  2. Evolutionary redefinition of immunoglobulin light chain isotypes in tetrapods using molecular markers.

    PubMed

    Das, Sabyasachi; Nikolaidis, Nikolas; Klein, Jan; Nei, Masatoshi

    2008-10-28

    The phylogenetic relationships of Ig light chain (IGL) genes are difficult to resolve, because these genes are short and evolve relatively fast. Here, we classify the IGL sequences from 12 tetrapod species into three distinct groups (kappa, lambda, and sigma isotypes) using conserved amino acid residues, recombination signal sequences, and genomic organization of IGL genes as cladistic markers. From the distribution of the markers we conclude that the earliest extant tetrapods, the amphibians, possess three IGL isotypes: kappa, lambda, and sigma. Of these, two (kappa and lambda) are also found in reptiles and some mammals. The lambda isotype is found in all tetrapods tested to date, whereas the kappa isotype seems to have been lost at least in some birds and in the microbat. Conservation of the cladistic molecular markers suggests that they are associated with functional specialization of the three IGL isotypes. The genomic maps of IGL loci reveal multiple gene rearrangements that occurred in the evolution of tetrapod species. These rearrangements have resulted in interspecific variation of the genomic lengths of the IGL loci and the number and order of IGL constituent genes, but the overall organization of the IGL loci has not changed.

  3. Molecular characterization and evolutionary study of spider tubuliform (eggcase) silk protein.

    PubMed

    Tian, Maozhen; Lewis, Randolph V

    2005-06-07

    As a result of hundreds of millions of years of evolution, orb-web-weaving spiders have developed the use of seven different silks produced by different abdominal glands for various functions. Tubuliform silk (eggcase silk) is unique among these spider silks due to its high serine and very low glycine content. In addition, tubuliform silk is the only silk produced just during a short period of time, the reproductive season, in the spider's life. To understand the molecular characteristics of the proteins composing this silk, we constructed tubuliform-gland-specific cDNA libraries from three different spider families, Nephila clavipes, Argiope aurantia, and Araneus gemmoides. Sequencing of tubuliform silk cDNAs reveals the repetitive architecture of its coding sequence and novel amino acid motifs. The inferred protein, tubuliform spidroin 1 (TuSp1), contains highly homogenized repeats in all three spiders. Amino acid composition comparison of the predicted tubuliform silk protein sequence to tubuliform silk indicates that TuSp1 is the major component of tubuliform silk. Repeat unit alignment of TuSp1 among three spider species shows high sequence conservation among tubuliform silk protein orthologue groups. Sequence comparison among TuSp1 repetitive units within species suggests intragenic concerted evolution, presumably through gene conversion and unequal crossover events. Comparative analysis demonstrates that TuSp1 represents a new orthologue in the spider silk gene family.

  4. Molecular cloning and evolutionary analysis of the GJA1 (connexin43) gene from bats (Chiroptera).

    PubMed

    Wang, Li; Li, Gang; Wang, Jinhong; Ye, Shaohui; Jones, Gareth; Zhang, Shuyi

    2009-04-01

    Gap junction protein connexin43 (Cx43), encoded by the GJA1 gene, is the most abundant connexin in the cardiovascular system and was reported as a crucial factor maintaining cardiac electrical conduction, as well as having a very important function in facilitating the recycling of potassium ions from hair cells in the cochlea back into the cochlear endolymph during auditory transduction processes. In mammals, bats are the only taxon possessing powered flight, placing exceptional demand on many organismal processes. To meet the demands of flying, the hearts of bats show many specialties. Moreover, ultrasonic echolocation allows bat species to orientate and often detect and locate food in darkness. In this study, we cloned the full-length coding region of GJA1 gene from 12 different species of bats and obtained orthologous sequences from other mammals. We used the maximum likelihood method to analyse the evolution of GJA1 gene in mammals and the lineage of bats. Our results showed this gene is much conserved in mammals, as well as in bats' lineage. Compared with other mammals, we found one private amino acid substitution shared by bats, which is located on the inner loop domain, as well as some species-specific amino acid substitutions. The evolution rate analyses showed the signature of purifying selection on not only different classification level lineages but also the different domains and amino acid residue sites of this gene. Also, we suggested that GJA1 gene could be used as a good molecular marker to do the phylogenetic reconstruction.

  5. Intrinsic Disorder in Pathogen Effectors: Protein Flexibility as an Evolutionary Hallmark in a Molecular Arms Race[W

    PubMed Central

    Marín, Macarena; Uversky, Vladimir N.; Ott, Thomas

    2013-01-01

    Effector proteins represent a refined mechanism of bacterial pathogens to overcome plants’ innate immune systems. These modular proteins often manipulate host physiology by directly interfering with immune signaling of plant cells. Even if host cells have developed efficient strategies to perceive the presence of pathogenic microbes and to recognize intracellular effector activity, it remains an open question why only few effectors are recognized directly by plant resistance proteins. Based on in-silico genome-wide surveys and a reevaluation of published structural data, we estimated that bacterial effectors of phytopathogens are highly enriched in long-disordered regions (>50 residues). These structurally flexible segments have no secondary structure under physiological conditions but can fold in a stimulus-dependent manner (e.g., during protein–protein interactions). The high abundance of intrinsic disorder in effectors strongly suggests positive evolutionary selection of this structural feature and highlights the dynamic nature of these proteins. We postulate that such structural flexibility may be essential for (1) effector translocation, (2) evasion of the innate immune system, and (3) host function mimicry. The study of these dynamical regions will greatly complement current structural approaches to understand the molecular mechanisms of these proteins and may help in the prediction of new effectors. PMID:24038649

  6. Cracking the egg: molecular dynamics and evolutionary aspects of the transition from the fully grown oocyte to embryo

    PubMed Central

    Evsikov, Alexei V.; Graber, Joel H.; Brockman, J. Michael; Hampl, Aleš; Holbrook, Andrea E.; Singh, Priyam; Eppig, John J.; Solter, Davor; Knowles, Barbara B.

    2006-01-01

    Fully grown oocytes (FGOs) contain all the necessary transcripts to activate molecular pathways underlying the oocyte-to-embryo transition (OET). To elucidate this critical period of development, an extensive survey of the FGO transcriptome was performed by analyzing 19,000 expressed sequence tags of the Mus musculus FGO cDNA library. Expression of 5400 genes and transposable elements is reported. For a majority of genes expressed in mouse FGOs, homologs transcribed in eggs of Xenopus laevis or Ciona intestinalis were found, pinpointing evolutionary conservation of most regulatory cascades underlying the OET in chordates. A large proportion of identified genes belongs to several gene families with oocyte-restricted expression, a likely result of lineage-specific genomic duplications. Gene loss by mutation and expression in female germline of retrotransposed genes specific to M. musculus is documented. These findings indicate rapid diversification of genes involved in female reproduction. Comparison of the FGO and two-cell embryo transcriptomes demarcated the processes important for oogenesis from those involved in OET and identified novel motifs in maternal mRNAs associated with transcript stability. Discovery of oocyte-specific eukaryotic translation initiation factor 4E distinguishes a novel system of translational regulation. These results implicate conserved pathways underlying transition from oogenesis to initiation of development and illustrate how genes acquire and lose reproductive functions during evolution, a potential mechanism for reproductive isolation. PMID:17015433

  7. Evolutionary History of the PER3 Variable Number of Tandem Repeats (VNTR): Idiosyncratic Aspect of Primate Molecular Circadian Clock

    PubMed Central

    Sabino, Flávia Cal; Ribeiro, Amanda Oliveira; Tufik, Sérgio; Torres, Laila Brito; Oliveira, José Américo; Mello, Luiz Eugênio Araújo Moraes; Cavalcante, Jeferson Souza; Pedrazzoli, Mario

    2014-01-01

    The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR) locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns. PMID:25222750

  8. Are Pharmaceuticals with Evolutionary Conserved Molecular Drug Targets More Potent to Cause Toxic Effects in Non-Target Organisms?

    PubMed Central

    Furuhagen, Sara; Fuchs, Anne; Lundström Belleza, Elin; Breitholtz, Magnus; Gorokhova, Elena

    2014-01-01

    The ubiquitous use of pharmaceuticals has resulted in a continuous discharge into wastewater and pharmaceuticals and their metabolites are found in the environment. Due to their design towards specific drug targets, pharmaceuticals may be therapeutically active already at low environmental concentrations. Several human drug targets are evolutionary conserved in aquatic organisms, raising concerns about effects of these pharmaceuticals in non-target organisms. In this study, we hypothesized that the toxicity of a pharmaceutical towards a non-target invertebrate depends on the presence of the human drug target orthologs in this species. This was tested by assessing toxicity of pharmaceuticals with (miconazole and promethazine) and without (levonorgestrel) identified drug target orthologs in the cladoceran Daphnia magna. The toxicity was evaluated using general toxicity endpoints at individual (immobility, reproduction and development), biochemical (RNA and DNA content) and molecular (gene expression) levels. The results provide evidence for higher toxicity of miconazole and promethazine, i.e. the drugs with identified drug target orthologs. At the individual level, miconazole had the lowest effect concentrations for immobility and reproduction (0.3 and 0.022 mg L−1, respectively) followed by promethazine (1.6 and 0.18 mg L−1, respectively). At the biochemical level, individual RNA content was affected by miconazole and promethazine already at 0.0023 and 0.059 mg L−1, respectively. At the molecular level, gene expression for cuticle protein was significantly suppressed by exposure to both miconazole and promethazine; moreover, daphnids exposed to miconazole had significantly lower vitellogenin expression. Levonorgestrel did not have any effects on any endpoints in the concentrations tested. These results highlight the importance of considering drug target conservation in environmental risk assessments of pharmaceuticals. PMID:25140792

  9. Phylogeny, evolutionary trends and classification of the Spathelia–Ptaeroxylon clade: morphological and molecular insights

    PubMed Central

    Appelhans, M. S.; Smets, E.; Razafimandimbison, S. G.; Haevermans, T.; van Marle, E. J.; Couloux, A.; Rabarison, H.; Randrianarivelojosia, M.; Keßler, P. J. A.

    2011-01-01

    Background and Aims The Spathelia–Ptaeroxylon clade is a group of morphologically diverse plants that have been classified together as a result of molecular phylogenetic studies. The clade is currently included in Rutaceae and recognized at a subfamilial level (Spathelioideae) despite the fact that most of its genera have traditionally been associated with other families and that there are no obvious morphological synapomorphies for the clade. The aim of the present study is to construct phylogenetic trees for the Spathelia–Ptaeroxylon clade and to investigate anatomical characters in order to decide whether it should be kept in Rutaceae or recognized at the familial level. Anatomical characters were plotted on a cladogram to help explain character evolution within the group. Moreover, phylogenetic relationships and generic limits within the clade are also addressed. Methods A species-level phylogenetic analysis of the Spathelia–Ptaeroxylon clade based on five plastid DNA regions (rbcL, atpB, trnL–trnF, rps16 and psbA–trnH) was conducted using Bayesian, maximum parsimony and maximum likelihood methods. Leaf and seed anatomical characters of all genera were (re)investigated by light and scanning electron microscopy. Key Results With the exception of Spathelia, all genera of the Spathelila–Ptaeroxylon clade are monophyletic. The typical leaf and seed anatomical characters of Rutaceae were found. Further, the presence of oil cells in the leaves provides a possible synapomorphy for the clade. Conclusions The Spathelia–Ptaeroxylon clade is well placed in Rutaceae and it is reasonable to unite the genera into one subfamily (Spathelioideae). We propose a new tribal classification of Spathelioideae. A narrow circumscription of Spathelia is established to make the genus monophyletic, and Sohnreyia is resurrected to accommodate the South American species of Spathelia. The most recent common ancestor of Spathelioideae probably had leaves with secretory cavities

  10. Morphological and molecular evidence for a stepwise evolutionary transition from teeth to baleen in mysticete whales.

    PubMed

    Deméré, Thomas A; McGowen, Michael R; Berta, Annalisa; Gatesy, John

    2008-02-01

    The origin of baleen in mysticete whales represents a major transition in the phylogenetic history of Cetacea. This key specialization, a keratinous sieve that enables filter-feeding, permitted exploitation of a new ecological niche and heralded the evolution of modern baleen-bearing whales, the largest animals on Earth. To date, all formally described mysticete fossils conform to two types: toothed species from Oligocene-age rocks ( approximately 24 to 34 million years old) and toothless species that presumably utilized baleen to feed (Recent to approximately 30 million years old). Here, we show that several Oligocene toothed mysticetes have nutrient foramina and associated sulci on the lateral portions of their palates, homologous structures in extant mysticetes house vessels that nourish baleen. The simultaneous occurrence of teeth and nutrient foramina implies that both teeth and baleen were present in these early mysticetes. Phylogenetic analyses of a supermatrix that includes extinct taxa and new data for 11 nuclear genes consistently resolve relationships at the base of Mysticeti. The combined data set of 27,340 characters supports a stepwise transition from a toothed ancestor, to a mosaic intermediate with both teeth and baleen, to modern baleen whales that lack an adult dentition but retain developmental and genetic evidence of their ancestral toothed heritage. Comparative sequence data for ENAM (enamelin) and AMBN (ameloblastin) indicate that enamel-specific loci are present in Mysticeti but have degraded to pseudogenes in this group. The dramatic transformation in mysticete feeding anatomy documents an apparently rare, stepwise mode of evolution in which a composite phenotype bridged the gap between primitive and derived morphologies; a combination of fossil and molecular evidence provides a multifaceted record of this macroevolutionary pattern.

  11. The Shark Alar Hypothalamus: Molecular Characterization of Prosomeric Subdivisions and Evolutionary Trends.

    PubMed

    Santos-Durán, Gabriel N; Ferreiro-Galve, Susana; Menuet, Arnaud; Quintana-Urzainqui, Idoia; Mazan, Sylvie; Rodríguez-Moldes, Isabel; Candal, Eva

    2016-01-01

    The hypothalamus is an important physiologic center of the vertebrate brain involved in the elaboration of individual and species survival responses. To better understand the ancestral organization of the alar hypothalamus we revisit previous data on ScOtp, ScDlx2/5, ScTbr1, ScNkx2.1 expression and Pax6 immunoreactivity jointly with new data on ScNeurog2, ScLhx9, ScLhx5, and ScNkx2.8 expression, in addition to immunoreactivity to serotonin (5-HT) and doublecortin (DCX) in the catshark Scyliorhinus canicula, a key species for this purpose since cartilaginous fishes are basal representatives of gnathostomes (jawed vertebrates). Our study revealed a complex genoarchitecture for the chondrichthyan alar hypothalamus. We identified terminal (rostral) and peduncular (caudal) subdivisions in the prosomeric paraventricular and subparaventricular areas (TPa/PPa and TSPa/PSPa, respectively) evidenced by the expression pattern of developmental genes like ScLhx5 (TPa) and immunoreactivity against Pax6 (PSPa) and 5-HT (PPa and PSPa). Dorso-ventral subdivisions were only evidenced in the SPa (SPaD, SPaV; respectively) by means of Pax6 and ScNkx2.8 (respectively). Interestingly, ScNkx2.8 expression overlaps over the alar-basal boundary, as Nkx2.2 does in other vertebrates. Our results reveal evidences for the existence of different groups of tangentially migrated cells expressing ScOtp, Pax6, and ScDlx2. The genoarchitectonic comparative analysis suggests alternative interpretations of the rostral-most alar plate in prosomeric terms and reveals a conserved molecular background for the vertebrate alar hypothalamus likely acquired before/during the agnathan-gnathostome transition, on which Otp, Pax6, Lhx5, and Neurog2 are expressed in the Pa while Dlx and Nkx2.2/Nkx2.8 are expressed in the SPa.

  12. Matrix Gla protein in Xenopus laevis: molecular cloning, tissue distribution, and evolutionary considerations.

    PubMed

    Cancela, M L; Ohresser, M C; Reia, J P; Viegas, C S; Williamson, M K; Price, P A

    2001-09-01

    Matrix Gla protein (MGP) belongs to the family of vitamin K-dependent, Gla-containing proteins and in higher vertebrates, is found in the extracellular matrix of mineralized tissues and soft tissues. MGP synthesis is highly regulated at the transcription and posttranscription levels and is now known to be involved in the regulation of extracellular matrix calcification and maintenance of cartilage and soft tissue integrity during growth and development. However, its mode of action at the molecular level remains unknown. Because there is a large degree of conservation between amino acid sequences of shark and human MGP, the function of MGP probably has been conserved throughout evolution. Given the complexity of the mammalian system, the study of MGP in a lower vertebrate might be advantageous to relate the onset of MGP expression with specific events during development. Toward this goal, MGP was purified from Xenopus long bones and its N-terminal amino acid sequence was determined and used to clone the Xenopus MGP complementary DNA (cDNA) by a mixture of reverse-transcription (RT)- and 5'- rapid amplification of cDNA ends (RACE)-polymerase chain reaction (PCR). MGP messenger RNA (mRNA) was present in all tissues analyzed although predominantly expressed in Xenopus bone and heart and its presence was detected early in development at the onset of chondrocranium development and long before the appearance of the first calcified structures and metamorphosis. These results show that in this system, as in mammals, MGP may be required to delay or prevent mineralization of cartilage and soft tissues during the early stages of development and indicate that Xenopus is an adequate model organism to further study MGP function during growth and development.

  13. Molecular bases and evolutionary dynamics of self-incompatibility in the Pyrinae (Rosaceae).

    PubMed

    De Franceschi, Paolo; Dondini, Luca; Sanzol, Javier

    2012-06-01

    The molecular bases of the gametophytic self-incompatibility (GSI) system of species of the subtribe Pyrinae (Rosaceae), such as apple and pear, have been widely studied in the last two decades. The characterization of S-locus genes and of the mechanisms underlying pollen acceptance or rejection have been topics of major interest. Besides the single pistil-side S determinant, the S-RNase, multiple related S-locus F-box genes seem to be involved in the determination of pollen S specificity. Here, we collect and review the state of the art of GSI in the Pyrinae. We emphasize recent genomic data that have contributed to unveiling the S-locus structure of the Pyrinae, and discuss their consistency with the models of self-recognition that have been proposed for Prunus and the Solanaceae. Experimental data suggest that the mechanism controlling pollen-pistil recognition specificity of the Pyrinae might fit well with the collaborative 'non-self' recognition system proposed for Petunia (Solanaceae), whereas it presents relevant differences with the mechanism exhibited by the species of the closely related genus Prunus, which uses a single evolutionarily divergent F-box gene as the pollen S determinant. The possible involvement of multiple pollen S genes in the GSI system of Pyrinae, still awaiting experimental confirmation, opens up new perspectives to our understanding of the evolution of S haplotypes, and of the evolution of S-RNase-based GSI within the Rosaceae family. Whereas S-locus genes encode the players determining self-recognition, pollen rejection in the Pyrinae seems to involve a complex cascade of downstream cellular events with significant similarities to programmed cell death.

  14. The Shark Alar Hypothalamus: Molecular Characterization of Prosomeric Subdivisions and Evolutionary Trends

    PubMed Central

    Santos-Durán, Gabriel N.; Ferreiro-Galve, Susana; Menuet, Arnaud; Quintana-Urzainqui, Idoia; Mazan, Sylvie; Rodríguez-Moldes, Isabel; Candal, Eva

    2016-01-01

    The hypothalamus is an important physiologic center of the vertebrate brain involved in the elaboration of individual and species survival responses. To better understand the ancestral organization of the alar hypothalamus we revisit previous data on ScOtp, ScDlx2/5, ScTbr1, ScNkx2.1 expression and Pax6 immunoreactivity jointly with new data on ScNeurog2, ScLhx9, ScLhx5, and ScNkx2.8 expression, in addition to immunoreactivity to serotonin (5-HT) and doublecortin (DCX) in the catshark Scyliorhinus canicula, a key species for this purpose since cartilaginous fishes are basal representatives of gnathostomes (jawed vertebrates). Our study revealed a complex genoarchitecture for the chondrichthyan alar hypothalamus. We identified terminal (rostral) and peduncular (caudal) subdivisions in the prosomeric paraventricular and subparaventricular areas (TPa/PPa and TSPa/PSPa, respectively) evidenced by the expression pattern of developmental genes like ScLhx5 (TPa) and immunoreactivity against Pax6 (PSPa) and 5-HT (PPa and PSPa). Dorso-ventral subdivisions were only evidenced in the SPa (SPaD, SPaV; respectively) by means of Pax6 and ScNkx2.8 (respectively). Interestingly, ScNkx2.8 expression overlaps over the alar-basal boundary, as Nkx2.2 does in other vertebrates. Our results reveal evidences for the existence of different groups of tangentially migrated cells expressing ScOtp, Pax6, and ScDlx2. The genoarchitectonic comparative analysis suggests alternative interpretations of the rostral-most alar plate in prosomeric terms and reveals a conserved molecular background for the vertebrate alar hypothalamus likely acquired before/during the agnathan-gnathostome transition, on which Otp, Pax6, Lhx5, and Neurog2 are expressed in the Pa while Dlx and Nkx2.2/Nkx2.8 are expressed in the SPa. PMID:27932958

  15. Evolutionary implications of morphogenesis and molecular patterning of the blind gut in the planarian Schmidtea polychroa.

    PubMed

    Martín-Durán, José María; Romero, Rafael

    2011-04-01

    The formation of a through-gut was a key innovation in the evolution of metazoans. There is still controversy regarding the origin of the anus and how it may have been either gained or lost during evolution in different bilaterian taxa. Thus, the study of groups with a blind gut is of great importance for understanding the evolution of this organ system. Here, we describe the morphogenesis and molecular patterning of the blind gut in the sexual triclad Schmidtea polychroa. We identify and analyze the expression of goosecoid, commonly associated with the foregut, and the GATA, ParaHox and T-box genes, members of which commonly are associated with gut regionalization. We show that GATA456a is expressed in the blind gut of triclads, while GATA456b is localized in dorsal parenchymal cells. Goosecoid is expressed in the central nervous system, and the unique ParaHox gene identified, Xlox, is detected in association with the nervous system. We have not isolated any brachyury gene in the T-box complement of S. polychroa, which consists of one tbx1/10, three tbx2/3 and one tbx20. Furthermore, the absence of genes like brachyury and caudal is also present in other groups of Platyhelminthes. This study suggests that GATA456, in combination with foxA, is a gut-specific patterning mechanism conserved in the triclad S. polychroa, while the conserved gut-associated expression of foregut, midgut and hindgut markers is absent. Based on these data and the deviations in spiral cleavage found in more basal flatworms, we propose that the lack of an anus is an innovation of Platyhelminthes. This may be associated with loss of gut gene expression or even gene loss.

  16. Use of phylogenetics in the molecular epidemiology and evolutionary studies of viral infections.

    PubMed

    Lam, Tommy Tsan-Yuk; Hon, Chung-Chau; Tang, Julian W

    2010-01-01

    Since DNA sequencing techniques first became available almost 30 years ago, the amount of nucleic acid sequence data has increased enormously. Phylogenetics, which is widely applied to compare and analyze such data, is particularly useful for the analysis of genes from rapidly evolving viruses. It has been used extensively to describe the molecular epidemiology and transmission of the human immunodeficiency virus (HIV), the origins and subsequent evolution of the severe acute respiratory syndrome (SARS)-associated coronavirus (SCoV), and, more recently, the evolving epidemiology of avian influenza as well as seasonal and pandemic human influenza viruses. Recent advances in phylogenetic methods can infer more in-depth information about the patterns of virus emergence, adding to the conventional approaches in viral epidemiology. Examples of this information include estimations (with confidence limits) of the actual time of the origin of a new viral strain or its emergence in a new species, viral recombination and reassortment events, the rate of population size change in a viral epidemic, and how the virus spreads and evolves within a specific population and geographical region. Such sequence-derived information obtained from the phylogenetic tree can assist in the design and implementation of public health and therapeutic interventions. However, application of many of these advanced phylogenetic methods are currently limited to specialized phylogeneticists and statisticians, mainly because of their mathematical basis and their dependence on the use of a large number of computer programs. This review attempts to bridge this gap by presenting conceptual, technical, and practical aspects of applying phylogenetic methods in studies of influenza, HIV, and SCoV. It aims to provide, with minimal mathematics and statistics, a practical overview of how phylogenetic methods can be incorporated into virological studies by clinical and laboratory specialists.

  17. Introducing Molecular Biology to Environmental Engineers through Development of a New Course.

    ERIC Educational Resources Information Center

    Oerther, Daniel B.

    2002-01-01

    Introduces a molecular biology course designed for environmental engineering majors using 16S ribosomal ribonucleic acid-targeted technology that allows students to identify and study microorganisms in bioreactor environments. (Contains 17 references.) (YDS)

  18. Applications of molecular self-assembly in tissue engineering

    NASA Astrophysics Data System (ADS)

    Harrington, Daniel Anton

    This thesis studied the application of three self-assembling molecular systems, as potential biomaterials for tissue engineering applications. Cholesteryl-(L-lactic acid)n molecules form thermotropic liquid crystals, which could be coated onto the inner and outer pores of biodegradable PLLA scaffolds, while retaining the lamellar order of the neat material. Primary bovine chondrocytes were cultured on these structures, demonstrating improved attachment and extended retention of phenotype on the C-LA-coated scaffolds. No difference in fibronectin adsorption to C-LA and PLLA surfaces was observed, suggesting a strong role for cholesterol in influencing cell phenotype. A family of peptide-amphiphiles, bearing the "RGD" adhesion sequence from fibronectin, was also assessed in the contexts of cartilage and bladder repair. These molecules self-assemble into one-dimensional fibers, with diameters of 6--8 nm, and lengths of 500 nm or greater. Chondrocytes were seeded and cultured on covalently-crosslinked PA gels and embedded within calcium-triggered PA gels. Cells became dormant over time, but remained viable, suggesting an inappropriate display of the adhesion sequence to cells. A family of "branched" PA molecules with lysine dendron headgroups was designed, in an effort to increase the spatial separation between molecules in the assembled state, and to theoretically improve epitope accessibility. These molecules coated reliably onto PGA fiber scaffolds, and dramatically increased the attachment of human bladder smooth muscle cells, possibly through better epitope display or electrostatic attraction. They also formed strong gels with several negatively-charged biologically-relevant macromolecules. In a third system, amphiphilic segmented dendrimers based on phenylene vinylene and L-lysine entered cells through an endocytic pathway with no discernible toxic effect on cell proliferation or morphology. These amphiphiles formed complex aggregates in aqueous solution, likely

  19. Molecular Modeling as a Self-Taught Component of a Conventional Undergraduate Chemical Reaction Engineering Course

    ERIC Educational Resources Information Center

    Rothe, Erhard W.; Zygmunt, William E.

    2016-01-01

    We inserted a self-taught molecular modeling project into an otherwise conventional undergraduate chemical-reaction-engineering course. Our objectives were that students should (a) learn with minimal instructor intervention, (b) gain an appreciation for the relationship between molecular structure and, first, macroscopic state functions in…

  20. Teaching Applied Genetics and Molecular Biology to Agriculture Engineers. Application of the European Credit Transfer System

    ERIC Educational Resources Information Center

    Weiss, J.; Egea-Cortines, M.

    2008-01-01

    We have been teaching applied molecular genetics to engineers and adapted the teaching methodology to the European Credit Transfer System. We teach core principles of genetics that are universal and form the conceptual basis of most molecular technologies. The course then teaches widely used techniques and finally shows how different techniques…

  1. Evolutionary History of the Grey-Faced Sengi, Rhynchocyon udzungwensis, from Tanzania: A Molecular and Species Distribution Modelling Approach

    PubMed Central

    Ricci, Silvia; Rovero, Francesco

    2013-01-01

    Rhynchocyon udzungwensis is a recently described and poorly understood sengi (giant elephant-shrew) endemic to two small montane forests in Southern Tanzania, and surrounded in lower forests by R. cirnei reichardi. In this study, we investigate the molecular genetic relationship between R. udzungwensis and R. c. reichardi, and the possible role that shifting species distributions in response to climate fluctuations may have played in shaping their evolutionary history. Rhynchocyon udzungwensis and R. c. reichardi individuals were sampled from five localities for genetic analyses. Three mitochondrial and two nuclear loci were used to construct species trees for delimitation and to determine whether introgression was detectable either from ancient or ongoing hybridization. All species-tree results show R. udzungwensis and R. c. reichardi as distinct lineages, though mtDNA shows evidence of introgression in some populations. Nuclear loci of each species were monophyletic, implying introgression is exclusively historical. Because we found evidence of introgression, we used distribution data and species distribution modelling for present, glacial, and interglacial climate cycles to predict how shifting species distributions may have facilitated hybridization in some populations. Though interpretations are affected by the limited range of these species, a likely scenario is that the mtDNA introgression found in eastern mid-elevation populations was facilitated by low numbers of R. udzungwensis that expanded into lowland heavily occupied R. c. reichardi areas during interglacial climate cycles. These results imply that relationships within the genus Rhynchocyon may be confounded by porous species boundaries and introgression, even if species are not currently sympatric. PMID:24015252

  2. Mechanisms other than activation of the iron regulon account for the hyper-resistance to cobalt of a Saccharomyces cerevisiae strain obtained by evolutionary engineering.

    PubMed

    Alkim, Ceren; Benbadis, Laurent; Yilmaz, Ulku; Cakar, Z Petek; François, Jean Marie

    2013-08-01

    Cobalt is an important metal ion with magnetic properties that is widely used for several industrial applications. Overexposure to cobalt ions can be highly toxic for the organisms because they usually overwhelm the endogenous physiological system that maintains their homeostasis causing (geno)toxic effects. To gain insight into the mechanism of cobalt toxicity, we characterized at the molecular and genetic levels a cobalt resistant CI25E Saccharomyces cerevisiae strain previously isolated by an in vivo evolutionary engineering strategy, and which was able to grow on 5 to 10 mM CoCl2. This evolved strain showed cross-resistance to other metal ions including iron, manganese, nickel and zinc, but not to copper. Moreover, the cobalt resistant trait was semi-dominant, and linked to more than one gene, as indicated by the absence of 2(+):2(-) segregation of the cobalt resistance. Genome wide transcriptional profiling revealed a constitutive activation of the iron regulon that could be accounted for by a constitutive nuclear localization of the transcriptional activator Aft1. However, the presence of Aft1 in the nucleus was not a prerequisite for hyper-resistance to cobalt, since a mutant defective in nuclear monothiol glutaredoxin encoding GRX3 and GRX4 that also leads to nuclear localization of Aft1 was cobalt hypersensitive. In addition, the loss of AFT1 only partially abolished the cobalt resistance in the evolved strain, and the deletion of COT1 encoding the major vacuolar transporter of cobalt had only a minor effect on this trait. Paradoxically to the activation of iron regulon, the evolved strain was hypersensitive to the iron chelator BPS, and this hypersensitivity was abrogated by cobalt ions. Taken together, this work suggested that cobalt resistance is not merely dependent upon activation of AFT1, but it likely implicates other mechanisms including intracellular reallocation of iron into important compartments whose function is dependent on this metal and

  3. Key innovations and island colonization as engines of evolutionary diversification: a comparative test with the Australasian diplodactyloid geckos.

    PubMed

    Garcia-Porta, J; Ord, T J

    2013-12-01

    The acquisition of key innovations and the invasion of new areas constitute two major processes that facilitate ecological opportunity and subsequent evolutionary diversification. Using a major lizard radiation as a model, the Australasian diplodactyloid geckos, we explored the effects of two key innovations (adhesive toepads and a snake-like phenotype) and the invasion of new environments (island colonization) in promoting the evolution of phenotypic and species diversity. We found no evidence that toepads had significantly increased evolutionary diversification, which challenges the common assumption that the evolution of toepads has been responsible for the extensive radiation of geckos. In contrast, a snakelike phenotype was associated with increased rates of body size evolution and, to a lesser extent, species diversification. However, the clearest impact on evolutionary diversification has been the colonization of New Zealand and New Caledonia, which were associated with increased rates of both body size evolution and species diversification. This highlights that colonizing new environments can drive adaptive diversification in conjunction or independently of the evolution of a key innovation. Studies wishing to confirm the putative link between a key innovation and subsequent evolutionary diversification must therefore show that it has been the acquisition of an innovation specifically, not the colonization of new areas more generally, that has prompted diversification.

  4. Importance of gene duplication in the evolution of genomic imprinting revealed by molecular evolutionary analysis of the type I MADS-box gene family in Arabidopsis species.

    PubMed

    Yoshida, Takanori; Kawabe, Akira

    2013-01-01

    The pattern of molecular evolution of imprinted genes is controversial and the entire picture is still to be unveiled. Recently, a relationship between the formation of imprinted genes and gene duplication was reported in genome-wide survey of imprinted genes in Arabidopsis thaliana. Because gene duplications influence the molecular evolution of the duplicated gene family, it is necessary to investigate both the pattern of molecular evolution and the possible relationship between gene duplication and genomic imprinting for a better understanding of evolutionary aspects of imprinted genes. In this study, we investigated the evolutionary changes of type I MADS-box genes that include imprinted genes by using relative species of Arabidopsis thaliana (two subspecies of A. lyrata and three subspecies of A. halleri). A duplicated gene family enables us to compare DNA sequences between imprinted genes and its homologs. We found an increased number of gene duplications within species in clades containing the imprinted genes, further supporting the hypothesis that local gene duplication is one of the driving forces for the formation of imprinted genes. Moreover, data obtained by phylogenetic analysis suggested "rapid evolution" of not only imprinted genes but also its closely related orthologous genes, which implies the effect of gene duplication on molecular evolution of imprinted genes.

  5. Spin-dependent Otto quantum heat engine based on a molecular substance

    NASA Astrophysics Data System (ADS)

    Hübner, Wolfgang; Lefkidis, Georgios; Dong, Chuanding; Chaudhuri, Debapriya; Chotorlishvili, Levan; Berakdar, Jamal

    2015-03-01

    We explore the potential of single molecules for thermodynamic cycles. To this end we propose two molecular heat engines based on the realistic Ni2 dimer: a quantum Otto engine and a modified quantum Otto engine for which laser-induced optical excitations substitute for one of the heat-exchange points. For reliable predictions and to inspect the role of spin and electronic correlations we perform fully correlated ab initio calculations of the electronic structure and the excited states. We analyze the efficiency and the word output of the derived engines and find an enhancement when the spin degree of freedom is included. We also use the von Neumann entropy to describe correlations and entanglement of the engines during the cycles. Furthermore, we link our results to previous results regarding an isobaric stroke and a magnetic quantum Diesel engine on the same substance.

  6. Evolutionary novelties.

    PubMed

    Wagner, Günter P; Lynch, Vincent J

    2010-01-26

    How novel traits arise in organisms has long been a major problem in biology. Indeed, the sharpest critiques of Darwin's theory of evolution by natural selection often centered on explaining how novel body parts arose. In his response to The Origin of Species, St. George J. Mivart challenged Darwin to explain the origin of evolutionary novelties such as the mammary gland, asking if it was "conceivable that the young of any animal was ever saved from destruction by accidentally sucking a drop of scarcely nutritious fluid from an accidentally hypertrophied cutaneous gland of its mother?" It is only now that modern molecular and genomic tools are being brought to bear on this question that we are finally in a position to answer Mivart's challenge and explain one of the most fundamental questions of biology: how does novelty arise in evolution?

  7. Engineering nanomaterials with a combined electrochemical and molecular biomimetic approach

    NASA Astrophysics Data System (ADS)

    Dai, Haixia

    Biocomposite materials, such as bones, teeth, and shells, are created using mild aqueous solution-based processes near room temperature. Proteins add flexibility to these processes by facilitating the nucleation, growth, and ordering of specific inorganic materials into hierarchical structures. We aim to develop a biomimetic strategy for engineering technologically relevant inorganic materials with controlled compositions and structures, as Nature does, using proteins to orchestrate material formation and assembly. This approach involves three basic steps: (i) preparation of inorganic substrates compatible with combinatorial polypeptide screening; (ii) identification of inorganic-binding polypeptides and their engineering into inorganic-binding proteins; and (iii) protein-mediated inorganic nucleation and organization. Cuprous oxide (Cu2O), a p-type semiconductor, has been used to demonstrate all three steps. Zinc oxide (ZnO), an n-type semiconductor, has been used to show the generality of selected steps. Step (i), preparation of high quality inorganic substrates to select inorganic-binding polypeptides, was accomplished using electrochemical microfabrication to grow and pattern Cu2O and ZnO. Raman spectroscopy and x-ray photoelectron spectroscopy were used to verify phase purity and compositional stability of these surfaces during polypeptide screening. Step (ii), accomplished in collaboration with personnel in Prof Baneyx' lab at the University of Washington, involved incubating the inorganic substrates with the FliTrx(TM) random peptide library to identify cysteine-constrained dodecapeptides that bind the targeted inorganic. Insertion of a Cu2O-binding dodecapeptide into the DNA-binding protein TraI endowed the engineered TraI with strong affinity for Cu2O (Kd ≈ 10 -8 M). Finally, step (iii) involved nonequilibrium synthesis and organization of Cu2O nanoparticles, taking advantage of the inorganic and DNA recognition properties of the engineered TraI. The

  8. Spin-dependent Otto quantum heat engine based on a molecular substance

    NASA Astrophysics Data System (ADS)

    Hübner, W.; Lefkidis, G.; Dong, C. D.; Chaudhuri, D.; Chotorlishvili, L.; Berakdar, J.

    2014-07-01

    We explore the potential of single molecules for thermodynamic cycles. To this end we propose two molecular heat engines based on the Ni2 dimer in the presence of a static magnetic field: (a) a quantum Otto engine and (b) a modified quantum Otto engine for which optical excitations induced by a laser pulse substitute for one of the heat-exchange points. For reliable predictions and to inspect the role of spin and electronic correlations we perform fully correlated ab initio calculations of the molecular electronic structure including spin-orbital effects. We analyze the efficiency of the engines in dependence of the electronic level scheme and the entanglement and find a significant possible enhancement connected to the quantum nature and the heat capacity of the dimer, as well as to the zero-field triplet states splitting.

  9. Molecular Strategy for the Construction of a Genetically Engineered Vaccine for Venezuelan Equine Encephalitis Virus

    DTIC Science & Technology

    1991-03-29

    AD-A236 920 MOLECULAR STRATEGY FOR THE CONSTRUCTION OF A GENETICALLY ENGINEERED VACCINE FOR VENEZUELAN EQUINE ENCEPHALITIS VIRUS FINAL REPORT ROBERT...89-C-9089 engineered vaccine for Venezuelan Equine Encephalitis Virus 62787A 3M162787A871 AD Robert Edward Johnston WUDA318408 Nancy Lee Davis...multiple mutants were more attenuated than those containing a single attenuating Venezuelan equine encephalitis virus (VEE) full-length clones; In vitro

  10. The molecular evolutionary dynamics of the vomeronasal receptor (class 1) genes in primates: a gene family on the verge of a functional breakdown

    PubMed Central

    Yoder, Anne D.; Larsen, Peter A.

    2014-01-01

    Olfaction plays a critical role in both survival of the individual and in the propagation of species. Studies from across the mammalian clade have found a remarkable correlation between organismal lifestyle and molecular evolutionary properties of receptor genes in both the main olfactory system (MOS) and the vomeronasal system (VNS). When a large proportion of intact (and putatively functional) copies is observed, the inference is made that a particular mode of chemoreception is critical for an organism’s fit to its environment and is thus under strong positive selection. Conversely, when the receptors in question show a disproportionately large number of pseudogene copies, this contraction is interpreted as evidence of relaxed selection potentially leading to gene family extinction. Notably, it appears that a risk factor for gene family extinction is a high rate of nonsynonymous substitution. A survey of intact vs. pseudogene copies among primate vomeronasal receptor Class one genes (V1Rs) appears to substantiate this hypothesis. Molecular evolutionary complexities in the V1R gene family combine rapid rates of gene duplication, gene conversion, lineage-specific expansions, deletions, and/or pseudogenization. An intricate mix of phylogenetic footprints and current adaptive landscapes have left their mark on primate V1Rs suggesting that the primate clade offers an ideal model system for exploring the molecular evolutionary and functional properties of the VNS of mammals. Primate V1Rs tell a story of ancestral function and divergent selection as species have moved into ever diversifying adaptive regimes. The sensitivity to functional collapse in these genes, consequent to their precariously high rates of nonsynonymous substitution, confer a remarkable capacity to reveal the lifestyles of the genomes that they presently occupy as well as those of their ancestors. PMID:25565978

  11. The molecular evolutionary dynamics of the vomeronasal receptor (class 1) genes in primates: a gene family on the verge of a functional breakdown.

    PubMed

    Yoder, Anne D; Larsen, Peter A

    2014-01-01

    Olfaction plays a critical role in both survival of the individual and in the propagation of species. Studies from across the mammalian clade have found a remarkable correlation between organismal lifestyle and molecular evolutionary properties of receptor genes in both the main olfactory system (MOS) and the vomeronasal system (VNS). When a large proportion of intact (and putatively functional) copies is observed, the inference is made that a particular mode of chemoreception is critical for an organism's fit to its environment and is thus under strong positive selection. Conversely, when the receptors in question show a disproportionately large number of pseudogene copies, this contraction is interpreted as evidence of relaxed selection potentially leading to gene family extinction. Notably, it appears that a risk factor for gene family extinction is a high rate of nonsynonymous substitution. A survey of intact vs. pseudogene copies among primate vomeronasal receptor Class one genes (V1Rs) appears to substantiate this hypothesis. Molecular evolutionary complexities in the V1R gene family combine rapid rates of gene duplication, gene conversion, lineage-specific expansions, deletions, and/or pseudogenization. An intricate mix of phylogenetic footprints and current adaptive landscapes have left their mark on primate V1Rs suggesting that the primate clade offers an ideal model system for exploring the molecular evolutionary and functional properties of the VNS of mammals. Primate V1Rs tell a story of ancestral function and divergent selection as species have moved into ever diversifying adaptive regimes. The sensitivity to functional collapse in these genes, consequent to their precariously high rates of nonsynonymous substitution, confer a remarkable capacity to reveal the lifestyles of the genomes that they presently occupy as well as those of their ancestors.

  12. Exploiting molecular motors as nanomachines: the mechanisms of de novo and re-engineered cytoskeletal motors.

    PubMed

    DelRosso, Nicole V; Derr, Nathan D

    2017-01-11

    Cytoskeletal molecular motors provide exciting proof that nanoscale transporters can be highly efficient, moving for microns along filamentous tracks by hydrolyzing ATP to fuel nanometer-size steps. For nanotechnology, such conversion of chemical energy into productive work serves as an enticing platform for re-purposing and re-engineering. It also provides a roadmap for successful molecular mechanisms that can be mimicked to create de novo molecular motors for nanotechnology applications. Here we focus specifically on how the mechanisms of molecular motors are being re-engineered for greater control over their transport parameters. We then discuss mechanistic work to create fully synthetic motors de novo and conclude with future directions in creating novel motor systems.

  13. Engineered elastomeric proteins with dual elasticity can be controlled by a molecular regulator.

    PubMed

    Cao, Yi; Li, Hongbin

    2008-08-01

    Elastomeric proteins are molecular springs that confer excellent mechanical properties to many biological tissues and biomaterials. Depending on the role performed by the tissue or biomaterial, elastomeric proteins can behave as molecular springs or shock absorbers. Here we combine single-molecule atomic force microscopy and protein engineering techniques to create elastomeric proteins that can switch between two distinct types of mechanical behaviour in response to the binding of a molecular regulator. The proteins are mechanically labile by design and behave as entropic springs with an elasticity that is governed by their configurational entropy. However, when a molecular regulator binds to the protein, it switches into a mechanically stable state and can act as a shock absorber. These engineered proteins effectively mimic and combine the two extreme forms of elastic behaviour found in natural elastomeric proteins, and thus represent a new type of smart nanomaterial that will find potential applications in nanomechanics and material sciences.

  14. Engineering molecular circuits using synthetic biology in mammalian cells.

    PubMed

    Wieland, Markus; Fussenegger, Martin

    2012-01-01

    Synthetic biology has made significant leaps over the past decade, and it now enables rational and predictable reprogramming of cells to conduct complex physiological activities. The bases for cellular reprogramming are mainly genetic control components affecting gene expression. A huge variety of these modules, ranging from engineered fusion proteins regulating transcription to artificial RNA devices affecting translation, is available, and they often feature a highly modular scaffold. First endeavors to combine these modules have led to autoregulated expression systems and genetic cascades. Analogous to the rational engineering of electronic circuits, the existing repertoire of artificial regulatory elements has further enabled the ambitious reprogramming of cells to perform Boolean calculations or to mimic the oscillation of circadian clocks. Cells harboring synthetic gene circuits are not limited to cell culture, as they have been successfully implanted in animals to obtain tailor-made therapeutics that have made it possible to restore urea or glucose homeostasis as well as to offer an innovative approach to artificial insemination.

  15. Molecular and evolutionary characteristics of the fraction of human alpha satellite DNA associated with CENP-A at the centromeres of chromosomes 1, 5, 19, and 21

    PubMed Central

    2010-01-01

    Background The mode of evolution of the highly homogeneous Higher-Order-Repeat-containing alpha satellite arrays is still subject to discussion. This is also true of the CENP-A associated repeats where the centromere is formed. Results In this paper, we show that the molecular mechanisms by which these arrays evolve are identical in multiple chromosomes: i) accumulation of crossovers that homogenise and expand the arrays into different domains and subdomains that are mostly unshared between homologues and ii) sporadic mutations and conversion events that simultaneously differentiate them from one another. Individual arrays are affected by these mechanisms to different extents that presumably increase with time. Repeats associated with CENP-A, where the centromere is formed, are subjected to the same evolutionary mechanisms, but constitute minor subsets that exhibit subtle sequence differences from those of the bulk repeats. While the DNA sequence per se is not essential for centromere localisation along an array, it appears that certain sequences can be selected against. On chromosomes 1 and 19, which are more affected by the above evolutionary mechanisms than are chromosomes 21 and 5, CENP-A associated repeats were also recovered from a second homogeneous array present on each chromosome. This could be a way for chromosomes to sustain mitosis and meiosis when the normal centromere locus is ineluctably undermined by the above mechanisms. Conclusion We discuss, in light of these observations, possible scenarios for the normal evolutionary fates of human centromeric regions. PMID:20331851

  16. Engineering responsive polymer building blocks with host-guest molecular recognition for functional applications.

    PubMed

    Hu, Jinming; Liu, Shiyong

    2014-07-15

    CONSPECTUS: All living organisms and soft matter are intrinsically responsive and adaptive to external stimuli. Inspired by this fact, tremendous effort aiming to emulate subtle responsive features exhibited by nature has spurred the invention of a diverse range of responsive polymeric materials. Conventional stimuli-responsive polymers are constructed via covalent bonds and can undergo reversible or irreversible changes in chemical structures, physicochemical properties, or both in response to a variety of external stimuli. They have been imparted with a variety of emerging applications including drug and gene delivery, optical sensing and imaging, diagnostics and therapies, smart coatings and textiles, and tissue engineering. On the other hand, in comparison with molecular chemistry held by covalent bonds, supramolecular chemistry built on weak and reversible noncovalent interactions has emerged as a powerful and versatile strategy for materials fabrication due to its facile accessibility, extraordinary reversibility and adaptivity, and potent applications in diverse fields. Typically involving more than one type of noncovalent interactions (e.g., hydrogen bonding, metal coordination, hydrophobic association, electrostatic interactions, van der Waals forces, and π-π stacking), host-guest recognition refers to the formation of supramolecular inclusion complexes between two or more entities connected together in a highly controlled and cooperative manner. The inherently reversible and adaptive nature of host-guest molecular recognition chemistry, stemming from multiple noncovalent interactions, has opened up a new platform to construct novel types of stimuli-responsive materials. The introduction of host-guest chemistry not only enriches the realm of responsive materials but also confers them with promising new applications. Most intriguingly, the integration of responsive polymer building blocks with host-guest recognition motifs will endow the former with

  17. The methionine-rich low-molecular-weight chloroplast heat-shock protein: evolutionary conservation and accumulation in relation to thermotolerance.

    PubMed

    Downs, C; Heckathorn, S; Bryan, J; Coleman, J

    1998-02-01

    The evolutionary conservation of the low-molecular-weight chloroplast-localized heat-shock protein (LMW chlpHsp) in vascular plants was examined using immunological methods. An antibody (Abmet) specific to the LMW chlpHsp was produced using a synthetic 28-residue peptide containing the most conserved elements of its unique "methionine-rich domain" as an antigen. This antibody detected a heat-inducible low-molecular-weight chloroplast protein in plants of six divergent Anthophyta species, including C3, C4, CAM, monocot, and dicot species. Abmet also detected a LMW chlpHsp in species from the Divisions Psilotophyta, Equisetophyta, Polypodiophyta, and Ginkgophyta. A preliminary examination of the relationship between accumulation of the LMW chlpHsp and habitat was also conducted. Seven Anthophyta species originating from both warm- and cool-temperature habitats were grown at 28C and then heat stressed at 40C. A positive qualitative relationship between the accumulation of the LMW chlpHsp and organismal thermotolerance in these species was observed; similar results were obtained separately with four nonAnthophyta species. The strong evolutionary conservation of this LMW Hsp and its localization to the chloroplast, and the correlation between production of this protein and plant thermotolerance, suggest that the LMW chlpHsp plays an important role in adaptation to heat stress.

  18. Molecular Evolutionary Analysis of ABCB5: The Ancestral Gene Is a Full Transporter with Potentially Deleterious Single Nucleotide Polymorphisms

    PubMed Central

    McGee, Kate; Lancaster, Germaine; Gold, Bert; Dean, Michael

    2011-01-01

    Background ABCB5 is a member of the ABC protein superfamily, which includes the transporters ABCB1, ABCC1 and ABCG2 responsible for causing drug resistance in cancer patients and also several other transporters that have been linked to human disease. The ABCB5 full transporter (ABCB5.ts) is expressed in human testis and its functional significance is presently unknown. Another variant of this transporter, ABCB5 beta posses a “half-transporter-like” structure and is expressed in melanoma stem cells, normal melanocytes, and other types of pigment cells. ABCB5 beta has important clinical implications, as it may be involved with multidrug resistance in melanoma stem cells, allowing these stem cells to survive chemotherapeutic regimes. Methodology/Principal Findings We constructed and examined in detail topological structures of the human ABCB5 protein and determined in-silico the cSNPs (coding single nucleotide polymorphisms) that may affect its function. Evolutionary analysis of ABCB5 indicated that ABCB5, ABCB1, ABCB4, and ABCB11 share a common ancestor, which began duplicating early in the evolutionary history of chordates. This suggests that ABCB5 has evolved as a full transporter throughout its evolutionary history. Conclusions/Significance From our in-silco analysis of cSNPs we found that a large number of non-synonymous cSNPs map to important functional regions of the protein suggesting that these SNPs if present in human populations may play a role in diseases associated with ABCB5. From phylogenetic analyses, we have shown that ABCB5 evolved as a full transporter throughout its evolutionary history with an absence of any major shifts in selection between the various lineages suggesting that the function of ABCB5 has been maintained during mammalian evolution. This finding would suggest that ABCB5 beta may have evolved to play a specific role in human pigment cells and/or melanoma cells where it is predominantly expressed. PMID:21298007

  19. Recent advances in developing molecular tools for targeted genome engineering of mammalian cells.

    PubMed

    Lim, Kwang-il

    2015-01-01

    Various biological molecules naturally existing in diversified species including fungi, bacteria, and bacteriophage have functionalities for DNA binding and processing. The biological molecules have been recently actively engineered for use in customized genome editing of mammalian cells as the molecule-encoding DNA sequence information and the underlying mechanisms how the molecules work are unveiled. Excitingly, multiple novel methods based on the newly constructed artificial molecular tools have enabled modifications of specific endogenous genetic elements in the genome context at efficiencies that are much higher than that of the conventional homologous recombination based methods. This minireview introduces the most recently spotlighted molecular genome engineering tools with their key features and ongoing modifications for better performance. Such ongoing efforts have mainly focused on the removal of the inherent DNA sequence recognition rigidity from the original molecular platforms, the addition of newly tailored targeting functions into the engineered molecules, and the enhancement of their targeting specificity. Effective targeted genome engineering of mammalian cells will enable not only sophisticated genetic studies in the context of the genome, but also widely-applicable universal therapeutics based on the pinpointing and correction of the disease-causing genetic elements within the genome in the near future.

  20. Evolutionary history and molecular epidemiology of rabbit haemorrhagic disease virus in the Iberian Peninsula and Western Europe

    PubMed Central

    2010-01-01

    Background Rabbit haemorrhagic disease virus (RHDV) is a highly virulent calicivirus, first described in domestic rabbits in China in 1984. RHDV appears to be a mutant form of a benign virus that existed in Europe long before the first outbreak. In the Iberian Peninsula, the first epidemic in 1988 severely reduced the populations of autochthonous European wild rabbit. To examine the evolutionary history of RHDV in the Iberian Peninsula, we collected virus samples from wild rabbits and sequenced a fragment of the capsid protein gene VP60. These data together with available sequences from other Western European countries, were analyzed following Bayesian Markov chain Monte Carlo methods to infer their phylogenetic relationships, evolutionary rates and demographic history. Results Evolutionary relationships of RHDV revealed three main lineages with significant phylogeographic structure. All lineages seem to have emerged at a common period of time, between ~1875 and ~1976. The Iberian Peninsula showed evidences of genetic isolation, probably due to geographic barriers to gene flow, and was also the region with the youngest MRCA. Overall, demographic analyses showed an initial increase and stabilization of the relative genetic diversity of RHDV, and a subsequent reduction in genetic diversity after the first epidemic breakout in 1984, which is compatible with a decline in effective population size. Conclusions Results were consistent with the hypothesis that the current Iberian RHDV arose from a single infection between 1869 and 1955 (95% HPD), and rendered a temporal pattern of appearance and extinction of lineages. We propose that the rising positive selection pressure observed throughout the history of RHDV is likely mediated by the host immune system as a consequence of the genetic changes that rendered the virus virulent. Consequently, this relationship is suggested to condition RHDV demographic history. PMID:21067589

  1. Proteomics in evolutionary ecology.

    PubMed

    Baer, B; Millar, A H

    2016-03-01

    Evolutionary ecologists are traditionally gene-focused, as genes propagate phenotypic traits across generations and mutations and recombination in the DNA generate genetic diversity required for evolutionary processes. As a consequence, the inheritance of changed DNA provides a molecular explanation for the functional changes associated with natural selection. A direct focus on proteins on the other hand, the actual molecular agents responsible for the expression of a phenotypic trait, receives far less interest from ecologists and evolutionary biologists. This is partially due to the central dogma of molecular biology that appears to define proteins as the 'dead-end of molecular information flow' as well as technical limitations in identifying and studying proteins and their diversity in the field and in many of the more exotic genera often favored in ecological studies. Here we provide an overview of a newly forming field of research that we refer to as 'Evolutionary Proteomics'. We point out that the origins of cellular function are related to the properties of polypeptide and RNA and their interactions with the environment, rather than DNA descent, and that the critical role of horizontal gene transfer in evolution is more about coopting new proteins to impact cellular processes than it is about modifying gene function. Furthermore, post-transcriptional and post-translational processes generate a remarkable diversity of mature proteins from a single gene, and the properties of these mature proteins can also influence inheritance through genetic and perhaps epigenetic mechanisms. The influence of post-transcriptional diversification on evolutionary processes could provide a novel mechanistic underpinning for elements of rapid, directed evolutionary changes and adaptations as observed for a variety of evolutionary processes. Modern state-of the art technologies based on mass spectrometry are now available to identify and quantify peptides, proteins, protein

  2. Peeling back the evolutionary layers of molecular mechanisms responsive to exercise-stress in the skeletal muscle of the racing horse.

    PubMed

    Kim, Hyeongmin; Lee, Taeheon; Park, Woncheoul; Lee, Jin Woo; Kim, Jaemin; Lee, Bo-Young; Ahn, Hyeonju; Moon, Sunjin; Cho, Seoae; Do, Kyoung-Tag; Kim, Heui-Soo; Lee, Hak-Kyo; Lee, Chang-Kyu; Kong, Hong-Sik; Yang, Young-Mok; Park, Jongsun; Kim, Hak-Min; Kim, Byung Chul; Hwang, Seungwoo; Bhak, Jong; Burt, Dave; Park, Kyoung-Do; Cho, Byung-Wook; Kim, Heebal

    2013-06-01

    The modern horse (Equus caballus) is the product of over 50 million yrs of evolution. The athletic abilities of the horse have been enhanced during the past 6000 yrs under domestication. Therefore, the horse serves as a valuable model to understand the physiology and molecular mechanisms of adaptive responses to exercise. The structure and function of skeletal muscle show remarkable plasticity to the physical and metabolic challenges following exercise. Here, we reveal an evolutionary layer of responsiveness to exercise-stress in the skeletal muscle of the racing horse. We analysed differentially expressed genes and their co-expression networks in a large-scale RNA-sequence dataset comparing expression before and after exercise. By estimating genome-wide dN/dS ratios using six mammalian genomes, and FST and iHS using re-sequencing data derived from 20 horses, we were able to peel back the evolutionary layers of adaptations to exercise-stress in the horse. We found that the oldest and thickest layer (dN/dS) consists of system-wide tissue and organ adaptations. We further find that, during the period of horse domestication, the older layer (FST) is mainly responsible for adaptations to inflammation and energy metabolism, and the most recent layer (iHS) for neurological system process, cell adhesion, and proteolysis.

  3. Cell death in mammalian cell culture: molecular mechanisms and cell line engineering strategies

    PubMed Central

    Krampe, Britta

    2010-01-01

    Cell death is a fundamentally important problem in cell lines used by the biopharmaceutical industry. Environmental stress, which can result from nutrient depletion, by-product accumulation and chemical agents, activates through signalling cascades regulators that promote death. The best known key regulators of death process are the Bcl-2 family proteins which constitute a critical intracellular checkpoint of apoptosis cell death within a common death pathway. Engineering of several members of the anti-apoptosis Bcl-2 family genes in several cell types has extended the knowledge of their molecular function and interaction with other proteins, and their regulation of cell death. In this review, we describe the various modes of cell death and their death pathways at molecular and organelle level and discuss the relevance of the growing knowledge of anti-apoptotic engineering strategies to inhibit cell death and increase productivity in mammalian cell culture. PMID:20502964

  4. Molecular Engineering of Vector-Based Oncolytic and Imaging Approaches for Advanced Prostate Cancer

    DTIC Science & Technology

    2006-02-01

    Oncolytic and Imaging Approaches for Advanced Prostate Cancer PRINCIPAL INVESTIGATOR: Lily Wu, M.D., Ph.D. CONTRACTING ORGANIZATION...SUBTITLE Molecular Engineering of Vector-based Oncolytic and Imaging Approaches for 5a. CONTRACT NUMBER Advanced Prostate Cancer 5b. GRANT...reproductions will be in black and white. 14. ABSTRACT Hormone refractory and metastatic prostate cancer are not well understood. Better animal models

  5. Molecular Engineering Combined with Cosensitization Leads to Record Photovoltaic Efficiency for Non-ruthenium Solar Cells.

    PubMed

    Hill, Jonathan P

    2016-02-24

    Here comes the sun: By using a combined strategy of molecular engineering and cosensitization, impressively high Jsc and Voc values were achieved for porphyrin dyes, resulting in high photovoltaic efficiencies up to 11.5 %, a record for non-ruthenium dye-sensitized solar cells (DSSCs) with the I(-) /I3 (-) electrolyte. The results provide insight into furthering the development of efficient DSSCs through synergistically enhanced photovoltage and photocurrent.

  6. Molecular characterization and phylogenetic analysis of Eimeria from turkeys and gamebirds: implications for evolutionary relationships in Galliform birds.

    PubMed

    Miska, K B; Schwarz, R S; Jenkins, M C; Rathinam, T; Chapman, H D

    2010-10-01

    In order to determine the evolutionary relationships among Eimeria species that parasitize birds of the Galliformes, the 18s rDNA gene and a portion of the cytochrome oxidase subunit 1 (cox-1) were amplified from Eimeria species isolated from turkeys, chukars, and pheasants. The phylogenetic analysis of these sequences suggests that species infecting chickens are polyphyletic and, therefore, do not all share a direct common ancestor. Both the 18s rDNA and the cox-1 sequences indicate that Eimeria tenella and Eimeria necatrix are more closely related to Eimeria of turkeys and pheasants than to other species that infect the chicken. It is, therefore, likely that the chicken Eimeria spp. represent 2 separate ancestral colonizations of the gut, one of which comprises E. tenella and E. necatrix that infect the ceca, while the other includes Eimeria acervulina, Eimeria brunetti, Eimeria maxima, and Eimeria mitis, which infect the upper regions of the intestine.

  7. 3D molecular modeling and evolutionary study of the Trypanosoma brucei DNA Topoisomerase IB, as a new emerging pharmacological target.

    PubMed

    Vlachakis, Dimitrios; Pavlopoulou, Athanasia; Roubelakis, Maria G; Feidakis, Christos; Anagnou, Nikolaos P; Kossida, Sophia

    2014-01-01

    In the present study, an outline is proposed that may lead to specific drug design targeting of the Trypanosoma brucei DNA Topoisomerase IB. In this direction, an unequivocally specific platform was designed for the development of selective modulators. The designed platform is focused on the unique structural and catalytic features of the enzyme. Extensive phylogenetic analysis based on all available published genomes indicated a broad distribution of DNA topoisomerases across eukaryotic species and revealed structurally important amino acids which could be assigned as potentially strong contributors to the regulation of the mechanism of the T. brucei DNA Topoisomerase IB. Based on the above, we propose a comprehensive in silico 3D model for the structure of the T. brucei DNA Topoisomerase IB. Our approach provides an efficient intergraded platform with both evolutionary and structural insights for the rational design of pharmacophore models as well as novel modulators as the anti-T. brucei DNA Topoisomerase IB agents with therapeutic potential.

  8. Molecular and evolutionary analyses of formyl peptide receptors suggest the absence of VNO-specific FPRs in primates.

    PubMed

    Yang, Hui; Shi, Peng

    2010-12-01

    Formyl peptide receptors (FPRs) were observed to expand in rodents and were recently suggested as candidate vomeronasal chemosensory receptors. Since vomeronasal chemosensory receptors usually underwent positive selection and evolved concordantly with the vomeronasal organ (VNO) morphology, we surveyed FPRs in primates in which VNO morphology is greatly diverse and thus it would provide us a clearer view of VNO-FPRs evolution. By screening available primate genome sequences, we obtained the FPR repertoires in representative primate species. As a result, we did not find FPR family size expansion in primates. Further analyses showed no evolutionary force variance between primates with or without VNO structure, which indicated that there was no functional divergence among primates FPRs. Our results suggest that primates lack the VNO-specific FPRs and the FPR expansion is not a common phenomenon in mammals outside rodent lineage, regardless of VNO complexity.

  9. In-cylinder engine flow measurement using stereoscopic molecular tagging velocimetry (SMTV)

    NASA Astrophysics Data System (ADS)

    Mittal, M.; Sadr, R.; Schock, H. J.; Fedewa, A.; Naqwi, A.

    2009-02-01

    The stereoscopic molecular tagging velocimetry (SMTV) technique is used to obtain the multiple point measurement of an instantaneous three-component velocity field inside the cylinder of an internal combustion (IC) engine assembly. A novel image processing technique is implemented to obtain the velocity data. The technique has the advantage that it eliminates the geometric details required to obtain the three components of the velocity field. The procedure involves two major steps: (i) calibration process and (ii) data acquisition and reduction. Cycle-to-cycle variations of the three-component velocity field and out-of-plane vorticity are presented inside an engine cylinder. Preliminary results show that cycle-to-cycle variations are more prominent in the velocity component perpendicular to the tumble plane, as opposed to the in-plane components. Such new insights will help better understand the details of these flows and further improve CFD models for IC engines.

  10. On the Brink of Shifting Paradigms, Molecular Systems Engineering Ethics Needs to Take a Proactive Approach.

    PubMed

    Heidari, Raheleh; Elger, Bernice S; Stutzki, Ralf

    2016-01-01

    Molecular Systems Engineering (MSE) is a paradigm shift in both engineering and life sciences. While the field is still in its infancy the perspectives of MSE in revolutionising technology is promising. MSE will offer a wide range of applications in clinical, biotechnological and engineering fields while simultaneously posing serious questions on the ethical and societal aspects of such technology. The moral and societal aspects of MSE need systematic investigation from scientific and social perspectives. In a democratic setting, the societal outcomes of MSE's cutting-edge technology need to be consulted and influenced by society itself. For this purpose MSE needs inclusive public engagement strategies that bring together the public, ethicists, scientists and policy makers for optimum flow of information that maximizes the impact of public engagement. In this report we present an MSE consortium and its ethics framework for establishing a proactive approach in the study of the ethics of MSE technology.

  11. Evolutionary and Biogeographic Insights on the Macaronesian Beta-Patellifolia Species (Amaranthaceae) from a Time-Scaled Molecular Phylogeny

    PubMed Central

    Romeiras, Maria M.; Vieira, Ana; Silva, Diogo N.; Moura, Monica; Santos-Guerra, Arnoldo; Batista, Dora; Duarte, Maria Cristina; Paulo, Octávio S.

    2016-01-01

    The Western Mediterranean Region and Macaronesian Islands are one of the top biodiversity hotspots of Europe, containing a significant native genetic diversity of global value among the Crop Wild Relatives (CWR). Sugar beet is the primary crop of the genus Beta (subfamily Betoideae, Amaranthaceae) and despite the great economic importance of this genus, and of the close relative Patellifolia species, a reconstruction of their evolutionary history is still lacking. We analyzed nrDNA (ITS) and cpDNA gene (matK, trnH-psbA, trnL intron, rbcL) sequences to: (i) investigate the phylogenetic relationships within the Betoideae subfamily, and (ii) elucidate the historical biogeography of wild beet species in the Western Mediterranean Region, including the Macaronesian Islands. The results support the Betoideae as a monophyletic group (excluding the Acroglochin genus) and provide a detailed inference of relationships within this subfamily, revealing: (i) a deep genetic differentiation between Beta and Patellifolia species, which may have occurred in Late Oligocene; and (ii) the occurrence of a West-East genetic divergence within Beta, indicating that the Mediterranean species probably differentiated by the end of the Miocene. This was interpreted as a signature of species radiation induced by dramatic habitat changes during the Messinian Salinity Crisis (MSC, 5.96–5.33 Mya). Moreover, colonization events during the Pleistocene also played a role in shaping the current diversity patterns among and within the Macaronesian Islands. The origin and number of these events could not be revealed due to insufficient phylogenetic resolution, suggesting that the diversification was quite recent in these archipelagos, and unravelling potential complex biogeographic patterns with hybridization and gene flow playing an important role. Finally, three evolutionary lineages were identified corresponding to major gene pools of sugar beet wild relatives, which provide useful information for

  12. Molecular phylogenetic and evolutionary analyses of Muar strain of Japanese encephalitis virus reveal it is the missing fifth genotype.

    PubMed

    Mohammed, Manal A F; Galbraith, Sareen E; Radford, Alan D; Dove, Winifred; Takasaki, Tomohiko; Kurane, Ichiro; Solomon, Tom

    2011-07-01

    Japanese encephalitis virus (JEV) is the most important cause of epidemic encephalitis worldwide but its origin is unknown. Epidemics of encephalitis suggestive of Japanese encephalitis (JE) were described in Japan from the 1870s onwards. Four genotypes of JEV have been characterised and representatives of each genotype have been fully sequenced. Based on limited information, a single isolate from Malaysia is thought to represent a putative fifth genotype. We have determined the complete nucleotide and amino acid sequence of Muar strain and compared it with other fully sequenced JEV genomes. Muar was the least similar, with nucleotide divergence ranging from 20.2 to 21.2% and amino acid divergence ranging from 8.5 to 9.9%. Phylogenetic analysis of Muar strain revealed that it does represent a distinct fifth genotype of JEV. We elucidated Muar signature amino acids in the envelope (E) protein, including E327 Glu on the exposed lateral surface of the putative receptor binding domain which distinguishes Muar strain from the other four genotypes. Evolutionary analysis of full-length JEV genomes revealed that the mean evolutionary rate is 4.35 × 10(-4) (3.4906 × 10(-4) to 5.303 × 10(-4)) nucleotides substitutions per site per year and suggests JEV originated from its ancestral virus in the mid 1500s in the Indonesia-Malaysia region and evolved there into different genotypes, which then spread across Asia. No strong evidence for positive selection was found between JEV strains of the five genotypes and the E gene has generally been subjected to strong purifying selection.

  13. Army ants: an evolutionary bestseller?

    PubMed

    Berghoff, Stefanie M

    2003-09-02

    Army ants are characterized by a complex combination of behavioral and morphological traits. Molecular data now indicate that army ant behavior has a unique evolutionary origin and has been conserved for over more than 100 million years.

  14. Molecularly defined plasmonic engineering to visualize antibody binding events by eye

    NASA Astrophysics Data System (ADS)

    Clark, A. W.; Cooper, J. M.

    2013-02-01

    We report a novel plasmonic tuning technique which allows colorimetric, naked-eye detection of protein-protein binding at extreme sensitivities. Utilizing an engineered approach to molecularly-driven plasmonic-coupling, we construct three-part plasmonic "bowtie" structures within protein nanoarrays using single biomolecular binding events. Precise molecular positioning of single gold nanaoparticles inside plasmonic bowties allows us to shape the plasmon supported by each array element in order to engineer a visible color-shift. By ensuring that only a single binding site is available inside each feature, we ensure plasmon homogeneity across the array, a unique technological solution which is essential to providing the sensitivity and observability we demonstrate here. This work represents a step-change in molecularly-mediated plasmonics and colorimetric biosensing, enabling biologically-controlled nanoengineering at single-protein resolutions. The potential applications of this powerful technique are not limited to biosensing and point-of-care diagnostics, and will also impact the emerging fields of molecularly driven nanoengineering and electronics.

  15. Molecular evolution under increasing transposable element burden in Drosophila: A speed limit on the evolutionary arms race

    PubMed Central

    2011-01-01

    Background Genome architecture is profoundly influenced by transposable elements (TEs), and natural selection against their harmful effects is a critical factor limiting their spread. Genome defense by the piRNA silencing pathway also plays a crucial role in limiting TE proliferation. How these two forces jointly determine TE abundance is not well understood. To shed light on the nature of factors that predict TE success, we test three distinct hypotheses in the Drosophila genus. First, we determine whether TE abundance and relaxed genome-wide purifying selection on protein sequences are positively correlated. This serves to test the hypothesis that variation in TE abundance in the Drosophila genus can be explained by the strength of natural selection, relative to drift, acting in parallel against mildly deleterious non-synonymous mutations. Second, we test whether increasing TE abundance is correlated with an increased rate of amino-acid evolution in genes encoding the piRNA machinery, as might be predicted by an evolutionary arms race model. Third, we test whether increasing TE abundance is correlated with greater codon bias in genes of the piRNA machinery. This is predicted if increasing TE abundance selects for increased efficiency in the machinery of genome defense. Results Surprisingly, we find neither of the first two hypotheses to be true. Specifically, we found that genome-wide levels of purifying selection, measured by the ratio of non-synonymous to synonymous substitution rates (ω), were greater in species with greater TE abundance. In addition, species with greater TE abundance have greater levels of purifying selection in the piRNA machinery. In contrast, it appears that increasing TE abundance has primarily driven adaptation in the piRNA machinery by increasing codon bias. Conclusions These results indicate that within the Drosophila genus, a historically reduced strength of selection relative to drift is unlikely to explain patterns of increased TE

  16. Template engineered biopotent macrocyclic complexes involving furan moiety: Molecular modeling and molecular docking

    NASA Astrophysics Data System (ADS)

    Rathi, Parveen; Singh, D. P.

    2015-08-01

    Bioactive cobalt(II), nickel(II), copper(II) and zinc(II) complexes of octaazamacrocycle, 19, 20-dioxa-2,3,5,6,11,12,14,15-octaazatricyclo[14.2.1.1]icosa-1,6,8,10,15,17-hexaene-4,13-dithione, derived from furan-2,5-dione and thiocarbonohydrazide in the mole ratio 2:2:1 have been engineered via template methodology. The synthesized metal complexes have also been structurally characterized in the light of various physicochemical techniques and evaluated for antimicrobial and antioxidant activities. All these studies point toward the formation of divalent macrocyclic complexes possessing distorted octahedral geometry and having significant antimicrobial and antioxidant properties as compared to the starting precursors. Virtual screening of a representative complex was done through docking to the binding site of COX-2 to evaluate the anti-inflammatory activity of the series. Non-electrolytic nature of the complexes has been predicted on the basis of low value of molar conductivity in DMSO. All the complexes were having notable activities against pathogenic microbes as compared to precursors-thiocarbonohydrazide and furan-2,5-dione however, the complex 5, [Ni (C10H8N8O2S2) (NO3)2], shows the best antimicrobial activity.

  17. Molecular basis of evolutionary adaptation at the lactate dehydrogenase-B locus in the fish Fundulus heteroclitus.

    PubMed Central

    Crawford, D L; Powers, D A

    1989-01-01

    At the extremes of its natural distribution, populations of the common killifish Fundulus heteroclitus experience a difference of more than 15 degrees C in mean annual temperature. These populations are virtually fixed for two different codominant alleles at the heart-type lactate dehydrogenase locus (Ldh-B) which code for allozymes with different and adaptive kinetic responses to temperature. Two populations near the extremes of the species range (i.e., Maine and Georgia) were further studied for thermal adaptation at this locus. In the absence of any kinetic differences one would predict that to maintain a constant reaction velocity, 2 to 3 times as much enzyme would be required for each 10 degrees C decrease in environmental temperature. Consistent with this adaptive strategy and in addition to the adaptive kinetic characteristics, the LDH-B4 enzyme (EC 1.1.1.27) concentration and its mRNA concentration were approximately twice as great in the northern population as in the southern population. Acclimation experiments allow us to conclude that these differences are due to a combination of fixed genetic traits (evolutionary adaptation) and plastic responses to temperature (physiological acclimation). Furthermore, our calculations show that the LDH-B4 reaction velocities are essentially equivalent for these two populations, even though they live in significantly different thermal environments. PMID:2594773

  18. Open Issues in Evolutionary Robotics.

    PubMed

    Silva, Fernando; Duarte, Miguel; Correia, Luís; Oliveira, Sancho Moura; Christensen, Anders Lyhne

    2016-01-01

    One of the long-term goals in evolutionary robotics is to be able to automatically synthesize controllers for real autonomous robots based only on a task specification. While a number of studies have shown the applicability of evolutionary robotics techniques for the synthesis of behavioral control, researchers have consistently been faced with a number of issues preventing the widespread adoption of evolutionary robotics for engineering purposes. In this article, we review and discuss the open issues in evolutionary robotics. First, we analyze the benefits and challenges of simulation-based evolution and subsequent deployment of controllers versus evolution on real robotic hardware. Second, we discuss specific evolutionary computation issues that have plagued evolutionary robotics: (1) the bootstrap problem, (2) deception, and (3) the role of genomic encoding and genotype-phenotype mapping in the evolution of controllers for complex tasks. Finally, we address the absence of standard research practices in the field. We also discuss promising avenues of research. Our underlying motivation is the reduction of the current gap between evolutionary robotics and mainstream robotics, and the establishment of evolutionary robotics as a canonical approach for the engineering of autonomous robots.

  19. Homoplasy in genome-wide analysis of rare amino acid replacements: the molecular-evolutionary basis for Vavilov's law of homologous series

    PubMed Central

    Rogozin, Igor B; Thomson, Karen; Csürös, Miklós; Carmel, Liran; Koonin, Eugene V

    2008-01-01

    Background Rare genomic changes (RGCs) that are thought to comprise derived shared characters of individual clades are becoming an increasingly important class of markers in genome-wide phylogenetic studies. Recently, we proposed a new type of RGCs designated RGC_CAMs (after Conserved Amino acids-Multiple substitutions) that were inferred using genome-wide identification of amino acid replacements that were: i) located in unambiguously aligned regions of orthologous genes, ii) shared by two or more taxa in positions that contain a different, conserved amino acid in a much broader range of taxa, and iii) require two or three nucleotide substitutions. When applied to animal phylogeny, the RGC_CAM approach supported the coelomate clade that unites deuterostomes with arthropods as opposed to the ecdysozoan (molting animals) clade. However, a non-negligible level of homoplasy was detected. Results We provide a direct estimate of the level of homoplasy caused by parallel changes and reversals among the RGC_CAMs using 462 alignments of orthologous genes from 19 eukaryotic species. It is shown that the impact of parallel changes and reversals on the results of phylogenetic inference using RGC_CAMs cannot explain the observed support for the Coelomata clade. In contrast, the evidence in support of the Ecdysozoa clade, in large part, can be attributed to parallel changes. It is demonstrated that parallel changes are significantly more common in internal branches of different subtrees that are separated from the respective common ancestor by relatively short times than in terminal branches separated by longer time intervals. A similar but much weaker trend was detected for reversals. The observed evolutionary trend of parallel changes is explained in terms of the covarion model of molecular evolution. As the overlap between the covarion sets in orthologous genes from different lineages decreases with time after divergence, the likelihood of parallel changes decreases as well

  20. Deep sequencing revealed molecular signature of horizontal gene transfer of plant like transcripts in the mosquito Anopheles culicifacies: an evolutionary puzzle

    PubMed Central

    Sharma, Punita; Das De, Tanwee; Sharma, Swati; Kumar Mishra, Ashwani; Thomas, Tina; Verma, Sonia; Kumari, Vandana; Lata, Suman; Singh, Namita; Valecha, Neena; Chand Pandey, Kailash; Dixit, Rajnikant

    2015-01-01

    In prokaryotes, horizontal gene transfer (HGT) has been regarded as an important evolutionary drive to acquire and retain beneficial genes for their survival in diverse ecologies. However, in eukaryotes, the functional role of HGTs remains questionable, although current genomic tools are providing increased evidence of acquisition of novel traits within non-mating metazoan species. Here, we provide another transcriptomic evidence for the acquisition of massive plant genes in the mosquito, Anopheles culicifacies. Our multiple experimental validations including genomic PCR, RT-PCR, real-time PCR, immuno-blotting and immuno-florescence microscopy, confirmed that plant like transcripts (PLTs) are of mosquito origin and may encode functional proteins. A comprehensive molecular analysis of the PLTs and ongoing metagenomic analysis of salivary microbiome provide initial clues that mosquitoes may have survival benefits through the acquisition of nuclear as well as chloroplast encoded plant genes. Our findings of PLTs further support the similar questionable observation of HGTs in other higher organisms, which is still a controversial and debatable issue in the community of evolutionists. We believe future understanding of the underlying mechanism of the feeding associated molecular responses may shed new insights in the functional role of PLTs in the mosquito. PMID:26998230

  1. Evolutionary thinking

    PubMed Central

    Hunt, Tam

    2014-01-01

    Evolution as an idea has a lengthy history, even though the idea of evolution is generally associated with Darwin today. Rebecca Stott provides an engaging and thoughtful overview of this history of evolutionary thinking in her 2013 book, Darwin's Ghosts: The Secret History of Evolution. Since Darwin, the debate over evolution—both how it takes place and, in a long war of words with religiously-oriented thinkers, whether it takes place—has been sustained and heated. A growing share of this debate is now devoted to examining how evolutionary thinking affects areas outside of biology. How do our lives change when we recognize that all is in flux? What can we learn about life more generally if we study change instead of stasis? Carter Phipps’ book, Evolutionaries: Unlocking the Spiritual and Cultural Potential of Science's Greatest Idea, delves deep into this relatively new development. Phipps generally takes as a given the validity of the Modern Synthesis of evolutionary biology. His story takes us into, as the subtitle suggests, the spiritual and cultural implications of evolutionary thinking. Can religion and evolution be reconciled? Can evolutionary thinking lead to a new type of spirituality? Is our culture already being changed in ways that we don't realize by evolutionary thinking? These are all important questions and Phipps book is a great introduction to this discussion. Phipps is an author, journalist, and contributor to the emerging “integral” or “evolutionary” cultural movement that combines the insights of Integral Philosophy, evolutionary science, developmental psychology, and the social sciences. He has served as the Executive Editor of EnlightenNext magazine (no longer published) and more recently is the co-founder of the Institute for Cultural Evolution, a public policy think tank addressing the cultural roots of America's political challenges. What follows is an email interview with Phipps. PMID:26478766

  2. Molecular structure of photosynthetic microbial biofuels for improved engine combustion and emissions characteristics.

    PubMed

    Hellier, Paul; Purton, Saul; Ladommatos, Nicos

    2015-01-01

    The metabolic engineering of photosynthetic microbes for production of novel hydrocarbons presents an opportunity for development of advanced designer biofuels. These can be significantly more sustainable, throughout the production-to-consumption lifecycle, than the fossil fuels and crop-based biofuels they might replace. Current biofuels, such as bioethanol and fatty acid methyl esters, have been developed primarily as drop-in replacements for existing fossil fuels, based on their physical properties and autoignition characteristics under specific combustion regimes. However, advances in the genetic engineering of microalgae and cyanobacteria, and the application of synthetic biology approaches offer the potential of designer strains capable of producing hydrocarbons and oxygenates with specific molecular structures. Furthermore, these fuel molecules can be designed for higher efficiency of energy release and lower exhaust emissions during combustion. This paper presents a review of potential fuel molecules from photosynthetic microbes and the performance of these possible fuels in modern internal combustion engines, highlighting which modifications to the molecular structure of such fuels may enhance their suitability for specific combustion regimes.

  3. Molecular Engineering of Conjugated Polymers for Solar Cells: An Updated Report.

    PubMed

    Xiao, Shengqiang; Zhang, Qianqian; You, Wei

    2016-12-30

    The device efficiency of polymer:fullerene bulk heterojunction solar cells has recently surpassed 11%, as a result of synergistic efforts among chemists, physicists, and engineers. Since polymers are unequivocally the "heart" of this emerging technology, their design and synthesis have consistently played the key role in the device efficiency enhancement. In this article, the first focus is a discussion on molecular engineering (e.g., backbone, side chains, and substituents), then the discussion moves on to polymer engineering (e.g., molecular weight). Examples are primarily selected from the authors contributions; yet other significant discoveries/developments are also included to put the discussion in a broader context. Given that the synthesis, morphology, and device physics are inherently related in explaining the measured device output parameters (Jsc , Voc and FF), we will attempt to apply an integrated and comprehensive approach (synthesis, morphology, and device physics) to elucidate the fundamental, underlying principles that govern the device characteristics, in particular, in the context of disclosing structure-property correlations. Such correlations are crucial to the design and synthesis of next generation materials to further improve the device efficiency.

  4. Molecular Structure of Photosynthetic Microbial Biofuels for Improved Engine Combustion and Emissions Characteristics

    PubMed Central

    Hellier, Paul; Purton, Saul; Ladommatos, Nicos

    2015-01-01

    The metabolic engineering of photosynthetic microbes for production of novel hydrocarbons presents an opportunity for development of advanced designer biofuels. These can be significantly more sustainable, throughout the production-to-consumption lifecycle, than the fossil fuels and crop-based biofuels they might replace. Current biofuels, such as bioethanol and fatty acid methyl esters, have been developed primarily as drop-in replacements for existing fossil fuels, based on their physical properties and autoignition characteristics under specific combustion regimes. However, advances in the genetic engineering of microalgae and cyanobacteria, and the application of synthetic biology approaches offer the potential of designer strains capable of producing hydrocarbons and oxygenates with specific molecular structures. Furthermore, these fuel molecules can be designed for higher efficiency of energy release and lower exhaust emissions during combustion. This paper presents a review of potential fuel molecules from photosynthetic microbes and the performance of these possible fuels in modern internal combustion engines, highlighting which modifications to the molecular structure of such fuels may enhance their suitability for specific combustion regimes. PMID:25941673

  5. "The Environment is Everything That Isn't Me": Molecular Mechanisms and Evolutionary Dynamics of Insect Clocks in Variable Surroundings.

    PubMed

    Rivas, Gustavo B S; Bauzer, Luiz G S da R; Meireles-Filho, Antonio C A

    2015-01-01

    Circadian rhythms are oscillations in behavior, metabolism and physiology that have a period close to 24 h. These rhythms are controlled by an internal pacemaker that evolved under strong selective pressures imposed by environmental cyclical changes, mainly of light and temperature. The molecular nature of the circadian pacemaker was extensively studied in a number of organisms under controlled laboratory conditions. But although these studies were fundamental to our understanding of the circadian clock, most of the environmental conditions used resembled rather crudely the relatively constant situation at lower latitudes. At higher latitudes light-dark and temperature cycles vary considerably across different seasons, with summers having long and hot days and winters short and cold ones. Considering these differences and other external cues, such as moonlight, recent studies in more natural and semi-natural situations revealed unexpected features at both molecular and behavioral levels, highlighting the dramatic influence of multiple environmental variables in the molecular clockwork. This emphasizes the importance of studying the circadian clock in the wild, where seasonal environmental changes fine-tune the underlying circadian mechanism, affecting population dynamics and impacting the geographical variation in clock genes. Indeed, latitudinal clines in clock gene frequencies suggest that natural selection and demography shape the circadian clock over wide geographical ranges. In this review we will discuss the recent advances in understanding the molecular underpinnings of the circadian clock, how it resonates with the surrounding variables (both in the laboratory and in semi-natural conditions) and its impact on population dynamics and evolution. In addition, we will elaborate on how next-generation sequencing technologies will complement classical reductionist approaches by identifying causal variants in natural populations that will link genetic variation to

  6. Evolutionary processes in a continental island system: molecular phylogeography of the Aegean Nigella arvensis alliance (Ranunculaceae) inferred from chloroplast DNA.

    PubMed

    Bittkau, C; Comes, H P

    2005-11-01

    Continental shelf island systems, created by rising sea levels, provide a premier setting for studying the effects of past fragmentation, dispersal, and genetic drift on taxon diversification. We used phylogeographical (nested clade) and population genetic analyses to elucidate the relative roles of these processes in the evolutionary history of the Aegean Nigella arvensis alliance (= 'coenospecies'). We surveyed chloroplast DNA (cpDNA) variation in 455 individuals from 47 populations (nine taxa) of the alliance throughout its core range in the Aegean Archipelago and surrounding mainland areas of Greece and Turkey. The study revealed the presence of three major lineages, with largely nonoverlapping distributions in the Western, Central, and Eastern Aegean. There is evidence supporting the idea that these major lineages evolved in situ from a widespread (pan-Aegean) ancestral stock as a result of multiple fragmentation events, possibly due to the influence of post-Messinian sea flooding, Pleistocene eustatic changes and corresponding climate fluctuations. Over-sea dispersal and founder events appear to have played a rather insignificant role in the group's history. Rather, all analytical approaches identified the alliance as an organism group with poor seed dispersal capabilities and a susceptibility to genetic drift. In particular, we inferred that the observed level of cpDNA differentiation between Kikladian island populations of Nigella degenii largely reflects population history, (viz. Holocene island fragmentation) and genetic drift in the near absence of seed flow since their time of common ancestry. Overall, our cpDNA data for the N. arvensis alliance in general, and N. degenii in particular, indicate that historical events were important in determining the phylogeographical patterns seen, and that genetic drift has historically been relatively more influential on population structure than has cytoplasmic gene flow.

  7. Molecular mechanisms and metabolic engineering of glutamate overproduction in Corynebacterium glutamicum.

    PubMed

    Hirasawa, Takashi; Kim, Jongpill; Shirai, Tomokazu; Furusawa, Chikara; Shimizu, Hiroshi

    2012-01-01

    Glutamate is a commercially important chemical. It is used as a flavor enhancer and is a major raw material for producing industrially useful chemicals. A coryneform bacterium, Corynebacterium glutamicum, was isolated in 1956 by Japanese researchers as a glutamate-overproducing bacterium and since then, remarkable progress in glutamate production has been made using this microorganism. Currently, the global market for glutamate is over 2.5 million tons per year. Glutamate overproduction by C. glutamicum is induced by specific treatments-biotin limitation, addition of fatty acid ester surfactants such as Tween 40, and addition of β-lactam antibiotics such as penicillin. Molecular biology and metabolic engineering studies on glutamate overproduction have revealed that metabolic flow is significantly altered by these treatments. These studies have also provided insight into the molecular mechanisms underlying these changes. In this chapter, we review our current understanding of the molecular mechanisms of glutamate overproduction in C. glutamicum, and we discuss the advances made by metabolic engineering of this microorganism.

  8. Engineering and Evolution of Molecular Chaperones and Protein Disaggregases with Enhanced Activity

    PubMed Central

    Mack, Korrie L.; Shorter, James

    2016-01-01

    Cells have evolved a sophisticated proteostasis network to ensure that proteins acquire and retain their native structure and function. Critical components of this network include molecular chaperones and protein disaggregases, which function to prevent and reverse deleterious protein misfolding. Nevertheless, proteostasis networks have limits, which when exceeded can have fatal consequences as in various neurodegenerative disorders, including Parkinson's disease and amyotrophic lateral sclerosis. A promising strategy is to engineer proteostasis networks to counter challenges presented by specific diseases or specific proteins. Here, we review efforts to enhance the activity of individual molecular chaperones or protein disaggregases via engineering and directed evolution. Remarkably, enhanced global activity or altered substrate specificity of various molecular chaperones, including GroEL, Hsp70, ClpX, and Spy, can be achieved by minor changes in primary sequence and often a single missense mutation. Likewise, small changes in the primary sequence of Hsp104 yield potentiated protein disaggregases that reverse the aggregation and buffer toxicity of various neurodegenerative disease proteins, including α-synuclein, TDP-43, and FUS. Collectively, these advances have revealed key mechanistic and functional insights into chaperone and disaggregase biology. They also suggest that enhanced chaperones and disaggregases could have important applications in treating human disease as well as in the purification of valuable proteins in the pharmaceutical sector. PMID:27014702

  9. Testing the evolutionary and biogeographical history of Glypthelmins (Digenea: Plagiorchiida), a parasite of anurans, through a simultaneous analysis of molecular and morphological data.

    PubMed

    Razo-Mendivil, Ulises; de León, Gerardo Pérez-Ponce

    2011-05-01

    The genus Glypthelmins includes some of the most common digeneans inhabiting the intestine of anurans in the Americas. Phylogenetic analyses of eight species of Glypthelmins and five outgroups, using 26 morphological characters and sequences of cox1, 18S, 5.8S, 28S genes and ITS2 were performed. Additionally, 2 species for which no molecular data have been obtained were included in the analyses. Following a simultaneous analysis approach and using different methods of phylogenetic inference we obtained a phylogenetic tree where the eight studied species conform a monophyletic clade which is well supported by Bremer support, bootstrap, and posterior probabilities. The mapping of morphological characters showed that traits such as serrate scale-like spines, bipartite seminal vesicle, metraterm running dorsal to the cirrus pouch, and ovary sinistral are unequivocal synapomorphies that support the monophyly of Glypthelmins. Phylogenetic hypothesis based on combined data sets was used to re-evaluate the evolutionary and biogeographical history of this group of digeneans. New information provided in this study, in the context of a more robust analytical method allowed us to corroborate that members of the "Rana pipiens" group were the plesiomorphic group of hosts for Glypthelmins, with two host switching events occurring from the "Rana pipiens" group to the "Rana palmipes" group and to Hylidae during the evolutionary history of this group of parasites, and the origin of the group is proposed in Nearctic frogs, with a colonization of Neotropical hosts represented by a monophyletic clade constituted by G. brownorumae, G. facioi, and G. tuxtlasensis.

  10. Evolutionary synthetic biology.

    PubMed

    Peisajovich, Sergio G

    2012-06-15

    Signaling networks process vast amounts of environmental information to generate specific cellular responses. As cellular environments change, signaling networks adapt accordingly. Here, I will discuss how the integration of synthetic biology and directed evolution approaches is shedding light on the molecular mechanisms that guide the evolution of signaling networks. In particular, I will review studies that demonstrate how different types of mutations, from the replacement of individual amino acids to the shuffling of modular domains, lead to markedly different evolutionary trajectories and consequently to diverse network rewiring. Moreover, I will argue that intrinsic evolutionary properties of signaling proteins, such as the robustness of wild type functions, the promiscuous nature of evolutionary intermediates, and the modular decoupling between binding and catalysis, play important roles in the evolution of signaling networks. Finally, I will argue that rapid advances in our ability to synthesize DNA will radically alter how we study signaling network evolution at the genome-wide level.

  11. Biological Activities of Natural and Engineered Cyclotides, a Novel Molecular Scaffold for Peptide-Based Therapeutics

    PubMed Central

    Garcia, Angie E.; Camarero, Julio A.

    2012-01-01

    Cyclotides are a growing family of large plant-derived backbone-cyclized polypeptides (≈30 amino acids long) that share a disulfide-stabilized core characterized by an unusual knotted structure. Their unique circular backbone topology and knotted arrangement of three disulfide bonds makes them exceptionally stable to thermal, chemical, and enzymatic degradation compared to other peptides of similar size. Currently more than 100 sequences of different cyclotides have been characterized and the number is expected to increase dramatically in the coming years. Considering their stability, biological activities and ability to cross the cell membrane, cyclotides can be exploited to develop new peptide-based drugs with high potential for success. The cyclotide scaffold can be engineered or evolved using molecular evolution to inhibit protein-protein interactions implicated in cancer and other human diseases, or design new antimicrobial. The present review reports the biological diversity and therapeutic potential of natural and engineered cyclotides. PMID:20858197

  12. Reverse engineering the mechanical and molecular pathways in stem cell morphogenesis.

    PubMed

    Lu, Kai; Gordon, Richard; Cao, Tong

    2015-03-01

    The formation of relevant biological structures poses a challenge for regenerative medicine. During embryogenesis, embryonic cells differentiate into somatic tissues and undergo morphogenesis to produce three-dimensional organs. Using stem cells, we can recapitulate this process and create biological constructs for therapeutic transplantation. However, imperfect imitation of nature sometimes results in in vitro artifacts that fail to recapitulate the function of native organs. It has been hypothesized that developing cells may self-organize into tissue-specific structures given a correct in vitro environment. This proposition is supported by the generation of neo-organoids from stem cells. We suggest that morphogenesis may be reverse engineered to uncover its interacting mechanical pathway and molecular circuitry. By harnessing the latent architecture of stem cells, novel tissue-engineering strategies may be conceptualized for generating self-organizing transplants.

  13. Magnetically engineered smart thin films: toward lab-on-chip ultra-sensitive molecular imaging.

    PubMed

    Hassan, Muhammad A; Saqib, Mudassara; Shaikh, Haseeb; Ahmad, Nasir M; Elaissari, Abdelhamid

    2013-03-01

    Magnetically responsive engineered smart thin films of nanoferrites as contrast agent are employed to develop surface based magnetic resonance imaging to acquire simple yet fast molecular imaging. The work presented here can be of significant potential for future lab-on-chip point-of-care diagnostics from the whole blood pool on almost any substrates to reduce or even prevent clinical studies involve a living organism to enhance the non-invasive imaging to advance the '3Rs' of work in animals-replacement, refinement and reduction.

  14. Type I interferon receptors in goose: molecular cloning, structural identification, evolutionary analysis and age-related tissue expression profile.

    PubMed

    Zhou, Hao; Chen, Shun; Qi, Yulin; Zhou, Qin; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Sun, Kunfeng; Liu, Fei; Chen, Xiaoyue; Cheng, Anchun

    2015-04-25

    The cDNAs encoding two distinct type I interferon receptors were firstly cloned from the spleen of white goose (the Chinese goose, Anser cygnoides). The cDNA of goose IFNAR1 consisted of 1616 bp and encoded 406 amino acids with a predicted molecular weight of 46.4 kDa, while the cDNA of goose IFNAR2 consisted of 1525 bp and encoded 294 amino acids with a predicted molecular weight of 32.6 kDa. The IFNAR1 shared 85.4% identity in deduced amino acid sequence with duck IFNAR1, while IFNAR2 amino acid sequence showed 86% identity with that of duck IFNAR2. The age-related analysis of gene expression revealed that goose IFNα and IFNARs were all highly transcribed in pancreas, which may due to a reasonable amount of dendritic cells aggregated in pancreas. And goose IFNα and its cognate receptors had different structural features and tissue expression patterns during the period from embryonic goose to adult goose, suggesting that IFNα and IFNARs may maintain a developmental dynamic immune competence in unstimulated states. The data provided in this study may contribute to future understanding of the interaction between interferon and interferon receptors in immune mechanism. And it also helps us to understand the age-related susceptibility to pathogens in birds better.

  15. Molecular Basis of Clay Mineral Structure and Dynamics in Subsurface Engineering Applications

    NASA Astrophysics Data System (ADS)

    Cygan, R. T.

    2015-12-01

    Clay minerals and their interfaces play an essential role in many geochemical, environmental, and subsurface engineering applications. Adsorption, dissolution, precipitation, nucleation, and growth mechanisms, in particular, are controlled by the interplay of structure, thermodynamics, kinetics, and transport at clay mineral-water interfaces. Molecular details of these processes are typically beyond the sensitivity of experimental and analytical methods, and therefore require accurate models and simulations. Also, basal surfaces and interlayers of clay minerals provide constrained interfacial environments to facilitate the evaluation of these complex processes. We have developed and used classical molecular and quantum methods to examine the complex behavior of clay mineral-water interfaces and dynamics of interlayer species. Bulk structures, swelling behavior, diffusion, and adsorption processes are evaluated and compared to experimental and spectroscopic findings. Analysis of adsorption mechanisms of radionuclides on clay minerals provides a scientific basis for predicting the suitability of engineered barriers associated with nuclear waste repositories and the fate of contaminants in the environment. Similarly, the injection of supercritical carbon dioxide into geological reservoirs—to mitigate the impact of climate change—is evaluated by molecular models of multi-fluid interactions with clay minerals. Molecular dynamics simulations provide insights into the wettability of different fluids—water, electrolyte solutions, and supercritical carbon dioxide—on clay surfaces, and which ultimately affects capillary fluid flow and the integrity of shale caprocks. This work is supported as part of Center for Frontiers of Subsurface Energy Security, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science and by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Geosciences Research Program

  16. A molecular phylogeny of the Littorininae (Gastropoda: Littorinidae): unequal evolutionary rates, morphological parallelism, and biogeography of the Southern Ocean.

    PubMed

    Williams, S T; Reid, D G; Littlewood, D T J

    2003-07-01

    A molecular phylogeny is presented for the subfamily Littorininae (including representatives of all subgeneric taxa and all members of a group of southern-temperate species formerly classified as 'Nodilittorina'), based on sequence data from two nuclear (18S rRNA, 28S rRNA) and two mitochondrial (12S rRNA, CO1) genes. The phylogeny shows considerable disagreement with earlier hypotheses derived from morphological data. In particular, 'Nodilittorina' is polyphyletic and is here divided into four genera (Echinolittorina, Austrolittorina, Afrolittorina new genus, and the monotypic Nodilittorina s.s.). The phylogenetic relationships of 'Littorina' striata have been controversial and it is here transferred to the genus Tectarius, a surprising relationship for which there is little morphological support. The relationships of the enigmatic Mainwaringia remain poorly resolved, but it is not a basal member of the subfamily. The two living species of Mainwaringia are remarkable for a greatly elevated rate of evolution in all four genes examined; it is suggested that this may be connected with their protandrous hermaphroditism, which is unique in the family. The molecular phylogeny provides a new framework for the adaptive radiation of the Littorininae, showing more frequent shifts between habitats and climatic regimes than previously suspected, and striking parallelism of morphological characters. The fossil record of littorinids is poor, but ages of clades are estimated using a calibration based on a Lower Eocene age of the genus Littoraria. Using these estimates, the antitropical distribution of Littorina and Afrolittorina is an ancient pattern of possibly Cretaceous age. The five members of Austrolittorina show a Gondwanan distribution in Australia, New Zealand, and South America. Based on the morphological uniformity within this clade, relatively recent (Plio-Pleistocene) trans-Pacific dispersal events seemed a likely explanation, as proposed for numerous other

  17. Molecular evolutionary dynamics of cytochrome b in strepsirrhine primates: the phylogenetic significance of third-position transversions.

    PubMed

    Yoder, A D; Vilgalys, R; Ruvolo, M

    1996-12-01

    DNA sequences of the complete cytochrome b gene are shown to contain robust phylogenetic signal for the strepsirrhine primates (i.e., lemurs and lorises). The phylogeny derived from these data conforms to other molecular studies of strepsirrhine relationships despite the fact that uncorrected nucleotide distances are high for nearly all intrastrepsirrhine comparisons, with most in the 15%-20% range. Cytochrome b sequences support the hypothesis that Malagasy lemuriforms and Afro-Asian lorisiforms each comprise clades that share a sister-group relationship. A study (Adkins and Honeycutt 1994) of the cytochrome c oxidase subunit II (COII) gene placed one Malagasy primate (Daubentonia) at the base of the strepsirrhine clade, thereby suggesting a diphyletic Lemuriformes. The reanalysis of COII third-position transversions, either alone or in combination with cytochrome b third-position transversions, however, yields a tree that is congruent with phylogenetic hypotheses derived from cytochrome b and other genetic data sets.

  18. Molecular fingerprinting of Salmonella typhimurium by IS200-typing as a tool for epidemiological and evolutionary studies.

    PubMed

    Soria, G; Barbé, J; Gibert, I

    1994-01-01

    The aim of this work was to develop and evaluate a molecular typing strategy for Salmonella based on hybridization of chromosomal DNA with two different probes derived from insertion sequence IS200. Probe IS200-TT was specifically constructed for this study as a trimer of a 112 pb TaqI-TaqI fragment of IS200. Among several restriction enzymes evaluated, two were selected: EcoRI, which cuts the insertion sequence in two pieces, each one complementary to one of the probes used, and PstI, a restriction enzyme with no recognition site into IS200. With several combinations of these restrictions enzymes and probes, 43 Salmonella typhimurium strains were analyzed for copy number and location of IS200, as well as reproducibility and stability of the patterns. IS200 types have been shown to be stable, both in strains isolated from different patients implicated in the same salmonellosis outbreak and in strains isolated from the same patient at different times or from different specimens. The discriminatory power of the method has been 0.91 to 0.94. As a comparison, S. typhimurium strains were also ribotyped. Discriminatory power of the ribotypes oscillated between 0.44 and 0.55, depending on the enzyme used, and achieved a 0.78 value when the information obtained with two restriction enzymes was combined. Moreover, IS200 typing was able to differentiate among a group of S. typhimurium strains which were identical by ribotype and enzymatic electrophoretic mobility. These results enable us to conclude that, for the stability, reproducibility and discriminatory power of the patterns generated, IS200 probes can be a very useful tool in the molecular typing of S. typhimurium.

  19. Divergence Times and the Evolutionary Radiation of New World Monkeys (Platyrrhini, Primates): An Analysis of Fossil and Molecular Data

    PubMed Central

    Perez, S. Ivan; Tejedor, Marcelo F.; Novo, Nelson M.; Aristide, Leandro

    2013-01-01

    The estimation of phylogenetic relationships and divergence times among a group of organisms is a fundamental first step toward understanding its biological diversification. The time of the most recent or last common ancestor (LCA) of extant platyrrhines is one of the most controversial among scholars of primate evolution. Here we use two molecular based approaches to date the initial divergence of the platyrrhine clade, Bayesian estimations under a relaxed-clock model and substitution rate plus generation time and body size, employing the fossil record and genome datasets. We also explore the robustness of our estimations with respect to changes in topology, fossil constraints and substitution rate, and discuss the implications of our findings for understanding the platyrrhine radiation. Our results suggest that fossil constraints, topology and substitution rate have an important influence on our divergence time estimates. Bayesian estimates using conservative but realistic fossil constraints suggest that the LCA of extant platyrrhines existed at ca. 29 Ma, with the 95% confidence limit for the node ranging from 27–31 Ma. The LCA of extant platyrrhine monkeys based on substitution rate corrected by generation time and body size was established between 21–29 Ma. The estimates based on the two approaches used in this study recalibrate the ages of the major platyrrhine clades and corroborate the hypothesis that they constitute very old lineages. These results can help reconcile several controversial points concerning the affinities of key early Miocene fossils that have arisen among paleontologists and molecular systematists. However, they cannot resolve the controversy of whether these fossil species truly belong to the extant lineages or to a stem platyrrhine clade. That question can only be resolved by morphology. Finally, we show that the use of different approaches and well supported fossil information gives a more robust divergence time estimate of a clade

  20. Cloning, molecular characterization, and phylogeny of two evolutionary distinct glutamine synthetase isoforms in the green microalga Haematococcus pluvialis (Chlorophyceae).

    PubMed

    Reinecke, Diana L; Zarka, Aliza; Leu, Stefan; Boussiba, Sammy

    2016-12-01

    Haematococcus pluvialis (Chlorophyta) is a widely used microalga of great economic potential, yet its molecular genetics and evolution are largely unknown. We present new detailed molecular and phylogenetic analysis of two glutamine synthetase (GS) enzymes and genes (gln) under the Astaxanthin-inducing conditions of light- and nitrogen-stress. Structure analysis identified key residues and confirmed two decameric GS2 holoenzymes, a cytoplasmic enzyme, termed GS2c , and a plastidic form, termed GS2p , due to chloroplast-transit peptides at its N-terminus. Gene expression analysis showed dissociation of mRNA, protein, and enzyme activity levels for both GS2 under different growth conditions, indicating the strong post-transcriptional regulation. Data-mining identified novel and specified published gln genes from Prasinophyceae, Chlorophyta, Trebouxiophyceae, Charophyceae, Bryophyta, Lycopodiophyta, Spermatophyta, and Rhodophyta. Phylogenetic analysis found homologues to the cytosolic GS2c of H. pluvialis in all other photo- and non-photosynthetic Eukaryota. The chloroplastic GS2p was restricted to Chlorophyta, Bryophyta, some Proteobacteria and Fungii; no homologues were identified in Spermatophyta or other Eukaryota. This indicates two independent prokaryotic donors for these two gln genes in H. pluvialis. Combined phylogenetic analysis of GS, chl-b synthase, elongation factor, and light harvesting complex homologues project a newly refined model of Viridiplantae evolution. Herein, a GS1 evolved into the cytosolic GS2c and was passed on to all Eukaryota. Later, the chloroplastic GS2p entered the Archaeplastida lineage via a horizontal gene transfer at the divergence of Chlorophyta and Rhodophyta lineages. GS2p persisted in Chlorophyta and Bryophyta, but was lost during Spermatophyta evolution. These data suggest the revision of GS classification and nomenclature, and extend our understanding of the photosynthetic Eukaryota evolution.

  1. An evolutionary model for collapsing molecular clouds and their star formation activity. II. Mass dependence of the star formation rate

    SciTech Connect

    Zamora-Avilés, Manuel; Vázquez-Semadeni, Enrique

    2014-10-01

    We discuss the evolution and dependence on cloud mass of the star formation rate (SFR) and efficiency (SFE) of star-forming molecular clouds (MCs) within the scenario that clouds are undergoing global collapse and that the SFR is controlled by ionization feedback. We find that low-mass clouds (M {sub max} ≲ 10{sup 4} M {sub ☉}) spend most of their evolution at low SFRs, but end their lives with a mini-burst, reaching a peak SFR ∼10{sup 4} M {sub ☉} Myr{sup –1}, although their time-averaged SFR is only (SFR) ∼ 10{sup 2} M {sub ☉} Myr{sup –1}. The corresponding efficiencies are SFE{sub final} ≲ 60% and (SFE) ≲ 1%. For more massive clouds (M {sub max} ≳ 10{sup 5} M {sub ☉}), the SFR first increases and then reaches a plateau because the clouds are influenced by stellar feedback since earlier in their evolution. As a function of cloud mass, (SFR) and (SFE) are well represented by the fits (SFR) ≈ 100(1 + M {sub max}/1.4 × 10{sup 5} M {sub ☉}){sup 1.68} M {sub ☉} Myr{sup –1} and (SFE) ≈ 0.03(M {sub max}/2.5 × 10{sup 5} M {sub ☉}){sup 0.33}, respectively. Moreover, the SFR of our model clouds follows closely the SFR-dense gas mass relation recently found by Lada et al. during the epoch when their instantaneous SFEs are comparable to those of the clouds considered by those authors. Collectively, a Monte Carlo integration of the model-predicted SFR(M) over a Galactic giant molecular cloud mass spectrum yields values for the total Galactic SFR that are within half an order of magnitude of the relation obtained by Gao and Solomon. Our results support the scenario that star-forming MCs may be in global gravitational collapse and that the low observed values of the SFR and SFE are a result of the interruption of each SF episode, caused primarily by the ionizing feedback from massive stars.

  2. Discovery of gigantic molecular nanostructures using a flow reaction array as a search engine

    NASA Astrophysics Data System (ADS)

    Zang, Hong-Ying; de La Oliva, Andreu Ruiz; Miras, Haralampos N.; Long, De-Liang; McBurney, Roy T.; Cronin, Leroy

    2014-04-01

    The discovery of gigantic molecular nanostructures like coordination and polyoxometalate clusters is extremely time-consuming since a vast combinatorial space needs to be searched, and even a systematic and exhaustive exploration of the available synthetic parameters relies on a great deal of serendipity. Here we present a synthetic methodology that combines a flow reaction array and algorithmic control to give a chemical ‘real-space’ search engine leading to the discovery and isolation of a range of new molecular nanoclusters based on [Mo2O2S2]2+-based building blocks with either fourfold (C4) or fivefold (C5) symmetry templates and linkers. This engine leads us to isolate six new nanoscale cluster compounds: 1, {Mo10(C5)}; 2, {Mo14(C4)4(C5)2}; 3, {Mo60(C4)10}; 4, {Mo48(C4)6}; 5, {Mo34(C4)4}; 6, {Mo18(C4)9}; in only 200 automated experiments from a parameter space spanning ~5 million possible combinations.

  3. Discovery of gigantic molecular nanostructures using a flow reaction array as a search engine.

    PubMed

    Zang, Hong-Ying; de la Oliva, Andreu Ruiz; Miras, Haralampos N; Long, De-Liang; McBurney, Roy T; Cronin, Leroy

    2014-04-28

    The discovery of gigantic molecular nanostructures like coordination and polyoxometalate clusters is extremely time-consuming since a vast combinatorial space needs to be searched, and even a systematic and exhaustive exploration of the available synthetic parameters relies on a great deal of serendipity. Here we present a synthetic methodology that combines a flow reaction array and algorithmic control to give a chemical 'real-space' search engine leading to the discovery and isolation of a range of new molecular nanoclusters based on [Mo(2)O(2)S(2)](2+)-based building blocks with either fourfold (C4) or fivefold (C5) symmetry templates and linkers. This engine leads us to isolate six new nanoscale cluster compounds: 1, {Mo(10)(C5)}; 2, {Mo(14)(C4)4(C5)2}; 3, {Mo(60)(C4)10}; 4, {Mo(48)(C4)6}; 5, {Mo(34)(C4)4}; 6, {Mo(18)(C4)9}; in only 200 automated experiments from a parameter space spanning ~5 million possible combinations.

  4. Discovery of gigantic molecular nanostructures using a flow reaction array as a search engine

    PubMed Central

    Zang, Hong-Ying; de la Oliva, Andreu Ruiz; Miras, Haralampos N.; Long, De-Liang; McBurney, Roy T.; Cronin, Leroy

    2014-01-01

    The discovery of gigantic molecular nanostructures like coordination and polyoxometalate clusters is extremely time-consuming since a vast combinatorial space needs to be searched, and even a systematic and exhaustive exploration of the available synthetic parameters relies on a great deal of serendipity. Here we present a synthetic methodology that combines a flow reaction array and algorithmic control to give a chemical ‘real-space’ search engine leading to the discovery and isolation of a range of new molecular nanoclusters based on [Mo2O2S2]2+-based building blocks with either fourfold (C4) or fivefold (C5) symmetry templates and linkers. This engine leads us to isolate six new nanoscale cluster compounds: 1, {Mo10(C5)}; 2, {Mo14(C4)4(C5)2}; 3, {Mo60(C4)10}; 4, {Mo48(C4)6}; 5, {Mo34(C4)4}; 6, {Mo18(C4)9}; in only 200 automated experiments from a parameter space spanning ~5 million possible combinations. PMID:24770632

  5. Molecular evolutionary dynamics of cytochrome P450 monooxygenases across kingdoms: Special focus on mycobacterial P450s

    PubMed Central

    Parvez, Mohammad; Qhanya, Lehlohonolo Benedict; Mthakathi, Ntsane Trevor; Kgosiemang, Ipeleng Kopano Rosinah; Bamal, Hans Denis; Pagadala, Nataraj Sekhar; Xie, Ting; Yang, Haoran; Chen, Hengye; Theron, Chrispian William; Monyaki, Richie; Raselemane, Seiso Caiphus; Salewe, Vuyani; Mongale, Bogadi Lorato; Matowane, Retshedisitswe Godfrey; Abdalla, Sara Mohamed Hasaan; Booi, Wool Isaac; van Wyk, Mari; Olivier, Dedré; Boucher, Charlotte E.; Nelson, David R.; Tuszynski, Jack A.; Blackburn, Jonathan Michael; Yu, Jae-Hyuk; Mashele, Samson Sitheni; Chen, Wanping; Syed, Khajamohiddin

    2016-01-01

    Since the initial identification of cytochrome P450 monooxygenases (CYPs/P450s), great progress has been made in understanding their structure-function relationship, diversity and application in producing compounds beneficial to humans. However, the molecular evolution of P450s in terms of their dynamics both at protein and DNA levels and functional conservation across kingdoms still needs investigation. In this study, we analyzed 17 598 P450s belonging to 113 P450 families (bacteria −42; fungi −19; plant −28; animal −22; plant and animal −1 and common P450 family −1) and found highly conserved and rapidly evolving P450 families. Results suggested that bacterial P450s, particularly P450s belonging to mycobacteria, are highly conserved both at protein and DNA levels. Mycobacteria possess the highest P450 diversity percentage compared to other microbes and have a high coverage of P450s (≥1%) in their genomes, as found in fungi and plants. Phylogenetic and functional analyses revealed the functional conservation of P450s despite belonging to different biological kingdoms, suggesting the adherence of P450s to their innate function such as their involvement in either generation or oxidation of steroids and structurally related molecules, fatty acids and terpenoids. This study’s results offer new understanding of the dynamic structural nature of P450s. PMID:27616185

  6. Evolutionary Covariance Combined with Molecular Dynamics Predicts a Framework for Allostery in the MutS DNA Mismatch Repair Protein

    PubMed Central

    2017-01-01

    Mismatch repair (MMR) is an essential, evolutionarily conserved pathway that maintains genome stability by correcting base-pairing errors in DNA. Here we examine the sequence and structure of MutS MMR protein to decipher the amino acid framework underlying its two key activities—recognizing mismatches in DNA and using ATP to initiate repair. Statistical coupling analysis (SCA) identified a network (sector) of coevolved amino acids in the MutS protein family. The potential functional significance of this SCA sector was assessed by performing molecular dynamics (MD) simulations for alanine mutants of the top 5% of 160 residues in the distribution, and control nonsector residues. The effects on three independent metrics were monitored: (i) MutS domain conformational dynamics, (ii) hydrogen bonding between MutS and DNA/ATP, and (iii) relative ATP binding free energy. Each measure revealed that sector residues contribute more substantively to MutS structure–function than nonsector residues. Notably, sector mutations disrupted MutS contacts with DNA and/or ATP from a distance via contiguous pathways and correlated motions, supporting the idea that SCA can identify amino acid networks underlying allosteric communication. The combined SCA/MD approach yielded novel, experimentally testable hypotheses for unknown roles of many residues distributed across MutS, including some implicated in Lynch cancer syndrome. PMID:28135092

  7. Molecular analysis of the amphioxus frontal eye unravels the evolutionary origin of the retina and pigment cells of the vertebrate eye.

    PubMed

    Vopalensky, Pavel; Pergner, Jiri; Liegertova, Michaela; Benito-Gutierrez, Elia; Arendt, Detlev; Kozmik, Zbynek

    2012-09-18

    The origin of vertebrate eyes is still enigmatic. The "frontal eye" of amphioxus, our most primitive chordate relative, has long been recognized as a candidate precursor to the vertebrate eyes. However, the amphioxus frontal eye is composed of simple ciliated cells, unlike vertebrate rods and cones, which display more elaborate, surface-extended cilia. So far, the only evidence that the frontal eye indeed might be sensitive to light has been the presence of a ciliated putative sensory cell in the close vicinity of dark pigment cells. We set out to characterize the cell types of the amphioxus frontal eye molecularly, to test their possible relatedness to the cell types of vertebrate eyes. We show that the cells of the frontal eye specifically coexpress a combination of transcription factors and opsins typical of the vertebrate eye photoreceptors and an inhibitory Gi-type alpha subunit of the G protein, indicating an off-responding phototransductory cascade. Furthermore, the pigmented cells match the retinal pigmented epithelium in melanin content and regulatory signature. Finally, we reveal axonal projections of the frontal eye that resemble the basic photosensory-motor circuit of the vertebrate forebrain. These results support homology of the amphioxus frontal eye and the vertebrate eyes and yield insights into their evolutionary origin.

  8. Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases.

    PubMed

    Redondo, Pilar; Prieto, Jesús; Muñoz, Inés G; Alibés, Andreu; Stricher, Francois; Serrano, Luis; Cabaniols, Jean-Pierre; Daboussi, Fayza; Arnould, Sylvain; Perez, Christophe; Duchateau, Philippe; Pâques, Frédéric; Blanco, Francisco J; Montoya, Guillermo

    2008-11-06

    Xeroderma pigmentosum is a monogenic disease characterized by hypersensitivity to ultraviolet light. The cells of xeroderma pigmentosum patients are defective in nucleotide excision repair, limiting their capacity to eliminate ultraviolet-induced DNA damage, and resulting in a strong predisposition to develop skin cancers. The use of rare cutting DNA endonucleases-such as homing endonucleases, also known as meganucleases-constitutes one possible strategy for repairing DNA lesions. Homing endonucleases have emerged as highly specific molecular scalpels that recognize and cleave DNA sites, promoting efficient homologous gene targeting through double-strand-break-induced homologous recombination. Here we describe two engineered heterodimeric derivatives of the homing endonuclease I-CreI, produced by a semi-rational approach. These two molecules-Amel3-Amel4 and Ini3-Ini4-cleave DNA from the human XPC gene (xeroderma pigmentosum group C), in vitro and in vivo. Crystal structures of the I-CreI variants complexed with intact and cleaved XPC target DNA suggest that the mechanism of DNA recognition and cleavage by the engineered homing endonucleases is similar to that of the wild-type I-CreI. Furthermore, these derivatives induced high levels of specific gene targeting in mammalian cells while displaying no obvious genotoxicity. Thus, homing endonucleases can be designed to recognize and cleave the DNA sequences of specific genes, opening up new possibilities for genome engineering and gene therapy in xeroderma pigmentosum patients whose illness can be treated ex vivo.

  9. Molecular engineering of exocytic vesicle traffic enhances the productivity of Chinese hamster ovary cells.

    PubMed

    Peng, Ren-Wang; Fussenegger, Martin

    2009-03-01

    A complex vesicle trafficking system manages the precise and regulated distribution of proteins, membranes and other molecular cargo between cellular compartments as well as the secretion of (heterologous) proteins in mammalian cells. Sec1/Munc18 (SM) proteins are key components of the system by regulating membrane fusion. However, it is not clear how SM proteins contribute to the overall exocytosis. Here, functional analysis of the SM protein Sly1 and Munc18c suggested a united, positive impact upon SNARE-based fusion of ER-to-Golgi- and Golgi-to-plasma membrane-addressed exocytic vesicles and increased the secretory capacity of different therapeutic proteins in Chinese hamster ovary cells up to 40 pg/cell/day. Sly1- and Munc18c-based vesicle traffic engineering cooperated with Xbp-1-mediated ER/Golgi organelle engineering. Our study supports a model for united function of SM proteins in stimulating vesicle trafficking machinery and provides a generic secretion engineering strategy to improve biopharmaceutical manufacturing of important protein therapeutics.

  10. Not drowning, (hand)waving? Molecular phylogenetics, biogeography and evolutionary tempo of the 'Gondwanan' midge Stictocladius Edwards (Diptera: Chironomidae).

    PubMed

    Krosch, Matt; Cranston, Peter S

    2013-09-01

    Many insect clades, especially within the Diptera (true flies), have been considered classically 'Gondwanan', with an inference that distributions derive from vicariance of the southern continents. Assessing the role that vicariance has played in the evolution of austral taxa requires testing the location and tempo of diversification and speciation against the well-established predictions of fragmentation of the ancient super-continent. Several early (anecdotal) hypotheses that current austral distributions originate from the breakup of Gondwana derive from studies of taxa within the family Chironomidae (non-biting midges). With the advent of molecular phylogenetics and biogeographic analytical software, these studies have been revisited and expanded to test such conclusions better. Here we studied the midge genus Stictocladius Edwards, from the subfamily Orthocladiinae, which contains austral-distributed clades that match vicariance-based expectations. We resolve several issues of systematic relationships among morphological species and reveal cryptic diversity within many taxa. Time-calibrated phylogenetic relationships among taxa accorded partially with the predicted tempo from geology. For these apparently vagile insects, vicariance-dated patterns persist for South America and Australia. However, as often found, divergence time estimates for New Zealand at c. 50 mya post-date separation of Zealandia from Antarctica and the remainder of Gondwana, but predate the proposed Oligocene 'drowning' of these islands. We detail other such 'anomalous' dates and suggest a single common explanation rather than stochastic processes. This could involve synchronous establishment following recovery from 'drowning' and/or deleteriously warming associated with the mid-Eocene climatic optimum (hence 'waving', which refers to cycles of drowning events) plus new availability of topography providing of cool running waters, or all these factors in combination. Alternatively a

  11. Molecular cloning and evolutionary analysis of captive forest musk deer bitter taste receptor gene T2R16.

    PubMed

    Zhao, G J; Wu, N; Li, D Y; Zeng, D J; Chen, Q; Lu, L; Feng, X L; Zhang, C L; Zheng, C L; Jie, H

    2015-12-08

    Sensing bitter tastes is crucial for most animals because it can prevent them from ingesting harmful food. This process is mainly mediated by the bitter taste receptors (T2R) that are largely expressed in the taste buds. Previous studies have identified some T2R gene repertoires. Marked variation in repertoire size has been noted among species. However, research on T2Rs is still limited and the mechanisms underlying the evolution of vertebrate T2Rs remain poorly understood. In the present study, we analyzed the structure and features of the protein encoded by the forest musk deer (Moschus berezovskii) T2R16 and submitted the gene sequence to NCBI GenBank. The results showed that the full coding DNA sequence (CDS) of musk deer T2R16 (GenBank accession No. KP677279) was 906 bp, encoding 301 amino acids, which contained ATG start codon and TGA stop codon, with a calculated molecular weight of 35.03 kDa and an isoelectric point of 9.56. The T2R16 protein receptor had seven conserved transmembrane regions. Hydrophobicity analysis showed that most amino acid residues in T2R16 protein were hydrophobic, and the grand average of hydrophobicity (GRAVY) was 0.657. Phylogenetic analysis based on this gene revealed that forest musk deer had the closest association with sheep (Ovis aries), as compared to cow (Bos taurus), Tursiops truncatus, and other species, whereas it was genetically farthest from humans (Homo sapiens). We hope these results would complement the existing data on T2R16 and encourage further research in this respect.

  12. Lessons learned from comparing molecular dynamics engines on the SAMPL5 dataset

    NASA Astrophysics Data System (ADS)

    Shirts, Michael R.; Klein, Christoph; Swails, Jason M.; Yin, Jian; Gilson, Michael K.; Mobley, David L.; Case, David A.; Zhong, Ellen D.

    2017-01-01

    We describe our efforts to prepare common starting structures and models for the SAMPL5 blind prediction challenge. We generated the starting input files and single configuration potential energies for the host-guest in the SAMPL5 blind prediction challenge for the GROMACS, AMBER, LAMMPS, DESMOND and CHARMM molecular simulation programs. All conversions were fully automated from the originally prepared AMBER input files using a combination of the ParmEd and InterMol conversion programs. We find that the energy calculations for all molecular dynamics engines for this molecular set agree to better than 0.1 % relative absolute energy for all energy components, and in most cases an order of magnitude better, when reasonable choices are made for different cutoff parameters. However, there are some surprising sources of statistically significant differences. Most importantly, different choices of Coulomb's constant between programs are one of the largest sources of discrepancies in energies. We discuss the measures required to get good agreement in the energies for equivalent starting configurations between the simulation programs, and the energy differences that occur when simulations are run with program-specific default simulation parameter values. Finally, we discuss what was required to automate this conversion and comparison.

  13. Catalytically active polymers obtained by molecular imprinting and their application in chemical reaction engineering.

    PubMed

    Brüggemann, O

    2001-08-01

    Molecular imprinting is a way of creating polymers bearing artificial receptors. It allows the fabrication of highly selective plastics by polymerizing monomers in the presence of a template. This technique primarily had been developed for the generation of biomimetic materials to be used in chromatographic separation, in extraction approaches and in sensors and assays. Beyond these applications, in the past few years molecular imprinting has become a tool for producing new kinds of catalysts. For catalytic applications, the template must be chosen, so that it is structurally comparable with the transition state (a transition state analogue, TSA) of a reaction, or with the product or substrate. The advantage of using these polymeric catalysts is obvious: the backbone withstands more aggressive conditions than a bio material could ever survive. Results are presented showing the applicability of a molecularly imprinted catalyst in different kinds of chemical reactors. It is demonstrated that the catalysts can be utilized not only in batch but also in continuously driven reactors and that their performance can be improved by means of chemical reaction engineering.

  14. Development of a D-xylose fermenting and inhibitor tolerant industrial Saccharomyces cerevisiae strain with high performance in lignocellulose hydrolysates using metabolic and evolutionary engineering

    PubMed Central

    2013-01-01

    Background The production of bioethanol from lignocellulose hydrolysates requires a robust, D-xylose-fermenting and inhibitor-tolerant microorganism as catalyst. The purpose of the present work was to develop such a strain from a prime industrial yeast strain, Ethanol Red, used for bioethanol production. Results An expression cassette containing 13 genes including Clostridium phytofermentans XylA, encoding D-xylose isomerase (XI), and enzymes of the pentose phosphate pathway was inserted in two copies in the genome of Ethanol Red. Subsequent EMS mutagenesis, genome shuffling and selection in D-xylose-enriched lignocellulose hydrolysate, followed by multiple rounds of evolutionary engineering in complex medium with D-xylose, gradually established efficient D-xylose fermentation. The best-performing strain, GS1.11-26, showed a maximum specific D-xylose consumption rate of 1.1 g/g DW/h in synthetic medium, with complete attenuation of 35 g/L D-xylose in about 17 h. In separate hydrolysis and fermentation of lignocellulose hydrolysates of Arundo donax (giant reed), spruce and a wheat straw/hay mixture, the maximum specific D-xylose consumption rate was 0.36, 0.23 and 1.1 g/g DW inoculum/h, and the final ethanol titer was 4.2, 3.9 and 5.8% (v/v), respectively. In simultaneous saccharification and fermentation of Arundo hydrolysate, GS1.11-26 produced 32% more ethanol than the parent strain Ethanol Red, due to efficient D-xylose utilization. The high D-xylose fermentation capacity was stable after extended growth in glucose. Cell extracts of strain GS1.11-26 displayed 17-fold higher XI activity compared to the parent strain, but overexpression of XI alone was not enough to establish D-xylose fermentation. The high D-xylose consumption rate was due to synergistic interaction between the high XI activity and one or more mutations in the genome. The GS1.11-26 had a partial respiratory defect causing a reduced aerobic growth rate. Conclusions An industrial yeast strain for

  15. Surface engineering on mesoporous silica chips for enriching low molecular weight phosphorylated proteins

    NASA Astrophysics Data System (ADS)

    Hu, Ye; Peng, Yang; Lin, Kevin; Shen, Haifa; Brousseau, Louis C., III; Sakamoto, Jason; Sun, Tong; Ferrari, Mauro

    2011-02-01

    Phosphorylated peptides and proteins play an important role in normal cellular activities, e.g., gene expression, mitosis, differentiation, proliferation, and apoptosis, as well as tumor initiation, progression and metastasis. However, technical hurdles hinder the use of common fractionation methods to capture phosphopeptides from complex biological fluids such as human sera. Herein, we present the development of a dual strategy material that offers enhanced capture of low molecular weight phosphoproteins: mesoporous silica thin films with precisely engineered pore sizes that sterically select for molecular size combined with chemically selective surface modifications (i.e. Ga3+, Ti4+ and Zr4+) that target phosphoroproteins. These materials provide high reproducibility (CV = 18%) and increase the stability of the captured proteins by excluding degrading enzymes, such as trypsin. The chemical and physical properties of the composite mesoporous thin films were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy and ellipsometry. Using mass spectroscopy and biostatistics analysis, the enrichment efficiency of different metal ions immobilized on mesoporous silica chips was investigated. The novel technology reported provides a platform capable of efficiently profiling the serum proteome for biomarker discovery, forensic sampling, and routine diagnostic applications.Phosphorylated peptides and proteins play an important role in normal cellular activities, e.g., gene expression, mitosis, differentiation, proliferation, and apoptosis, as well as tumor initiation, progression and metastasis. However, technical hurdles hinder the use of common fractionation methods to capture phosphopeptides from complex biological fluids such as human sera. Herein, we present the development of a dual strategy material that offers enhanced capture of low molecular weight phosphoproteins: mesoporous

  16. The effect of oxygenate molecular structure on soot production in direct-injection diesel engines.

    SciTech Connect

    Westbrook, Charles K.; Pitz, William J.; Mueller, Charles J.; Martin, Glen M.; Pickett, Lyle M.

    2003-06-01

    A combined experimental and kinetic modeling study of soot formation in diesel engine combustion has been used to study the addition of oxygenated species to diesel fuel to reduce soot emissions. This work indicates that the primary role of oxygen atoms in the fuel mixture is to reduce the levels of carbon atoms available for soot formation by fixing them in the form of CO or COz. When the structure of the oxygenate leads to prompt and direct formation of CO2, the oxygenate is less effective in reducing soot production than in cases when all fuel-bound 0 atoms produce only CO. The kinetic and molecular structure principles leading to this conclusion are described.

  17. Insights into Laccase Engineering from Molecular Simulations: Toward a Binding-Focused Strategy.

    PubMed

    Monza, Emanuele; Lucas, M Fatima; Camarero, Susana; Alejaldre, Lorea C; Martínez, Angel T; Guallar, Victor

    2015-04-16

    Understanding the molecular determinants of enzyme performance is of primary importance for the rational design of ad hoc mutants. A novel approach, which combines efficient conformational sampling and quick reactivity scoring, is used here to shed light on how substrate oxidation was improved during the directed evolution experiment of a fungal laccase (from Pycnoporus cinnabarinus), an industrially relevant class of oxidoreductases. It is found that the enhanced activity of the evolved enzyme is mainly the result of substrate arrangement in the active site, with no important change in the redox potential of the T1 copper. Mutations at the active site shift the binding mode into a more buried substrate position and provide a more favorable electrostatic environment for substrate oxidation. As a consequence, engineering the binding event seems to be a viable way to in silico evolution of oxidoreductases.

  18. Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of DNA vaccines

    NASA Astrophysics Data System (ADS)

    Wang, Chun; Ge, Qing; Ting, David; Nguyen, David; Shen, Hui-Rong; Chen, Jianzhu; Eisen, Herman N.; Heller, Jorge; Langer, Robert; Putnam, David

    2004-03-01

    Genetic vaccination using plasmid DNA presents a unique opportunity for achieving potent immune responses without the potential limitations of many conventional vaccines. Here we report the design of synthetic biodegradable polymers specifically for enhancing DNA vaccine efficacy in vivo. We molecularly engineered poly(ortho ester) microspheres that are non-toxic to cells, protect DNA from degradation, enable uptake by antigen-presenting cells, and release DNA rapidly in response to phagosomal pH. One type of microsphere of poly(ortho esters) that releases DNA vaccines in synchrony with the natural development of adaptive immunity, elicited distinct primary and secondary humoral and cellular immune responses in mice, and suppressed the growth of tumour cells bearing a model antigen. This polymer microparticulate system could, with further study, have implications for advancing the clinical utility of DNA vaccines as well as other nucleic-acid-based therapeutics against viral infections and cancer.

  19. Engineering Molecular Recognition with Bio-mimetic Polymers on Single Walled Carbon Nanotubes.

    PubMed

    Del Bonis-O'Donnell, Jackson T; Beyene, Abraham; Chio, Linda; Demirer, Gözde; Yang, Darwin; Landry, Markita P

    2017-01-10

    Semiconducting single-wall carbon nanotubes (SWNTs) are a class of optically active nanomaterial that fluoresce in the near infrared, coinciding with the optical window where biological samples are most transparent. Here, we outline techniques to adsorb amphiphilic polymers and polynucleic acids onto the surface of SWNTs to engineer their corona phases and create novel molecular sensors for small molecules and proteins. These functionalized SWNT sensors are both biocompatible and stable. Polymers are adsorbed onto the nanotube surface either by direct sonication of SWNTs and polymer or by suspending SWNTs using a surfactant followed by dialysis with polymer. The fluorescence emission, stability, and response of these sensors to target analytes are confirmed using absorbance and near-infrared fluorescence spectroscopy. Furthermore, we demonstrate surface immobilization of the sensors onto glass slides to enable single-molecule fluorescence microscopy to characterize polymer adsorption and analyte binding kinetics.

  20. Molecular engineering of Schiff-base linked covalent polymers with diverse topologies by gas-solid interface reaction.

    PubMed

    Liu, Xuan-He; Guan, Cui-Zhong; Zheng, Qing-Na; Wang, Dong; Wan, Li-Jun

    2015-03-14

    The design and construction of molecular nanostructures with tunable topological structures are great challenges in molecular nanotechnology. Herein, we demonstrate the molecular engineering of Schiff-base bond connected molecular nanostructures. Building module construction has been adopted to modulate the symmetry of resulted one dimensional (1D) and two dimensional (2D) polymers. Specifically, we have designed and constructed 1D linear and zigzag polymers, 2D hexagonal and chessboard molecular nanostructures by varying the number of reactive sites and geometry and symmetry of precursors. It is demonstrated that high-quality conjugated polymers can be fabricated by using gas-solid interface reaction. The on-demanding synthesis of polymeric architectures with diverse topologies paves the way to fabricate molecular miniature devices with various desired functionalities.

  1. Evolutionary objections to "alien design" models.

    NASA Astrophysics Data System (ADS)

    Coffey, E. J.

    A previous paper demonstrated that the principal supporters of SETI have ignored the biological and evolutionary consequences of a creature's body form. In fact, the supporting evidence they provide actually contradicts their view. The approach they employ is that of the engineer: the process of "designing" a hypothetical creature to a specification irrespective of biological or evolutionary considerations. The principal types of "alien designs" which have been employed shall be discussed, and the evolutionary objections to them given.

  2. Residue contacts predicted by evolutionary covariance extend the application of ab initio molecular replacement to larger and more challenging protein folds.

    PubMed

    Simkovic, Felix; Thomas, Jens M H; Keegan, Ronan M; Winn, Martyn D; Mayans, Olga; Rigden, Daniel J

    2016-07-01

    For many protein families, the deluge of new sequence information together with new statistical protocols now allow the accurate prediction of contacting residues from sequence information alone. This offers the possibility of more accurate ab initio (non-homology-based) structure prediction. Such models can be used in structure solution by molecular replacement (MR) where the target fold is novel or is only distantly related to known structures. Here, AMPLE, an MR pipeline that assembles search-model ensembles from ab initio structure predictions ('decoys'), is employed to assess the value of contact-assisted ab initio models to the crystallographer. It is demonstrated that evolutionary covariance-derived residue-residue contact predictions improve the quality of ab initio models and, consequently, the success rate of MR using search models derived from them. For targets containing β-structure, decoy quality and MR performance were further improved by the use of a β-strand contact-filtering protocol. Such contact-guided decoys achieved 14 structure solutions from 21 attempted protein targets, compared with nine for simple Rosetta decoys. Previously encountered limitations were superseded in two key respects. Firstly, much larger targets of up to 221 residues in length were solved, which is far larger than the previously benchmarked threshold of 120 residues. Secondly, contact-guided decoys significantly improved success with β-sheet-rich proteins. Overall, the improved performance of contact-guided decoys suggests that MR is now applicable to a significantly wider range of protein targets than were previously tractable, and points to a direct benefit to structural biology from the recent remarkable advances in sequencing.

  3. Residue contacts predicted by evolutionary covariance extend the application of ab initio molecular replacement to larger and more challenging protein folds

    PubMed Central

    Simkovic, Felix; Thomas, Jens M. H.; Keegan, Ronan M.; Winn, Martyn D.; Mayans, Olga; Rigden, Daniel J.

    2016-01-01

    For many protein families, the deluge of new sequence information together with new statistical protocols now allow the accurate prediction of contacting residues from sequence information alone. This offers the possibility of more accurate ab initio (non-homology-based) structure prediction. Such models can be used in structure solution by molecular replacement (MR) where the target fold is novel or is only distantly related to known structures. Here, AMPLE, an MR pipeline that assembles search-model ensembles from ab initio structure predictions (‘decoys’), is employed to assess the value of contact-assisted ab initio models to the crystallographer. It is demonstrated that evolutionary covariance-derived residue–residue contact predictions improve the quality of ab initio models and, consequently, the success rate of MR using search models derived from them. For targets containing β-structure, decoy quality and MR performance were further improved by the use of a β-strand contact-filtering protocol. Such contact-guided decoys achieved 14 structure solutions from 21 attempted protein targets, compared with nine for simple Rosetta decoys. Previously encountered limitations were superseded in two key respects. Firstly, much larger targets of up to 221 residues in length were solved, which is far larger than the previously benchmarked threshold of 120 residues. Secondly, contact-guided decoys significantly improved success with β-sheet-rich proteins. Overall, the improved performance of contact-guided decoys suggests that MR is now applicable to a significantly wider range of protein targets than were previously tractable, and points to a direct benefit to structural biology from the recent remarkable advances in sequencing. PMID:27437113

  4. Intervertebral disc regeneration: from the degenerative cascade to molecular therapy and tissue engineering.

    PubMed

    Vadalà, Gianluca; Russo, Fabrizio; Di Martino, Alberto; Denaro, Vincenzo

    2015-06-01

    Low back pain is one of the major health problems in industrialized countries, as a leading source of disability in the working population. Intervertebral disc degeneration has been identified as its main cause, being a progressive process mainly characterized by alteration of extracellular matrix composition and water content. Many factors are involved in the degenerative cascade, such as anabolism/catabolism imbalance, reduction of nutrition supply and progressive cell loss. Currently available treatments are symptomatic, and surgical procedures consisting of disc removal are often necessary. Recent advances in our understanding of intervertebral disc biology led to an increased interest in the development of novel biological treatments aimed at disc regeneration. Growth factors, gene therapy, stem cell transplantation and biomaterials-based tissue engineering might support intervertebral disc regeneration by overcoming the limitation of the self-renewal mechanism. The aim of this paper is to overview the literature discussing the current status of our knowledge from the degenerative cascade of the intervertebral disc to the latest molecular, cell-based therapies and tissue-engineering strategies for disc regeneration.

  5. Molecular Engineering with Organic Carbonyl Electrode Materials for Advanced Stationary and Redox Flow Rechargeable Batteries.

    PubMed

    Zhao, Qing; Zhu, Zhiqiang; Chen, Jun

    2017-04-03

    Organic carbonyl electrode materials that have the advantages of high capacity, low cost and being environmentally friendly, are regarded as powerful candidates for next-generation stationary and redox flow rechargeable batteries (RFBs). However, low carbonyl utilization, poor electronic conductivity and undesired dissolution in electrolyte are urgent issues to be solved. Here, we summarize a molecular engineering approach for tuning the capacity, working potential, concentration of active species, kinetics, and stability of stationary and redox flow batteries, which well resolves the problems of organic carbonyl electrode materials. As an example, in stationary batteries, 9,10-anthraquinone (AQ) with two carbonyls delivers a capacity of 257 mAh g(-1) (2.27 V vs Li(+) /Li), while increasing the number of carbonyls to four with the formation of 5,7,12,14-pentacenetetrone results in a higher capacity of 317 mAh g(-1) (2.60 V vs Li(+) /Li). In RFBs, AQ, which is less soluble in aqueous electrolyte, reaches 1 M by grafting -SO3 H with the formation of 9,10-anthraquinone-2,7-disulphonic acid, resulting in a power density exceeding 0.6 W cm(-2) with long cycling life. Therefore, through regulating substituent groups, conjugated structures, Coulomb interactions, and the molecular weight, the electrochemical performance of carbonyl electrode materials can be rationally optimized. This review offers fundamental principles and insight into designing advanced carbonyl materials for the electrodes of next-generation rechargeable batteries.

  6. A novel characterization of organic molecular crystal structures for the purpose of crystal engineering.

    PubMed

    Thomas, Noel W

    2015-08-01

    A novel analytical approach is proposed for the characterization of organic molecular crystal structures where close packing is an important factor. It requires the identification of a unique reference axis within the crystal, along which three-dimensional space is divided into close-packed blocks (CPB) and junction zones (JZ). The degree of close packing along the reference axis is quantified by a two-dimensional packing function, ϕ2D, of symmetry determined by the space group. Values of ϕ2D reflect the degree of area-filling in planes perpendicular to this axis. The requirement of close packing within CPB allows the planar structures perpendicular to the reference axis to be analysed as tessellations of area-filling molecular-based cells (MBC), which are generally hexagonal. The form of these cells reflects the molecular shape in the cross-section, since their vertices are given by the centres of the voids between molecules. There are two basic types of MBC, Type 1, of glide or pseudo-glide symmetry, and Type 2, which is formed by lattice translations alone and generally requires a short unit-cell axis. MBC at layers of special symmetry are used to characterize the structures in terms of equivalent ellipses with parameters aell, bell and χell. The ratio aell/bell allows the established α, β, γ classification to be integrated into the current framework. The values of parameters aell and bell arising from all the structures considered, polynuclear aromatic hydrocarbons (PAH), substituted anthracenes and anthraquinones (SAA) and 2-benzyl-5-benzylidene (BBCP) are mapped onto a universal curve. The division of three-dimensional space into CPB and JZ is fundamentally useful for crystal engineering, since the structural perturbations brought about by substitution at hydrogen positions located within JZ are minimal. A contribution is also made to ongoing debate concerning the adoption of polar space groups, isomorphism and polymorphism.

  7. Evolutionary theory, psychiatry, and psychopharmacology.

    PubMed

    Stein, Dan J

    2006-07-01

    Darwin's seminal publications in the nineteenth century laid the foundation for an evolutionary approach to psychology and psychiatry. Advances in 20th century evolutionary theory facilitated the development of evolutionary psychology and psychiatry as recognized areas of scientific investigation. In this century, advances in understanding the molecular basis of evolution, of the mind, and of psychopathology, offer the possibility of an integrated approach to understanding the proximal (psychobiological) and distal (evolutionary) mechanisms of interest to psychiatry and psychopharmacology. There is, for example, growing interest in the question of whether specific genetic variants mediate psychobiological processes that have evolutionary value in specific contexts, and of the implications of this for understanding the vulnerability to psychopathology and for considering the advantages and limitations of pharmacotherapy. The evolutionary value, and gene-environmental mediation, of early life programming is potentially a particularly rich area of investigation. Although evolutionary approaches to psychology and to medicine face important conceptual and methodological challenges, current work is increasingly sophisticated, and may prove to be an important foundational discipline for clinicians and researchers in psychiatry and psychopharmacology.

  8. Reverse engineering of an affinity-switchable molecular interaction characterized by atomic force microscopy single-molecule force spectroscopy.

    PubMed

    Anselmetti, Dario; Bartels, Frank Wilco; Becker, Anke; Decker, Björn; Eckel, Rainer; McIntosh, Matthew; Mattay, Jochen; Plattner, Patrik; Ros, Robert; Schäfer, Christian; Sewald, Norbert

    2008-02-19

    Tunable and switchable interaction between molecules is a key for regulation and control of cellular processes. The translation of the underlying physicochemical principles to synthetic and switchable functional entities and molecules that can mimic the corresponding molecular functions is called reverse molecular engineering. We quantitatively investigated autoinducer-regulated DNA-protein interaction in bacterial gene regulation processes with single atomic force microscopy (AFM) molecule force spectroscopy in vitro, and developed an artificial bistable molecular host-guest system that can be controlled and regulated by external signals (UV light exposure and thermal energy). The intermolecular binding functionality (affinity) and its reproducible and reversible switching has been proven by AFM force spectroscopy at the single-molecule level. This affinity-tunable optomechanical switch will allow novel applications with respect to molecular manipulation, nanoscale rewritable molecular memories, and/or artificial ion channels, which will serve for the controlled transport and release of ions and neutral compounds in the future.

  9. Evolutionary Design in Biology

    NASA Astrophysics Data System (ADS)

    Wiese, Kay C.

    Much progress has been achieved in recent years in molecular biology and genetics. The sheer volume of data in the form of biological sequences has been enormous and efficient methods for dealing with these huge amounts of data are needed. In addition, the data alone does not provide information on the workings of biological systems; hence much research effort has focused on designing mathematical and computational models to address problems from molecular biology. Often, the terms bioinformatics and computational biology are used to refer to the research fields concerning themselves with designing solutions to molecular problems in biology. However, there is a slight distinction between bioinformatics and computational biology: the former is concerned with managing the enormous amounts of biological data and extracting information from it, while the latter is more concerned with the design and development of new algorithms to address problems such as protein or RNA folding. However, the boundary is blurry, and there is no consistent usage of the terms. We will use the term bioinformatics to encompass both fields. To cover all areas of research in bioinformatics is beyond the scope of this section and we refer the interested reader to [2] for a general introduction. A large part of what bioinformatics is concerned about is evolution and function of biological systems on a molecular level. Evolutionary computation and evolutionary design are concerned with developing computational systems that "mimic" certain aspects of natural evolution (mutation, crossover, selection, fitness). Much of the inner workings of natural evolutionary systems have been copied, sometimes in modified format into evolutionary computation systems. Artificial neural networks mimic the functioning of simple brain cell clusters. Fuzzy systems are concerned with the "fuzzyness" in decision making, similar to a human expert. These three computational paradigms fall into the category of

  10. Evolutionary Aspects of Enzyme Dynamics*

    PubMed Central

    Klinman, Judith P.; Kohen, Amnon

    2014-01-01

    The role of evolutionary pressure on the chemical step catalyzed by enzymes is somewhat enigmatic, in part because chemistry is not rate-limiting for many optimized systems. Herein, we present studies that examine various aspects of the evolutionary relationship between protein dynamics and the chemical step in two paradigmatic enzyme families, dihydrofolate reductases and alcohol dehydrogenases. Molecular details of both convergent and divergent evolution are beginning to emerge. The findings suggest that protein dynamics across an entire enzyme can play a role in adaptation to differing physiological conditions. The growing tool kit of kinetics, kinetic isotope effects, molecular biology, biophysics, and bioinformatics provides means to link evolutionary changes in structure-dynamics function to the vibrational and conformational states of each protein. PMID:25210031

  11. Molecularly Engineered Azobenzene Derivatives for High Energy Density Solid-State Solar Thermal Fuels.

    PubMed

    Cho, Eugene N; Zhitomirsky, David; Han, Grace G D; Liu, Yun; Grossman, Jeffrey C

    2017-03-15

    Solar thermal fuels (STFs) harvest and store solar energy in a closed cycle system through conformational change of molecules and can release the energy in the form of heat on demand. With the aim of developing tunable and optimized STFs for solid-state applications, we designed three azobenzene derivatives functionalized with bulky aromatic groups (phenyl, biphenyl, and tert-butyl phenyl groups). In contrast to pristine azobenzene, which crystallizes and makes nonuniform films, the bulky azobenzene derivatives formed uniform amorphous films that can be charged and discharged with light and heat for many cycles. Thermal stability of the films, a critical metric for thermally triggerable STFs, was greatly increased by the bulky functionalization (up to 180 °C), and we were able to achieve record high energy density of 135 J/g for solid-state STFs, over a 30% improvement compared to previous solid-state reports. Furthermore, the chargeability in the solid state was improved, up to 80% charged from 40% charged in previous solid-state reports. Our results point toward molecular engineering as an effective method to increase energy storage in STFs, improve chargeability, and improve the thermal stability of the thin film.

  12. Molecular engineering of two-photon fluorescent probes for bioimaging applications.

    PubMed

    Liu, Hong-Wen; Liu, Yongchao; Wang, Peng; Zhang, Xiao-Bing

    2017-03-22

    During the past two decades, two-photon microscopy (TPM), which utilizes two near-infrared photons as the excitation source, has emerged as a novel, attractive imaging tool for biological research. Compared with one-photon microscopy, TPM offers several advantages, such as lowering background fluorescence in living cells and tissues, reducing photodamage to biosamples, and a photobleaching phenomenon, offering better 3D spatial localization, and increasing penetration depth. Small-molecule-based two-photon fluorescent probes have been well developed for the detection and imaging of various analytes in biological systems. In this review, we will give a general introduction of molecular engineering of two-photon fluorescent probes based on different fluorescence response mechanisms for bioimaging applications during the past decade. Inspired by the desired advantages of small-molecule two-photon fluorescent probes in biological imaging applications, we expect that more attention will be devoted to the development of new two-photon fluorophores and applications of TPM in areas of bioanalysis and disease diagnosis.

  13. Molecular scanning: combining random mutagenesis, ribosome display, and bioinformatic analysis for protein engineering.

    PubMed

    Darmanin-Sheehan, Alfredo; Finlay, William James Jonathan; Cunningham, Orla; Fennell, Brian Joseph

    2012-01-01

    Protein engineering techniques can facilitate the direct de-convolution of specific domains, regions, and particular amino acids that contribute to protein function. Many tools are available to aid this enterprise and herein we describe one such tool, a technique we term "Molecular Scanning" (MS). MS is analogous to previously described alanine scanning in that it samples potentially functional sequence space, but differs in that it uses Error-Prone polymerase chain reaction to randomly introduce all amino acids across the sequence space, as opposed to simply introducing alanine at each desired position. We commonly use MS in conjunction with ribosome-display, selecting for specific character traits (e.g., improved affinity) which allows us to sample functionally relevant diversity on a reasonably large scale. This approach is amenable to a variety of different mutational techniques and display technologies as dictated by user requirements or needs. In this chapter we present a general outline of the process as we have previously successfully applied it.

  14. Molecular engineering of two-photon fluorescent probes for bioimaging applications

    NASA Astrophysics Data System (ADS)

    Liu, Hong-Wen; Liu, Yongchao; Wang, Peng; Zhang, Xiao-Bing

    2017-03-01

    During the past two decades, two-photon microscopy (TPM), which utilizes two near-infrared photons as the excitation source, has emerged as a novel, attractive imaging tool for biological research. Compared with one-photon microscopy, TPM offers several advantages, such as lowering background fluorescence in living cells and tissues, reducing photodamage to biosamples, and a photobleaching phenomenon, offering better 3D spatial localization, and increasing penetration depth. Small-molecule-based two-photon fluorescent probes have been well developed for the detection and imaging of various analytes in biological systems. In this review, we will give a general introduction of molecular engineering of two-photon fluorescent probes based on different fluorescence response mechanisms for bioimaging applications during the past decade. Inspired by the desired advantages of small-molecule two-photon fluorescent probes in biological imaging applications, we expect that more attention will be devoted to the development of new two-photon fluorophores and applications of TPM in areas of bioanalysis and disease diagnosis.

  15. A molecularly engineered hole-transporting material for efficient perovskite solar cells

    NASA Astrophysics Data System (ADS)

    Saliba, Michael; Orlandi, Simonetta; Matsui, Taisuke; Aghazada, Sadig; Cavazzini, Marco; Correa-Baena, Juan-Pablo; Gao, Peng; Scopelliti, Rosario; Mosconi, Edoardo; Dahmen, Klaus-Hermann; de Angelis, Filippo; Abate, Antonio; Hagfeldt, Anders; Pozzi, Gianluca; Graetzel, Michael; Nazeeruddin, Mohammad Khaja

    2016-02-01

    Solution-processable perovskite solar cells have recently achieved certified power conversion efficiencies of over 20%, challenging the long-standing perception that high efficiencies must come at high costs. One major bottleneck for increasing the efficiency even further is the lack of suitable hole-transporting materials, which extract positive charges from the active light absorber and transmit them to the electrode. In this work, we present a molecularly engineered hole-transport material with a simple dissymmetric fluorene-dithiophene (FDT) core substituted by N,N-di-p-methoxyphenylamine donor groups, which can be easily modified, providing the blueprint for a family of potentially low-cost hole-transport materials. We use FDT on state-of-the-art devices and achieve power conversion efficiencies of 20.2% which compare favourably with control devices with 2,2‧,7,7‧-tetrakis(N,N-di-p-methoxyphenylamine)-9,9‧-spirobifluorene (spiro-OMeTAD). Thus, this new hole transporter has the potential to replace spiro-OMeTAD.

  16. Chapter 2. Fasciola, lymnaeids and human fascioliasis, with a global overview on disease transmission, epidemiology, evolutionary genetics, molecular epidemiology and control.

    PubMed

    Mas-Coma, Santiago; Valero, María Adela; Bargues, María Dolores

    2009-01-01

    Fascioliasis, caused by liver fluke species of the genus Fasciola, has always been well recognized because of its high veterinary impact but it has been among the most neglected diseases for decades with regard to human infection. However, the increasing importance of human fascioliasis worldwide has re-launched interest in fascioliasis. From the 1990s, many new concepts have been developed regarding human fascioliasis and these have furnished a new baseline for the human disease that is very different to a simple extrapolation from fascioliasis in livestock. Studies have shown that human fascioliasis presents marked heterogeneity, including different epidemiological situations and transmission patterns in different endemic areas. This heterogeneity, added to the present emergence/re-emergence of the disease both in humans and animals in many regions, confirms a worrying global scenario. The huge negative impact of fascioliasis on human communities demands rapid action. When analyzing how better to define control measures for endemic areas differing at such a level, it would be useful to have genetic markers that could distinguish each type of transmission pattern and epidemiological situation. Accordingly, this chapter covers aspects of aetiology, geographical distribution, epidemiology, transmission and control in order to obtain a solid baseline for the interpretation of future results. The origins and geographical spread of F. hepatica and F. gigantica in both the ruminant pre-domestication times and the livestock post-domestication period are analyzed. Paleontological, archaeological and historical records, as well as genetic data on recent dispersal of livestock species, are taken into account to establish an evolutionary framework for the two fasciolids across all continents. Emphasis is given to the distributional overlap of both species and the roles of transportation, transhumance and trade in the different overlap situations. Areas with only one Fasciola

  17. Lipid-shelled vehicles: engineering for ultrasound molecular imaging and drug delivery.

    PubMed

    Ferrara, Katherine W; Borden, Mark A; Zhang, Hua

    2009-07-21

    Ultrasound pressure waves can map the location of lipid-stabilized gas micro-bubbles after their intravenous administration in the body, facilitating an estimate of vascular density and microvascular flow rate. Microbubbles are currently approved by the Food and Drug Administration as ultrasound contrast agents for visualizing opacification of the left ventricle in echocardiography. However, the interaction of ultrasound waves with intravenously-injected lipid-shelled particles, including both liposomes and microbubbles, is a far richer field. Particles can be designed for molecular imaging and loaded with drugs or genes; the mechanical and thermal properties of ultrasound can then effect localized drug release. In this Account, we provide an overview of the engineering of lipid-shelled microbubbles (typical diameter 1000-10 000 nm) and liposomes (typical diameter 65-120 nm) for ultrasound-based applications in molecular imaging and drug delivery. The chemistries of the shell and core can be optimized to enhance stability, circulation persistence, drug loading and release, targeting to and fusion with the cell membrane, and therapeutic biological effects. To assess the biodistribution and pharmacokinetics of these particles, we incorporated positron emission tomography (PET) radioisotopes on the shell. The radionuclide (18)F (half-life approximately 2 h) was covalently coupled to a dipalmitoyl lipid, followed by integration of the labeled lipid into the shell, facilitating short-term analysis of particle pharmacokinetics and metabolism of the lipid molecule. Alternately, labeling a formed particle with (64)Cu (half-life 12.7 h), after prior covalent incorporation of a copper-chelating moiety onto the lipid shell, permits pharmacokinetic study of particles over several days. Stability and persistence in circulation of both liposomes and microbubbles are enhanced by long acyl chains and a poly(ethylene glycol) coating. Vascular targeting has been demonstrated with

  18. Molecular characterization and phylogenetic analysis of Eimeria from turkeys and gamebirds, and the implication on the evolutionary relationships OF Eimeria FROM galliforme birds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to evaluate the evolutionary relationships of Eimeria that infect galliforme birds, the 18s rDNA gene, and a portion of the cytochrome oxidase subunit 1 (cox-1) were amplified from Eimeria that infect turkeys, chukars, and pheasants. The phylogenetic analysis of these sequences suggests th...

  19. The Best and the Worst of Times for Evolutionary Biology.

    ERIC Educational Resources Information Center

    Avise, John C.

    2003-01-01

    Discusses opportunities and challenges for the field of evolutionary biology, particularly in areas related to molecular genetic technologies, the environment, biodiversity, and public education. (Author/KHR)

  20. Structural and functional diversity among amyloid proteins: Agents of disease, building blocks of biology, and implications for molecular engineering.

    PubMed

    Bleem, Alissa; Daggett, Valerie

    2017-01-01

    Amyloids have long been associated with protein dysfunction and neurodegenerative diseases, but recent research has demonstrated that some organisms utilize the unique properties of the amyloid fold to create functional structures with important roles in biological processes. Additionally, new engineering approaches have taken advantage of amyloid structures for implementation in a wide variety of materials and devices. In this review, the role of amyloid in human disease is discussed and compared to the functional amyloids, which serve a largely structural purpose. We then consider the use of amyloid constructs in engineering applications, including their utility as building blocks for synthetic biology and molecular engineering. Biotechnol. Bioeng. 2017;114: 7-20. © 2016 Wiley Periodicals, Inc.

  1. Phylogenetic Patterns of Human Coxsackievirus B5 Arise from Population Dynamics between Two Genogroups and Reveal Evolutionary Factors of Molecular Adaptation and Transmission

    PubMed Central

    Mirand, Audrey; Richter, Jan; Schuffenecker, Isabelle; Böttiger, Blenda; Diedrich, Sabine; Terletskaia-Ladwig, Elena; Christodoulou, Christina; Peigue-Lafeuille, Hélène; Bailly, Jean-Luc

    2013-01-01

    The aim of this study was to gain insights into the tempo and mode of the evolutionary processes that sustain genetic diversity in coxsackievirus B5 (CVB5) and into the interplay with virus transmission. We estimated phylodynamic patterns with a large sample of virus strains collected in Europe by Bayesian statistical methods, reconstructed the ancestral states of genealogical nodes, and tested for selection. The genealogies estimated with the structural one-dimensional gene encoding the VP1 protein and nonstructural 3CD locus allowed the precise description of lineages over time and cocirculating virus populations within the two CVB5 clades, genogroups A and B. Strong negative selection shaped the evolution of both loci, but compelling phylogenetic data suggested that immune selection pressure resulted in the emergence of the two genogroups with opposed evolutionary pathways. The genogroups also differed in the temporal occurrence of the amino acid changes. The virus strains of genogroup A were characterized by sequential acquisition of nonsynonymous changes in residues exposed at the virus 5-fold axis. The genogroup B viruses were marked by selection of three changes in a different domain (VP1 C terminus) during its early emergence. These external changes resulted in a selective sweep, which was followed by an evolutionary stasis that is still ongoing after 50 years. The inferred population history of CVB5 showed an alternation of the prevailing genogroup during meningitis epidemics across Europe and is interpreted to be a consequence of partial cross-immunity. PMID:24006446

  2. Biotechnology and genetic engineering in the new drug development. Part III. Biocatalysis, metabolic engineering and molecular modelling.

    PubMed

    Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław

    2013-01-01

    Industrial biotechnology has been defined as the use and application of biotechnology for the sustainable processing and production of chemicals, materials and fuels. It makes use of biocatalysts such as microbial communities, whole-cell microorganisms or purified enzymes. In the review these processes are described. Drug design is an iterative process which begins when a chemist identifies a compound that displays an interesting biological profile and ends when both the activity profile and the chemical synthesis of the new chemical entity are optimized. Traditional approaches to drug discovery rely on a stepwise synthesis and screening program for large numbers of compounds to optimize activity profiles. Over the past ten to twenty years, scientists have used computer models of new chemical entities to help define activity profiles, geometries and relativities. This article introduces inter alia the concepts of molecular modelling and contains references for further reading.

  3. Molecular cloning, sequencing and tissue expression of vasotocin and isotocin precursor genes from Ostariophysian catfishes: phylogeny and evolutionary considerations in teleosts

    PubMed Central

    Banerjee, Putul; Chaube, Radha; Joy, Keerikkattil P.

    2015-01-01

    Basic and neutral neurohypophyseal (NH) nonapeptides have evolved from vasotocin (VT) by a gene duplication at the base of the gnathostome lineage. In teleosts, VT and IT are the basic and neutral peptides, respectively. In the present study, VT and IT precursor genes of Heteropneustes fossilis and Clarias batrachus (Siluriformes, Ostariophysi) were cloned and sequenced. The channel catfish Icatalurus punctatus NH precursor sequences were obtained from EST database. The catfish NH sequences were used along with the available Acanthopterygii and other vertebrate NH precursor sequences to draw phylogenetic inference on the evolutionary history of the teleost NH peptides. Synteny analysis of the NH gene loci in various teleost species was done to complement the phylogenetic analysis. In H. fossilis, the NH transcripts were also sequenced from the ovary. The cloned genes and the deduced precursor proteins showed conserved characteristics of the NH nonapeptide precursors. The genes are expressed in brain and ovary (follicular envelope) of H. fossilis with higher transcript abundance in the brain. The addition of the catfish sequences in the phylogenetic analysis revealed that the VT and IT precursors of the species-rich superorders of teleosts have a distinct phylogenetic history with the Acanthopterygii VT and IT precursors sharing a less evolutionary distance and the Ostariophysi VT and IT having a greater evolutionary distance. The genomic location of VT and IT precursors, and synteny analysis of the NH loci lend support to the phylogenetic inference and suggest a footprint of fish- specific whole genome duplication (3R) and subsequent diploidization in the NH loci. The VT and IT precursor genes are most likely lineage-specific paralogs resulting from differential losses of the 3R NH paralogs in the two superorders. The independent yet consistent retention of VT and IT in the two superorders might be directed by a stringent ligand-receptor selectivity. PMID:26029040

  4. Modifying the photoelectric behavior of bacteriorhodopsin by site-directed mutagenesis: electrochemical and genetic engineering approaches to molecular devices

    NASA Astrophysics Data System (ADS)

    Hong, F. T.; Hong, F. H.; Needleman, R. B.; Ni, B.; Chang, M.

    1992-07-01

    Bacteriorhodopsins (bR's) modified by substitution of the chromophore with synthetic vitamin A analogues or by spontaneous mutation have been reported as successful examples of using biomaterials to construct molecular optoelectronic devices. The operation of these devices depends on desirable optical properties derived from molecular engineering. This report examines the effect of site-directed mutagenesis on the photoelectric behavior of bR thin films with an emphasis on their application to the construction of molecular devices based on their unique photoelectric behavior. We examine the photoelectric signals induced by a microsecond light pulse in thin films which contain reconstituted oriented purple membrane sheets isolated from several mutant strains of Halobacterium halobium. A recently developed expression system is used to synthesize mutant bR's in their natural host, H. halobium. We then use a unique analytical method (tunable voltage clamp method) to investigate the effect of pH on the relaxation of two components of the photoelectric signals, B1 and B2. We found that for the four mutant bR's examined, the pH dependence of the B2 component varies significantly. Our results suggest that genetic engineering approaches can produce mutant bR's with altered photoelectric characteristics that can be exploited in the construction of devices.

  5. Density functional theory based study of molecular interactions, recognition, engineering, and quantum transport in π molecular systems.

    PubMed

    Cho, Yeonchoo; Cho, Woo Jong; Youn, Il Seung; Lee, Geunsik; Singh, N Jiten; Kim, Kwang S

    2014-11-18

    CONSPECTUS: In chemical and biological systems, various interactions that govern the chemical and physical properties of molecules, assembling phenomena, and electronic transport properties compete and control the microscopic structure of materials. The well-controlled manipulation of each component can allow researchers to design receptors or sensors, new molecular architectures, structures with novel morphology, and functional molecules or devices. In this Account, we describe the structures and electronic and spintronic properties of π-molecular systems that are important for controlling the architecture of a variety of carbon-based systems. Although DFT is an important tool for describing molecular interactions, the inability of DFT to accurately represent dispersion interactions has made it difficult to properly describe π-interactions. However, the recently developed dispersion corrections for DFT have allowed us to include these dispersion interactions cost-effectively. We have investigated noncovalent interactions of various π-systems including aromatic-π, aliphatic-π, and non-π systems based on dispersion-corrected DFT (DFT-D). In addition, we have addressed the validity of DFT-D compared with the complete basis set (CBS) limit values of coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)] and Møller-Plesset second order perturbation theory (MP2). The DFT-D methods are still unable to predict the correct ordering in binding energies within the benzene dimer and the cyclohexane dimer. Nevertheless, the overall DFT-D predicted binding energies are in reasonable agreement with the CCSD(T) results. In most cases, results using the B97-D3 method closely reproduce the CCSD(T) results with the optimized energy-fitting parameters. On the other hand, vdW-DF2 and PBE0-TS methods estimate the dispersion energies from the calculated electron density. In these approximations, the interaction energies around the equilibrium

  6. Quantification of Extracellular Matrix Proteins from a Rat Lung Scaffold to Provide a Molecular Readout for Tissue Engineering*

    PubMed Central

    Hill, Ryan C.; Calle, Elizabeth A.; Dzieciatkowska, Monika; Niklason, Laura E.; Hansen, Kirk C.

    2015-01-01

    The use of extracellular matrix (ECM)1 scaffolds, derived from decellularized tissues for engineered organ generation, holds enormous potential in the field of regenerative medicine. To support organ engineering efforts, we developed a targeted proteomics method to extract and quantify extracellular matrix components from tissues. Our method provides more complete and accurate protein characterization than traditional approaches. This is accomplished through the analysis of both the chaotrope-soluble and -insoluble protein fractions and using recombinantly generated stable isotope labeled peptides for endogenous protein quantification. Using this approach, we have generated 74 peptides, representing 56 proteins to quantify protein in native (nondecellularized) and decellularized lung matrices. We have focused on proteins of the ECM and additional intracellular proteins that are challenging to remove during the decellularization procedure. Results indicate that the acellular lung scaffold is predominantly composed of structural collagens, with the majority of these proteins found in the insoluble ECM, a fraction that is often discarded using widely accepted proteomic methods. The decellularization procedure removes over 98% of intracellular proteins evaluated and retains, to varying degrees, proteoglycans and glycoproteins of the ECM. Accurate characterization of ECM proteins from tissue samples will help advance organ engineering efforts by generating a molecular readout that can be correlated with functional outcome to drive the next generation of engineered organs. PMID:25660013

  7. RNA based evolutionary optimization

    NASA Astrophysics Data System (ADS)

    Schuster, Peter

    1993-12-01

    The notion of an RNA world has been introduced for a prebiotic scenario that is dominated by RNA molecules and their properties, in particular their capabilities to act as templates for reproduction and as catalysts for several cleavage and ligation reactions of polynucleotides and polypeptides. This notion is used here also for simple experimental assays which are well suited to study evolution in the test tube. In molecular evolution experiments fitness is determined in essence by the molecular structures of RNA molecules. Evidence is presented for adaptation to environment in cell-free media. RNA based molecular evolution experiments have led to interesting spin-offs in biotechnology, commonly called ‘applied molecular evolution’, which make use of Darwinian trial-and-error strategies in order to synthesize new pharmacological compounds and other advanced materials on a biological basis. Error-propagation in RNA replication leads to formation of mutant spectra called ‘quasispecies’. An increase in the error rate broadens the mutant spectrum. There exists a sharply defined threshold beyond which heredity breaks down and evolutionary adaptation becomes impossible. Almost all RNA viruses studied so far operate at conditions close to this error threshold. Quasispecies and error thresholds are important for an understanding of RNA virus evolution, and they may help to develop novel antiviral strategies. Evolution of RNA molecules can be studied and interpreted by considering secondary structures. The notion of sequence space introduces a distance between pairs of RNA sequences which is tantamount to counting the minimal number of point mutations required to convert the sequences into each other. The mean sensitivity of RNA secondary structures to mutation depends strongly on the base pairing alphabet: structures from sequences which contain only one base pair (GC or AU are much less stable against mutation than those derived from the natural (AUGC) sequences

  8. Relationship between the monosomy X phenotype and Y-linked ribosomal protein S4 (Rps4) in several species of mammals: A molecular evolutionary analysis of Rps4 homologs

    SciTech Connect

    Omoe, Katsuhiko; Endo, Akira

    1996-01-01

    Two isoforms of the human ribosomal protein S4 gene, RPS4X and RPS4Y, are located on the X and Y chromsomes. It has been postulated and haploinsufficiency of these genes may contribute to Turner syndrome. We show here that several animal species that show the Turner-like phenotype on monosomy X have no Y-linked Rps4 homolog. There may be another gene(s) that contributes to abnormal phenotypes of monosomy X. Molecular evolutionary analysis shows that the Y-linked and RPS4X-related homologs diverged prior to the radiation of placental mammals and evolved independently. Furthermore, the functional constraints against the RPS4X-related homologs are much stronger than those against the Y-linked homologs. 37 refs., 3 figs., 1 tab.

  9. Evolutionary history of the Afro-Madagascan Ixora species (Rubiaceae): species diversification and distribution of key morphological traits inferred from dated molecular phylogenetic trees

    PubMed Central

    Tosh, J.; Dessein, S.; Buerki, S.; Groeninckx, I.; Mouly, A.; Bremer, B.; Smets, E. F.; De Block, P.

    2013-01-01

    Background and Aims Previous work on the pantropical genus Ixora has revealed an Afro-Madagascan clade, but as yet no study has focused in detail on the evolutionary history and morphological trends in this group. Here the evolutionary history of Afro-Madagascan Ixora spp. (a clade of approx. 80 taxa) is investigated and the phylogenetic trees compared with several key morphological traits in taxa occurring in Madagascar. Methods Phylogenetic relationships of Afro-Madagascan Ixora are assessed using sequence data from four plastid regions (petD, rps16, rpoB-trnC and trnL-trnF) and nuclear ribosomal external transcribed spacer (ETS) and internal transcribed spacer (ITS) regions. The phylogenetic distribution of key morphological characters is assessed. Bayesian inference (implemented in BEAST) is used to estimate the temporal origin of Ixora based on fossil evidence. Key Results Two separate lineages of Madagascan taxa are recovered, one of which is nested in a group of East African taxa. Divergence in Ixora is estimated to have commenced during the mid Miocene, with extensive cladogenesis occurring in the Afro-Madagascan clade during the Pliocene onwards. Conclusions Both lineages of Madagascan Ixora exhibit morphological innovations that are rare throughout the rest of the genus, including a trend towards pauciflorous inflorescences and a trend towards extreme corolla tube length, suggesting that the same ecological and selective pressures are acting upon taxa from both Madagascan lineages. Novel ecological opportunities resulting from climate-induced habitat fragmentation and corolla tube length diversification are likely to have facilitated species radiation on Madagascar. PMID:24142919

  10. The complex evolutionary history of seeing red: molecular phylogeny and the evolution of an adaptive visual system in deep-sea dragonfishes (Stomiiformes: Stomiidae).

    PubMed

    Kenaley, Christopher P; Devaney, Shannon C; Fjeran, Taylor T

    2014-04-01

    The vast majority of deep-sea fishes have retinas composed of only rod cells sensitive to only shortwave blue light, approximately 480-490 nm. A group of deep-sea dragonfishes, the loosejaws (family Stomiidae), possesses far-red emitting photophores and rhodopsins sensitive to long-wave emissions greater than 650 nm. In this study, the rhodopsin diversity within the Stomiidae is surveyed based on an analysis of rod opsin-coding sequences from representatives of 23 of the 28 genera. Using phylogenetic inference, fossil-calibrated estimates of divergence times, and a comparative approach scanning the stomiid phylogeny for shared genotypes and substitution histories, we explore the evolution and timing of spectral tuning in the family. Our results challenge both the monophyly of the family Stomiidae and the loosejaws. Despite paraphyly of the loosejaws, we infer for the first time that far-red visual systems have a single evolutionary origin within the family and that this shift in phenotype occurred at approximately 15.4 Ma. In addition, we found strong evidence that at approximately 11.2 Ma the most recent common ancestor of two dragonfish genera reverted to a primitive shortwave visual system during its evolution from a far-red sensitive dragonfish. According to branch-site tests for adaptive evolution, we hypothesize that positive selection may be driving spectral tuning in the Stomiidae. These results indicate that the evolutionary history of visual systems in deep-sea species is complex and a more thorough understanding of this system requires an integrative comparative approach.

  11. Molecular Engineering of Supramolecular Scaffold Coatings that Can Reduce Static Platelet Adhesion

    PubMed Central

    Kumar, Aryavarta M. S.; Sivakova, Sona; Fox, Justin D.; Green, Jennifer E.; Marchant, Roger E.; Rowan, Stuart J.

    2008-01-01

    Novel supramolecular coatings that make use of low molecular weight ditopic monomers with guanine end groups are studied using fluid tapping AFM. These molecules assemble on highly oriented pyrolytic graphite (HOPG) from aqueous solutions to form nano-sized banding structures whose sizes can be systematically tuned at the nano-scale by tailoring the molecular structure of the monomers. The nature of the self-assembly in these systems has been studied through a combination of the self-assembly of structural derivatives and molecular modeling. Furthermore, we introduce the concept of using these molecular assemblies as scaffolds to organize functional groups on the surface. As a first demonstrationof this concept, scaffold monomers that contain a monomethyl triethyleneglycol branch were used to organize these “functional” units on a HOPG surface. These supramolecular grafted assemblies have been shown to be stable in biologically-relevant environments and even have the ability to significantly reduce static platelet adhesion. PMID:18177047

  12. Overview of regulatory strategies and molecular elements in metabolic engineering of bacteria.

    PubMed

    Wang, Tianwen; Ma, Xingyuan; Du, Guocheng; Chen, Jian

    2012-11-01

    From a viewpoint of biotechnology, metabolic engineering mainly aims to change the natural status of a pathway in a microorganism towards the overproduction of certain bioproducts. The biochemical nature of a pathway implies us that changed pathway is often the collective results of altered behavior of the metabolic enzymes encoded by corresponding genes. By finely modulating the expression of these genes or the properties of the enzyme, we can gain efficient control on the pathway. In this article, we reviewed the typical methods that have been applied to regulate the expression of genes in metabolic engineering. These methods are grouped according to the operation targets in a typical gene. The transcription of a gene is controlled by an indispensable promoter. By utilizing promoters with different strengths, expected levels of expression can be easily achieved, and screening a promoter library may find suitable mutant promoters that can provide tunable expression of a gene. Auto-responsive promoter (quorum sensing (QS)-based or oxygen-inducible) simplifies the induction process by driving the expression of a gene in an automated manner. Light responsive promoter enables reversible and noninvasive control on gene activity, providing a promising method in controlling gene expression with time and space resolution in metabolic engineering involving complicated genetic circuits. Through directed evolution and/or rational design, the encoding sequences of a gene can be altered, leading to the possibly most profound changes in properties of a metabolic enzyme. Introducing an engineered riboswitch in mRNA can make it a regulatory molecule at the same time; ribosomal binding site is commonly engineered to be more attractive for a ribosome through design. Terminator of a gene will affect the stability of an mRNA, and intergenic region will influence the expression of many related genes. Improving the performance of these elements are generally the main activities in

  13. Molecularly Engineered Organic-Inorganic Hybrid Perovskite with Multiple Quantum Well Structure for Multicolored Light-Emitting Diodes

    PubMed Central

    Hu, Hongwei; Salim, Teddy; Chen, Bingbing; Lam, Yeng Ming

    2016-01-01

    Organic-inorganic hybrid perovskites have the potential to be used as a new class of emitters with tunable emission, high color purity and good ease of fabrication. Recent studies have so far been focused on three-dimensional (3D) perovskites, such as CH3NH3PbBr3 and CH3NH3PbI3 for green and infrared emission. Here, we explore a new series of hybrid perovskite emitters with a general formula of (C4H9NH3)2(CH3NH3)n−1PbnI3n+1 (where n = 1, 2, 3), which possesses a multiple quantum well structure. The quantum well thickness of these materials is adjustable through simple molecular engineering which results in a continuously tunable bandgap and emission spectra. Deep saturated red emission was obtained with a peak external quantum efficiency of 2.29% and a maximum luminance of 214 cd/m2. Green and blue LEDs were also demonstrated through halogen substitutions in these hybrid perovskites. We expect these results to open up the way towards high performance perovskite LEDs through molecular-structure engineering of these perovskite emitters. PMID:27633084

  14. Phylogeny of the Baldratiina (Diptera: Cecidomyiidae) inferred from morphological, ecological and molecular data sources, and evolutionary patterns in plant-galler relationships.

    PubMed

    Dorchin, Netta; Freidberg, Amnon; Mokady, Ofer

    2004-03-01

    The phylogeny of the gall-midge subtribe Baldratiina (Diptera: Cecidomyiidae) was reconstructed from molecular (partial sequence of the mitochondrial 12S rDNA), morphological and ecological data sets, using 16 representative species of most of the genera. The morphological and ecological data were combined in a single character matrix and analyzed separately from the molecular data, resulting in an eco-morphological cladogram and a molecular cladogram. Attributes of galls and host associations were superimposed on the molecular cladogram in order to detect possible trends in the evolution of these traits. The cladograms resulting from the two independent analyses were statistically incongruent, although both provide evidence for the monophyly of the genera Baldratia and Careopalpis and the paraphyly of the genera Stefaniola and Izeniola. The results suggest a minor impact of the morphological characters traditionally used in the classification of the Baldratiina, whereas ecological data had a major impact on the phylogenetic inference. Mapping of gall and host attributes on the molecular cladogram suggests that multi-chambered stem galls constitute the ancestral state in the subtribe, with several subsequent shifts to leaf galls. It is concluded that in contrast to other studied groups of gall insects, related baldratiine species induce different types of galls, attesting to speciation driven by gall-type shifts at least as often as host shifts.

  15. Directed Molecular Evolution of an Engineered Gammaretroviral Envelope Protein with Dual Receptor Use Shows Stable Maintenance of Both Receptor Specificities

    PubMed Central

    Friis, Kristina Pagh; Iturrioz, Xavier; Thomsen, Jonas; Alvear-Perez, Rodrigo; Bahrami, Shervin; Llorens-Cortes, Catherine

    2015-01-01

    ABSTRACT We have previously reported the construction of a murine leukemia virus-based replication-competent gammaretrovirus (SL3-AP) capable of utilizing the human G protein-coupled receptor APJ (hAPJ) as its entry receptor and its natural receptor, the murine Xpr1 receptor, with equal affinities. The apelin receptor has previously been shown to function as a coreceptor for HIV-1, and thus, adaptation of the viral vector to this receptor is of significant interest. Here, we report the molecular evolution of the SL3-AP envelope protein when the virus is cultured in cells harboring either the Xpr1 or the hAPJ receptor. Interestingly, the dual receptor affinity is maintained even after 10 passages in these cells. At the same time, the chimeric viral envelope protein evolves in a distinct pattern in the apelin cassette when passaged on D17 cells expressing hAPJ in three separate molecular evolution studies. This pattern reflects selection for reduced ligand-receptor interaction and is compatible with a model in which SL3-AP has evolved not to activate hAPJ receptor internalization. IMPORTANCE Few successful examples of engineered retargeting of a retroviral vector exist. The engineered SL3-AP envelope is capable of utilizing either the murine Xpr1 or the human APJ receptor for entry. In addition, SL3-AP is the first example of an engineered retrovirus retaining its dual tropism after several rounds of passaging on cells expressing only one of its receptors. We demonstrate that the virus evolves toward reduced ligand-receptor affinity, which sheds new light on virus adaptation. We provide indirect evidence that such reduced affinity leads to reduced receptor internalization and propose a novel model in which too rapid receptor internalization may decrease virus entry. PMID:26608314

  16. Engineering of a novel Ca{sup 2+}-regulated kinesin molecular motor using a calmodulin dimer linker

    SciTech Connect

    Shishido, Hideki; Maruta, Shinsaku

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer Engineered kinesin-M13 and calmodulin involving single cysteine were prepared. Black-Right-Pointing-Pointer CaM mutant was cross-linked to dimer by bifunctional thiol reactive reagent. Black-Right-Pointing-Pointer Kinesin-M13 was dimerized via CaM dimer in the presence of calcium. Black-Right-Pointing-Pointer Function of the engineered kinesin was regulated by a Ca{sup 2+}-calmodulin dimer linker. -- Abstract: The kinesin-microtubule system holds great promise as a molecular shuttle device within biochips. However, one current barrier is that such shuttles do not have 'on-off' control of their movement. Here we report the development of a novel molecular motor powered by an accelerator and brake system, using a kinesin monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355-M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and crosslinkers that react with cysteine residues. Following induction of K355-M13 dimerization with CaM dimers, we measured K355-M13 motility and found that it can be reversibly regulated in a Ca{sup 2+}-dependent manner. We also found that velocities of K355-M13 varied depending on the type and crosslink position of the CaM dimer used; crosslink length also had a moderate effect on motility. These results suggest Ca{sup 2+}-dependent dimerization of K355-M13 could be used as a novel molecular shuttle, equipped with an accelerator and brake system, for biochip applications.

  17. Mimicking biopolymers on a molecular scale: nano(bio)technology based on engineered proteins.

    PubMed

    Grunwald, Ingo; Rischka, Klaus; Kast, Stefan M; Scheibel, Thomas; Bargel, Hendrik

    2009-05-13

    Proteins are ubiquitous biopolymers that adopt distinct three-dimensional structures and fulfil a multitude of elementary functions in organisms. Recent systematic studies in molecular biology and biotechnology have improved the understanding of basic functional and architectural principles of proteins, making them attractive candidates as concept generators for technological development in material science, particularly in biomedicine and nano(bio)technology. This paper highlights the potential of molecular biomimetics in mimicking high-performance proteins and provides concepts for applications in four case studies, i.e. spider silk, antifreeze proteins, blue mussel adhesive proteins and viral ion channels.

  18. An engineering assessment of gas/surface interactions in free-molecular aerodynamics

    NASA Technical Reports Server (NTRS)

    Knox, E. C.; Liver, Peter A.; Collins, Frank G.

    1991-01-01

    Data available on the gas/surface interaction (GSI) phenomenon, particularly in the rarefied to near-free-molecular flow regime are collected, categorized, and analyzed with a purpose of developing a GSI model that could be used as a guide to spacecraft designers. The study shows that there are not enough useful data for building a high-confidence GSI model. However, sufficient results are obtained to suggest that continued reliance on the diffuse GSI model is inappropriate, particularly in the near-free-molecular regime.

  19. Molecular characterization and evolutionary insights into potential sex-determination genes in the western orchard predatory mite Metaseiulus occidentalis (Chelicerata: Arachnida: Acari: Phytoseiidae).

    PubMed

    Pomerantz, Aaron F; Hoy, Marjorie A; Kawahara, Akito Y

    2015-01-01

    Little is known about the process of sex determination at the molecular level in species belonging to the subclass Acari, a taxon of arachnids that contains mites and ticks. The recent sequencing of the transcriptome and genome of the western orchard predatory mite Metaseiulus occidentalis allows investigation of molecular mechanisms underlying the biological processes of sex determination in this predator of phytophagous pest mites. We identified four doublesex-and-mab-3-related transcription factor (dmrt) genes, one transformer-2 gene, one intersex gene, and two fruitless-like genes in M. occidentalis. Phylogenetic analyses were conducted to infer the molecular relationships to sequences from species of arthropods, including insects, crustaceans, acarines, and a centipede, using available genomic data. Comparative analyses revealed high sequence identity within functional domains and confirmed that the architecture for certain sex-determination genes is conserved in arthropods. This study provides a framework for identifying potential target genes that could be implicated in the process of sex determination in M. occidentalis and provides insight into the conservation and change of the molecular components of sex determination in arthropods.

  20. A molecular mechanism for the origin of a key evolutionary innovation, the bird beak and palate, revealed by an integrative approach to major transitions in vertebrate history.

    PubMed

    Bhullar, Bhart-Anjan S; Morris, Zachary S; Sefton, Elizabeth M; Tok, Atalay; Tokita, Masayoshi; Namkoong, Bumjin; Camacho, Jasmin; Burnham, David A; Abzhanov, Arhat

    2015-07-01

    The avian beak is a key evolutionary innovation whose flexibility has permitted birds to diversify into a range of disparate ecological niches. We approached the problem of the mechanism behind this innovation using an approach bridging paleontology, comparative anatomy, and experimental developmental biology. First, we used fossil and extant data to show the beak is distinctive in consisting of fused premaxillae that are geometrically distinct from those of ancestral archosaurs. To elucidate underlying developmental mechanisms, we examined candidate gene expression domains in the embryonic face: the earlier frontonasal ectodermal zone (FEZ) and the later midfacial WNT-responsive region, in birds and several reptiles. This permitted the identification of an autapomorphic median gene expression region in Aves. To test the mechanism, we used inhibitors of both pathways to replicate in chicken the ancestral amniote expression. Altering the FEZ altered later WNT responsiveness to the ancestral pattern. Skeletal phenotypes from both types of experiments had premaxillae that clustered geometrically with ancestral fossil forms instead of beaked birds. The palatal region was also altered to a more ancestral phenotype. This is consistent with the fossil record and with the tight functional association of avian premaxillae and palate in forming a kinetic beak.

  1. Engineered complex molecular order in liquid crystals towards unusual optics and responsive mechanics

    NASA Astrophysics Data System (ADS)

    Sánchez-Somolinos, Carlos; de Haan, Laurens T.; Schenning, Albert P. H. J.; Bastiaansen, Cees W. M.; Broer, Dirk J.

    2013-03-01

    Defects in liquid crystals have been studied over decades to disclose information and knowledge on the structure of LC phases. More recently, LC defects have been identified as a tool to implement new physical functions useful in optical films for polarization conversion or mechanical actuators able to adopt novel exotic shapes. In the present paper we describe a general methodology to engineer different defect patterns by combining the use of linear photopolymerizable polymers and liquid crystals.

  2. Engineering of an ultra-thin molecular superconductor by charge transfer

    DOEpatents

    Hla, Saw Wai; Hassanien, Abdelrahim; Kendal, Clark

    2016-06-07

    A method of forming a superconductive device of a single layer of (BETS).sub.2GaCl.sub.4 molecules on a substrate surface which displays a superconducting gap that increases exponentially with the length of the molecular chain is provided.

  3. Genetic engineered molecular imaging probes for applications in cell therapy: emphasis on MRI approach

    PubMed Central

    Cho, In K; Wang, Silun; Mao, Hui; Chan, Anthony WS

    2016-01-01

    Recent advances in stem cell-based regenerative medicine, cell replacement therapy, and genome editing technologies (i.e. CRISPR-Cas 9) have sparked great interest in in vivo cell monitoring. Molecular imaging promises a unique approach to noninvasively monitor cellular and molecular phenomena, including cell survival, migration, proliferation, and even differentiation at the whole organismal level. Several imaging modalities and strategies have been explored for monitoring cell grafts in vivo. We begin this review with an introduction describing the progress in stem cell technology, with a perspective toward cell replacement therapy. The importance of molecular imaging in reporting and assessing the status of cell grafts and their relation to the local microenvironment is highlighted since the current knowledge gap is one of the major obstacles in clinical translation of stem cell therapy. Based on currently available imaging techniques, we provide a brief discussion on the pros and cons of each imaging modality used for monitoring cell grafts with particular emphasis on magnetic resonance imaging (MRI) and the reporter gene approach. Finally, we conclude with a comprehensive discussion of future directions of applying molecular imaging in regenerative medicine to emphasize further the importance of correlating cell graft conditions and clinical outcomes to advance regenerative medicine. PMID:27766183

  4. Molecularly imprinted sol-gel nanoparticles for mass-sensitive engine oil degradation sensing.

    PubMed

    Lieberzeit, Peter A; Afzal, Adeel; Glanzing, Gerd; Dickert, Franz L

    2007-09-01

    Titanate sol-gel layers imprinted with midchain carbonic acids have proven highly useful for detecting engine oil degradation processes owing to selective incorporation of oxidised base oil components. Synthesising the material from TiCl(4) in CCl(4) and precipitating with water leads to imprinted TiO(2) nanoparticles with a diameter of 200-300 nm. Replacing the water by a 1 M ammonium hydroxide solution reduces the average particle size to 50-100 nm with retention of the interaction capabilities. Experiments with the latter solution revealed that the 100-nm particles take up substantially more analyte, indicating a size-dependent phenomenon. As the number of interaction sites within each material is the same, this cannot be a consequence of thermodynamics but must be one of accessibility. The sensor characteristic of water-precipitated particles towards engine oil degradation products shows substantially increased sensitivity and dynamic range compared with the corresponding thin films. Coating quartz crystal microbalances with such nanoparticle materials leads to engine oil degradation sensors owing to incorporation of acidic base oil oxidation products. Interaction studies over a large range of layer thicknesses revealed that both the absolute signal and the steepness of the correlation between the sensor signal and the layer height is 2 times higher for the particles.

  5. Evolutionary engineering of a glycerol-3-phosphate dehydrogenase-negative, acetate-reducing Saccharomyces cerevisiae strain enables anaerobic growth at high glucose concentrations.

    PubMed

    Guadalupe-Medina, Víctor; Metz, Benjamin; Oud, Bart; van Der Graaf, Charlotte M; Mans, Robert; Pronk, Jack T; van Maris, Antonius J A

    2014-01-01

    Glycerol production by Saccharomyces cerevisiae, which is required for redox-cofactor balancing in anaerobic cultures, causes yield reduction in industrial bioethanol production. Recently, glycerol formation in anaerobic S. cerevisiae cultures was eliminated by expressing Escherichia coli (acetylating) acetaldehyde dehydrogenase (encoded by mhpF) and simultaneously deleting the GPD1 and GPD2 genes encoding glycerol-3-phosphate dehydrogenase, thus coupling NADH reoxidation to reduction of acetate to ethanol. Gpd⁻ strains are, however, sensitive to high sugar concentrations, which complicates industrial implementation of this metabolic engineering concept. In this study, laboratory evolution was used to improve osmotolerance of a Gpd⁻ mhpF-expressing S. cerevisiae strain. Serial batch cultivation at increasing osmotic pressure enabled isolation of an evolved strain that grew anaerobically at 1 M glucose, at a specific growth rate of 0.12 h⁻¹. The evolved strain produced glycerol at low concentrations (0.64 ± 0.33 g l⁻¹). However, these glycerol concentrations were below 10% of those observed with a Gpd⁺ reference strain. Consequently, the ethanol yield on sugar increased from 79% of the theoretical maximum in the reference strain to 92% for the evolved strains. Genetic analysis indicated that osmotolerance under aerobic conditions required a single dominant chromosomal mutation, and one further mutation in the plasmid-borne mhpF gene for anaerobic growth.

  6. “The Environment is Everything That Isn't Me”: Molecular Mechanisms and Evolutionary Dynamics of Insect Clocks in Variable Surroundings

    PubMed Central

    Rivas, Gustavo B. S.; Bauzer, Luiz G. S. da R.; Meireles-Filho, Antonio C. A.

    2016-01-01

    Circadian rhythms are oscillations in behavior, metabolism and physiology that have a period close to 24 h. These rhythms are controlled by an internal pacemaker that evolved under strong selective pressures imposed by environmental cyclical changes, mainly of light and temperature. The molecular nature of the circadian pacemaker was extensively studied in a number of organisms under controlled laboratory conditions. But although these studies were fundamental to our understanding of the circadian clock, most of the environmental conditions used resembled rather crudely the relatively constant situation at lower latitudes. At higher latitudes light-dark and temperature cycles vary considerably across different seasons, with summers having long and hot days and winters short and cold ones. Considering these differences and other external cues, such as moonlight, recent studies in more natural and semi-natural situations revealed unexpected features at both molecular and behavioral levels, highlighting the dramatic influence of multiple environmental variables in the molecular clockwork. This emphasizes the importance of studying the circadian clock in the wild, where seasonal environmental changes fine-tune the underlying circadian mechanism, affecting population dynamics and impacting the geographical variation in clock genes. Indeed, latitudinal clines in clock gene frequencies suggest that natural selection and demography shape the circadian clock over wide geographical ranges. In this review we will discuss the recent advances in understanding the molecular underpinnings of the circadian clock, how it resonates with the surrounding variables (both in the laboratory and in semi-natural conditions) and its impact on population dynamics and evolution. In addition, we will elaborate on how next-generation sequencing technologies will complement classical reductionist approaches by identifying causal variants in natural populations that will link genetic variation to

  7. Plant progesterone 5beta-reductase is not homologous to the animal enzyme. Molecular evolutionary characterization of P5betaR from Digitalis purpurea.

    PubMed

    Gavidia, Isabel; Tarrío, Rosa; Rodríguez-Trelles, Francisco; Pérez-Bermúdez, Pedro; Seitz, H Ulrich

    2007-03-01

    Plants of the genus Digitalis produce cardiac glycosides, i.e. digoxin, which are widely used for congestive heart failure. Progesterone 5beta-reductase (P5betaR) is a key enzyme in the biosynthesis of these natural products. Here, we have carried out the purification and partial amino acid sequencing of the native P5betaR from foxglove (Digitalis purpurea), and isolated a cDNA encoding this enzyme. Similarly to other steroid 5beta-reductases, the recombinant P5betaR catalyzes the stereospecific reduction of the Delta(4)-double bond of several steroids with a 3-oxo,Delta(4,5) structure. The gene encoding P5betaR is expressed in all plant organs, and maximally transcribed in leaves and mature flowers. P5betaR belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, bearing no structural homology to its mammalian counterpart, which is a member of the aldo-keto reductase (AKR) superfamily. A similar situation occurs with 3beta-hydroxy-Delta(5)-steroid dehydrogenase (3betaHSD), the gene immediately preceding P5betaR in the cardenolide pathway, which suggests that the entire route has evolved independently in animals and plants. P5betaR is retained only in plants, where it is ubiquitous, and a few distantly related bacterial lineages after its diversification from the last universal common ancestor. Evolutionary conserved changes in its putative active site suggest that plant P5betaR is a member of a novel subfamily of extended SDRs, or a new SDR family.

  8. Molecular Evolutionary Analysis of pH1N1 2009 Influenza Virus in Reunion Island, South West Indian Ocean Region: A Cohort Study

    PubMed Central

    Turpin, Magali; de Lamballerie, Xavier; Dellagi, Koussay

    2012-01-01

    Background/Objectives Molecular epidemiology is a powerful tool to decipher the dynamics of viral transmission, quasispecies temporal evolution and origins. Little is known about the pH1N1 molecular dynamics in general population. A prospective study (CoPanFlu-RUN) was carried out in Reunion Island to characterize pH1N1 genetic variability and molecular evolution occurring in population during the pH1N1 Influenza pandemic in 2009. Methodology We directly amplified pH1N1 genomes from 28 different nasal swabs (26 individuals from 21 households). Fifteen strains were fully sequenced and 13 partially. This includes pairs of sequences from different members of 5 separate households; and two pairs from individuals, collected at different times. We assessed the molecular evolution of pH1N1 by genetic variability and phylogenetic analyses. Principal Findings We found that i) Reunion pH1N1 sequences stemmed from global “clade 7” but shaped two phylogenetic sub-clades; ii) D239E mutation was identified in the hemagglutinin protein of all Reunion sequences, a mutation which has been associated elsewhere with mild-, upper-respiratory tract pH1N1 infecting strains; iii) Date estimates from molecular phylogenies predicted clade emergence some time before the first detection of pH1N1 by the epidemiological surveillance system; iv) Phylogenetic relatedness was observed between Reunion pH1N1 viruses and those from other countries in South-western Indian Ocean area; v) Quasispecies populations were observed within households and individuals of the cohort-study. Conclusions Surveillance and/or prevention systems presently based on Influenza virus sequence variation should take into account that the majority of studies of pH1N1 Influenza generate genetic data for the HA/NA viral segments obtained from hospitalized-patients, which is potentially non-representative of the overall viral diversity within whole populations. Our observations highlight the importance of collecting

  9. Engineering molecularly-active nanoplasmonic surfaces for DNA detection via colorimetry and Raman scattering

    NASA Astrophysics Data System (ADS)

    Heydari, Esmaeil; Mabbott, Samuel; Thompson, David; Graham, Duncan; Cooper, Jonathan M.; Clark, Alasdair W.

    2016-03-01

    We report a novel nanophotonic biosensor surface capable of both colorimetric detection and Raman-scattered detection of DNA infection markers at extreme sensitivities. Combining direct-write lithography, dip-pen nanolithography based DNA patterning, and molecular self-assembly, we create molecularly-active plasmonic nanostructures onto which metallic nanoparticles are located via DNA-hybridization. Arraying these structures enables optical surfaces that change state when contacted by specific DNA sequences; shifting the surface color while simultaneously generating strong Raman-scattering signals. Patterning the DNA markers onto the plasmonic surface as micro-scale symbols results in easily identifiable color shifts, making this technique applicable to multiplexed lab-on-a-chip and point-of-care diagnostic applications.

  10. Evidence for entanglement at high temperatures in an engineered molecular magnet

    SciTech Connect

    Reis, Mario S; Soriano, Stephane; Moreira Dos Santos, Antonio F; Sales, Brian C; Soares-Pinto, D O; Brandao, Paula

    2012-01-01

    The molecular compound [Fe-2(mu(2)-oxo)(C3H4N2)(6)(C2O4)(2)] was designed and synthesized for the first time and its structure was determined using single-crystal X-ray diffraction. The magnetic susceptibility of this compound was measured from 2 to 300 K. The analysis of the susceptibility data using protocols developed for other spin singlet ground-state systems indicates that the quantum entanglement would remain at temperatures up to 732 K, significantly above the highest entanglement temperature reported to date. The large gap between the ground state and the first-excited state (282 K) suggests that the spin system may be somewhat immune to decohering mechanisms. Our measurements strongly suggest that molecular magnets are promising candidate platforms for quantum information processing.

  11. Charge carrier mobilities in organic semiconductors: crystal engineering and the importance of molecular contacts.

    PubMed

    Bashir, Asif; Heck, Alexander; Narita, Akimitsu; Feng, Xinliang; Nefedov, Alexei; Rohwerder, Michael; Müllen, Klaus; Elstner, Marcus; Wöll, Christof

    2015-09-14

    We have conducted a combined experimental and theoretical study on the optimization of hexa-peri-hexabenzocoronene (HBC) as organic semiconductor. While orientations with high electronic coupling are unfavorable in the native liquid crystalline phase of HBC, we enforced such orientations by applying external constraints. To this end, self-assembled monolayers (SAMs) were formed by a non-conventional preparation method on an Au-substrate using electrochemical control. Within these SAMs the HBC units are forced into favorable orientations that cannot be achieved by unconstrained crystallization. For simulating the charge transport we applied a recently developed approach, where the molecular structure and the charge carrier are propagated simultaneously during a molecular dynamics simulation. Experiments as well as simulations are mutually supportive of an improved mobility in these novel materials. The implication of these findings for a rational design of future organic semiconductors will be discussed.

  12. Effect of fuel molecular structure on soot formation in gas turbine engines

    NASA Technical Reports Server (NTRS)

    Naegeli, D. W.; Moses, C. A.

    1980-01-01

    A high-pressure research combustor operating over a wide range of burner inlet conditions was used to determine the effects of fuel molecular structure on soot formation. Six test fuels with equal hydrogen content (12.8 percent) were blended to stress different molecular components and final boiling points. The fuels containing high concentrations (20 percent) of poly-cyclic aromatics and partially saturated polycyclic structures such as tetralin, produced more soot than would be expected from a hydrogen content correlation for typical petroleum based fuels. However, fuels containing naphthenes, such as decalin, agreed with the hydrogen content correlation. The contribution of polycylic aromatics to soot formation was equivalent to a reduction in fuel hydrogen content of about 1%. The fuel sensitivity to soot formation due to the polycyclic aromatic contribution decreased as burner inlet pressure and fuel/air ratio increased.

  13. Integrated Testing of a 4-Bed Molecular Sieve, Air-Cooled Temperature Swing Adsorption Compressor, and Sabatier Engineering Development Unit

    NASA Technical Reports Server (NTRS)

    Knox, James C.; Miller, Lee; Campbell, Melissa; Mulloth, Lila; Varghese, Mini

    2006-01-01

    Accumulation and subsequent compression of carbon dioxide that is removed from the space cabin are two important processes involved in a closed-loop air revitalization scheme of the International Space Station (ISS). The 4-Bed Molecular Sieve (4BMS) of ISS currently operates in an open loop mode without a compressor. The Sabatier Engineering Development Unit (EDU) processes waste CO2 to provide water to the crew. This paper reports the integrated 4BMS, air-cooled Temperature Swing Adsorption Compressor (TSAC), and Sabatier EDU testing. The TSAC prototype was developed at NASA Ames Research Center (ARC). The 4BMS was modified to a functionally flight-like condition at NASA Marshall Space Flight Center (MSFC). Testing was conducted at MSFC. The paper provides details of the TSAC operation at various CO2 loadings and corresponding performance of the 4BMS and Sabatier.

  14. Molecular beam epitaxy engineered III-V semiconductor structures for low-power optically addressed spatial light modulators

    NASA Technical Reports Server (NTRS)

    Larsson, Anders G.; Maserjian, Joseph

    1992-01-01

    Device approaches are investigated for optically addressed SLMs based on molecular-beam epitaxy (MBE) engineered III-V materials and structures. Strong photooptic effects can be achieved in periodically delta-doped multiple-quantum-well structures, but are still insufficient for high-contrast modulation with only single- or double-pass absorption through active layers of practical thickness. The asymmetric Fabry-Perot cavity approach is employed to permit extinction of light due to interference of light reflected from the front and back surfaces of the cavity. This approach is realized with an all-MBE-grown structure consisting of GaAs/AlAs quarter-wave stack reflector grown over the GaAs substrate as the high reflectance mirror and the GaAs surface as the low reflectance mirror. High-contrast modulation is achieved using a low-power InGaAs/GaAs quantum well laser for the control signal.

  15. Evolutionary stability on graphs

    PubMed Central

    Ohtsuki, Hisashi; Nowak, Martin A.

    2008-01-01

    Evolutionary stability is a fundamental concept in evolutionary game theory. A strategy is called an evolutionarily stable strategy (ESS), if its monomorphic population rejects the invasion of any other mutant strategy. Recent studies have revealed that population structure can considerably affect evolutionary dynamics. Here we derive the conditions of evolutionary stability for games on graphs. We obtain analytical conditions for regular graphs of degree k > 2. Those theoretical predictions are compared with computer simulations for random regular graphs and for lattices. We study three different update rules: birth-death (BD), death-birth (DB), and imitation (IM) updating. Evolutionary stability on sparse graphs does not imply evolutionary stability in a well-mixed population, nor vice versa. We provide a geometrical interpretation of the ESS condition on graphs. PMID:18295801

  16. Evolutionary medicine: its scope, interest and potential

    PubMed Central

    Stearns, Stephen C.

    2012-01-01

    This review is aimed at readers seeking an introductory overview, teaching courses and interested in visionary ideas. It first describes the range of topics covered by evolutionary medicine, which include human genetic variation, mismatches to modernity, reproductive medicine, degenerative disease, host–pathogen interactions and insights from comparisons with other species. It then discusses priorities for translational research, basic research and health management. Its conclusions are that evolutionary thinking should not displace other approaches to medical science, such as molecular medicine and cell and developmental biology, but that evolutionary insights can combine with and complement established approaches to reduce suffering and save lives. Because we are on the cusp of so much new research and innovative insights, it is hard to estimate how much impact evolutionary thinking will have on medicine, but it is already clear that its potential is enormous. PMID:22933370

  17. Electrospinning of gelatin for tissue engineering--molecular conformation as one of the overlooked problems.

    PubMed

    Sajkiewicz, P; Kołbuk, D

    2014-01-01

    Gelatin is one of the most promising materials in tissue engineering as a scaffold component. This biopolymer indicates biocompatibility and bioactivity caused by the existence of specific amino acid sequences, being preferred sites for interactions with cells, with high similarity to natural extracellular matrix. The present paper does not aspire to be a full review of electrospinning of gelatin and gelatin containing nanofibers as scaffolds in tissue engineering. It is focused on the still open question of the role of the higher order structures of gelatin in scaffold's bioactivity/functionality. Gelatin molecules can adopt various conformations depending on temperature, solvent, pH, etc. Our review indicates the potential ways for formation of α-helix conformation during electrospinning and the methods of further structure stabilization. It is intuitively expected that the native α-helix conformation appearing as a result of partial renaturation of gelatin can be beneficial from the viewpoint of bioactivity of scaffolds, providing thus a much cheaper alternative approach as opposed to expensive electrospinning of native collagen.

  18. Molecular-based environmental risk assessment of three varieties of genetically engineered cows.

    PubMed

    Xu, Jianxiang; Zhao, Jie; Wang, Jianwu; Zhao, Yaofeng; Zhang, Lei; Chu, Mingxing; Li, Ning

    2011-10-01

    The development of animal biotechnology has led to an increase in attention to biosafety issues. Here we evaluated the impact of genetically engineered cows on the environment. The probability of horizontal gene transfer and the impact on the microbial communities in cow gut and soil were tested using three varieties of genetically engineered cows that were previously transformed with a human gene encoding lysozyme, lactoferrin, or human alpha lactalbumin. The results showed that the transgenes were not detectable by polymerase chain reaction (PCR) or quantitative real-time PCR in gut microbial DNA extracts of manure or microbial DNA extracts of topsoil. In addition, the transgenes had no impact on the microbial communities in cow gut or soil as assessed by PCR-denaturing gradient gel electrophoresis or 16S rDNA sequencing. Furthermore, phylogenetic analyses showed that the manure bacteria sampled during each of the four seasons belonged primarily to two groups, Firmicutes and Bacteroidetes, and the soil bacteria belonged to four groups, Firmicutes, Bacteroidetes, Actinobacteria, and α-proteobacteria. Other groups, such as β-proteobacteria, γ-proteobacteria, δ-proteobacteria, ε-proteobacteria, Spirochaetes, Acidobacteria, Chloroflexi, and Nitrospira, were not dominant in the manure or soil.

  19. Genetic Engineering: A Promising Tool to Engender Physiological, Biochemical, and Molecular Stress Resilience in Green Microalgae

    PubMed Central

    Guihéneuf, Freddy; Khan, Asif; Tran, Lam-Son P.

    2016-01-01

    As we march into the 21st century, the prevailing scenario of depleting energy resources, global warming and ever increasing issues of human health and food security will quadruple. In this context, genetic and metabolic engineering of green microalgae complete the quest toward a continuum of environmentally clean fuel and food production. Evolutionarily related, but unlike land plants, microalgae need nominal land or water, and are best described as unicellular autotrophs using light energy to fix atmospheric carbon dioxide (CO2) into algal biomass, mitigating fossil CO2 pollution in the process. Remarkably, a feature innate to most microalgae is synthesis and accumulation of lipids (60–65% of dry weight), carbohydrates and secondary metabolites like pigments and vitamins, especially when grown under abiotic stress conditions. Particularly fruitful, such an application of abiotic stress factors such as nitrogen starvation, salinity, heat shock, etc., can be used in a biorefinery concept for production of multiple valuable products. The focus of this mini-review underlies metabolic reorientation practices and tolerance mechanisms as applied to green microalgae under specific stress stimuli for a sustainable pollution-free future. Moreover, we entail current progress on genetic engineering as a promising tool to grasp adaptive processes for improving strains with potential biotechnological interests. PMID:27066043

  20. East African cassava mosaic-like viruses from Africa to Indian ocean islands: molecular diversity, evolutionary history and geographical dissemination of a bipartite begomovirus

    PubMed Central

    2012-01-01

    Background Cassava (Manihot esculenta) is a major food source for over 200 million sub-Saharan Africans. Unfortunately, its cultivation is severely hampered by cassava mosaic disease (CMD). Caused by a complex of bipartite cassava mosaic geminiviruses (CMG) species (Family: Geminivirideae; Genus: Begomovirus) CMD has been widely described throughout Africa and it is apparent that CMG's are expanding their geographical distribution. Determining where and when CMG movements have occurred could help curtail its spread and reveal the ecological and anthropic factors associated with similar viral invasions. We applied Bayesian phylogeographic inference and recombination analyses to available and newly described CMG sequences to reconstruct a plausible history of CMG diversification and migration between Africa and South West Indian Ocean (SWIO) islands. Results The isolation and analysis of 114 DNA-A and 41 DNA-B sequences demonstrated the presence of three CMG species circulating in the Comoros and Seychelles archipelagos (East African cassava mosaic virus, EACMV; East African cassava mosaic Kenya virus, EACMKV; and East African cassava mosaic Cameroon virus, EACMCV). Phylogeographic analyses suggest that CMG’s presence on these SWIO islands is probably the result of at least four independent introduction events from mainland Africa occurring between 1988 and 2009. Amongst the islands of the Comoros archipelago, two major migration pathways were inferred: One from Grande Comore to Mohéli and the second from Mayotte to Anjouan. While only two recombination events characteristic of SWIO islands isolates were identified, numerous re-assortments events were detected between EACMV and EACMKV, which seem to almost freely interchange their genome components. Conclusions Rapid and extensive virus spread within the SWIO islands was demonstrated for three CMG complex species. Strong evolutionary or ecological interaction between CMG species may explain both their propensity

  1. Software Engineering Guidebook

    NASA Technical Reports Server (NTRS)

    Connell, John; Wenneson, Greg

    1993-01-01

    The Software Engineering Guidebook describes SEPG (Software Engineering Process Group) supported processes and techniques for engineering quality software in NASA environments. Three process models are supported: structured, object-oriented, and evolutionary rapid-prototyping. The guidebook covers software life-cycles, engineering, assurance, and configuration management. The guidebook is written for managers and engineers who manage, develop, enhance, and/or maintain software under the Computer Software Services Contract.

  2. Remembering the evolutionary Freud.

    PubMed

    Young, Allan

    2006-03-01

    Throughout his career as a writer, Sigmund Freud maintained an interest in the evolutionary origins of the human mind and its neurotic and psychotic disorders. In common with many writers then and now, he believed that the evolutionary past is conserved in the mind and the brain. Today the "evolutionary Freud" is nearly forgotten. Even among Freudians, he is regarded to be a red herring, relevant only to the extent that he diverts attention from the enduring achievements of the authentic Freud. There are three ways to explain these attitudes. First, the evolutionary Freud's key work is the "Overview of the Transference Neurosis" (1915). But it was published at an inopportune moment, forty years after the author's death, during the so-called "Freud wars." Second, Freud eventually lost interest in the "Overview" and the prospect of a comprehensive evolutionary theory of psychopathology. The publication of The Ego and the Id (1923), introducing Freud's structural theory of the psyche, marked the point of no return. Finally, Freud's evolutionary theory is simply not credible. It is based on just-so stories and a thoroughly discredited evolutionary mechanism, Lamarckian use-inheritance. Explanations one and two are probably correct but also uninteresting. Explanation number three assumes that there is a fundamental difference between Freud's evolutionary narratives (not credible) and the evolutionary accounts of psychopathology that currently circulate in psychiatry and mainstream journals (credible). The assumption is mistaken but worth investigating.

  3. Engineered absorption enhancement and induced transparency in coupled molecular and plasmonic resonator systems.

    PubMed

    Adato, Ronen; Artar, Alp; Erramilli, Shyamsunder; Altug, Hatice

    2013-06-12

    Coupled plasmonic resonators have become the subject of significant research interest in recent years as they provide a route to dramatically enhanced light-matter interactions. Often, the design of these coupled mode systems draws intuition and inspiration from analogies to atomic and molecular physics systems. In particular, they have been shown to mimic quantum interference effects, such as electromagnetically induced transparency (EIT) and Fano resonances. This analogy also been used to describe the surface-enhanced absorption effect where a plasmonic resonance is coupled to a weak molecular resonance. These important phenomena are typically described using simple driven harmonic (or linear) oscillators (i.e., mass-on-a-spring) coupled to each other. In this work, we demonstrate the importance of an essential interdependence between the rate at which the system can be driven by an external field and its damping rate through radiative loss. This link is required in systems exhibiting time-reversal symmetry and energy conservation. Not only does it ensure an accurate and physically consistent description of resonant systems but leads directly to interesting new effects. Significantly, we demonstrate this dependence to predict a transition between EIT and electromagnetically induced absorption that is solely a function of the ratio of the radiative to intrinsic loss rates in coupled resonator systems. Leveraging the temporal coupled mode theory, we introduce a unique and intuitive picture that accurately describes these effects in coupled plasmonic/molecular and fully plasmonic systems. We demonstrate our approach's key features and advantages analytically as well as experimentally through surface-enhanced absorption spectroscopy and plasmonic metamaterial applications.

  4. Human molecular genetics research at the International Centre for Genetic Engineering and Biotechnology.

    PubMed

    Falaschi, P A

    1997-01-01

    The ICGEB started its activity in 1987 as a special project of UNIDO (United Nations Industrial Development Organization) and operates now as a fully autonomous International Organization, of which 40 countries are members at present. The mandate of ICGEB is to become a Centre of excellence for research and training in modern biology addressed to the needs of the developing world. The ICGEB consists of two main laboratories, one in Trieste (where the direction of the Centre is also located) and one in New Delhi, plus a network of 30 Affiliated Centres. The Centre operates through: 1) specific research programs of hish scientific content at the Trieste and New Delhi laboratories; 2) long term training through post-doctoral and pre-doctoral fellowships; 3) short term training; 4) collaborative research program, through which the Centre finances research projects of major impact to the need of the Member States; 5) scientific services, namely consultation for scientific programs, distribution of reagents and a bioinformatics network particularly geared to the human genome research. The research on human molecular genetics in particularly active in the Trieste Component and concerns the study at the molecular level of several genes important for human health: control of DNA replication, response to infectious diseases, cardiocirculatory diseases, cystic fibrosis and cancer. The methodologies for developing new diagnostic methods and for developing gene therapy protocols are actively pursued. Through these programs, the member countries have access to state-of-the-art technologies anf know-how essential for the development of the molecular approaches to medicine brought forward by the study of the human genome.

  5. First comparative study of primate morphological and molecular evolutionary rates including muscle data: implications for the tempo and mode of primate and human evolution

    PubMed Central

    Diogo, Rui; Peng, Zuogang; Wood, Bernard

    2013-01-01

    Here we provide the first report about the rates of muscle evolution derived from Bayesian and parsimony cladistic analyses of primate higher-level phylogeny, and compare these rates with published rates of molecular evolution. It is commonly accepted that there is a ‘general molecular slow-down of hominoids’, but interestingly the rates of muscle evolution in the nodes leading and within the hominoid clade are higher than those in the vast majority of other primate clades. The rate of muscle evolution at the node leading to Homo (1.77) is higher than that at the nodes leading to Pan (0.89) and particularly to Gorilla (0.28). Notably, the rates of muscle evolution at the major euarchontan and primate nodes are different, but within each major primate clade (Strepsirrhini, Platyrrhini, Cercopithecidae and Hominoidea) the rates at the various nodes, and particularly at the nodes leading to the higher groups (i.e. including more than one genera), are strikingly similar. We explore the implications of these new data for the tempo and mode of primate and human evolution. PMID:23320764

  6. OOPSE: an object-oriented parallel simulation engine for molecular dynamics.

    PubMed

    Meineke, Matthew A; Vardeman, Charles F; Lin, Teng; Fennell, Christopher J; Gezelter, J Daniel

    2005-02-01

    OOPSE is a new molecular dynamics simulation program that is capable of efficiently integrating equations of motion for atom types with orientational degrees of freedom (e.g. "sticky" atoms and point dipoles). Transition metals can also be simulated using the embedded atom method (EAM) potential included in the code. Parallel simulations are carried out using the force-based decomposition method. Simulations are specified using a very simple C-based meta-data language. A number of advanced integrators are included, and the basic integrator for orientational dynamics provides substantial improvements over older quaternion-based schemes.

  7. Four- and five-component molecular solids: crystal engineering strategies based on structural inequivalence.

    PubMed

    Mir, Niyaz A; Dubey, Ritesh; Desiraju, Gautam R

    2016-03-01

    A synthetic strategy is described for the co-crystallization of four- and five-component molecular crystals, based on the fact that if any particular chemical constituent of a lower cocrystal is found in two different structural environments, these differences may be exploited to increase the number of components in the solid. 2-Methylresorcinol and tetramethylpyrazine are basic template molecules that allow for further supramolecular homologation. Ten stoichiometric quaternary cocrystals and one quintinary cocrystal with some solid solution character are reported. Cocrystals that do not lend themselves to such homologation are termed synthetic dead ends.

  8. Spatiotemporal control of cell–cell reversible interactions using molecular engineering

    PubMed Central

    Shi, Peng; Ju, Enguo; Yan, Zhengqing; Gao, Nan; Wang, Jiasi; Hou, Jianwen; Zhang, Yan; Ren, Jinsong; Qu, Xiaogang

    2016-01-01

    Manipulation of cell–cell interactions has potential applications in basic research and cell-based therapy. Herein, using a combination of metabolic glycan labelling and bio-orthogonal click reaction, we engineer cell membranes with β-cyclodextrin and subsequently manipulate cell behaviours via photo-responsive host-guest recognition. With this methodology, we demonstrate reversible manipulation of cell assembly and disassembly. The method enables light-controllable reversible assembly of cell–cell adhesion, in contrast with previously reported irreversible effects, in which altered structure could not be reused. We also illustrate the utility of the method by designing a cell-based therapy. Peripheral blood mononuclear cells modified with aptamer are effectively redirected towards target cells, resulting in enhanced cell apoptosis. Our approach allows precise control of reversible cell–cell interactions and we expect that it will promote further developments of cell-based therapy. PMID:27708265

  9. Spatiotemporal control of cell-cell reversible interactions using molecular engineering

    NASA Astrophysics Data System (ADS)

    Shi, Peng; Ju, Enguo; Yan, Zhengqing; Gao, Nan; Wang, Jiasi; Hou, Jianwen; Zhang, Yan; Ren, Jinsong; Qu, Xiaogang

    2016-10-01

    Manipulation of cell-cell interactions has potential applications in basic research and cell-based therapy. Herein, using a combination of metabolic glycan labelling and bio-orthogonal click reaction, we engineer cell membranes with β-cyclodextrin and subsequently manipulate cell behaviours via photo-responsive host-guest recognition. With this methodology, we demonstrate reversible manipulation of cell assembly and disassembly. The method enables light-controllable reversible assembly of cell-cell adhesion, in contrast with previously reported irreversible effects, in which altered structure could not be reused. We also illustrate the utility of the method by designing a cell-based therapy. Peripheral blood mononuclear cells modified with aptamer are effectively redirected towards target cells, resulting in enhanced cell apoptosis. Our approach allows precise control of reversible cell-cell interactions and we expect that it will promote further developments of cell-based therapy.

  10. Molecular engineering aspects for the production of new and modified biosurfactants.

    PubMed

    Koglin, Alexander; Doetsch, Volker; Bernhard, Frank

    2010-01-01

    Biosurfactants are of considerable industrial value as their high tenside activity in combination with their biocompatibility makes them attractive for many applications. In particular members of the lipopeptide family of biosurfactants contain significant potentials for the pharmaceutical industry due to their intrinsic antibiotic characteristics. The high frequency of lipopeptide (LP) production in common soil microorganisms in combination with the enormous structural diversity of the synthesized biosurfactants has created an abundant natural pool of compounds with potentially interesting properties. Unfortunately, the bioactivity of lipopetides against pathogenic microorganisms is often associated with problematic side effects that restrict or even prevent medically relevant applications. The accumulated knowledge of lipopetide biosynthesis and their frequent structural variations caused by natural genetic rearrangements has therefore motivated numerous approaches in order to manipulate biosurfactant composition and production mechanisms. This chapter will give an overview on current engineering strategies that aim to obtain lipopeptide biosurfactants with redesigned structures and optimized properties.

  11. Intraparticle Molecular Orbital Engineering of Semiconducting Polymer Nanoparticles as Amplified Theranostics for in Vivo Photoacoustic Imaging and Photothermal Therapy.

    PubMed

    Lyu, Yan; Fang, Yuan; Miao, Qingqing; Zhen, Xu; Ding, Dan; Pu, Kanyi

    2016-04-26

    Optical theranostic nanoagents that seamlessly and synergistically integrate light-generated signals with photothermal or photodynamic therapy can provide opportunities for cost-effective precision medicine, while the potential for clinical translation requires them to have good biocompatibility and high imaging/therapy performance. We herein report an intraparticle molecular orbital engineering approach to simultaneously enhance photoacoustic brightness and photothermal therapy efficacy of semiconducting polymer nanoparticles (SPNs) for in vivo imaging and treatment of cancer. The theranostic SPNs have a binary optical component nanostructure, wherein a near-infrared absorbing semiconducting polymer and an ultrasmall carbon dot (fullerene) interact with each other to induce photoinduced electron transfer upon light irradiation. Such an intraparticle optoelectronic interaction augments heat generation and consequently enhances the photoacoustic signal and maximum photothermal temperature of SPNs by 2.6- and 1.3-fold, respectively. With the use of the amplified SPN as the theranostic nanoagent, it permits enhanced photoacoustic imaging and photothermal ablation of tumor in living mice. Our study thus not only introduces a category of purely organic optical theranostics but also highlights a molecular guideline to amplify the effectiveness of light-intensive imaging and therapeutic nanosystems.

  12. Tuning the electrical properties of Si nanowire field-effect transistors by molecular engineering.

    PubMed

    Bashouti, Muhammad Y; Tung, Raymond T; Haick, Hossam

    2009-12-01

    Exposed facets of n-type silicon nanowires (Si NWs) fabricated by a top-down approach are successfully terminated with different organic functionalities, including 1,3-dioxan-2-ethyl, butyl, allyl, and propyl-alcohol, using a two-step chlorination/alkylation method. X-ray photoemission spectroscopy and spectroscopic ellipsometry establish the bonding and the coverage of these molecular layers. Field-effect transistors fabricated from these Si NWs displayed characteristics that depended critically on the type of molecular termination. Without molecules the source-drain conduction is unable to be turned off by negative gate voltages as large as -20 V. Upon adsorption of organic molecules there is an observed increase in the "on" current at large positive gate voltages and also a reduction, by several orders of magnitude, of the "off" current at large negative gate voltages. The zero-gate voltage transconductance of molecule-terminated Si NW correlates with the type of organic molecule. Adsorption of butyl and 1,3-dioxan-2-ethyl molecules improves the channel conductance over that of the original SiO(2)-Si NW, while adsorption of molecules with propyl-alcohol leads to a reduction. It is shown that a simple assumption based on the possible creation of surface states alongside the attachment of molecules may lead to a qualitative explanation of these electrical characteristics. The possibility and potential implications of modifying semiconductor devices by tuning the distribution of surface states via the functionality of attached molecules are discussed.

  13. Engineering Botulinum Neurotoxin C1 as a Molecular Vehicle for Intra-Neuronal Drug Delivery.

    PubMed

    Vazquez-Cintron, Edwin J; Beske, Phillip H; Tenezaca, Luis; Tran, Bao Q; Oyler, Jonathan M; Glotfelty, Elliot J; Angeles, Christopher A; Syngkon, Aurelia; Mukherjee, Jean; Kalb, Suzanne R; Band, Philip A; McNutt, Patrick M; Shoemaker, Charles B; Ichtchenko, Konstantin

    2017-02-21

    Botulinum neurotoxin (BoNT) binds to and internalizes its light chain into presynaptic compartments with exquisite specificity. While the native toxin is extremely lethal, bioengineering of BoNT has the potential to eliminate toxicity without disrupting neuron-specific targeting, thereby creating a molecular vehicle capable of delivering therapeutic cargo into the neuronal cytosol. Building upon previous work, we have developed an atoxic derivative (ad) of BoNT/C1 through rationally designed amino acid substitutions in the metalloprotease domain of wild type (wt) BoNT/C1. To test if BoNT/C1 ad retains neuron-specific targeting without concomitant toxic host responses, we evaluated the localization, activity, and toxicity of BoNT/C1 ad in vitro and in vivo. In neuronal cultures, BoNT/C1 ad light chain is rapidly internalized into presynaptic compartments, but does not cleave SNARE proteins nor impair spontaneous neurotransmitter release. In mice, systemic administration resulted in the specific co-localization of BoNT/C1 ad with diaphragmatic motor nerve terminals. The mouse LD50 of BoNT/C1 ad is 5 mg/kg, with transient neurological symptoms emerging at sub-lethal doses. Given the low toxicity and highly specific neuron-targeting properties of BoNT/C1 ad, these data suggest that BoNT/C1 ad can be useful as a molecular vehicle for drug delivery to the neuronal cytoplasm.

  14. Engineering Botulinum Neurotoxin C1 as a Molecular Vehicle for Intra-Neuronal Drug Delivery

    PubMed Central

    Vazquez-Cintron, Edwin J.; Beske, Phillip H.; Tenezaca, Luis; Tran, Bao Q.; Oyler, Jonathan M.; Glotfelty, Elliot J.; Angeles, Christopher A.; Syngkon, Aurelia; Mukherjee, Jean; Kalb, Suzanne R.; Band, Philip A.; McNutt, Patrick M.; Shoemaker, Charles B.; Ichtchenko, Konstantin

    2017-01-01

    Botulinum neurotoxin (BoNT) binds to and internalizes its light chain into presynaptic compartments with exquisite specificity. While the native toxin is extremely lethal, bioengineering of BoNT has the potential to eliminate toxicity without disrupting neuron-specific targeting, thereby creating a molecular vehicle capable of delivering therapeutic cargo into the neuronal cytosol. Building upon previous work, we have developed an atoxic derivative (ad) of BoNT/C1 through rationally designed amino acid substitutions in the metalloprotease domain of wild type (wt) BoNT/C1. To test if BoNT/C1 ad retains neuron-specific targeting without concomitant toxic host responses, we evaluated the localization, activity, and toxicity of BoNT/C1 ad in vitro and in vivo. In neuronal cultures, BoNT/C1 ad light chain is rapidly internalized into presynaptic compartments, but does not cleave SNARE proteins nor impair spontaneous neurotransmitter release. In mice, systemic administration resulted in the specific co-localization of BoNT/C1 ad with diaphragmatic motor nerve terminals. The mouse LD50 of BoNT/C1 ad is 5 mg/kg, with transient neurological symptoms emerging at sub-lethal doses. Given the low toxicity and highly specific neuron-targeting properties of BoNT/C1 ad, these data suggest that BoNT/C1 ad can be useful as a molecular vehicle for drug delivery to the neuronal cytoplasm. PMID:28220863

  15. Exploring Evolutionary Patterns in Genetic Sequence: A Computer Exercise

    ERIC Educational Resources Information Center

    Shumate, Alice M.; Windsor, Aaron J.

    2010-01-01

    The increase in publications presenting molecular evolutionary analyses and the availability of comparative sequence data through resources such as NCBI's GenBank underscore the necessity of providing undergraduates with hands-on sequence analysis skills in an evolutionary context. This need is particularly acute given that students have been…

  16. Engineered Molecular Layers For Organic Electronic Applications: A Confocal Scanning Raman Spectroscopy (CSRS) Investigation

    NASA Astrophysics Data System (ADS)

    Paez-Sierra, Beynor-Antonio; Kolotovska, Viktoriia; Rangel-Kuoppa, Victor-Tapio

    2011-12-01

    We present CSRS maps of magnetically modified vanadyl phthalocyanine (VOPc) thin films forming conduction channels in organic field-effect transistors (OFETs). The VOPc films with a nominal thickness of about 100 nm were produced by organic molecular beam deposition in high vacuum. During the growth conditions the substrates were exposed to a magnetic field (B) from a bar magnet. The CSRS maps revealed significant changes of the organic fields upon preparation conditions. The highest field effect mobility, electrical current and anisotropy of the CSRS-topography is achieved in layers grown with B parallel to the substrate plane, while intermediate and lowest values are achieved in devices grown with B perpendicular to the substrate and without, respectively.

  17. Engineered Molecular Layers For Organic Electronic Applications: A Confocal Scanning Raman Spectroscopy (CSRS) Investigation

    SciTech Connect

    Paez-Sierra, Beynor-Antonio; Kolotovska, Viktoriia; Rangel-Kuoppa, Victor-Tapio

    2011-12-23

    We present CSRS maps of magnetically modified vanadyl phthalocyanine (VOPc) thin films forming conduction channels in organic field-effect transistors (OFETs). The VOPc films with a nominal thickness of about 100 nm were produced by organic molecular beam deposition in high vacuum. During the growth conditions the substrates were exposed to a magnetic field (B) from a bar magnet. The CSRS maps revealed significant changes of the organic fields upon preparation conditions. The highest field effect mobility, electrical current and anisotropy of the CSRS-topography is achieved in layers grown with B parallel to the substrate plane, while intermediate and lowest values are achieved in devices grown with B perpendicular to the substrate and without, respectively.

  18. Metabolic engineering of Pichia pastoris for production of hyaluronic acid with high molecular weight.

    PubMed

    Jeong, Euijoon; Shim, Woo Yong; Kim, Jung Hoe

    2014-09-20

    The high molecular weight (>1 MDa) of hyaluronic acid (HA) is important for its biological functions. The reported limiting factors for the production of HA with high molecular weight (MW) by microbial fermentation are the insufficient HA precursor pool and cell growth inhibition. To overcome these issues, the Xenopus laevis xhasA2 and xhasB genes encoding hyaluronan synthase 2 (xhasA2) and UDP-glucose dehydrogenase (xhasB), were expressed in Pichia pastoris widely used for production of heterologous proteins. In this study, expression vectors containing various combination cassettes of HA pathway genes including xhasA2 and xhasB from X. laevis as well as UDP-glucose pyrophosphorylase (hasC), UDP-N-acetylglucosamine pyrophosphorylase (hasD) and phosphoglucose isomerase (hasE) from P. pastoris were constructed and tested. First, HA pathway genes were overexpressed using pAO815 and pGAPZB vectors, resulting in the production of 1.2 MDa HA polymers. Second, in order to decrease hyaluronan synthase expression a strong AOX1 promoter in the xhasA2 gene was replaced by a weak AOX2 promoter which increased the mean MW of HA to 2.1 MDa. Finally, the MW of HA polymer was further increased to 2.5 MDa by low-temperature cultivation (26 °C) which reduced cell growth inhibition. The yield of HA production by the P. pastoris recombinant strains in 1L of fermentation culture was 0.8-1.7 g/L.

  19. When population and evolutionary genetics met behaviour.

    PubMed

    Costa, Rodolfo; Stanewsky, Ralf

    2013-01-01

    In this review, we analyse the impact of a population and evolutionary genetics approach on the study of insect behaviour. Our attention is focused on the model organism Drosophila melanogaster and several other insect species. In particular, we explore the relationship between rhythmic behaviours and the molecular evolution of clock and ion channel genes.

  20. Molecular Characterization of the 14-3-3 Gene Family in Brachypodium distachyon L. Reveals High Evolutionary Conservation and Diverse Responses to Abiotic Stresses

    PubMed Central

    Cao, Hui; Xu, Yuxing; Yuan, Linlin; Bian, Yanwei; Wang, Lihui; Zhen, Shoumin; Hu, Yingkao; Yan, Yueming

    2016-01-01

    The 14-3-3 gene family identified in all eukaryotic organisms is involved in a wide range of biological processes, particularly in resistance to various abiotic stresses. Here, we performed the first comprehensive study on the molecular characterization, phylogenetics, and responses to various abiotic stresses of the 14-3-3 gene family in Brachypodium distachyon L. A total of seven 14-3-3 genes from B. distachyon and 120 from five main lineages among 12 species were identified, which were divided into five well-conserved subfamilies. The molecular structure analysis showed that the plant 14-3-3 gene family is highly evolutionarily conserved, although certain divergence had occurred in different subfamilies. The duplication event investigation revealed that segmental duplication seemed to be the predominant form by which the 14-3-3 gene family had expanded. Moreover, seven critical amino acids were detected, which may contribute to functional divergence. Expression profiling analysis showed that BdGF14 genes were abundantly expressed in the roots, but showed low expression in the meristems. All seven BdGF14 genes showed significant expression changes under various abiotic stresses, including heavy metal, phytohormone, osmotic, and temperature stresses, which might play important roles in responses to multiple abiotic stresses mainly through participating in ABA-dependent signaling and reactive oxygen species-mediated MAPK cascade signaling pathways. In particular, BdGF14 genes generally showed upregulated expression in response to multiple stresses of high temperature, heavy metal, abscisic acid (ABA), and salicylic acid (SA), but downregulated expression under H2O2, NaCl, and polyethylene glycol (PEG) stresses. Meanwhile, dynamic transcriptional expression analysis of BdGF14 genes under longer treatments with heavy metals (Cd2+, Cr3+, Cu2+, and Zn2+) and phytohormone (ABA) and recovery revealed two main expression trends in both roots and leaves: up-down and up

  1. Polymorphic Evolutionary Games.

    PubMed

    Fishman, Michael A

    2016-06-07

    In this paper, I present an analytical framework for polymorphic evolutionary games suitable for explicitly modeling evolutionary processes in diploid populations with sexual reproduction. The principal aspect of the proposed approach is adding diploid genetics cum sexual recombination to a traditional evolutionary game, and switching from phenotypes to haplotypes as the new game׳s pure strategies. Here, the relevant pure strategy׳s payoffs derived by summing the payoffs of all the phenotypes capable of producing gametes containing that particular haplotype weighted by the pertinent probabilities. The resulting game is structurally identical to the familiar Evolutionary Games with non-linear pure strategy payoffs (Hofbauer and Sigmund, 1998. Cambridge University Press), and can be analyzed in terms of an established analytical framework for such games. And these results can be translated into the terms of genotypic, and whence, phenotypic evolutionary stability pertinent to the original game.

  2. Dynamic control over cell adhesive properties using molecular-based surface engineering strategies.

    PubMed

    Robertus, Jort; Browne, Wesley R; Feringa, Ben L

    2010-01-01

    In complex organisms, cells are often dependent on their extracellular matrix (ECM) for structural integrity, the mechanical properties of tissues, and for signaled regulation of cellular processes including adhesion, migration, growth, secretion, gene expression and apoptosis. Achieving dynamic control, i.e. by using an external stimulus, over the interactions between cells and artificial interfaces holds considerable promise in tissue engineering, medicine, cell biology and immunology. For example, improved spatial control over cell-surface interaction is potentially useful in the design of cell-based screening devices. Dynamic control over SAMs for cell adhesion provides an additional handle to direct and study the attachment of cells to surfaces, e.g., in studying cell spreading from a predetermined pattern in order to screen the cytotoxicity of drug candidates. However, 'reversible' control of cell adhesion onto substrates is an area that is still in its infancy. In this critical review recent developments in cell adhesion of mammalian cells to SAM-modified surfaces, the physical properties of which can be controlled by an external stimulus, e.g. by light, electrochemistry, etc., are discussed (118 references).

  3. Evolutionary Fingerprinting of Genes

    PubMed Central

    Kosakovsky Pond, Sergei L.; Scheffler, Konrad; Gravenor, Michael B.; Poon, Art F.Y.; Frost, Simon D.W.

    2010-01-01

    Over time, natural selection molds every gene into a unique mosaic of sites evolving rapidly or resisting change—an “evolutionary fingerprint” of the gene. Aspects of this evolutionary fingerprint, such as the site-specific ratio of nonsynonymous to synonymous substitution rates (dN/dS), are commonly used to identify genetic features of potential biological interest; however, no framework exists for comparing evolutionary fingerprints between genes. We hypothesize that protein-coding genes with similar protein structure and/or function tend to have similar evolutionary fingerprints and that comparing evolutionary fingerprints can be useful for discovering similarities between genes in a way that is analogous to, but independent of, discovery of similarity via sequence-based comparison tools such as Blast. To test this hypothesis, we develop a novel model of coding sequence evolution that uses a general bivariate discrete parameterization of the evolutionary rates. We show that this approach provides a better fit to the data using a smaller number of parameters than existing models. Next, we use the model to represent evolutionary fingerprints as probability distributions and present a methodology for comparing these distributions in a way that is robust against variations in data set size and divergence. Finally, using sequences of three rapidly evolving RNA viruses (HIV-1, hepatitis C virus, and influenza A virus), we demonstrate that genes within the same functional group tend to have similar evolutionary fingerprints. Our framework provides a sound statistical foundation for efficient inference and comparison of evolutionary rate patterns in arbitrary collections of gene alignments, clustering homologous and nonhomologous genes, and investigation of biological and functional correlates of evolutionary rates. PMID:19864470

  4. The Molecular Epidemiology and Evolutionary Dynamics of Influenza B Virus in Two Italian Regions during 2010-2015: The Experience of Sicily and Liguria.

    PubMed

    Tramuto, Fabio; Orsi, Andrea; Maida, Carmelo Massimo; Costantino, Claudio; Trucchi, Cecilia; Alicino, Cristiano; Vitale, Francesco; Ansaldi, Filippo

    2016-04-13

    Molecular epidemiology of influenza B virus remained poorly studied in Italy, despite representing a major contributor to seasonal epidemics. This study aimed to reconstruct the phylogenetic relationships and genetic diversity of the hemagglutinin gene sequences of 197 influenza B strains circulating in both Southern (Sicily) and Northern (Liguria) Italy between 2010 and 2015. Upper respiratory tract specimens of patients displaying symptoms of influenza-like illness were screened by real-time RT-PCR assay for the presence of influenza B virus. PCR-positive influenza B samples were further analyzed by sequencing. Neighbor-joining phylogenetic trees were constructed and the amino-acid alignments were analyzed. Phylogenetic analysis showed clusters in B/Victoria clade 1A/1B (n = 29, 14.7%), and B/Yamagata clades 2 (n = 112, 56.8%) and 3 (n = 56, 28.4%). Both influenza B lineages were found to co-circulate during the study period, although a lineage swap from B/Victoria to B/Yamagata occurred in Italy between January 2011 and January 2013. The most represented amino-acid substitutions were N116K in the 120-loop (83.9% of B/Yamagata clade 3 strains) and I146V in the 150-loop (89.6% of B/Victoria clade 1 strains). D197N in 190-helix was found in almost all viruses collected. Our findings provide further evidence to support the adoption of quadrivalent influenza vaccines in our country.

  5. Strain-Engineered Graphene Grown on Hexagonal Boron Nitride by Molecular Beam Epitaxy.

    PubMed

    Summerfield, Alex; Davies, Andrew; Cheng, Tin S; Korolkov, Vladimir V; Cho, YongJin; Mellor, Christopher J; Foxon, C Thomas; Khlobystov, Andrei N; Watanabe, Kenji; Taniguchi, Takashi; Eaves, Laurence; Novikov, Sergei V; Beton, Peter H

    2016-03-01

    Graphene grown by high temperature molecular beam epitaxy on hexagonal boron nitride (hBN) forms continuous domains with dimensions of order 20 μm, and exhibits moiré patterns with large periodicities, up to ~30 nm, indicating that the layers are highly strained. Topological defects in the moiré patterns are observed and attributed to the relaxation of graphene islands which nucleate at different sites and subsequently coalesce. In addition, cracks are formed leading to strain relaxation, highly anisotropic strain fields, and abrupt boundaries between regions with different moiré periods. These cracks can also be formed by modification of the layers with a local probe resulting in the contraction and physical displacement of graphene layers. The Raman spectra of regions with a large moiré period reveal split and shifted G and 2D peaks confirming the presence of strain. Our work demonstrates a new approach to the growth of epitaxial graphene and a means of generating and modifying strain in graphene.

  6. In silico molecular engineering for a targeted replacement in a tumor-homing peptide

    PubMed Central

    Zanuy, David; Flores-Ortega, Alejandra; Jiménez, Ana I.; Calaza, M. Isabel; Cativiela, Carlos; Nussinov, Ruth; Ruoslahti, Erkki; Alemán, Carlos

    2009-01-01

    A new amino acid has been designed as a replacement for arginine (Arg, R) to protect the tumor-homing pentapeptide CREKA from proteases. This amino acid, denoted (Pro)hArg, is characterized by a proline skeleton bearing a specifically oriented guanidinium side chain. This residue combines the ability of Pro to induce turn-like conformations with the Arg side-chain functionality. The conformational profile of the CREKA analogue incorporating this Arg substitute has been investigated by a combination of simulated annealing and Molecular Dynamics. Comparison of the results with those previously obtained for the natural CREKA shows that (Pro)hArg significantly reduces the conformational flexibility of the peptide. Although some changes are observed in the backbone···backbone and side chain···side chain interactions, the modified peptide exhibits a strong tendency to accommodate turn conformations centered at the (Pro)hArg residue and the overall shape of the molecule in the lowest energy conformations characterized for the natural and the modified peptide exhibit a high degree of similarity. In particular, the turn orients the backbone such that the Arg, Glu and Lys side chains face the same side of the molecule, which is considered essential for bioactivity. These results suggest that replacement of Arg by (Pro)hArg in CREKA may be useful in providing resistance against proteolytic enzymes while retaining conformational features which are essential for tumor-homing activity. PMID:19432404

  7. Plant immunity triggered by engineered in vivo release of oligogalacturonides, damage-associated molecular patterns

    PubMed Central

    Benedetti, Manuel; Pontiggia, Daniela; Raggi, Sara; Cheng, Zhenyu; Scaloni, Flavio; Ferrari, Simone; Ausubel, Frederick M.; Cervone, Felice; De Lorenzo, Giulia

    2015-01-01

    Oligogalacturonides (OGs) are fragments of pectin that activate plant innate immunity by functioning as damage-associated molecular patterns (DAMPs). We set out to test the hypothesis that OGs are generated in planta by partial inhibition of pathogen-encoded polygalacturonases (PGs). A gene encoding a fungal PG was fused with a gene encoding a plant polygalacturonase-inhibiting protein (PGIP) and expressed in transgenic Arabidopsis plants. We show that expression of the PGIP–PG chimera results in the in vivo production of OGs that can be detected by mass spectrometric analysis. Transgenic plants expressing the chimera under control of a pathogen-inducible promoter are more resistant to the phytopathogens Botrytis cinerea, Pectobacterium carotovorum, and Pseudomonas syringae. These data provide strong evidence for the hypothesis that OGs released in vivo act as a DAMP signal to trigger plant immunity and suggest that controlled release of these molecules upon infection may be a valuable tool to protect plants against infectious diseases. On the other hand, elevated levels of expression of the chimera cause the accumulation of salicylic acid, reduced growth, and eventually lead to plant death, consistent with the current notion that trade-off occurs between growth and defense. PMID:25870275

  8. Evolution on a volcanic conveyor belt: using phylogeographic reconstructions and K-Ar-based ages of the Hawaiian Islands to estimate molecular evolutionary rates.

    PubMed

    Fleischer, R C; McIntosh, C E; Tarr, C L

    1998-04-01

    The Hawaiian Islands form as the Pacific Plate moves over a 'hot spot' in the earth's mantle where magma extrudes through the crust to build huge shield volcanos. The islands subside and erode as the plate carries them to the north-west, eventually to become coral atolls and seamounts. Thus islands are ordered linearly by age, with the oldest islands in the north-west (e.g. Kauai at 5.1 Ma) and the youngest in the south-east (e.g. Hawaii at 0.43 Ma). K-Ar estimates of the date of an island's formation provide a maximum age for the taxa inhabiting the island. These ages can be used to calibrate rates of molecular change under the following assumptions: (i) K-Ar dates are accurate; (ii) tree topologies show that derivation of taxa parallels the timing of island formation; (iii) populations do not colonize long after island emergence; (iv) the coalescent point for sister taxa does not greatly predate the formation of the colonized younger island; (v) saturation effects and (vi) among-lineage rate variation are minimal or correctable; and (vii) unbiased standard errors of distances and regressions can be estimated from multiple pairwise comparisons. We use the approach to obtain overall corrected rate calibrations for: (i) part of the mitochondrial cytochrome b gene in Hawaiian drepanidines (0.016 sequence divergence/Myr); (ii) the Yp1 gene in Hawaiian Drosophila (0.019/Myr Kambysellis et al. 1995); and (iii) parts of the mitochondrial 12S and 16S rRNA and tRNAval in Laupala crickets (0.024-0.102/Myr, Shaw 1996). We discuss the reliability of the estimates given the assumptions (i-vii) above and contrast the results with previous calibrations of Adh in Hawaiian Drosophila and chloroplast DNA in lobeliods.

  9. Unifying evolutionary and network dynamics

    NASA Astrophysics Data System (ADS)

    Swarup, Samarth; Gasser, Les

    2007-06-01

    Many important real-world networks manifest small-world properties such as scale-free degree distributions, small diameters, and clustering. The most common model of growth for these networks is preferential attachment, where nodes acquire new links with probability proportional to the number of links they already have. We show that preferential attachment is a special case of the process of molecular evolution. We present a single-parameter model of network growth that unifies varieties of preferential attachment with the quasispecies equation (which models molecular evolution), and also with the Erdős-Rényi random graph model. We suggest some properties of evolutionary models that might be applied to the study of networks. We also derive the form of the degree distribution resulting from our algorithm, and we show through simulations that the process also models aspects of network growth. The unification allows mathematical machinery developed for evolutionary dynamics to be applied in the study of network dynamics, and vice versa.

  10. n-alkane profiles of engine lubricating oil and particulate matter by molecular sieve extraction.

    PubMed

    Caravaggio, Gianni A; Charland, Jean-Pierre; Macdonald, Penny; Graham, Lisa

    2007-05-15

    As part of the Canadian Atmospheric Fine Particle Research Program to obtain reliable primary source emission profiles, a molecular sieve method was developed to reliably determine n-alkanes in lubricating oils, vehicle emissions, and mobile source dominated ambient particulate matter (PM). This work was also initiated to better calculate carbon preference index values (CPI: the ratio of the sums of odd over even n-alkanes), a parameter for estimating anthropogenic versus biogenic contributions in PM. n-Alkanes in lubricating oil and mobile source dominated PM are difficult to identify and quantify by gas chromatography due to the presence of similar components that cannot be fully resolved. This results in a hump, the unresolved complex mixture (UCM) that leads to incorrect n-alkane concentrations and CPI values. The sieve method yielded better chromatography, unambiguous identification of n-alkanes and allowed examination of differences between n-alkane profiles in light (LDV) and heavy duty vehicle (HDV) lubricating oils that would have been otherwise difficult. These profile differences made it possible to relate the LDV profile to that of the PM samples collected during a tunnel study in August 2001 near Vancouver (British Columbia, Canada). The n-alkane PM data revealed that longer sampling times result in a negative artifact, i.e., the desorption of the more volatile n-alkanes from the filters. Furthermore, the sieve procedure yielded n-alkane data that allowed calculation of accurate CPI values for lubricating oils and PM samples. Finally, this method may prove helpful in estimating the respective diesel and gasoline contributions to ambient PM.

  11. Molluscan Evolutionary Genomics

    SciTech Connect

    Simison, W. Brian; Boore, Jeffrey L.

    2005-12-01

    In the last 20 years there have been dramatic advances in techniques of high-throughput DNA sequencing, most recently accelerated by the Human Genome Project, a program that has determined the three billion base pair code on which we are based. Now this tremendous capability is being directed at other genome targets that are being sampled across the broad range of life. This opens up opportunities as never before for evolutionary and organismal biologists to address questions of both processes and patterns of organismal change. We stand at the dawn of a new 'modern synthesis' period, paralleling that of the early 20th century when the fledgling field of genetics first identified the underlying basis for Darwin's theory. We must now unite the efforts of systematists, paleontologists, mathematicians, computer programmers, molecular biologists, developmental biologists, and others in the pursuit of discovering what genomics can teach us about the diversity of life. Genome-level sampling for mollusks to date has mostly been limited to mitochondrial genomes and it is likely that these will continue to provide the best targets for broad phylogenetic sampling in the near future. However, we are just beginning to see an inroad into complete nuclear genome sequencing, with several mollusks and other eutrochozoans having been selected for work about to begin. Here, we provide an overview of the state of molluscan mitochondrial genomics, highlight a few of the discoveries from this research, outline the promise of broadening this dataset, describe upcoming projects to sequence whole mollusk nuclear genomes, and challenge the community to prepare for making the best use of these data.

  12. Unraveling the evolutionary radiation of the thoracican barnacles using molecular and morphological evidence: a comparison of several divergence time estimation approaches.

    PubMed

    Pérez-Losada, Marcos; Høeg, Jens T; Crandall, Keith A

    2004-04-01

    The Thoracica includes the ordinary barnacles found along the sea shore and is the most diverse and well-studied superorder of Cirripedia. However, although the literature abounds with scenarios explaining the evolution of these barnacles, very few studies have attempted to test these hypotheses in a phylogenetic context. The few attempts at phylogenetic analyses have suffered from a lack of phylogenetic signal and small numbers of taxa. We collected DNA sequences from the nuclear 18S, 28S, and histone H3 genes and the mitochondrial 12S and 16S genes (4,871 bp total) and data for 37 adult and 53 larval morphological characters from 43 taxa representing all the extant thoracican suborders (except the monospecific Brachylepadomorpha). Four Rhizocephala (highly modified parasitic barnacles) taxa and a Rhizocephala + Acrothoracica (burrowing barnacles) hypothetical ancestor were used as the outgroup for the molecular and morphological analyses, respectively. We analyzed these data separately and combined using maximum likelihood (ML) under "hill-climbing" and genetic algorithm heuristic searches, maximum parsimony procedures, and Bayesian inference coupled with Markov chain Monte Carlo techniques under mixed and homogeneous models of nucleotide substitution. The resulting phylogenetic trees answered key questions in barnacle evolution. The four-plated Iblomorpha were shown as the most primitive thoracican, and the plateless Heteralepadomorpha were placed as the sister group of the Lepadomorpha. These relationships suggest for the first time in an invertebrate that exoskeleton biomineralization may have evolved from phosphatic to calcitic. Sessilia (nonpedunculate) barnacles were depicted as monophyletic and appear to have evolved from a stalked (pedunculate) multiplated (5+) scalpelloidlike ancestor rather than a five-plated lepadomorphan ancestor. The Balanomorpha (symmetric sessile barnacles) appear to have the following relationship: (Chthamaloidea

  13. Evolutionary Genomics of Life in (and from) the Sea

    SciTech Connect

    Boore, Jeffrey L.; Dehal, Paramvir; Fuerstenberg, Susan I.

    2006-01-09

    High throughput genome sequencing centers that were originally built for the Human Genome Project (Lander et al., 2001; Venter et al., 2001) have now become an engine for comparative genomics. The six largest centers alone are now producing over 150 billion nucleotides per year, more than 50 times the amount of DNA in the human genome, and nearly all of this is directed at projects that promise great insights into the pattern and processes of evolution. Unfortunately, this data is being produced at a pace far exceeding the capacity of the scientific community to provide insightful analysis, and few scientists with training and experience in evolutionary biology have played prominent roles to date. One of the consequences is that poor quality analyses are typical; for example, orthology among genes is generally determined by simple measures of sequence similarity, when this has been discredited by molecular evolutionary biologists decades ago. Here we discuss the how genomes are chosen for sequencing and how the scientific community can have input. We describe the PhIGs database and web tools (Dehal and Boore 2005a; http://PhIGs.org), which provide phylogenetic analysis of all gene families for all completely sequenced genomes and the associated 'Synteny Viewer', which allows comparisons of the relative positions of orthologous genes. This is the best tool available for inferring gene function across multiple genomes. We also describe how we have used the PhIGs methods with the whole genome sequences of a tunicate, fish, mouse, and human to conclusively demonstrate that two rounds of whole genome duplication occurred at the base of vertebrates (Dehal and Boore 2005b). This evidence is found in the large scale structure of the positions of paralogous genes that arose from duplications inferred by evolutionary analysis to have occurred at the base of vertebrates.

  14. Evolutionary tree reconstruction

    NASA Technical Reports Server (NTRS)

    Cheeseman, Peter; Kanefsky, Bob

    1990-01-01

    It is described how Minimum Description Length (MDL) can be applied to the problem of DNA and protein evolutionary tree reconstruction. If there is a set of mutations that transform a common ancestor into a set of the known sequences, and this description is shorter than the information to encode the known sequences directly, then strong evidence for an evolutionary relationship has been found. A heuristic algorithm is described that searches for the simplest tree (smallest MDL) that finds close to optimal trees on the test data. Various ways of extending the MDL theory to more complex evolutionary relationships are discussed.

  15. Topological insulator engineering of Bi2Se3 through molecular beam epitaxy

    NASA Astrophysics Data System (ADS)

    Oh, Seongshik

    2013-03-01

    Despite numerous reports proving the presence of the surface states on various topological insulator (TI) materials, all existing TI materials suffer from the bulk conductance problem at various levels. Therefore, achieving a truly insulating bulk state without degrading the surface state in their transport properties is one of the most important tasks of the TI materials research. In this talk, I will present how we address this problem by utilizing various molecular beam epitaxy (MBE) schemes with focus on Bi2Se3 family of materials. Considering that the bulk conductance problem originates mostly from the selenium vacancies in Bi2Se3, the typical MBE growth condition characterized by low growth temperature and high selenium vapor pressure is ideal for solving this bulk conductance problem. Moreover, thin films have another advantage of naturally reduced bulk effect due to the enhanced surface-to-bulk ratio. These intrinsic advantages of MBE-grown TI thin films recently led to a number of new findings. High quality Bi2Se3 thin films did show the expected dominant surface transport characters with negligible bulk conductance. However, the strong tendency toward downward band bending in undoped Bi2Se3 introduces trivial surface transport channels in addition to the topological surface states, leading to complications in the interpretations of transport results. Furthermore, even if reducing the thickness of TI samples helps reveal the surface transport channels by reducing the bulk contribution, it does not really solve the bulk conductance problem because regardless of how small it may be, the bulk state still remains metallic, shorting the top and bottom surfaces. According to the Mott-criterion of metal-insulator transition, in order to implement a truly insulating bulk state in the current generation TI materials, it is necessary to suppress the defect density below ~ 1014 cm-3, which might be fundamentally impossible considering the weak Van der Waals bonding

  16. Ancient hyaenas highlight the old problem of estimating evolutionary rates.

    PubMed

    Shapiro, Beth; Ho, Simon Y W

    2014-02-01

    Phylogenetic analyses of ancient DNA data can provide a timeline for evolutionary change even in the absence of fossils. The power to infer the evolutionary rate is, however, highly dependent on the number and age of samples, the information content of the sequence data and the demographic history of the sampled population. In this issue of Molecular Ecology, Sheng et al. (2014) analysed mitochondrial DNA sequences isolated from a combination of ancient and present-day hyaenas, including three Pleistocene samples from China. Using an evolutionary rate inferred from the ages of the ancient sequences, they recalibrated the timing of hyaena diversification and suggest a much more recent evolutionary history than was believed previously. Their results highlight the importance of accurately estimating the evolutionary rate when inferring timescales of geographical and evolutionary diversification.

  17. Evolutionary genetics of insect innate immunity

    PubMed Central

    2015-01-01

    Patterns of evolution in immune defense genes help to understand the evolutionary dynamics between hosts and pathogens. Multiple insect genomes have been sequenced, with many of them having annotated immune genes, which paves the way for a comparative genomic analysis of insect immunity. In this review, I summarize the current state of comparative and evolutionary genomics of insect innate immune defense. The focus is on the conserved and divergent components of immunity with an emphasis on gene family evolution and evolution at the sequence level; both population genetics and molecular evolution frameworks are considered. PMID:25750410

  18. Evolutionary explosions and the phylogenetic fuse.

    PubMed

    Cooper, A; Fortey, R

    1998-04-01

    A literal reading of the fossil record indicates that the early Cambrian (c. 545 million years ago) and early Tertiary (c. 65 million years ago) were characterized by enormously accelerated periods of morphological evolution marking the appearance of the animal phyla, and modern bird and placental mammal orders, respectively. Recently, the evidence for these evolutionary `explosions' has been questioned by cladistic and biogeographic studies which reveal that periods of diversification before these events are missing from the fossil record. Furthermore, molecular evidence indicates that prolonged periods of evolutionary innovation and cladogenesis lit the fuse long before the `explosions' apparent in the fossil record.

  19. Genomes, Phylogeny, and Evolutionary Systems Biology

    SciTech Connect

    Medina, Monica

    2005-03-25

    With the completion of the human genome and the growing number of diverse genomes being sequenced, a new age of evolutionary research is currently taking shape. The myriad of technological breakthroughs in biology that are leading to the unification of broad scientific fields such as molecular biology, biochemistry, physics, mathematics and computer science are now known as systems biology. Here I present an overview, with an emphasis on eukaryotes, of how the postgenomics era is adopting comparative approaches that go beyond comparisons among model organisms to shape the nascent field of evolutionary systems biology.

  20. Ultrahigh-throughput exfoliation of graphite into pristine 'single-layer' graphene using microwaves and molecularly engineered ionic liquids.

    PubMed

    Matsumoto, Michio; Saito, Yusuke; Park, Chiyoung; Fukushima, Takanori; Aida, Takuzo

    2015-09-01

    Graphene has shown much promise as an organic electronic material but, despite recent achievements in the production of few-layer graphene, the quantitative exfoliation of graphite into pristine single-layer graphene has remained one of the main challenges in developing practical devices. Recently, reduced graphene oxide has been recognized as a non-feasible alternative to graphene owing to variable defect types and levels, and attention is turning towards reliable methods for the high-throughput exfoliation of graphite. Here we report that microwave irradiation of graphite suspended in molecularly engineered oligomeric ionic liquids allows for ultrahigh-efficiency exfoliation (93% yield) with a high selectivity (95%) towards 'single-layer' graphene (that is, with thicknesses <1 nm) in a short processing time (30 minutes). The isolated graphene sheets show negligible structural deterioration. They are also readily redispersible in oligomeric ionic liquids up to ~100 mg ml(-1), and form physical gels in which an anisotropic orientation of graphene sheets, once induced by a magnetic field, is maintained.

  1. Eco-evolutionary feedbacks, adaptive dynamics and evolutionary rescue theory.

    PubMed

    Ferriere, Regis; Legendre, Stéphane

    2013-01-19

    Adaptive dynamics theory has been devised to account for feedbacks between ecological and evolutionary processes. Doing so opens new dimensions to and raises new challenges about evolutionary rescue. Adaptive dynamics theory predicts that successive trait substitutions driven by eco-evolutionary feedbacks can gradually erode population size or growth rate, thus potentially raising the extinction risk. Even a single trait substitution can suffice to degrade population viability drastically at once and cause 'evolutionary suicide'. In a changing environment, a population may track a viable evolutionary attractor that leads to evolutionary suicide, a phenomenon called 'evolutionary trapping'. Evolutionary trapping and suicide are commonly observed in adaptive dynamics models in which the smooth variation of traits causes catastrophic changes in ecological state. In the face of trapping and suicide, evolutionary rescue requires that the population overcome evolutionary threats generated by the adaptive process itself. Evolutionary repellors play an important role in determining how variation in environmental conditions correlates with the occurrence of evolutionary trapping and suicide, and what evolutionary pathways rescue may follow. In contrast with standard predictions of evolutionary rescue theory, low genetic variation may attenuate the threat of evolutionary suicide and small population sizes may facilitate escape from evolutionary traps.

  2. Evolutionary behavioral genetics

    PubMed Central

    Zietsch, Brendan P.; de Candia, Teresa R; Keller, Matthew C.

    2014-01-01

    We describe the scientific enterprise at the intersection of evolutionary psychology and behavioral genetics—a field that could be termed Evolutionary Behavioral Genetics—and how modern genetic data is revolutionizing our ability to test questions in this field. We first explain how genetically informative data and designs can be used to investigate questions about the evolution of human behavior, and describe some of the findings arising from these approaches. Second, we explain how evolutionary theory can be applied to the investigation of behavioral genetic variation. We give examples of how new data and methods provide insight into the genetic architecture of behavioral variation and what this tells us about the evolutionary processes that acted on the underlying causal genetic variants. PMID:25587556

  3. Evolutionary Mechanisms for Loneliness

    PubMed Central

    Cacioppo, John T.; Cacioppo, Stephanie; Boomsma, Dorret I.

    2013-01-01

    Robert Weiss (1973) conceptualized loneliness as perceived social isolation, which he described as a gnawing, chronic disease without redeeming features. On the scale of everyday life, it is understandable how something as personally aversive as loneliness could be regarded as a blight on human existence. However, evolutionary time and evolutionary forces operate at such a different scale of organization than we experience in everyday life that personal experience is not sufficient to understand the role of loneliness in human existence. Research over the past decade suggests a very different view of loneliness than suggested by personal experience, one in which loneliness serves a variety of adaptive functions in specific habitats. We review evidence on the heritability of loneliness and outline an evolutionary theory of loneliness, with an emphasis on its potential adaptive value in an evolutionary timescale. PMID:24067110

  4. Evolutionary mechanisms for loneliness.

    PubMed

    Cacioppo, John T; Cacioppo, Stephanie; Boomsma, Dorret I

    2014-01-01

    Robert Weiss (1973) conceptualised loneliness as perceived social isolation, which he described as a gnawing, chronic disease without redeeming features. On the scale of everyday life, it is understandable how something as personally aversive as loneliness could be regarded as a blight on human existence. However, evolutionary time and evolutionary forces operate at such a different scale of organisation than we experience in everyday life that personal experience is not sufficient to understand the role of loneliness in human existence. Research over the past decade suggests a very different view of loneliness than suggested by personal experience, one in which loneliness serves a variety of adaptive functions in specific habitats. We review evidence on the heritability of loneliness and outline an evolutionary theory of loneliness, with an emphasis on its potential adaptive value in an evolutionary timescale.

  5. Evolutionary software for autonomous path planning

    SciTech Connect

    Couture, S; Hage, M

    1999-02-10

    This research project demonstrated the effectiveness of using evolutionary software techniques in the development of path-planning algorithms and control programs for mobile vehicles in radioactive environments. The goal was to take maximum advantage of the programmer's intelligence by tasking the programmer with encoding the measures of success for a path-planning algorithm, rather than developing the path-planning algorithms themselves. Evolutionary software development techniques could then be used to develop algorithms most suitable to the particular environments of interest. The measures of path-planning success were encoded in the form of a fitness function for an evolutionary software development engine. The task for the evolutionary software development engine was to evaluate the performance of individual algorithms, select the best performers for the population based on the fitness function, and breed them to evolve the next generation of algorithms. The process continued for a set number of generations or until the algorithm converged to an optimal solution. The task environment was the navigation of a rover from an initial location to a goal, then to a processing point, in an environment containing physical and radioactive obstacles. Genetic algorithms were developed for a variety of environmental configurations. Algorithms were simple and non-robust strings of behaviors, but they could be evolved to be nearly optimal for a given environment. In addition, a genetic program was evolved in the form of a control algorithm that operates at every motion of the robot. Programs were more complex than algorithms and less optimal in a given environment. However, after training in a variety of different environments, they were more robust and could perform acceptably in environments they were not trained in. This paper describes the evolutionary software development engine and the performance of algorithms and programs evolved by it for the chosen task.

  6. Multiobjective Multifactorial Optimization in Evolutionary Multitasking.

    PubMed

    Gupta, Abhishek; Ong, Yew-Soon; Feng, Liang; Tan, Kay Chen

    2016-05-03

    In recent decades, the field of multiobjective optimization has attracted considerable interest among evolutionary computation researchers. One of the main features that makes evolutionary methods particularly appealing for multiobjective problems is the implicit parallelism offered by a population, which enables simultaneous convergence toward the entire Pareto front. While a plethora of related algorithms have been proposed till date, a common attribute among them is that they focus on efficiently solving only a single optimization problem at a time. Despite the known power of implicit parallelism, seldom has an attempt been made to multitask, i.e., to solve multiple optimization problems simultaneously. It is contended that the notion of evolutionary multitasking leads to the possibility of automated transfer of information across different optimization exercises that may share underlying similarities, thereby facilitating improved convergence characteristics. In particular, the potential for automated transfer is deemed invaluable from the standpoint of engineering design exercises where manual knowledge adaptation and reuse are routine. Accordingly, in this paper, we present a realization of the evolutionary multitasking paradigm within the domain of multiobjective optimization. The efficacy of the associated evolutionary algorithm is demonstrated on some benchmark test functions as well as on a real-world manufacturing process design problem from the composites industry.

  7. Synthesis of logic circuits with evolutionary algorithms

    SciTech Connect

    JONES,JAKE S.; DAVIDSON,GEORGE S.

    2000-01-26

    In the last decade there has been interest and research in the area of designing circuits with genetic algorithms, evolutionary algorithms, and genetic programming. However, the ability to design circuits of the size and complexity required by modern engineering design problems, simply by specifying required outputs for given inputs has as yet eluded researchers. This paper describes current research in the area of designing logic circuits using an evolutionary algorithm. The goal of the research is to improve the effectiveness of this method and make it a practical aid for design engineers. A novel method of implementing the algorithm is introduced, and results are presented for various multiprocessing systems. In addition to evolving standard arithmetic circuits, work in the area of evolving circuits that perform digital signal processing tasks is described.

  8. Transposable elements as a molecular evolutionary force

    NASA Technical Reports Server (NTRS)

    Fedoroff, N. V.

    1999-01-01

    This essay addresses the paradoxes of the complex and highly redundant genomes. The central theses developed are that: (1) the distinctive feature of complex genomes is the existence of epigenetic mechanisms that permit extremely high levels of both tandem and dispersed redundancy; (2) the special contribution of transposable elements is to modularize the genome; and (3) the labilizing forces of recombination and transposition are just barely contained, giving a dynamic genetic system of ever increasing complexity that verges on the chaotic.

  9. Michaelis-Menten at 100 and allosterism at 50: driving molecular motors in a hailstorm with noisy ATPase engines and allosteric transmission.

    PubMed

    Chowdhury, Debashish

    2014-01-01

    Cytoskeletal motor proteins move on filamentous tracks by converting input chemical energy that they derive by catalyzing the hydrolysis of ATP. The ATPase site is the analogue of an engine and hydrolysis of ATP is the analogue of burning of chemical fuel. Moreover, the functional role of a segment of the motor is analogous to that of the transmission system of an automobile, which consists of a shaft, gear, clutch, etc. The operation of the engine is intrinsically 'noisy' and the motor faces a molecular 'hailstorm' in the aqueous medium. In this commemorative review, we celebrate the centenary of Michaelis and Menten's landmark paper of 1913 and the golden jubilee of Monod and colleagues classic paper of 1963 by highlighting their relevance with respect to explaining the operational mechanisms of the engine and the transmission system, respectively, of cytoskeletal motors.

  10. A Powerful Molecular Engineering Tool Provided Efficient Chlamydomonas Mutants as Bio-Sensing Elements for Herbicides Detection

    PubMed Central

    Lambreva, Maya D.; Giardi, Maria Teresa; Rambaldi, Irene; Antonacci, Amina; Pastorelli, Sandro; Bertalan, Ivo; Husu, Ivan; Johanningmeier, Udo; Rea, Giuseppina

    2013-01-01

    This study was prompted by increasing concerns about ecological damage and human health threats derived by persistent contamination of water and soil with herbicides, and emerging of bio-sensing technology as powerful, fast and efficient tool for the identification of such hazards. This work is aimed at overcoming principal limitations negatively affecting the whole-cell-based biosensors performance due to inadequate stability and sensitivity of the bio-recognition element. The novel bio-sensing elements for the detection of herbicides were generated exploiting the power of molecular engineering in order to improve the performance of photosynthetic complexes. The new phenotypes were produced by an in vitro directed evolution strategy targeted at the photosystem II (PSII) D1 protein of Chlamydomonas reinhardtii, using exposures to radical-generating ionizing radiation as selection pressure. These tools proved successful to identify D1 mutations conferring enhanced stability, tolerance to free-radical-associated stress and competence for herbicide perception. Long-term stability tests of PSII performance revealed the mutants capability to deal with oxidative stress-related conditions. Furthermore, dose-response experiments indicated the strains having increased sensitivity or resistance to triazine and urea type herbicides with I50 values ranging from 6×10−8 M to 2×10−6 M. Besides stressing the relevance of several amino acids for PSII photochemistry and herbicide sensing, the possibility to improve the specificity of whole-cell-based biosensors, via coupling herbicide-sensitive with herbicide-resistant strains, was verified. PMID:23613953

  11. Systematic molecular engineering of Zn-ketoiminates for application as precursors in atomic layer depositions of zinc oxide.

    PubMed

    O' Donoghue, Richard; Peeters, Daniel; Rogalla, Detlef; Becker, Hans-Werner; Rechmann, Julian; Henke, Sebastian; Winter, Manuela; Devi, Anjana

    2016-12-21

    Molecular engineering of seven closely related zinc ketoiminates, namely, [Zn(dapki)2], [Zn(daeki)2], [Zn(epki)2], [Zn(eeki)2], [Zn(mpki)2], [Zn(meki)2], and [Zn((n)pki)2], leads to the optimisation of precursor thermal properties in terms of volatilisation rate, onset of volatilisation, reactivity and thermal stability. The influence of functional groups at the imine side chain of the ligands on the precursor properties is studied with regard to their viability as precursors for atomic layer deposition (ALD) of ZnO. The synthesis of [Zn(eeki)2], [Zn(epki)2] and [Zn(dapki)2] and the crystal structures of [Zn(mpki)2], [Zn(eeki)2], [Zn(dapki)2] and [Zn((n)pki)2] are presented. From the investigation of the physico-chemical characteristics, it was inferred that all compounds are monomeric, volatile and exhibit high thermal stability, all of which make them promising ALD precursors. Compound [Zn(eeki)2] is in terms of thermal properties the most promising Zn-ketoiminate. It is reactive towards water, possesses a melting point of 39 °C, is stable up to 24 days at 220 °C and has an extended volatilisation rate compared to the literature known Zn-ketoiminates. It demonstrated self-saturated, water assisted growth of zinc oxide (ZnO) with growth rates in the order of 1.3 Å per cycle. Moreover, it displayed a broad temperature window from TDep = 175-300 °C and is the first report of a stable high temperature (>200 °C) ALD process for ZnO returning highly promising growth rates.

  12. Electrochemical reverse engineering: A systems-level tool to probe the redox-based molecular communication of biology.

    PubMed

    Li, Jinyang; Liu, Yi; Kim, Eunkyoung; March, John C; Bentley, William E; Payne, Gregory F

    2016-12-29

    The intestine is the site of digestion and forms a critical interface between the host and the outside world. This interface is composed of host epithelium and a complex microbiota which is "connected" through an extensive web of chemical and biological interactions that determine the balance between health and disease for the host. This biology and the associated chemical dialogues occur within a context of a steep oxygen gradient that provides the driving force for a variety of reduction and oxidation (redox) reactions. While some redox couples (e.g., catecholics) can spontaneously exchange electrons, many others are kinetically "insulated" (e.g., biothiols) allowing the biology to set and control their redox states far from equilibrium. It is well known that within cells, such non-equilibrated redox couples are poised to transfer electrons to perform reactions essential to immune defense (e.g., transfer from NADH to O2 for reactive oxygen species, ROS, generation) and protection from such oxidative stresses (e.g., glutathione-based reduction of ROS). More recently, it has been recognized that some of these redox-active species (e.g., H2O2) cross membranes and diffuse into the extracellular environment including lumen to transmit redox information that is received by atomically-specific receptors (e.g., cysteine-based sulfur switches) that regulate biological functions. Thus, redox has emerged as an important modality in the chemical signaling that occurs in the intestine and there have been emerging efforts to develop the experimental tools needed to probe this modality. We suggest that electrochemistry provides a unique tool to experimentally probe redox interactions at a systems level. Importantly, electrochemistry offers the potential to enlist the extensive theories established in signal processing in an effort to "reverse engineer" the molecular communication occurring in this complex biological system. Here, we review our efforts to develop this

  13. Applying Evolutionary Anthropology

    PubMed Central

    Gibson, Mhairi A; Lawson, David W

    2015-01-01

    Evolutionary anthropology provides a powerful theoretical framework for understanding how both current environments and legacies of past selection shape human behavioral diversity. This integrative and pluralistic field, combining ethnographic, demographic, and sociological methods, has provided new insights into the ultimate forces and proximate pathways that guide human adaptation and variation. Here, we present the argument that evolutionary anthropological studies of human behavior also hold great, largely untapped, potential to guide the design, implementation, and evaluation of social and public health policy. Focusing on the key anthropological themes of reproduction, production, and distribution we highlight classic and recent research demonstrating the value of an evolutionary perspective to improving human well-being. The challenge now comes in transforming relevance into action and, for that, evolutionary behavioral anthropologists will need to forge deeper connections with other applied social scientists and policy-makers. We are hopeful that these developments are underway and that, with the current tide of enthusiasm for evidence-based approaches to policy, evolutionary anthropology is well positioned to make a strong contribution. PMID:25684561

  14. Paleoanthropology and evolutionary theory.

    PubMed

    Tattersall, Ian

    2012-01-01

    Paleoanthropologists of the first half of the twentieth century were little concerned either with evolutionary theory or with the technicalities and broader implications of zoological nomenclature. In consequence, the paleoanthropological literature of the period consisted largely of a series of descriptions accompanied by authoritative pronouncements, together with a huge excess of hominid genera and species. Given the intellectual flimsiness of the resulting paleoanthropological framework, it is hardly surprising that in 1950 the ornithologist Ernst Mayr met little resistance when he urged the new postwar generation of paleoanthropologists to accept not only the elegant reductionism of the Evolutionary Synthesis but a vast oversimplification of hominid phylogenetic history and nomenclature. Indeed, the impact of Mayr's onslaught was so great that even when developments in evolutionary biology during the last quarter of the century brought other paleontologists to the realization that much more has been involved in evolutionary histories than the simple action of natural selection within gradually transforming lineages, paleoanthropologists proved highly reluctant to follow. Even today, paleoanthropologists are struggling to reconcile an intuitive realization that the burgeoning hominid fossil record harbors a substantial diversity of species (bringing hominid evolutionary patterns into line with that of other successful mammalian families), with the desire to cram a huge variety of morphologies into an unrealistically minimalist systematic framework. As long as this theoretical ambivalence persists, our perception of events in hominid phylogeny will continue to be distorted.

  15. Applying evolutionary anthropology.

    PubMed

    Gibson, Mhairi A; Lawson, David W

    2015-01-01

    Evolutionary anthropology provides a powerful theoretical framework for understanding how both current environments and legacies of past selection shape human behavioral diversity. This integrative and pluralistic field, combining ethnographic, demographic, and sociological methods, has provided new insights into the ultimate forces and proximate pathways that guide human adaptation and variation. Here, we present the argument that evolutionary anthropological studies of human behavior also hold great, largely untapped, potential to guide the design, implementation, and evaluation of social and public health policy. Focusing on the key anthropological themes of reproduction, production, and distribution we highlight classic and recent research demonstrating the value of an evolutionary perspective to improving human well-being. The challenge now comes in transforming relevance into action and, for that, evolutionary behavioral anthropologists will need to forge deeper connections with other applied social scientists and policy-makers. We are hopeful that these developments are underway and that, with the current tide of enthusiasm for evidence-based approaches to policy, evolutionary anthropology is well positioned to make a strong contribution.

  16. Genomic clocks and evolutionary timescales

    NASA Technical Reports Server (NTRS)

    Blair Hedges, S.; Kumar, Sudhir

    2003-01-01

    For decades, molecular clocks have helped to illuminate the evolutionary timescale of life, but now genomic data pose a challenge for time estimation methods. It is unclear how to integrate data from many genes, each potentially evolving under a different model of substitution and at a different rate. Current methods can be grouped by the way the data are handled (genes considered separately or combined into a 'supergene') and the way gene-specific rate models are applied (global versus local clock). There are advantages and disadvantages to each of these approaches, and the optimal method has not yet emerged. Fortunately, time estimates inferred using many genes or proteins have greater precision and appear to be robust to different approaches.

  17. Ecological and evolutionary traps

    USGS Publications Warehouse

    Schlaepfer, Martin A.; Runge, M.C.; Sherman, P.W.

    2002-01-01

    Organisms often rely on environmental cues to make behavioral and life-history decisions. However, in environments that have been altered suddenly by humans, formerly reliable cues might no longer be associated with adaptive outcomes. In such cases, organisms can become 'trapped' by their evolutionary responses to the cues and experience reduced survival or reproduction. Ecological traps occur when organisms make poor habitat choices based on cues that correlated formerly with habitat quality. Ecological traps are part of a broader phenomenon, evolutionary traps, involving a dissociation between cues that organisms use to make any behavioral or life-history decision and outcomes normally associated with that decision. A trap can lead to extinction if a population falls below a critical size threshold before adaptation to the novel environment occurs. Conservation and management protocols must be designed in light of, rather than in spite of, the behavioral mechanisms and evolutionary history of populations and species to avoid 'trapping' them.

  18. Human nutrition: evolutionary perspectives.

    PubMed

    Barnicot, N A

    2005-01-01

    In recent decades, much new evidence relating to the ape forerunners of modern humans has come to hand and diet appears to be an important factor. At some stage, there must have been a transition from a largely vegetarian ape diet to a modern human hunting economy providing significant amounts of meat. On an even longer evolutionary time scale the change was more complex. The mechanisms of evolutionary change are now better understood than they were in Darwin's time, thanks largely to great advances in genetics, both experimental and theoretical. It is virtually certain that diet, as a major component of the human environment, must have exerted evolutionary effects, but researchers still have little good evidence.

  19. Evolutionary Debunking Arguments.

    PubMed

    Kahane, Guy

    2011-03-01

    Evolutionary debunking arguments (EDAs) are arguments that appeal to the evolutionary origins of evaluative beliefs to undermine their justification. This paper aims to clarify the premises and presuppositions of EDAs-a form of argument that is increasingly put to use in normative ethics. I argue that such arguments face serious obstacles. It is often overlooked, for example, that they presuppose the truth of metaethical objectivism. More importantly, even if objectivism is assumed, the use of EDAs in normative ethics is incompatible with a parallel and more sweeping global evolutionary debunking argument that has been discussed in recent metaethics. After examining several ways of responding to this global debunking argument, I end by arguing that even if we could resist it, this would still not rehabilitate the current targeted use of EDAs in normative ethics given that, if EDAs work at all, they will in any case lead to a truly radical revision of our evaluative outlook.

  20. Evolutionary Debunking Arguments

    PubMed Central

    Kahane, Guy

    2011-01-01

    Evolutionary debunking arguments (EDAs) are arguments that appeal to the evolutionary origins of evaluative beliefs to undermine their justification. This paper aims to clarify the premises and presuppositions of EDAs—a form of argument that is increasingly put to use in normative ethics. I argue that such arguments face serious obstacles. It is often overlooked, for example, that they presuppose the truth of metaethical objectivism. More importantly, even if objectivism is assumed, the use of EDAs in normative ethics is incompatible with a parallel and more sweeping global evolutionary debunking argument that has been discussed in recent metaethics. After examining several ways of responding to this global debunking argument, I end by arguing that even if we could resist it, this would still not rehabilitate the current targeted use of EDAs in normative ethics given that, if EDAs work at all, they will in any case lead to a truly radical revision of our evaluative outlook. PMID:21949447

  1. Evolutionary genomics of animal personality.

    PubMed

    van Oers, Kees; Mueller, Jakob C

    2010-12-27

    Research on animal personality can be approached from both a phenotypic and a genetic perspective. While using a phenotypic approach one can measure present selection on personality traits and their combinations. However, this approach cannot reconstruct the historical trajectory that was taken by evolution. Therefore, it is essential for our understanding of the causes and consequences of personality diversity to link phenotypic variation in personality traits with polymorphisms in genomic regions that code for this trait variation. Identifying genes or genome regions that underlie personality traits will open exciting possibilities to study natural selection at the molecular level, gene-gene and gene-environment interactions, pleiotropic effects and how gene expression shapes personality phenotypes. In this paper, we will discuss how genome information revealed by already established approaches and some more recent techniques such as high-throughput sequencing of genomic regions in a large number of individuals can be used to infer micro-evolutionary processes, historical selection and finally the maintenance of personality trait variation. We will do this by reviewing recent advances in molecular genetics of animal personality, but will also use advanced human personality studies as case studies of how molecular information may be used in animal personality research in the near future.

  2. Investigating human evolutionary history

    PubMed Central

    WOOD, BERNARD

    2000-01-01

    We rely on fossils for the interpretation of more than 95% of our evolutionary history. Fieldwork resulting in the recovery of fresh fossil evidence is an important component of reconstructing human evolutionary history, but advances can also be made by extracting additional evidence for the existing fossil record, and by improving the methods used to interpret the fossil evidence. This review shows how information from imaging and dental microstructure has contributed to improving our understanding of the hominin fossil record. It also surveys recent advances in the use of the fossil record for phylogenetic inference. PMID:10999269

  3. Evolutionary Design in Art

    NASA Astrophysics Data System (ADS)

    McCormack, Jon

    Evolution is one of the most interesting and creative processes we currently understand, so it should come as no surprise that artists and designers are embracing the use of evolution in problems of artistic creativity. The material in this section illustrates the diversity of approaches being used by artists and designers in relation to evolution at the boundary of art and science. While conceptualising human creativity as an evolutionary process in itself may be controversial, what is clear is that evolutionary processes can be used to complement, even enhance human creativity, as the chapters in this section aptly demonstrate.

  4. The fastest evolutionary trajectory

    PubMed Central

    Traulsen, Arne; Iwasa, Yoh; Nowak, Martin A.

    2008-01-01

    Given two mutants, A and B, separated by n mutational steps, what is the evolutionary trajectory which allows a homogeneous population of A to reach B in the shortest time? We show that the optimum evolutionary trajectory (fitness landscape) has the property that the relative fitness increase between any two consecutive steps is constant. Hence, the optimum fitness landscape between A and B is given by an exponential function. Our result is precise for small mutation rates and excluding back mutations. We discuss deviations for large mutation rates and including back mutations. For very large mutation rates, the optimum fitness landscape is flat and has a single peak at type B. PMID:17900629

  5. A framework for evolutionary systems biology

    PubMed Central

    Loewe, Laurence

    2009-01-01

    Background Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects. Results Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions in silico. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism. Conclusion EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications. PMID:19239699

  6. Forming and maintaining a heat engine for quantum biology.

    PubMed

    Matsuno, Koichiro

    2006-07-01

    Chemical reactions upholding biological functions and structures are the process of measurement taking place among the participating chemical reactants. Chemical reactions occurring in thermal environments are either endothermic or exothermic. In particular, exothermic reactions that can live with temperature gradients of exogenous origin could potentially be competent enough to synthesize a robust quantum as a heat engine. Molecular organizations leading to the origin of the phenomenon of life might have been associated with the emergence of a quantum coherence embodied in a robust heat engine feeding on quantum decoherence. Evolutionary maintenance of a robust quantum heat engine, once appeared, can further be empowered by the build-up of temperature gradients of endogenous origin. Biology enriches the repertoire of quantum mechanics so as to include a robust heat engine as a legitimate member of a quantum in addition to the already established member of a quantum including an atom, molecule, and macromolecule.

  7. Evolutionary Developmental Psychology.

    ERIC Educational Resources Information Center

    Geary, David C.; Bjorklund, David F.

    2000-01-01

    Describes evolutionary developmental psychology as the study of the genetic and ecological mechanisms that govern the development of social and cognitive competencies common to all human beings and the epigenetic (gene-environment interactions) processes that adapt these competencies to local conditions. Outlines basic assumptions and domains of…

  8. Evolutionary developmental psychology.

    PubMed

    King, Ashley C; Bjorklund, David F

    2010-02-01

    The field of evolutionary developmental psychology can potentially broaden the horizons of mainstream evolutionary psychology by combining the principles of Darwinian evolution by natural selection with the study of human development, focusing on the epigenetic effects that occur between humans and their environment in a way that attempts to explain how evolved psychological mechanisms become expressed in the phenotypes of adults. An evolutionary developmental perspective includes an appreciation of comparative research and we, among others, argue that contrasting the cognition of humans with that of nonhuman primates can provide a framework with which to understand how human cognitive abilities and intelligence evolved. Furthermore, we argue that several aspects of childhood (e.g., play and immature cognition) serve both as deferred adaptations as well as imparting immediate benefits. Intense selection pressure was surely exerted on childhood over human evolutionary history and, as a result, neglecting to consider the early developmental period of children when studying their later adulthood produces an incomplete picture of the evolved adaptations expressed through human behavior and cognition.

  9. Learning: An Evolutionary Analysis

    ERIC Educational Resources Information Center

    Swann, Joanna

    2009-01-01

    This paper draws on the philosophy of Karl Popper to present a descriptive evolutionary epistemology that offers philosophical solutions to the following related problems: "What happens when learning takes place?" and "What happens in human learning?" It provides a detailed analysis of how learning takes place without any direct transfer of…

  10. Evolutionary Theory under Fire.

    ERIC Educational Resources Information Center

    Lewin, Roger

    1980-01-01

    Summarizes events of a conference on evolutionary biology in Chicago entitled: "Macroevolution." Reviews the theory of modern synthesis, a term used to explain Darwinism in terms of population biology and genetics. Issues presented at the conference are discussed in detail. (CS)

  11. Evolutionary Theories of Detection

    SciTech Connect

    Fitch, J P

    2005-04-29

    Current, mid-term and long range technologies for detection of pathogens and toxins are briefly described in the context of performance metrics and operational scenarios. Predictive (evolutionary) and speculative (revolutionary) assessments are given with trade-offs identified, where possible, among competing performance goals.

  12. Evolutionary pattern search algorithms

    SciTech Connect

    Hart, W.E.

    1995-09-19

    This paper defines a class of evolutionary algorithms called evolutionary pattern search algorithms (EPSAs) and analyzes their convergence properties. This class of algorithms is closely related to evolutionary programming, evolutionary strategie and real-coded genetic algorithms. EPSAs are self-adapting systems that modify the step size of the mutation operator in response to the success of previous optimization steps. The rule used to adapt the step size can be used to provide a stationary point convergence theory for EPSAs on any continuous function. This convergence theory is based on an extension of the convergence theory for generalized pattern search methods. An experimental analysis of the performance of EPSAs demonstrates that these algorithms can perform a level of global search that is comparable to that of canonical EAs. We also describe a stopping rule for EPSAs, which reliably terminated near stationary points in our experiments. This is the first stopping rule for any class of EAs that can terminate at a given distance from stationary points.

  13. Molecular Engineering of Fungal GH5 and GH26 Beta-(1,4)-Mannanases toward Improvement of Enzyme Activity

    PubMed Central

    Couturier, Marie; Féliu, Julia; Bozonnet, Sophie; Roussel, Alain; Berrin, Jean-Guy

    2013-01-01

    Microbial mannanases are biotechnologically important enzymes since they target the hydrolysis of hemicellulosic polysaccharides of softwood biomass into simple molecules like manno-oligosaccharides and mannose. In this study, we have implemented a strategy of molecular engineering in the yeast Yarrowia lipolytica to improve the specific activity of two fungal endo-mannanases, PaMan5A and PaMan26A, which belong to the glycoside hydrolase (GH) families GH5 and GH26, respectively. Following random mutagenesis and two steps of high-throughput enzymatic screening, we identified several PaMan5A and PaMan26A mutants that displayed improved kinetic constants for the hydrolysis of galactomannan. Examination of the three-dimensional structures of PaMan5A and PaMan26A revealed which of the mutated residues are potentially important for enzyme function. Among them, the PaMan5A-G311S single mutant, which displayed an impressive 8.2-fold increase in kcat/KM due to a significant decrease of KM, is located within the core of the enzyme. The PaMan5A-K139R/Y223H double mutant revealed modification of hydrolysis products probably in relation to an amino-acid substitution located nearby one of the positive subsites. The PaMan26A-P140L/D416G double mutant yielded a 30% increase in kcat/KM compared to the parental enzyme. It displayed a mutation in the linker region (P140L) that may confer more flexibility to the linker and another mutation (D416G) located at the entrance of the catalytic cleft that may promote the entrance of the substrate into the active site. Taken together, these results show that the directed evolution strategy implemented in this study was very pertinent since a straightforward round of random mutagenesis yielded significantly improved variants, in terms of catalytic efiiciency (kcat/KM). PMID:24278180

  14. Genomic basis of evolutionary change: evolving immunity

    PubMed Central

    Wertheim, Bregje

    2015-01-01

    Complex traits are manifestations of intricate gene interaction networks. Evolution of complex traits revolves around the genetic variation in such networks. Genomics has increased our ability to investigate the complex gene interaction networks, and characterize the extent of genetic variation in these networks. Immunity is a complex trait, for which the ecological drivers and molecular networks are fairly well understood in Drosophila. By characterizing the natural variation in immunity, and mapping how the genome changes during the evolution of immunity in Drosophila, we can integrate our knowledge on the complex genetic architecture of traits and the molecular basis of evolutionary processes. PMID:26150830

  15. Using Carbon-14 Isotope Tracing to Investigate Molecular Structure Effects of the Oxygenate Dibutyl Maleate on Soot Emissions from a DI Diesel Engine

    SciTech Connect

    Buchholz, B A; Mueller, C J; Upatnieks, A; Martin, G C; Pitz, W J; Westbrook, C K

    2004-01-07

    The effect of oxygenate molecular structure on soot emissions from a DI diesel engine was examined using carbon-14 ({sup 14}C) isotope tracing. Carbon atoms in three distinct chemical structures within the diesel oxygenate dibutyl maleate (DBM) were labeled with {sup 14}C. The {sup 14}C from the labeled DBM was then detected in engine-out particulate matter (PM), in-cylinder deposits, and CO{sub 2} emissions using accelerator mass spectrometry (AMS). The results indicate that molecular structure plays an important role in determining whether a specific carbon atom either does or does not form soot. Chemical-kinetic modeling results indicate that structures that produce CO{sub 2} directly from the fuel are less effective at reducing soot than structures that produce CO before producing CO{sub 2}. Because they can follow individual carbon atoms through a real combustion process, {sup 14}C isotope tracing studies help strengthen the connection between actual engine emissions and chemical-kinetic models of combustion and soot formation/oxidation processes.

  16. Combination of phenylpyruvic acid (PPA) pathway engineering and molecular engineering of L-amino acid deaminase improves PPA production with an Escherichia coli whole-cell biocatalyst.

    PubMed

    Hou, Ying; Hossain, Gazi Sakir; Li, Jianghua; Shin, Hyun-Dong; Du, Guocheng; Liu, Long

    2016-03-01

    In our previous study, we produced phenylpyruvic acid (PPA) in one step from L-phenylalanine by using an Escherichia coli whole-cell biocatalyst expressing an L-amino acid deaminase (L-AAD) from Proteus mirabilis KCTC2566. However, the PPA titer was low due to the degradation of PPA and low substrate specificity of L-AAD. In this study, metabolic engineering of the L-phenylalanine degradation pathway in E. coli and protein engineering of L-AAD from P. mirabilis were performed to improve the PPA titer. First, three aminotransferase genes were knocked out to block PPA degradation, which increased the PPA titer from 3.3 ± 0.2 to 3.9 ± 0.1 g/L and the substrate conversion ratio to 97.5 %. Next, L-AAD was engineered via error-prone polymerase chain reaction, followed by site-saturation mutation to improve its catalytic performance. The triple mutant D165K/F263M/L336M produced the highest PPA titer of 10.0 ± 0.4 g/L, with a substrate conversion ratio of 100 %, which was 3.0 times that of wild-type L-AAD. Comparative kinetics analysis showed that compared with wild-type L-AAD, the triple mutant had higher substrate-binding affinity and catalytic efficiency. Finally, an optimal fed-batch biotransformation process was developed to achieve a maximal PPA titer of 21 ± 1.8 g/L within 8 h. This study developed a robust whole-cell E. coli biocatalyst for PPA production by integrating metabolic and protein engineering, strategies that may be useful for the construction of other biotransformation biocatalysts.

  17. Automated Antenna Design with Evolutionary Algorithms

    NASA Technical Reports Server (NTRS)

    Hornby, Gregory S.; Globus, Al; Linden, Derek S.; Lohn, Jason D.

    2006-01-01

    Current methods of designing and optimizing antennas by hand are time and labor intensive, and limit complexity. Evolutionary design techniques can overcome these limitations by searching the design space and automatically finding effective solutions. In recent years, evolutionary algorithms have shown great promise in finding practical solutions in large, poorly understood design spaces. In particular, spacecraft antenna design has proven tractable to evolutionary design techniques. Researchers have been investigating evolutionary antenna design and optimization since the early 1990s, and the field has grown in recent years as computer speed has increased and electromagnetic simulators have improved. Two requirements-compliant antennas, one for ST5 and another for TDRS-C, have been automatically designed by evolutionary algorithms. The ST5 antenna is slated to fly this year, and a TDRS-C phased array element has been fabricated and tested. Such automated evolutionary design is enabled by medium-to-high quality simulators and fast modern computers to evaluate computer-generated designs. Evolutionary algorithms automate cut-and-try engineering, substituting automated search though millions of potential designs for intelligent search by engineers through a much smaller number of designs. For evolutionary design, the engineer chooses the evolutionary technique, parameters and the basic form of the antenna, e.g., single wire for ST5 and crossed-element Yagi for TDRS-C. Evolutionary algorithms then search for optimal configurations in the space defined by the engineer. NASA's Space Technology 5 (ST5) mission will launch three small spacecraft to test innovative concepts and technologies. Advanced evolutionary algorithms were used to automatically design antennas for ST5. The combination of wide beamwidth for a circularly-polarized wave and wide impedance bandwidth made for a challenging antenna design problem. From past experience in designing wire antennas, we chose to

  18. Product Mix Selection Using AN Evolutionary Technique

    NASA Astrophysics Data System (ADS)

    Tsoulos, Ioannis G.; Vasant, Pandian

    2009-08-01

    This paper proposes an evolutionary technique for the solution of a real—life industrial problem and particular for the product mix selection problem. The evolutionary technique is a combination of a genetic algorithm that preserves the feasibility of the trial solutions with penalties and some local optimization method. The goal of this paper has been achieved in finding the best near optimal solution for the profit fitness function respect to vagueness factor and level of satisfaction. The findings of the profit values will be very useful for the decision makers in the industrial engineering sector for the implementation purpose. It's possible to improve the solutions obtained in this study by employing other meta-heuristic methods such as simulated annealing, tabu Search, ant colony optimization, particle swarm optimization and artificial immune systems.

  19. Evolutionary lunar transportation family

    NASA Technical Reports Server (NTRS)

    Capps, Stephen

    1992-01-01

    The development of an evolutionary lunar transportation family (LTF) that can accommodate evolving human exploration goals is discussed. An evolutionary system is aimed at minimizing program costs while preserving programmatic versatility. Technical requirements that affect the design strategy for LTF include aerobraking technology and packaging constraints; mixed, unsymmetrical payload manifests; crew and payload exchange operations; crew and cargo off-loading on the lunar surface; and cryogenic lunar transfer and storage. It is concluded that the LTF is capable of meeting exploration goals, which include the provision for a significant early manned lunar surface science and exploration capability, the avoidance or reduction of some major operational and infrastructure requirements, and the incorporation of common vehicle designs and existing/near-term technology.

  20. Evolutionary Determinants of Cancer

    PubMed Central

    Greaves, Mel

    2015-01-01

    ‘Nothing in biology makes sense except in the light of evolution’ Th. Dobzhansky, 1973 Our understanding of cancer is being transformed by exploring clonal diversity, drug resistance and causation within an evolutionary framework. The therapeutic resilience of advanced cancer is a consequence of its character as complex, dynamic and adaptive ecosystem engendering robustness, underpinned by genetic diversity and epigenetic plasticity. The risk of mutation-driven escape by self-renewing cells is intrinsic to multicellularity but is countered by multiple restraints facilitating increasing complexity and longevity of species. But our own has disrupted this historical narrative by rapidly escalating intrinsic risk. Evolutionary principles illuminate these challenges and provide new avenues to explore for more effective control. PMID:26193902

  1. Evolutionary primacy of sodium bioenergetics

    PubMed Central

    Mulkidjanian, Armen Y; Galperin, Michael Y; Makarova, Kira S; Wolf, Yuri I; Koonin, Eugene V

    2008-01-01

    Background The F- and V-type ATPases are rotary molecular machines that couple translocation of protons or sodium ions across the membrane to the synthesis or hydrolysis of ATP. Both the F-type (found in most bacteria and eukaryotic mitochondria and chloroplasts) and V-type (found in archaea, some bacteria, and eukaryotic vacuoles) ATPases can translocate either protons or sodium ions. The prevalent proton-dependent ATPases are generally viewed as the primary form of the enzyme whereas the sodium-translocating ATPases of some prokaryotes are usually construed as an exotic adaptation to survival in extreme environments. Results We combine structural and phylogenetic analyses to clarify the evolutionary relation between the proton- and sodium-translocating ATPases. A comparison of the structures of the membrane-embedded oligomeric proteolipid rings of sodium-dependent F- and V-ATPases reveals nearly identical sets of amino acids involved in sodium binding. We show that the sodium-dependent ATPases are scattered among proton-dependent ATPases in both the F- and the V-branches of the phylogenetic tree. Conclusion Barring convergent emergence of the same set of ligands in several lineages, these findings indicate that the use of sodium gradient for ATP synthesis is the ancestral modality of membrane bioenergetics. Thus, a primitive, sodium-impermeable but proton-permeable cell membrane that harboured a set of sodium-transporting enzymes appears to have been the evolutionary predecessor of the more structurally demanding proton-tight membranes. The use of proton as the coupling ion appears to be a later innovation that emerged on several independent occasions. Reviewers This article was reviewed by J. Peter Gogarten, Martijn A. Huynen, and Igor B. Zhulin. For the full reviews, please go to the Reviewers' comments section. PMID:18380897

  2. Predicting evolutionary dynamics

    NASA Astrophysics Data System (ADS)

    Balazsi, Gabor

    We developed an ordinary differential equation-based model to predict the evolutionary dynamics of yeast cells carrying a synthetic gene circuit. The predicted aspects included the speed at which the ancestral genotype disappears from the population; as well as the types of mutant alleles that establish in each environmental condition. We validated these predictions by experimental evolution. The agreement between our predictions and experimental findings suggests that cellular and population fitness landscapes can be useful to predict short-term evolution.

  3. Evolutionary mysteries in meiosis.

    PubMed

    Lenormand, Thomas; Engelstädter, Jan; Johnston, Susan E; Wijnker, Erik; Haag, Christoph R

    2016-10-19

    Meiosis is a key event of sexual life cycles in eukaryotes. Its mechanistic details have been uncovered in several model organisms, and most of its essential features have received various and often contradictory evolutionary interpretations. In this perspective, we present an overview of these often 'weird' features. We discuss the origin of meiosis (origin of ploidy reduction and recombination, two-step meiosis), its secondary modifications (in polyploids or asexuals, inverted meiosis), its importance in punctuating life cycles (meiotic arrests, epigenetic resetting, meiotic asymmetry, meiotic fairness) and features associated with recombination (disjunction constraints, heterochiasmy, crossover interference and hotspots). We present the various evolutionary scenarios and selective pressures that have been proposed to account for these features, and we highlight that their evolutionary significance often remains largely mysterious. Resolving these mysteries will likely provide decisive steps towards understanding why sex and recombination are found in the majority of eukaryotes.This article is part of the themed issue 'Weird sex: the underappreciated diversity of sexual reproduction'.

  4. Weapon Release Scheduling from Multiple-Bay Aircraft using Multi-Objective Evolutionary Algorithms

    DTIC Science & Technology

    2005-03-01

    Morgan Kaufmann, San Mateo, CA, 1993. URL citeseer.ist.psu.edu/fang93promising.html. 32. Fogel, David. Introduction to evolutionary computation , chapter 1...Aircraft using Multi-Objective Evolutionary Algorithms THESIS Presented to the Faculty Department of Electrical and Computer Engineering Graduate School...8 2.2.2 Schedule Metrics . . . . . . . . . . . . . . . . 9 2.2.3 Algorithms . . . . . . . . . . . . . . . . . . . 10 2.3 Evolutionary Computation

  5. Evolutionary Computational Methods for Identifying Emergent Behavior in Autonomous Systems

    NASA Technical Reports Server (NTRS)

    Terrile, Richard J.; Guillaume, Alexandre

    2011-01-01

    A technique based on Evolutionary Computational Methods (ECMs) was developed that allows for the automated optimization of complex computationally modeled systems, such as autonomous systems. The primary technology, which enables the ECM to find optimal solutions in complex search spaces, derives from evolutionary algorithms such as the genetic algorithm and differential evolution. These methods are based on biological processes, particularly genetics, and define an iterative process that evolves parameter sets into an optimum. Evolutionary computation is a method that operates on a population of existing computational-based engineering models (or simulators) and competes them using biologically inspired genetic operators on large parallel cluster computers. The result is the ability to automatically find design optimizations and trades, and thereby greatly amplify the role of the system engineer.

  6. Liquid Rocket Engine Testing Overview

    NASA Technical Reports Server (NTRS)

    Rahman, Shamim

    2005-01-01

    Contents include the following: Objectives and motivation for testing. Technology, Research and Development Test and Evaluation (RDT&E), evolutionary. Representative Liquid Rocket Engine (LRE) test compaigns. Apollo, shuttle, Expandable Launch Vehicles (ELV) propulsion. Overview of test facilities for liquid rocket engines. Boost, upper stage (sea-level and altitude). Statistics (historical) of Liquid Rocket Engine Testing. LOX/LH, LOX/RP, other development. Test project enablers: engineering tools, operations, processes, infrastructure.

  7. Molecular engineering and theoretical investigation of organic sensitizers based on indoline dyes for quasi-solid state dye-sensitized solar cells.

    PubMed

    Liu, Bo; Wu, Wenjun; Li, Xiaoyan; Li, Lei; Guo, Shaofu; Wei, Xiaoru; Zhu, Weihong; Liu, Qingbin

    2011-05-21

    Novel indoline dyes, I-1-I-4, with structural modification of π-linker group in the D-π-A system have been synthesized and fully characterized. Molecular engineering through expanding the π-linker segment has been performed. The ground and excited state properties of the dyes have been studied by means of density functional theory (DFT) and time-dependent DFT (TD-DFT). Larger π-conjugation linkers would lead to broader spectral response and higher molar extinction coefficient but would decrease dye-loaded amount on TiO(2) electrode and LUMO level. While applied in DSSCs, the variation trends in short-circuit current density (J(sc)) and open-circuit voltage (V(oc)) were observed to be opposite to each other. The internal reasons were studied by experimental data and theoretical calculations in detail. Notably, I-2 showed comparable photocurrent values with liquid and quasi-solid state electrolyte, which suggested through molecular engineering of organic sensitizers the dilemma between optical absorption and charge diffusion lengths can be balanced well. Through studies of photophysical, electrochemical, and theoretical calculation results, the internal relations between chemical structure and efficiency have been revealed, which serve to enhance our knowledge regarding design and optimization of new sensitizers for quasi-solid state DSSCs, providing a powerful strategy for prediction of photovoltaic performances.

  8. Hybrid Robust Multi-Objective Evolutionary Optimization Algorithm

    DTIC Science & Technology

    2009-03-10

    Orlando, FL, November 15-19, 2009. 2. Optimizing Concentrations of Alloying Elements and Tempering of Corrosion Resistant Aluminum Alloys (with...Optimization of Corrosion Resistant Aluminum Alloys ", M.Sc. degree in Mechanical Engineering, Florida International University, Miami, FL, expected...International Journal of Thermophysical Properties Research. 5. Evolutionary Wavelet Neural Network for Multidimensional Function Estimation in

  9. Landscape evolutionary genomics.

    PubMed

    Lowry, David B

    2010-08-23

    Tremendous advances in genetic and genomic techniques have resulted in the capacity to identify genes involved in adaptive evolution across numerous biological systems. One of the next major steps in evolutionary biology will be to determine how landscape-level geographical and environmental features are involved in the distribution of this functional adaptive genetic variation. Here, I outline how an emerging synthesis of multiple disciplines has and will continue to facilitate a deeper understanding of the ways in which heterogeneity of the natural landscapes mould the genomes of organisms.

  10. Evolutionary dynamics of enzymes.

    PubMed

    Demetrius, L

    1995-08-01

    This paper codifies and rationalizes the large diversity in reaction rates and substrate specificity of enzymes in terms of a model which postulates that the kinetic properties of present-day enzymes are the consequence of the evolutionary force of mutation and selection acting on a class of primordial enzymes with poor catalytic activity and broad substrate specificity. Enzymes are classified in terms of their thermodynamic parameters, activation enthalpy delta H* and activation entropy delta S*, in their kinetically significant transition states as follows: type 1, delta H* > 0, delta S* < 0; type 2, delta H* < or = 0, delta S* < or = 0; type 3, delta H* > 0, delta S* > 0. We study the evolutionary dynamics of these three classes of enzymes subject to mutation, which acts at the level of the gene which codes for the enzyme and selection, which acts on the organism that contains the enzyme. Our model predicts the following evolutionary trends in the reaction rate and binding specificity for the three classes of molecules. In type 1 enzymes, evolution results in random, non-directional changes in the reaction rate and binding specificity. In type 2 and 3 enzymes, evolution results in a unidirectional increase in both the reaction rate and binding specificity. We exploit these results in order to codify the diversity in functional properties of present-day enzymes. Type 1 molecules will be described by intermediate reaction rates and broad substrate specificity. Type 2 enzymes will be characterized by diffusion-controlled rates and absolute substrate specificity. The type 3 catalysts can be further subdivided in terms of their activation enthalpy into two classes: type 3a (delta H* small) and type 3b (delta H* large). We show that type 3a will be represented by the same functional properties that identify type 2, namely, diffusion-controlled rates and absolute substrate specificity, whereas type 3b will be characterized by non-diffusion-controlled rates and absolute

  11. Thermodynamics and evolutionary genetics

    NASA Astrophysics Data System (ADS)

    Müller, Ingo

    2010-03-01

    Thermodynamics and evolutionary genetics have something in common. Thus, the randomness of mutation of cells may be likened to the random thermal fluctuations in a gas. And the probabilistic nature of entropy in statistical thermodynamics can be carried over to a population of haploid and diploid cells without any conceptual change. The energetic potential wells in which the atoms of a liquid are caught correspond to selective advantages for some phenotype over others. Thus, the eventual stable state in a population comes about as a compromise in the universal competition between entropy and energy.

  12. Ultrasound Molecular Imaging of the Breast Cancer Neovasculature using Engineered Fibronectin Scaffold Ligands: A Novel Class of Targeted Contrast Ultrasound Agent

    PubMed Central

    Abou-Elkacem, Lotfi; Wilson, Katheryne E.; Johnson, Sadie M.; Chowdhury, Sayan M.; Bachawal, Sunitha; Hackel, Benjamin J.; Tian, Lu; Willmann, Jürgen K.

    2016-01-01

    Molecularly-targeted microbubbles (MBs) are increasingly being recognized as promising contrast agents for oncological molecular imaging with ultrasound. With the detection and validation of new molecular imaging targets, novel binding ligands are needed that bind to molecular imaging targets with high affinity and specificity. In this study we assessed a novel class of potentially clinically translatable MBs using an engineered 10th type III domain of human-fibronectin (MB-FN3VEGFR2) scaffold-ligand to image VEGFR2 on the neovasculature of cancer. The in vitro binding of MB-FN3VEGFR2 to a soluble VEGFR2 was assessed by flow-cytometry (FACS) and binding to VEGFR2-expressing cells was assessed by flow-chamber cell attachment studies under flow shear stress conditions. In vivo binding of MB-FN3VEGFR2 was tested in a transgenic mouse model (FVB/N Tg(MMTV/PyMT634Mul) of breast cancer and control litter mates with normal mammary glands. In vitro FACS and flow-chamber cell attachment studies showed significantly (P<0.01) higher binding to VEGFR2 using MB-FN3VEGFR2 than control agents. In vivo ultrasound molecular imaging (USMI) studies using MB-FN3VEGFR2 demonstrated specific binding to VEGFR2 and was significantly higher (P<0.01) in breast cancer compared to normal breast tissue. Ex vivo immunofluorescence-analysis showed significantly (P<0.01) increased VEGFR2-expression in breast cancer compared to normal mammary tissue. Our results suggest that MBs coupled to FN3-scaffolds can be designed and used for USMI of breast cancer neoangiogenesis. Due to their small size, stability, solubility, the lack of glycosylation and disulfide bonds, FN3-scaffolds can be recombinantly produced with the advantage of generating small, high affinity ligands in a cost efficient way for USMI. PMID:27570547

  13. Practical advantages of evolutionary computation

    NASA Astrophysics Data System (ADS)

    Fogel, David B.

    1997-10-01

    Evolutionary computation is becoming a common technique for solving difficult, real-world problems in industry, medicine, and defense. This paper reviews some of the practical advantages to using evolutionary algorithms as compared with classic methods of optimization or artificial intelligence. Specific advantages include the flexibility of the procedures, as well as their ability to self-adapt the search for optimum solutions on the fly. As desktop computers increase in speed, the application of evolutionary algorithms will become routine.

  14. Automated Hardware Design via Evolutionary Search

    NASA Technical Reports Server (NTRS)

    Lohn, Jason D.; Colombano, Silvano P.

    2000-01-01

    The goal of this research is to investigate the application of evolutionary search to the process of automated engineering design. Evolutionary search techniques involve the simulation of Darwinian mechanisms by computer algorithms. In recent years, such techniques have attracted much attention because they are able to tackle a wide variety of difficult problems and frequently produce acceptable solutions. The results obtained are usually functional, often surprising, and typically "messy" because the algorithms are told to concentrate on the overriding objective and not elegance or simplicity. advantages. First, faster design cycles translate into time and, hence, cost savings. Second, automated design techniques can be made to scale well and hence better deal with increasing amounts of design complexity. Third, design quality can increase because design properties can be specified a priori. For example, size and weight specifications of a device, smaller and lighter than the best known design, might be optimized by the automated design technique. The domain of electronic circuit design is an advantageous platform in which to study automated design techniques because it is a rich design space that is well understood, permitting human-created designs to be compared to machine- generated designs. developed for circuit design was to automatically produce high-level integrated electronic circuit designs whose properties permit physical implementation in silicon. This process entailed designing an effective evolutionary algorithm and solving a difficult multiobjective optimization problem. FY 99 saw many accomplishments in this effort.

  15. Evolutionary status of Polaris

    NASA Astrophysics Data System (ADS)

    Fadeyev, Yu. A.

    2015-05-01

    Hydrodynamic models of short-period Cepheids were computed to determine the pulsation period as a function of evolutionary time during the first and third crossings of the instability strip. The equations of radiation hydrodynamics and turbulent convection for radial stellar pulsations were solved with the initial conditions obtained from the evolutionary models of Population I stars (X = 0.7, Z = 0.02) with masses from 5.2 to 6.5 M⊙ and the convective core overshooting parameter 0.1 ≤ αov ≤ 0.3. In Cepheids with period of 4 d the rate of pulsation period change during the first crossing of the instability strip is over 50 times larger than that during the third crossing. Polaris is shown to cross the instability strip for the first time and to be the fundamental mode pulsator. The best agreement between the predicted and observed rates of period change was obtained for the model with mass of 5.4 M⊙ and the overshooting parameter αov = 0.25. The bolometric luminosity and radius are L = 1.26 × 103 L⊙ and R = 37.5 R⊙, respectively. In the HR diagram, Polaris is located at the red edge of the instability strip.

  16. On evolutionary systems.

    PubMed

    Alvarez de Lorenzana, J M; Ward, L M

    1987-01-01

    This paper develops a metatheoretical framework for understanding evolutionary systems (systems that develop in ways that increase their own variety). The framework addresses shortcomings seen in other popular systems theories. It concerns both living and nonliving systems, and proposes a metahierarchy of hierarchical systems. Thus, it potentially addresses systems at all descriptive levels. We restrict our definition of system to that of a core system whose parts have a different ontological status than the system, and characterize the core system in terms of five global properties: minimal length interval, minimal time interval, system cycle, total receptive capacity, and system potential. We propose two principles through the interaction of which evolutionary systems develop. The Principle of Combinatorial Expansion describes how a core system realizes its developmental potential through a process of progressive differentiation of the single primal state up to a limit stage. The Principle of Generative Condensation describes how the components of the last stage of combinatorial expansion condense and become the environment for and components of new, enriched systems. The early evolution of the Universe after the "big bang" is discussed in light of these ideas as an example of the application of the framework.

  17. Discovery of Emphysema Relevant Molecular Networks from an A/J Mouse Inhalation Study Using Reverse Engineering and Forward Simulation (REFS™).

    PubMed

    Xiang, Yang; Kogel, Ulrike; Gebel, Stephan; Peck, Michael J; Peitsch, Manuel C; Akmaev, Viatcheslav R; Hoeng, Julia

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a respiratory disorder caused by extended exposure of the airways to noxious stimuli, principally cigarette smoke (CS). The mechanisms through which COPD develops are not fully understood, though it is believed that the disease process includes a genetic component, as not all smokers develop COPD. To investigate the mechanisms that lead to the development of COPD/emphysema, we measured whole genome gene expression and several COPD-relevant biological endpoints in mouse lung tissue after exposure to two CS doses for various lengths of time. A novel and powerful method, Reverse Engineering and Forward Simulation (REFS™), was employed to identify key molecular drivers by integrating the gene expression data and four measured COPD-relevant endpoints (matrix metalloproteinase (MMP) activity, MMP-9 levels, tissue inhibitor of metalloproteinase-1 levels and lung weight). An ensemble of molecular networks was generated using REFS™, and simulations showed that it could successfully recover the measured experimental data for gene expression and COPD-relevant endpoints. The ensemble of networks was then employed to simulate thousands of in silico gene knockdown experiments. Thirty-three molecular key drivers for the above four COPD-relevant endpoints were therefore identified, with the majority shown to be enriched in inflammation and COPD.

  18. Polymer Physics Prize Lecture: Self-assemblies of Giant Molecular Shape Amphiphiles as a New Platform for Engineering Structures with Sub-Nanometer Feature Sizes

    NASA Astrophysics Data System (ADS)

    Cheng, Stephen Z. D.

    2013-03-01

    Utilizing nano-building blocks rather than atoms to construct and engineer new structures is a fresh approach to design and develop functional materials for the purpose of transferring and amplifying microscopic functionality to macroscopic materials' property. As one of the important elements of these nano-building blocks, giant molecular shape amphiphiles (GMSAs) provide a latest platform for generating self-assembled ordered structures at nanometer scale, which are stabilized by collective physical bonds (such as collective hydrogen bonding). In this talk, two topics will be focused on. First, composed of functionalized hydrophilic molecular nanoparticles as the heads with rigid shape and fixed volume, and tethered polymer chains as the tails (such as giant molecular surfactants and lipids and other topologies), these GMSAs of various architectures can self-assemble into highly diversified, thermodynamically stable microstructures at sub-10 nm length scale in the bulk, thin film and solution states. Second, GMSAs could also be constructed solely from nanoparticles interconnected via different numbers of the rigid linkages in specific symmetry, simulating the overall shapes of small molecules but with sizes that are one-order of magnitude larger in length and three-order of magnitude larger in volume. Giant crystal structures can then be obtained from this class of ``giant molecules'' via supramolecular crystallization. These findings are not only scientifically intriguing in understanding the physical principles underlying their self-assembly, but also technologically relevant in industrial applications.

  19. A Decade of Molecular Understanding of Withanolide Biosynthesis and In vitro Studies in Withania somnifera (L.) Dunal: Prospects and Perspectives for Pathway Engineering

    PubMed Central

    Dhar, Niha; Razdan, Sumeer; Rana, Satiander; Bhat, Wajid W.; Vishwakarma, Ram; Lattoo, Surrinder K.

    2015-01-01

    Withania somnifera, a multipurpose medicinal plant is a rich reservoir of pharmaceutically active triterpenoids that are steroidal lactones known as withanolides. Though the plant has been well-characterized in terms of phytochemical profiles as well as pharmaceutical activities, limited attempts have been made to decipher the biosynthetic route and identification of key regulatory genes involved in withanolide biosynthesis. This scenario limits biotechnological interventions for enhanced production of bioactive compounds. Nevertheless, recent emergent trends vis-à-vis, the exploration of genomic, transcriptomic, proteomic, metabolomics, and in vitro studies have opened new vistas regarding pathway engineering of withanolide production. During recent years, various strategic pathway genes have been characterized with significant amount of regulatory studies which allude toward development of molecular circuitries for production of key intermediates or end products in heterologous hosts. Another pivotal aspect covering redirection of metabolic flux for channelizing the precursor pool toward enhanced withanolide production has also been attained by deciphering decisive branch point(s) as robust targets for pathway modulation. With these perspectives, the current review provides a detailed overview of various studies undertaken by the authors and collated literature related to molecular and in vitro approaches employed in W. somnifera for understanding various molecular network interactions in entirety. PMID:26640469

  20. Molecular design of glycoprotein mimetics: glycoblotting by engineered proteins with an oxylamino-functionalized amino acid residue.

    PubMed

    Matsubara, Naoki; Oiwa, Kei; Hohsaka, Takahiro; Sadamoto, Reiko; Niikura, Kenichi; Fukuhara, Norio; Takimoto, Akio; Kondo, Hirosato; Nishimura, Shin-Ichiro

    2005-11-18

    The general and efficient method for the site-directed glycosylation of proteins is a key step in order to understand the biological importance of the carbohydrate chains of proteins and to control functional roles of the engineered glycoproteins in terms of the development of improved glycoprotein therapeutics. We have developed a novel method for site-directed glycosylation of proteins based on chemoselective blotting of common reducing sugars by genetically encoded proteins. The oxylamino-functionalized L-homoserine residues, 2-amino-4-O-(N-methylaminooxy) butanoic acid and 2-amino-4-aminooxy butanoic acid, were efficiently incorporated into proteins by using the four-base codon/anticodon pair strategy in Escherichia coli in vitro translation. Direct and chemoselective coupling between unmodified simple sugars and N-methylaminooxy group displayed on the engineered streptavidin allowed for the combinatorial synthesis of novel glycoprotein mimetics.

  1. Molecular Self-Assembly and Interfacial Engineering for Highly Efficient Organic Field Effect Transistors and Solar Cells

    DTIC Science & Technology

    2012-09-23

    dielectric layer modified by the genetically engineered polypeptide (GEP) and (6) graphene oxide (GO) nanosheet-based OFETs and one diode -one resistor...polypeptide (GEP) and (6) graphene oxide (GO) nanosheet-based OFETs and one diode -one resistor cell arrays for non-volatile memory have been also... Graphene oxide (GO) nanosheet-based OFETs and one diode -one resistor cell arrays for non-volatile memory We have demonstrated ONVMTs using

  2. Engineering functional protein interfaces for immunologically modified field effect transistor (ImmunoFET) by molecular genetic means.

    PubMed

    Eteshola, Edward; Keener, Matthew T; Elias, Mark; Shapiro, John; Brillson, Leonard J; Bhushan, Bharat; Lee, Stephen Craig

    2008-01-06

    The attachment and interactions of analyte receptor biomolecules at solid-liquid interfaces are critical to development of hybrid biological-synthetic sensor devices across all size regimes. We use protein engineering approaches to engineer the sensing interface of biochemically modified field effect transistor sensors (BioFET). To date, we have deposited analyte receptor proteins on FET sensing channels by direct adsorption, used self-assembled monolayers to tether receptor proteins to planar FET SiO2 sensing gates and demonstrated interface biochemical function and electrical function of the corresponding sensors. We have also used phage display to identify short peptides that recognize thermally grown SiO2. Our interest in these peptides is as affinity domains that can be inserted as translational fusions into receptor proteins (antibody fragments or other molecules) to drive oriented interaction with FET sensing surfaces. We have also identified single-chain fragment variables (scFvs, antibody fragments) that recognize an analyte of interest as potential sensor receptors. In addition, we have developed a protein engineering technology (scanning circular permutagenesis) that allows us to alter protein topography to manipulate the position of functional domains of the protein relative to the BioFET sensing surface.

  3. ABB Combustion Engineering`s nuclear experience and technologies

    SciTech Connect

    Matzie, R.A.

    1994-12-31

    ABB Combustion Engineering`s nuclear experience and technologies are outlined. The following topics are discussed: evolutionary approach using proven technology, substantial improvement to plant safety, utility perspective up front in developing design, integrated design, competitive plant cost, operability and maintainability, standardization, and completion of US NRC technical review.

  4. The multiple applications of DNA barcodes in avian evolutionary studies.

    PubMed

    Barreira, Ana S; Lijtmaer, Darío A; Tubaro, Pablo L

    2016-11-01

    DNA barcodes of birds are currently available for 41% of known species and for many different geographic areas; therefore, they are a rich data source to answer evolutionary questions. We review studies that have used DNA barcodes to investigate evolutionary processes in birds using diverse approaches. We also review studies that have investigated species in depth where taxonomy and DNA barcodes present inconsistencies. Species that showed low genetic interspecific divergence and lack of reciprocal monophyly either are the result of recent radiation and (or) hybridize, while species with large genetic splits in their COI sequences were determined to be more than one independent evolutionary unit. In addition, we review studies that employed large DNA barcode datasets to study the molecular evolution of mitochondrial genes and the biogeography of islands, continents, and even at a multi-continental scale. These studies showed that DNA barcodes offer high-quality data well beyond their main purpose of serving as a molecular tool for species identification.

  5. Cryptic Genetic Variation in Evolutionary Developmental Genetics.

    PubMed

    Paaby, Annalise B; Gibson, Greg

    2016-06-13

    Evolutionary developmental genetics has traditionally been conducted by two groups: Molecular evolutionists who emphasize divergence between species or higher taxa, and quantitative geneticists who study variation within species. Neither approach really comes to grips with the complexities of evolutionary transitions, particularly in light of the realization from genome-wide association studies that most complex traits fit an infinitesimal architecture, being influenced by thousands of loci. This paper discusses robustness, plasticity and lability, phenomena that we argue potentiate major evolutionary changes and provide a bridge between the conceptual treatments of macro- and micro-evolution. We offer cryptic genetic variation and conditional neutrality as mechanisms by which standing genetic variation can lead to developmental system drift and, sheltered within canalized processes, may facilitate developmental transitions and the evolution of novelty. Synthesis of the two dominant perspectives will require recognition that adaptation, divergence, drift and stability all depend on similar underlying quantitative genetic processes-processes that cannot be fully observed in continuously varying visible traits.

  6. Evolutionary game theory: cells as players.

    PubMed

    Hummert, Sabine; Bohl, Katrin; Basanta, David; Deutsch, Andreas; Werner, Sarah; Theissen, Günter; Schroeter, Anja; Schuster, Stefan

    2014-12-01

    In two papers we review game theory applications in biology below the level of cognitive living beings. It can be seen that evolution and natural selection replace the rationality of the actors appropriately. Even in these micro worlds, competing situations and cooperative relationships can be found and modeled by evolutionary game theory. Also those units of the lowest levels of life show different strategies for different environmental situations or different partners. We give a wide overview of evolutionary game theory applications to microscopic units. In this first review situations on the cellular level are tackled. In particular metabolic problems are discussed, such as ATP-producing pathways, secretion of public goods and cross-feeding. Further topics are cyclic competition among more than two partners, intra- and inter-cellular signalling, the struggle between pathogens and the immune system, and the interactions of cancer cells. Moreover, we introduce the theoretical basics to encourage scientists to investigate problems in cell biology and molecular biology by evolutionary game theory.

  7. Virulence in malaria: an evolutionary viewpoint.

    PubMed Central

    Mackinnon, Margaret J; Read, Andrew F

    2004-01-01

    Malaria parasites cause much morbidity and mortality to their human hosts. From our evolutionary perspective, this is because virulence is positively associated with parasite transmission rate. Natural selection therefore drives virulence upwards, but only to the point where the cost to transmission caused by host death begins to outweigh the transmission benefits. In this review, we summarize data from the laboratory rodent malaria model, Plasmodium chabaudi, and field data on the human malaria parasite, P. falciparum, in relation to this virulence trade-off hypothesis. The data from both species show strong positive correlations between asexual multiplication, transmission rate, infection length, morbidity and mortality, and therefore support the underlying assumptions of the hypothesis. Moreover, the P. falciparum data show that expected total lifetime transmission of the parasite is maximized in young children in whom the fitness cost of host mortality balances the fitness benefits of higher transmission rates and slower clearance rates, thus exhibiting the hypothesized virulence trade-off. This evolutionary explanation of virulence appears to accord well with the clinical and molecular explanations of pathogenesis that involve cytoadherence, red cell invasion and immune evasion, although direct evidence of the fitness advantages of these mechanisms is scarce. One implication of this evolutionary view of virulence is that parasite populations are expected to evolve new levels of virulence in response to medical interventions such as vaccines and drugs. PMID:15306410

  8. Cryptic Genetic Variation in Evolutionary Developmental Genetics

    PubMed Central

    Paaby, Annalise B.; Gibson, Greg

    2016-01-01

    Evolutionary developmental genetics has traditionally been conducted by two groups: Molecular evolutionists who emphasize divergence between species or higher taxa, and quantitative geneticists who study variation within species. Neither approach really comes to grips with the complexities of evolutionary transitions, particularly in light of the realization from genome-wide association studies that most complex traits fit an infinitesimal architecture, being influenced by thousands of loci. This paper discusses robustness, plasticity and lability, phenomena that we argue potentiate major evolutionary changes and provide a bridge between the conceptual treatments of macro- and micro-evolution. We offer cryptic genetic variation and conditional neutrality as mechanisms by which standing genetic variation can lead to developmental system drift and, sheltered within canalized processes, may facilitate developmental transitions and the evolution of novelty. Synthesis of the two dominant perspectives will require recognition that adaptation, divergence, drift and stability all depend on similar underlying quantitative genetic processes—processes that cannot be fully observed in continuously varying visible traits. PMID:27304973

  9. Evolutionary mechanism unifies the hallmarks of cancer.

    PubMed

    Horne, Steven D; Pollick, Sarah A; Heng, Henry H Q

    2015-05-01

    The basis for the gene mutation theory of cancer that dominates current molecular cancer research consists of: the belief that gene-level aberrations such as mutations are the main cause of cancers, the concept that stepwise gene mutation accumulation drives cancer progression, and the hallmarks of cancer. The research community swiftly embraced the hallmarks of cancer, as such synthesis has supported the notions that common cancer genes are responsible for the majority of cancers and the complexity of cancer can be dissected into simplified molecular principles. The gene/pathway classification based on individual hallmarks provides explanation for the large number of diverse gene mutations, which is in contrast to the original estimation that only a handful of gene mutations would be discovered. Further, these hallmarks have been highly influential as they also provide the rationale and research direction for continued gene-based cancer research. While the molecular knowledge of these hallmarks is drastically increasing, the clinical implication remains limited, as cancer dynamics cannot be summarized by a few isolated/fixed molecular principles. Furthermore, the highly heterogeneous genetic signature of cancers, including massive stochastic genome alterations, challenges the utility of continuously studying each individual gene mutation under the framework of these hallmarks. It is therefore necessary to re-evaluate the concept of cancer hallmarks through the lens of cancer evolution. In this analysis, the evolutionary basis for the hallmarks of cancer will be discussed and the evolutionary mechanism of cancer suggested by the genome theory will be employed to unify the diverse molecular mechanisms of cancer.

  10. The great opportunity: Evolutionary applications to medicine and public health

    PubMed Central

    Nesse, Randolph M; Stearns, Stephen C

    2008-01-01

    Abstract Evolutionary biology is an essential basic science for medicine, but few doctors and medical researchers are familiar with its most relevant principles. Most medical schools have geneticists who understand evolution, but few have even one evolutionary biologist to suggest other possible applications. The canyon between evolutionary biology and medicine is wide. The question is whether they offer each other enough to make bridge building worthwhile. What benefits could be expected if evolution were brought fully to bear on the problems of medicine? How would studying medical problems advance evolutionary research? Do doctors need to learn evolution, or is it valuable mainly for researchers? What practical steps will promote the application of evolutionary biology in the areas of medicine where it offers the most? To address these questions, we review current and potential applications of evolutionary biology to medicine and public health. Some evolutionary technologies, such as population genetics, serial transfer production of live vaccines, and phylogenetic analysis, have been widely applied. Other areas, such as infectious disease and aging research, illustrate the dramatic recent progress made possible by evolutionary insights. In still other areas, such as epidemiology, psychiatry, and understanding the regulation of bodily defenses, applying evolutionary principles remains an open opportunity. In addition to the utility of specific applications, an evolutionary perspective fundamentally challenges the prevalent but fundamentally incorrect metaphor of the body as a machine designed by an engineer. Bodies are vulnerable to disease – and remarkably resilient – precisely because they are not machines built from a plan. They are, instead, bundles of compromises shaped by natural selection in small increments to maximize reproduction, not health. Understanding the body as a product of natural selection, not design, offers new research questions and a

  11. Spore: Spawning Evolutionary Misconceptions?

    NASA Astrophysics Data System (ADS)

    Bean, Thomas E.; Sinatra, Gale M.; Schrader, P. G.

    2010-10-01

    The use of computer simulations as educational tools may afford the means to develop understanding of evolution as a natural, emergent, and decentralized process. However, special consideration of developmental constraints on learning may be necessary when using these technologies. Specifically, the essentialist (biological forms possess an immutable essence), teleological (assignment of purpose to living things and/or parts of living things that may not be purposeful), and intentionality (assumption that events are caused by an intelligent agent) biases may be reinforced through the use of computer simulations, rather than addressed with instruction. We examine the video game Spore for its depiction of evolutionary content and its potential to reinforce these cognitive biases. In particular, we discuss three pedagogical strategies to mitigate weaknesses of Spore and other computer simulations: directly targeting misconceptions through refutational approaches, targeting specific principles of scientific inquiry, and directly addressing issues related to models as cognitive tools.

  12. Anxiety: an evolutionary approach.

    PubMed

    Bateson, Melissa; Brilot, Ben; Nettle, Daniel

    2011-12-01

    Anxiety disorders are among the most common mental illnesses, with huge attendant suffering. Current treatments are not universally effective, suggesting that a deeper understanding of the causes of anxiety is needed. To understand anxiety disorders better, it is first necessary to understand the normal anxiety response. This entails considering its evolutionary function as well as the mechanisms underlying it. We argue that the function of the human anxiety response, and homologues in other species, is to prepare the individual to detect and deal with threats. We use a signal detection framework to show that the threshold for expressing the anxiety response ought to vary with the probability of threats occurring, and the individual's vulnerability to them if they do occur. These predictions are consistent with major patterns in the epidemiology of anxiety. Implications for research and treatment are discussed.

  13. Itegrated Test and Evaluation of a 4-Bed Molecular Sieve (4BMS) Carbon Dioxide Removtal System (CDRA), Mechanical Compressor Engineering Development Unit (EDU), and Sabitier Engineering Development Unit (EDU)

    NASA Technical Reports Server (NTRS)

    Knox, James C.; Campbell, Melissa; Murdoch, Karen; Miller, Lee A.; Jeng, Frank

    2005-01-01

    Currently on the International Space Station s (ISS) U.S. Segment, carbon dioxide (CO2) scrubbed from the cabin by a 4-Bed Molecular Sieve (4BMS) Carbon Dioxide Removal Assembly (CDRA) is vented overboard as a waste product. Likewise, the product hydrogen (H2) that will be generated by the Oxygen Generation Assembly (OGA) planned for installation will also be vented. A flight experiment has been proposed that will take the waste CO2 removed from the cabin, and via the catalytic Sabatier process, reduce it with waste H2 to generate water and methane. The water produced may provide cost and logistics savings for ISS by reducing the amount of water periodically re-supplied to orbit. To make this concept viable, a mechanical piston compressor and accumulator were developed for collecting and storing the CO2 from the CDRA. The compressor, accumulator and Sabatier system would be packaged together as one unit and referred to as the Carbon Dioxide Reduction Assembly (CRA). Testing was required to evaluate the performance of a 4BMS CDRA, compressor, accumulator, and Sabatier performance along with their operating rules when integrated together. This had been numerically modeled and simulated; however, testing was necessary to verify the results from the engineering analyses. Testing also allowed a better understanding of the practical inefficiencies and control issues involved in a fully integrated system versus the theoretical ideals in the model. This paper presents and discusses the results of an integrated engineering development unit test.

  14. Selective Synthesis of Molecular Borromean Rings: Engineering of Supramolecular Topology via Coordination-Driven Self-Assembly.

    PubMed

    Kim, Taegeun; Singh, Nem; Oh, Jihun; Kim, Eun-Hee; Jung, Jaehoon; Kim, Hyunuk; Chi, Ki-Whan

    2016-07-13

    Molecular Borromean rings (BRs) is one of the rare topology among interlocked molecules. Template-free synthesis of BRs via coordination-driven self-assembly of tetracene-based Ru(II) acceptor and ditopic pyridyl donors is reported. NMR and single-crystal XRD analysis observed sequential transformation of a fully characterized monomeric rectangle to molecular BRs and vice versa. Crystal structure of BRs revealed that the particular topology was enforced by the appropriate geometry of the metallacycle and multiple parallel-displaced π-π interactions between the donor and tetracene moiety of the acceptor. Computational studies based on density functional theory also supported the formation of BRs through dispersive intermolecular interactions in solution.

  15. Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies.

    PubMed

    Soler, Miguel A; de Marco, Ario; Fortuna, Sara

    2016-10-10

    Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

  16. Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies

    PubMed Central

    Soler, Miguel A.; de Marco, Ario; Fortuna, Sara

    2016-01-01

    Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules. PMID:27721441

  17. Molecular dynamics simulations and docking enable to explore the biophysical factors controlling the yields of engineered nanobodies

    NASA Astrophysics Data System (ADS)

    Soler, Miguel A.; De Marco, Ario; Fortuna, Sara

    2016-10-01

    Nanobodies (VHHs) have proved to be valuable substitutes of conventional antibodies for molecular recognition. Their small size represents a precious advantage for rational mutagenesis based on modelling. Here we address the problem of predicting how Camelidae nanobody sequences can tolerate mutations by developing a simulation protocol based on all-atom molecular dynamics and whole-molecule docking. The method was tested on two sets of nanobodies characterized experimentally for their biophysical features. One set contained point mutations introduced to humanize a wild type sequence, in the second the CDRs were swapped between single-domain frameworks with Camelidae and human hallmarks. The method resulted in accurate scoring approaches to predict experimental yields and enabled to identify the structural modifications induced by mutations. This work is a promising tool for the in silico development of single-domain antibodies and opens the opportunity to customize single functional domains of larger macromolecules.

  18. Fueling the central engine of radio galaxies. III. Molecular gas and star formation efficiency of 3C 293

    NASA Astrophysics Data System (ADS)

    Labiano, A.; García-Burillo, S.; Combes, F.; Usero, A.; Soria-Ruiz, R.; Piqueras López, J.; Fuente, A.; Hunt, L.; Neri, R.

    2014-04-01

    Context. Powerful radio galaxies show evidence of ongoing active galactic nuclei (AGN) feedback, mainly in the form of fast, massive outflows. But it is not clear how these outflows affect the star formation of their hosts. Aims: We investigate the different manifestations of AGN feedback in the evolved, powerful radio source 3C 293 and their impact on the molecular gas of its host galaxy, which harbors young star-forming regions and fast outflows of H i and ionized gas. Methods: We study the distribution and kinematics of the molecular gas of 3C 293 using high spatial resolution observations of the 12CO(1-0) and 12CO(2-1) lines, and the 3 mm and 1 continuum taken with the IRAM Plateau de Bure interferometer. We mapped the molecular gas of 3C 293 and compared it with the dust and star-formation images of the host. We searched for signatures of outflow motions in the CO kinematics, and re-examined the evidence of outflowing gas in the H i spectra. We also derived the star formation rate (SFR) and star formation efficiency (SFE) of the host with all available SFR tracers from the literature, and compared them with the SFE of young and evolved radio galaxies and normal star-forming galaxies. Results: The 12CO(1-0) emission line shows that the molecular gas in 3C 293 is distributed along a massive (M(H2) ~ 2.2 × 1010M⊙) ~24″(21 kpc-) diameter warped disk, that rotates around the AGN. Our data show that the dust and the star formation are clearly associated with the CO disk. The 12CO(2-1) emission is located in the inner 7 kpc (diameter) region around the AGN, coincident with the inner part of the 12CO(1-0) disk. Both the 12CO(1-0) and 12CO(2-1) spectra reveal the presence of an absorber against the central regions of 3C 293 that is associated with the disk. We do not detect any fast (≳500 km s-1) outflow motions in the cold molecular gas. The host of 3C 293 shows an SFE consistent with the Kennicutt-Schmidt law of normal galaxies and young radio galaxies, and it

  19. Observability in dynamic evolutionary models.

    PubMed

    López, I; Gámez, M; Carreño, R

    2004-02-01

    In the paper observability problems are considered in basic dynamic evolutionary models for sexual and asexual populations. Observability means that from the (partial) knowledge of certain phenotypic characteristics the whole evolutionary process can be uniquely recovered. Sufficient conditions are given to guarantee observability for both sexual and asexual populations near an evolutionarily stable state.

  20. Engineering of a novel Ca²⁺-regulated kinesin molecular motor using a calmodulin dimer linker.

    PubMed

    Shishido, Hideki; Maruta, Shinsaku

    2012-06-29

    The kinesin-microtubule system holds great promise as a molecular shuttle device within biochips. However, one current barrier is that such shuttles do not have "on-off" control of their movement. Here we report the development of a novel molecular motor powered by an accelerator and brake system, using a kinesin monomer and a calmodulin (CaM) dimer. The kinesin monomer, K355, was fused with a CaM target peptide (M13 peptide) at the C-terminal part of the neck region (K355-M13). We also prepared CaM dimers using CaM mutants (Q3C), (R86C), or (A147C) and crosslinkers that react with cysteine residues. Following induction of K355-M13 dimerization with CaM dimers, we measured K355-M13 motility and found that it can be reversibly regulated in a Ca(2+)-dependent manner. We also found that velocities of K355-M13 varied depending on the type and crosslink position of the CaM dimer used; crosslink length also had a moderate effect on motility. These results suggest Ca(2+)-dependent dimerization of K355-M13 could be used as a novel molecular shuttle, equipped with an accelerator and brake system, for biochip applications.

  1. Band-gap engineering by molecular mechanical strain-induced giant tuning of the luminescence in colloidal amorphous porous silicon nanostructures.

    PubMed

    Mughal, A; El Demellawi, J K; Chaieb, Sahraoui

    2014-12-14

    Nano-silicon is a nanostructured material in which quantum or spatial confinement is the origin of the material's luminescence. When nano-silicon is broken into colloidal crystalline nanoparticles, its luminescence can be tuned across the visible spectrum only when the sizes of the nanoparticles, which are obtained via painstaking filtration methods that are difficult to scale up because of low yield, vary. Bright and tunable colloidal amorphous porous silicon nanostructures have not yet been reported. In this letter, we report on a 100 nm modulation in the emission of freestanding colloidal amorphous porous silicon nanostructures via band-gap engineering. The mechanism responsible for this tunable modulation, which is independent of the size of the individual particles and their distribution, is the distortion of the molecular orbitals by a strained silicon-silicon bond angle. This mechanism is also responsible for the amorphous-to-crystalline transformation of silicon.

  2. Advantages of an Improved Rhesus Macaque Genome for Evolutionary Analyses

    PubMed Central

    Gradnigo, Julien S.; Majumdar, Abhishek; Norgren, Robert B.; Moriyama, Etsuko N.

    2016-01-01

    The rhesus macaque (Macaca mulatta) is widely used in molecular evolutionary analyses, particularly to identify genes under adaptive or unique evolution in the human lineage. For such studies, it is necessary to align nucleotide sequences of homologous protein-coding genes among multiple species. The validity of these analyses is dependent on high quality genomic data. However, for most mammalian species (other than humans and mice), only draft genomes are available. There has been concern that some results obtained from evolutionary analyses using draft genomes may not be correct. The rhesus macaque provides a unique opportunity to determine whether an improved genome (MacaM) yields better results than a draft genome (rheMac2) for evolutionary studies. We compared protein-coding genes annotated in the rheMac2 and MacaM genomes with their human orthologs. We found many genes annotated in rheMac2 had apparently spurious sequences not present in genes derived from MacaM. The rheMac2 annotations also appeared to inflate a frequently used evolutionary index, ω (the ratio of nonsynonymous to synonymous substitution rates). Genes with these spurious sequences must be filtered out from evolutionary analyses to obtain correct results. With the MacaM genome, improved sequence information means many more genes can be examined for indications of selection. These results indicate how upgrading genomes from draft status to a higher level of quality can improve interpretation of evolutionary patterns. PMID:27911958

  3. Applying evolutionary genetics to developmental toxicology and risk assessment.

    PubMed

    Leung, Maxwell C K; Procter, Andrew C; Goldstone, Jared V; Foox, Jonathan; DeSalle, Robert; Mattingly, Carolyn J; Siddall, Mark E; Timme-Laragy, Alicia R

    2017-03-04

    Evolutionary thinking continues to challenge our views on health and disease. Yet, there is a communication gap between evolutionary biologists and toxicologists in recognizing the connections among developmental pathways, high-throughput screening, and birth defects in humans. To increase our capability in identifying potential developmental toxicants in humans, we propose to apply evolutionary genetics to improve the experimental design and data interpretation with various in vitro and whole-organism models. We review five molecular systems of stress response and update 18 consensual cell-cell signaling pathways that are the hallmark for early development, organogenesis, and differentiation; and revisit the principles of teratology in light of recent advances in high-throughput screening, big data techniques, and systems toxicology. Multiscale systems modeling plays an integral role in the evolutionary approach to cross-species extrapolation. Phylogenetic analysis and comparative bioinformatics are both valuable tools in identifying and validating the molecular initiating events that account for adverse developmental outcomes in humans. The discordance of susceptibility between test species and humans (ontogeny) reflects their differences in evolutionary history (phylogeny). This synthesis not only can lead to novel applications in developmental toxicity and risk assessment, but also can pave the way for applying an evo-devo perspective to the study of developmental origins of health and disease.

  4. Evolutionary history of the genus Trisopterus.

    PubMed

    Gonzalez, Elena G; Cunha, Regina L; Sevilla, Rafael G; Ghanavi, Hamid R; Krey, Grigorios; Bautista, José M

    2012-03-01

    The group of small poor cods and pouts from the genus Trisopterus, belonging to the Gadidae family, comprises four described benthopelagic species that occur across the North-eastern Atlantic, from the Baltic Sea to the coast of Morocco, and the Mediterranean. Here, we combined molecular data from mitochondrial (cytochrome b) and nuclear (rhodopsin) genes to confirm the taxonomic status of the described species and to disentangle the evolutionary history of the genus. Our analyses supported the monophyly of the genus Trisopterus and confirmed the recently described species Trisopterus capelanus. A relaxed molecular clock analysis estimated an Oligocene origin for the group (~30 million years ago; mya) indicating this genus as one of the most ancestral within the Gadidae family. The closure and re-opening of the Strait of Gibraltar after the Messinian Salinity Crisis (MSC) probably triggered the speciation process that resulted in the recently described T. capelanus.

  5. Evolutionary genomics of fast evolving tunicates.

    PubMed

    Berná, Luisa; Alvarez-Valin, Fernando

    2014-07-08

    Tunicates have been extensively studied because of their crucial phylogenetic location (the closest living relatives of vertebrates) and particular developmental plan. Recent genome efforts have disclosed that tunicates are also remarkable in their genome organization and molecular evolutionary patterns. Here, we review these latter aspects, comparing the similarities and specificities of two model species of the group: Oikopleura dioica and Ciona intestinalis. These species exhibit great genome plasticity and Oikopleura in particular has undergone a process of extreme genome reduction and compaction that can be explained in part by gene loss, but is mostly due to other mechanisms such as shortening of intergenic distances and introns, and scarcity of mobile elements. In Ciona, genome reorganization was less severe being more similar to the other chordates in several aspects. Rates and patterns of molecular evolution are also peculiar in tunicates, being Ciona about 50% faster than vertebrates and Oikopleura three times faster. In fact, the latter species is considered as the fastest evolving metazoan recorded so far. Two processes of increase in evolutionary rates have taken place in tunicates. One of them is more extreme, and basically restricted to genes encoding regulatory proteins (transcription regulators, chromatin remodeling proteins, and metabolic regulators), and the other one is less pronounced but affects the whole genome. Very likely adaptive evolution has played a very significant role in the first, whereas the functional and/or evolutionary causes of the second are less clear and the evidence is not conclusive. The evidences supporting the incidence of increased mutation and less efficient negative selection are presented and discussed.

  6. Evolutionary Genomics of Fast Evolving Tunicates

    PubMed Central

    Berná, Luisa; Alvarez-Valin, Fernando

    2014-01-01

    Tunicates have been extensively studied because of their crucial phylogenetic location (the closest living relatives of vertebrates) and particular developmental plan. Recent genome efforts have disclosed that tunicates are also remarkable in their genome organization and molecular evolutionary patterns. Here, we review these latter aspects, comparing the similarities and specificities of two model species of the group: Oikopleura dioica and Ciona intestinalis. These species exhibit great genome plasticity and Oikopleura in particular has undergone a process of extreme genome reduction and compaction that can be explained in part by gene loss, but is mostly due to other mechanisms such as shortening of intergenic distances and introns, and scarcity of mobile elements. In Ciona, genome reorganization was less severe being more similar to the other chordates in several aspects. Rates and patterns of molecular evolution are also peculiar in tunicates, being Ciona about 50% faster than vertebrates and Oikopleura three times faster. In fact, the latter species is considered as the fastest evolving metazoan recorded so far. Two processes of increase in evolutionary rates have taken place in tunicates. One of them is more extreme, and basically restricted to genes encoding regulatory proteins (transcription regulators, chromatin remodeling proteins, and metabolic regulators), and the other one is less pronounced but affects the whole genome. Very likely adaptive evolution has played a very significant role in the first, whereas the functional and/or evolutionary causes of the second are less clear and the evidence is not conclusive. The evidences supporting the incidence of increased mutation and less efficient negative selection are presented and discussed. PMID:25008364

  7. Assistance of molecular vibrations on coherent energy transfer in photosynthesis from the view of a quantum heat engine.

    PubMed

    Zhang, Zhedong; Wang, Jin

    2015-04-02

    Recently, the quantum nature in the energy transport in solar cells and light-harvesting complexes has attracted much attention as being triggered by the experimental observations. We model the light-harvesting complex (i.e., PEB50 dimer) as a quantum heat engine (QHE) and study the effect of the undamped intramolecule vibrational modes on the coherent energy-transfer process and quantum transport. We find that the exciton-vibration interaction has nontrivial contribution to the promotion of quantum yield as well as transport properties of the QHE at steady state by enhancing the quantum coherence quantified by entanglement entropy. The perfect quantum yield over 90% has been obtained, with the exciton-vibration coupling. We attribute these improvements to the renormalization of the electronic couplings effectively induced by exciton-vibration interaction and the subsequent delocalization of excitons. Finally, we demonstrate that the thermal relaxation and dephasing can help the excitation energy transfer in the PEB50 dimer.

  8. The evolutionary position of turtles revised

    NASA Astrophysics Data System (ADS)

    Zardoya, Rafael; Meyer, Axel

    2001-05-01

    Consensus on the evolutionary position of turtles within the amniote phylogeny has eluded evolutionary biologists for more than a century. This phylogenetic problem has remained unsolved partly because turtles have such a unique morphology that only few characters can be used to link them with any other group of amniotes. Among the many alternative hypotheses that have been postulated to explain the origin and phylogenetic relationships of turtles, a general agreement among paleontologists emerged in favoring the placement of turtles as the only living survivors of the anapsid reptiles (those that lack temporal fenestrae in the skull). However, recent morphological and molecular studies have radically changed our view of amniote phylogenetic relationships, and evidence is accumulating that supports the diapsid affinities of turtles. Molecular studies favor archosaurs (crocodiles and birds) as the living sister group of turtles, whereas morphological studies support lepidosaurs (tuatara, lizards, and snakes) as the closest living relatives of turtles. Accepting these hypotheses implies that turtles cannot be viewed any longer as primitive reptiles, and that they might have lost the temporal holes in the skull secondarily rather than never having had them.

  9. Evolutionary history of African mongoose rabies.

    PubMed

    Van Zyl, N; Markotter, W; Nel, L H

    2010-06-01

    Two biotypes or variants of rabies virus (RABV) occur in southern Africa. These variants are respectively adapted to hosts belonging to the Canidae family (the canid variant) and hosts belonging to the Herpestidae family (the mongoose variant). Due to the distinct host adaptation and differences in epidemiology and pathogenesis, it has been hypothesized that the two variants were introduced into Africa at different times. The objective of this study was to investigate the molecular phylogeny of representative RABV isolates of the mongoose variant towards a better understanding of the origins of this group. The study was based on an analysis of the full nucleoprotein and glycoprotein gene sequences of a panel of 27 viruses. Phylogenetic analysis of this dataset confirmed extended evolutionary adaptation of isolates in specific geographic areas. The evolutionary dynamics of this virus variant was investigated using Bayesian methodology, allowing for rate variation among viral lineages. Molecular clock analysis estimated the age of the African mongoose RABV to be approximately 200 years old, which is in concurrence with literature describing rabies in mongooses since the early 1800 s.

  10. Communication: Low-energy free-electron driven molecular engineering: In situ preparation of intrinsically short-lived carbon-carbon covalent dimer of CO

    NASA Astrophysics Data System (ADS)

    Davis, Daly; Sajeev, Y.

    2017-02-01

    Molecular modification induced through the resonant attachment of a low energy electron (LEE) is a novel approach for molecular engineering. In this communication, we explore the possibility to use the LEE as a quantum tool for the in situ preparation of short lived molecules. Using ab initio quantum chemical methods, this possibility is best illustrated for the in situ preparation of the intrinsically short-lived carbon-carbon covalent dimer of CO from a glyoxal molecule. The chemical conversion of glyoxal to the covalent dimer of CO is initiated and driven by the resonant capture of a near 11 eV electron by the glyoxal molecule. The resulting two-particle one-hole (2p-1h) negative ion resonant state (NIRS) of the glyoxal molecule undergoes a barrierless radical dehydrogenation reaction and produces the covalent dimer of CO. The autoionization electron spectra from the 2p-1h NIRS at the dissociation limit of the dehydrogenation reaction provides access to the electronic states of the CO dimer. The overall process is an example of a catalytic electron reaction channel.

  11. Molecular biomimetics: GEPI-based biological routes to technology.

    PubMed

    Tamerler, Candan; Khatayevich, Dmitriy; Gungormus, Mustafa; Kacar, Turgay; Oren, E Emre; Hnilova, Marketa; Sarikaya, Mehmet

    2010-01-01

    In nature, the viability of biological systems is sustained via specific interactions among the tens of thousands of proteins, the major building blocks of organisms from the simplest single-celled to the most complex multicellular species. Biomolecule-material interaction is accomplished with molecular specificity and efficiency leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, Mother Nature developed molecular recognition by successive cycles of mutation and selection. Molecular specificity of probe-target interactions, e.g., ligand-receptor, antigen-antibody, is always based on specific peptide molecular recognition. Using biology as a guide, we can now understand, engineer, and control peptide-material interactions and exploit them as a new design tool for novel materials and systems. We adapted the protocols of combinatorially designed peptide libraries, via both cell surface or phage display methods; using these we select short peptides with specificity to a variety of practical materials. These genetically engineered peptides for inorganics (GEPI) are then studied experimentally to establish their binding kinetics and surface stability. The bound peptide structure and conformations are interrogated both experimentally and via modeling, and self-assembly characteristics are tested via atomic force microscopy. We further engineer the peptide binding and assembly characteristics using a computational biomimetics approach where bioinformatics based peptide-sequence similarity analysis is developed to design higher generation function-specific peptides. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems in a wide-range of applications from tissue engineering, disease diagnostics, and therapeutics to various areas of nanotechnology where integration is required among inorganic, organic and biological materials. Here, we

  12. Genetic engineering compared to natural genetic variations.

    PubMed

    Arber, Werner

    2010-11-30

    By comparing strategies of genetic alterations introduced in genetic engineering with spontaneously occurring genetic variation, we have come to conclude that both processes depend on several distinct and specific molecular mechanisms. These mechanisms can be attributed, with regard to their evolutionary impact, to three different strategies of genetic variation. These are local nucleotide sequence changes, intragenomic rearrangement of DNA segments and the acquisition of a foreign DNA segment by horizontal gene transfer. Both the strategies followed in genetic engineering and the amounts of DNA sequences thereby involved are identical to, or at least very comparable with, those involved in natural genetic variation. Therefore, conjectural risks of genetic engineering must be of the same order as those for natural biological evolution and for conventional breeding methods. These risks are known to be quite low. There is no scientific reason to assume special long-term risks for GM crops. For future agricultural developments, a road map is designed that can be expected to lead, by a combination of genetic engineering and conventional plant breeding, to crops that can insure food security and eliminate malnutrition and hunger for the entire human population on our planet. Public-private partnerships should be formed with the mission to reach the set goals in the coming decades.

  13. Evolutionary and Developmental Modules

    PubMed Central

    Lacquaniti, Francesco; Ivanenko, Yuri P.; d’Avella, Andrea; Zelik, Karl E.; Zago, Myrka

    2013-01-01

    The identification of biological modules at the systems level often follows top-down decomposition of a task goal, or bottom-up decomposition of multidimensional data arrays into basic elements or patterns representing shared features. These approaches traditionally have been applied to mature, fully developed systems. Here we review some results from two other perspectives on modularity, namely the developmental and evolutionary perspective. There is growing evidence that modular units of development were highly preserved and recombined during evolution. We first consider a few examples of modules well identifiable from morphology. Next we consider the more difficult issue of identifying functional developmental modules. We dwell especially on modular control of locomotion to argue that the building blocks used to construct different locomotor behaviors are similar across several animal species, presumably related to ancestral neural networks of command. A recurrent theme from comparative studies is that the developmental addition of new premotor modules underlies the postnatal acquisition and refinement of several different motor behaviors in vertebrates. PMID:23730285

  14. Evolutionary Tracks for Betelgeuse

    NASA Astrophysics Data System (ADS)

    Dolan, Michelle; Mathews, Grant; Dearborn, David

    2008-04-01

    We have constructed a series of quasi-hydrostatic evolutionary models for the M2 Iab supergiant Betelgeuse (Õrionis). Our models are constrained by the observed temperature, luminosity, surface composition and mass loss for this star, along with recent parallax measurements and high resolution imagery which directly determine its radius. The surface convective zone obtained in our model naturally accounts for observed variations in surface luminosity and the size of detected surface bright spots. In our models these result from upflowing convective material from regions of high temperature in a surface convective zone. We also account for the observed periodic variability as the result of the effective equation of state in a simple linear pulsation model. Based upon a comparison between the accumulated mass loss in the observed circumstellar shell, and the lower limit on luminosity we suggest that this star most likely has a mass of either 16 ±2 M if a Reimers lass loss rate applies or 20 ±2 for the de Jager mass loss rate. For any mass loss rate the star must be close to the tip of the first ascent up the giant branch.

  15. Evolutionary cytogenetics in salamanders.

    PubMed

    Sessions, Stanley K

    2008-01-01

    Salamanders (Amphibia: Caudata/Urodela) have been the subject of numerous cytogenetic studies, and data on karyotypes and genome sizes are available for most groups. Salamanders show a more-or-less distinct dichotomy between families with large chromosome numbers and interspecific variation in chromosome number, relative size, and shape (i.e. position of the centromere), and those that exhibit very little variation in these karyological features. This dichotomy is the basis of a major model of karyotype evolution in salamanders involving a kind of 'karyotypic orthoselection'. Salamanders are also characterized by extremely large genomes (in terms of absolute mass of nuclear DNA) and extensive variation in genome size (and overall size of the chromosomes), which transcends variation in chromosome number and shape. The biological significance and evolution of chromosome number and shape within the karyotype is not yet understood, but genome size variation has been found to have strong phenotypic, biogeographic, and phylogenetic correlates that reveal information about the biological significance of this cytogenetic variable. Urodeles also present the advantage of only 10 families and less than 600 species, which facilitates the analysis of patterns within the entire order. The purpose of this review is to present a summary of what is currently known about overall patterns of variation in karyology and genome size in salamanders. These patterns are discussed within an evolutionary context.

  16. Evolutionary financial market models

    NASA Astrophysics Data System (ADS)

    Ponzi, A.; Aizawa, Y.

    2000-12-01

    We study computer simulations of two financial market models, the second a simplified model of the first. The first is a model of the self-organized formation and breakup of crowds of traders, motivated by the dynamics of competitive evolving systems which shows interesting self-organized critical (SOC)-type behaviour without any fine tuning of control parameters. This SOC-type avalanching and stasis appear as realistic volatility clustering in the price returns time series. The market becomes highly ordered at ‘crashes’ but gradually loses this order through randomization during the intervening stasis periods. The second model is a model of stocks interacting through a competitive evolutionary dynamic in a common stock exchange. This model shows a self-organized ‘market-confidence’. When this is high the market is stable but when it gets low the market may become highly volatile. Volatile bursts rapidly increase the market confidence again. This model shows a phase transition as temperature parameter is varied. The price returns time series in the transition region is very realistic power-law truncated Levy distribution with clustered volatility and volatility superdiffusion. This model also shows generally positive stock cross-correlations as is observed in real markets. This model may shed some light on why such phenomena are observed.

  17. Molecular tools and protocols for engineering the acid-tolerant yeast Zygosaccharomyces bailii as a potential cell factory.

    PubMed

    Branduardi, Paola; Dato, Laura; Porro, Danilo

    2014-01-01

    Microorganisms offer a tremendous potential as cell factories, and they are indeed used by humans for centuries for biotransformations. Among them, yeasts combine the advantage of unicellular state with a eukaryotic organization, and, in the era of biorefineries, their biodiversity can offer solutions to specific process constraints. Zygosaccharomyces bailii, an ascomycetales budding yeast, is widely known for its peculiar tolerance to various stresses, among which are organic acids. Despite the possibility to apply with this yeast some of the molecular tools and protocols routinely used to manipulate Saccharomyces cerevisiae, adjustments and optimizations are necessary. Here, we describe in detail protocols for transformation, for target gene disruption or gene integration, and for designing episomal expression plasmids helpful for developing and further studying the yeast Z. bailii.

  18. PACE4-based molecular targeting of prostate cancer using an engineered ⁶⁴Cu-radiolabeled peptide inhibitor.

    PubMed

    Couture, Frédéric; Levesque, Christine; Dumulon-Perreault, Véronique; Ait-Mohand, Samia; D'Anjou, François; Day, Robert; Guérin, Brigitte

    2014-08-01

    The potential of PACE4 as a pharmacological target in prostate cancer has been demonstrated as this proprotein convertase is strongly overexpressed in human prostate cancer tissues and its inhibition, using molecular or pharmacological approaches, results in reduced cell proliferation and tumor progression in mouse tumor xenograft models. We developed a PACE4 high-affinity peptide inhibitor, namely, the multi-leucine (ML), and sought to determine whether this peptide could be exploited for the targeting of prostate cancer for diagnostic or molecular imaging purposes. We conjugated a bifunctional chelator 1,4,7-triazacyclononane-1,4,7- triacetic acid (NOTA) to the ML peptide for copper-64 ((64)Cu) labeling and positron emission tomography (PET)- based prostate cancer detection. Enzyme kinetic assays against recombinant PACE4 showed that the NOTA-modified ML peptide displays identical inhibitory properties compared to the unmodified peptide. In vivo biodistribution of the (64)Cu/NOTA-ML peptide evaluated in athymic nude mice bearing xenografts of two human prostate carcinoma cell lines showed a rapid and high uptake in PACE4-expressing LNCaP tumor at an early time point and in PACE4-rich organs. Co-injection of unlabeled peptide confirmed that tumor uptake was target-specific. PACE4-negative tumors displayed no tracer uptake 15 minutes after injection, while the kidneys, demonstrated high uptake due to rapid renal clearance of the peptide. The present study supports the feasibility of using a (64)Cu/NOTA-ML peptide for PACE4-targeted prostate cancer detection and PACE4 status determination by PET imaging but also provides evidence that ML inhibitor-based drugs would readily reach tumor sites under in vivo conditions for pharmacological intervention or targeted radiation therapy.

  19. Molecular dynamics-based triangulation algorithm of free-form parametric surfaces for computer-aided engineering

    NASA Astrophysics Data System (ADS)

    Zheleznyakova, A. L.

    2015-05-01

    A new computational approach for automated triangulation of Computer-Aided Design (CAD) surface models, applicable to various CFD (Computational Fluid Dynamics) problems of practical interest is proposed. The complex shaped product configurations are represented by a set of Non-Uniform Rational B-Splines (NURBS) surface patches. The suggested technique is based on the molecular dynamics method. The main idea of the approach is that the mesh nodes are considered as similarly charged interacting particles which move within the region to be meshed under the influence of internal (such as particle-particle interaction forces) and external forces as well as optional additional forces. Moreover, the particles experience a medium resistance due to which the system comes to equilibrium within a relatively short period of time. The proposed 3D surface mesh generation algorithm uses a parametric NURBS representation as initial definition of the domain boundary. This method first distributes the interacting nodes into optimal locations in the parametric domain of the NURBS surface patch using molecular dynamics simulation. Then, the well-shaped triangles can be created after connecting the nodes by Delaunay triangulation. Finally, the mapping from parametric space to 3D physical space is performed. Since the presented interactive algorithm allows to control the distance between a pair of nodes depending on the curvature of the NURBS surface, the method generates high quality triangular mesh. The algorithm enables to produce uniform mesh, as well as anisotropic adaptive mesh with refinement in the large gradient regions. The mesh generation approach has the abilities to preserve the representation accuracy of the input geometry model, create a close relationship between geometry modeling and grid generation process, be automated to a large degree. Some examples are considered in order to illustrate the method's ability to generate a surface mesh for a complicated CAD model.

  20. Human Germline Mutation and the Erratic Evolutionary Clock

    PubMed Central

    Przeworski, Molly

    2016-01-01

    Our understanding of the chronology of human evolution relies on the “molecular clock” provided by the steady accumulation of substitutions on an evolutionary lineage. Recent analyses of human pedigrees have called this understanding into question by revealing unexpectedly low germline mutation rates, which imply that substitutions accrue more slowly than previously believed. Translating mutation rates estimated from pedigrees into substitution rates is not as straightforward as it may seem, however. We dissect the steps involved, emphasizing that dating evolutionary events requires not “a mutation rate” but a precise characterization of how mutations accumulate in development in males and females—knowledge that remains elusive. PMID:27760127

  1. Enhancing dye-sensitized solar cell performances by molecular engineering: highly efficient π-extended organic sensitizers.

    PubMed

    Grisorio, Roberto; De Marco, Luisa; Agosta, Rita; Iacobellis, Rosabianca; Giannuzzi, Roberto; Manca, Michele; Mastrorilli, Piero; Gigli, Giuseppe; Suranna, Gian Paolo

    2014-09-01

    This study deals with the synthesis and characterization of two π-extended organic sensitizers (G1 and G2) for applications in dye-sensitized solar cells. The materials are designed with a D-A-π-A structure constituted by i) a triarylamine group as the donor part, ii) a dithienyl-benzothiadiazole chromophore followed by iii) a further ethynylene-thiophene (G1) or ethynylene-benzene (G2) π-spacer and iv) a cyano-acrylic moiety as acceptor and anchoring part. An unusual structural extension of the π-bridge characterizes these structures. The so-configured sensitizers exhibit a broad absorption profile, the origin of which is supported by density functional theory. The absence of hypsochromic shifts as a consequence of deprotonation as well as notable optical and electrochemical stabilities are also observed. Concerning the performances in devices, electrochemical impedance spectroscopy indicates that the structural modification of the π-spacer mainly increases the electron lifetime of G2 with respect to G1. In devices, this feature translates into a superior power conversion efficiency of G2, reaching 8.1%. These results are comparable to those recorded for N719 and are higher with respect to literature congeners, supporting further structural engineering of the π-bridge extension in the search for better performing π-extended organic sensitizers.

  2. Evolutionary rescue beyond the models

    PubMed Central

    Gomulkiewicz, Richard; Shaw, Ruth G.

    2013-01-01

    Laboratory model systems and mathematical models have shed considerable light on the fundamental properties and processes of evolutionary rescue. But it remains to determine the extent to which these model-based findings can help biologists predict when evolution will fail or succeed in rescuing natural populations that are facing novel conditions that threaten their persistence. In this article, we present a prospectus for transferring our basic understanding of evolutionary rescue to wild and other non-laboratory populations. Current experimental and theoretical results emphasize how the interplay between inheritance processes and absolute fitness in changed environments drive population dynamics and determine prospects of extinction. We discuss the challenge of inferring these elements of the evolutionary rescue process in field and natural settings. Addressing this challenge will contribute to a more comprehensive understanding of population persistence that combines processes of evolutionary rescue with developmental and ecological mechanisms. PMID:23209173

  3. On the evolutionary relationship between chondrocytes and osteoblasts

    PubMed Central

    Gómez-Picos, Patsy; Eames, B. Frank

    2015-01-01

    Vertebrates are the only animals that produce bone, but the molecular genetic basis for this evolutionary novelty remains obscure. Here, we synthesize information from traditional evolutionary and modern molecular genetic studies in order to generate a working hypothesis on the evolution of the gene regulatory network (GRN) underlying bone formation. Since transcription factors are often core components of GRNs (i.e., kernels), we focus our analyses on Sox9 and Runx2. Our argument centers on three skeletal tissues that comprise the majority of the vertebrate skeleton: immature cartilage, mature cartilage, and bone. Immature cartilage is produced during early stages of cartilage differentiation and can persist into adulthood, whereas mature cartilage undergoes additional stages of differentiation, including hypertrophy and mineralization. Functionally, histologically, and embryologically, these three skeletal tissues are very similar, yet unique, suggesting that one might have evolved from another. Traditional studies of the fossil record, comparative anatomy and embryology demonstrate clearly that immature cartilage evolved before mature cartilage or bone. Modern molecular approaches show that the GRNs regulating differentiation of these three skeletal cell fates are similar, yet unique, just like the functional and histological features of the tissues themselves. Intriguingly, the Sox9 GRN driving cartilage formation appears to be dominant to the Runx2 GRN of bone. Emphasizing an embryological and evolutionary transcriptomic view, we hypothesize that the Runx2 GRN underlying bone formation was co-opted from mature cartilage. We discuss how modern molecular genetic experiments, such as comparative transcriptomics, can test this hypothesis directly, meanwhile permitting levels of constraint and adaptation to be evaluated quantitatively. Therefore, comparative transcriptomics may revolutionize understanding of not only the clade-specific evolution of skeletal cells

  4. Evolutionary constraints or opportunities?

    PubMed Central

    Sharov, Alexei A.

    2014-01-01

    Natural selection is traditionally viewed as a leading factor of evolution, whereas variation is assumed to be random and non-directional. Any order in variation is attributed to epigenetic or developmental constraints that can hinder the action of natural selection. In contrast I consider the positive role of epigenetic mechanisms in evolution because they provide organisms with opportunities for rapid adaptive change. Because the term “constraint” has negative connotations, I use the term “regulated variation” to emphasize the adaptive nature of phenotypic variation, which helps populations and species to survive and evolve in changing environments. The capacity to produce regulated variation is a phenotypic property, which is not described in the genome. Instead, the genome acts as a switchboard, where mostly random mutations switch “on” or “off” preexisting functional capacities of organism components. Thus, there are two channels of heredity: informational (genomic) and structure-functional (phenotypic). Functional capacities of organisms most likely emerged in a chain of modifications and combinations of more simple ancestral functions. The role of DNA has been to keep records of these changes (without describing the result) so that they can be reproduced in the following generations. Evolutionary opportunities include adjustments of individual functions, multitasking, connection between various components of an organism, and interaction between organisms. The adaptive nature of regulated variation can be explained by the differential success of lineages in macro-evolution. Lineages with more advantageous patterns of regulated variation are likely to produce more species and secure more resources (i.e., long-term lineage selection). PMID:24769155

  5. Reverse engineering the euglenoid movement

    PubMed Central

    Arroyo, Marino; Heltai, Luca; Millán, Daniel; DeSimone, Antonio

    2012-01-01

    Euglenids exhibit an unconventional motility strategy amongst unicellular eukaryotes, consisting of large-amplitude highly concerted deformations of the entire body (euglenoid movement or metaboly). A plastic cell envelope called pellicle mediates these deformations. Unlike ciliary or flagellar motility, the biophysics of this mode is not well understood, including its efficiency and molecular machinery. We quantitatively examine video recordings of four euglenids executing such motions with statistical learning methods. This analysis reveals strokes of high uniformity in shape and pace. We then interpret the observations in the light of a theory for the pellicle kinematics, providing a precise understanding of the link between local actuation by pellicle shear and shape control. We systematically understand common observations, such as the helical conformations of the pellicle, and identify previously unnoticed features of metaboly. While two of our euglenids execute their stroke at constant body volume, the other two exhibit deviations of about 20% from their average volume, challenging current models of low Reynolds number locomotion. We find that the active pellicle shear deformations causing shape changes can reach 340%, and estimate the velocity of the molecular motors. Moreover, we find that metaboly accomplishes locomotion at hydrodynamic efficiencies comparable to those of ciliates and flagellates. Our results suggest new quantitative experiments, provide insight into the evolutionary history of euglenids, and suggest that the pellicle may serve as a model for engineered active surfaces with applications in microfluidics. PMID:23047705

  6. Reverse engineering of modified genes by Bayesian network analysis defines molecular determinants critical to the development of glioblastoma.

    PubMed

    Kunkle, Brian W; Yoo, Changwon; Roy, Deodutta

    2013-01-01

    In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV), and 'key genes' within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96-100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential 'hubs of activity'. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several 'key genes' may be required for the development of glioblastoma. Further studies are needed to validate these 'key genes' as useful tools for early detection and novel therapeutic options for these tumors.

  7. Molecular engineering of a TBET-based two-photon fluorescent probe for ratiometric imaging of living cells and tissues.

    PubMed

    Zhou, Liyi; Zhang, Xiaobing; Wang, Qianqian; Lv, Yifan; Mao, Guojiang; Luo, Aili; Wu, Yongxiang; Wu, Yuan; Zhang, Jing; Tan, Weihong

    2014-07-16

    In contrast to one-photon microscopy, two-photon probe-based fluorescent imaging can provide improved three-dimensional spatial localization and increased imaging depth. Consequently, it has become one of the most attractive techniques for studying biological events in living cells and tissues. However, the quantitation of these probes is primarily based on single-emission intensity change, which tends to be affected by a variety of environmental factors. Ratiometric probes, on the other hand, can eliminate these interferences by the built-in correction of the dual emission bands, resulting in a more favorable system for imaging living cells and tissues. Herein, for the first time, we adopted a through-bond energy transfer (TBET) strategy to design and synthesize a small molecular ratiometric two-photon fluorescent probe for imaging living cells and tissues in real time. Specifically, a two-photon fluorophore (D-π-A-structured naphthalene derivative) and a rhodamine B fluorophore are directly connected by electronically conjugated bond to form a TBET probe, or Np-Rh, which shows a target-modulated ratiometric two-photon fluorescence response with highly efficient energy transfer (93.7%) and two well-resolved emission peaks separated by 100 nm. This novel probe was then applied for two-photon imaging of living cells and tissues and showed high ratiometric imaging resolution and deep-tissue imaging depth of 180 μm, thus demonstrating its practical application in biological systems.

  8. Engineering the magnetic coupling and anisotropy at the molecule-magnetic surface interface in molecular spintronic devices

    NASA Astrophysics Data System (ADS)

    Campbell, Victoria E.; Tonelli, Monica; Cimatti, Irene; Moussy, Jean-Baptiste; Tortech, Ludovic; Dappe, Yannick J.; Rivière, Eric; Guillot, Régis; Delprat, Sophie; Mattana, Richard; Seneor, Pierre; Ohresser, Philippe; Choueikani, Fadi; Otero, Edwige; Koprowiak, Florian; Chilkuri, Vijay Gopal; Suaud, Nicolas; Guihéry, Nathalie; Galtayries, Anouk; Miserque, Frederic; Arrio, Marie-Anne; Sainctavit, Philippe; Mallah, Talal

    2016-12-01

    A challenge in molecular spintronics is to control the magnetic coupling between magnetic molecules and magnetic electrodes to build efficient devices. Here we show that the nature of the magnetic ion of anchored metal complexes highly impacts the exchange coupling of the molecules with magnetic substrates. Surface anchoring alters the magnetic anisotropy of the cobalt(II)-containing complex (Co(Pyipa)2), and results in blocking of its magnetization due to the presence of a magnetic hysteresis loop. In contrast, no hysteresis loop is observed in the isostructural nickel(II)-containing complex (Ni(Pyipa)2). Through XMCD experiments and theoretical calculations we find that Co(Pyipa)2 is strongly ferromagnetically coupled to the surface, while Ni(Pyipa)2 is either not coupled or weakly antiferromagnetically coupled to the substrate. These results highlight the importance of the synergistic effect that the electronic structure of a metal ion and the organic ligands has on the exchange interaction and anisotropy occurring at the molecule-electrode interface.

  9. Development of Direct and Optical Polarized Nuclear Magnetic Resonance (NMR) Methods for Characterization and Engineering of Mesophased Molecular Structures

    SciTech Connect

    Maxwell, R; Baumann, T; Taylor, B

    2002-01-29

    The development of NMR methods for the characterization of structure and dynamics in mesophase composite systems was originally proposed in this LDRD. Mesophase systems are organic/inorganic hybrid materials whose size and motional properties span the definition of liquids and solids, such as highly viscous gels or colloidal suspensions. They are often composite, ill defined, macromolecular structures that prove difficult to characterize. Mesophase materials are of broad scientific and programmatic interest and include composite load bearing foams, aerogels, optical coatings, silicate oligomers, porous heterogeneous catalysts, and nanostructured materials such as semiconductor quantum dot superlattices. Since mesophased materials and precursors generally lack long-range order they have proven to be difficult to characterize beyond local, shortrange order. NMR methods are optimal for such a task since NMR observables are sensitive to wide ranges of length (0-30{angstrom}) and time (10{sup -9}-10{sup 0}sec) scales. We have developed a suit of NMR methods to measure local, intermediate, and long range structure in a series of mesophase systems and have constructed correlations between NMR observables and molecular size, topology, and network structure. The goal of this research was the development of a strong LLNL capability in the characterization of mesophased materials by NMR spectroscopy that will lead to a capability in rational synthesis of such materials and a fundamental understanding of their structure-property relationships. We demonstrate our progress towards attaining this goal by presenting NMR results on four mesophased model systems.

  10. Deconstructing a plant macromolecular assembly: chemical architecture, molecular flexibility, and mechanical performance of natural and engineered potato suberins.

    PubMed

    Serra, Olga; Chatterjee, Subhasish; Figueras, Mercè; Molinas, Marisa; Stark, Ruth E

    2014-03-10

    Periderms present in plant barks are essential protective barriers to water diffusion, mechanical breakdown, and pathogenic invasion. They consist of densely packed layers of dead cells with cell walls that are embedded with suberin. Understanding the interplay of molecular structure, dynamics, and biomechanics in these cell wall-associated insoluble amorphous polymeric assemblies presents substantial investigative challenges. We report solid-state NMR coordinated with FT-IR and tensile strength measurements for periderms from native and wound-healing potatoes and from potatoes with genetically modified suberins. The analyses include the intact suberin aromatic-aliphatic polymer and cell-wall polysaccharides, previously reported soluble depolymerized transmethylation products, and undegraded residues including suberan. Wound-healing suberized potato cell walls, which are 2 orders of magnitude more permeable to water than native periderms, display a strikingly enhanced hydrophilic-hydrophobic balance, a degradation-resistant aromatic domain, and flexibility suggestive of an altered supramolecular organization in the periderm. Suppression of ferulate ester formation in suberin and associated wax remodels the periderm with more flexible aliphatic chains and abundant aromatic constituents that can resist transesterification, attenuates cooperative hydroxyfatty acid motions, and produces a mechanically compromised and highly water-permeable periderm.

  11. Deconstructing a Plant Macromolecular Assembly: Chemical Architecture, Molecular Flexibility, And Mechanical Performance of Natural and Engineered Potato Suberins

    PubMed Central

    2015-01-01

    Periderms present in plant barks are essential protective barriers to water diffusion, mechanical breakdown, and pathogenic invasion. They consist of densely packed layers of dead cells with cell walls that are embedded with suberin. Understanding the interplay of molecular structure, dynamics, and biomechanics in these cell wall-associated insoluble amorphous polymeric assemblies presents substantial investigative challenges. We report solid-state NMR coordinated with FT-IR and tensile strength measurements for periderms from native and wound-healing potatoes and from potatoes with genetically modified suberins. The analyses include the intact suberin aromatic–aliphatic polymer and cell-wall polysaccharides, previously reported soluble depolymerized transmethylation products, and undegraded residues including suberan. Wound-healing suberized potato cell walls, which are 2 orders of magnitude more permeable to water than native periderms, display a strikingly enhanced hydrophilic–hydrophobic balance, a degradation-resistant aromatic domain, and flexibility suggestive of an altered supramolecular organization in the periderm. Suppression of ferulate ester formation in suberin and associated wax remodels the periderm with more flexible aliphatic chains and abundant aromatic constituents that can resist transesterification, attenuates cooperative hydroxyfatty acid motions, and produces a mechanically compromised and highly water-permeable periderm. PMID:24502663

  12. Engineering the magnetic coupling and anisotropy at the molecule-magnetic surface interface in molecular spintronic devices.

    PubMed

    Campbell, Victoria E; Tonelli, Monica; Cimatti, Irene; Moussy, Jean-Baptiste; Tortech, Ludovic; Dappe, Yannick J; Rivière, Eric; Guillot, Régis; Delprat, Sophie; Mattana, Richard; Seneor, Pierre; Ohresser, Philippe; Choueikani, Fadi; Otero, Edwige; Koprowiak, Florian; Chilkuri, Vijay Gopal; Suaud, Nicolas; Guihéry, Nathalie; Galtayries, Anouk; Miserque, Frederic; Arrio, Marie-Anne; Sainctavit, Philippe; Mallah, Talal

    2016-12-08

    A challenge in molecular spintronics is to control the magnetic coupling between magnetic molecules and magnetic electrodes to build efficient devices. Here we show that the nature of the magnetic ion of anchored metal complexes highly impacts the exchange coupling of the molecules with magnetic substrates. Surface anchoring alters the magnetic anisotropy of the cobalt(II)-containing complex (Co(Pyipa)2), and results in blocking of its magnetization due to the presence of a magnetic hysteresis loop. In contrast, no hysteresis loop is observed in the isostructural nickel(II)-containing complex (Ni(Pyipa)2). Through XMCD experiments and theoretical calculations we find that Co(Pyipa)2 is strongly ferromagnetically coupled to the surface, while Ni(Pyipa)2 is either not coupled or weakly antiferromagnetically coupled to the substrate. These results highlight the importance of the synergistic effect that the electronic structure of a metal ion and the organic ligands has on the exchange interaction and anisotropy occurring at the molecule-electrode interface.

  13. A Preliminary Engineering Design of Intravascular Dual-Frequency Transducers for Contrast-Enhanced Acoustic Angiography and Molecular Imaging

    PubMed Central

    Ma, Jianguo; Martin, K. Heath; Dayton, Paul A.; Jiang, Xiaoning

    2014-01-01

    Current intravascular ultrasound (IVUS) probes are not optimized for contrast detection because of their design for high-frequency fundamental-mode imaging. However, data from transcutaneous contrast imaging suggests the possibility of utilizing contrast ultrasound for molecular imaging or vasa vasorum assessment to further elucidate atherosclerotic plaque deposition. This paper presents the design, fabrication, and characterization of a small-aperture (0.6 × 3 mm) IVUS probe optimized for high-frequency contrast imaging. The design utilizes a dual-frequency (6.5 MHz/30 MHz) transducer arrangement for exciting microbubbles at low frequencies (near their resonance) and detecting their broadband harmonics at high frequencies, minimizing detected tissue backscatter. The prototype probe is able to generate nonlinear microbubble response with more than 1.2 MPa of rarefractional pressure (mechanical index: 0.48) at 6.5 MHz, and is also able to detect microbubble response with a broadband receiving element (center frequency: 30 MHz, −6-dB fractional bandwidth: 58.6%). Nonlinear super-harmonics from microbubbles flowing through a 200-μm-diameter micro-tube were clearly detected with a signal-to-noise ratio higher than 12 dB. Preliminary phantom imaging at the fundamental frequency (30 MHz) and dual-frequency super-harmonic imaging results suggest the promise of small aperture, dual-frequency IVUS transducers for contrast-enhanced IVUS imaging. PMID:24801226

  14. Evolutionary diversification in stickleback affects ecosystem functioning.

    PubMed

    Harmon, Luke J; Matthews, Blake; Des Roches, Simone; Chase, Jonathan M; Shurin, Jonathan B; Schluter, Dolph

    2009-04-30

    Explaining the ecological causes of evolutionary diversification is a major focus of biology, but surprisingly little has been said about the effects of evolutionary diversification on ecosystems. The number of species in an ecosystem and their traits are key predictors of many ecosystem-level processes, such as rates of productivity, biomass sequestration and decomposition. Here we demonstrate short-term ecosystem-level effects of adaptive radiation in the threespine stickleback (Gasterosteus aculeatus) over the past 10,000 years. These fish have undergone recent parallel diversification in several lakes in coastal British Columbia, resulting in the formation of two specialized species (benthic and limnetic) from a generalist ancestor. Using a mesocosm experiment, we demonstrate that this diversification has strong effects on ecosystems, affecting prey community structure, total primary production, and the nature of dissolved organic materials that regulate the spectral properties of light transmission in the system. However, these ecosystem effects do not simply increase in their relative strength with increasing specialization and species richness; instead, they reflect the complex and indirect consequences of ecosystem engineering by sticklebacks. It is well known that ecological factors influence adaptive radiation. We demonstrate that adaptive radiation, even over short timescales, can have profound effects on ecosystems.

  15. Active Processor Scheduling Using Evolutionary Algorithms

    DTIC Science & Technology

    2002-12-01

    xiii Active Processor Scheduling Using Evolutionary Algorithms I. Introduction A distributed system offers the ability to run applications across...calculations are made. This model is sometimes referred to as a form of the island model of evolutionary computation because each population is evolved... Evolutionary Algorithms for Solving Multi-Objective Problems. Genetic Algorithms and Evolutionary Computation , New York: Kluwer Academic Publishers, 2002

  16. Buried treasure: evolutionary perspectives on microbial iron piracy

    PubMed Central

    Barber, Matthew F.; Elde, Nels C.

    2015-01-01

    Host-pathogen interactions provide valuable systems for the study of evolutionary genetics and natural selection. The sequestration of essential iron has emerged as a critical innate defense system termed nutritional immunity, leading pathogens to evolve mechanisms of `iron piracy' to scavenge this metal from host proteins. This battle for iron carries numerous consequences not only for host-pathogen evolution, but also microbial community interactions. Here we highlight recent and potential future areas of investigation on the evolutionary implications of microbial iron piracy in relation to molecular arms races, host range, competition, and virulence. Applying evolutionary genetic approaches to the study of microbial iron acquisition could also provide new inroads for understanding and combating infectious disease. PMID:26431675

  17. Evolutionary systems biology: what it is and why it matters.

    PubMed

    Soyer, Orkun S; O'Malley, Maureen A

    2013-08-01

    Evolutionary systems biology (ESB) is a rapidly growing integrative approach that has the core aim of generating mechanistic and evolutionary understanding of genotype-phenotype relationships at multiple levels. ESB's more specific objectives include extending knowledge gained from model organisms to non-model organisms, predicting the effects of mutations, and defining the core network structures and dynamics that have evolved to cause particular intracellular and intercellular responses. By combining mathematical, molecular, and cellular approaches to evolution, ESB adds new insights and methods to the modern evolutionary synthesis, and offers ways in which to enhance its explanatory and predictive capacities. This combination of prediction and explanation marks ESB out as a research manifesto that goes further than its two contributing fields. Here, we summarize ESB via an analysis of characteristic research examples and exploratory questions, while also making a case for why these integrative efforts are worth pursuing.

  18. An experimentally determined evolutionary model dramatically improves phylogenetic fit.

    PubMed

    Bloom, Jesse D

    2014-08-01

    All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.

  19. Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy.

    PubMed

    Barber, Matthew F; Elde, Nels C

    2015-11-01

    Host-pathogen interactions provide valuable systems for the study of evolutionary genetics and natural selection. The sequestration of essential iron has emerged as a crucial innate defense system termed nutritional immunity, leading pathogens to evolve mechanisms of 'iron piracy' to scavenge this metal from host proteins. This battle for iron carries numerous consequences not only for host-pathogen evolution but also microbial community interactions. Here we highlight recent and potential future areas of investigation on the evolutionary implications of microbial iron piracy in relation to molecular arms races, host range, competition, and virulence. Applying evolutionary genetic approaches to the study of microbial iron acquisition could also provide new inroads for understanding and combating infectious disease.

  20. Fundamentals of fungal molecular population genetic analyses.

    PubMed

    Xu, Jianping

    2006-07-01

    The last two decades have seen tremendous growth in the development and application of molecular methods in the analyses of fungal species and populations. In this paper, I provide an overview of the molecular techniques and the basic analytical tools used to address various fundamental population and evolutionary genetic questions in fungi. With increasing availability and decreasing cost, DNA sequencing is becoming a mainstream data acquisition method in fungal evolutionary genetic studies. However, other methods, especially those based on the polymerase chain reaction, remain powerful in addressing specific questions for certain groups of taxa. These developments are bringing fungal population and evolutionary genetics into mainstream ecology and evolutionary biology.

  1. Molecular Characterization of the Gas-Particle Interface of Soot Sampled from a Diesel Engine Using a Titration Method.

    PubMed

    Tapia, A; Salgado, M S; Martín, María Pilar; Lapuerta, M; Rodríguez-Fernández, J; Rossi, M J; Cabañas, B

    2016-03-15

    Surface functional groups of two different types of combustion aerosols, a conventional diesel (EN 590) and a hydrotreated vegetable oil (HVO) soot, have been investigated using heterogeneous chemistry (i.e., gas-particle surface reactions). A commercial sample of amorphous carbon (Printex XE2-B) was analyzed as a reference substrate. A Knudsen flow reactor was used to carry out the experiments under molecular flow conditions. The selected gases for the titration experiments were: N(CH3)3 for the identification of acidic sites, NH2OH for the presence of carbonyl groups, CF3COOH and HCl for basic sites of different strength, and O3 and NO2 for reducing groups. Reactivity with N(CH3)3 indicates a lower density of acidic functionalities for Printex XE2-B in relation to diesel and HVO soot. Results for NH2OH experiments indicates that commercial amorphous carbon exhibits a lower abundance of available carbonyl groups at the interface compared to the results from diesel and HVO soot, the latter being the one with the largest abundance of carbonyl functions. Reactions with acids indicate the presence of weak basic oxides on the particle surface that preferentially interact with the strong acid CF3COOH. Finally, reactions with O3 and NO2 reveal that diesel and especially HVO have a significantly higher reactivity with both oxidizers compared to that of Printex XE2-B because they have more reducing sites by roughly a factor of 10 and 30, respectively. The kinetics of titration reactions have also been investigated.

  2. The evolutionary origin and diversification of feathers.

    PubMed

    Prum, Richard O; Brush, Alan H

    2002-09-01

    Progress on the evolutionary origin and diversification of feathers has been hampered by conceptual problems and by the lack of plesiomorphic feather fossils. Recently, both of these limitations have been overcome by the proposal of the developmental theory of the origin of feathers, and the discovery of primitive feather fossils on nonavian theropod dinosaurs. The conceptual problems of previous theories of the origin of feathers are reviewed, and the alternative developmental theory is presented and discussed. The developmental theory proposes that feathers evolved through a series of evolutionary novelties in developmental mechanisms of the follicle and feather germ. The discovery of primitive and derived fossil feathers on a diversity of coelurosaurian theropod dinosaurs documents that feathers evolved and diversified in nonavian theropods before the origin of birds and before the origin of flight. The morphologies of these primitive feathers are congruent with the predictions of the developmental theory. Alternatives to the theropod origin of feathers are critique and rejected. Hypotheses for the initial function of feathers are reviewed. The aerodynamic theory of feather origins is falsified, but many other functions remain developmentally and phylogenetically plausible. Whatever their function, feathers evolved by selection for a follicle that would grow an emergent tubular appendage. Feathers are inherently tubular structures. The homology of feathers and scales is weakly supported. Feathers are composed of a suite of evolutionary novelties that evolved by the duplication, hierarchical organization, interaction, dissociation, and differentiation of morphological modules. The unique capacity for modular subdivision of the tubular feather follicle and germ has fostered the evolution of numerous innovations that characterize feathers. The evolution of feather keratin and the molecular basis of feather development are also discussed.

  3. Antibiotic resistance in the wild: an eco-evolutionary perspective.

    PubMed

    Hiltunen, Teppo; Virta, Marko; Laine, Anna-Liisa

    2017-01-19

    The legacy of the use and misuse of antibiotics in recent decades has left us with a global public health crisis: antibiotic-resistant bacteria are on the rise, making it harder to treat infections. At the same time, evolution of antibiotic resistance is probably the best-documented case of contemporary evolution. To date, research on antibiotic resistance has largely ignored the complexity of interactions that bacteria engage in. However, in natural populations, bacteria interact with other species; for example, competition and grazing are import interactions influencing bacterial population dynamics. Furthermore, antibiotic leakage to natural environments can radically alter bacterial communities. Overall, we argue that eco-evolutionary feedback loops in microbial communities can be modified by residual antibiotics and evolution of antibiotic resistance. The aim of this review is to connect some of the well-established key concepts in evolutionary biology and recent advances in the study of eco-evolutionary dynamics to research on antibiotic resistance. We also identify some key knowledge gaps related to eco-evolutionary dynamics of antibiotic resistance, and review some of the recent technical advantages in molecular microbiology that offer new opportunities for tackling these questions. Finally, we argue that using the full potential of evolutionary theory and active communication across the different fields is needed for solving this global crisis more efficiently.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'.

  4. Antibiotic resistance in the wild: an eco-evolutionary perspective

    PubMed Central

    Virta, Marko

    2017-01-01

    The legacy of the use and misuse of antibiotics in recent decades has left us with a global public health crisis: antibiotic-resistant bacteria are on the rise, making it harder to treat infections. At the same time, evolution of antibiotic resistance is probably the best-documented case of contemporary evolution. To date, research on antibiotic resistance has largely ignored the complexity of interactions that bacteria engage in. However, in natural populations, bacteria interact with other species; for example, competition and grazing are import interactions influencing bacterial population dynamics. Furthermore, antibiotic leakage to natural environments can radically alter bacterial communities. Overall, we argue that eco-evolutionary feedback loops in microbial communities can be modified by residual antibiotics and evolution of antibiotic resistance. The aim of this review is to connect some of the well-established key concepts in evolutionary biology and recent advances in the study of eco-evolutionary dynamics to research on antibiotic resistance. We also identify some key knowledge gaps related to eco-evolutionary dynamics of antibiotic resistance, and review some of the recent technical advantages in molecular microbiology that offer new opportunities for tackling these questions. Finally, we argue that using the full potential of evolutionary theory and active communication across the different fields is needed for solving this global crisis more efficiently. This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences'. PMID:27920384

  5. Evolutionary Development of the Simulation by Logical Modeling System (SIBYL)

    NASA Technical Reports Server (NTRS)

    Wu, Helen

    1995-01-01

    Through the evolutionary development of the Simulation by Logical Modeling System (SIBYL) we have re-engineered the expensive and complex IBM mainframe based Long-term Hardware Projection Model (LHPM) to a robust cost-effective computer based mode that is easy to use. We achieved significant cost reductions and improved productivity in preparing long-term forecasts of Space Shuttle Main Engine (SSME) hardware. The LHPM for the SSME is a stochastic simulation model that projects the hardware requirements over 10 years. SIBYL is now the primary modeling tool for developing SSME logistics proposals and Program Operating Plan (POP) for NASA and divisional marketing studies.

  6. Evolutionary inference via the Poisson Indel Process.

    PubMed

    Bouchard-Côté, Alexandre; Jordan, Michael I

    2013-01-22

    We address the problem of the joint statistical inference of phylogenetic trees and multiple sequence alignments from unaligned molecular sequences. This problem is generally formulated in terms of string-valued evolutionary processes along the branches of a phylogenetic tree. The classic evolutionary process, the TKF91 model [Thorne JL, Kishino H, Felsenstein J (1991) J Mol Evol 33(2):114-124] is a continuous-time Markov chain model composed of insertion, deletion, and substitution events. Unfortunately, this model gives rise to an intractable computational problem: The computation of the marginal likelihood under the TKF91 model is exponential in the number of taxa. In this work, we present a stochastic process, the Poisson Indel Process (PIP), in which the complexity of this computation is reduced to linear. The Poisson Indel Process is closely related to the TKF91 model, differing only in its treatment of insertions, but it has a global characterization as a Poisson process on the phylogeny. Standard results for Poisson processes allow key computations to be decoupled, which yields the favorable computational profile of inference under the PIP model. We present illustrative experiments in which Bayesian inference under the PIP model is compared with separate inference of phylogenies and alignments.

  7. Molecular isotopic engineering (MIE): industrial manufacture of naproxen of predetermined stable carbon-isotopic compositions for authenticity and security protection and intellectual property considerations

    NASA Astrophysics Data System (ADS)

    Jasper, J. P.; Farina, P.; Pearson, A.; Mezes, P. S.; Sabatelli, A. D.

    2016-05-01

    Molecular Isotopic Engineering (MIE) is the directed stable-isotopic synthesis of chemical products for reasons of product identification and of product security, and also for intellectual property considerations. We report here a generally excellent correspondence between the observed and predicted stable carbon-isotopic (δ13C) results for a successful directed synthesis of racemic mixture from its immediate precursors. The observed results are readily explained by the laws of mass balance and isotope mass balance. Oxygen- and hydrogen isotopic results which require an additional assessment of the effects of O and H exchange, presumably due to interaction with water in the reaction solution, are addressed elsewhere. A previous, cooperative study with the US FDA-DPA showed that individual manufacturers of naproxen could readily be differentiated by their stable-isotopic provenance (δ13C, δ18O, and δD ref. 1). We suggest that MIE can be readily employed in the bio/pharmaceutical industry without alteration of present manufacturing processes other than isotopically selecting and/or monitoring reactants and products.

  8. Rational molecular engineering of cyclopentadithiophene-bridged D-A-π-A sensitizers combining high photovoltaic efficiency with rapid dye adsorption

    PubMed Central

    Chai, Qipeng; Li, Wenqin; Liu, Jingchuan; Geng, Zhiyuan; Tian, He; Zhu, Wei-hong

    2015-01-01

    Dye-sensitized solar cell (DSSC) is considered as a feasible route to the clean and renewable energy conversion technique. The commercial application requires further enhancements on photovoltaic efficiency and simplification on the device fabrication. For avoiding the unpreferable trade-off between photocurrent (JSC) and photovoltage (VOC), here we report the molecular engineering and comprehensive photovoltaic characterization of three cyclopentadithiophene-bridged D-A-π-A motif sensitizers with a change in donor group. We make a careful choice on the donor and conjugation bridge for synergistically increasing JSC and VOC. Comparing with the reference dye WS-2, the photovoltaic efficiency with the single component dye of WS-51 increases by 18%, among one of the rare examples in pure metal-free organic dyes exceeding 10% in combination with traditional iodine redox couples. Moreover, WS-51 exhibits several prominent merits on potentially scale-up industrial application: i) facile synthetic route to target molecule, ii) simple dipping procedure without requirement of co-sensitization, and iii) rapid dye adsorption capability. PMID:26066974

  9. Rational molecular engineering of cyclopentadithiophene-bridged D-A-π-A sensitizers combining high photovoltaic efficiency with rapid dye adsorption

    NASA Astrophysics Data System (ADS)

    Chai, Qipeng; Li, Wenqin; Liu, Jingchuan; Geng, Zhiyuan; Tian, He; Zhu, Wei-Hong

    2015-06-01

    Dye-sensitized solar cell (DSSC) is considered as a feasible route to the clean and renewable energy conversion technique. The commercial application requires further enhancements on photovoltaic efficiency and simplification on the device fabrication. For avoiding the unpreferable trade-off between photocurrent (JSC) and photovoltage (VOC), here we report the molecular engineering and comprehensive photovoltaic characterization of three cyclopentadithiophene-bridged D-A-π-A motif sensitizers with a change in donor group. We make a careful choice on the donor and conjugation bridge for synergistically increasing JSC and VOC. Comparing with the reference dye WS-2, the photovoltaic efficiency with the single component dye of WS-51 increases by 18%, among one of the rare examples in pure metal-free organic dyes exceeding 10% in combination with traditional iodine redox couples. Moreover, WS-51 exhibits several prominent merits on potentially scale-up industrial application: i) facile synthetic route to target molecule, ii) simple dipping procedure without requirement of co-sensitization, and iii) rapid dye adsorption capability.

  10. Rational molecular engineering of cyclopentadithiophene-bridged D-A-π-A sensitizers combining high photovoltaic efficiency with rapid dye adsorption.

    PubMed

    Chai, Qipeng; Li, Wenqin; Liu, Jingchuan; Geng, Zhiyuan; Tian, He; Zhu, Wei-Hong

    2015-06-11

    Dye-sensitized solar cell (DSSC) is considered as a feasible route to the clean and renewable energy conversion technique. The commercial application requires further enhancements on photovoltaic efficiency and simplification on the device fabrication. For avoiding the unpreferable trade-off between photocurrent (JSC) and photovoltage (VOC), here we report the molecular engineering and comprehensive photovoltaic characterization of three cyclopentadithiophene-bridged D-A-π-A motif sensitizers with a change in donor group. We make a careful choice on the donor and conjugation bridge for synergistically increasing JSC and VOC. Comparing with the reference dye WS-2, the photovoltaic efficiency with the single component dye of WS-51 increases by 18%, among one of the rare examples in pure metal-free organic dyes exceeding 10% in combination with traditional iodine redox couples. Moreover, WS-51 exhibits several prominent merits on potentially scale-up industrial application: i) facile synthetic route to target molecule, ii) simple dipping procedure without requirement of co-sensitization, and iii) rapid dye adsorption capability.

  11. Evolutionary foundations for cancer biology

    PubMed Central

    Aktipis, C Athena; Nesse, Randolph M

    2013-01-01

    New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the significance of within-tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large-scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles—cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations—provide a foundation for understanding, preventing, and treating cancer. PMID:23396885

  12. Evolutionary foundations for cancer biology.

    PubMed

    Aktipis, C Athena; Nesse, Randolph M

    2013-01-01

    New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the significance of within-tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large-scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles-cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations-provide a foundation for understanding, preventing, and treating cancer.

  13. Evolutionary genetics of maternal effects

    PubMed Central

    Wolf, Jason B.; Wade, Michael J.

    2016-01-01

    Maternal genetic effects (MGEs), where genes expressed by mothers affect the phenotype of their offspring, are important sources of phenotypic diversity in a myriad of organisms. We use a single‐locus model to examine how MGEs contribute patterns of heritable and nonheritable variation and influence evolutionary dynamics in randomly mating and inbreeding populations. We elucidate the influence of MGEs by examining the offspring genotype‐phenotype relationship, which determines how MGEs affect evolutionary dynamics in response to selection on offspring phenotypes. This approach reveals important results that are not apparent from classic quantitative genetic treatments of MGEs. We show that additive and dominance MGEs make different contributions to evolutionary dynamics and patterns of variation, which are differentially affected by inbreeding. Dominance MGEs make the offspring genotype‐phenotype relationship frequency dependent, resulting in the appearance of negative frequency‐dependent selection, while additive MGEs contribute a component of parent‐of‐origin dependent variation. Inbreeding amplifies the contribution of MGEs to the additive genetic variance and, therefore enhances their evolutionary response. Considering evolutionary dynamics of allele frequency change on an adaptive landscape, we show that this landscape differs from the mean fitness surface, and therefore, under some condition, fitness peaks can exist but not be “available” to the evolving population. PMID:26969266

  14. The major synthetic evolutionary transitions

    PubMed Central

    Solé, Ricard

    2016-01-01

    Evolution is marked by well-defined events involving profound innovations that are known as ‘major evolutionary transitions'. They involve the integration of autonomous elements into a new, higher-level organization whereby the former isolated units interact in novel ways, losing their original autonomy. All major transitions, which include the origin of life, cells, multicellular systems, societies or language (among other examples), took place millions of years ago. Are these transitions unique, rare events? Have they instead universal traits that make them almost inevitable when the right pieces are in place? Are there general laws of evolutionary innovation? In order to approach this problem under a novel perspective, we argue that a parallel class of evolutionary transitions can be explored involving the use of artificial evolutionary experiments where alternative paths to innovation can be explored. These ‘synthetic’ transitions include, for example, the artificial evolution of multicellular systems or the emergence of language in evolved communicating robots. These alternative scenarios could help us to understand the underlying laws that predate the rise of major innovations and the possibility for general laws of evolved complexity. Several key examples and theoretical approaches are summarized and future challenges are outlined. This article is part of the themed issue ‘The major synthetic evolutionary transitions’. PMID:27431528

  15. Using Nonlinear Stochastic Evolutionary Game Strategy to Model an Evolutionary Biological Network of Organ Carcinogenesis Under a Natural Selection Scheme

    PubMed Central

    Chen, Bor-Sen; Tsai, Kun-Wei; Li, Cheng-Wei

    2015-01-01

    Molecular biologists have long recognized carcinogenesis as an evolutionary process that involves natural selection. Cancer is driven by the somatic evolution of cell lineages. In this study, the evolution of somatic cancer cell lineages during carcinogenesis was modeled as an equilibrium point (ie, phenotype of attractor) shifting, the process of a nonlinear stochastic evolutionary biological network. This process is subject to intrinsic random fluctuations because of somatic genetic and epigenetic variations, as well as extrinsic disturbances because of carcinogens and stressors. In order to maintain the normal function (ie, phenotype) of an evolutionary biological network subjected to random intrinsic fluctuations and extrinsic disturbances, a network robustness scheme that incorporates natural selection needs to be developed. This can be accomplished by selecting certain genetic and epigenetic variations to modify the network structure to attenuate intrinsic fluctuations efficiently and to resist extrinsic disturbances in order to maintain the phenotype of the evolutionary biological network at an equilibrium point (attractor). However, during carcinogenesis, the remaining (or neutral) genetic and epigenetic variations accumulate, and the extrinsic disturbances become too large to maintain the normal phenotype at the desired equilibrium point for the nonlinear evolutionary biological network. Thus, the network is shifted to a cancer phenotype at a new equilibrium point that begins a new evolutionary process. In this study, the natural selection scheme of an evolutionary biological network of carcinogenesis was derived from a robust negative feedback scheme based on the nonlinear stochastic Nash game strategy. The evolvability and phenotypic robustness criteria of the evolutionary cancer network were also estimated by solving a Hamilton–Jacobi inequality – constrained optimization problem. The simulation revealed that the phenotypic shift of the lung cancer

  16. Exploring the evolutionary history of centrosomes

    PubMed Central

    Azimzadeh, Juliette

    2014-01-01

    The centrosome is the main organizer of the microtubule cytoskeleton in animals, higher fungi and several other eukaryotic lineages. Centrosomes are usually located at the centre of cell in tight association with the nuclear envelope and duplicate at each cell cycle. Despite a great structural diversity between the different types of centrosomes, they are functionally equivalent and share at least some of their molecular components. In this paper, we explore the evolutionary origin of the different centrosomes, in an attempt to understand whether they are derived from an ancestral centrosome or evolved independently from the motile apparatus of distinct flagellated ancestors. We then discuss the evolution of centrosome structure and function within the animal lineage. PMID:25047607

  17. Choroid plexus in developmental and evolutionary perspective

    PubMed Central

    Bill, Brent Roy; Korzh, Vladimir

    2014-01-01

    The blood-cerebrospinal fluid boundary is present at the level of epithelial cells of the choroid plexus. As one of the sources of the cerebrospinal fluid (CSF), the choroid plexus (CP) plays an important role during brain development and function. Its formation has been studied largely in mammalian species. Lately, progress in other model animals, in particular the zebrafish, has brought a deeper understanding of CP formation, due in part to the ability to observe CP development in vivo. At the same time, advances in comparative genomics began providing information, which opens a possibility to understand further the molecular mechanisms involved in evolution of the CP and the blood-cerebrospinal fluid boundary formation. Hence this review focuses on analysis of the CP from developmental and evolutionary perspectives. PMID:25452709

  18. The evolutionary journey of Argonaute proteins

    PubMed Central

    Swarts, Daan C; Makarova, Kira; Wang, Yanli; Nakanishi, Kotaro; Ketting, René F; Koonin, Eugene V; Patel, Dinshaw J; van der Oost, John

    2015-01-01

    Argonaute proteins are conserved throughout all domains of life. Recently characterized prokaryotic Argonaute proteins (pAgos) participate in host defense by DNA interference, whereas eukaryotic Argonaute proteins (eAgos) control a wide range of processes by RNA interference. Here we review molecular mechanisms of guide and target binding by Argonaute proteins, and describe how the conformational changes induced by target binding lead to target cleavage. On the basis of structural comparisons and phylogenetic analyses of pAgos and eAgos, we reconstruct the evolutionary journey of the Argonaute proteins through the three domains of life and discuss how different structural features of pAgos and eAgos relate to their distinct physiological roles. PMID:25192263

  19. Neuronal boost to evolutionary dynamics.

    PubMed

    de Vladar, Harold P; Szathmáry, Eörs

    2015-12-06

    Standard evolutionary dynamics is limited by the constraints of the genetic system. A central message of evolutionary neurodynamics is that evolutionary dynamics in the brain can happen in a neuronal niche in real time, despite the fact that neurons do not reproduce. We show that Hebbian learning and structural synaptic plasticity broaden the capacity for informational replication and guided variability provided a neuronally plausible mechanism of replication is in place. The synergy between learning and selection is more efficient than the equivalent search by mutation selection. We also consider asymmetric landscapes and show that the learning weights become correlated with the fitness gradient. That is, the neuronal complexes learn the local properties of the fitness landscape, resulting in the generation of variability directed towards the direction of fitness increase, as if mutations in a genetic pool were drawn such that they would increase reproductive success. Evolution might thus be more efficient within evolved brains than among organisms out in the wild.

  20. Neuronal boost to evolutionary dynamics

    PubMed Central

    de Vladar, Harold P.; Szathmáry, Eörs

    2015-01-01