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Sample records for dynamic genetic repertoire

  1. Immune Repertoire Characteristics and Dynamics in Cancer

    DEFF Research Database (Denmark)

    Liu, Xiao

    The diversity of T and B cells in terms of their receptors is huge in the invertebrate’s immune system, to provide broad protection against the vast diversity of pathogens. Immune repertoire is defined as the sum of total subtypes that makes the organism’s immune system, either T cell receptor or...

  2. Systems Analysis Reveals High Genetic and Antigen-Driven Predetermination of Antibody Repertoires throughout B Cell Development

    Directory of Open Access Journals (Sweden)

    Victor Greiff

    2017-05-01

    Full Text Available Antibody repertoire diversity and plasticity is crucial for broad protective immunity. Repertoires change in size and diversity across multiple B cell developmental stages and in response to antigen exposure. However, we still lack fundamental quantitative understanding of the extent to which repertoire diversity is predetermined. Therefore, we implemented a systems immunology framework for quantifying repertoire predetermination on three distinct levels: (1 B cell development (pre-B cell, naive B cell, plasma cell, (2 antigen exposure (three structurally different proteins, and (3 four antibody repertoire components (V-gene usage, clonal expansion, clonal diversity, repertoire size extracted from antibody repertoire sequencing data (400 million reads. Across all three levels, we detected a dynamic balance of high genetic (e.g., >90% for V-gene usage and clonal expansion in naive B cells and antigen-driven (e.g., 40% for clonal diversity in plasma cells predetermination and stochastic variation. Our study has implications for the prediction and manipulation of humoral immunity.

  3. Degeneracy-driven self-structuring dynamics in selective repertoires.

    Science.gov (United States)

    Atamas, Sergei P; Bell, Jonathan

    2009-08-01

    Numerous biological interactions, such as interactions between T cell receptors or antibodies with antigens, interactions between enzymes and substrates, or interactions between predators and prey are often not strictly specific. In such less specific, or "sloppy," systems, referred to here as degenerate systems, a given unit of a diverse resource (antigens, enzymatic substrates, prey) is at risk of being recognized and consumed by multiple consumers (lymphocytes, enzymes, predators). In this study, we model generalized degenerate consumer-resource systems of Lotka-Volterra and Verhulst types. In the degenerate systems of Lotka-Volterra, there is a continuum of types of consumer and resource based on variation of a single trait (characteristic, or preference). The consumers experience competition for a continuum of resource types. This non-local interaction system is modeled with partial differential-integral equations and shows spontaneous self-structuring of the consumer population that depends on the degree of interaction degeneracy between resource and consumer, but does not mirror the distribution of resource. We also show that the classical Verhulst (i.e. logistic) single population model can be generalized to a degenerate model, which shows qualitative behavior similar to that in the degenerate Lotka-Volterra model. These results provide better insight into the dynamics of selective systems in biology, suggesting that adaptation of degenerate repertoires is not a simple "mirroring" of the environment by the "fittest" elements of population.

  4. Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD.

    Science.gov (United States)

    Atasoy, Selen; Roseman, Leor; Kaelen, Mendel; Kringelbach, Morten L; Deco, Gustavo; Carhart-Harris, Robin L

    2017-12-15

    Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used 'connectome-harmonic decomposition', a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.

  5. Frequency and genetic characterization of V(DD)J recombinants in the human peripheral blood antibody repertoire.

    Science.gov (United States)

    Briney, Bryan S; Willis, Jordan R; Hicar, Mark D; Thomas, James W; Crowe, James E

    2012-09-01

    Antibody heavy-chain recombination that results in the incorporation of multiple diversity (D) genes, although uncommon, contributes substantially to the diversity of the human antibody repertoire. Such recombination allows the generation of heavy chain complementarity determining region 3 (HCDR3) regions of extreme length and enables junctional regions that, because of the nucleotide bias of N-addition regions, are difficult to produce through normal V(D)J recombination. Although this non-classical recombination process has been observed infrequently, comprehensive analysis of the frequency and genetic characteristics of such events in the human peripheral blood antibody repertoire has not been possible because of the rarity of such recombinants and the limitations of traditional sequencing technologies. Here, through the use of high-throughput sequencing of the normal human peripheral blood antibody repertoire, we analysed the frequency and genetic characteristics of V(DD)J recombinants. We found that these recombinations were present in approximately 1 in 800 circulating B cells, and that the frequency was severely reduced in memory cell subsets. We also found that V(DD)J recombination can occur across the spectrum of diversity genes, indicating that virtually all recombination signal sequences that flank diversity genes are amenable to V(DD)J recombination. Finally, we observed a repertoire bias in the diversity gene repertoire at the upstream (5') position, and discovered that this bias was primarily attributable to the order of diversity genes in the genomic locus. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

  6. Targeted capture massively parallel sequencing analysis of LCIS and invasive lobular cancer: Repertoire of somatic genetic alterations and clonal relationships.

    Science.gov (United States)

    Sakr, Rita A; Schizas, Michail; Carniello, Jose V Scarpa; Ng, Charlotte K Y; Piscuoglio, Salvatore; Giri, Dilip; Andrade, Victor P; De Brot, Marina; Lim, Raymond S; Towers, Russell; Weigelt, Britta; Reis-Filho, Jorge S; King, Tari A

    2016-02-01

    Lobular carcinoma in situ (LCIS) has been proposed as a non-obligate precursor of invasive lobular carcinoma (ILC). Here we sought to define the repertoire of somatic genetic alterations in pure LCIS and in synchronous LCIS and ILC using targeted massively parallel sequencing. DNA samples extracted from microdissected LCIS, ILC and matched normal breast tissue or peripheral blood from 30 patients were subjected to massively parallel sequencing targeting all exons of 273 genes, including the genes most frequently mutated in breast cancer and DNA repair-related genes. Single nucleotide variants and insertions and deletions were identified using state-of-the-art bioinformatics approaches. The constellation of somatic mutations found in LCIS (n = 34) and ILC (n = 21) were similar, with the most frequently mutated genes being CDH1 (56% and 66%, respectively), PIK3CA (41% and 52%, respectively) and CBFB (12% and 19%, respectively). Among 19 LCIS and ILC synchronous pairs, 14 (74%) had at least one identical mutation in common, including identical PIK3CA and CDH1 mutations. Paired analysis of independent foci of LCIS from 3 breasts revealed at least one common mutation in each of the 3 pairs (CDH1, PIK3CA, CBFB and PKHD1L1). LCIS and ILC have a similar repertoire of somatic mutations, with PIK3CA and CDH1 being the most frequently mutated genes. The presence of identical mutations between LCIS-LCIS and LCIS-ILC pairs demonstrates that LCIS is a clonal neoplastic lesion, and provides additional evidence that at least some LCIS are non-obligate precursors of ILC. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  7. From observational to dynamic genetics

    Directory of Open Access Journals (Sweden)

    Claire M. A. Haworth

    2014-01-01

    Full Text Available Twin and family studies have shown that most traits are at least moderately heritable. But what are the implications of finding genetic influence for the design of intervention and prevention programs? For complex traits, heritability does not mean immutability, and research has shown that genetic influences can change with age, context and in response to behavioural and drug interventions. The most significant implications for intervention will come when we move from observational genetics to investigating dynamic genetics, including genetically sensitive interventions. Future interventions should be designed to overcome genetic risk and draw upon genetic strengths by changing the environment.

  8. The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast.

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    David Gresham

    2008-12-01

    Full Text Available The experimental evolution of laboratory populations of microbes provides an opportunity to observe the evolutionary dynamics of adaptation in real time. Until very recently, however, such studies have been limited by our inability to systematically find mutations in evolved organisms. We overcome this limitation by using a variety of DNA microarray-based techniques to characterize genetic changes -- including point mutations, structural changes, and insertion variation -- that resulted from the experimental adaptation of 24 haploid and diploid cultures of Saccharomyces cerevisiae to growth in either glucose, sulfate, or phosphate-limited chemostats for approximately 200 generations. We identified frequent genomic amplifications and rearrangements as well as novel retrotransposition events associated with adaptation. Global nucleotide variation detection in ten clonal isolates identified 32 point mutations. On the basis of mutation frequencies, we infer that these mutations and the subsequent dynamics of adaptation are determined by the batch phase of growth prior to initiation of the continuous phase in the chemostat. We relate these genotypic changes to phenotypic outcomes, namely global patterns of gene expression, and to increases in fitness by 5-50%. We found that the spectrum of available mutations in glucose- or phosphate-limited environments combined with the batch phase population dynamics early in our experiments allowed several distinct genotypic and phenotypic evolutionary pathways in response to these nutrient limitations. By contrast, sulfate-limited populations were much more constrained in both genotypic and phenotypic outcomes. Thus, the reproducibility of evolution varies with specific selective pressures, reflecting the constraints inherent in the system-level organization of metabolic processes in the cell. We were able to relate some of the observed adaptive mutations (e.g., transporter gene amplifications to known features

  9. Analysis of B Cell Repertoire Dynamics Following Hepatitis B Vaccination in Humans, and Enrichment of Vaccine-specific Antibody Sequences

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    Jacob D. Galson

    2015-12-01

    Full Text Available Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7 days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity-determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21 days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation.

  10. Analysis of B Cell Repertoire Dynamics Following Hepatitis B Vaccination in Humans, and Enrichment of Vaccine-specific Antibody Sequences.

    Science.gov (United States)

    Galson, Jacob D; Trück, Johannes; Fowler, Anna; Clutterbuck, Elizabeth A; Münz, Márton; Cerundolo, Vincenzo; Reinhard, Claudia; van der Most, Robbert; Pollard, Andrew J; Lunter, Gerton; Kelly, Dominic F

    2015-12-01

    Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7 days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity-determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21 days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation.

  11. Dynamic traffic assignment : genetic algorithms approach

    Science.gov (United States)

    1997-01-01

    Real-time route guidance is a promising approach to alleviating congestion on the nations highways. A dynamic traffic assignment model is central to the development of guidance strategies. The artificial intelligence technique of genetic algorithm...

  12. Flexible cultural repertoires

    DEFF Research Database (Denmark)

    Lindegaard, Marie Rosenkrantz; Zimmermann, Francisca

    2017-01-01

    Despite extensive studies of street culture and the risks of offending and victimization in urban marginalized areas, little is known about the role of cultural repertoires for variation in victimization risks among young men not involved in crime. Based on two ethnographic studies, conducted...... independently of the authors in neighbouring township areas of Cape Town, we offer insights into patterns of victimization among young men not involved in crime who live and attend school in the townships. Young men WHO perform decent cultural repertoires are highly exposed to victimization due to their moral...... rejection of crime-involved youth. Young men who perform flexible cultural repertoires, by incorporating and shifting between gang and decent repertoires, experience low victimization due to their adaptation to crime-involved youth. Findings emphasize the importance of detailed investigations of the way...

  13. Television as a Hybrid Repertoire of Memory. New Dynamic Practices of Cultural Memory in the Multi-Platform Era

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    Berber Hagedoorn

    2013-06-01

    Full Text Available In this article, television is reconsidered as a hybrid ‘repertoire’ ofmemory. It is demonstrated how new dynamic production and scheduling practicesin connection with highly accessible and participatory forms of user engagementoffer opportunities for television users to engage with the past, and how suchpractices affect television as a practice of memory. The media platform HollandDoc is discussed as a principal casestudy. By adopting and expanding Aleida Assmann’s model of the dynamics ofcultural memory between remembering and forgetting, a new model to studytelevision as cultural memory is proposed which represents the medium’shybridity in the multi-platform era.

  14. Television as a Hybrid Repertoire of Memory. New Dynamic Practices of Cultural Memory in the Multi-Platform Era

    NARCIS (Netherlands)

    Hagedoorn, Berber

    2013-01-01

    abstractIn this article, television is reconsidered as a hybrid ‘repertoire’ ofmemory. It is demonstrated how new dynamic production and scheduling practicesin connection with highly accessible and participatory forms of user engagementoffer opportunities for television users to engage with the

  15. The Variable Regions of Lactobacillus rhamnosus Genomes Reveal the Dynamic Evolution of Metabolic and Host-Adaptation Repertoires.

    Science.gov (United States)

    Ceapa, Corina; Davids, Mark; Ritari, Jarmo; Lambert, Jolanda; Wels, Michiel; Douillard, François P; Smokvina, Tamara; de Vos, Willem M; Knol, Jan; Kleerebezem, Michiel

    2016-07-02

    Lactobacillus rhamnosus is a diverse Gram-positive species with strains isolated from different ecological niches. Here, we report the genome sequence analysis of 40 diverse strains of L. rhamnosus and their genomic comparison, with a focus on the variable genome. Genomic comparison of 40 L. rhamnosus strains discriminated the conserved genes (core genome) and regions of plasticity involving frequent rearrangements and horizontal transfer (variome). The L. rhamnosus core genome encompasses 2,164 genes, out of 4,711 genes in total (the pan-genome). The accessory genome is dominated by genes encoding carbohydrate transport and metabolism, extracellular polysaccharides (EPS) biosynthesis, bacteriocin production, pili production, the cas system, and the associated clustered regularly interspaced short palindromic repeat (CRISPR) loci, and more than 100 transporter functions and mobile genetic elements like phages, plasmid genes, and transposons. A clade distribution based on amino acid differences between core (shared) proteins matched with the clade distribution obtained from the presence-absence of variable genes. The phylogenetic and variome tree overlap indicated that frequent events of gene acquisition and loss dominated the evolutionary segregation of the strains within this species, which is paralleled by evolutionary diversification of core gene functions. The CRISPR-Cas system could have contributed to this evolutionary segregation. Lactobacillus rhamnosus strains contain the genetic and metabolic machinery with strain-specific gene functions required to adapt to a large range of environments. A remarkable congruency of the evolutionary relatedness of the strains' core and variome functions, possibly favoring interspecies genetic exchanges, underlines the importance of gene-acquisition and loss within the L. rhamnosus strain diversification. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  16. An improved genetic algorithm with dynamic topology

    International Nuclear Information System (INIS)

    Cai Kai-Quan; Tang Yan-Wu; Zhang Xue-Jun; Guan Xiang-Min

    2016-01-01

    The genetic algorithm (GA) is a nature-inspired evolutionary algorithm to find optima in search space via the interaction of individuals. Recently, researchers demonstrated that the interaction topology plays an important role in information exchange among individuals of evolutionary algorithm. In this paper, we investigate the effect of different network topologies adopted to represent the interaction structures. It is found that GA with a high-density topology ends up more likely with an unsatisfactory solution, contrarily, a low-density topology can impede convergence. Consequently, we propose an improved GA with dynamic topology, named DT-GA, in which the topology structure varies dynamically along with the fitness evolution. Several experiments executed with 15 well-known test functions have illustrated that DT-GA outperforms other test GAs for making a balance of convergence speed and optimum quality. Our work may have implications in the combination of complex networks and computational intelligence. (paper)

  17. Stochastic dynamics of genetic broadcasting networks

    Science.gov (United States)

    Potoyan, Davit A.; Wolynes, Peter G.

    2017-11-01

    The complex genetic programs of eukaryotic cells are often regulated by key transcription factors occupying or clearing out of a large number of genomic locations. Orchestrating the residence times of these factors is therefore important for the well organized functioning of a large network. The classic models of genetic switches sidestep this timing issue by assuming the binding of transcription factors to be governed entirely by thermodynamic protein-DNA affinities. Here we show that relying on passive thermodynamics and random release times can lead to a "time-scale crisis" for master genes that broadcast their signals to a large number of binding sites. We demonstrate that this time-scale crisis for clearance in a large broadcasting network can be resolved by actively regulating residence times through molecular stripping. We illustrate these ideas by studying a model of the stochastic dynamics of the genetic network of the central eukaryotic master regulator NFκ B which broadcasts its signals to many downstream genes that regulate immune response, apoptosis, etc.

  18. Dynamic airspace configuration by genetic algorithm

    Directory of Open Access Journals (Sweden)

    Marina Sergeeva

    2017-06-01

    Full Text Available With the continuous air traffic growth and limits of resources, there is a need for reducing the congestion of the airspace systems. Nowadays, several projects are launched, aimed at modernizing the global air transportation system and air traffic management. In recent years, special interest has been paid to the solution of the dynamic airspace configuration problem. Airspace sector configurations need to be dynamically adjusted to provide maximum efficiency and flexibility in response to changing weather and traffic conditions. The main objective of this work is to automatically adapt the airspace configurations according to the evolution of traffic. In order to reach this objective, the airspace is considered to be divided into predefined 3D airspace blocks which have to be grouped or ungrouped depending on the traffic situation. The airspace structure is represented as a graph and each airspace configuration is created using a graph partitioning technique. We optimize airspace configurations using a genetic algorithm. The developed algorithm generates a sequence of sector configurations for one day of operation with the minimized controller workload. The overall methodology is implemented and successfully tested with air traffic data taken for one day and for several different airspace control areas of Europe.

  19. Dynamic conservation of forest genetic resources in 33 European countries

    NARCIS (Netherlands)

    Lefevre, F.; Koskela, J.; Hubert, J.; Kraigher, H.; Longauer, R.; Olrik, D.C.; Vries, de S.M.G.

    2013-01-01

    Dynamic conservation of forest genetic resources (FGR) means maintaining the genetic diversity of trees within an evolutionary process and allowing generation turnover in the forest. We assessed the network of forests areas managed for the dynamic conservation of FGR (conservation units) across

  20. Quantitative Analysis of Repertoire Scale Immunoglobulin properties in Vaccine Induced B cell Responses

    Science.gov (United States)

    Immunosequencing now readily generates 103105 sequences per sample ; however, statistical analysis of these repertoires is challenging because of the high genetic...diversity of BCRs and the elaborate clonal relationships among them. To date, most immunosequencing analyses have focused on reporting qualitative ...repertoire differences, (2) identifying how two repertoires differ, and (3) determining appropriate confidence intervals for assessing the size of the differences and their potential biological relevance.

  1. PM Synchronous Motor Dynamic Modeling with Genetic Algorithm ...

    African Journals Online (AJOL)

    Adel

    This paper proposes dynamic modeling simulation for ac Surface Permanent Magnet Synchronous ... Simulations are implemented using MATLAB with its genetic algorithm toolbox. .... selection, the process that drives biological evolution.

  2. Genetic analysis of environmental strains of the plant pathogen Phytophthora capsici reveals heterogeneous repertoire of effectors and possible effector evolution via genomic island.

    Science.gov (United States)

    Iribarren, María Josefina; Pascuan, Cecilia; Soto, Gabriela; Ayub, Nicolás Daniel

    2015-11-01

    Phytophthora capsici is a virulent oomycete pathogen of many vegetable crops. Recently, it has been demonstrated that the recognition of the RXLR effector AVR3a1 of P. capsici (PcAVR3a1) triggers a hypersensitive response and plays a critical role in mediating non-host resistance. Here, we analyzed the occurrence of PcAVR3a1 in 57 isolates of P. capsici derived from globe squash, eggplant, tomato and bell pepper cocultivated in a small geographical area. The occurrence of PcAVR3a1 in environmental strains of P. capsici was confirmed by PCR in only 21 of these pathogen isolates. To understand the presence-absence pattern of PcAVR3a1 in environmental strains, the flanking region of this gene was sequenced. PcAVR3a1 was found within a genetic element that we named PcAVR3a1-GI (PcAVR3a1 genomic island). PcAVR3a1-GI was flanked by a 22-bp direct repeat, which is related to its site-specific recombination site. In addition to the PcAVR3a1 gene, PcAVR3a1-GI also encoded a phage integrase probably associated with the excision and integration of this mobile element. Exposure to plant induced the presence of an episomal circular intermediate of PcAVR3a1-GI, indicating that this mobile element is functional. Collectively, these findings provide evidence of PcAVR3a1 evolution via mobile elements in environmental strains of Phytophthora. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Intraspecific Genetic dynamics under Climate Change

    DEFF Research Database (Denmark)

    Florez Rodriguez, Alexander

    Climate change has a deep influence on the maintenance and generation of global biodiversity. Past contractions, expansions and shifts in species’ ranges drove to changes in species genetic diversity. Noteworthy, the interaction among: climate change, range, population size and extinction is often...

  4. Antibody Repertoire Development in Swine

    Czech Academy of Sciences Publication Activity Database

    Butler, J. E.; Wertz, N.; Šinkora, Marek

    2017-01-01

    Roč. 5, FEB 17 (2017), s. 255-279 ISSN 2165-8102 R&D Projects: GA ČR GA15-02274S; GA ČR(CZ) GA16-09296S Institutional support: RVO:61388971 Keywords : swine * pre-immune antibody repertoire * ileal Peyer's patches Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.708, year: 2016

  5. Personal receptor repertoires: olfaction as a model

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    Olender Tsviya

    2012-08-01

    Full Text Available Abstract Background Information on nucleotide diversity along completely sequenced human genomes has increased tremendously over the last few years. This makes it possible to reassess the diversity status of distinct receptor proteins in different human individuals. To this end, we focused on the complete inventory of human olfactory receptor coding regions as a model for personal receptor repertoires. Results By performing data-mining from public and private sources we scored genetic variations in 413 intact OR loci, for which one or more individuals had an intact open reading frame. Using 1000 Genomes Project haplotypes, we identified a total of 4069 full-length polypeptide variants encoded by these OR loci, average of ~10 per locus, constituting a lower limit for the effective human OR repertoire. Each individual is found to harbor as many as 600 OR allelic variants, ~50% higher than the locus count. Because OR neuronal expression is allelically excluded, this has direct effect on smell perception diversity of the species. We further identified 244 OR segregating pseudogenes (SPGs, loci showing both intact and pseudogene forms in the population, twenty-six of which are annotatively “resurrected” from a pseudogene status in the reference genome. Using a custom SNP microarray we validated 150 SPGs in a cohort of 468 individuals, with every individual genome averaging 36 disrupted sequence variations, 15 in homozygote form. Finally, we generated a multi-source compendium of 63 OR loci harboring deletion Copy Number Variations (CNVs. Our combined data suggest that 271 of the 413 intact OR loci (66% are affected by nonfunctional SNPs/indels and/or CNVs. Conclusions These results portray a case of unusually high genetic diversity, and suggest that individual humans have a highly personalized inventory of functional olfactory receptors, a conclusion that might apply to other receptor multigene families.

  6. Intertidal population genetic dynamics at a microgeographic seascape scale.

    Science.gov (United States)

    Hu, Zi-Min

    2013-06-01

    The intertidal community is among the most physically harsh niches on earth, with highly heterogeneous environmental and biological factors that impose strong habitat selection on population abundance, genetic connectivity and ecological adaptation of organisms in nature. However, most genetic studies to date have concentrated on the influence of basin-wide or regional marine environments (e.g. habitat discontinuities, oceanic currents and fronts, and geographic barriers) on spatiotemporal distribution and composition of intertidal invertebrates having planktonic stages or long-distance dispersal capability. Little is known about sessile marine organisms (e.g. seaweeds) in the context of topographic tidal gradients and reproductive traits at the microgeographic scale. In this issue of Molecular Ecology, Krueger-Hadfield et al. () implemented an elaborate sampling strategy with red seaweed (Chondrus crispus) from a 90-m transect stand near Roscoff and comprehensively detected genome-scale genetic differentiation and biases in ploidy level. This study not only revealed that tidal height resulted in genetic differentiation between high- and low-shore stands and restricted the genetic exchange within the high-shore habitat, but also demonstrated that intergametophytic nonrandom fertilization in C. crispus can cause significant deviation from Hardy-Weinberg equilibrium. Such new genetic insights highlight the importance of microgeographic genetic dynamics and life history characteristics for better understanding the evolutionary processes of speciation and diversification of intertidal marine organisms. © 2013 John Wiley & Sons Ltd.

  7. Growth-rate-dependent dynamics of a bacterial genetic oscillator

    Science.gov (United States)

    Osella, Matteo; Lagomarsino, Marco Cosentino

    2013-01-01

    Gene networks exhibiting oscillatory dynamics are widespread in biology. The minimal regulatory designs giving rise to oscillations have been implemented synthetically and studied by mathematical modeling. However, most of the available analyses generally neglect the coupling of regulatory circuits with the cellular “chassis” in which the circuits are embedded. For example, the intracellular macromolecular composition of fast-growing bacteria changes with growth rate. As a consequence, important parameters of gene expression, such as ribosome concentration or cell volume, are growth-rate dependent, ultimately coupling the dynamics of genetic circuits with cell physiology. This work addresses the effects of growth rate on the dynamics of a paradigmatic example of genetic oscillator, the repressilator. Making use of empirical growth-rate dependencies of parameters in bacteria, we show that the repressilator dynamics can switch between oscillations and convergence to a fixed point depending on the cellular state of growth, and thus on the nutrients it is fed. The physical support of the circuit (type of plasmid or gene positions on the chromosome) also plays an important role in determining the oscillation stability and the growth-rate dependence of period and amplitude. This analysis has potential application in the field of synthetic biology, and suggests that the coupling between endogenous genetic oscillators and cell physiology can have substantial consequences for their functionality.

  8. Complex and unexpected dynamics in simple genetic regulatory networks

    Science.gov (United States)

    Borg, Yanika; Ullner, Ekkehard; Alagha, Afnan; Alsaedi, Ahmed; Nesbeth, Darren; Zaikin, Alexey

    2014-03-01

    One aim of synthetic biology is to construct increasingly complex genetic networks from interconnected simpler ones to address challenges in medicine and biotechnology. However, as systems increase in size and complexity, emergent properties lead to unexpected and complex dynamics due to nonlinear and nonequilibrium properties from component interactions. We focus on four different studies of biological systems which exhibit complex and unexpected dynamics. Using simple synthetic genetic networks, small and large populations of phase-coupled quorum sensing repressilators, Goodwin oscillators, and bistable switches, we review how coupled and stochastic components can result in clustering, chaos, noise-induced coherence and speed-dependent decision making. A system of repressilators exhibits oscillations, limit cycles, steady states or chaos depending on the nature and strength of the coupling mechanism. In large repressilator networks, rich dynamics can also be exhibited, such as clustering and chaos. In populations of Goodwin oscillators, noise can induce coherent oscillations. In bistable systems, the speed with which incoming external signals reach steady state can bias the network towards particular attractors. These studies showcase the range of dynamical behavior that simple synthetic genetic networks can exhibit. In addition, they demonstrate the ability of mathematical modeling to analyze nonlinearity and inhomogeneity within these systems.

  9. Bistable responses in bacterial genetic networks: Designs and dynamical consequences

    Science.gov (United States)

    Tiwari, Abhinav; Ray, J. Christian J.; Narula, Jatin; Igoshin, Oleg A.

    2011-01-01

    A key property of living cells is their ability to react to stimuli with specific biochemical responses. These responses can be understood through the dynamics of underlying biochemical and genetic networks. Evolutionary design principles have been well studied in networks that display graded responses, with a continuous relationship between input signal and system output. Alternatively, biochemical networks can exhibit bistable responses so that over a range of signals the network possesses two stable steady states. In this review, we discuss several conceptual examples illustrating network designs that can result in a bistable response of the biochemical network. Next, we examine manifestations of these designs in bacterial master-regulatory genetic circuits. In particular, we discuss mechanisms and dynamic consequences of bistability in three circuits: two-component systems, sigma-factor networks, and a multistep phosphorelay. Analyzing these examples allows us to expand our knowledge of evolutionary design principles for networks with bistable responses. PMID:21385588

  10. Using Genetic Algorithms for Navigation Planning in Dynamic Environments

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    Ferhat Uçan

    2012-01-01

    Full Text Available Navigation planning can be considered as a combination of searching and executing the most convenient flight path from an initial waypoint to a destination waypoint. Generally the aim is to follow the flight path, which provides minimum fuel consumption for the air vehicle. For dynamic environments, constraints change dynamically during flight. This is a special case of dynamic path planning. As the main concern of this paper is flight planning, the conditions and objectives that are most probable to be used in navigation problem are considered. In this paper, the genetic algorithm solution of the dynamic flight planning problem is explained. The evolutionary dynamic navigation planning algorithm is developed for compensating the existing deficiencies of the other approaches. The existing fully dynamic algorithms process unit changes to topology one modification at a time, but when there are several such operations occurring in the environment simultaneously, the algorithms are quite inefficient. The proposed algorithm may respond to the concurrent constraint updates in a shorter time for dynamic environment. The most secure navigation of the air vehicle is planned and executed so that the fuel consumption is minimum.

  11. Dynamic modeling of genetic networks using genetic algorithm and S-system.

    Science.gov (United States)

    Kikuchi, Shinichi; Tominaga, Daisuke; Arita, Masanori; Takahashi, Katsutoshi; Tomita, Masaru

    2003-03-22

    The modeling of system dynamics of genetic networks, metabolic networks or signal transduction cascades from time-course data is formulated as a reverse-problem. Previous studies focused on the estimation of only network structures, and they were ineffective in inferring a network structure with feedback loops. We previously proposed a method to predict not only the network structure but also its dynamics using a Genetic Algorithm (GA) and an S-system formalism. However, it could predict only a small number of parameters and could rarely obtain essential structures. In this work, we propose a unified extension of the basic method. Notable improvements are as follows: (1) an additional term in its evaluation function that aims at eliminating futile parameters; (2) a crossover method called Simplex Crossover (SPX) to improve its optimization ability; and (3) a gradual optimization strategy to increase the number of predictable parameters. The proposed method is implemented as a C program called PEACE1 (Predictor by Evolutionary Algorithms and Canonical Equations 1). Its performance was compared with the basic method. The comparison showed that: (1) the convergence rate increased about 5-fold; (2) the optimization speed was raised about 1.5-fold; and (3) the number of predictable parameters was increased about 5-fold. Moreover, we successfully inferred the dynamics of a small genetic network constructed with 60 parameters for 5 network variables and feedback loops using only time-course data of gene expression.

  12. The past, present and future of immune repertoire biology – the rise of next-generation repertoire analysis

    Directory of Open Access Journals (Sweden)

    Adrien eSix

    2013-11-01

    Full Text Available T and B cell repertoires are collections of lymphocytes, each characterised by its antigen-specific receptor. We review here classical technologies and analysis strategies developed to assess Immunoglobulin (IG and T cell receptor (TR repertoire diversity, and describe recent advances in the field. First, we describe the broad range of available methodological tools developed in the past decades, each of which answering different questions and showing complementarity for progressive identification of the level of repertoire alterations: global overview of the diversity by flow cytometry, IG repertoire descriptions at the protein level for the identification of IG reactivities, IG/TR CDR3 spectratyping strategies, and related molecular quantification or dynamics of T/B cell differentiation. Additionally, we introduce the recent technological advances in molecular biology tools allowing deeper analysis of IG/TR diversity by next-generation sequencing (NGS, offering systematic and comprehensive sequencing of IG/TR transcripts in a short amount of time. NGS provides several angles of analysis such as clonotype frequency, CDR3 diversity, CDR3 sequence analysis, V allele identification with a quantitative dimension, therefore requiring high-throughput analysis tools development. In this line, we discuss the recent efforts made for nomenclature standardisation and ontology development. We then present the variety of available statistical analysis and modelling approaches developed with regards to the various levels of diversity analysis, and reveal the increasing sophistication of modelling approaches. To conclude, we provide some examples of recent mathematical modelling strategies and perspectives that illustrate the active rise of a next-generation of repertoire analysis.

  13. A depauperate immune repertoire precedes evolution of sociality in bees.

    Science.gov (United States)

    Barribeau, Seth M; Sadd, Ben M; du Plessis, Louis; Brown, Mark J F; Buechel, Severine D; Cappelle, Kaat; Carolan, James C; Christiaens, Olivier; Colgan, Thomas J; Erler, Silvio; Evans, Jay; Helbing, Sophie; Karaus, Elke; Lattorff, H Michael G; Marxer, Monika; Meeus, Ivan; Näpflin, Kathrin; Niu, Jinzhi; Schmid-Hempel, Regula; Smagghe, Guy; Waterhouse, Robert M; Yu, Na; Zdobnov, Evgeny M; Schmid-Hempel, Paul

    2015-04-24

    Sociality has many rewards, but can also be dangerous, as high population density and low genetic diversity, common in social insects, is ideal for parasite transmission. Despite this risk, honeybees and other sequenced social insects have far fewer canonical immune genes relative to solitary insects. Social protection from infection, including behavioral responses, may explain this depauperate immune repertoire. Here, based on full genome sequences, we describe the immune repertoire of two ecologically and commercially important bumblebee species that diverged approximately 18 million years ago, the North American Bombus impatiens and European Bombus terrestris. We find that the immune systems of these bumblebees, two species of honeybee, and a solitary leafcutting bee, are strikingly similar. Transcriptional assays confirm the expression of many of these genes in an immunological context and more strongly in young queens than males, affirming Bateman's principle of greater investment in female immunity. We find evidence of positive selection in genes encoding antiviral responses, components of the Toll and JAK/STAT pathways, and serine protease inhibitors in both social and solitary bees. Finally, we detect many genes across pathways that differ in selection between bumblebees and honeybees, or between the social and solitary clades. The similarity in immune complement across a gradient of sociality suggests that a reduced immune repertoire predates the evolution of sociality in bees. The differences in selection on immune genes likely reflect divergent pressures exerted by parasites across social contexts.

  14. Genetic algorithm enhanced by machine learning in dynamic aperture optimization

    Science.gov (United States)

    Li, Yongjun; Cheng, Weixing; Yu, Li Hua; Rainer, Robert

    2018-05-01

    With the aid of machine learning techniques, the genetic algorithm has been enhanced and applied to the multi-objective optimization problem presented by the dynamic aperture of the National Synchrotron Light Source II (NSLS-II) Storage Ring. During the evolution processes employed by the genetic algorithm, the population is classified into different clusters in the search space. The clusters with top average fitness are given "elite" status. Intervention on the population is implemented by repopulating some potentially competitive candidates based on the experience learned from the accumulated data. These candidates replace randomly selected candidates among the original data pool. The average fitness of the population is therefore improved while diversity is not lost. Maintaining diversity ensures that the optimization is global rather than local. The quality of the population increases and produces more competitive descendants accelerating the evolution process significantly. When identifying the distribution of optimal candidates, they appear to be located in isolated islands within the search space. Some of these optimal candidates have been experimentally confirmed at the NSLS-II storage ring. The machine learning techniques that exploit the genetic algorithm can also be used in other population-based optimization problems such as particle swarm algorithm.

  15. Imaging dynamic redox processes with genetically encoded probes.

    Science.gov (United States)

    Ezeriņa, Daria; Morgan, Bruce; Dick, Tobias P

    2014-08-01

    Redox signalling plays an important role in many aspects of physiology, including that of the cardiovascular system. Perturbed redox regulation has been associated with numerous pathological conditions; nevertheless, the causal relationships between redox changes and pathology often remain unclear. Redox signalling involves the production of specific redox species at specific times in specific locations. However, until recently, the study of these processes has been impeded by a lack of appropriate tools and methodologies that afford the necessary redox species specificity and spatiotemporal resolution. Recently developed genetically encoded fluorescent redox probes now allow dynamic real-time measurements, of defined redox species, with subcellular compartment resolution, in intact living cells. Here we discuss the available genetically encoded redox probes in terms of their sensitivity and specificity and highlight where uncertainties or controversies currently exist. Furthermore, we outline major goals for future probe development and describe how progress in imaging methodologies will improve our ability to employ genetically encoded redox probes in a wide range of situations. This article is part of a special issue entitled "Redox Signalling in the Cardiovascular System." Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. On the Organizational Dynamics of the Genetic Code

    KAUST Repository

    Zhang, Zhang

    2011-06-07

    The organization of the canonical genetic code needs to be thoroughly illuminated. Here we reorder the four nucleotides—adenine, thymine, guanine and cytosine—according to their emergence in evolution, and apply the organizational rules to devising an algebraic representation for the canonical genetic code. Under a framework of the devised code, we quantify codon and amino acid usages from a large collection of 917 prokaryotic genome sequences, and associate the usages with its intrinsic structure and classification schemes as well as amino acid physicochemical properties. Our results show that the algebraic representation of the code is structurally equivalent to a content-centric organization of the code and that codon and amino acid usages under different classification schemes were correlated closely with GC content, implying a set of rules governing composition dynamics across a wide variety of prokaryotic genome sequences. These results also indicate that codons and amino acids are not randomly allocated in the code, where the six-fold degenerate codons and their amino acids have important balancing roles for error minimization. Therefore, the content-centric code is of great usefulness in deciphering its hitherto unknown regularities as well as the dynamics of nucleotide, codon, and amino acid compositions.

  17. On the Organizational Dynamics of the Genetic Code

    KAUST Repository

    Zhang, Zhang; Yu, Jun

    2011-01-01

    The organization of the canonical genetic code needs to be thoroughly illuminated. Here we reorder the four nucleotides—adenine, thymine, guanine and cytosine—according to their emergence in evolution, and apply the organizational rules to devising an algebraic representation for the canonical genetic code. Under a framework of the devised code, we quantify codon and amino acid usages from a large collection of 917 prokaryotic genome sequences, and associate the usages with its intrinsic structure and classification schemes as well as amino acid physicochemical properties. Our results show that the algebraic representation of the code is structurally equivalent to a content-centric organization of the code and that codon and amino acid usages under different classification schemes were correlated closely with GC content, implying a set of rules governing composition dynamics across a wide variety of prokaryotic genome sequences. These results also indicate that codons and amino acids are not randomly allocated in the code, where the six-fold degenerate codons and their amino acids have important balancing roles for error minimization. Therefore, the content-centric code is of great usefulness in deciphering its hitherto unknown regularities as well as the dynamics of nucleotide, codon, and amino acid compositions.

  18. VLADIMIR AXIONOV ABOUT GHEORGHE NEAGADS COMPONISTIC REPERTOIRE

    Directory of Open Access Journals (Sweden)

    CHICIUC NATALIA

    2015-03-01

    Full Text Available This article presents one side of Vladimir Axionov’s scientific research, namely the one referring to Gheorghe NeagaUs componistic repertoire. A frequent analysis of Gh. NeagaUs works, practically, all the musicologyst’s studies, separately or together with the works of other authors, show that this composer’s repertoire played an important role in the creative processes occurring in Moldovan music, Gheorghe Neaga exemplifying many trends that have emerged in native composition.

  19. Dynamic characterization of oil fields, complex stratigraphically using genetic algorithms

    International Nuclear Information System (INIS)

    Gonzalez, Santiago; Hidrobo, Eduardo A

    2004-01-01

    A novel methodology is presented in this paper for the characterization of highly heterogeneous oil fields by integration of the oil fields dynamic information to the static updated model. The objective of the oil field's characterization process is to build an oil field model, as realistic as possible, through the incorporation of all the available information. The classical approach consists in producing a model based in the oil field's static information, having as the process final stage the validation model with the dynamic information available. It is important to clarify that the term validation implies a punctual process by nature, generally intended to secure the required coherence between productive zones and petrophysical properties. The objective of the proposed methodology is to enhance the prediction capacity of the oil field's model by previously integrating, parameters inherent to the oil field's fluid dynamics by a process of dynamic data inversion through an optimization procedure based on evolutionary computation. The proposed methodology relies on the construction of the oil field's high-resolution static model, escalated by means of hybrid techniques while aiming to preserve the oil field's heterogeneity. Afterwards, using an analytic simulator as reference, the scaled model is methodically modified by means of an optimization process that uses genetic algorithms and production data as conditional information. The process's final product is a model that observes the static and dynamic conditions of the oil field with the capacity to minimize the economic impact that generates production historical adjustments to the simulation tasks. This final model features some petrophysical properties (porosity, permeability and water saturation), as modified to achieve a better adjustment of the simulated production's history versus the real one history matching. Additionally, the process involves a slight modification of relative permeability, which has

  20. Genetic algorithm optimization for dynamic construction site layout planning

    Directory of Open Access Journals (Sweden)

    Farmakis Panagiotis M.

    2018-02-01

    Full Text Available The dynamic construction site layout planning (DCSLP problem refers to the efficient placement and relocation of temporary construction facilities within a dynamically changing construction site environment considering the characteristics of facilities and work interrelationships, the shape and topography of the construction site, and the time-varying project needs. A multi-objective dynamic optimization model is developed for this problem that considers construction and relocation costs of facilities, transportation costs of resources moving from one facility to another or to workplaces, as well as safety and environmental considerations resulting from facilities’ operations and interconnections. The latter considerations are taken into account in the form of preferences or constraints regarding the proximity or remoteness of particular facilities to other facilities or work areas. The analysis of multiple project phases and the dynamic facility relocation from phase to phase highly increases the problem size, which, even in its static form, falls within the NP (for Nondeterministic Polynomial time- hard class of combinatorial optimization problems. For this reason, a genetic algorithm has been implemented for the solution due to its capability to robustly search within a large solution space. Several case studies and operational scenarios have been implemented through the Palisade’s Evolver software for model testing and evaluation. The results indi­cate satisfactory model response to time-varying input data in terms of solution quality and computation time. The model can provide decision support to site managers, allowing them to examine alternative scenarios and fine-tune optimal solutions according to their experience by introducing desirable preferences or constraints in the decision process.

  1. Computational Strategies for Dissecting the High-Dimensional Complexity of Adaptive Immune Repertoires

    Directory of Open Access Journals (Sweden)

    Enkelejda Miho

    2018-02-01

    Full Text Available The adaptive immune system recognizes antigens via an immense array of antigen-binding antibodies and T-cell receptors, the immune repertoire. The interrogation of immune repertoires is of high relevance for understanding the adaptive immune response in disease and infection (e.g., autoimmunity, cancer, HIV. Adaptive immune receptor repertoire sequencing (AIRR-seq has driven the quantitative and molecular-level profiling of immune repertoires, thereby revealing the high-dimensional complexity of the immune receptor sequence landscape. Several methods for the computational and statistical analysis of large-scale AIRR-seq data have been developed to resolve immune repertoire complexity and to understand the dynamics of adaptive immunity. Here, we review the current research on (i diversity, (ii clustering and network, (iii phylogenetic, and (iv machine learning methods applied to dissect, quantify, and compare the architecture, evolution, and specificity of immune repertoires. We summarize outstanding questions in computational immunology and propose future directions for systems immunology toward coupling AIRR-seq with the computational discovery of immunotherapeutics, vaccines, and immunodiagnostics.

  2. Germline V repertoires: Origin, maintenance, diversification.

    Science.gov (United States)

    Steele, E J; Lindley, R A

    2018-06-01

    In our view, Melvin Cohn (Scand J Immunol. 2018;87:e12640) has set out the logical guidelines towards a resolution of the very real enigma of the selectability of vertebrate germline Ig V repertoires under the current evolutionary paradigm…" A somatically derived repertoire scrambles this (germline VL + VH) substrate so that its specificities are lost, making it un-selectable in the germline. Consequently, evolution faced an incompatibility." It is argued here in Reply that a reverse transcriptase-based soma-to-germline process (S->G) targeting germline V segment arrays goes some considerable way to resolving fundamental contradictions on the origin, maintenance and then real-time adaptive diversification of these limited sets of V segments encoded within various V repertoire arrays. © 2018 The Foundation for the Scandinavian Journal of Immunology.

  3. Quantitative Analysis of Repertoire-Scale Immunoglobulin Properties in Vaccine-Induced B-Cell Responses

    Directory of Open Access Journals (Sweden)

    Ilja V. Khavrutskii

    2017-08-01

    Full Text Available Recent advances in the next-generation sequencing of B-cell receptors (BCRs enable the characterization of humoral responses at a repertoire-wide scale and provide the capability for identifying unique features of immune repertoires in response to disease, vaccination, or infection. Immunosequencing now readily generates 103–105 sequences per sample; however, statistical analysis of these repertoires is challenging because of the high genetic diversity of BCRs and the elaborate clonal relationships among them. To date, most immunosequencing analyses have focused on reporting qualitative trends in immunoglobulin (Ig properties, such as usage or somatic hypermutation (SHM percentage of the Ig heavy chain variable (IGHV gene segment family, and on reducing complex Ig property distributions to simple summary statistics. However, because Ig properties are typically not normally distributed, any approach that fails to assess the distribution as a whole may be inadequate in (1 properly assessing the statistical significance of repertoire differences, (2 identifying how two repertoires differ, and (3 determining appropriate confidence intervals for assessing the size of the differences and their potential biological relevance. To address these issues, we have developed a technique that uses Wilcox’ robust statistics toolbox to identify statistically significant vaccine-specific differences between Ig repertoire properties. The advantage of this technique is that it can determine not only whether but also where the distributions differ, even when the Ig repertoire properties are non-normally distributed. We used this technique to characterize murine germinal center (GC B-cell repertoires in response to a complex Ebola virus-like particle (eVLP vaccine candidate with known protective efficacy. The eVLP-mediated GC B-cell responses were highly diverse, consisting of thousands of clonotypes. Despite this staggering diversity, we identified statistically

  4. Genomic organization and evolution of the Atlantic salmon hemoglobin repertoire

    Directory of Open Access Journals (Sweden)

    Phillips Ruth B

    2010-10-01

    Full Text Available Abstract Background The genomes of salmonids are considered pseudo-tetraploid undergoing reversion to a stable diploid state. Given the genome duplication and extensive biological data available for salmonids, they are excellent model organisms for studying comparative genomics, evolutionary processes, fates of duplicated genes and the genetic and physiological processes associated with complex behavioral phenotypes. The evolution of the tetrapod hemoglobin genes is well studied; however, little is known about the genomic organization and evolution of teleost hemoglobin genes, particularly those of salmonids. The Atlantic salmon serves as a representative salmonid species for genomics studies. Given the well documented role of hemoglobin in adaptation to varied environmental conditions as well as its use as a model protein for evolutionary analyses, an understanding of the genomic structure and organization of the Atlantic salmon α and β hemoglobin genes is of great interest. Results We identified four bacterial artificial chromosomes (BACs comprising two hemoglobin gene clusters spanning the entire α and β hemoglobin gene repertoire of the Atlantic salmon genome. Their chromosomal locations were established using fluorescence in situ hybridization (FISH analysis and linkage mapping, demonstrating that the two clusters are located on separate chromosomes. The BACs were sequenced and assembled into scaffolds, which were annotated for putatively functional and pseudogenized hemoglobin-like genes. This revealed that the tail-to-tail organization and alternating pattern of the α and β hemoglobin genes are well conserved in both clusters, as well as that the Atlantic salmon genome houses substantially more hemoglobin genes, including non-Bohr β globin genes, than the genomes of other teleosts that have been sequenced. Conclusions We suggest that the most parsimonious evolutionary path leading to the present organization of the Atlantic salmon

  5. Genomic organization and evolution of the Atlantic salmon hemoglobin repertoire

    Science.gov (United States)

    2010-01-01

    Background The genomes of salmonids are considered pseudo-tetraploid undergoing reversion to a stable diploid state. Given the genome duplication and extensive biological data available for salmonids, they are excellent model organisms for studying comparative genomics, evolutionary processes, fates of duplicated genes and the genetic and physiological processes associated with complex behavioral phenotypes. The evolution of the tetrapod hemoglobin genes is well studied; however, little is known about the genomic organization and evolution of teleost hemoglobin genes, particularly those of salmonids. The Atlantic salmon serves as a representative salmonid species for genomics studies. Given the well documented role of hemoglobin in adaptation to varied environmental conditions as well as its use as a model protein for evolutionary analyses, an understanding of the genomic structure and organization of the Atlantic salmon α and β hemoglobin genes is of great interest. Results We identified four bacterial artificial chromosomes (BACs) comprising two hemoglobin gene clusters spanning the entire α and β hemoglobin gene repertoire of the Atlantic salmon genome. Their chromosomal locations were established using fluorescence in situ hybridization (FISH) analysis and linkage mapping, demonstrating that the two clusters are located on separate chromosomes. The BACs were sequenced and assembled into scaffolds, which were annotated for putatively functional and pseudogenized hemoglobin-like genes. This revealed that the tail-to-tail organization and alternating pattern of the α and β hemoglobin genes are well conserved in both clusters, as well as that the Atlantic salmon genome houses substantially more hemoglobin genes, including non-Bohr β globin genes, than the genomes of other teleosts that have been sequenced. Conclusions We suggest that the most parsimonious evolutionary path leading to the present organization of the Atlantic salmon hemoglobin genes involves

  6. Antibodies: From novel repertoires to defining and refining the structure of biologically important targets.

    Science.gov (United States)

    Conroy, Paul J; Law, Ruby H P; Caradoc-Davies, Tom T; Whisstock, James C

    2017-03-01

    Antibodies represent a highly successful class of molecules that bind a wide-range of targets in therapeutic-, diagnostic- and research-based applications. The antibody repertoire is composed of the building blocks required to develop an effective adaptive immune response against foreign insults. A number of species have developed novel genetic and structural mechanisms from which they derive these antibody repertoires, however, traditionally antibodies are isolated from human, and rodent sources. Due to their high-value therapeutic, diagnostic, biotechnological and research applications, much innovation has resulted in techniques and approaches to isolate novel antibodies. These approaches are bolstered by advances in our understanding of species immune repertoires, next generation sequencing capacity, combinatorial antibody discovery and high-throughput screening. Structural determination of antibodies and antibody-antigen complexes has proven to be pivotal to our current understanding of the immune repertoire for a range of species leading to advances in man-made libraries and fine tuning approaches to develop antibodies from immune-repertoires. Furthermore, the isolation of antibodies directed against antigens of importance in health, disease and developmental processes, has yielded a plethora of structural and functional insights. This review highlights the significant contribution of antibody-based crystallography to our understanding of adaptive immunity and its application to providing critical information on a range of human-health related indications. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Characterization of the sortase repertoire in Bacillus anthracis.

    Directory of Open Access Journals (Sweden)

    Willy Aucher

    Full Text Available LPXTG proteins, present in most if not all Gram-positive bacteria, are known to be anchored by sortases to the bacterial peptidoglycan. More than one sortase gene is often encoded in a bacterial species, and each sortase is supposed to specifically anchor given LPXTG proteins, depending of the sequence of the C-terminal cell wall sorting signal (cwss, bearing an LPXTG motif or another recognition sequence. B. anthracis possesses three sortase genes. B. anthracis sortase deleted mutant strains are not affected in their virulence. To determine the sortase repertoires, we developed a genetic screen using the property of the gamma phage to lyse bacteria only when its receptor, GamR, an LPXTG protein, is exposed at the surface. We identified 10 proteins that contain a cell wall sorting signal and are covalently anchored to the peptidoglycan. Some chimeric proteins yielded phage lysis in all sortase mutant strains, suggesting that cwss proteins remained surface accessible in absence of their anchoring sortase, probably as a consequence of membrane localization of yet uncleaved precursor proteins. For definite assignment of the sortase repertoires, we consequently relied on a complementary test, using a biochemical approach, namely immunoblot experiments. The sortase anchoring nine of these proteins has thus been determined. The absence of virulence defect of the sortase mutants could be a consequence of the membrane localization of the cwss proteins.

  8. Genetic algorithms with memory- and elitism-based immigrants in dynamic environments

    OpenAIRE

    Yang, S

    2008-01-01

    Copyright @ 2008 by the Massachusetts Institute of Technology In recent years the genetic algorithm community has shown a growing interest in studying dynamic optimization problems. Several approaches have been devised. The random immigrants and memory schemes are two major ones. The random immigrants scheme addresses dynamic environments by maintaining the population diversity while the memory scheme aims to adapt genetic algorithms quickly to new environments by reusing historical inform...

  9. Genetic algorithms with memory- and elitism-based immigrants in dynamic environments.

    Science.gov (United States)

    Yang, Shengxiang

    2008-01-01

    In recent years the genetic algorithm community has shown a growing interest in studying dynamic optimization problems. Several approaches have been devised. The random immigrants and memory schemes are two major ones. The random immigrants scheme addresses dynamic environments by maintaining the population diversity while the memory scheme aims to adapt genetic algorithms quickly to new environments by reusing historical information. This paper investigates a hybrid memory and random immigrants scheme, called memory-based immigrants, and a hybrid elitism and random immigrants scheme, called elitism-based immigrants, for genetic algorithms in dynamic environments. In these schemes, the best individual from memory or the elite from the previous generation is retrieved as the base to create immigrants into the population by mutation. This way, not only can diversity be maintained but it is done more efficiently to adapt genetic algorithms to the current environment. Based on a series of systematically constructed dynamic problems, experiments are carried out to compare genetic algorithms with the memory-based and elitism-based immigrants schemes against genetic algorithms with traditional memory and random immigrants schemes and a hybrid memory and multi-population scheme. The sensitivity analysis regarding some key parameters is also carried out. Experimental results show that the memory-based and elitism-based immigrants schemes efficiently improve the performance of genetic algorithms in dynamic environments.

  10. Developing Professional “Game Teacher” Repertoires

    DEFF Research Database (Denmark)

    Lieberoth, Andreas; Hanghøj, Thorkild

    2017-01-01

    for in their professional careers. We expand and explain these findings using embedded mixed methods analysis, and conclude that games are a good practical case for training various teaching competences, but that building flexible professional repertoires requires more varied experiences than a single course can muster.......The first Danish Game-Based Learning course offered by a teachers college enrolled 42 students with a variety of backgrounds and interests in games. We characterize the students who enrolled in the course in terms of gaming literacies and preferences, and gauge the impact of the course in terms...... of building actionable skill sets. Following Schön (1986) we use these data to frame students’ transition from gamers or game curious teachers to developing professional repertoires.Interviews and statistical comparison to other students indicate that while student’s existing preferences for the “heavier...

  11. Antibody repertoire profiling with mimotope arrays

    OpenAIRE

    Pashova, Shina; Schneider, Christoph; von Gunten, Stephan; Pashov, Anastas

    2016-01-01

    Large-scale profiling and monitoring of antibody repertoires is possible through next generation sequencing (NGS), phage display libraries and microarrays. These methods can be combined in a pipeline, which ultimately maps the antibody reactivities onto defined arrays of structures - peptides or carbohydrates. The arrays can help analyze the individual specificities or can be used as complex patterns. In any case, the targets recognized should formally be considered mimotopes unless they are ...

  12. Temporal dynamics of genetic variability in a mountain goat (Oreamnos americanus) population.

    Science.gov (United States)

    Ortego, Joaquín; Yannic, Glenn; Shafer, Aaron B A; Mainguy, Julien; Festa-Bianchet, Marco; Coltman, David W; Côté, Steeve D

    2011-04-01

    The association between population dynamics and genetic variability is of fundamental importance for both evolutionary and conservation biology. We combined long-term population monitoring and molecular genetic data from 123 offspring and their parents at 28 microsatellite loci to investigate changes in genetic diversity over 14 cohorts in a small and relatively isolated population of mountain goats (Oreamnos americanus) during a period of demographic increase. Offspring heterozygosity decreased while parental genetic similarity and inbreeding coefficients (F(IS) ) increased over the study period (1995-2008). Immigrants introduced three novel alleles into the population and matings between residents and immigrants produced more heterozygous offspring than local crosses, suggesting that immigration can increase population genetic variability. The population experienced genetic drift over the study period, reflected by a reduced allelic richness over time and an 'isolation-by-time' pattern of genetic structure. The temporal decline of individual genetic diversity despite increasing population size probably resulted from a combination of genetic drift due to small effective population size, inbreeding and insufficient counterbalancing by immigration. This study highlights the importance of long-term genetic monitoring to understand how demographic processes influence temporal changes of genetic diversity in long-lived organisms. © 2011 Blackwell Publishing Ltd.

  13. Warehouse stocking optimization based on dynamic ant colony genetic algorithm

    Science.gov (United States)

    Xiao, Xiaoxu

    2018-04-01

    In view of the various orders of FAW (First Automotive Works) International Logistics Co., Ltd., the SLP method is used to optimize the layout of the warehousing units in the enterprise, thus the warehouse logistics is optimized and the external processing speed of the order is improved. In addition, the relevant intelligent algorithms for optimizing the stocking route problem are analyzed. The ant colony algorithm and genetic algorithm which have good applicability are emphatically studied. The parameters of ant colony algorithm are optimized by genetic algorithm, which improves the performance of ant colony algorithm. A typical path optimization problem model is taken as an example to prove the effectiveness of parameter optimization.

  14. Dynamic Load Balanced Clustering using Elitism based Random Immigrant Genetic Approach for Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    K. Mohaideen Pitchai

    2017-07-01

    Full Text Available Wireless Sensor Network (WSN consists of a large number of small sensors with restricted energy. Prolonged network lifespan, scalability, node mobility and load balancing are important needs for several WSN applications. Clustering the sensor nodes is an efficient technique to reach these goals. WSN have the characteristics of topology dynamics because of factors like energy conservation and node movement that leads to Dynamic Load Balanced Clustering Problem (DLBCP. In this paper, Elitism based Random Immigrant Genetic Approach (ERIGA is proposed to solve DLBCP which adapts to topology dynamics. ERIGA uses the dynamic Genetic Algorithm (GA components for solving the DLBCP. The performance of load balanced clustering process is enhanced with the help of this dynamic GA. As a result, the ERIGA achieves to elect suitable cluster heads which balances the network load and increases the lifespan of the network.

  15. Fractional Dynamics of Genetic Algorithms Using Hexagonal Space Tessellation

    Directory of Open Access Journals (Sweden)

    J. A. Tenreiro Machado

    2013-01-01

    Full Text Available The paper formulates a genetic algorithm that evolves two types of objects in a plane. The fitness function promotes a relationship between the objects that is optimal when some kind of interface between them occurs. Furthermore, the algorithm adopts an hexagonal tessellation of the two-dimensional space for promoting an efficient method of the neighbour modelling. The genetic algorithm produces special patterns with resemblances to those revealed in percolation phenomena or in the symbiosis found in lichens. Besides the analysis of the spacial layout, a modelling of the time evolution is performed by adopting a distance measure and the modelling in the Fourier domain in the perspective of fractional calculus. The results reveal a consistent, and easy to interpret, set of model parameters for distinct operating conditions.

  16. Implementation and Characterization of Dynamic Genetic Networks in Vitro

    OpenAIRE

    Niederholtmeyer, Henrike Marie

    2015-01-01

    Transcription and translation (TX-TL) can be performed in vitro, outside of cells, allowing the assembly and analysis of genetic networks. This approach to engineering biological networks in a less complex and more controllable environment could one day allow rapid prototyping of network designs before implementing them in living cells. Furthermore, the in vitro approach provides insight into how natural biological systems are built and is instructive to define the rules for engineering biolo...

  17. Synthetic multicellular oscillatory systems: controlling protein dynamics with genetic circuits

    International Nuclear Information System (INIS)

    Koseska, Aneta; Volkov, Evgenii; Kurths, Juergen

    2011-01-01

    Synthetic biology is a relatively new research discipline that combines standard biology approaches with the constructive nature of engineering. Thus, recent efforts in the field of synthetic biology have given a perspective to consider cells as 'programmable matter'. Here, we address the possibility of using synthetic circuits to control protein dynamics. In particular, we show how intercellular communication and stochasticity can be used to manipulate the dynamical behavior of a population of coupled synthetic units and, in this manner, finely tune the expression of specific proteins of interest, e.g. in large bioreactors.

  18. The collective biology of the gene: Towards genetic dynamics engineering

    International Nuclear Information System (INIS)

    Chela-Flores, J.

    1985-11-01

    Chromatin dynamics is studied in terms of coupled vibrations (phonon pairing); this is shown to lead to a collective variable Δ, interpreted as a gene inhibition factor, which behaves as a biological switch turned off, not only by enzymatic action or metabolic energy, but also by means of an external probe:irradiation. We discuss the inactivation of the X chromosome and puffing. The relevance of being able to modulate Δ is emphasized, since it is equivalent to controlling chromatin dynamics without interfering with chromatin structure, unlike in the usual recombinant DNA techniques. (author)

  19. Fractional dynamics of globally slow transcription and its impact on deterministic genetic oscillation.

    Directory of Open Access Journals (Sweden)

    Kun Wei

    Full Text Available In dynamical systems theory, a system which can be described by differential equations is called a continuous dynamical system. In studies on genetic oscillation, most deterministic models at early stage are usually built on ordinary differential equations (ODE. Therefore, gene transcription which is a vital part in genetic oscillation is presupposed to be a continuous dynamical system by default. However, recent studies argued that discontinuous transcription might be more common than continuous transcription. In this paper, by appending the inserted silent interval lying between two neighboring transcriptional events to the end of the preceding event, we established that the running time for an intact transcriptional event increases and gene transcription thus shows slow dynamics. By globally replacing the original time increment for each state increment by a larger one, we introduced fractional differential equations (FDE to describe such globally slow transcription. The impact of fractionization on genetic oscillation was then studied in two early stage models--the Goodwin oscillator and the Rössler oscillator. By constructing a "dual memory" oscillator--the fractional delay Goodwin oscillator, we suggested that four general requirements for generating genetic oscillation should be revised to be negative feedback, sufficient nonlinearity, sufficient memory and proper balancing of timescale. The numerical study of the fractional Rössler oscillator implied that the globally slow transcription tends to lower the chance of a coupled or more complex nonlinear genetic oscillatory system behaving chaotically.

  20. Fractional dynamics of globally slow transcription and its impact on deterministic genetic oscillation.

    Science.gov (United States)

    Wei, Kun; Gao, Shilong; Zhong, Suchuan; Ma, Hong

    2012-01-01

    In dynamical systems theory, a system which can be described by differential equations is called a continuous dynamical system. In studies on genetic oscillation, most deterministic models at early stage are usually built on ordinary differential equations (ODE). Therefore, gene transcription which is a vital part in genetic oscillation is presupposed to be a continuous dynamical system by default. However, recent studies argued that discontinuous transcription might be more common than continuous transcription. In this paper, by appending the inserted silent interval lying between two neighboring transcriptional events to the end of the preceding event, we established that the running time for an intact transcriptional event increases and gene transcription thus shows slow dynamics. By globally replacing the original time increment for each state increment by a larger one, we introduced fractional differential equations (FDE) to describe such globally slow transcription. The impact of fractionization on genetic oscillation was then studied in two early stage models--the Goodwin oscillator and the Rössler oscillator. By constructing a "dual memory" oscillator--the fractional delay Goodwin oscillator, we suggested that four general requirements for generating genetic oscillation should be revised to be negative feedback, sufficient nonlinearity, sufficient memory and proper balancing of timescale. The numerical study of the fractional Rössler oscillator implied that the globally slow transcription tends to lower the chance of a coupled or more complex nonlinear genetic oscillatory system behaving chaotically.

  1. Characterizing source-sink dynamics with genetic parentage assignments

    NARCIS (Netherlands)

    Peery, M. Zachariah; Beissinger, Steven R.; House, Roger F.; Berube, Martine; Hall, Laurie A.; Sellas, Anna; Palsboll, Per J.

    2008-01-01

    Source-sink dynamics have been suggested to characterize the population structure of many species, but the prevalence of source-sink systems in nature is uncertain because of inherent challenges in estimating migration rates among populations. Migration rates are often difficult to estimate directly

  2. Nonlinear dynamics optimization with particle swarm and genetic algorithms for SPEAR3 emittance upgrade

    International Nuclear Information System (INIS)

    Huang, Xiaobiao; Safranek, James

    2014-01-01

    Nonlinear dynamics optimization is carried out for a low emittance upgrade lattice of SPEAR3 in order to improve its dynamic aperture and Touschek lifetime. Two multi-objective optimization algorithms, a genetic algorithm and a particle swarm algorithm, are used for this study. The performance of the two algorithms are compared. The result shows that the particle swarm algorithm converges significantly faster to similar or better solutions than the genetic algorithm and it does not require seeding of good solutions in the initial population. These advantages of the particle swarm algorithm may make it more suitable for many accelerator optimization applications

  3. Nonlinear dynamics optimization with particle swarm and genetic algorithms for SPEAR3 emittance upgrade

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Xiaobiao, E-mail: xiahuang@slac.stanford.edu; Safranek, James

    2014-09-01

    Nonlinear dynamics optimization is carried out for a low emittance upgrade lattice of SPEAR3 in order to improve its dynamic aperture and Touschek lifetime. Two multi-objective optimization algorithms, a genetic algorithm and a particle swarm algorithm, are used for this study. The performance of the two algorithms are compared. The result shows that the particle swarm algorithm converges significantly faster to similar or better solutions than the genetic algorithm and it does not require seeding of good solutions in the initial population. These advantages of the particle swarm algorithm may make it more suitable for many accelerator optimization applications.

  4. Identification and comparative analysis of sixteen fungal peptidyl-prolyl cis/trans isomerase repertoires

    Directory of Open Access Journals (Sweden)

    Pemberton Trevor J

    2006-09-01

    functions, the FKBPs have evolved to perform more variable roles. Also, the repertoire of Cryptococcus neoformans may represent a better model fungal system within which to study the functions of the PPIases as its genome size and genetic tractability are equal to those of Saccharomyces cerevisiae, whilst its repertoires exhibits greater orthology to that of humans. However, further experimental investigations are required to confirm this.

  5. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna

    2011-03-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.

  6. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna; Marcatili, Paolo; Cirillo, Davide; Tramontano, Anna

    2011-01-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.

  7. Programming in the Zone: Repertoire Selection for the Large Ensemble

    Science.gov (United States)

    Hopkins, Michael

    2013-01-01

    One of the great challenges ensemble directors face is selecting high-quality repertoire that matches the musical and technical levels of their ensembles. Thoughtful repertoire selection can lead to increased student motivation as well as greater enthusiasm for the music program from parents, administrators, teachers, and community members. Common…

  8. An Annotated Guide and Interactive Database for Solo Horn Repertoire

    Science.gov (United States)

    Schouten, Sarah

    2012-01-01

    Given the horn's lengthy history, it is not surprising that many scholars have examined the evolution of the instrument from the natural horn to the modern horn and its expansive repertoire. Numerous dissertations, theses, and treatises illuminate specific elements of the horn's solo repertoire; however, no scholar has produced a…

  9. Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population

    Science.gov (United States)

    Arenas, I. A.; Tremblay, J.; Deslauriers, B.; Sandoval, J.; Šeda, O.; Gaudet, D.; Merlo, E.; Kotchen, T.; Cowley, A. W.

    2013-01-01

    Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation. PMID:23269701

  10. B cell and antibody repertoire development in rabbits: the requirement of gut-associated lymphoid tissues.

    Science.gov (United States)

    Mage, Rose G; Lanning, Dennis; Knight, Katherine L

    2006-01-01

    The antibody repertoire of rabbits has interested immunologists for decades, in part because of the ease with which large quantities of high affinity antibodies can be obtained in serum, and in part because of the presence of genetic variants, allotypes, within V(H), C(H) and C(L) regions. Studies of these allotypes led to the initial descriptions of allelic exclusion, and neonatal suppression of serum Ig production (allotype suppression), and were instrumental in demonstrating that V and C regions are encoded by separate genes and are usually expressed in cis. The immune system of rabbit continues to be of interest primarily because of the use of both gene conversion and somatic hypermutation to diversify rearranged heavy and light chain genes and the role that gut-associated lymphoid tissues (GALT) and intestinal flora play in developing the primary (preimmune) antibody repertoire.

  11. Dynamic organization of genetic recombination proteins and chromosomes

    International Nuclear Information System (INIS)

    Essers, J.; Van Cappellen, G.; Van Drunen, E.; Theil, A.; Jaspers, N.N.G.J.; Houtsmuller, A.B.; Vermeulen, W.; Kanaar, R.

    2003-01-01

    Homologous recombination requires the co-ordinated action of the RAD52 group proteins, including Rad51, Rad52 and Rad54. Upon treatment of mammalian cells with ionizing radiation, these proteins accumulate into foci at sites of DSB induction. We probed the nature of the DNA damage-induced foci in living cells with the use of photobleaching techniques. These foci are not static assemblies of DNA repair proteins. Instead, they are dynamic structures of which Rad51 is a stable core component, while Rad52 and Rad54 reversibly interact with the structure. Furthermore, even though the RAD52 group proteins colocalize in the DNA damage-induced foci, the majority of the proteins are not part of the same multi-protein complex in the absence of DNA damage. Executing DNA transactions through dynamic multi-protein complexes, rather than stable holo-complexes, allows greater flexibility during the transaction. In case of DNA repair, for example, it allows cross talk between different DNA repair pathways and coupling to other DNA transactions, such as replication. In addition to the behavior of proteins in living cells, we have tracked chromosomes during cell division. Our results suggest that the relative position of chromosomes in the mother cell is conserved in its daughter cells

  12. YouGenMap: a web platform for dynamic multi-comparative mapping and visualization of genetic maps

    Science.gov (United States)

    Keith Batesole; Kokulapalan Wimalanathan; Lin Liu; Fan Zhang; Craig S. Echt; Chun Liang

    2014-01-01

    Comparative genetic maps are used in examination of genome organization, detection of conserved gene order, and exploration of marker order variations. YouGenMap is an open-source web tool that offers dynamic comparative mapping capability of users' own genetic mapping between 2 or more map sets. Users' genetic map data and optional gene annotations are...

  13. Landscape genetics highlights the role of bank vole metapopulation dynamics in the epidemiology of Puumala hantavirus.

    Science.gov (United States)

    Guivier, E; Galan, M; Chaval, Y; Xuéreb, A; Ribas Salvador, A; Poulle, M-L; Voutilainen, L; Henttonen, H; Charbonnel, N; Cosson, J F

    2011-09-01

    Rodent host dynamics and dispersal are thought to be critical for hantavirus epidemiology as they determine pathogen persistence and transmission within and between host populations. We used landscape genetics to investigate how the population dynamics of the bank vole Myodes glareolus, the host of Puumala hantavirus (PUUV), vary with forest fragmentation and influence PUUV epidemiology. We sampled vole populations within the Ardennes, a French PUUV endemic area. We inferred demographic features such as population size, isolation and migration with regard to landscape configuration. We next analysed the influence of M. glareolus population dynamics on PUUV spatial distribution. Our results revealed that the global metapopulation dynamics of bank voles were strongly shaped by landscape features, including suitable patch size and connectivity. Large effective size in forest might therefore contribute to the higher observed levels of PUUV prevalence. By contrast, populations from hedge networks highly suffered from genetic drift and appeared strongly isolated from all other populations. This might result in high probabilities of local extinction for both M. glareolus and PUUV. Besides, we detected signatures of asymmetric bank vole migration from forests to hedges. These movements were likely to sustain PUUV in fragmented landscapes. In conclusion, our study provided arguments in favour of source-sink dynamics shaping PUUV persistence and spread in heterogeneous, Western European temperate landscapes. It illustrated the potential contribution of landscape genetics to the understanding of the epidemiological processes occurring at this local scale. © 2011 Blackwell Publishing Ltd.

  14. The dynamics of maternal-effect selfish genetic elements.

    Science.gov (United States)

    Smith, N G

    1998-03-21

    Maternal-effect selfish genes such as Medea or Scat act to kill progeny that do not bear a copy of the selfish gene present in the mother. Previous models of this system allowed for two types of allele, the selfish (killer) type and the sensitive (susceptible) wild-type. These models predict that the invasion conditions of the selfish allele are quite broad and that if invasion is possible a high frequency equilibrium is to be expected. The selfish element is therefore predicted to persist. Here a hypothetical third allele that neither kills nor is killed (i.e. insensitive) is considered. Such an allele could enter a population by recombination, mutation or migration. The incorporation of this third allele profoundly affects the dynamics of the system and, under some parameter values, it is possible for the spread of the insensitive allele to lead, eventually, to the fixation of the wild-type allele (reversible evolution). This is most likely if the death of progeny provides no direct benefit to the surviving sibs (i.e. in the absence of fitness compensation), as in insects without gregarious broods. Under these circumstances the selfish element cannot spread when infinitely rare, only after having risen to some finite frequency. A fitness cost to bearing the killer allele then causes its loss. However, if fitness compensation is found (e.g. in placental mammals) the invasion of the selfish element from an infinitely low level is possible for a wide range of costs and both stable coexistences of all three alleles and limit cycles of all three are then found. It is therefore to be expected that in mammals selfish maternal-effect genes are more likely both to spread and to persist than in insects, due to their different levels of fitness compensation.

  15. High-throughput Sequencing Based Immune Repertoire Study during Infectious Disease

    Directory of Open Access Journals (Sweden)

    Dongni Hou

    2016-08-01

    Full Text Available The selectivity of the adaptive immune response is based on the enormous diversity of T and B cell antigen-specific receptors. The immune repertoire, the collection of T and B cells with functional diversity in the circulatory system at any given time, is dynamic and reflects the essence of immune selectivity. In this article, we review the recent advances in immune repertoire study of infectious diseases that achieved by traditional techniques and high-throughput sequencing techniques. High-throughput sequencing techniques enable the determination of complementary regions of lymphocyte receptors with unprecedented efficiency and scale. This progress in methodology enhances the understanding of immunologic changes during pathogen challenge, and also provides a basis for further development of novel diagnostic markers, immunotherapies and vaccines.

  16. Introduction: Repertoires and Performances of Academic Identity

    Directory of Open Access Journals (Sweden)

    Herman Paul

    2016-12-01

    Full Text Available The idea that academic work requires certain personal qualities, character traits or dispositions is as old as the university. However, no matter how ubiquitous the phenomenon, it is only in recent years, in the wake of a ‘cultural turn’ in the history of science, that historians have begun exploring ideals and practices of scholarly selfhood. This theme issue seeks to make a modest contribution to this emerging field of scholarship with articles that offer conceptual reflection, as well as case studies drawn from the Low Countries. They do so under the banner of ‘scholarly personae’, not with the intention of excluding competing vocabularies, but by way of entry into a new and not yet clearly defined field of study. Introductie: repertoires voor de academische identiteitHet idee dat academisch onderzoek bepaalde persoonlijke kwaliteiten, karaktertrekken en talenten vereist is zo oud als de universiteit zelf. Toch zijn historici pas recent, in het kielzog van de ‘cultural turn’ in de wetenschapsgeschiedenis, de idealen en praktijken van de academische identiteit gaan onderzoeken. Dit themanummer wil met conceptuele reflecties en casestudies over de Lage Landen een bescheiden bijdrage leveren aan dit opkomende veld van onderzoek. De artikelen gebruiken daarvoor het concept ‘schoarly personae’, niet met de bedoeling om andere benaderingen uit te sluiten, maar bij wijze van ingang in een nieuw en nog niet helder afgebakend onderzoeksgebied.

  17. Introduction: Repertoires and Performances of Academic Identity.

    Directory of Open Access Journals (Sweden)

    H. Paul

    2016-12-01

    Full Text Available The idea that academic work requires certain personal qualities, character traits or dispositions is as old as the university. However, no matter how ubiquitous the phenomenon, it is only in recent years, in the wake of a ‘cultural turn’ in the history of science, that historians have begun exploring ideals and practices of scholarly selfhood. This theme issue seeks to make a modest contribution to this emerging field of scholarship with articles that offer conceptual reflection, as well as case studies drawn from the Low Countries. They do so under the banner of ‘scholarly personae’, not with the intention of excluding competing vocabularies, but by way of entry into a new and not yet clearly defined field of study. Introductie: repertoires voor de academische identiteit. Het idee dat academisch onderzoek bepaalde persoonlijke kwaliteiten, karaktertrekken en talenten vereist is zo oud als de universiteit zelf. Toch zijn historici pas recent, in het kielzog van de ‘cultural turn’ in de wetenschapsgeschiedenis, de idealen en praktijken van de academische identiteit gaan onderzoeken. Dit themanummer wil met conceptuele reflecties en casestudies over de Lage Landen een bescheiden bijdrage leveren aan dit opkomende veld van onderzoek. De artikelen gebruiken daarvoor het concept ‘schoarly personae’, niet met de bedoeling om andere benaderingen uit te sluiten, maar bij wijze van ingang in een nieuw en nog niet helder afgebakend onderzoeksgebied.

  18. Rapid evolution of the sequences and gene repertoires of secreted proteins in bacteria.

    Directory of Open Access Journals (Sweden)

    Teresa Nogueira

    Full Text Available Proteins secreted to the extracellular environment or to the periphery of the cell envelope, the secretome, play essential roles in foraging, antagonistic and mutualistic interactions. We hypothesize that arms races, genetic conflicts and varying selective pressures should lead to the rapid change of sequences and gene repertoires of the secretome. The analysis of 42 bacterial pan-genomes shows that secreted, and especially extracellular proteins, are predominantly encoded in the accessory genome, i.e. among genes not ubiquitous within the clade. Genes encoding outer membrane proteins might engage more frequently in intra-chromosomal gene conversion because they are more often in multi-genic families. The gene sequences encoding the secretome evolve faster than the rest of the genome and in particular at non-synonymous positions. Cell wall proteins in Firmicutes evolve particularly fast when compared with outer membrane proteins of Proteobacteria. Virulence factors are over-represented in the secretome, notably in outer membrane proteins, but cell localization explains more of the variance in substitution rates and gene repertoires than sequence homology to known virulence factors. Accordingly, the repertoires and sequences of the genes encoding the secretome change fast in the clades of obligatory and facultative pathogens and also in the clades of mutualists and free-living bacteria. Our study shows that cell localization shapes genome evolution. In agreement with our hypothesis, the repertoires and the sequences of genes encoding secreted proteins evolve fast. The particularly rapid change of extracellular proteins suggests that these public goods are key players in bacterial adaptation.

  19. Dynamics of genetic processes in chronically irradiated populations of small mammals

    International Nuclear Information System (INIS)

    Ryabokon', N.I.; Goncharova, R.I.; Smolich, I.I.; Kapitanova, N.P.; Nikitchenko, N.V.

    2000-01-01

    The distinctive features of dynamics of mutagenesis in mammalian populations under chronic low-intensive irradiation were first revealed. The main of them is gradual increase in mutability in somatic cells and embryonal lethality during series of irradiated generations of animals (bank vole - Clethrionomys glareolus). The data obtained strongly suggest that there are oppositely directed processes in natural populations after irradiation of more than 20 generations of animals: on the one hand, accumulation of mutations (genetic load of populations) and pre-mutation events which increase genome instability of germ and somatic cells in consecutive generations of animals, and on the other, formation of genetic radio adaptation through better functioning protection systems. In this period of micro evolution in chronically irradiated populations, the frequencies of genetic damages could be higher if the radiation adaptation doesn't form. (authors)

  20. An Adaptive Genetic Algorithm with Dynamic Population Size for Optimizing Join Queries

    OpenAIRE

    Vellev, Stoyan

    2008-01-01

    The problem of finding the optimal join ordering executing a query to a relational database management system is a combinatorial optimization problem, which makes deterministic exhaustive solution search unacceptable for queries with a great number of joined relations. In this work an adaptive genetic algorithm with dynamic population size is proposed for optimizing large join queries. The performance of the algorithm is compared with that of several classical non-determinis...

  1. The Effects of Predator Evolution and Genetic Variation on Predator-Prey Population-Level Dynamics.

    Science.gov (United States)

    Cortez, Michael H; Patel, Swati

    2017-07-01

    This paper explores how predator evolution and the magnitude of predator genetic variation alter the population-level dynamics of predator-prey systems. We do this by analyzing a general eco-evolutionary predator-prey model using four methods: Method 1 identifies how eco-evolutionary feedbacks alter system stability in the fast and slow evolution limits; Method 2 identifies how the amount of standing predator genetic variation alters system stability; Method 3 identifies how the phase lags in predator-prey cycles depend on the amount of genetic variation; and Method 4 determines conditions for different cycle shapes in the fast and slow evolution limits using geometric singular perturbation theory. With these four methods, we identify the conditions under which predator evolution alters system stability and shapes of predator-prey cycles, and how those effect depend on the amount of genetic variation in the predator population. We discuss the advantages and disadvantages of each method and the relations between the four methods. This work shows how the four methods can be used in tandem to make general predictions about eco-evolutionary dynamics and feedbacks.

  2. Analysis and design of a genetic circuit for dynamic metabolic engineering.

    Science.gov (United States)

    Anesiadis, Nikolaos; Kobayashi, Hideki; Cluett, William R; Mahadevan, Radhakrishnan

    2013-08-16

    Recent advances in synthetic biology have equipped us with new tools for bioprocess optimization at the genetic level. Previously, we have presented an integrated in silico design for the dynamic control of gene expression based on a density-sensing unit and a genetic toggle switch. In the present paper, analysis of a serine-producing Escherichia coli mutant shows that an instantaneous ON-OFF switch leads to a maximum theoretical productivity improvement of 29.6% compared to the mutant. To further the design, global sensitivity analysis is applied here to a mathematical model of serine production in E. coli coupled with a genetic circuit. The model of the quorum sensing and the toggle switch involves 13 parameters of which 3 are identified as having a significant effect on serine concentration. Simulations conducted in this reduced parameter space further identified the optimal ranges for these 3 key parameters to achieve productivity values close to the maximum theoretical values. This analysis can now be used to guide the experimental implementation of a dynamic metabolic engineering strategy and reduce the time required to design the genetic circuit components.

  3. Dopamine receptor repertoire of human granulosa cells

    Directory of Open Access Journals (Sweden)

    Kunz Lars

    2007-10-01

    Full Text Available Abstract Background High levels of dopamine (DA were described in human ovary and recently evidence for DA receptors in granulosa and luteal cells has been provided, as well. However, neither the full repertoire of ovarian receptors for DA, nor their specific role, is established. Human granulosa cells (GCs derived from women undergoing in vitro fertilization (IVF are an adequate model for endocrine cells of the follicle and the corpus luteum and were therefore employed in an attempt to decipher their DA receptor repertoire and functionality. Methods Cells were obtained from patients undergoing IVF and examined using cDNA-array, RT-PCR, Western blotting and immunocytochemistry. In addition, calcium measurements (with FLUO-4 were employed. Expression of two DA receptors was also examined by in-situ hybridization in rat ovary. Effects of DA on cell viability and cell volume were studied by using an ATP assay and an electronic cell counter system. Results We found members of the two DA receptor families (D1- and D2 -like associated with different signaling pathways in human GCs, namely D1 (as expected and D5 (both are Gs coupled and linked to cAMP increase and D2, D4 (Gi/Gq coupled and linked to IP3/DAG. D3 was not found. The presence of the trophic hormone hCG (10 IU/ml in the culture medium for several days did not alter mRNA (semiquantitative RT-PCR or protein levels (immunocytochemistry/Western blotting of D1,2,4,5 DA receptors. Expression of prototype receptors for the two families, D1 and D2, was furthermore shown in rat granulosa and luteal cells by in situ hybridization. Among the DA receptors found in human GCs, D2 expression was marked both at mRNA and protein levels and it was therefore further studied. Results of additional RT-PCR and Western blots showed two splice variants (D2L, D2S. Irrespective of these variants, D2 proved to be functional, as DA raised intracellular calcium levels. This calcium mobilizing effect of DA was observed

  4. A cat's tale: the impact of genetic restoration on Florida panther population dynamics and persistence.

    Science.gov (United States)

    Hostetler, Jeffrey A; Onorato, David P; Jansen, Deborah; Oli, Madan K

    2013-05-01

    1. Genetic restoration has been suggested as a management tool for mitigating detrimental effects of inbreeding depression in small, inbred populations, but the demographic mechanisms underlying population-level responses to genetic restoration remain poorly understood. 2. We studied the dynamics and persistence of the endangered Florida panther Puma concolor coryi population and evaluated the potential influence of genetic restoration on population growth and persistence parameters. As part of the genetic restoration programme, eight female Texas pumas P. c. stanleyana were released into Florida panther habitat in southern Florida in 1995. 3. The overall asymptotic population growth rate (λ) was 1.04 (5th and 95th percentiles: 0.95-1.14), suggesting an increase in the panther population of approximately 4% per year. Considering the effects of environmental and demographic stochasticities and density-dependence, the probability that the population will fall below 10 panthers within 100 years was 0.072 (0-0.606). 4. Our results suggest that the population would have declined at 5% per year (λ = 0.95; 0.83-1.08) in the absence of genetic restoration. Retrospective life table response experiment analysis revealed that the positive effect of genetic restoration on survival of kittens was primarily responsible for the substantial growth of the panther population that would otherwise have been declining. 5. For comparative purposes, we also estimated probability of quasi-extinction under two scenarios - implementation of genetic restoration and no genetic restoration initiative - using the estimated abundance of panthers in 1995, the year genetic restoration was initiated. Assuming no density-dependence, the probability that the panther population would fall below 10 panthers by 2010 was 0.098 (0.002-0.332) for the restoration scenario and 0.445 (0.032-0.944) for the no restoration scenario, providing further evidence that the panther population would have faced a

  5. Repertoire of intensive care unit pneumonia microbiota.

    Directory of Open Access Journals (Sweden)

    Sabri Bousbia

    Full Text Available Despite the considerable number of studies reported to date, the causative agents of pneumonia are not completely identified. We comprehensively applied modern and traditional laboratory diagnostic techniques to identify microbiota in patients who were admitted to or developed pneumonia in intensive care units (ICUs. During a three-year period, we tested the bronchoalveolar lavage (BAL of patients with ventilator-associated pneumonia, community-acquired pneumonia, non-ventilator ICU pneumonia and aspiration pneumonia, and compared the results with those from patients without pneumonia (controls. Samples were tested by amplification of 16S rDNA, 18S rDNA genes followed by cloning and sequencing and by PCR to target specific pathogens. We also included culture, amoeba co-culture, detection of antibodies to selected agents and urinary antigen tests. Based on molecular testing, we identified a wide repertoire of 160 bacterial species of which 73 have not been previously reported in pneumonia. Moreover, we found 37 putative new bacterial phylotypes with a 16S rDNA gene divergence ≥ 98% from known phylotypes. We also identified 24 fungal species of which 6 have not been previously reported in pneumonia and 7 viruses. Patients can present up to 16 different microorganisms in a single BAL (mean ± SD; 3.77 ± 2.93. Some pathogens considered to be typical for ICU pneumonia such as Pseudomonas aeruginosa and Streptococcus species can be detected as commonly in controls as in pneumonia patients which strikingly highlights the existence of a core pulmonary microbiota. Differences in the microbiota of different forms of pneumonia were documented.

  6. A Variable Interval Rescheduling Strategy for Dynamic Flexible Job Shop Scheduling Problem by Improved Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2017-01-01

    Full Text Available In real-world manufacturing systems, production scheduling systems are often implemented under random or dynamic events like machine failure, unexpected processing times, stochastic arrival of the urgent orders, cancellation of the orders, and so on. These dynamic events will lead the initial scheduling scheme to be nonoptimal and/or infeasible. Hence, appropriate dynamic rescheduling approaches are needed to overcome the dynamic events. In this paper, we propose a dynamic rescheduling method based on variable interval rescheduling strategy (VIRS to deal with the dynamic flexible job shop scheduling problem considering machine failure, urgent job arrival, and job damage as disruptions. On the other hand, an improved genetic algorithm (GA is proposed for minimizing makespan. In our improved GA, a mix of random initialization population by combining initialization machine and initialization operation with random initialization is designed for generating high-quality initial population. In addition, the elitist strategy (ES and improved population diversity strategy (IPDS are used to avoid falling into the local optimal solution. Experimental results for static and several dynamic events in the FJSP show that our method is feasible and effective.

  7. Genetic variation in foundation species governs the dynamics of trophic interactions

    Science.gov (United States)

    Valencia-Cuevas, Leticia; Mussali-Galante, Patricia; Cano-Santana, Zenón; Pujade-Villar, Juli; Equihua-Martínez, Armando

    2018-01-01

    Abstract Various studies have demonstrated that the foundation species genetic diversity can have direct effects that extend beyond the individual or population level, affecting the dependent communities. Additionally, these effects may be indirectly extended to higher trophic levels throughout the entire community. Quercus castanea is an oak species with characteristics of foundation species beyond presenting a wide geographical distribution and being a dominant element of Mexican temperate forests. In this study, we analyzed the influence of population (He) and individual (HL) genetic diversity of Q. castanea on its canopy endophagous insect community and associated parasitoids. Specifically, we studied the composition, richness (S) and density of leaf-mining moths (Lepidoptera: Tischeridae, Citheraniidae), gall-forming wasps (Hymenoptera: Cynipidae), and canopy parasitoids of Q. castanea. We sampled 120 trees belonging to six populations (20/site) through the previously recognized gradient of genetic diversity. In total, 22 endophagous insect species belonging to three orders (Hymenoptera, Lepidoptera, and Diptera) and 20 parasitoid species belonging to 13 families were identified. In general, we observed that the individual genetic diversity of the host plant (HL) has a significant positive effect on the S and density of the canopy endophagous insect communities. In contrast, He has a significant negative effect on the S of endophagous insects. Additionally, indirect effects of HL were observed, affecting the S and density of parasitoid insects. Our results suggest that genetic variation in foundation species can be one of the most important factors governing the dynamics of tritrophic interactions that involve oaks, herbivores, and parasitoids. PMID:29492034

  8. Element repertoire: change and development with age in Whitethroat Sylvia communis song

    DEFF Research Database (Denmark)

    Balsby, T.J.S.; Hansen, P.

    2010-01-01

    Song repertoires are often important determining factors in sexual selection. In several species, older males have larger repertoires than 1-year-old males. The development of large song repertoires by an individual is, however, poorly understood. We studied song element repertoire changes in five...... based on the first-year repertoire, which may explain why large song repertoires are mainly expressed by males at least 2 years of age. It would appear, therefore, that song element repertoire size could be a reliable signal of male age....

  9. Extraction of Static and Dynamic Reservoir Operation Rules by Genetic Programming

    Directory of Open Access Journals (Sweden)

    Habib Akbari Alashti

    2014-11-01

    Full Text Available Considering the necessity of desirable operation of limited water resources and assuming the significant role of dams in controlling and consuming the surface waters, highlights the advantageous of suitable operation rules for optimal and sustainable operation of dams. This study investigates the hydroelectric supply of a one-reservoir system of Karoon3 using nonlinear programming (NLP, genetic algorithm (GA, genetic programming (GP and fixed length gen GP (FLGGP in real-time operation of dam considering two approaches of static and dynamic operation rules. In static operation rule, only one rule curve is extracted for all months in a year whereas in dynamic operation rule, monthly rule curves (12 rules are extracted for each month of a year. In addition, nonlinear decision rule (NLDR curves are considered, and the total deficiency function as the target (objective function have been used for evaluating the performance of each method and approach. Results show appropriate efficiency of GP and FLGGP methods in extracting operation rules in both approaches. Superiority of these methods to operation methods yielded by GA and NLP is 5%. Moreover, according to the results, it can be remarked that, FLGGP method is an alternative for GP method, whereas the GP method cannot be used due to its limitations. Comparison of two approaches of static and dynamic operation rules demonstrated the superiority of dynamic operation rule to static operation rule (about 10% and therefore this method has more capabilities in real-time operation of the reservoirs systems.

  10. Accurate and High-Coverage Immune Repertoire Sequencing Reveals Characteristics of Antibody Repertoire Diversification in Young Children with Malaria

    Science.gov (United States)

    Jiang, Ning

    Accurately measuring the immune repertoire sequence composition, diversity, and abundance is important in studying repertoire response in infections, vaccinations, and cancer immunology. Using molecular identifiers (MIDs) to tag mRNA molecules is an effective method in improving the accuracy of immune repertoire sequencing (IR-seq). However, it is still difficult to use IR-seq on small amount of clinical samples to achieve a high coverage of the repertoire diversities. This is especially challenging in studying infections and vaccinations where B cell subpopulations with fewer cells, such as memory B cells or plasmablasts, are often of great interest to study somatic mutation patterns and diversity changes. Here, we describe an approach of IR-seq based on the use of MIDs in combination with a clustering method that can reveal more than 80% of the antibody diversity in a sample and can be applied to as few as 1,000 B cells. We applied this to study the antibody repertoires of young children before and during an acute malaria infection. We discovered unexpectedly high levels of somatic hypermutation (SHM) in infants and revealed characteristics of antibody repertoire development in young children that would have a profound impact on immunization in children.

  11. The repertoire of bitter taste receptor genes in canids.

    Science.gov (United States)

    Shang, Shuai; Wu, Xiaoyang; Chen, Jun; Zhang, Huanxin; Zhong, Huaming; Wei, Qinguo; Yan, Jiakuo; Li, Haotian; Liu, Guangshuai; Sha, Weilai; Zhang, Honghai

    2017-07-01

    Bitter taste receptors (Tas2rs) play important roles in mammalian defense mechanisms by helping animals detect and avoid toxins in food. Although Tas2r genes have been widely studied in several mammals, minimal research has been performed in canids. To analyze the genetic basis of Tas2r genes in canids, we first identified Tas2r genes in the wolf, maned wolf, red fox, corsac fox, Tibetan fox, fennec fox, dhole and African hunting dog. A total of 183 Tas2r genes, consisting of 118 intact genes, 6 partial genes and 59 pseudogenes, were detected. Differences in the pseudogenes were observed among nine canid species. For example, Tas2r4 was a pseudogene in the dog but might play a functional role in other canid species. The Tas2r42 and Tas2r10 genes were pseudogenes in the maned wolf and dhole, respectively, and the Tas2r5 and Tas2r34 genes were pseudogenes in the African hunting dog; however, these genes were intact genes in other canid species. The differences in Tas2r pseudogenes among canids might suggest that the loss of intact Tas2r genes in canid species is species-dependent. We further compared the 183 Tas2r genes identified in this study with Tas2r genes from ten additional carnivorous species to evaluate the potential influence of diet on the evolution of the Tas2r gene repertoire. Phylogenetic analysis revealed that most of the Tas2r genes from the 18 species intermingled across the tree, suggesting that Tas2r genes are conserved among carnivores. Within canids, we found that some Tas2r genes corresponded to the traditional taxonomic groupings, while some did not. PIC analysis showed that the number of Tas2r genes in carnivores exhibited no positive correlation with diet composition, which might be due to the limited number of carnivores included in our study.

  12. Spatial and temporal dynamics of the genetic organization of small mammal populations

    International Nuclear Information System (INIS)

    Smith, M.H.; Manlove, M.N.; Joule, J.

    1978-01-01

    A functional population is a group of organisms and their offspring that contributes to a common gene pool within a certain area and time period. It is also the unit of evolution and should be viewed both in quantitative and qualitative terms. Selection, drift, dispersal, and mutation can alter the composition of populations. Spatial heterogeneity in allele frequencies argues for a conceptual model that has a series of relatively small populations semi-isolated from one another. Because of the relatively high levels of genetic variability characteristic of most mammalian species, significant amounts of gene flow between these spatially subdivided populations must occur when longer time periods are considered. Fluctuations in the genetic structure of populations seem to be important in altering the fitness of the individuals within the populations. The interaction of populations through gene flow is important in changing the levels of intrapopulational genetic variability. Populations can be characterized as existing on a continuum from relatively stable to unstable numbers and by other associated changes in their characteristics. Temporal changes in allele frequency occur in a variety of mammals. Conceptually, a species can be viewed as a series of dynamic populations that vary in numbers and quality in both a spatial and temporal context even over short distances and time periods. Short term changes in the quality of individuals in a population can be important in altering the short term dynamics of a population

  13. An enhanced dynamic model of battery using genetic algorithm suitable for photovoltaic applications

    International Nuclear Information System (INIS)

    Blaifi, S.; Moulahoum, S.; Colak, I.; Merrouche, W.

    2016-01-01

    Highlights: • We proposed a developed dynamic battery model suitable for photovoltaic systems. • We used genetic algorithm optimization method to find parameters that gives minimized error. • The validation was carried out with real measurements from stand-alone photovoltaic string. - Abstract: Modeling of batteries in photovoltaic systems has been a major issue related to the random dynamic regime imposed by the changes of solar irradiation and ambient temperature added to the complexity of battery electrochemical and electrical behaviors. However, various approaches have been proposed to model the battery behavior by predicting from detailed electrochemical, electrical or analytical models to high-level stochastic models. In this paper, an improvement of dynamic electrical battery model is proposed by automatic parameter extraction using genetic algorithm in order to give usefulness and future implementation for practical application. It is highlighted that the enhancement of 21 values of the parameters of CEIMAT model presents a good agreement with real measurements for different modes like charge or discharge and various conditions.

  14. EXAFS study on dynamic structural property of porous morph-genetic SiC

    International Nuclear Information System (INIS)

    Ding, J.; Sun, B.H.; Fan, T.X.; Zhang, D.; Kamada, M.; Ogawa, H.; Guo, Q.X.

    2005-01-01

    Novel porous morph-genetic silicon carbide has been fabricated through sintering treatment, after infiltrating the methyl organic silicone resin to the bio-template. Its dynamic transition of structure during sintering process is investigated by extended X-ray absorption fine structure (EXAFS) for the first time. By analyzing Si K-edge EXAFS, it is found that the coordination number of the nearest C shell remains almost unchanged while that of the nearest Si shell dramatically changes when the structure is transformed from amorphous into crystalline state

  15. Using genetic algorithms for calibrating simplified models of nuclear reactor dynamics

    International Nuclear Information System (INIS)

    Marseguerra, Marzio; Zio, Enrico; Canetta, Raffaele

    2004-01-01

    In this paper the use of genetic algorithms for the estimation of the effective parameters of a model of nuclear reactor dynamics is investigated. The calibration of the effective parameters is achieved by best fitting the model responses of the quantities of interest (e.g., reactor power, average fuel and coolant temperatures) to the actual evolution profiles, here simulated by the Quandry based reactor kinetics (Quark) code available from the Nuclear Energy Agency. Alternative schemes of single- and multi-objective optimization are investigated. The efficiency of convergence of the algorithm with respect to the different effective parameters to be calibrated is studied with reference to the physical relationships involved

  16. Using genetic algorithms for calibrating simplified models of nuclear reactor dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Marseguerra, Marzio E-mail: marzio.marseguerra@polimi.it; Zio, Enrico E-mail: enrico.zio@polimi.it; Canetta, Raffaele

    2004-07-01

    In this paper the use of genetic algorithms for the estimation of the effective parameters of a model of nuclear reactor dynamics is investigated. The calibration of the effective parameters is achieved by best fitting the model responses of the quantities of interest (e.g., reactor power, average fuel and coolant temperatures) to the actual evolution profiles, here simulated by the Quandry based reactor kinetics (Quark) code available from the Nuclear Energy Agency. Alternative schemes of single- and multi-objective optimization are investigated. The efficiency of convergence of the algorithm with respect to the different effective parameters to be calibrated is studied with reference to the physical relationships involved.

  17. Extracting quantum dynamics from genetic learning algorithms through principal control analysis

    International Nuclear Information System (INIS)

    White, J L; Pearson, B J; Bucksbaum, P H

    2004-01-01

    Genetic learning algorithms are widely used to control ultrafast optical pulse shapes for photo-induced quantum control of atoms and molecules. An unresolved issue is how to use the solutions found by these algorithms to learn about the system's quantum dynamics. We propose a simple method based on covariance analysis of the control space, which can reveal the degrees of freedom in the effective control Hamiltonian. We have applied this technique to stimulated Raman scattering in liquid methanol. A simple model of two-mode stimulated Raman scattering is consistent with the results. (letter to the editor)

  18. VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires.

    Directory of Open Access Journals (Sweden)

    Mikhail Shugay

    2015-11-01

    Full Text Available Despite the growing number of immune repertoire sequencing studies, the field still lacks software for analysis and comprehension of this high-dimensional data. Here we report VDJtools, a complementary software suite that solves a wide range of T cell receptor (TCR repertoires post-analysis tasks, provides a detailed tabular output and publication-ready graphics, and is built on top of a flexible API. Using TCR datasets for a large cohort of unrelated healthy donors, twins, and multiple sclerosis patients we demonstrate that VDJtools greatly facilitates the analysis and leads to sound biological conclusions. VDJtools software and documentation are available at https://github.com/mikessh/vdjtools.

  19. Transitions in genetic toggle switches driven by dynamic disorder in rate coefficients

    International Nuclear Information System (INIS)

    Chen, Hang; Thill, Peter; Cao, Jianshu

    2016-01-01

    In biochemical systems, intrinsic noise may drive the system switch from one stable state to another. We investigate how kinetic switching between stable states in a bistable network is influenced by dynamic disorder, i.e., fluctuations in the rate coefficients. Using the geometric minimum action method, we first investigate the optimal transition paths and the corresponding minimum actions based on a genetic toggle switch model in which reaction coefficients draw from a discrete probability distribution. For the continuous probability distribution of the rate coefficient, we then consider two models of dynamic disorder in which reaction coefficients undergo different stochastic processes with the same stationary distribution. In one, the kinetic parameters follow a discrete Markov process and in the other they follow continuous Langevin dynamics. We find that regulation of the parameters modulating the dynamic disorder, as has been demonstrated to occur through allosteric control in bistable networks in the immune system, can be crucial in shaping the statistics of optimal transition paths, transition probabilities, and the stationary probability distribution of the network.

  20. Transitions in genetic toggle switches driven by dynamic disorder in rate coefficients

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Hang, E-mail: hangchen@mit.edu; Thill, Peter; Cao, Jianshu [Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States)

    2016-05-07

    In biochemical systems, intrinsic noise may drive the system switch from one stable state to another. We investigate how kinetic switching between stable states in a bistable network is influenced by dynamic disorder, i.e., fluctuations in the rate coefficients. Using the geometric minimum action method, we first investigate the optimal transition paths and the corresponding minimum actions based on a genetic toggle switch model in which reaction coefficients draw from a discrete probability distribution. For the continuous probability distribution of the rate coefficient, we then consider two models of dynamic disorder in which reaction coefficients undergo different stochastic processes with the same stationary distribution. In one, the kinetic parameters follow a discrete Markov process and in the other they follow continuous Langevin dynamics. We find that regulation of the parameters modulating the dynamic disorder, as has been demonstrated to occur through allosteric control in bistable networks in the immune system, can be crucial in shaping the statistics of optimal transition paths, transition probabilities, and the stationary probability distribution of the network.

  1. Insights into dynamics of mobile genetic elements in hyperthermophilic environments from five new Thermococcus plasmids.

    Directory of Open Access Journals (Sweden)

    Mart Krupovic

    Full Text Available Mobilome of hyperthermophilic archaea dwelling in deep-sea hydrothermal vents is poorly characterized. To gain insight into genetic diversity and dynamics of mobile genetic elements in these environments we have sequenced five new plasmids from different Thermococcus strains that have been isolated from geographically remote hydrothermal vents. The plasmids were ascribed to two subfamilies, pTN2-like and pEXT9a-like. Gene content and phylogenetic analyses illuminated a robust connection between pTN2-like plasmids and Pyrococcus abyssi virus 1 (PAV1, with roughly half of the viral genome being composed of genes that have homologues in plasmids. Unexpectedly, pEXT9a-like plasmids were found to be closely related to the previously sequenced plasmid pMETVU01 from Methanocaldococcus vulcanius M7. Our data suggests that the latter observation is most compatible with an unprecedented horizontal transfer of a pEXT9a-like plasmid from Thermococcales to Methanococcales. Gene content analysis revealed that thermococcal plasmids encode Hfq-like proteins and toxin-antitoxin (TA systems of two different families, VapBC and RelBE. Notably, although abundant in archaeal genomes, to our knowledge, TA and hfq-like genes have not been previously found in archaeal plasmids or viruses. Finally, the plasmids described here might prove to be useful in developing new genetic tools for hyperthermophiles.

  2. Drosophila growth cones: a genetically tractable platform for the analysis of axonal growth dynamics.

    Science.gov (United States)

    Sánchez-Soriano, Natalia; Gonçalves-Pimentel, Catarina; Beaven, Robin; Haessler, Ulrike; Ofner-Ziegenfuss, Lisa; Ballestrem, Christoph; Prokop, Andreas

    2010-01-01

    The formation of neuronal networks, during development and regeneration, requires outgrowth of axons along reproducible paths toward their appropriate postsynaptic target cells. Axonal extension occurs at growth cones (GCs) at the tips of axons. GC advance and navigation requires the activity of their cytoskeletal networks, comprising filamentous actin (F-actin) in lamellipodia and filopodia as well as dynamic microtubules (MTs) emanating from bundles of the axonal core. The molecular mechanisms governing these two cytoskeletal networks, their cross-talk, and their response to extracellular signaling cues are only partially understood, hindering our conceptual understanding of how regulated changes in GC behavior are controlled. Here, we introduce Drosophila GCs as a suitable model to address these mechanisms. Morphological and cytoskeletal readouts of Drosophila GCs are similar to those of other models, including mammals, as demonstrated here for MT and F-actin dynamics, axonal growth rates, filopodial structure and motility, organizational principles of MT networks, and subcellular marker localization. Therefore, we expect fundamental insights gained in Drosophila to be translatable into vertebrate biology. The advantage of the Drosophila model over others is its enormous amenability to combinatorial genetics as a powerful strategy to address the complexity of regulatory networks governing axonal growth. Thus, using pharmacological and genetic manipulations, we demonstrate a role of the actin cytoskeleton in a specific form of MT organization (loop formation), known to regulate GC pausing behavior. We demonstrate these events to be mediated by the actin-MT linking factor Short stop, thus identifying an essential molecular player in this context.

  3. Alleles versus genotypes: Genetic interactions and the dynamics of selection in sexual populations

    Science.gov (United States)

    Neher, Richard

    2010-03-01

    Physical interactions between amino-acids are essential for protein structure and activity, while protein-protein interactions and regulatory interactions are central to cellular function. As a consequence of these interactions, the combined effect of two mutations can differ from the sum of the individual effects of the mutations. This phenomenon of genetic interaction is known as epistasis. However, the importance of epistasis and its effects on evolutionary dynamics are poorly understood, especially in sexual populations where recombination breaks up existing combinations of alleles to produce new ones. Here, we present a computational model of selection dynamics involving many epistatic loci in a recombining population. We demonstrate that a large number of polymorphic interacting loci can, despite frequent recombination, exhibit cooperative behavior that locks alleles into favorable genotypes leading to a population consisting of a set of competing clones. As the recombination rate exceeds a certain critical value this ``genotype selection'' phase disappears in an abrupt transition giving way to ``allele selection'' - the phase where different loci are only weakly correlated as expected in sexually reproducing populations. Clustering of interacting sets of genes on a chromosome leads to the emergence of an intermediate regime, where localized blocks of cooperating alleles lock into genetic modules. Large populations attain highest fitness at a recombination rate just below critical, suggesting that natural selection might tune recombination rates to balance the beneficial aspect of exploration of genotype space with the breaking up of synergistic allele combinations.

  4. Translating conservation genetics into management: Pan-European minimum requirements for dynamic conservation units of forest tree genetic diversity

    OpenAIRE

    Koskela, Jarkko; Lefèvre, François; Schueler, Silvio; Kraigher, Hojka; Olrik, Ditte C.; Hubert, Jason; Longauer, Roman; Bozzano, Michele; Yrjänä, Leena; Alizoti, Paraskevi; Rotach, Peter; Vietto, Lorenzo; Bordács, Sándor; Myking, Tor; Eysteinsson, Thröstur

    2013-01-01

    This paper provides a review of theoretical and practical aspects related to genetic management of forest trees. The implementation of international commitments on forest genetic diversity has been slow and partly neglected. Conservation of forest genetic diversity is still riddled with problems, and complexities of national legal and administrative structures. Europe is an example of a complex region where the dis- tribution ranges of tree species extend across large geographical areas with ...

  5. Visualization of local Ca2+ dynamics with genetically encoded bioluminescent reporters.

    Science.gov (United States)

    Rogers, Kelly L; Stinnakre, Jacques; Agulhon, Cendra; Jublot, Delphine; Shorte, Spencer L; Kremer, Eric J; Brûlet, Philippe

    2005-02-01

    Measurements of local Ca2+ signalling at different developmental stages and/or in specific cell types is important for understanding aspects of brain functioning. The use of light excitation in fluorescence imaging can cause phototoxicity, photobleaching and auto-fluorescence. In contrast, bioluminescence does not require the input of radiative energy and can therefore be measured over long periods, with very high temporal resolution. Aequorin is a genetically encoded Ca(2+)-sensitive bioluminescent protein, however, its low quantum yield prevents dynamic measurements of Ca2+ responses in single cells. To overcome this limitation, we recently reported the bi-functional Ca2+ reporter gene, GFP-aequorin (GA), which was developed specifically to improve the light output and stability of aequorin chimeras [V. Baubet, et al., (2000) PNAS, 97, 7260-7265]. In the current study, we have genetically targeted GA to different microdomains important in synaptic transmission, including to the mitochondrial matrix, endoplasmic reticulum, synaptic vesicles and to the postsynaptic density. We demonstrate that these reporters enable 'real-time' measurements of subcellular Ca2+ changes in single mammalian neurons using bioluminescence. The high signal-to-noise ratio of these reporters is also important in that it affords the visualization of Ca2+ dynamics in cell-cell communication in neuronal cultures and tissue slices. Further, we demonstrate the utility of this approach in ex-vivo preparations of mammalian retina, a paradigm in which external light input should be controlled. This represents a novel molecular imaging approach for non-invasive monitoring of local Ca2+ dynamics and cellular communication in tissue or whole animal studies.

  6. Beyond Languages, beyond Modalities: Transforming the Study of Semiotic Repertoires

    Science.gov (United States)

    Kusters, Annelies; Spotti, Massimiliano; Swanwick, Ruth; Tapio, Elina

    2017-01-01

    This paper presents a critical examination of key concepts in the study of (signed and spoken) language and multimodality. It shows how shifts in conceptual understandings of language use, moving from bilingualism to multilingualism and (trans)languaging, have resulted in the revitalisation of the concept of language repertoires. We discuss key…

  7. Global genetic response in a cancer cell: self-organized coherent expression dynamics.

    Directory of Open Access Journals (Sweden)

    Masa Tsuchiya

    Full Text Available Understanding the basic mechanism of the spatio-temporal self-control of genome-wide gene expression engaged with the complex epigenetic molecular assembly is one of major challenges in current biological science. In this study, the genome-wide dynamical profile of gene expression was analyzed for MCF-7 breast cancer cells induced by two distinct ErbB receptor ligands: epidermal growth factor (EGF and heregulin (HRG, which drive cell proliferation and differentiation, respectively. We focused our attention to elucidate how global genetic responses emerge and to decipher what is an underlying principle for dynamic self-control of genome-wide gene expression. The whole mRNA expression was classified into about a hundred groups according to the root mean square fluctuation (rmsf. These expression groups showed characteristic time-dependent correlations, indicating the existence of collective behaviors on the ensemble of genes with respect to mRNA expression and also to temporal changes in expression. All-or-none responses were observed for HRG and EGF (biphasic statistics at around 10-20 min. The emergence of time-dependent collective behaviors of expression occurred through bifurcation of a coherent expression state (CES. In the ensemble of mRNA expression, the self-organized CESs reveals distinct characteristic expression domains for biphasic statistics, which exhibits notably the presence of criticality in the expression profile as a route for genomic transition. In time-dependent changes in the expression domains, the dynamics of CES reveals that the temporal development of the characteristic domains is characterized as autonomous bistable switch, which exhibits dynamic criticality (the temporal development of criticality in the genome-wide coherent expression dynamics. It is expected that elucidation of the biophysical origin for such critical behavior sheds light on the underlying mechanism of the control of whole genome.

  8. Genetics

    International Nuclear Information System (INIS)

    Hubitschek, H.E.

    1975-01-01

    Progress is reported on the following research projects: genetic effects of high LET radiations; genetic regulation, alteration, and repair; chromosome replication and the division cycle of Escherichia coli; effects of radioisotope decay in the DNA of microorganisms; initiation and termination of DNA replication in Bacillus subtilis; mutagenesis in mouse myeloma cells; lethal and mutagenic effects of near-uv radiation; effect of 8-methoxypsoralen on photodynamic lethality and mutagenicity in Escherichia coli; DNA repair of the lethal effects of far-uv; and near uv irradiation of bacterial cells

  9. Graphics Processing Unit-Enhanced Genetic Algorithms for Solving the Temporal Dynamics of Gene Regulatory Networks.

    Science.gov (United States)

    García-Calvo, Raúl; Guisado, J L; Diaz-Del-Rio, Fernando; Córdoba, Antonio; Jiménez-Morales, Francisco

    2018-01-01

    Understanding the regulation of gene expression is one of the key problems in current biology. A promising method for that purpose is the determination of the temporal dynamics between known initial and ending network states, by using simple acting rules. The huge amount of rule combinations and the nonlinear inherent nature of the problem make genetic algorithms an excellent candidate for finding optimal solutions. As this is a computationally intensive problem that needs long runtimes in conventional architectures for realistic network sizes, it is fundamental to accelerate this task. In this article, we study how to develop efficient parallel implementations of this method for the fine-grained parallel architecture of graphics processing units (GPUs) using the compute unified device architecture (CUDA) platform. An exhaustive and methodical study of various parallel genetic algorithm schemes-master-slave, island, cellular, and hybrid models, and various individual selection methods (roulette, elitist)-is carried out for this problem. Several procedures that optimize the use of the GPU's resources are presented. We conclude that the implementation that produces better results (both from the performance and the genetic algorithm fitness perspectives) is simulating a few thousands of individuals grouped in a few islands using elitist selection. This model comprises 2 mighty factors for discovering the best solutions: finding good individuals in a short number of generations, and introducing genetic diversity via a relatively frequent and numerous migration. As a result, we have even found the optimal solution for the analyzed gene regulatory network (GRN). In addition, a comparative study of the performance obtained by the different parallel implementations on GPU versus a sequential application on CPU is carried out. In our tests, a multifold speedup was obtained for our optimized parallel implementation of the method on medium class GPU over an equivalent

  10. Graphics Processing Unit–Enhanced Genetic Algorithms for Solving the Temporal Dynamics of Gene Regulatory Networks

    Science.gov (United States)

    García-Calvo, Raúl; Guisado, JL; Diaz-del-Rio, Fernando; Córdoba, Antonio; Jiménez-Morales, Francisco

    2018-01-01

    Understanding the regulation of gene expression is one of the key problems in current biology. A promising method for that purpose is the determination of the temporal dynamics between known initial and ending network states, by using simple acting rules. The huge amount of rule combinations and the nonlinear inherent nature of the problem make genetic algorithms an excellent candidate for finding optimal solutions. As this is a computationally intensive problem that needs long runtimes in conventional architectures for realistic network sizes, it is fundamental to accelerate this task. In this article, we study how to develop efficient parallel implementations of this method for the fine-grained parallel architecture of graphics processing units (GPUs) using the compute unified device architecture (CUDA) platform. An exhaustive and methodical study of various parallel genetic algorithm schemes—master-slave, island, cellular, and hybrid models, and various individual selection methods (roulette, elitist)—is carried out for this problem. Several procedures that optimize the use of the GPU’s resources are presented. We conclude that the implementation that produces better results (both from the performance and the genetic algorithm fitness perspectives) is simulating a few thousands of individuals grouped in a few islands using elitist selection. This model comprises 2 mighty factors for discovering the best solutions: finding good individuals in a short number of generations, and introducing genetic diversity via a relatively frequent and numerous migration. As a result, we have even found the optimal solution for the analyzed gene regulatory network (GRN). In addition, a comparative study of the performance obtained by the different parallel implementations on GPU versus a sequential application on CPU is carried out. In our tests, a multifold speedup was obtained for our optimized parallel implementation of the method on medium class GPU over an equivalent

  11. Human IgG repertoire of malaria antigen-immunized human immune system (HIS) mice.

    Science.gov (United States)

    Nogueira, Raquel Tayar; Sahi, Vincent; Huang, Jing; Tsuji, Moriya

    2017-08-01

    Humanized mouse models present an important tool for preclinical evaluation of new vaccines and therapeutics. Here we show the human variable repertoire of antibody sequences cloned from a previously described human immune system (HIS) mouse model that possesses functional human CD4+ T cells and B cells, namely HIS-CD4/B mice. We sequenced variable IgG genes from single memory B-cell and plasma-cell sorted from splenocytes or whole blood lymphocytes of HIS-CD4/B mice that were vaccinated with a human plasmodial antigen, a recombinant Plasmodium falciparum circumsporozoite protein (rPfCSP). We demonstrate that rPfCSP immunization triggers a diverse B-cell IgG repertoire composed of various human VH family genes and distinct V(D)J recombinations that constitute diverse CDR3 sequences similar to humans, although low hypermutated sequences were generated. These results demonstrate the substantial genetic diversity of responding human B cells of HIS-CD4/B mice and their capacity to mount human IgG class-switched antibody response upon vaccination. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  12. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  13. Understanding the Broad Substrate Repertoire of Nitroreductase Based on Its Kinetic Mechanism*

    Science.gov (United States)

    Pitsawong, Warintra; Hoben, John P.; Miller, Anne-Frances

    2014-01-01

    The oxygen-insensitive nitroreductase from Enterobacter cloacae (NR) catalyzes two-electron reduction of nitroaromatics to the corresponding nitroso compounds and, subsequently, to hydroxylamine products. NR has an unusually broad substrate repertoire, which may be related to protein dynamics (flexibility) and/or a simple non-selective kinetic mechanism. To investigate the possible role of mechanism in the broad substrate repertoire of NR, the kinetics of oxidation of NR by para-nitrobenzoic acid (p-NBA) were investigated using stopped-flow techniques at 4 °C. The results revealed a hyperbolic dependence on the p-NBA concentration with a limiting rate of 1.90 ± 0.09 s−1, indicating one-step binding before the flavin oxidation step. There is no evidence for a distinct binding step in which specificity might be enforced. The reduction of p-NBA is rate-limiting in steady-state turnover (1.7 ± 0.3 s−1). The pre-steady-state reduction kinetics of NR by NADH indicate that NADH reduces the enzyme with a rate constant of 700 ± 20 s−1 and a dissociation constant of 0.51 ± 0.04 mm. Thus, we demonstrate simple transient kinetics in both the reductive and oxidative half-reactions that help to explain the broad substrate repertoire of NR. Finally, we tested the ability of NR to reduce para-hydroxylaminobenzoic acid, demonstrating that the corresponding amine does not accumulate to significant levels even under anaerobic conditions. Thus E. cloacae NR is not a good candidate for enzymatic production of aromatic amines. PMID:24706760

  14. Bayesian state space models for dynamic genetic network construction across multiple tissues.

    Science.gov (United States)

    Liang, Yulan; Kelemen, Arpad

    2016-08-01

    Construction of gene-gene interaction networks and potential pathways is a challenging and important problem in genomic research for complex diseases while estimating the dynamic changes of the temporal correlations and non-stationarity are the keys in this process. In this paper, we develop dynamic state space models with hierarchical Bayesian settings to tackle this challenge for inferring the dynamic profiles and genetic networks associated with disease treatments. We treat both the stochastic transition matrix and the observation matrix time-variant and include temporal correlation structures in the covariance matrix estimations in the multivariate Bayesian state space models. The unevenly spaced short time courses with unseen time points are treated as hidden state variables. Hierarchical Bayesian approaches with various prior and hyper-prior models with Monte Carlo Markov Chain and Gibbs sampling algorithms are used to estimate the model parameters and the hidden state variables. We apply the proposed Hierarchical Bayesian state space models to multiple tissues (liver, skeletal muscle, and kidney) Affymetrix time course data sets following corticosteroid (CS) drug administration. Both simulation and real data analysis results show that the genomic changes over time and gene-gene interaction in response to CS treatment can be well captured by the proposed models. The proposed dynamic Hierarchical Bayesian state space modeling approaches could be expanded and applied to other large scale genomic data, such as next generation sequence (NGS) combined with real time and time varying electronic health record (EHR) for more comprehensive and robust systematic and network based analysis in order to transform big biomedical data into predictions and diagnostics for precision medicine and personalized healthcare with better decision making and patient outcomes.

  15. Genetic variation and dynamics of infections of equid herpesvirus 5 in individual horses.

    Science.gov (United States)

    Back, Helena; Ullman, Karin; Leijon, Mikael; Söderlund, Robert; Penell, Johanna; Ståhl, Karl; Pringle, John; Valarcher, Jean-François

    2016-01-01

    Equid herpesvirus 5 (EHV-5) is related to the human Epstein-Barr virus (human herpesvirus 4) and has frequently been observed in equine populations worldwide. EHV-5 was previously assumed to be low to non-pathogenic; however, studies have also related the virus to the severe lung disease equine multinodular pulmonary fibrosis (EMPF). Genetic information of EHV-5 is scanty: the whole genome was recently described and only limited nucleotide sequences are available. In this study, samples were taken twice 1 year apart from eight healthy horses at the same professional training yard and samples from a ninth horse that was diagnosed with EMPF with samples taken pre- and post-mortem to analyse partial glycoprotein B (gB) gene of EHV-5 by using next-generation sequencing. The analysis resulted in 27 partial gB gene sequences, 11 unique sequence types and five amino acid sequences. These sequences could be classified within four genotypes (I-IV) of the EHV-5 gB gene based on the degree of similarity of the nucleotide and amino acid sequences, and in this work horses were shown to be identified with up to three different genotypes simultaneously. The observations showed a range of interactions between EHV-5 and the host over time, where the same virus persists in some horses, whereas others have a more dynamic infection pattern including strains from different genotypes. This study provides insight into the genetic variation and dynamics of EHV-5, and highlights that further work is needed to understand the EHV-5 interaction with its host.

  16. Dynamical patterning modules: physico-genetic determinants of morphological development and evolution

    International Nuclear Information System (INIS)

    Newman, Stuart A; Bhat, Ramray

    2008-01-01

    The shapes and forms of multicellular organisms arise by the generation of new cell states and types and changes in the numbers and rearrangements of the various kinds of cells. While morphogenesis and pattern formation in all animal species are widely recognized to be mediated by the gene products of an evolutionarily conserved 'developmental-genetic toolkit', the link between these molecular players and the physics underlying these processes has been generally ignored. This paper introduces the concept of 'dynamical patterning modules' (DPMs), units consisting of one or more products of the 'toolkit' genes that mobilize physical processes characteristic of chemically and mechanically excitable meso- to macroscopic systems such as cell aggregates: cohesion, viscoelasticity, diffusion, spatiotemporal heterogeneity based on lateral inhibition and multistable and oscillatory dynamics. We suggest that ancient toolkit gene products, most predating the emergence of multicellularity, assumed novel morphogenetic functions due to change in the scale and context inherent to multicellularity. We show that DPMs, acting individually and in concert with each other, constitute a 'pattern language' capable of generating all metazoan body plans and organ forms. The physical dimension of developmental causation implies that multicellular forms during the explosive radiation of animal body plans in the middle Cambrian, approximately 530 million years ago, could have explored an extensive morphospace without concomitant genotypic change or selection for adaptation. The morphologically plastic body plans and organ forms generated by DPMs, and their ontogenetic trajectories, would subsequently have been stabilized and consolidated by natural selection and genetic drift. This perspective also solves the apparent 'molecular homology-analogy paradox', whereby widely divergent modern animal types utilize the same molecular toolkit during development by proposing, in contrast to the Neo

  17. Multivariate analysis using high definition flow cytometry reveals distinct T cell repertoires between the foetal-maternal interface and the peripheral blood

    Directory of Open Access Journals (Sweden)

    Michelle eNeller

    2014-02-01

    Full Text Available The human T-cell compartment is a complex system and while some information is known on repertoire composition and dynamics in the peripheral blood, little is known on repertoire composition at different anatomical sites. Here, we determine the T-cell receptor β-variable (TRBV repertoire at the decidua and compare it with the peripheral blood during normal pregnancy and preclampsia. We found total T-cell subset disparity of up to 58% between sites, including large signature TRBV expansions unique to the foetal-maternal interface. Defining the functional nature and specificity of compartment-specific T-cells will be necessary if we are to understand localised immunity, tolerance and pathogenesis.

  18. Dynamics and genetic fuzzy neural network vibration control design of a smart flexible four-bar linkage mechanism

    International Nuclear Information System (INIS)

    Rong Bao; Rui Xiaoting; Tao Ling

    2012-01-01

    In this paper, a dynamic modeling method and an active vibration control scheme for a smart flexible four-bar linkage mechanism featuring piezoelectric actuators and strain gauge sensors are presented. The dynamics of this smart mechanism is described by the Discrete Time Transfer Matrix Method of Multibody System (MS-DTTMM). Then a nonlinear fuzzy neural network control is employed to suppress the vibration of this smart mechanism. For improving the dynamic performance of the fuzzy neural network, a genetic algorithm based on the MS-DTTMM is designed offline to tune the initial parameters of the fuzzy neural network. The MS-DTTMM avoids the global dynamics equations of the system, which results in the matrices involved are always very small, so the computational efficiency of the dynamic analysis and control system optimization can be greatly improved. Formulations of the method as well as a numerical simulation are given to demonstrate the proposed dynamic method and control scheme.

  19. Multiobjective genetic algorithm optimization of the beam dynamics in linac drivers for free electron lasers

    Directory of Open Access Journals (Sweden)

    R. Bartolini

    2012-03-01

    Full Text Available Linac driven free electron lasers (FELs operating in the x-ray region require a high brightness electron beam in order to reach saturation within a reasonable distance in the undulator train or to enable sophisticated seeding schemes using external lasers. The beam dynamics optimization is usually a time consuming process in which many parameters of the accelerator and the compression system have to be controlled simultaneously. The requirements on the electron beam quality may also vary significantly with the particular application. For example, the beam dynamics optimization strategy for self-amplified spontaneous emission operation and seeded operation are rather different: seeded operation requires a more careful control of the beam uniformity over a relatively large portion of the longitudinal current distribution of the electron bunch and is therefore more challenging from an accelerator physics point of view. Multiobjective genetic algorithms are particularly well suited when the optimization of many parameters is targeting several objectives simultaneously, often with conflicting requirements. In this paper we propose a novel optimization strategy based on a combination of multiobjective optimization with a fast computation of the FEL performance. The application to the proposed UK’s New Light Source is reported and the benefits of this method are highlighted.

  20. Fast two-photon imaging of subcellular voltage dynamics in neuronal tissue with genetically encoded indicators.

    Science.gov (United States)

    Chamberland, Simon; Yang, Helen H; Pan, Michael M; Evans, Stephen W; Guan, Sihui; Chavarha, Mariya; Yang, Ying; Salesse, Charleen; Wu, Haodi; Wu, Joseph C; Clandinin, Thomas R; Toth, Katalin; Lin, Michael Z; St-Pierre, François

    2017-07-27

    Monitoring voltage dynamics in defined neurons deep in the brain is critical for unraveling the function of neuronal circuits but is challenging due to the limited performance of existing tools. In particular, while genetically encoded voltage indicators have shown promise for optical detection of voltage transients, many indicators exhibit low sensitivity when imaged under two-photon illumination. Previous studies thus fell short of visualizing voltage dynamics in individual neurons in single trials. Here, we report ASAP2s, a novel voltage indicator with improved sensitivity. By imaging ASAP2s using random-access multi-photon microscopy, we demonstrate robust single-trial detection of action potentials in organotypic slice cultures. We also show that ASAP2s enables two-photon imaging of graded potentials in organotypic slice cultures and in Drosophila . These results demonstrate that the combination of ASAP2s and fast two-photon imaging methods enables detection of neural electrical activity with subcellular spatial resolution and millisecond-timescale precision.

  1. From everyday communicative figurations to rigorous audience news repertoires

    DEFF Research Database (Denmark)

    Kobbernagel, Christian; Schrøder, Kim Christian

    2016-01-01

    In the last couple of decades there has been an unprecedented explosion of news media platforms and formats, as a succession of digital and social media have joined the ranks of legacy media. We live in a ‘hybrid media system’ (Chadwick, 2013), in which people build their cross-media news...... repertoires from the ensemble of old and new media available. This article presents an innovative mixed-method approach with considerable explanatory power to the exploration of patterns of news media consumption. This approach tailors Q-methodology in the direction of a qualitative study of news consumption......, in which a card sorting exercise serves to translate the participants’ news media preferences into a form that enables the researcher to undertake a rigorous factor-analytical construction of their news consumption repertoires. This interpretive, factor-analytical procedure, which results in the building...

  2. Friendship Repertoires and Care Arrangement: A Praxeological Approach.

    Science.gov (United States)

    Hahmann, Julia

    2017-01-01

    Friends are important companions and serve as sources for diverse dimensions of social support, including elderly care. Rather than researching populations that have already established care arrangements including friends, the author seeks to understand relationship systems with a focus on the inner logic friendship to consequently describe and understand involved care arrangements, be it with family members or friends. To illustrate the diversity of friendship repertoires, qualitative interviews with older adult Germans are analyzed regarding cognitive concepts of friendships in contrast to familiar ties as well as social practices around relationship systems. While some repertoires successfully include chosen ties in their care arrangements, others not only focus on family, they do not wish to receive care from friends. The article's praxeological approach highlights the need to reflect habitual differences when thinking about elderly informal care arrangements. © The Author(s) 2016.

  3. Linking experiences with emotions and the development of interpretive repertoires

    Science.gov (United States)

    McRae, Norah I.

    2010-03-01

    In this paper I consider the case of one student, Todd Alexander, through analyzing the transcripts of his interviews between him and his teacher (Wolff-Michael Roth). I examine the role that emotions play in the development of the interpretive repertoires that Todd employed as he talked about his scientific and his religious beliefs. I identify how lived experiences support the development of emotions and what educational conditions are necessary to allow for appropriate lived experiences. In so doing we might be able to support educational conditions that result in interpretive repertoires that allow for acceptance of multiple perspectives with a moral grounding, leading to students who are well positioned to be valuable contributors to society.

  4. BRAZILIAN FEMINIST MOVEMENT: REPERTOIRE AND STRATEGIES FOR ACTION

    Directory of Open Access Journals (Sweden)

    Carla de Paiva Bezerra

    2014-08-01

    Full Text Available This article aims at analyzing the development of and changes in, the repertoire and strategies for action of the Brazilian feminist movement, in the period between the democratic “re-opening” set in the 1980s and the first decade of the XXI century. Our interest is centered in two foci of analysis: on the one hand, it focuses on the movement’s positioning in relation to the State, which varied from a situation of opposition, or even of indifference, to direct attempts at influencing public policies and actions in the State sphere, whether through party politics or participative institutions. On the other hand, we are interested in analyzing how, and in which specific moments, agency beyond the national feminist frontiers takes place and in which measure this influences the local repertoires and vice-versa.

  5. Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches.

    Directory of Open Access Journals (Sweden)

    Ruben Perez-Carrasco

    2016-10-01

    Full Text Available During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules-morphogens-guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can

  6. Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches

    Science.gov (United States)

    Page, Karen M.

    2016-01-01

    During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules—morphogens—guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can qualitatively

  7. Next-Generation Sequencing of Antibody Display Repertoires

    Directory of Open Access Journals (Sweden)

    Romain Rouet

    2018-02-01

    Full Text Available In vitro selection technology has transformed the development of therapeutic monoclonal antibodies. Using methods such as phage, ribosome, and yeast display, high affinity binders can be selected from diverse repertoires. Here, we review strategies for the next-generation sequencing (NGS of phage- and other antibody-display libraries, as well as NGS platforms and analysis tools. Moreover, we discuss recent examples relating to the use of NGS to assess library diversity, clonal enrichment, and affinity maturation.

  8. METHODOLOGICAL PRINCIPLES OF FORMING REPERTOIRE OF STUDENTS’ FOLK INSTRUMENTAL ORCHESTRA

    Directory of Open Access Journals (Sweden)

    Mykola Pshenychnykh

    2016-11-01

    Full Text Available One of the main aspects of forming future music teachers’ professional competence, connected with mastering professional musical and performing skills in the course “Orchestra Class” and realized in the activity of students’ performing group, is revealed. Nowadays the problem of creative personality development is relevant, as creative future music art teachers freely orient themselves and guide pupils students in today's cultural environment, music and media space, have a strong musical taste and aesthetic guidelines. The music genre groups have been characterized in the article. It is thought that these groups are the traditional components of repertoire of folk and orchestra student groups: arrangements of folk tunes; works of Ukrainian and world classics, orchestrated for the folk groups, taking into account each orchestra performing possibilities; works by contemporary authors, written specifically for the orchestra of folk instruments. The main methodological principles of selecting the repertoire for the student orchestra of folk instruments are disclosed, including: technical, artistic and performing capabilities of student groups; involvement of works of different genres into the repertoire; correspondence of orchestra scores to instrumental composition of the student orchestra, and their correction if it is necessary; selecting works, whose performing arouses interest of the student audience; using the experience of the leading professional ensembles of folk instruments; constant updating the orchestra's repertoire. In the conclusion the author emphasizes that taking into account the methodological tips helps solve the main tasks within the course of “Orchestra Class”. These tips are the following: students’ acquaintance with the history of foundation, composition, ways of musicianship, technique of playing the instrument of folk instrument orchestra and acquaintance with specific orchestral music; development of all

  9. Acquisition of repertoires of suppressor T cells under the influence of macrophages

    International Nuclear Information System (INIS)

    Soejima, T.; Nagayama, A.; Sado, T.; Taniguchi, M.

    1988-01-01

    Acquisition of repertoires and genetic restriction specificities of suppressor T cells (Ts) and their factors were studied by using full allogeneic radiation bone marrow chimera and H-2 congenic pairs, B10.A(3R) and B10.A(5R), which received conventional or cloned macrophages by cell transfer. Suppressor T-cell factor (TsF) from C3H----C57BL/6 or C57BL/6----C3H chimera suppressed only donor but not host-type responses of either C3H or C57BL/6, in an antigen-specific fashion. However, if chimera mice were given conventional or cloned macrophages of the host type, the chimera TsF in turn suppressed both the responses of C3H and C57BL/6 mice but not those of the third party, BALB/c, indicating that macrophages are responsible for the acquisition of host restriction specificity. Similarly, B10.A(5R) mice developed I-Jb restricted Ts or TsF when the B10.A(3R) macrophage cell line was injected at the time of antigen priming. The reverse was also true. B10.A(3R) mice did generate I-Jk restricted Ts when they received the B10.A(5R) macrophage cell line. Thus, the results clearly demonstrated that B10.A(3R) or B10.A(5R) mice potentially possessed their ability to express both I-Jk and I-Jb determinants and that repertoires and genetic restriction specificity of Ts and their TsF were acquired at a macrophage level at the time of antigen-priming

  10. Vulnerability of dynamic genetic conservation units of forest trees in Europe to climate change.

    Science.gov (United States)

    Schueler, Silvio; Falk, Wolfgang; Koskela, Jarkko; Lefèvre, François; Bozzano, Michele; Hubert, Jason; Kraigher, Hojka; Longauer, Roman; Olrik, Ditte C

    2014-05-01

    A transnational network of genetic conservation units for forest trees was recently documented in Europe aiming at the conservation of evolutionary processes and the adaptive potential of natural or man-made tree populations. In this study, we quantified the vulnerability of individual conservation units and the whole network to climate change using climate favourability models and the estimated velocity of climate change. Compared to the overall climate niche of the analysed target species populations at the warm and dry end of the species niche are underrepresented in the network. However, by 2100, target species in 33-65 % of conservation units, mostly located in southern Europe, will be at the limit or outside the species' current climatic niche as demonstrated by favourabilities below required model sensitivities of 95%. The highest average decrease in favourabilities throughout the network can be expected for coniferous trees although they are mainly occurring within units in mountainous landscapes for which we estimated lower velocities of change. Generally, the species-specific estimates of favourabilities showed only low correlations to the velocity of climate change in individual units, indicating that both vulnerability measures should be considered for climate risk analysis. The variation in favourabilities among target species within the same conservation units is expected to increase with climate change and will likely require a prioritization among co-occurring species. The present results suggest that there is a strong need to intensify monitoring efforts and to develop additional conservation measures for populations in the most vulnerable units. Also, our results call for continued transnational actions for genetic conservation of European forest trees, including the establishment of dynamic conservation populations outside the current species distribution ranges within European assisted migration schemes. © 2013 John Wiley & Sons Ltd.

  11. Repertoires of emotion regulation: A person-centered approach to assessing emotion regulation strategies and links to psychopathology.

    Science.gov (United States)

    Dixon-Gordon, Katherine L; Aldao, Amelia; De Los Reyes, Andres

    2015-01-01

    Despite growing research on emotion regulation (ER) strategies and psychopathology, research has primarily focused on identifying one-to-one associations between ER strategies and symptoms. Thus, little is known about how patterns in the repertoires of ER strategies are associated with different mental disorders. We utilised latent class analysis to identify distinct repertoires of ER strategies, and their links with various psychopathology domains (i.e., anxiety, depression, disordered eating, borderline personality). Participants (N = 531) reported on their use of seven ER strategies in six recalled stressful contexts, as well as on their symptoms of psychopathology. We identified five classes of ER strategies: Low Regulators (n = 168), High Regulators (n = 140), Adaptive Regulators (n = 99), Worriers/Ruminators (n = 96) and Avoiders (n = 28). Generally, High Regulators and Worriers/Ruminators endorsed greater levels of psychopathology, relative to Low and Adaptive Regulators. Our findings underscore the importance of characterising the dynamics of ER repertoires when seeking to understand links between ER strategies and psychopathology.

  12. Genetic and environmental control of seasonal carbohydrate dynamics in trees of diverse Pinus sylvestris populations.

    Science.gov (United States)

    Oleksyn, J.; Zytkowiak, R.; Karolewski, P.; Reich, P. B.; Tjoelker, M. G.

    2000-06-01

    We explored environmental and genetic factors affecting seasonal dynamics of starch and soluble nonstructural carbohydrates in needle and twig cohorts and roots of Scots pine (Pinus sylvestris L.) trees of six populations originating between 49 degrees and 60 degrees N, and grown under common garden conditions in western Poland. Trees of each population were sampled once or twice per month over a 3-year period from age 15 to 17 years. Based on similarity in starch concentration patterns in needles, two distinct groups of populations were identified; one comprised northern populations from Sweden and Russia (59-60 degrees N), and another comprised central European populations from Latvia, Poland, Germany and France (49-56 degrees N). Needle starch concentrations of northern populations started to decline in late spring and reached minimum values earlier than those of central populations. For all populations, starch accumulation in spring started when minimum air temperature permanently exceeded 0 degrees C. Starch accumulation peaked before bud break and was highest in 1-year-old needles, averaging 9-13% of dry mass. Soluble carbohydrate concentrations were lowest in spring and summer and highest in autumn and winter. There were no differences among populations in seasonal pattern of soluble carbohydrate concentrations. Averaged across all populations, needle soluble carbohydrate concentrations increased from about 4% of needle dry mass in developing current-year needles, to about 9% in 1- and 2-year-old needles. Root carbohydrate concentration exhibited a bimodal pattern with peaks in spring and autumn. Northern populations had higher concentrations of fine-root starch in spring and autumn than central populations. Late-summer carbohydrate accumulation in roots started only after depletion of starch in needles and woody shoots. We conclude that Scots pine carbohydrate dynamics depend partially on inherited properties that are probably related to phenology of root

  13. Strategies for B-cell receptor repertoire analysis in Primary Immunodeficiencies:From severe combined immunodeficiency to common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Hanna eIJspeert

    2015-04-01

    Full Text Available The antigen receptor repertoires of B and T cells form the basis of the adaptive immune response. The repertoires should be sufficiently diverse to recognize all possible pathogens. However, careful selection is needed to prevent responses to self or harmless antigens. Limited antigen receptor repertoire diversity leads to immunodeficiency, whereas unselected or misdirected repertoires can result in autoimmunity. The antigen receptor repertoire harbors information about abnormalities in many immunological disorders. Recent developments in next generation sequencing allow the analysis of the antigen receptor repertoire in much greater detail than ever before. Analyzing the antigen receptor repertoire in patients with mutations in genes responsible for the generation of the antigen receptor repertoire will give new insights into repertoire formation and selection. In this perspective we describe strategies and considerations for analysis of the naive and antigen selected B-cell repertoires in primary immunodeficiency (PID patients with a focus on severe combined immunodeficiency (SCID and common variable immunodeficiency (CVID.

  14. DMPD: The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10669111 The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. Qur...e The Lps locus: genetic regulation of host responses to bacteriallipopolysaccharide. Authors Qur

  15. Inverse Analysis of Pavement Structural Properties Based on Dynamic Finite Element Modeling and Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Xiaochao Tang

    2013-03-01

    Full Text Available With the movement towards the implementation of mechanistic-empirical pavement design guide (MEPDG, an accurate determination of pavement layer moduli is vital for predicting pavement critical mechanistic responses. A backcalculation procedure is commonly used to estimate the pavement layer moduli based on the non-destructive falling weight deflectometer (FWD tests. Backcalculation of flexible pavement layer properties is an inverse problem with known input and output signals based upon which unknown parameters of the pavement system are evaluated. In this study, an inverse analysis procedure that combines the finite element analysis and a population-based optimization technique, Genetic Algorithm (GA has been developed to determine the pavement layer structural properties. A lightweight deflectometer (LWD was used to infer the moduli of instrumented three-layer scaled flexible pavement models. While the common practice in backcalculating pavement layer properties still assumes a static FWD load and uses only peak values of the load and deflections, dynamic analysis was conducted to simulate the impulse LWD load. The recorded time histories of the LWD load were used as the known inputs into the pavement system while the measured time-histories of surface central deflections and subgrade deflections measured with a linear variable differential transformers (LVDT were considered as the outputs. As a result, consistent pavement layer moduli can be obtained through this inverse analysis procedure.

  16. A genetic algorithm for a bi-objective mathematical model for dynamic virtual cell formation problem

    Science.gov (United States)

    Moradgholi, Mostafa; Paydar, Mohammad Mahdi; Mahdavi, Iraj; Jouzdani, Javid

    2016-09-01

    Nowadays, with the increasing pressure of the competitive business environment and demand for diverse products, manufacturers are force to seek for solutions that reduce production costs and rise product quality. Cellular manufacturing system (CMS), as a means to this end, has been a point of attraction to both researchers and practitioners. Limitations of cell formation problem (CFP), as one of important topics in CMS, have led to the introduction of virtual CMS (VCMS). This research addresses a bi-objective dynamic virtual cell formation problem (DVCFP) with the objective of finding the optimal formation of cells, considering the material handling costs, fixed machine installation costs and variable production costs of machines and workforce. Furthermore, we consider different skills on different machines in workforce assignment in a multi-period planning horizon. The bi-objective model is transformed to a single-objective fuzzy goal programming model and to show its performance; numerical examples are solved using the LINGO software. In addition, genetic algorithm (GA) is customized to tackle large-scale instances of the problems to show the performance of the solution method.

  17. Comparison between dynamic programming and genetic algorithm for hydro unit economic load dispatch

    Directory of Open Access Journals (Sweden)

    Bin Xu

    2014-10-01

    Full Text Available The hydro unit economic load dispatch (ELD is of great importance in energy conservation and emission reduction. Dynamic programming (DP and genetic algorithm (GA are two representative algorithms for solving ELD problems. The goal of this study was to examine the performance of DP and GA while they were applied to ELD. We established numerical experiments to conduct performance comparisons between DP and GA with two given schemes. The schemes included comparing the CPU time of the algorithms when they had the same solution quality, and comparing the solution quality when they had the same CPU time. The numerical experiments were applied to the Three Gorges Reservoir in China, which is equipped with 26 hydro generation units. We found the relation between the performance of algorithms and the number of units through experiments. Results show that GA is adept at searching for optimal solutions in low-dimensional cases. In some cases, such as with a number of units of less than 10, GA's performance is superior to that of a coarse-grid DP. However, GA loses its superiority in high-dimensional cases. DP is powerful in obtaining stable and high-quality solutions. Its performance can be maintained even while searching over a large solution space. Nevertheless, due to its exhaustive enumerating nature, it costs excess time in low-dimensional cases.

  18. DMPD: The Toll-like receptors: analysis by forward genetic methods. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16001129 The Toll-like receptors: analysis by forward genetic methods. Beutler B. I...mmunogenetics. 2005 Jul;57(6):385-92. (.png) (.svg) (.html) (.csml) Show The Toll-like receptors: analysis by forwar...d genetic methods. PubmedID 16001129 Title The Toll-like receptors: analysis by forward genetic meth

  19. Flexible knowledge repertoires: communication by leaders in trauma teams

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    Jacobsson Maritha

    2012-07-01

    Full Text Available Abstract Background In emergency situations, it is important for the trauma team to efficiently communicate their observations and assessments. One common communication strategy is “closed-loop communication”, which can be described as a transmission model in which feedback is of great importance. The role of the leader is to create a shared goal in order to achieve consensus in the work for the safety of the patient. The purpose of this study was to analyze how formal leaders communicate knowledge, create consensus, and position themselves in relation to others in the team. Methods Sixteen trauma teams were audio- and video-recorded during high fidelity training in an emergency department. Each team consisted of six members: one surgeon or emergency physician (the designated team leader, one anaesthesiologist, one nurse anaesthetist, one enrolled nurse from the theatre ward, one registered nurse and one enrolled nurse from the emergency department (ED. The communication was transcribed and analyzed, inspired by discourse psychology and Strauss’ concept of “negotiated order”. The data were organized and coded in NVivo 9. Results The findings suggest that leaders use coercive, educational, discussing and negotiating strategies to work things through. The leaders in this study used different repertoires to convey their knowledge to the team, in order to create a common goal of the priorities of the work. Changes in repertoires were dependent on the urgency of the situation and the interaction between team members. When using these repertoires, the leaders positioned themselves in different ways, either on an authoritarian or a more egalitarian level. Conclusion This study indicates that communication in trauma teams is complex and consists of more than just transferring messages quickly. It also concerns what the leaders express, and even more importantly, how they speak to and involve other team members.

  20. Flexible knowledge repertoires: communication by leaders in trauma teams

    Science.gov (United States)

    2012-01-01

    Background In emergency situations, it is important for the trauma team to efficiently communicate their observations and assessments. One common communication strategy is “closed-loop communication”, which can be described as a transmission model in which feedback is of great importance. The role of the leader is to create a shared goal in order to achieve consensus in the work for the safety of the patient. The purpose of this study was to analyze how formal leaders communicate knowledge, create consensus, and position themselves in relation to others in the team. Methods Sixteen trauma teams were audio- and video-recorded during high fidelity training in an emergency department. Each team consisted of six members: one surgeon or emergency physician (the designated team leader), one anaesthesiologist, one nurse anaesthetist, one enrolled nurse from the theatre ward, one registered nurse and one enrolled nurse from the emergency department (ED). The communication was transcribed and analyzed, inspired by discourse psychology and Strauss’ concept of “negotiated order”. The data were organized and coded in NVivo 9. Results The findings suggest that leaders use coercive, educational, discussing and negotiating strategies to work things through. The leaders in this study used different repertoires to convey their knowledge to the team, in order to create a common goal of the priorities of the work. Changes in repertoires were dependent on the urgency of the situation and the interaction between team members. When using these repertoires, the leaders positioned themselves in different ways, either on an authoritarian or a more egalitarian level. Conclusion This study indicates that communication in trauma teams is complex and consists of more than just transferring messages quickly. It also concerns what the leaders express, and even more importantly, how they speak to and involve other team members. PMID:22747848

  1. Flexible knowledge repertoires: communication by leaders in trauma teams.

    Science.gov (United States)

    Jacobsson, Maritha; Hargestam, Maria; Hultin, Magnus; Brulin, Christine

    2012-07-02

    In emergency situations, it is important for the trauma team to efficiently communicate their observations and assessments. One common communication strategy is "closed-loop communication", which can be described as a transmission model in which feedback is of great importance. The role of the leader is to create a shared goal in order to achieve consensus in the work for the safety of the patient. The purpose of this study was to analyze how formal leaders communicate knowledge, create consensus, and position themselves in relation to others in the team. Sixteen trauma teams were audio- and video-recorded during high fidelity training in an emergency department. Each team consisted of six members: one surgeon or emergency physician (the designated team leader), one anaesthesiologist, one nurse anaesthetist, one enrolled nurse from the theatre ward, one registered nurse and one enrolled nurse from the emergency department (ED). The communication was transcribed and analyzed, inspired by discourse psychology and Strauss' concept of "negotiated order". The data were organized and coded in NVivo 9. The findings suggest that leaders use coercive, educational, discussing and negotiating strategies to work things through. The leaders in this study used different repertoires to convey their knowledge to the team, in order to create a common goal of the priorities of the work. Changes in repertoires were dependent on the urgency of the situation and the interaction between team members. When using these repertoires, the leaders positioned themselves in different ways, either on an authoritarian or a more egalitarian level. This study indicates that communication in trauma teams is complex and consists of more than just transferring messages quickly. It also concerns what the leaders express, and even more importantly, how they speak to and involve other team members.

  2. The porcine antibody repertoire: Variations on the textbook theme

    Directory of Open Access Journals (Sweden)

    John eButler

    2012-06-01

    Full Text Available The genes encoding the heavy and light chains of swine antibodies are organized in the same manner as in other eutherian mammals. There are ~ 30 VH genes, two functional DH genes and one functional JH gene. There are 14-60 V genes and 5 J segments, >22V genes and at least four JC cassettes. The heavy chain constant regions encode the same repertoire of isotypes common to other eutherian mammals. The piglet models offers advantage over rodent models since the fetal repertoire develops without maternal influences and the precocial nature of their multiple offspring allows the experimenter to control the influences of environmental and maternal factors on repertoire development postnatally. B cell lymphogenesis in swine begins in the fetal yolk sac at 20 days of gestation (DG, moves to the fetal liver at 30 DG and eventually to the bone marrow which dominates until birth (114 DG and to at least 5 weeks postpartum. There is no evidence that the ileal Peyers patches are a site of B cell lymphogenesis or are required for B cell maintenance. Unlike rodents and humans, light chain rearrangement begins first in the lambda locus; kappa rearrangements are not seen until late gestation.Dissimilar to lab rodents and more in the direction of the rabbit, swine utilize a small number of VH genes to form >90% of their pre-immune repertoire. Diversification in response to environmental antigen does not alter this pattern and is achieved by somatic hypermutation (SHM of the same small number of VH genes. The situation for light chains is less-well studied, but certain V and J and V and J are dominant in transcripts. The transcribed and secreted pre-immune antibodies of the fetus include mainly IgM, IgA and IgG3; this last isotype may provide a type of first responder mucosal immunity. Development of functional adaptive immunity is dependent on bacterial PAMPs or PAMPs provided by viral infections, indicating the importance of innate

  3. A REPERTOIRE OF INSTRUMENTS EMPLOYED IN PSYCHOLOGICAL COUNSELING

    Directory of Open Access Journals (Sweden)

    Dorina Maria PASCA

    2014-10-01

    Full Text Available According to Carl Rogers and Albert Ellis [1] [2], a new approach to psychological counseling is needed. Consequently, new and practical means to solve problems that ensue as part of the counseling process are required. From this point of view, this article aims at offering a range of alternatives to approach and involve the client (student in order to achieve the envisaged results of counseling. As such, it offers a concise repertoire of instruments that can be employed in psychological counseling.

  4. Temporal dynamics and population genetic structure of Fusarium graminearum in the upper Midwestern United States.

    Science.gov (United States)

    Liang, J M; Xayamongkhon, H; Broz, K; Dong, Y; McCormick, S P; Abramova, S; Ward, T J; Ma, Z H; Kistler, H C

    2014-12-01

    Fusarium graminearum sensu stricto causes Fusarium head blight (FHB) in wheat and barley, and contaminates grains with several trichothecene mycotoxins, causing destructive yield losses and economic impact in the United States. Recently, a F. graminearum strain collected from Minnesota (MN) was determined to produce a novel trichothecene toxin, called NX-2. In order to determine the spatial and temporal dynamics of NX-2 producing strains in MN, North Dakota (ND) and South Dakota (SD), a total of 463 F. graminearum strains were collected from three sampling periods, 1999-2000, 2006-2007 and 2011-2013. A PCR-RFLP based diagnostic test was developed and validated for NX-2 producing strains based on polymorphisms in the Tri1 gene. Trichothecene biosynthesis gene (Tri gene)-based polymerase chain reaction (PCR) assays and ten PCR-restriction fragment length polymorphism (RFLP) markers were used to genotype all strains. NX-2 strains were detected in each sampling period but with a very low overall frequency (2.8%) and were mainly collected near the borders of MN, ND and SD. Strains with the 3ADON chemotype were relatively infrequent in 1999-2000 (4.5%) but increased to 29.4% in 2006-2007 and 17.2% in 2011-2013. The distribution of 3ADON producing strains also expanded from a few border counties between ND and MN in 1999-2000, southward toward the border between SD and MN in 2006-2007 and westward in 2011-2013. Genetic differentiation between 2006-2007 and 2011-2013 populations (3%) was much lower than that between 1999-2000 and 2006-2007 (22%) or 1999-2000 and 2011-2013 (20%) suggesting that most change to population genetic structure of F. graminearum occurred between 1999-2000 and 2006-2007. This change was associated with the emergence of a new population consisting largely of individuals with a 3ADON chemotype. A Bayesian clustering analysis suggested that NX-2 chemotype strains are part of a previously described Upper Midwestern population. However, these analyses

  5. Song repertoire size correlates with measures of body size in Eurasian blackbirds

    DEFF Research Database (Denmark)

    Hesler, Nana; Mundry, Roger; Sacher, Thomas

    2012-01-01

    In most oscine bird species males possess a repertoire of different song patterns. The size of these repertoires is assumed to serve as an honest signal of male quality. The Eurasian blackbird’s (Turdus merula) song contains a large repertoire of different element types with a flexible song...... organisation. Here we investigated whether repertoire size in Eurasian blackbirds correlates with measures of body size, namely length of wing, 8th primary, beak and tarsus. So far, very few studies have investigated species with large repertoires and a flexible song organisation in this context. We found...... positive correlations, meaning that larger males had larger repertoires. Larger males may have better fighting abilities and, thus, advantages in territorial defence. Larger structural body size may also reflect better conditions during early development. Therefore, under the assumption that body size...

  6. Rule-Governed Behavior: Teaching a Preliminary Repertoire of Rule-Following to Children With Autism

    OpenAIRE

    Tarbox, Jonathan; Zuckerman, Carrie K; Bishop, Michele R; Olive, Melissa L; O'Hora, Denis P

    2011-01-01

    Rule-governed behavior is generally considered an integral component of complex verbal repertoires but has rarely been the subject of empirical research. In particular, little or no previous research has attempted to establish rule-governed behavior in individuals who do not already display the repertoire. This study consists of two experiments that evaluated multiple exemplar training procedures for teaching a simple component skill, which may be necessary for developing a repertoire of rule...

  7. Repertoire of free-living protozoa in contact lens solutions.

    Science.gov (United States)

    Bouchoucha, Ibtissem; Aziz, Aurore; Hoffart, Louis; Drancourt, Michel

    2016-10-29

    The repertoire of free-living protozoa in contact lens solutions is poorly known despite the fact that such protozoa may act as direct pathogens and may harbor intra-cellular pathogens. Between 2009 and 2014, the contact lens solutions collected from patients presenting at our Ophthalmology Department for clinically suspected keratitis, were cultured on non-nutrient agar examined by microscope for the presence of free-living protozoa. All protozoa were identified by 18S rRNA gene sequencing. A total of 20 of 233 (8.6 %) contact lens solution specimens collected from 16 patients were cultured. Acanthamoeba amoeba in 16 solutions (80 %) collected from 12 patients and Colpoda steini, Cercozoa sp., Protostelium sp. and a eukaryotic more closely related to Vermamoeba sp., were each isolated in one solution. Cercozoa sp., Colpoda sp., Protostelium sp. and Vermamoeba sp. are reported for the first time as contaminating contact lens solutions. The repertoire of protozoa in contact lens solutions is larger than previously known.

  8. The mimetic repertoire of the spotted bowerbird Ptilonorhynchus maculatus

    Science.gov (United States)

    Kelley, Laura A.; Healy, Susan D.

    2011-06-01

    Although vocal mimicry in songbirds is well documented, little is known about the function of such mimicry. One possibility is that the mimic produces the vocalisations of predatory or aggressive species to deter potential predators or competitors. Alternatively, these sounds may be learned in error as a result of their acoustic properties such as structural simplicity. We determined the mimetic repertoires of a population of male spotted bowerbirds Ptilonorhynchus maculatus, a species that mimics predatory and aggressive species. Although male mimetic repertoires contained an overabundance of vocalisations produced by species that were generally aggressive, there was also a marked prevalence of mimicry of sounds that are associated with alarm such as predator calls, alarm calls and mobbing calls, irrespective of whether the species being mimicked was aggressive or not. We propose that it may be the alarming context in which these sounds are first heard that may lead both to their acquisition and to their later reproduction. We suggest that enhanced learning capability during acute stress may explain vocal mimicry in many species that mimic sounds associated with alarm.

  9. Can rarefaction be used to estimate song repertoire size in birds?

    Directory of Open Access Journals (Sweden)

    Kathleen R. PESHEK, Daniel T. BLUMSTEIN

    2011-06-01

    Full Text Available Song repertoire size is the number of distinct syllables, phrases, or song types produced by an individual or population. Repertoire size estimation is particularly difficult for species that produce highly variable songs and those that produce many song types. Estimating repertoire size is important for ecological and evolutionary studies of speciation, studies of sexual selection, as well as studies of how species may adapt their songs to various acoustic environments. There are several methods to estimate repertoire size, however prior studies discovered that all but a full numerical count of song types might have substantial inaccuracies associated with them. We evaluated a somewhat novel approach to estimate repertoire size—rarefaction; a technique ecologists use to measure species diversity on individual and population levels. Using the syllables within American robins’ Turdus migratorius repertoire, we compared the most commonly used techniques of estimating repertoires to the results of a rarefaction analysis. American robins have elaborate and unique songs with few syllables shared between individuals, and there is no evidence that robins mimic their neighbors. Thus, they are an ideal system in which to compare techniques. We found that the rarefaction technique results resembled that of the numerical count, and were better than two alternative methods (behavioral accumulation curves, and capture-recapture to estimate syllable repertoire size. Future estimates of repertoire size, particularly in vocally complex species, may benefit from using rarefaction techniques when numerical counts are unable to be performed [Current Zoology 57 (3: 300–306, 2011].

  10. Temporal dynamics of bacterial and fungal communities in a genetically modified (GM) rice ecosystem.

    Science.gov (United States)

    Lee, Seung-Hoon; Kim, Chang-Gi; Kang, Hojeong

    2011-04-01

    We assessed the temporal dynamics of bacterial and fungal communities in a soil ecosystem supporting genetically modified (GM) rice (Oryza sativa L., ABC-TPSP; fusion of trehalose-6-phosphate synthase and phosphatase). Using terminal restriction fragment length polymorphism analysis and real-time quantitative PCR, we compared bacterial and fungal communities in the soils underlying GM rice (ABC-TPSP), and its host cultivar (Nakdong) during growing seasons and non-growing seasons. Overall, the soils supporting GM and non-GM rice did not differ significantly in diversity indices, including ribotype numbers, for either bacteria or fungi. The diversity index (H) in both the bacterial and fungal communities was correlated with water content, dissolved organic carbon (DOC), and ammonium nitrogen, and the correlation was stronger in fungi than in bacteria. Multivariate analysis showed no differences in microbial community structures between the two crop genotypes, but such differences did appear in time, with significant changes observed after harvest. Gene copy number was estimated as 10(8)~10(11) and 10(5)~10(7) per gram of soil for bacteria and fungi, respectively. As observed for community structure, the rice genotypes did not differ significantly in either bacterial- or fungal-specific gene copy numbers, although we observed a seasonal change in number. We summarize the results of this study as follows. (1) GM rice did not influence soil bacterial and fungal community structures as compared to non-GM rice in our system, (2) both bacterial and fungal communities changed with the growth stage of either rice genotype, (3) fungal communities were less variable than bacterial communities, and (4) although several environmental factors, including ammonium nitrogen and DOC correlated with shifts in microbial community structure, no single factor stood out.

  11. Seasonal genetic variation associated with population dynamics of a poecilogonous polychaete worm

    DEFF Research Database (Denmark)

    Thonig, Anne; Banta, Gary Thomas; Hansen, Benni Winding

    2017-01-01

    Poecilogonous species show variation in developmental mode, with larvae that differ both morphologically and ecologically. The spionid polychaete Pygospio elegans shows variation in developmental mode not only between populations, but also seasonally within populations. We investigated...... differentiation at two of the sites. The seasonal genetic shift correlated with the appearance of new size cohorts in the populations. Additionally, we found that the genetic composition of reproductive individuals did not always reflect the genetic composition of the entire sample, indicating that variance...

  12. Gel-based and gel-free search for plasma membrane proteins in chickpea (Cicer arietinum L.) augments the comprehensive data sets of membrane protein repertoire.

    Science.gov (United States)

    Barua, Pragya; Subba, Pratigya; Lande, Nilesh Vikram; Mangalaparthi, Kiran K; Prasad, T S Keshava; Chakraborty, Subhra; Chakraborty, Niranjan

    2016-06-30

    Plasma membrane (PM) encompasses total cellular contents, serving as semi-porous barrier to cell exterior. This living barrier regulates all cellular exchanges in a spatio-temporal fashion. Most of the essential tasks of PMs including molecular transport, cell-cell interaction and signal transduction are carried out by their proteinaceous components, which make the PM protein repertoire to be diverse and dynamic. Here, we report the systematic analysis of PM proteome of a food legume, chickpea and develop a PM proteome reference map. Proteins were extracted from highly enriched PM fraction of four-week-old seedlings using aqueous two-phase partitioning. To address a population of PM proteins that is as comprehensive as possible, both gel-based and gel-free approaches were employed, which led to the identification of a set of 2732 non-redundant proteins. These included both integral proteins having bilayer spanning domains as well as peripheral proteins associated with PMs through posttranslational modifications or protein-protein interactions. Further, the proteins were subjected to various in-silico analyses and functionally classified based on their gene ontology. Finally an inventory of the complete set of PM proteins, identified in several monocot and dicot species, was created for comparative study with the generated PM protein dataset of chickpea. Chickpea, a rich source of dietary proteins, is the second most cultivated legume, which is grown over 10 million hectares of land worldwide. The annual global production of chickpea hovers around 8.5 million metric tons. Recent chickpea genome sequencing effort has provided a broad genetic basis for highlighting the important traits that may fortify other crop legumes. Improvement in chickpea varieties can further strengthen the world food security, which includes food availability, access and utilization. It is known that the phenotypic trait of a cultivar is the manifestation of the orchestrated functions of its

  13. Complex spatial dynamics maintain northern leopard frog (Lithobates pipiens) genetic diversity in a temporally varying landscape

    Science.gov (United States)

    Mushet, David M.; Euliss, Ned H.; Chen, Yongjiu; Stockwell, Craig A.

    2013-01-01

    In contrast to most local amphibian populations, northeastern populations of the Northern Leopard Frog (Lithobates pipiens) have displayed uncharacteristically high levels of genetic diversity that have been attributed to large, stable populations. However, this widely distributed species also occurs in areas known for great climatic fluctuations that should be reflected in corresponding fluctuations in population sizes and reduced genetic diversity. To test our hypothesis that Northern Leopard Frog genetic diversity would be reduced in areas subjected to significant climate variability, we examined the genetic diversity of L. pipiens collected from 12 sites within the Prairie Pothole Region of North Dakota. Despite the region's fluctuating climate that includes periods of recurring drought and deluge, we found unexpectedly high levels of genetic diversity approaching that of northeastern populations. Further, genetic structure at a landscape scale was strikingly homogeneous; genetic differentiation estimates (Dest) averaged 0.10 (SD = 0.036) across the six microsatellite loci we studied, and two Bayesian assignment tests (STRUCTURE and BAPS) failed to reveal the development of significant population structure across the 68 km breadth of our study area. These results suggest that L. pipiens in the Prairie Pothole Region consists of a large, panmictic population capable of maintaining high genetic diversity in the face of marked climate variability.

  14. Local genetic diversity of sorghum in a village in northern Cameroon: structure and dynamics of landraces.

    Science.gov (United States)

    Barnaud, Adeline; Deu, Monique; Garine, Eric; McKey, Doyle; Joly, Hélène I

    2007-01-01

    We present the first study of patterns of genetic diversity of sorghum landraces at the local scale. Understanding landrace diversity aids in deciphering evolutionary forces under domestication, and has applications in the conservation of genetic resources and their use in breeding programs. Duupa farmers in a village in Northern Cameroon distinguished 59 named sorghum taxa, representing 46 landraces. In each field, seeds are sown as a mixture of landraces (mean of 12 landraces per field), giving the potential for extensive gene flow. What level of genetic diversity underlies the great morphological diversity observed among landraces? Given the potential for gene flow, how well defined genetically is each landrace? To answer these questions, we recorded spatial patterns of planting and farmers' perceptions of landraces, and characterized 21 landraces using SSR markers. Analysis using distance and clustering methods grouped the 21 landraces studied into four clusters. These clusters correspond to functionally and ecologically distinct groups of landraces. Within-landrace genetic variation accounted for 30% of total variation. The average F(is) over landraces was 0.68, suggesting high inbreeding within landraces. Differentiation among landraces was substantial and significant (F(st) = 0.36). Historical factors, variation in breeding systems, and farmers' practices all affected patterns of genetic variation. Farmers' practices are key to the maintenance, despite gene flow, of landraces with different combinations of agronomically and ecologically pertinent traits. They must be taken into account in strategies of conservation and use of genetic resources.

  15. A survey of the gene repertoire of Gigaspora rosea unravels conserved features among Glomeromycota for obligate biotrophy

    Directory of Open Access Journals (Sweden)

    Nianwu eTANG

    2016-03-01

    for forthcoming studies into the genomics of Diversisporales, and also illuminates the utility of comparing gene repertoires of species from Diversisporales and other clades of Glomeromycota to gain more insights into the genetics and evolution of this fungal group.

  16. Building the repertoire of measures of walking in Rett syndrome

    DEFF Research Database (Denmark)

    Stahlhut, Michelle; Downs, Jenny; Leonard, Helen

    2017-01-01

    performance as measured with the FMS-RS was more strongly consistent with other clinical measures supporting its concurrent validity. Test-retest reliability was good for both the FMS-RS and the 2MWT. Therefore, these measures have the potential to be used in clinical practice and research. Implications...... with Rett syndrome (median 18.4 years, range 2.4-60.9 years) were assessed for clinical severity, gross motor skills, and mobility. To measure walking capacity, 27 of this group completed a 2MWT twice on two different assessment days. To assess walking performance, the FMS-RS was administered to the total......BACKGROUND: The repertoire of measures of walking in Rett syndrome is limited. This study aimed to determine measurement properties of a modified two-minute walk test (2MWT) and a modified Rett syndrome-specific functional mobility scale (FMS-RS) in Rett syndrome. METHODS: Forty-two girls and women...

  17. Dynamics and genetic structure of Argentine ant supercolonies in their native range

    DEFF Research Database (Denmark)

    Vogel, Valérie; Pedersen, Jes S; d'Ettorre, Patrizia

    2009-01-01

    analyses revealed the presence of 11 supercolonies (width 1 to 515 m) over a 3-km transect. As in the introduced range, there was always strong aggression between but never within supercolonies. The genetic data were in perfect agreement with the behavioral tests, all nests being assigned to identical...... supercolonies with the different methods. There was strong genetic differentiation between supercolonies but no genetic differentiation among nests within supercolonies. We never found more than a single mitochondrial haplotype per supercolony, further supporting the view that supercolonies are closed breeding...

  18. Self assertion modeled as a network repertoire of multi-determinant antibodies

    NARCIS (Netherlands)

    Takumi, K.; Boer, R.J. de

    1996-01-01

    We study repertoire selection in a network of natural antibodies that is maintained by stimulatory idiotypic interactions. The natural antibody repertoire develops in an environment of self epitopes to which the self-reactive B cell clones are completely tolerant. For the modeling formalism, we

  19. Evolution of the Immune Repertoire with and without Somatic DNA Recombination

    NARCIS (Netherlands)

    Takumi, K.; Hogeweg, P.

    1998-01-01

    Repertoire of an immune system is a set of antigen receptors each having a unique specificity to bind an antigen. In many vertebrate species, antigen receptors are produced via combinatorial arrangements of DNA segments in specialized immune cells. Due to this molecular mechanism, repertoire

  20. Iterative Design toward Equity: Youth Repertoires of Practice in a High School Maker Space

    Science.gov (United States)

    Martin, Lee; Dixon, Colin; Betser, Sagit

    2018-01-01

    Despite their potential, maker activities do not always support equitable engagement. The authors report on a design research study where they worked to support equitable engagement of youth repertoires of practice in a high school makerspace. Their orientation toward equity is grounded in the construct of repertoires of practice, and they focus…

  1. Rule-Governed Behavior: Teaching a Preliminary Repertoire of Rule-Following to Children with Autism

    Science.gov (United States)

    Tarbox, Jonathan; Zuckerman, Carrie K.; Bishop, Michele R.; Olive, Melissa L.; O'Hora, Denis P.

    2011-01-01

    Rule-governed behavior is generally considered an integral component of complex verbal repertoires but has rarely been the subject of empirical research. In particular, little or no previous research has attempted to establish rule-governed behavior in individuals who do not already display the repertoire. This study consists of two experiments…

  2. A Comparison of the Basic Song Repertoire of Vocal/Choral and Instrumental Music Education Majors.

    Science.gov (United States)

    Prickett, Carol A.; Bridges, Madeline S.

    2000-01-01

    Explores whether the basic song repertoire of vocal/choral music education majors is significantly better than instrumental music education majors. Participants attempted to identify 25 standard songs. Reveals no significant difference between the two groups, indicating that neither had developed a strong repertoire of songs. (CMK)

  3. Antibody repertoires in humanized NOD-scid-IL2Rγ(null mice and human B cells reveals human-like diversification and tolerance checkpoints in the mouse.

    Directory of Open Access Journals (Sweden)

    Gregory C Ippolito

    Full Text Available Immunodeficient mice reconstituted with human hematopoietic stem cells enable the in vivo study of human hematopoiesis. In particular, NOD-scid-IL2Rγ(null engrafted mice have been shown to have reasonable levels of T and B cell repopulation and can mount T-cell dependent responses; however, antigen-specific B-cell responses in this model are generally poor. We explored whether developmental defects in the immunoglobulin gene repertoire might be partly responsible for the low level of antibody responses in this model. Roche 454 sequencing was used to obtain over 685,000 reads from cDNA encoding immunoglobulin heavy (IGH and light (IGK and IGL genes isolated from immature, naïve, or total splenic B cells in engrafted NOD-scid-IL2Rγ(null mice, and compared with over 940,000 reads from peripheral B cells of two healthy volunteers. We find that while naïve B-cell repertoires in humanized mice are chiefly indistinguishable from those in human blood B cells, and display highly correlated patterns of immunoglobulin gene segment use, the complementarity-determining region H3 (CDR-H3 repertoires are nevertheless extremely diverse and are specific for each individual. Despite this diversity, preferential D(H-J(H pairings repeatedly occur within the CDR-H3 interval that are strikingly similar across all repertoires examined, implying a genetic constraint imposed on repertoire generation. Moreover, CDR-H3 length, charged amino-acid content, and hydropathy are indistinguishable between humans and humanized mice, with no evidence of global autoimmune signatures. Importantly, however, a statistically greater usage of the inherently autoreactive IGHV4-34 and IGKV4-1 genes was observed in the newly formed immature B cells relative to naïve B or total splenic B cells in the humanized mice, a finding consistent with the deletion of autoreactive B cells in humans. Overall, our results provide evidence that key features of the primary repertoire are shaped by

  4. Water-level fluctuations and metapopulation dynamics as drivers of genetic diversity in populations of three Tanganyikan cichlid fish species.

    Science.gov (United States)

    Nevado, B; Mautner, S; Sturmbauer, C; Verheyen, E

    2013-08-01

    Understanding how genetic variation is generated and maintained in natural populations, and how this process unfolds in a changing environment, remains a central issue in biological research. In this work, we analysed patterns of genetic diversity from several populations of three cichlid species from Lake Tanganyika in parallel, using the mitochondrial DNA control region. We sampled populations inhabiting the littoral rocky habitats in both very deep and very shallow areas of the lake. We hypothesized that the former would constitute relatively older, more stable and genetically more diverse populations, because they should have been less severely affected by the well-documented episodes of dramatic water-level fluctuations. In agreement with our predictions, populations of all three species sampled in very shallow shorelines showed traces of stronger population growth than populations of the same species inhabiting deep shorelines. However, contrary to our working hypothesis, we found a significant trend towards increased genetic diversity in the younger, demographically less stable populations inhabiting shallow areas, in comparison with the older and more stable populations inhabiting the deep shorelines. We interpret this finding as the result of the establishment of metapopulation dynamics in the former shorelines, by the frequent perturbation and reshuffling of individuals between populations due to the lake-level fluctuations. The repeated succession of periods of allopatric separation and secondary contact is likely to have further increased the rapid pace of speciation in lacustrine cichlids. © 2013 John Wiley & Sons Ltd.

  5. Population genetic dynamics of an invasion reconstructed from the sediment egg bank

    Czech Academy of Sciences Publication Activity Database

    Möst, M.; Oexle, S.; Marková, Silvia; Aidukaite, D.; Baumgartner, L.; Stich, H. B.; Wessels, M.; Martin-Creuzburg, D.; Spaak, P.

    2015-01-01

    Roč. 24, č. 16 (2015), s. 4074-4093 ISSN 0962-1083 Institutional support: RVO:67985904 Keywords : ancient DNA * asexual * Daphnia Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.947, year: 2015

  6. A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the nervous system

    Science.gov (United States)

    Raimondo, Joseph V.; Joyce, Bradley; Kay, Louise; Schlagheck, Theresa; Newey, Sarah E.; Srinivas, Shankar; Akerman, Colin J.

    2013-01-01

    Within the nervous system, intracellular Cl− and pH regulate fundamental processes including cell proliferation, metabolism, synaptic transmission, and network excitability. Cl− and pH are often co-regulated, and network activity results in the movement of both Cl− and H+. Tools to accurately measure these ions are crucial for understanding their role under physiological and pathological conditions. Although genetically-encoded Cl− and pH sensors have been described previously, these either lack ion specificity or are unsuitable for neuronal use. Here we present ClopHensorN—a new genetically-encoded ratiometric Cl− and pH sensor that is optimized for the nervous system. We demonstrate the ability of ClopHensorN to dissociate and simultaneously quantify Cl− and H+ concentrations under a variety of conditions. In addition, we establish the sensor's utility by characterizing activity-dependent ion dynamics in hippocampal neurons. PMID:24312004

  7. A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the nervous system.

    Science.gov (United States)

    Raimondo, Joseph V; Joyce, Bradley; Kay, Louise; Schlagheck, Theresa; Newey, Sarah E; Srinivas, Shankar; Akerman, Colin J

    2013-01-01

    Within the nervous system, intracellular Cl(-) and pH regulate fundamental processes including cell proliferation, metabolism, synaptic transmission, and network excitability. Cl(-) and pH are often co-regulated, and network activity results in the movement of both Cl(-) and H(+). Tools to accurately measure these ions are crucial for understanding their role under physiological and pathological conditions. Although genetically-encoded Cl(-) and pH sensors have been described previously, these either lack ion specificity or are unsuitable for neuronal use. Here we present ClopHensorN-a new genetically-encoded ratiometric Cl(-) and pH sensor that is optimized for the nervous system. We demonstrate the ability of ClopHensorN to dissociate and simultaneously quantify Cl(-) and H(+) concentrations under a variety of conditions. In addition, we establish the sensor's utility by characterizing activity-dependent ion dynamics in hippocampal neurons.

  8. A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the nervous system

    Directory of Open Access Journals (Sweden)

    Joseph Valentino Raimondo

    2013-11-01

    Full Text Available Within the nervous system, intracellular Cl- and pH regulate fundamental processes including cell proliferation, metabolism, synaptic transmission and network excitability. Cl- and pH are often co-regulated, and network activity results in the movement of both Cl- and H+. Tools to accurately measure these ions are crucial for understanding their role under physiological and pathological conditions. Although genetically-encoded Cl- and pH sensors have been described previously, these either lack ion specificity or are unsuitable for neuronal use. Here we present ClopHensorN - a new genetically-encoded ratiometric Cl- and pH sensor that is optimized for the nervous system. We demonstrate the ability of ClopHensorN to dissociate and simultaneously quantify Cl- and H+ concentrations under a variety of conditions. In addition, we establish the sensor’s utility by characterizing activity-dependent ion dynamics in hippocampal neurons.

  9. Analysis of the Multi Strategy Goal Programming for Micro-Grid Based on Dynamic ant Genetic Algorithm

    Science.gov (United States)

    Qiu, J. P.; Niu, D. X.

    Micro-grid is one of the key technologies of the future energy supplies. Take economic planning. reliability, and environmental protection of micro grid as a basis for the analysis of multi-strategy objective programming problems for micro grid which contains wind power, solar power, and battery and micro gas turbine. Establish the mathematical model of each power generation characteristics and energy dissipation. and change micro grid planning multi-objective function under different operating strategies to a single objective model based on AHP method. Example analysis shows that in combination with dynamic ant mixed genetic algorithm can get the optimal power output of this model.

  10. In-Depth Analysis of Human Neonatal and Adult IgM Antibody Repertoires

    Directory of Open Access Journals (Sweden)

    Binbin Hong

    2018-02-01

    Full Text Available Although high-throughput sequencing and associated bioinformatics technologies have enabled the in-depth, sequence-based characterization of human immune repertoires, only a few studies on a relatively small number of sequences explored the characteristics of antibody repertoires in neonates, with contradictory conclusions. To gain a more comprehensive understanding of the human IgM antibody repertoire, we performed Illumina sequencing and IMGT/HighV-QUEST analysis of IgM heavy chain repertoire of the B lymphocytes from the cord blood (CB of neonates, as well as the repertoire from peripheral blood of healthy human adults (HH. The comparative study revealed unexpectedly high levels of similarity between the neonatal and adult repertoires. In both repertoires, the VDJ gene usage showed no significant difference, and the most frequently used VDJ gene was IGHV4-59, IGHD3-10, and IGHJ3. The average amino acid (aa length of CDR1 (CB: 8.5, HH: 8.4 and CDR2 (CB: 7.6, HH: 7.5, as well as the aa composition and the average hydrophobicity of the CDR3 demonstrated no significant difference between the two repertories. However, the average aa length of CDR3 was longer in the HH repertoire than the CB repertoire (CB: 14.5, HH: 15.5. Besides, the frequencies of aa mutations in CDR1 (CB: 19.33%, HH: 25.84% and CDR2 (CB: 9.26%, HH: 17.82% were higher in the HH repertoire compared to the CB repertoire. Interestingly, the most prominent difference between the two repertoires was the occurrence of N2 addition (CB: 64.87%, HH: 85.69%, a process that occurs during V-D-J recombination for introducing random nucleotide additions between D- and J-gene segments. The antibody repertoire of healthy adults was more diverse than that of neonates largely due to the higher occurrence of N2 addition. These findings may lead to a better understanding of antibody development and evolution pathways and may have potential practical value for facilitating the generation of more

  11. Microbial culturomics unravels the halophilic microbiota repertoire of table salt: description of Gracilibacillus massiliensis sp. nov.

    Directory of Open Access Journals (Sweden)

    Awa Diop

    2016-10-01

    Full Text Available Background: Microbial culturomics represents an ongoing revolution in the characterization of environmental and human microbiome. Methods: By using three media containing high salt concentration (100, 150, and 200 g/L, the halophilic microbial culturome of a commercial table salt was determined. Results: Eighteen species belonging to the Terrabacteria group were isolated including eight moderate halophilic and 10 halotolerant bacteria. Gracilibacillus massiliensis sp. nov., type strain Awa-1T (=CSUR P1441=DSM 29726, is a moderately halophilic gram-positive, non-spore-forming rod, and is motile by using a flagellum. Strain Awa-1T shows catalase activity but no oxidase activity. It is not only an aerobic bacterium but also able to grow in anaerobic and microaerophilic atmospheres. The draft genome of G. massiliensis is 4,207,226 bp long, composed of 13 scaffolds with 36.05% of G+C content. It contains 3,908 genes (3,839 protein-coding and 69 RNA genes. At least 1,983 (52% orthologous proteins were not shared with the closest phylogenetic species. Hundred twenty-six genes (3.3% were identified as ORFans. Conclusions: Microbial culturomics can dramatically improve the characterization of the food and environmental microbiota repertoire, deciphering new bacterial species and new genes. Further studies will clarify the geographic specificity and the putative role of these new microbes and their related functional genetic content in environment, health, and disease.

  12. Microbial culturomics unravels the halophilic microbiota repertoire of table salt: description of Gracilibacillus massiliensis sp. nov.

    Science.gov (United States)

    Diop, Awa; Khelaifia, Saber; Armstrong, Nicholas; Labas, Noémie; Fournier, Pierre-Edouard; Raoult, Didier; Million, Matthieu

    2016-01-01

    Microbial culturomics represents an ongoing revolution in the characterization of environmental and human microbiome. By using three media containing high salt concentration (100, 150, and 200 g/L), the halophilic microbial culturome of a commercial table salt was determined. Eighteen species belonging to the Terrabacteria group were isolated including eight moderate halophilic and 10 halotolerant bacteria. Gracilibacillus massiliensis sp. nov., type strain Awa-1 T (=CSUR P1441=DSM 29726), is a moderately halophilic gram-positive, non-spore-forming rod, and is motile by using a flagellum. Strain Awa-1 T shows catalase activity but no oxidase activity. It is not only an aerobic bacterium but also able to grow in anaerobic and microaerophilic atmospheres. The draft genome of G. massiliensis is 4,207,226 bp long, composed of 13 scaffolds with 36.05% of G+C content. It contains 3,908 genes (3,839 protein-coding and 69 RNA genes). At least 1,983 (52%) orthologous proteins were not shared with the closest phylogenetic species. Hundred twenty-six genes (3.3%) were identified as ORFans. Microbial culturomics can dramatically improve the characterization of the food and environmental microbiota repertoire, deciphering new bacterial species and new genes. Further studies will clarify the geographic specificity and the putative role of these new microbes and their related functional genetic content in environment, health, and disease.

  13. Population genetic dynamics of three-spined sticklebacks (Gasterosteus aculeatus) in anthropogenic altered habitats.

    Science.gov (United States)

    Scharsack, Joern P; Schweyen, Hannah; Schmidt, Alexander M; Dittmar, Janine; Reusch, Thorsten Bh; Kurtz, Joachim

    2012-06-01

    In industrialized and/or agriculturally used landscapes, inhabiting species are exposed to a variety of anthropogenic changes in their environments. Genetic diversity may be reduced if populations encounter founder events, bottlenecks, or isolation. Conversely, genetic diversity may increase if populations adapt to changes in selective regimes in newly created habitats. With the present study, genetic variability of 918 sticklebacks from 43 samplings (21.3 ± 3.8 per sample) at 36 locations from cultivated landscapes in Northwest Germany was analyzed at nine neutral microsatellite loci. To test if differentiation is influenced by habitat alterations, sticklebacks were collected from ancient running waters and adjacent artificial stagnant waters, from brooks with salt water inflow of anthropogenic and natural origin and adjacent freshwater sites. Overall population structure was dominated by isolation by distance (IBD), which was significant across all populations, and analysis of molecular variance (AMOVA) revealed that 10.6% of the variation was explained by river catchment area. Populations in anthropogenic modified habitats deviated from the general IBD structure and in the AMOVA, grouping by habitat type running/stagnant water explained 4.9% of variation and 1.4% of the variation was explained by salt-/freshwater habitat. Sticklebacks in salt-polluted water systems seem to exhibit elevated migratory activity between fresh- and saltwater habitats, reducing IBD. In other situations, populations showed distinct signs of genetic isolation, which in some locations was attributed to mechanical migration barriers, but in others to potential anthropogenic induced bottleneck or founder effects. The present study shows that anthropogenic habitat alterations may have diverse effects on the population genetic structure of inhabiting species. Depending on the type of habitat change, increased genetic differentiation, diversification, or isolation are possible consequences.

  14. Behavioral Repertoire Influences the Rate and Nature of Learning in Climbing: Implications for Individualized Learning Design in Preparation for Extreme Sports Participation

    Directory of Open Access Journals (Sweden)

    Dominic Orth

    2018-06-01

    Full Text Available Extreme climbing where participants perform while knowing that a simple mistake could result in death requires a skill set normally acquired in non-extreme environments. In the ecological dynamics approach to perception and action, skill acquisition involves a process where the existing repertoire of behavioral capabilities (or coordination repertoire of a learner are destabilized and re-organized through practice—this process can expand the individuals affordance boundaries allowing the individual to explore new environments. Change in coordination repertoire has been observed in bi-manual coordination and postural regulation tasks, where individuals begin practice using one mode of coordination before transitioning to another, more effective, coordination mode during practice. However, individuals may also improve through practice without qualitatively reorganizing movement system components—they do not find a new mode of coordination. To explain these individual differences during learning (i.e., whether or not a new action is discovered, a key candidate is the existing coordination repertoire present prior to practice. In this study, the learning dynamics of body configuration patterns organized with respect to an indoor climbing surface were observed and the existing repertoire of coordination evaluated prior to and after practice. Specifically, performance outcomes and movement patterns of eight beginners were observed across 42 trials of practice over a 7-week period. A pre- and post-test scanning procedure was used to determine existing patterns of movement coordination and the emergence of new movement patterns after the practice period. Data suggested the presence of different learning dynamics by examining trial-to-trial performance in terms of jerk (an indicator of climbing fluency, at the individual level of analysis. The different learning dynamics (identified qualitatively included: continuous improvement, sudden improvement

  15. Immune Repertoire after Immunization As Seen by Next-Generation Sequencing and Proteomics

    Directory of Open Access Journals (Sweden)

    Martijn M. VanDuijn

    2017-10-01

    Full Text Available The immune system produces a diverse repertoire of immunoglobulins in response to foreign antigens. During B-cell development, VDJ recombination and somatic mutations generate diversity, whereas selection processes remove it. Using both proteomic and NGS approaches, we characterized the immune repertoires in groups of rats after immunization with purified antigens. Proteomics and NGS data on the repertoire are in qualitative agreement, but did show quantitative differences that may relate to differences between the biological niches that were sampled for these approaches. Both methods contributed complementary information in the characterization of the immune repertoire. It was found that the immune repertoires resulting from each antigen had many similarities that allowed samples to cluster together, and that mutated immunoglobulin peptides were shared among animals with a response to the same antigen significantly more than for different antigens. However, the number of shared sequences decreased in a log-linear fashion relative to the number of animals that share them, which may affect future applications. A phylogenetic analysis on the NGS reads showed that reads from different individuals immunized with the same antigen populated distinct branches of the phylogram, an indication that the repertoire had converged. Also, similar mutation patterns were found in branches of the phylogenetic tree that were associated with antigen-specific immunoglobulins through proteomics data. Thus, data from different analysis methods and different experimental platforms show that the immunoglobulin repertoires of immunized animals have overlapping and converging features. With additional research, this may enable interesting applications in biotechnology and clinical diagnostics.

  16. Identification of antigen-specific human monoclonal antibodies using high-throughput sequencing of the antibody repertoire.

    Science.gov (United States)

    Liu, Ju; Li, Ruihua; Liu, Kun; Li, Liangliang; Zai, Xiaodong; Chi, Xiangyang; Fu, Ling; Xu, Junjie; Chen, Wei

    2016-04-22

    High-throughput sequencing of the antibody repertoire provides a large number of antibody variable region sequences that can be used to generate human monoclonal antibodies. However, current screening methods for identifying antigen-specific antibodies are inefficient. In the present study, we developed an antibody clone screening strategy based on clone dynamics and relative frequency, and used it to identify antigen-specific human monoclonal antibodies. Enzyme-linked immunosorbent assay showed that at least 52% of putative positive immunoglobulin heavy chains composed antigen-specific antibodies. Combining information on dynamics and relative frequency improved identification of positive clones and elimination of negative clones. and increase the credibility of putative positive clones. Therefore the screening strategy could simplify the subsequent experimental screening and may facilitate the generation of antigen-specific antibodies. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Scope and Limits of the Notion of "Repertoire of Contention" to Describe, Measure and Explain Conflictivity in XXI Century Chile

    Directory of Open Access Journals (Sweden)

    Nicolás Orellana Águila

    2017-09-01

    Full Text Available The aim of this article is to analyze the dynamics of social conflict in Chile during the period 2000-2011. We elaborate catalogues of contention actions from Clacso’s “Cronologías del Conflicto Social”, that are the basis to identify actors, actions, and adversaries. The specific objective is double: on one hand, to take to the limit the theoretical foundations in which a large part of academic interpretations of social conflict are based, evaluating their utility and possible criticisms; on the other, to evaluate whether those who mobilize respond to a heteronomous dynamics of conflict or rather are subjects with an autonomous capacity of action. With this analysis we expect to have enough elements to elaborate an outline of the repertoire of contention in Chile during this Century.

  18. A weed-crop complex in sorghum: The dynamics of genetic diversity in a traditional farming system.

    Science.gov (United States)

    Barnaud, Adeline; Deu, Monique; Garine, Eric; Chantereau, Jacques; Bolteu, Justin; Koïda, Esaei Ouin; McKey, Doyle; Joly, Hélène I

    2009-10-01

    Despite the major ecological and economic impacts of gene flow between domesticated plants and their wild relatives, many aspects of the process, particularly the relative roles of natural and human selection in facilitating or constraining gene flow, are still poorly understood. We developed a multidisciplinary approach, involving both biologists and social scientists, to investigate the dynamics of genetic diversity of a sorghum weed-crop complex in a village of Duupa farmers in northern Cameroon. Farmers distinguish a gradient from weedy morphotypes (naa baa see, haariya, and genkiya) to domesticated morphotypes; haariya and genkiya have intermediate morphological traits. We investigated the pattern of diversity in this complex using both morphological and genetic data. Our biological results are interpreted in the light of data on farmers' taxonomy and practices such as spatial pattern of planting and plant selection. Both morphological and genetic data are congruent with farmers' taxonomy and confirm the introgressed status of intermediate weedy morphotypes. Farmers actively select against weedy morphotypes, but several practices unconsciously favor gene flow. Furthermore, haariya and genkiya may facilitate introgression between naa baa see and domesticated morphotypes by virtue of their intermediate flowering period and their mode of management by farmers.

  19. D-VASim: Dynamic Virtual Analyzer and Simulator for Genetic Circuits

    DEFF Research Database (Denmark)

    Baig, Hasan; Madsen, Jan

    2015-01-01

    are either assembled from a standard library of well-defined genetic gates or from parts of an available library, for instance, BioBricks. The obtained behavior can be validated through in-silico analysis, solving reaction kinetics using ordinary differential equations (ODEs) or by stochastic simulation...

  20. Prediction of China's coal production-environmental pollution based on a hybrid genetic algorithm-system dynamics model

    International Nuclear Information System (INIS)

    Yu Shiwei; Wei Yiming

    2012-01-01

    This paper proposes a hybrid model based on genetic algorithm (GA) and system dynamics (SD) for coal production–environmental pollution load in China. GA has been utilized in the optimization of the parameters of the SD model to reduce implementation subjectivity. The chain of “Economic development–coal demand–coal production–environmental pollution load” of China in 2030 was predicted, and scenarios were analyzed. Results show that: (1) GA performs well in optimizing the parameters of the SD model objectively and in simulating the historical data; (2) The demand for coal energy continuously increases, although the coal intensity has actually decreased because of China's persistent economic development. Furthermore, instead of reaching a turning point by 2030, the environmental pollution load continuously increases each year even under the scenario where coal intensity decreased by 20% and investment in pollution abatement increased by 20%; (3) For abating the amount of “three types of wastes”, reducing the coal intensity is more effective than reducing the polluted production per tonne of coal and increasing investment in pollution control. - Highlights: ► We propos a GA-SD model for China's coal production-pollution prediction. ► Genetic algorithm (GA) can objectively and accurately optimize parameters of system dynamics (SD) model. ► Environmental pollution in China is projected to grow in our scenarios by 2030. ► The mechanism of reducing waste production per tonne of coal mining is more effective than others.

  1. Defensive repertoire of Drosophila larvae in response to toxic fungi.

    Science.gov (United States)

    Trienens, Monika; Kraaijeveld, Ken; Wertheim, Bregje

    2017-10-01

    Chemical warfare including insecticidal secondary metabolites is a well-known strategy for environmental microbes to monopolize a food source. Insects in turn have evolved behavioural and physiological defences to eradicate or neutralize the harmful microorganisms. We studied the defensive repertoire of insects in this interference competition by combining behavioural and developmental assays with whole-transcriptome time-series analysis. Confrontation with the toxic filamentous fungus Aspergillus nidulans severely reduced the survival of Drosophila melanogaster larvae. Nonetheless, the larvae did not behaviourally avoid the fungus, but aggregated at it. Confrontation with fungi strongly affected larval gene expression, including many genes involved in detoxification (e.g., CYP, GST and UGT genes) and the formation of the insect cuticle (e.g., Tweedle genes). The most strongly upregulated genes were several members of the insect-specific gene family Osiris, and CHK-kinase-like domains were over-represented. Immune responses were not activated, reflecting the competitive rather than pathogenic nature of the antagonistic interaction. While internal microbes are widely acknowledged as important, our study emphasizes the underappreciated role of environmental microbes as fierce competitors. © 2017 John Wiley & Sons Ltd.

  2. Dynamics and genetics of a disease-driven species decline to near extinction: lessons for conservation.

    Science.gov (United States)

    Hudson, M A; Young, R P; D'Urban Jackson, J; Orozco-terWengel, P; Martin, L; James, A; Sulton, M; Garcia, G; Griffiths, R A; Thomas, R; Magin, C; Bruford, M W; Cunningham, A A

    2016-08-03

    Amphibian chytridiomycosis has caused precipitous declines in hundreds of species worldwide. By tracking mountain chicken (Leptodactylus fallax) populations before, during and after the emergence of chytridiomycosis, we quantified the real-time species level impacts of this disease. We report a range-wide species decline amongst the fastest ever recorded, with a loss of over 85% of the population in fewer than 18 months on Dominica and near extinction on Montserrat. Genetic diversity declined in the wild, but emergency measures to establish a captive assurance population captured a representative sample of genetic diversity from Montserrat. If the Convention on Biological Diversity's targets are to be met, it is important to evaluate the reasons why they appear consistently unattainable. The emergence of chytridiomycosis in the mountain chicken was predictable, but the decline could not be prevented. There is an urgent need to build mitigation capacity where amphibians are at risk from chytridiomycosis.

  3. Vulnerability of dynamic genetic conservation units of forest trees in Europe to climate change

    OpenAIRE

    Schueler, Silvio; Falk, Wolfgang; Koskela, Jarkko; Lefèvre, François; Bozzano, Michele; Hubert, Jason; Kraigher, Hojka; Longauer, Roman; Olrik, Ditte C.

    2014-01-01

    A transnational network of genetic conservation units for forest trees was recently documented in Europe aiming at the conservation of evolutionary processes and the adaptive potential of natural or man-made tree populations. In this study, we quantified the vulnerability of individual conservation units and the whole network to climate change using climate favourability models and the estimated velocity of climate change. Compared to the overall climate niche of the analysed target species p...

  4. Genetically different isolates of Trypanosoma cruzi elicit different infection dynamics in raccoons (Procyon lotor) and Virginia opossums (Didelphis virginiana).

    Science.gov (United States)

    Roellig, Dawn M; Ellis, Angela E; Yabsley, Michael J

    2009-12-01

    Trypanosoma cruzi is a genetically and biologically diverse species. In the current study we determined T. cruzi infection dynamics in two common North American reservoirs, Virginia opossums (Didelphis virginiana) and raccoons (Procyon lotor). Based on previous molecular and culture data from naturally-exposed animals, we hypothesised that raccoons would have a longer patent period than opossums, and raccoons would be competent reservoirs for both genotypes T. cruzi I (TcI) and TcIIa, while opossums would only serve as hosts for TcI. Individuals (n=2 or 3) of each species were inoculated with 1x10(6) culture-derived T. cruzi trypomastigotes of TcIIa (North American (NA) - raccoon), TcI (NA - opossum), TcIIb (South American - human), or both TcI and TcIIa. Parasitemias in opossums gradually increased and declined rapidly, whereas parasitemias peaked sooner in raccoons and they maintained relatively high parasitemia for 5weeks. Raccoons became infected with all three T. cruzi strains, while opossums only became infected with TcI and TcIIb. Although opossums were susceptible to TcIIb, infection dynamics were dramatically different compared with TcI. Opossums inoculated with TcIIb seroconverted, but parasitemia duration was short and only detectable by PCR. In addition, raccoons seroconverted sooner (3-7days post inoculation) than opossums (10days post inoculation). These data suggest that infection dynamics of various T. cruzi strains can differ considerably in different wildlife hosts.

  5. Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires.

    Directory of Open Access Journals (Sweden)

    Mikhail V Pogorelyy

    2017-07-01

    Full Text Available The diversity of T-cell receptors recognizing foreign pathogens is generated through a highly stochastic recombination process, making the independent production of the same sequence rare. Yet unrelated individuals do share receptors, which together constitute a "public" repertoire of abundant clonotypes. The TCR repertoire is initially formed prenatally, when the enzyme inserting random nucleotides is downregulated, producing a limited diversity subset. By statistically analyzing deep sequencing T-cell repertoire data from twins, unrelated individuals of various ages, and cord blood, we show that T-cell clones generated before birth persist and maintain high abundances in adult organisms for decades, slowly decaying with age. Our results suggest that large, low-diversity public clones are created during pre-natal life, and survive over long periods, providing the basis of the public repertoire.

  6. Rules of song development and their use in vocal interactions by birds with large repertoires

    OpenAIRE

    Geberzahn Nicole; Hultsch Henrike

    2004-01-01

    Songbirds are well known for settling their disputes by vocal signals, and their singing plays a dominant role. Most studies on this issue have concentrated on bird species that develop and use small vocal repertoires. In this article we will go farther and focus on examples of how species with large song repertoires make use of their vocal competence. In particular, we will outline the study of interaction rules which have been elucidated by examining time- and pattern-specific relationships...

  7. High prevalence of abnormal motor repertoire at 3 months corrected age in extremely preterm infants.

    Science.gov (United States)

    Fjørtoft, Toril; Evensen, Kari Anne I; Øberg, Gunn Kristin; Songstad, Nils Thomas; Labori, Cathrine; Silberg, Inger Elisabeth; Loennecken, Marianne; Møinichen, Unn Inger; Vågen, Randi; Støen, Ragnhild; Adde, Lars

    2016-03-01

    To compare early motor repertoire between extremely preterm and term-born infants. An association between the motor repertoire and gestational age and birth weight was explored in extremely preterm infants without severe ultrasound abnormalities. In a multicentre study, the early motor repertoire of 82 infants born extremely preterm (ELGAN:<28 weeks) and/or with extremely low birth weight (ELBW:<1000 g) and 87 term-born infants were assessed by the "Assessment of Motor Repertoire - 2 to 5 Months" (AMR) which is part of Prechtl's "General Movement Assessment", at 12 weeks post-term age. Fidgety movements were classified as normal if present and abnormal if absent, sporadic or exaggerated. Concurrent motor repertoire was classified as normal if smooth and fluent and abnormal if monotonous, stiff, jerky and/or predominantly fast or slow. Eight-teen ELBW/ELGAN infants had abnormal fidgety movements (8 absent, 7 sporadic and 3 exaggerated fidgety movements) compared with 2 control infants (OR:12.0; 95%CI:2.7-53.4) and 46 ELBW/ELGAN infants had abnormal concurrent motor repertoire compared with 17 control infants (OR:5.3; 95%CI:2.6-10.5). Almost all detailed aspects of the AMR differed between the groups. Results were the same when three infants with severe ultrasound abnormalities were excluded. In the remaining ELBW/ELGAN infants, there was no association between motor repertoire and gestational age or birth weight. ELBW/ELGAN infants had poorer quality of early motor repertoire than term-born infants.The findings were not explained by severe abnormalities on neonatal ultrasound scans and were not correlated to the degree of prematurity. The consequences of these abnormal movement patterns remain to be seen in future follow-up studies. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  8. Dynamics and ethics of comprehensive preimplantation genetic testing: a review of the challenges.

    Science.gov (United States)

    Hens, Kristien; Dondorp, Wybo; Handyside, Alan H; Harper, Joyce; Newson, Ainsley J; Pennings, Guido; Rehmann-Sutter, Christoph; de Wert, Guido

    2013-01-01

    Genetic testing of preimplantation embryos has been used for preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Microarray technology is being introduced in both these contexts, and whole genome sequencing of blastomeres is also expeted to become possible soon. The amount of extra information such tests will yield may prove to be beneficial for embryo selection, will also raise various ethical issues. We present an overview of the developments and an agenda-setting exploration of the ethical issues. The paper is a joint endeavour by the presenters at an explorative 'campus meeting' organized by the European Society of Human Reproduction and Embryology in cooperation with the department of Health, Ethics & Society of the Maastricht University (The Netherlands). The increasing amount and detail of information that new screening techniques such as microarrays and whole genome sequencing offer does not automatically coincide with an increasing understanding of the prospects of an embryo. From a technical point of view, the future of comprehensive embryo testing may go together with developments in preconception carrier screening. From an ethical point of view, the increasing complexity and amount of information yielded by comprehensive testing techniques will lead to challenges to the principle of reproductive autonomy and the right of the child to an open future, and may imply a possible larger responsibility of the clinician towards the welfare of the future child. Combinations of preconception carrier testing and embryo testing may solve some of these ethical questions but could introduce others. As comprehensive testing techniques are entering the IVF clinic, there is a need for a thorough rethinking of traditional ethical paradigms regarding medically assisted reproduction.

  9. Dynamics of radioecological and genetic processes in populations of mammalian model species at contamination of ecosystems

    International Nuclear Information System (INIS)

    Ryabokon', N.I.; Goncharova, R.I.

    2008-01-01

    A short review of data on the time course of radiobiological and genetic processes in natural populations of mammalian model species inhabiting radiocontaminated ecosystems over many generations is presented here. The described time-courses of biological end-points in these populations do not reflect the time course of the whole-body dose rates, but do the outcome of multiple processes, including the direct response to individual irradiation, the transgeneration transmission and accumulation of induced damages and the development of adaptation. (authors)

  10. Investigating genetic diversity and habitat dynamics in Plantago brutia (Plantaginaceae), implications for the management of narrow endemics in Mediterranean mountain pastures.

    Science.gov (United States)

    De Vita, A; Bernardo, L; Gargano, D; Palermo, A M; Peruzzi, L; Musacchio, A

    2009-11-01

    Many factors have contributed to the richness of narrow endemics in the Mediterranean, including long-lasting human impact on pristine landscapes. The abandonment of traditional land-use practices is causing forest recovery throughout the Mediterranean mountains, by increasing reduction and fragmentation of open habitats. We investigated the population genetic structure and habitat dynamics of Plantago brutia Ten., a narrow endemic in mountain pastures of S Italy. Some plants were cultivated in the botanical garden to explore the species' breeding system. Genetic diversity was evaluated based on inter-simple sequence repeat (ISSR) polymorphisms in 150 individuals from most of known stands. Recent dynamics in the species habitat were checked over a 14-year period. Flower phenology, stigma receptivity and experimental pollinations revealed protogyny and self-incompatibility. With the exception of very small and isolated populations, high genetic diversity was found at the species and population level. amova revealed weak differentiation among populations, and the Mantel test suggested absence of isolation-by-distance. Multivariate analysis of population and genetic data distinguished the populations based on genetic richness, size and isolation. Landscape analyses confirmed recent reduction and isolation of potentially suitable habitats. Low selfing, recent isolation and probable seed exchange may have preserved P. brutia populations from higher loss of genetic diversity. Nonetheless, data related to very small populations suggest that this species may suffer further fragmentation and isolation. To preserve most of the species' genetic richness, future management efforts should consider the large and isolated populations recognised in our analyses.

  11. Visualizing presynaptic calcium dynamics and vesicle fusion with a single genetically encoded reporter at individual synapses

    Directory of Open Access Journals (Sweden)

    Rachel E Jackson

    2016-07-01

    Full Text Available Synaptic transmission depends on the influx of calcium into the presynaptic compartment, which drives neurotransmitter release. Genetically encoded reporters are widely used tools to understand these processes, particularly pHluorin-based reporters that report vesicle exocytosis and endocytosis through pH dependent changes in fluorescence, and genetically encoded calcium indicators (GECIs that exhibit changes in fluorescence upon binding to calcium. The recent expansion of the color palette of available indicators has made it possible to image multiple probes simultaneously within a cell. We have constructed a single molecule reporter capable of concurrent imaging of both presynaptic calcium influx and exocytosis, by fusion of sypHy, the vesicle associated protein synaptophysin containing a GFP-based pHluorin sensor, with the red-shifted GECI R-GECO1. Due to the fixed stoichiometry of the two probes, the ratio of the two responses can also be measured, providing an all optical correlate of the calcium dependence of release. Here, we have characterized stimulus-evoked sypHy-RGECO responses of hippocampal synapses in vitro, exploring the effects of different stimulus strengths and frequencies as well as variations in external calcium concentrations. By combining live sypHy-RGECO imaging with post-hoc fixation and immunofluorescence, we have also investigated correlations between structural and functional properties of synapses.

  12. Multiobjective genetic algorithm conjunctive use optimization for production, cost, and energy with dynamic return flow

    Science.gov (United States)

    Peralta, Richard C.; Forghani, Ali; Fayad, Hala

    2014-04-01

    Many real water resources optimization problems involve conflicting objectives for which the main goal is to find a set of optimal solutions on, or near to the Pareto front. E-constraint and weighting multiobjective optimization techniques have shortcomings, especially as the number of objectives increases. Multiobjective Genetic Algorithms (MGA) have been previously proposed to overcome these difficulties. Here, an MGA derives a set of optimal solutions for multiobjective multiuser conjunctive use of reservoir, stream, and (un)confined groundwater resources. The proposed methodology is applied to a hydraulically and economically nonlinear system in which all significant flows, including stream-aquifer-reservoir-diversion-return flow interactions, are simulated and optimized simultaneously for multiple periods. Neural networks represent constrained state variables. The addressed objectives that can be optimized simultaneously in the coupled simulation-optimization model are: (1) maximizing water provided from sources, (2) maximizing hydropower production, and (3) minimizing operation costs of transporting water from sources to destinations. Results show the efficiency of multiobjective genetic algorithms for generating Pareto optimal sets for complex nonlinear multiobjective optimization problems.

  13. Exploration of a rare population of Chinese chestnut in North America: stand dynamics, health and genetic relationships.

    Science.gov (United States)

    Miller, Amy C; Woeste, Keith E; Anagnostakis, Sandra L; Jacobs, Douglass F

    2014-10-20

    With the transport of plants around the globe, exotic species can readily spread disease to their native relatives; however, they can also provide genetic resistance to those relatives through hybrid breeding programmes. American chestnut (Castanea dentata) was an abundant tree species in North America until its decimation by introduced chestnut blight. To restore chestnut in North America, efforts are ongoing to test putative blight-resistant hybrids of Castanea dentata and Chinese chestnut (Castanea mollissima), but little is known about the ecology of C. mollissima. In a forest in northeastern USA in which C. mollissima has become established, we explored questions of stand dynamics, health and genetic relationships of C. mollissima offspring to an adjacent parent orchard. We found that C. mollissima was adapted and randomly distributed among native species in this relatively young forest. The genetics of the C. mollissima population compared with its parents indicated little effect of selection pressure as each of the parent trees contributed at least one offspring. The ease with which this exotic species proliferated calls to question why C. mollissima is rare elsewhere in forests of North America. It is likely that a time window of low animal predation allowed seedlings to establish, and the shallow soil at this site limited the maximum forest canopy height, permitting the characteristically short-statured C. mollissima to avoid suppression. Our results indicate that because C. mollissima exhibited pioneer species characteristics, hybrids between C. mollissima and C. dentata have the potential to be successful pioneer species of future forests in North America, and we challenge the paradigm that exotic tree species are wholly detrimental to native biodiversity. We contend that exotic tree species should be assessed not only by their level of threat to native species, but also by their potential positive impacts on ecosystems via hybrid breeding programmes

  14. Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Chen, T-C; Hou, H-A; Chou, W-C; Tang, J-L; Kuo, Y-Y; Chen, C-Y; Tseng, M-H; Huang, C-F; Lai, Y-J; Chiang, Y-C; Lee, F-Y; Liu, M-C; Liu, C-W; Liu, C-Y; Yao, M; Huang, S-Y; Ko, B-S; Hsu, S-C; Wu, S-J; Tsay, W; Chen, Y-C; Tien, H-F

    2014-01-01

    Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression

  15. Genetic disease in India and the West compared: provisional analysis of population dynamics.

    Science.gov (United States)

    Mitchison, Nicholas; Mitchison, Timothy

    2018-03-01

    The Indian Genetic Disease Database (IGDD) and Online Mendelian Inheritance in Man (OMIM) survey human populations that have different climate histories. Comparison of the two shows an outstanding difference in the relative frequency of recessive disease genes. Several of the diseases mediated at least in part by recessive gene mutations in India are not so mediated in the Western populations covered by OMIM, or are so mediated to a lesser extent. This we attribute to climate history, where population fall leading to inbreeding in the last ice age appears to have reduced the frequency of recessive disease genes in the Western world. This 'ice age benefit' hypothesis is further confirmed, partially by Kolmogorov-Smirnov analysis.

  16. Pre-emptive resource-constrained multimode project scheduling using genetic algorithm: A dynamic forward approach

    Directory of Open Access Journals (Sweden)

    Aidin Delgoshaei

    2016-09-01

    Full Text Available Purpose: The issue resource over-allocating is a big concern for project engineers in the process of scheduling project activities. Resource over-allocating drawback is frequently seen after scheduling of a project in practice which causes a schedule to be useless. Modifying an over-allocated schedule is very complicated and needs a lot of efforts and time. In this paper, a new and fast tracking method is proposed to schedule large scale projects which can help project engineers to schedule the project rapidly and with more confidence. Design/methodology/approach: In this article, a forward approach for maximizing net present value (NPV in multi-mode resource constrained project scheduling problem while assuming discounted positive cash flows (MRCPSP-DCF is proposed. The progress payment method is used and all resources are considered as pre-emptible. The proposed approach maximizes NPV using unscheduled resources through resource calendar in forward mode. For this purpose, a Genetic Algorithm is applied to solve. Findings: The findings show that the proposed method is an effective way to maximize NPV in MRCPSP-DCF problems while activity splitting is allowed. The proposed algorithm is very fast and can schedule experimental cases with 1000 variables and 100 resources in few seconds. The results are then compared with branch and bound method and simulated annealing algorithm and it is found the proposed genetic algorithm can provide results with better quality. Then algorithm is then applied for scheduling a hospital in practice. Originality/value: The method can be used alone or as a macro in Microsoft Office Project® Software to schedule MRCPSP-DCF problems or to modify resource over-allocated activities after scheduling a project. This can help project engineers to schedule project activities rapidly with more accuracy in practice.

  17. A theoretical interpersonal style repertoire for middle-level managers

    Directory of Open Access Journals (Sweden)

    P. Koortzen

    2005-10-01

    Full Text Available The development of the interpersonal behaviour of managers has received a good deal of attention, especially in terms of the most appropriate interpersonal styles in the work context and the skills involved in developing and maintaining effective interpersonal relationships. The design of effective interpersonal development programs requires a thorough evaluation of an individual’s interpersonal development needs. In order to do this, evaluators should have an understanding of the most appropriate interpersonal styles for managers. Given the aims of the investigation, the approach that was followed was to evaluate the relevant literature in this field. The theoretical goal was to study and describe the most appropriate theoretical interpersonal style repertoire of middle-level managers using the interpersonal approach, and specifically the 1982 Interpersonal Circle. The conclusions support the notion that dominant, assured, exhibitionistic, social, friendly, warm and trusting styles are the most relevant of the 16 interpersonal segments, while the assured-dominant, social-exhibitionistic and warm-friendly octants are viewed as the most appropriate. Opsomming Die ontwikkeling van die interpersoonlike gedrag van bestuurders het reeds heelwat aandag gekry. Dit geld veral vir aangeleenthede wat verband hou met die mees toepaslike interpersoonlike style binne die werkskonteks en die vaardighede wat die ontwikkeling van effektiewe interpersoonlike verhoudings onderlê. Die ontwikkeling van effektiewe interpersoonlike ontwikkelingsprogramme vereis ’n deeglike evaluering van ’n individu se interpersoonlike ontwikkelingsbehoeftes. Om dit te vermag, is dit nodig vir evalueerders om te verstaan wat die mees toepaslike interpersoonlike style vir bestuurders is. Gegee die doelwitte van die ondersoek is die metode wat gevolg is ’n evaluering van die relevante literatuur in hierdie gebied. Die teoretiese doel was om die mees toepaslike teoretiese

  18. Measurement correction method for force sensor used in dynamic pressure calibration based on artificial neural network optimized by genetic algorithm

    Science.gov (United States)

    Gu, Tingwei; Kong, Deren; Shang, Fei; Chen, Jing

    2017-12-01

    We present an optimization algorithm to obtain low-uncertainty dynamic pressure measurements from a force-transducer-based device. In this paper, the advantages and disadvantages of the methods that are commonly used to measure the propellant powder gas pressure, the applicable scope of dynamic pressure calibration devices, and the shortcomings of the traditional comparison calibration method based on the drop-weight device are firstly analysed in detail. Then, a dynamic calibration method for measuring pressure using a force sensor based on a drop-weight device is introduced. This method can effectively save time when many pressure sensors are calibrated simultaneously and extend the life of expensive reference sensors. However, the force sensor is installed between the drop-weight and the hammerhead by transition pieces through the connection mode of bolt fastening, which causes adverse effects such as additional pretightening and inertia forces. To solve these effects, the influence mechanisms of the pretightening force, the inertia force and other influence factors on the force measurement are theoretically analysed. Then a measurement correction method for the force measurement is proposed based on an artificial neural network optimized by a genetic algorithm. The training and testing data sets are obtained from calibration tests, and the selection criteria for the key parameters of the correction model is discussed. The evaluation results for the test data show that the correction model can effectively improve the force measurement accuracy of the force sensor. Compared with the traditional high-accuracy comparison calibration method, the percentage difference of the impact-force-based measurement is less than 0.6% and the relative uncertainty of the corrected force value is 1.95%, which can meet the requirements of engineering applications.

  19. Dynamic Source Inversion of a M6.5 Intraslab Earthquake in Mexico: Application of a New Parallel Genetic Algorithm

    Science.gov (United States)

    Díaz-Mojica, J. J.; Cruz-Atienza, V. M.; Madariaga, R.; Singh, S. K.; Iglesias, A.

    2013-05-01

    We introduce a novel approach for imaging the earthquakes dynamics from ground motion records based on a parallel genetic algorithm (GA). The method follows the elliptical dynamic-rupture-patch approach introduced by Di Carli et al. (2010) and has been carefully verified through different numerical tests (Díaz-Mojica et al., 2012). Apart from the five model parameters defining the patch geometry, our dynamic source description has four more parameters: the stress drop inside the nucleation and the elliptical patches; and two friction parameters, the slip weakening distance and the change of the friction coefficient. These parameters are constant within the rupture surface. The forward dynamic source problem, involved in the GA inverse method, uses a highly accurate computational solver for the problem, namely the staggered-grid split-node. The synthetic inversion presented here shows that the source model parameterization is suitable for the GA, and that short-scale source dynamic features are well resolved in spite of low-pass filtering of the data for periods comparable to the source duration. Since there is always uncertainty in the propagation medium as well as in the source location and the focal mechanisms, we have introduced a statistical approach to generate a set of solution models so that the envelope of the corresponding synthetic waveforms explains as much as possible the observed data. We applied the method to the 2012 Mw6.5 intraslab Zumpango, Mexico earthquake and determined several fundamental source parameters that are in accordance with different and completely independent estimates for Mexican and worldwide earthquakes. Our weighted-average final model satisfactorily explains eastward rupture directivity observed in the recorded data. Some parameters found for the Zumpango earthquake are: Δτ = 30.2+/-6.2 MPa, Er = 0.68+/-0.36x10^15 J, G = 1.74+/-0.44x10^15 J, η = 0.27+/-0.11, Vr/Vs = 0.52+/-0.09 and Mw = 6.64+/-0.07; for the stress drop

  20. Study on fitness functions of genetic algorithm for dynamically correcting nuclide atmospheric diffusion model

    International Nuclear Information System (INIS)

    Ji Zhilong; Ma Yuanwei; Wang Dezhong

    2014-01-01

    Background: In radioactive nuclides atmospheric diffusion models, the empirical dispersion coefficients were deduced under certain experiment conditions, whose difference with nuclear accident conditions is a source of deviation. A better estimation of the radioactive nuclide's actual dispersion process could be done by correcting dispersion coefficients with observation data, and Genetic Algorithm (GA) is an appropriate method for this correction procedure. Purpose: This study is to analyze the fitness functions' influence on the correction procedure and the forecast ability of diffusion model. Methods: GA, coupled with Lagrange dispersion model, was used in a numerical simulation to compare 4 fitness functions' impact on the correction result. Results: In the numerical simulation, the fitness function with observation deviation taken into consideration stands out when significant deviation exists in the observed data. After performing the correction procedure on the Kincaid experiment data, a significant boost was observed in the diffusion model's forecast ability. Conclusion: As the result shows, in order to improve dispersion models' forecast ability using GA, observation data should be given different weight in the fitness function corresponding to their error. (authors)

  1. Dynamic localisation of mature microRNAs in Human nucleoli is influenced by exogenous genetic materials.

    Science.gov (United States)

    Li, Zhou Fang; Liang, Yi Min; Lau, Pui Ngan; Shen, Wei; Wang, Dai Kui; Cheung, Wing Tai; Xue, Chun Jason; Poon, Lit Man; Lam, Yun Wah

    2013-01-01

    Although microRNAs are commonly known to function as a component of RNA-induced silencing complexes in the cytoplasm, they have been detected in other organelles, notably the nucleus and the nucleolus, of mammalian cells. We have conducted a systematic search for miRNAs in HeLa cell nucleoli, and identified 11 abundant miRNAs with a high level of nucleolar accumulation. Through in situ hybridisation, we have localised these miRNAs, including miR-191 and miR-484, in the nucleolus of a diversity of human and rodent cell lines. The nucleolar association of these miRNAs is resistant to various cellular stresses, but highly sensitive to the presence of exogenous nucleic acids. Introduction of both single- and double-stranded DNA as well as double stranded RNA rapidly induce the redistribution of nucleolar miRNAs to the cytoplasm. A similar change in subcellular distribution is also observed in cells infected with the influenza A virus. The partition of miRNAs between the nucleolus and the cytoplasm is affected by Leptomycin B, suggesting a role of Exportin-1 in the intracellular shuttling of miRNAs. This study reveals a previously unknown aspect of miRNA biology, and suggests a possible link between these small noncoding RNAs and the cellular management of foreign genetic materials.

  2. Dynamic localisation of mature microRNAs in Human nucleoli is influenced by exogenous genetic materials.

    Directory of Open Access Journals (Sweden)

    Zhou Fang Li

    Full Text Available Although microRNAs are commonly known to function as a component of RNA-induced silencing complexes in the cytoplasm, they have been detected in other organelles, notably the nucleus and the nucleolus, of mammalian cells. We have conducted a systematic search for miRNAs in HeLa cell nucleoli, and identified 11 abundant miRNAs with a high level of nucleolar accumulation. Through in situ hybridisation, we have localised these miRNAs, including miR-191 and miR-484, in the nucleolus of a diversity of human and rodent cell lines. The nucleolar association of these miRNAs is resistant to various cellular stresses, but highly sensitive to the presence of exogenous nucleic acids. Introduction of both single- and double-stranded DNA as well as double stranded RNA rapidly induce the redistribution of nucleolar miRNAs to the cytoplasm. A similar change in subcellular distribution is also observed in cells infected with the influenza A virus. The partition of miRNAs between the nucleolus and the cytoplasm is affected by Leptomycin B, suggesting a role of Exportin-1 in the intracellular shuttling of miRNAs. This study reveals a previously unknown aspect of miRNA biology, and suggests a possible link between these small noncoding RNAs and the cellular management of foreign genetic materials.

  3. Automatic Identification of Closed-Loop Wind Turbine Dynamics via Genetic Programming

    Energy Technology Data Exchange (ETDEWEB)

    La Cava, William; Danai, Kourosh; Lackner, Matthew; Spector, Lee; Fleming, Paul; Wright, Alan

    2015-10-03

    Wind turbines are nonlinear systems that operate in turbulent environments. As such, their behavior is difficult to characterize accurately across a wide range of operating conditions by physically meaningful models. Customarily, data-based models of wind turbines are defined in 'black box' format, lacking in both conciseness and physical intelligibility. To address this deficiency, we identify models of a modern horizontal-axis wind turbine in symbolic form using a recently developed symbolic regression method. The method used relies on evolutionary multi-objective optimization to produce succinct dynamic models from operational data without 'a priori' knowledge of the system. We compare the produced models with models derived by other methods for their estimation capacity and evaluate the tradeoff between model intelligibility and accuracy. Several succinct models are found that predict wind turbine behavior as well as or better than more complex alternatives derived by other methods.

  4. Evidence of strain structure in Plasmodium falciparum var gene repertoires in children from Gabon, West Africa.

    Science.gov (United States)

    Day, Karen P; Artzy-Randrup, Yael; Tiedje, Kathryn E; Rougeron, Virginie; Chen, Donald S; Rask, Thomas S; Rorick, Mary M; Migot-Nabias, Florence; Deloron, Philippe; Luty, Adrian J F; Pascual, Mercedes

    2017-05-16

    Existing theory on competition for hosts between pathogen strains has proposed that immune selection can lead to the maintenance of strain structure consisting of discrete, weakly overlapping antigenic repertoires. This prediction of strain theory has conceptual overlap with fundamental ideas in ecology on niche partitioning and limiting similarity between coexisting species in an ecosystem, which oppose the hypothesis of neutral coexistence. For Plasmodium falciparum , strain theory has been specifically proposed in relation to the major surface antigen of the blood stage, known as Pf EMP1 and encoded by the multicopy multigene family known as the var genes. Deep sampling of the DBLα domain of var genes in the local population of Bakoumba, West Africa, was completed to define whether patterns of repertoire overlap support a role of immune selection under the opposing force of high outcrossing, a characteristic of areas of intense malaria transmission. Using a 454 high-throughput sequencing protocol, we report extremely high diversity of the DBLα domain and a large parasite population with DBLα repertoires structured into nonrandom patterns of overlap. Such population structure, significant for the high diversity of var genes that compose it at a local level, supports the existence of "strains" characterized by distinct var gene repertoires. Nonneutral, frequency-dependent competition would be at play and could underlie these patterns. With a computational experiment that simulates an intervention similar to mass drug administration, we argue that the observed repertoire structure matters for the antigenic var diversity of the parasite population remaining after intervention.

  5. Infection dynamics and genetic variability of Mycoplasma hyopneumoniae in self-replacement gilts.

    Science.gov (United States)

    Takeuti, Karine L; de Barcellos, David E S N; de Andrade, Caroline P; de Almeida, Laura L; Pieters, Maria

    2017-09-01

    The aim of this study was to assess the longitudinal pattern of M. hyopneumoniae detection in self-replacement gilts at various farms and to characterize the genetic diversity among samples. A total of 298 gilts from three M. hyopneumoniae positive farms were selected at 150days of age (doa). Gilts were tested for M. hyopneumoniae antibodies by ELISA, once in serum at 150 doa and for M. hyopneumoniae detection in laryngeal swabs by real time PCR two or three times. Also, 425 piglets were tested for M. hyopneumoniae detection in laryngeal swabs. A total of 103 samples were characterized by Multiple Locus Variable-number tandem repeats Analysis. Multiple comparison tests were performed and adjusted using Bonferroni correction to compare prevalences of positive gilts by ELISA and real time PCR. Moderate to high prevalence of M. hyopneumoniae in gilts was detected at 150 doa, which decreased over time, and different detection patterns were observed among farms. Dam-to-piglet transmission of M. hyopneumoniae was not detected. The characterization of M. hyopneumoniae showed 17 different variants in all farms, with two identical variants detected in two of the farms. ELISA testing showed high prevalence of seropositive gilts at 150 doa in all farms. Results of this study showed that circulation of M. hyopneumoniae in self-replacement gilts varied among farms, even under similar production and management conditions. In addition, the molecular variability of M. hyopneumoniae detected within farms suggests that in cases of minimal replacement gilt introduction bacterial diversity maybe farm specific. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Acute Hepatopancreatic Necrosis Disease-Causing Vibrio parahaemolyticus Strains Maintain an Antibacterial Type VI Secretion System with Versatile Effector Repertoires.

    Science.gov (United States)

    Li, Peng; Kinch, Lisa N; Ray, Ann; Dalia, Ankur B; Cong, Qian; Nunan, Linda M; Camilli, Andrew; Grishin, Nick V; Salomon, Dor; Orth, Kim

    2017-07-01

    Acute hepatopancreatic necrosis disease (AHPND) is a newly emerging shrimp disease that has severely damaged the global shrimp industry. AHPND is caused by toxic strains of Vibrio parahaemolyticus that have acquired a "selfish plasmid" encoding the deadly binary toxins PirA vp /PirB vp To better understand the repertoire of virulence factors in AHPND-causing V. parahaemolyticus , we conducted a comparative analysis using the genome sequences of the clinical strain RIMD2210633 and of environmental non-AHPND and toxic AHPND isolates of V. parahaemolyticus Interestingly, we found that all of the AHPND strains, but none of the non-AHPND strains, harbor the antibacterial type VI secretion system 1 (T6SS1), which we previously identified and characterized in the clinical isolate RIMD2210633. This finding suggests that the acquisition of this T6SS might confer to AHPND-causing V. parahaemolyticus a fitness advantage over competing bacteria and facilitate shrimp infection. Additionally, we found highly dynamic effector loci in the T6SS1 of AHPND-causing strains, leading to diverse effector repertoires. Our discovery provides novel insights into AHPND-causing pathogens and reveals a potential target for disease control. IMPORTANCE Acute hepatopancreatic necrosis disease (AHPND) is a serious disease that has caused severe damage and significant financial losses to the global shrimp industry. To better understand and prevent this shrimp disease, it is essential to thoroughly characterize its causative agent, Vibrio parahaemolyticus Although the plasmid-encoded binary toxins PirA vp /PirB vp have been shown to be the primary cause of AHPND, it remains unknown whether other virulent factors are commonly present in V. parahaemolyticus and might play important roles during shrimp infection. Here, we analyzed the genome sequences of clinical, non-AHPND, and AHPND strains to characterize their repertoires of key virulence determinants. Our studies reveal that an antibacterial type

  7. Abscisic acid dynamics in roots detected with genetically encoded FRET sensors

    Science.gov (United States)

    Jones, Alexander M; Danielson, Jonas ÅH; ManojKumar, Shruti N; Lanquar, Viviane; Grossmann, Guido; Frommer, Wolf B

    2014-01-01

    Cytosolic hormone levels must be tightly controlled at the level of influx, efflux, synthesis, degradation and compartmentation. To determine ABA dynamics at the single cell level, FRET sensors (ABACUS) covering a range ∼0.2–800 µM were engineered using structure-guided design and a high-throughput screening platform. When expressed in yeast, ABACUS1 detected concentrative ABA uptake mediated by the AIT1/NRT1.2 transporter. Arabidopsis roots expressing ABACUS1-2µ (Kd∼2 µM) and ABACUS1-80µ (Kd∼80 µM) respond to perfusion with ABA in a concentration-dependent manner. The properties of the observed ABA accumulation in roots appear incompatible with the activity of known ABA transporters (AIT1, ABCG40). ABACUS reveals effects of external ABA on homeostasis, that is, ABA-triggered induction of ABA degradation, modification, or compartmentation. ABACUS can be used to study ABA responses in mutants and quantitatively monitor ABA translocation and regulation, and identify missing components. The sensor screening platform promises to enable rapid fine-tuning of the ABA sensors and engineering of plant and animal hormone sensors to advance our understanding of hormone signaling. DOI: http://dx.doi.org/10.7554/eLife.01741.001 PMID:24737862

  8. Ethics, genetics and dynamics: an emerging systematic approach to radiation protection of the environment

    International Nuclear Information System (INIS)

    Pentreath, R.J.

    2004-01-01

    There is now a general consensus of opinion that an explicit approach is necessary to demonstrate radiation protection of the environment, and that this approach needs to be developed in a systematic way. The framework that is emerging links ethical and moral issues (anthropocentric, biocentric, and ecocentric) to broad-based principles and objectives of environmental protection (sustainable development, maintaining biological diversity, and habitat protection) and then links these, in turn, to the needs of current environmental management practices, such as environmental exploitation, pollution control, and nature conservation. The relevance of this to radiation is that its effects (such as causing early mortality, morbidity, reduced reproductive success, as well as resulting in observable (scorable) cytogenetic damage) are those that may have a bearing on these same environmental management practices. The devise that would appear to be most useful to bridge the gap between our disparate data on radiation effects and the needs of environmental management, is that of adding to the concept of Reference Man in the shape of a small set of Reference Animals and Plants. This approach has now been adopted by the ICRP, adding new dynamics--the motive forces, both moral and physical--to the subject. The way is now clear for rapid progress to be made on a number of fronts

  9. Genetic and epigenetic variation in 5S ribosomal RNA genes reveals genome dynamics in Arabidopsis thaliana.

    Science.gov (United States)

    Simon, Lauriane; Rabanal, Fernando A; Dubos, Tristan; Oliver, Cecilia; Lauber, Damien; Poulet, Axel; Vogt, Alexander; Mandlbauer, Ariane; Le Goff, Samuel; Sommer, Andreas; Duborjal, Hervé; Tatout, Christophe; Probst, Aline V

    2018-04-06

    Organized in tandem repeat arrays in most eukaryotes and transcribed by RNA polymerase III, expression of 5S rRNA genes is under epigenetic control. To unveil mechanisms of transcriptional regulation, we obtained here in depth sequence information on 5S rRNA genes from the Arabidopsis thaliana genome and identified differential enrichment in epigenetic marks between the three 5S rDNA loci situated on chromosomes 3, 4 and 5. We reveal the chromosome 5 locus as the major source of an atypical, long 5S rRNA transcript characteristic of an open chromatin structure. 5S rRNA genes from this locus translocated in the Landsberg erecta ecotype as shown by linkage mapping and chromosome-specific FISH analysis. These variations in 5S rDNA locus organization cause changes in the spatial arrangement of chromosomes in the nucleus. Furthermore, 5S rRNA gene arrangements are highly dynamic with alterations in chromosomal positions through translocations in certain mutants of the RNA-directed DNA methylation pathway and important copy number variations among ecotypes. Finally, variations in 5S rRNA gene sequence, chromatin organization and transcripts indicate differential usage of 5S rDNA loci in distinct ecotypes. We suggest that both the usage of existing and new 5S rDNA loci resulting from translocations may impact neighboring chromatin organization.

  10. Flower development as an interplay between dynamical physical fields and genetic networks.

    Directory of Open Access Journals (Sweden)

    Rafael Ángel Barrio

    Full Text Available In this paper we propose a model to describe the mechanisms by which undifferentiated cells attain gene configurations underlying cell fate determination during morphogenesis. Despite the complicated mechanisms that surely intervene in this process, it is clear that the fundamental fact is that cells obtain spatial and temporal information that bias their destiny. Our main hypothesis assumes that there is at least one macroscopic field that breaks the symmetry of space at a given time. This field provides the information required for the process of cell differentiation to occur by being dynamically coupled to a signal transduction mechanism that, in turn, acts directly upon the gene regulatory network (GRN underlying cell-fate decisions within cells. We illustrate and test our proposal with a GRN model grounded on experimental data for cell fate specification during organ formation in early Arabidopsis thaliana flower development. We show that our model is able to recover the multigene configurations characteristic of sepal, petal, stamen and carpel primordial cells arranged in concentric rings, in a similar pattern to that observed during actual floral organ determination. Such pattern is robust to alterations of the model parameters and simulated failures predict altered spatio-temporal patterns that mimic those described for several mutants. Furthermore, simulated alterations in the physical fields predict a pattern equivalent to that found in Lacandonia schismatica, the only flowering species with central stamens surrounded by carpels.

  11. Flower development as an interplay between dynamical physical fields and genetic networks.

    Science.gov (United States)

    Barrio, Rafael Ángel; Hernández-Machado, Aurora; Varea, C; Romero-Arias, José Roberto; Alvarez-Buylla, Elena

    2010-10-27

    In this paper we propose a model to describe the mechanisms by which undifferentiated cells attain gene configurations underlying cell fate determination during morphogenesis. Despite the complicated mechanisms that surely intervene in this process, it is clear that the fundamental fact is that cells obtain spatial and temporal information that bias their destiny. Our main hypothesis assumes that there is at least one macroscopic field that breaks the symmetry of space at a given time. This field provides the information required for the process of cell differentiation to occur by being dynamically coupled to a signal transduction mechanism that, in turn, acts directly upon the gene regulatory network (GRN) underlying cell-fate decisions within cells. We illustrate and test our proposal with a GRN model grounded on experimental data for cell fate specification during organ formation in early Arabidopsis thaliana flower development. We show that our model is able to recover the multigene configurations characteristic of sepal, petal, stamen and carpel primordial cells arranged in concentric rings, in a similar pattern to that observed during actual floral organ determination. Such pattern is robust to alterations of the model parameters and simulated failures predict altered spatio-temporal patterns that mimic those described for several mutants. Furthermore, simulated alterations in the physical fields predict a pattern equivalent to that found in Lacandonia schismatica, the only flowering species with central stamens surrounded by carpels.

  12. Spatial waves of advance with bistable dynamics: cytoplasmic and genetic analogues of Allee effects.

    Science.gov (United States)

    Barton, N H; Turelli, Michael

    2011-09-01

    Unlike unconditionally advantageous "Fisherian" variants that tend to spread throughout a species range once introduced anywhere, "bistable" variants, such as chromosome translocations, have two alternative stable frequencies, absence and (near) fixation. Analogous to populations with Allee effects, bistable variants tend to increase locally only once they become sufficiently common, and their spread depends on their rate of increase averaged over all frequencies. Several proposed manipulations of insect populations, such as using Wolbachia or "engineered underdominance" to suppress vector-borne diseases, produce bistable rather than Fisherian dynamics. We synthesize and extend theoretical analyses concerning three features of their spatial behavior: rate of spread, conditions to initiate spread from a localized introduction, and wave stopping caused by variation in population densities or dispersal rates. Unlike Fisherian variants, bistable variants tend to spread spatially only for particular parameter combinations and initial conditions. Wave initiation requires introduction over an extended region, while subsequent spatial spread is slower than for Fisherian waves and can easily be halted by local spatial inhomogeneities. We present several new results, including robust sufficient conditions to initiate (and stop) spread, using a one-parameter cubic approximation applicable to several models. The results have both basic and applied implications.

  13. Genetic variation reveals influence of landscape connectivity on population dynamics and resiliency of western trout in disturbance-prone habitats

    Science.gov (United States)

    Helen M. Neville,; Gresswell, Robert E.; Dunham, Jason B.

    2012-01-01

    Salmonid fishes have evolved and persisted in dynamic ecosystems where disturbance events vary in frequency, magnitude, timing, and duration, as well as the specific nature of associated effects (e.g., changes in thermal or flow regimes, geomorphology, or water chemistry). In the western United States, one of the major drivers of disturbance in stream ecosystems is fire. Although there is a growing consensus that fish populations can ultimately benefit from the productive and heterogeneous habitats created by fire, to persist they obviously have to withstand the immediate and shorter-term effects of fire, which can reduce or even extirpate local populations. Movement among interconnected stream habitats is thought to be an important strategy enabling persistence during and following fire, and there is mounting concern that the extensive isolation of salmonid populations in fragmented habitats is reducing their resiliency to fire. In spite of this concern, there are few direct observations of salmonid responses to fire. In fact, guidance is based largely on a broader understanding of the influences of landscape structure and disturbance in general on salmonid fishes, and there is considerable uncertainty about how best to manage for salmonid resilience to wildfire. Studies are limited by the difficult logistics of following fish responses in the face of unpredictable events such as wildfires. Therefore, BACI (Before-After-Control-Impact) study designs are nearly impossible, and replication is similarly challenging because fires are often low-frequency events. Furthermore, conventional ecological study approaches (e.g., studies of fish distribution, abundance, life histories, and movement) are logistically difficult to implement. Overall, a major challenge to understanding resilience of salmonid populations in fire-prone environments is related to moving beyond localized case studies to those with broader applicability in wildfire management . Genetic data can be

  14. Expanding the repertoire of microsatellite markers for polymorphism studies in Indian accessions of mung bean (Vigna radiata L. Wilczek).

    Science.gov (United States)

    Shrivastava, Divya; Verma, Priyanka; Bhatia, Sabhyata

    2014-09-01

    Limited availability of validated, polymorphic microsatellite markers in mung bean (Vigna radiata), an important food legume of India, has been a major hurdle towards its improvement and higher yield. The present study was undertaken in order to develop a new set of microsatellite markers and utilize them for the analysis of genetic diversity within mung bean accessions from India. A GA/CT enriched library was constructed from V. radiata which resulted in 1,250 putative recombinant clones of which 850 were sequenced. SSR motifs were identified and their flanking sequences were utilized to design 328 SSR primer pairs. Of these, 48 SSR markers were employed for assessing genetic diversity among 76 mung bean accessions from various geographical locations in India. Two hundred and thirty four alleles with an average of 4.85 alleles per locus were detected at 48 loci. The polymorphic information content (PIC) per locus varied from 0.1 to 0.88 (average: 0.49 per locus). The observed and expected heterozygosities ranged from 0.40 to 0.95 and 0.40 to 0.81 respectively. Based on Jaccard's similarity matrix, a dendrogram was constructed using the unweighted pair-group method with arithmetic averages (UPGMA) analysis which revealed that one accession from Bundi, Rajasthan was clustered out separately while remaining accessions were grouped into two major clusters. The markers generated in this study will help in expanding the repertoire of the available SSR markers thereby facilitating analysis of genetic diversity, molecular mapping and ultimately broadening the scope for genetic improvement of this legume.

  15. Precarious Voices? Types of “Political Citizens” and Repertoires of Action among European Youth

    Directory of Open Access Journals (Sweden)

    Lara Monticelli

    2017-01-01

    Full Text Available This article’s goal is to explore the existence of ‘political citizens’ profiles across three European cities (Turin, Cologne and Lyon and to ascertain the role of an unstable occupational status on the repertoires of action deployed. For this purpose, a technique called latent class cluster analysis (LCCA is applied to a large sample, including young precarious and regular workers (deployed as a reference group. This technique allowed us to derive five descriptive probabilistic profiles of ‘political citizens’ and their repertoires of action in each city. The empirical findings underline the emergence of hybrid repertoires of action together with ‘single-issue’ or ‘cause-oriented’ forms of political participation. This study represents an attempt to encourage the dialogue between two strands of research in social sciences, namely sociology of work and political participation and to foster the formation of an innovative research agenda crossing these two fields.

  16. Identification of a bitter-taste receptor gene repertoire in different Lagomorphs species

    Directory of Open Access Journals (Sweden)

    Ana M. Ferreira

    2016-04-01

    Full Text Available The repertoires of bitter taste receptor (T2R gene have been described for several animal species, but these data are still scarce for Lagomorphs. The aim of the present work is to identify potential repertoires of T2R in several Lagomorph species, covering a wide geographical distribution. We studied these genes in Lepus timidus, Lepus europaeus, Oryctolagus cuniculus algirus, Romerolagus diazi and Sylvilagus floridanus, using Oryctolagus cuniculus cuniculus as control species for PCR and DNA sequencing. We studied the identities of the DNA sequences and built the corresponding phylogenetic tree. Sequencing was successful for both subspecies of Oryctolagus cuniculus for all T2R genes studied, for five genes in Lepus, and for three genes in Romerolagus diazi and Sylvilagus floridanus. We describe for the first time the partial repertoires of T2R genes for Lagomorphs species, other than the common rabbit. Our phylogenetic analyses indicate that sequence proximity levels follow the established taxonomic classification.

  17. Rules of song development and their use in vocal interactions by birds with large repertoires.

    Science.gov (United States)

    Geberzahn, Nicole; Hultsch, Henrike

    2004-06-01

    Songbirds are well known for settling their disputes by vocal signals, and their singing plays a dominant role. Most studies on this issue have concentrated on bird species that develop and use small vocal repertoires. In this article we will go farther and focus on examples of how species with large song repertoires make use of their vocal competence. In particular, we will outline the study of interaction rules which have been elucidated by examining time- and pattern-specific relationships between signals exchanged by territorial neighbors. First we present an inquiry into the rules of song learning and development. In birds with large song repertoires, the ontogeny of such rules proceeds along a number of trajectories which help in understanding the often remarkable accomplishments of adult birds. In both approaches, our model species will be the Common Nightingale Luscinia megarhynchos that has been investigated intensively in the field and in the laboratory.

  18. Population dynamics and genetic diversity of C4 strains of human enterovirus 71 in Mainland China, 1998-2010.

    Directory of Open Access Journals (Sweden)

    Dawei Guan

    Full Text Available BACKGROUND: Since 1997, several countries within the Asian Pacific region have been affected by one or more massive outbreaks of Hand Foot and Mouth Disease (HFMD. Virus typing experiments revealed that these outbreaks were caused by strains of human enterovirus 71 (EV71 belonging to several different, recently emerged subgenogroups. In mainland China, a different situation was observed. The first outbreak, localized in Shangdong Province, was reported in 2007, and was followed by a wide-spread outbreak in mainland China in 2008. Since then, numbers of reported HFMD cases have been persistently high. METHODOLOGY/PRINCIPAL FINDINGS: To gain insight in the epidemiological behavior of EV71 in China, we studied genetic diversity and EV71 population dynamics to address whether the increase in number of reported EV71 infections reflects a real increase in viral spread or is just the result of increased awareness and surveillance. We used systematically collected VP1 gene sequences of 257 EV71 strains collected in Guangdong province from 2008 to 2010 as part of HFMD surveillance activities, and supplemented them with 305 GenBank EV71 reference stains collected in China from 1998 to 2010. All isolates from Guangdong Province belonged to subgenogroup C4. Viral population dynamics indicated that the increased reporting of HFMD in China since 2007 reflects a real increase in viral spread and continued replacement of viral lineages through time. Amino acid sequence comparisons revealed substitution of amino acid in residues 22, 145 and 289 through time regularly with the VP1 gene of EV71 strains isolated in mainland China from 1998 to 2010. CONCLUSIONS: EV71 strains isolated in mainland China mainly belonged to subgenogroup C4. There was exponential growth of the EV71 virus population in 2007 and 2008. There was amino acid substitution through time regularly with the VP1 gene which possibly increased viral spread and/or ability of the virus to circulate

  19. Diversification of the Primary Antibody Repertoire by AID-Mediated Gene Conversion.

    Science.gov (United States)

    Lanning, Dennis K; Knight, Katherine L

    2015-01-01

    Gene conversion, mediated by activation-induced cytidine deaminase (AID), has been found to contribute to generation of the primary antibody repertoire in several vertebrate species. Generation of the primary antibody repertoire by gene conversion of immunoglobulin (Ig) genes occurs primarily in gut-associated lymphoid tissues (GALT) and is best described in chicken and rabbit. Here, we discuss current knowledge of the mechanism of gene conversion as well as the contribution of the microbiota in promoting gene conversion of Ig genes. Finally, we propose that the antibody diversification strategy used in GALT species, such as chicken and rabbit, is conserved in a subset of human and mouse B cells.

  20. Improving the Penetration of Wind Power with Dynamic Thermal Rating System, Static VAR Compensator and Multi-Objective Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Jiashen Teh

    2018-04-01

    Full Text Available The integration of renewable energy sources, especially wind energy, has been on the rise throughout power systems worldwide. Due to this relatively new introduction, the integration of wind energy is often not optimized. Moreover, owing to the technical constraints and transmission congestions of the power network, most of the wind energy has to be curtailed. Due to various factors that influence the connectivity of wind energy, this paper proposes a well-organized posterior multi-objective (MO optimization algorithm for maximizing the connections of wind energy. In this regard, the dynamic thermal rating (DTR system and the static VAR compensator (SVC have been identified as effective tools for improving the loadability of the network. The propose MO algorithm in this paper aims to minimize: (1 wind energy curtailment, (2 operation cost of the network considering all investments and operations, also known as the total social cost, and (3 SVC operation cost. The proposed MO problem was solved using the non-dominated sorting genetic algorithm (NSGA II and it was tested on the modified IEEE reliability test system (IEEE-RTS. The results demonstrate the applicability of the proposed algorithm in aiding power system enhancement planning for integrating wind energy.

  1. DMPD: Genetic regulation of macrophage priming/activation: the Lsh gene story. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 1757110 Genetic regulation of macrophage priming/activation: the Lsh gene story. Bl... (.svg) (.html) (.csml) Show Genetic regulation of macrophage priming/activation: the Lsh gene story. Pubmed...ID 1757110 Title Genetic regulation of macrophage priming/activation: the Lsh gen

  2. Dynamic genetic conservation in the presence of invasive insect and pathogen threats to forest tree species of the United States

    Science.gov (United States)

    J.L. Koch; R.A. Sniezko

    2017-01-01

    Ex-situ genetic conservation focused on collection and storage of seed can play an important role in conserving the genetic diversity of species under grave threat by biotic organisms or a changing climate. However, ex-situ genetic conservation is primarily a static activity and does not allow for evolution of the species under a continuing,...

  3. Dynamics of genetic variation at gliadin-coding loci in bread wheat cultivars developed in small grains research center (Kragujevac during last 35 years

    Directory of Open Access Journals (Sweden)

    Novosljska-Dragovič Aleksandra

    2005-01-01

    Full Text Available Multiple alleles of gliadin-coding loci are well-known genetic markers of common wheat genotypes. Based on analysis of gliadin patterns in common wheat cultivars developed at the Small Grains Research Center in Kragujevac dynamics of genetic variability at gliadin-coding loci has been surveyed for the period of 35 years. It was shown that long-term breeding of the wheat cultivars involved gradual replacement of ancient alleles for those widely spread in some regions in the world, which belong to well-known cultivars-donor of some important traits. Developing cultivars whose pedigree involved much new foreign genetic material has increased genetic diversity as well as has changed frequency of alleles of gliadin-coding loci. So we can conclude that the genetic profile of modern Serbian cultivars has changed considerably. Genetic formula of gliadin was made for each the cultivar studied. The most frequent alleles of gliadin-coding loci among modern cultivars should be of great interest of breeders because these alleles are probably linked with genes that confer advantage to their carriers at present.

  4. Strategies for B-cell receptor repertoire analysis in primary immunodeficiencies: From severe combined immunodeficiency to common variable immunodeficiency

    NARCIS (Netherlands)

    H. IJspeert (Hanna); M. Wentink (Marjolein); D. van Zessen (David); G.J.A. Driessen (Gertjan); V.A.S.H. Dalm (Virgil); M.P. van Hagen (Martin); I. Pico-Knijnenburg (Ingrid); E.J. Simons (Erik J.); J.J.M. van Dongen (Jacques); A. Stubbs (Andrew); M. van der Burg (Mirjam)

    2015-01-01

    textabstractThe antigen receptor repertoires of B- and T-cells form the basis of the adaptive immune response. The repertoires should be sufficiently diverse to recognize all possible pathogens. However, careful selection is needed to prevent responses to self or harmless antigens. Limited antigen

  5. A dynamic genetic-hormonal regulatory network model explains multiple cellular behaviors of the root apical meristem of Arabidopsis thaliana.

    Science.gov (United States)

    García-Gómez, Mónica L; Azpeitia, Eugenio; Álvarez-Buylla, Elena R

    2017-04-01

    The study of the concerted action of hormones and transcription factors is fundamental to understand cell differentiation and pattern formation during organ development. The root apical meristem of Arabidopsis thaliana is a useful model to address this. It has a stem cell niche near its tip conformed of a quiescent organizer and stem or initial cells around it, then a proliferation domain followed by a transition domain, where cells diminish division rate before transiting to the elongation zone; here, cells grow anisotropically prior to their final differentiation towards the plant base. A minimal model of the gene regulatory network that underlies cell-fate specification and patterning at the root stem cell niche was proposed before. In this study, we update and couple such network with both the auxin and cytokinin hormone signaling pathways to address how they collectively give rise to attractors that correspond to the genetic and hormonal activity profiles that are characteristic of different cell types along A. thaliana root apical meristem. We used a Boolean model of the genetic-hormonal regulatory network to integrate known and predicted regulatory interactions into alternative models. Our analyses show that, after adding some putative missing interactions, the model includes the necessary and sufficient components and regulatory interactions to recover attractors characteristic of the root cell types, including the auxin and cytokinin activity profiles that correlate with different cellular behaviors along the root apical meristem. Furthermore, the model predicts the existence of activity configurations that could correspond to the transition domain. The model also provides a possible explanation for apparently paradoxical cellular behaviors in the root meristem. For example, how auxin may induce and at the same time inhibit WOX5 expression. According to the model proposed here the hormonal regulation of WOX5 might depend on the cell type. Our results

  6. A dynamic genetic-hormonal regulatory network model explains multiple cellular behaviors of the root apical meristem of Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Mónica L García-Gómez

    2017-04-01

    Full Text Available The study of the concerted action of hormones and transcription factors is fundamental to understand cell differentiation and pattern formation during organ development. The root apical meristem of Arabidopsis thaliana is a useful model to address this. It has a stem cell niche near its tip conformed of a quiescent organizer and stem or initial cells around it, then a proliferation domain followed by a transition domain, where cells diminish division rate before transiting to the elongation zone; here, cells grow anisotropically prior to their final differentiation towards the plant base. A minimal model of the gene regulatory network that underlies cell-fate specification and patterning at the root stem cell niche was proposed before. In this study, we update and couple such network with both the auxin and cytokinin hormone signaling pathways to address how they collectively give rise to attractors that correspond to the genetic and hormonal activity profiles that are characteristic of different cell types along A. thaliana root apical meristem. We used a Boolean model of the genetic-hormonal regulatory network to integrate known and predicted regulatory interactions into alternative models. Our analyses show that, after adding some putative missing interactions, the model includes the necessary and sufficient components and regulatory interactions to recover attractors characteristic of the root cell types, including the auxin and cytokinin activity profiles that correlate with different cellular behaviors along the root apical meristem. Furthermore, the model predicts the existence of activity configurations that could correspond to the transition domain. The model also provides a possible explanation for apparently paradoxical cellular behaviors in the root meristem. For example, how auxin may induce and at the same time inhibit WOX5 expression. According to the model proposed here the hormonal regulation of WOX5 might depend on the cell

  7. Neoantigen landscape dynamics during human melanoma-T cell interactions

    DEFF Research Database (Denmark)

    Verdegaal, Els M. E.; De Miranda, Noel F. C. C.; Visser, Marten

    2016-01-01

    Recognition of neoantigens that are formed as a consequence of DNA damage is likely to form a major driving force behind the clinical activity of cancer immunotherapies such as T-cell checkpoint blockade and adoptive T-cell therapy. Therefore, strategies to selectively enhance T-cell reactivity...... against genetically defined neoantigens are currently under development. In mouse models, T-cell pressure can sculpt the antigenicity of tumours, resulting in the emergence of tumours that lack defined mutant antigens. However, whether the T-cell-recognized neoantigen repertoire in human cancers...... by overall reduced expression of the genes or loss of the mutant alleles. Notably, loss of expression of T-cell-recognized neoantigens was accompanied by development of neoantigen-specific T-cell reactivity in tumour-infiltrating lymphocytes. These data demonstrate the dynamic interactions between cancer...

  8. Investigating the Genetic Diversity, Population Differentiation and Population Dynamics of Cycas segmentifida (Cycadaceae Endemic to Southwest China by Multiple Molecular Markers

    Directory of Open Access Journals (Sweden)

    Xiuyan Feng

    2017-05-01

    Full Text Available Climate change, species dispersal ability and habitat fragmentation are major factors influencing species distribution and genetic diversity, especially for the range-restricted and threatened taxa. Here, using four sequences of chloroplast DNAs (cpDNAs, three nuclear genes (nDNAs and 12 nuclear microsatellites (SSRs, we investigated the genetic diversity, genetic structure, divergence time and population dynamics of Cycas segmentifida D. Y. Wang and C. Y. Deng, a threatened cycad species endemic to Southwest China. High levels of genetic diversity and genetic differentiation were revealed in C. segmentifida. Haplotypes of networks showed two evolutionary units in C. segmentifida, with the exception of the nuclear gene GTP network. Meanwhile, the UPGMA tree, structure and PCoA analyses suggested that 14 populations of C. segmentifida were divided into two clades. There was significant effect of isolation by distance (IBD in this species. However, this species did not display a significant phylogeographic structure. The divergence time estimation suggested that its haplotypes diverged during the Middle Pleistocene. Additionally, the population dynamics inferred from different DNA sequences analyses were discordant. Bottleneck analysis showed that populations of C. segmentifida did not experience any recent bottleneck effect, but rather pointed to a contraction of its effective population size over time. Furthermore, our results suggested that the population BM which held an intact population structure and occupied undisturbed habitat was at the Hardy–Weinberg equilibrium, implying that this population is a free-mating system. These genetic features provide important information for the sustainable management of C. segmentifida.

  9. Emotional Intelligence and the Conflict Resolution Repertoire of Couples in Tertiary Institutions in Imo State

    Science.gov (United States)

    Nnodum, B. I.; Ugwuegbulam, C. N.; Agbaenyi, I. G.

    2016-01-01

    This study is a descriptive survey that investigated the relationship between emotional intelligence and conflict resolution repertoire of couples in tertiary institutions. A sample of 250 married people were drawn from the population of couples in tertiary institutions in Imo State. Two researcher made and validated instruments were used in…

  10. Comprehensive assessment of peripheral blood TCRβ repertoire in infectious mononucleosis and chronic active EBV infection patients.

    Science.gov (United States)

    Liu, Shenglin; Zhang, Qian; Huang, Dongli; Zhang, Wenli; Zhong, Fengluan; Feng, Jia; Chen, Xueru; Meng, Qingxiang; Chen, Xiaofan; Zhang, Wei; Zhang, Hongyu

    2017-04-01

    Epstein-Barr virus (EBV) primary infection is usually asymptomatic, but it sometimes progresses to infectious mononucleosis (IM). Occasionally, some people develop chronic active EBV infection (CAEBV) with underlying immunodeficiency, which belongs to a continuous spectrum of EBV-associated lymphoproliferative disorders (EBV + LPD) with heterogeneous clinical presentations and high mortality. It has been well established that T cell-mediated immune response plays a critical role in the disease evolution of EBV infection. Recently, high-throughput sequencing of the hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (T cell receptor β (TCRβ)) has emerged as a sensitive approach to assess the T cell repertoire. In this study, we fully characterized the diversity of peripheral blood TCRβ repertoire in IM (n = 6) and CAEBV patients (n = 5) and EBV-seropositive controls (n = 5). Compared with the healthy EBV-seropositive controls, both IM and CAEBV patients demonstrate a significant decrease in peripheral blood TCRβ repertoire diversity, basically, including narrowed repertoire breadth, highly expanded clones, and skewed CDR3 length distribution. However, there is no significant difference between IM and CAEBV patients. Furthermore, we observed some disease-related preferences in TRBV/TRBJ usage and combinations, as well as lots of T cell clones shared by different groups (unique or overlapped) involved in public T cell responses, which provide more detailed insights into the divergent disease evolution.

  11. Repertoires, Characters and Scenes: Sociolinguistic Difference in Turkish-German Comedy

    Science.gov (United States)

    Androutsopoulos, Jannis

    2012-01-01

    This paper examines representations of sociolinguistic difference in a German "ethnic comedy" as a means to contribute to a framework for the sociolinguistic study of film. Three levels of analysis of sociolinguistic difference in film are distinguished: repertoire analysis reconstructs the entirety of codes used in a film and their…

  12. Effects of spaceflight on the immunoglobulin repertoire of unimmunized C57BL/6 mice

    Science.gov (United States)

    Ward, Claire; Rettig, Trisha A.; Hlavacek, Savannah; Bye, Bailey A.; Pecaut, Michael J.; Chapes, Stephen K.

    2018-02-01

    Spaceflight has been shown to suppress the adaptive immune response, altering the distribution and function of lymphocyte populations. B lymphocytes express highly specific and highly diversified receptors, known as immunoglobulins (Ig), that directly bind and neutralize pathogens. Ig diversity is achieved through the enzymatic splicing of gene segments within the genomic DNA of each B cell in a host. The collection of Ig specificities within a host, or Ig repertoire, has been increasingly characterized in both basic research and clinical settings using high-throughput sequencing technology (HTS). We utilized HTS to test the hypothesis that spaceflight affects the B-cell repertoire. To test this hypothesis, we characterized the impact of spaceflight on the unimmunized Ig repertoire of C57BL/6 mice that were flown aboard the International Space Station (ISS) during the Rodent Research One validation flight in comparison to ground controls. Individual gene segment usage was similar between ground control and flight animals, however, gene segment combinations and the junctions in which gene segments combine was varied among animals within and between treatment groups. We also found that spontaneous somatic mutations in the IgH and Igκ gene loci were not increased. These data suggest that space flight did not affect the B cell repertoire of mice flown and housed on the ISS over a short period of time.

  13. Discrete Emotion Regulation Strategy Repertoires and Parasympathetic Physiology Characterize Psychopathology Symptoms in Childhood

    Science.gov (United States)

    Quiñones-Camacho, Laura E.; Davis, Elizabeth L.

    2018-01-01

    Certain psychopathologies are often linked to dysregulation of specific emotions (e.g., anxiety is associated with dysregulation of fear), but few studies have examined how regulatory repertoires for specific emotions (e.g., the strategies a person uses to regulate fear) relate to psychopathology, and fewer still have examined this in childhood. A…

  14. Leisure repertoire among persons with a spinal cord injury: Interests, performance, and well-being

    Science.gov (United States)

    Lundström, Ulrica; Lilja, Margareta; Petersson, Ingela; Lexell, Jan; Isaksson, Gunilla

    2014-01-01

    Objective To explore and describe the leisure repertoire of persons with traumatic spinal cord injury (SCI) and how the repertoire is related to interest, performance, and well-being. Design Cross-sectional study. Setting A total of 97 persons with traumatic SCI were recruited from the non-profit national organization, RG Active Rehabilitation in Sweden. Outcome measure Data were collected through a two-part postal survey. The first comprised of questions investigating socio-demographic variables and injury characteristics; the second part included an interest checklist with 20 areas of leisure activities. Results The participants were mostly interested in, performed, and experienced well-being from social and culture activities and TV/DVD/movies. The areas of leisure activities in which they had most likely experienced changes after the SCI were outdoor activities, exercise, and gardening. Sex, age, and to some extent, time since injury were related to interest, performance, well-being, and changed performance. Conclusions The results provided an explanation and limited description of a changed leisure repertoire among persons after a traumatic SCI. The study showed that sex, age, and time since injury were more closely related to the choice of leisure activities to include in the leisure repertoire than the level of injury. This knowledge can be of importance when professionals in the field of rehabilitation are planning and implementing interventions concerning leisure activities for persons with SCI. PMID:24090284

  15. Expressed var gene repertoire and variant surface antigen diversity in a shrinking Plasmodium falciparum population.

    Science.gov (United States)

    Carlos, Bianca C; Fotoran, Wesley L; Menezes, Maria J; Cabral, Fernanda J; Bastos, Marcele F; Costa, Fabio T M; Sousa-Neto, Jayme A; Ribolla, Paulo E M; Wunderlich, Gerhard; Ferreira, Marcelo U

    2016-11-01

    The var gene-encoded erythrocyte membrane protein-1 of Plasmodium falciparum (PfEMP-1) is the main variant surface antigen (VSA) expressed on infected erythrocytes. The rate at which antibody responses to VSA expressed by circulating parasites are acquired depends on the size of the local VSA repertoire and the frequency of exposure to new VSA. Because parasites from areas with declining malaria endemicity, such as the Amazon, typically express a restricted PfEMP-1 repertoire, we hypothesized that Amazonians would rapidly acquire antibodies to most locally circulating VSA. Consistent with our expectations, the analysis of 5878 sequence tags expressed by 10 local P. falciparum samples revealed little PfEMP-1 DBL1α domain diversity. Among the most commonly expressed DBL1α types, 45% were shared by two or more independent parasite lines. Nevertheless, Amazonians displayed major gaps in their repertoire of anti-VSA antibodies, although the breadth of anti-VSA antibody responses correlated positively with their cumulative exposure to malaria. We found little antibody cross-reactivity even when testing VSA from related parasites expressing the same dominant DBL1α types. We conclude that variant-specific immunity to P. falciparum VSAs develops slowly despite the relatively restricted PfEMP-1 repertoire found in low-endemicity settings. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. The Effects of Multiple Exemplar Instruction on the Relation between Listener and Intraverbal Categorization Repertoires

    Science.gov (United States)

    Lechago, Sarah A.; Carr, James E.; Kisamore, April N.; Grow, Laura L.

    2015-01-01

    We evaluated the effects of multiple exemplar instruction (MEI) on the relation between listener and intraverbal categorization repertoires of six typically developing preschool-age children using a nonconcurrent multiple-probe design across participants. After failing to emit intraverbal categorization responses following listener categorization…

  17. Sustained multiplicity in everyday cholesterol reduction: repertoires and practices in talk about 'healthy living'.

    Science.gov (United States)

    Will, Catherine M; Weiner, Kate

    2014-02-01

    This article is concerned with talk about and the practices of healthy living in relation to cholesterol reduction. It draws on qualitative interviews with 89 people who are current or former users of either cholesterol-lowering functional foods or statins for cardiovascular risk reduction. Focusing on data about everyday activities including food preparation, shopping and exercise, we illustrate four repertoires that feature in talk about cholesterol reduction (health, pleasure, sociality and pragmatism). Using Gilbert and Mulkay's notion of a 'reconciliation device', we suggest ways in which apparently contradictory repertoires are combined (for example, through talk about moderation) or kept apart. We suggest that, in contrast to the interactiveness of the repertoires of health and pleasure, a pragmatic repertoire concerning food provisioning, storage and cooking as well as the realities of exercise, appears distinct from talk about health and is relatively inert. Finally we consider the implications of these discursive patterns for daily practices. Our data suggest there is little emphasis on coherence in people's practices and illustrate the significance of temporal, spatial and social distribution in allowing people to pursue different priorities in their everyday lives. Rather than the calculated trade-offs of earlier medical sociology we draw on Mol to foreground the possibility of sustained multiplicity in daily practices. © 2014 The Authors. Sociology of Health & Illness © 2014 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.

  18. Mother-Newborn Pairs in Malawi Have Similar Antibody Repertoires to Diverse Malaria Antigens.

    Science.gov (United States)

    Boudová, Sarah; Walldorf, Jenny A; Bailey, Jason A; Divala, Titus; Mungwira, Randy; Mawindo, Patricia; Pablo, Jozelyn; Jasinskas, Algis; Nakajima, Rie; Ouattara, Amed; Adams, Matthew; Felgner, Philip L; Plowe, Christopher V; Travassos, Mark A; Laufer, Miriam K

    2017-10-01

    Maternal antibodies may play a role in protecting newborns against malaria disease. Plasmodium falciparum parasite surface antigens are diverse, and protection from infection requires allele-specific immunity. Although malaria-specific antibodies have been shown to cross the placenta, the extent to which antibodies that respond to the full repertoire of diverse antigens are transferred from the mother to the infant has not been explored. Understanding the breadth of maternal antibody responses and to what extent these antibodies are transferred to the child can inform vaccine design and evaluation. We probed plasma from cord blood and serum from mothers at delivery using a customized protein microarray that included variants of malaria vaccine target antigens to assess the intensity and breadth of seroreactivity to three malaria vaccine candidate antigens in mother-newborn pairs in Malawi. Among the 33 paired specimens that were assessed, mothers and newborns had similar intensity and repertoire of seroreactivity. Maternal antibody levels against vaccine candidate antigens were the strongest predictors of infant antibody levels. Placental malaria did not significantly impair transplacental antibody transfer. However, mothers with placental malaria had significantly higher antibody levels against these blood-stage antigens than mothers without placental malaria. The repertoire and levels of infant antibodies against a wide range of malaria vaccine candidate antigen variants closely mirror maternal levels in breadth and magnitude regardless of evidence of placental malaria. Vaccinating mothers with an effective malaria vaccine during pregnancy may induce high and potentially protective antibody repertoires in newborns. Copyright © 2017 American Society for Microbiology.

  19. Distribution and development of the postnatal murine V delta 1 T-cell receptor repertoire

    Czech Academy of Sciences Publication Activity Database

    Holtmeier, W.; Gille, J.; Zeuzem, S.; Šinkora, Marek

    2010-01-01

    Roč. 131, č. 2 (2010), s. 192-201 ISSN 0019-2805 R&D Projects: GA ČR GA524/07/0087 Institutional research plan: CEZ:AV0Z50200510 Keywords : gene rearrangement * repertoire development * rodent Subject RIV: EE - Microbiology, Virology Impact factor: 3.302, year: 2010

  20. Leisure repertoire among persons with a spinal cord injury: interests, performance, and well-being.

    Science.gov (United States)

    Lundström, Ulrica; Lilja, Margareta; Petersson, Ingela; Lexell, Jan; Isaksson, Gunilla

    2014-03-01

    To explore and describe the leisure repertoire of persons with traumatic spinal cord injury (SCI) and how the repertoire is related to interest, performance, and well-being. Cross-sectional study. A total of 97 persons with traumatic SCI were recruited from the non-profit national organization, RG Active Rehabilitation in Sweden. Data were collected through a two-part postal survey. The first comprised of questions investigating socio-demographic variables and injury characteristics; the second part included an interest checklist with 20 areas of leisure activities. The participants were mostly interested in, performed, and experienced well-being from social and culture activities and TV/DVD/movies. The areas of leisure activities in which they had most likely experienced changes after the SCI were outdoor activities, exercise, and gardening. Sex, age, and to some extent, time since injury were related to interest, performance, well-being, and changed performance. The results provided an explanation and limited description of a changed leisure repertoire among persons after a traumatic SCI. The study showed that sex, age, and time since injury were more closely related to the choice of leisure activities to include in the leisure repertoire than the level of injury. This knowledge can be of importance when professionals in the field of rehabilitation are planning and implementing interventions concerning leisure activities for persons with SCI.

  1. Impaired recovery of syllable repertoires after unilateral lesions of the HVC of male domesticated canaries.

    NARCIS (Netherlands)

    Halle, F; Gahr, M.; Kreutzer, M.

    2003-01-01

    Particular features of the song of adult male canaries such as a large syllable repertoire resulting in a great diversity of song phrases and special so-called 'complex' syllables enhance various features of female reproductive behaviour. These features are produced in a species or strain dependent

  2. Co-regulation of a large and rapidly evolving repertoire of odorant receptor genes

    Directory of Open Access Journals (Sweden)

    Lane Robert P

    2007-09-01

    Full Text Available Abstract The olfactory system meets niche- and species-specific demands by an accelerated evolution of its odorant receptor repertoires. In this review, we describe evolutionary processes that have shaped olfactory and vomeronasal receptor gene families in vertebrate genomes. We emphasize three important periods in the evolution of the olfactory system evident by comparative genomics: the adaptation to land in amphibian ancestors, the decline of olfaction in primates, and the delineation of putative pheromone receptors concurrent with rodent speciation. The rapid evolution of odorant receptor genes, the sheer size of the repertoire, as well as their wide distribution in the genome, presents a developmental challenge: how are these ever-changing odorant receptor repertoires coordinated within the olfactory system? A central organizing principle in olfaction is the specialization of sensory neurons resulting from each sensory neuron expressing only ~one odorant receptor allele. In this review, we also discuss this mutually exclusive expression of odorant receptor genes. We have considered several models to account for co-regulation of odorant receptor repertoires, as well as discussed a new hypothesis that invokes important epigenetic properties of the system.

  3. Population genetics of the invasive ctenophore Mnemiopsis leidyi in Europe reveal source-sink dynamics and secondary dispersal to the Mediterranean Sea

    DEFF Research Database (Denmark)

    Bolte, Sören; Fuentes, Veronica; Haslob, Holger

    2013-01-01

    Repeated invasions of European waters by the ctenophore Mnemiopsis leidyi offer a unique opportunity to study population dynamics and dispersal in gelatinous zooplankton. Here we followed population establishment in two recently invaded areas, the North and Baltic Sea, and analysed changes...... maintained their allelic composition with virtually unchanged levels of genetic diversity and between-population differentiation. This demonstrates that gene flow between the two regions was limited and indicates successful reproduction in both areas. In contrast, at the eastern distribution limit...

  4. Dynamics of energy transfer from lycopene to bacteriochlorophyll in genetically-modified LH2 complexes of Rhodobacter sphaeroides.

    Science.gov (United States)

    Hörvin Billsten, H; Herek, J L; Garcia-Asua, G; Hashøj, L; Polívka, T; Hunter, C N; Sundström, V

    2002-03-26

    LH2 complexes from Rb. sphaeroides were modified genetically so that lycopene, with 11 saturated double bonds, replaced the native carotenoids which contain 10 saturated double bonds. Tuning the S1 level of the carotenoid in LH2 in this way affected the dynamics of energy transfer within LH2, which were investigated using both steady-state and time-resolved techniques. The S1 energy of lycopene in n-hexane was determined to be approximately 12 500 +/- 150 cm(-1), by direct measurement of the S1-S2 transient absorption spectrum using a femtosecond IR-probing technique, thus placing an upper limit on the S1 energy of lycopene in the LH2 complex. Fluorescence emission and excitation spectra demonstrated that energy can be transferred from lycopene to the bacteriochlorophyll molecules within this LH2 complex. The energy-transfer dynamics within the mutant complex were compared to wild-type LH2 from Rb. sphaeroides containing the carotenoid spheroidene and from Rs. molischianum, in which lycopene is the native carotenoid. The results show that the overall efficiency for Crt --> B850 energy transfer is approximately 80% in lyco-LH2 and approximately 95% in WT-LH2 of Rb. sphaeroides. The difference in overall Crt --> BChl transfer efficiency of lyco-LH2 and WT-LH2 mainly relates to the low efficiency of the Crt S(1) --> BChl pathway for complexes containing lycopene, which was 20% in lyco-LH2. These results show that in an LH2 complex where the Crt S1 energy is sufficiently high to provide efficient spectral overlap with both B800 and B850 Q(y) states, energy transfer via the Crt S1 state occurs to both pigments. However, the introduction of lycopene into the Rb. sphaeroides LH2 complex lowers the S1 level of the carotenoid sufficiently to prevent efficient transfer of energy to the B800 Q(y) state, leaving only the Crt S1 --> B850 channel, strongly suggesting that Crt S1 --> BChl energy transfer is controlled by the relative Crt S1 and BChl Q(y) energies.

  5. Genetic algorithm-based fuzzy-PID control methodologies for enhancement of energy efficiency of a dynamic energy system

    International Nuclear Information System (INIS)

    Jahedi, G.; Ardehali, M.M.

    2011-01-01

    The simplicity in coding the heuristic judgment of experienced operator by means of fuzzy logic can be exploited for enhancement of energy efficiency. Fuzzy logic has been used as an effective tool for scheduling conventional PID controllers gain coefficients (F-PID). However, to search for the most desirable fuzzy system characteristics that allow for best performance of the energy system with minimum energy input, optimization techniques such as genetic algorithm (GA) could be utilized and the control methodology is identified as GA-based F-PID (GA-F-PID). The objective of this study is to examine the performance of PID, F-PID, and GA-F-PID controllers for enhancement of energy efficiency of a dynamic energy system. The performance evaluation of the controllers is accomplished by means of two cost functions that are based on the quadratic forms of the energy input and deviation from a setpoint temperature, referred to as energy and comfort costs, respectively. The GA-F-PID controller is examined in two different forms, namely, global form and local form. For the global form, all possible combinations of fuzzy system characteristics in the search domain are explored by GA for finding the fittest chromosome for all discrete time intervals during the entire operation period. For the local form, however, GA is used in each discrete time interval to find the fittest chromosome for implementation. The results show that the global form GA-F-PID and local form GA-F-PID control methodologies, in comparison with PID controller, achieve higher energy efficiency by lowering energy costs by 51.2%, and 67.8%, respectively. Similarly, the comfort costs for deviation from setpoint are enhanced by 54.4%, and 62.4%, respectively. It is determined that GA-F-PID performs better in local from than global form.

  6. Dynamic interaction between fetal adversity and a genetic score reflecting dopamine function on developmental outcomes at 36 months.

    Directory of Open Access Journals (Sweden)

    Adrianne R Bischoff

    Full Text Available Fetal adversity, evidenced by poor fetal growth for instance, is associated with increased risk for several diseases later in life. Classical cut-offs to characterize small (SGA and large for gestational age (LGA newborns are used to define long term vulnerability. We aimed at exploring the possible dynamism of different birth weight cut-offs in defining vulnerability in developmental outcomes (through the Bayley Scales of Infant and Toddler Development, using the example of a gene vs. fetal adversity interaction considering gene choices based on functional relevance to the studied outcome.36-month-old children from an established prospective birth cohort (Maternal Adversity, Vulnerability, and Neurodevelopment were classified according to birth weight ratio (BWR (SGA ≤0.85, LGA >1.15, exploring a wide range of other cut-offs and genotyped for polymorphisms associated with dopamine signaling (TaqIA-A1 allele, DRD2-141C Ins/Ins, DRD4 7-repeat, DAT1-10- repeat, Met/Met-COMT, composing a score based on the described function, in which hypofunctional variants received lower scores.There were 251 children (123 girls and 128 boys. Using the classic cut-offs (0.85 and 1.15, there were no statistically significant interactions between the neonatal groups and the dopamine genetic score. However, when changing the cut-offs, it is possible to see ranges of BWR that could be associated with vulnerability to poorer development according to the variation in the dopamine function.The classic birth weight cut-offs to define SGA and LGA newborns should be seen with caution, as depending on the outcome in question, the protocols for long-term follow up could be either too inclusive-therefore most costly, or unable to screen true vulnerabilities-and therefore ineffective to establish early interventions and primary prevention.

  7. IgM repertoire biodiversity is reduced in HIV-1 infection and systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Li eYin

    2013-11-01

    Full Text Available Background: HIV-1 infection or systemic lupus erythematosus [SLE] disrupt B cell homeostasis, reduce memory B cells, and impair function of IgG and IgM antibodies. Objective: To determine how disturbances in B cell populations producing polyclonal antibodies relate to the IgM repertoire, the IgM transcriptome in health and disease was explored at the complementarity determining region 3 [CDRH3] sequence population level. Methods: 454-deep pyrosequencing in combination with a novel analysis pipeline was applied to define populations of IGHM CDRH3 sequences based on absence or presence of somatic hypermutations [SHM] in peripheral blood B cells. Results: HIV or SLE subjects have reduced biodiversity within their IGHM transcriptome compared to healthy subjects, mainly due to a significant decrease in the number of unique combinations of alleles, although recombination machinery was intact. While major differences between sequences without or with SHM occurred among all groups, IGHD and IGHJ allele use, CDRH3 length distribution, or generation of SHM were similar among study cohorts. Antiretroviral therapy failed to normalize IGHM biodiversity in HIV-infected individuals. All subjects had a low frequency of allelic combinations within the IGHM repertoire similar to known broadly-neutralizing HIV-1 antibodies. Conclusions: Polyclonal expansion would decrease overall IgM biodiversity independent of other mechanisms for development of the B cell repertoire. Applying deep sequencing as a strategy to follow development of the IgM repertoire in health and disease provides a novel molecular assessment of multiple points along the B cell differentiation pathway that is highly sensitive for detecting perturbations within the repertoire at the population level.

  8. Dynamic Evolution of Pathogenicity Revealed by Sequencing and Comparative Genomics of 19 Pseudomonas syringae Isolates

    Science.gov (United States)

    Romanchuk, Artur; Chang, Jeff H.; Mukhtar, M. Shahid; Cherkis, Karen; Roach, Jeff; Grant, Sarah R.; Jones, Corbin D.; Dangl, Jeffery L.

    2011-01-01

    Closely related pathogens may differ dramatically in host range, but the molecular, genetic, and evolutionary basis for these differences remains unclear. In many Gram- negative bacteria, including the phytopathogen Pseudomonas syringae, type III effectors (TTEs) are essential for pathogenicity, instrumental in structuring host range, and exhibit wide diversity between strains. To capture the dynamic nature of virulence gene repertoires across P. syringae, we screened 11 diverse strains for novel TTE families and coupled this nearly saturating screen with the sequencing and assembly of 14 phylogenetically diverse isolates from a broad collection of diseased host plants. TTE repertoires vary dramatically in size and content across all P. syringae clades; surprisingly few TTEs are conserved and present in all strains. Those that are likely provide basal requirements for pathogenicity. We demonstrate that functional divergence within one conserved locus, hopM1, leads to dramatic differences in pathogenicity, and we demonstrate that phylogenetics-informed mutagenesis can be used to identify functionally critical residues of TTEs. The dynamism of the TTE repertoire is mirrored by diversity in pathways affecting the synthesis of secreted phytotoxins, highlighting the likely role of both types of virulence factors in determination of host range. We used these 14 draft genome sequences, plus five additional genome sequences previously reported, to identify the core genome for P. syringae and we compared this core to that of two closely related non-pathogenic pseudomonad species. These data revealed the recent acquisition of a 1 Mb megaplasmid by a sub-clade of cucumber pathogens. This megaplasmid encodes a type IV secretion system and a diverse set of unknown proteins, which dramatically increases both the genomic content of these strains and the pan-genome of the species. PMID:21799664

  9. Genetic Differentiation, Isolation-by-Distance, and Metapopulation Dynamics of the Arizona Treefrog (Hyla wrightorum in an Isolated Portion of Its Range.

    Directory of Open Access Journals (Sweden)

    Meryl C Mims

    Full Text Available Population attributes such as diversity, connectivity, and structure are important components of understanding species persistence and vulnerability to extinction. Hyla wrightorum, the Arizona treefrog, is native to the southwestern United States and Mexico, and an isolated group of populations exists in the Huachuca Mountains and Canelo Hills (HMCH of southeastern Arizona, USA. Due to concerns about declining observations of the species within the isolated HMCH portion of its range, the HMCH group is currently a candidate for federal protection under the U.S. Endangered Species Act. We present results of a genetic study examining population diversity, structure, and connectivity within the HMCH region. We sampled DNA from H. wrightorum larvae and adults from ten distinct locations, 8 of which were breeding sites and 4 of which were previously undescribed localities for the species. We developed and genotyped 17 polymorphic microsatellite loci and quantified genetic diversity, population differentiation, and landscape influences on population genetic structure. We found evidence of larger than expected effective population sizes, significant genetic differentiation between populations, and evidence of distance being the primary driver of genetic structure of populations with some influence of slope and canopy cover. We found little evidence of recent genetic bottlenecks, and individual-based analyses indicate admixture between populations despite significant genetic differentiation. These patterns may indicate that the breeding sites within the Huachuca Mountains constitute a metapopulation. We suggest that the HMCH region may contain larger and more connected breeding populations than previously understood, but the dynamics of this system and the limited geographic extent of the HMCH group justify current concern for the persistence of the species in this region. Efforts to ensure availability of high-quality breeding habitats and control for

  10. Simultaneous determination of the repertoire of classical neurotransmitters released from embryonal carcinoma stem cells using online microdialysis coupled with hydrophilic interaction chromatography–tandem mass spectrometry

    International Nuclear Information System (INIS)

    Tang, Ya-Bin; Sun, Fan; Teng, Lin; Li, Wen-Bin; An, Shi-Min; Zhang, Chun; Yang, Xin-Jie; Lv, Hao-Yu; Ding, Xu-Ping; Zhu, Liang

    2014-01-01

    Highlights: • An online MD-HILIC–MS/MS method for simultaneously measuring the repertoire of classical transmitters was developed and validated. • Hydrophilic interaction chromatography (HILIC) was successfully employed to online system. • Stable isotope labeled internal standards and authentic matrix have been applied to guarantee reliable results. • The method features simple procedure (no sample preparation), high recovery (≥73%), high accuracy (89.36% ≤ RE ≤ 116.89%), good reproducibility (2.18% ≤ RSD ≤ 14.56%), and sensitive limits of detection (2 pg for acetylcholine, serotonin, and glutamate, 10 pg for dopamine, norepinephrine, GABA, and glycine). - Abstract: Dynamic, continuous, and simultaneous multi-analysis of transmitters is important for the delineation of the complex interactions between the neuronal and intercellular communications. But the analysis of the whole repertoire of classical transmitters of diverse structure is challenging due to their different physico-chemical properties and to their high polarity feature which leads to poor retention in traditional reversed-phase columns during LC–MS analysis. Here, an online microdialysis coupled with hydrophilic interaction chromatography–tandem mass spectrometry (online MD-HILIC–MS/MS) detection method was developed for the simultaneous measurement of the repertoire of classical transmitters (acetylcholine, serotonin, dopamine, norepinephrine, glutamate, GABA, and glycine). Stable isotope labeled internal standards and authentic matrix have been applied to guarantee reliable results. The method was successfully employed to reveal the characteristics of transmitter release from embryonal carcinoma stem cells. The method features simple procedure (no sample preparation), high recovery (≥73%), high accuracy (89.36% ≤ RE ≤ 116.89%), good reproducibility (2.18% ≤ RSD ≤ 14.56%), and sensitive limits of detection (2 pg for acetylcholine, serotonin, and glutamate, 10 pg

  11. Simultaneous determination of the repertoire of classical neurotransmitters released from embryonal carcinoma stem cells using online microdialysis coupled with hydrophilic interaction chromatography–tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Ya-Bin [Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Sun, Fan [Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Teng, Lin [Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Department of Cardiology and Institute of Cardiovascular Diseases, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang 443000, Hubei (China); Li, Wen-Bin; An, Shi-Min [Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Zhang, Chun; Yang, Xin-Jie; Lv, Hao-Yu; Ding, Xu-Ping [Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Zhu, Liang, E-mail: zhuliang17@gmail.com [Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); and others

    2014-11-07

    Highlights: • An online MD-HILIC–MS/MS method for simultaneously measuring the repertoire of classical transmitters was developed and validated. • Hydrophilic interaction chromatography (HILIC) was successfully employed to online system. • Stable isotope labeled internal standards and authentic matrix have been applied to guarantee reliable results. • The method features simple procedure (no sample preparation), high recovery (≥73%), high accuracy (89.36% ≤ RE ≤ 116.89%), good reproducibility (2.18% ≤ RSD ≤ 14.56%), and sensitive limits of detection (2 pg for acetylcholine, serotonin, and glutamate, 10 pg for dopamine, norepinephrine, GABA, and glycine). - Abstract: Dynamic, continuous, and simultaneous multi-analysis of transmitters is important for the delineation of the complex interactions between the neuronal and intercellular communications. But the analysis of the whole repertoire of classical transmitters of diverse structure is challenging due to their different physico-chemical properties and to their high polarity feature which leads to poor retention in traditional reversed-phase columns during LC–MS analysis. Here, an online microdialysis coupled with hydrophilic interaction chromatography–tandem mass spectrometry (online MD-HILIC–MS/MS) detection method was developed for the simultaneous measurement of the repertoire of classical transmitters (acetylcholine, serotonin, dopamine, norepinephrine, glutamate, GABA, and glycine). Stable isotope labeled internal standards and authentic matrix have been applied to guarantee reliable results. The method was successfully employed to reveal the characteristics of transmitter release from embryonal carcinoma stem cells. The method features simple procedure (no sample preparation), high recovery (≥73%), high accuracy (89.36% ≤ RE ≤ 116.89%), good reproducibility (2.18% ≤ RSD ≤ 14.56%), and sensitive limits of detection (2 pg for acetylcholine, serotonin, and glutamate, 10 pg

  12. Different papillomaviruses have different repertoires of transcription factor binding sites: convergence and divergence in the upstream regulatory region

    Directory of Open Access Journals (Sweden)

    Alonso Ángel

    2006-03-01

    Full Text Available Abstract Background Papillomaviruses (PVs infect stratified squamous epithelia in warm-blooded vertebrates and have undergone a complex evolutionary process. The control of the expression of the early ORFs in PVs depends on the binding of cellular and viral transcription factors to the upstream regulatory region (URR of the virus. It is believed that there is a core of transcription factor binding sites (TFBS common to all PVs, with additional individual differences, although most of the available information focuses only on a handful of viruses. Results We have studied the URR of sixty-one PVs, covering twenty different hosts. We have predicted the TFBS present in the URR and analysed these results by principal component analysis and genetic algorithms. The number and nature of TFBS in the URR might be much broader than thus far described, and different PVs have different repertoires of TFBS. Conclusion There are common fingerprints in the URR in PVs that infect primates, although the ancestors of these viruses diverged a long time ago. Additionally, there are obvious differences between the URR of alpha and beta PVs, despite these PVs infect similar histological cell types in the same host, i.e. human. A thorough analysis of the TFBS in the URR might provide crucial information about the differential biology of cancer-associated PVs.

  13. Quantitative Comparison of Abundance Structures of Generalized Communities: From B-Cell Receptor Repertoires to Microbiomes.

    Directory of Open Access Journals (Sweden)

    Mohammadkarim Saeedghalati

    2017-01-01

    Full Text Available The community, the assemblage of organisms co-existing in a given space and time, has the potential to become one of the unifying concepts of biology, especially with the advent of high-throughput sequencing experiments that reveal genetic diversity exhaustively. In this spirit we show that a tool from community ecology, the Rank Abundance Distribution (RAD, can be turned by the new MaxRank normalization method into a generic, expressive descriptor for quantitative comparison of communities in many areas of biology. To illustrate the versatility of the method, we analyze RADs from various generalized communities, i.e. assemblages of genetically diverse cells or organisms, including human B cells, gut microbiomes under antibiotic treatment and of different ages and countries of origin, and other human and environmental microbial communities. We show that normalized RADs enable novel quantitative approaches that help to understand structures and dynamics of complex generalized communities.

  14. Pan-European strategy for genetic conservation of forest trees and establishment of a core network of dynamic conservation units

    NARCIS (Netherlands)

    Vries, de S.M.G.; Alan, Murat; Bozzano, Michele; Burianek, Vaclav

    2015-01-01

    The diversity of forests, at the level of species and at the level of genetic diversity within species, is an important resource for Europe. Over the past several decades European countries have made considerable efforts to conserve the genetic diversity of tree species. According to the EUFGIS

  15. Negotiation over self-control and activity: an analysis of balancing in the repertoires of Finnish healthy lifestyles.

    Science.gov (United States)

    Pajari, Pia M; Jallinoja, Piia; Absetz, Pilvikki

    2006-05-01

    This study analyses arguments for and against the notion of healthy lifestyles, and the construction of responsibility for health, in group discussions in Finland. With data from four focus groups, we identified five interpretative repertoires: a strong activity repertoire reflects the dominant cultural value of health and emphasizes self-control. Three other repertoires--illness, external barriers, and weak character--share the underlying values of the activity repertoire, but exemplify situations where the individual lacks control, seeking to justify deviations from the norm of activity. One counter-repertoire, the pleasure repertoire, questions the hegemonic value of health, and discusses other competing values. The discussion of health is an ongoing dialectical process drawing from the different repertoires. In order to avoid stigmatization and to save face in the social situation of a focus group, the subjects strive to balance their accounts of behaviours considered unhealthy by also claiming healthy behaviours. They also strike a balance between extreme rigidity and carelessness, emphasizing the ideal of moderation and harmony. The findings point to a need to consider variations in and underpinnings of a "good life" at the individual level. Encouraging people to specify the meaning and content of moderation in their personal lives could provide a new perspective for health education and health promotion.

  16. Immune Antibody Libraries: Manipulating The Diverse Immune Repertoire for Antibody Discovery.

    Science.gov (United States)

    Lim, Theam Soon; Chan, Soo Khim

    2016-01-01

    Antibody phage display is highly dependent on the availability of antibody libraries. There are several forms of libraries depending mainly on the origin of the source materials. There are three major classes of libraries, mainly the naïve, immune and synthetic libraries. Immune antibody libraries are designed to isolate specific and high affinity antibodies against disease antigens. The pre-exposure of the host to an infection results in the production of a skewed population of antibodies against the particular infection. This characteristic takes advantage of the in vivo editing machinery to generate bias and specific immune repertoire. The skewed but diverse repertoire of immune libraries has been adapted successfully in the generation of antibodies against a wide range of diseases. We envisage immune antibody libraries to play a greater role in the discovery of antibodies for diseases in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. When are nursing students on clinical placements ready to expand their learning repertoire?

    DEFF Research Database (Denmark)

    Holmberg, Marlene; Stisen, Bente Kjærgaard; Grau, Sarah M.

    2018-01-01

    Learning styles indicate an individual’s preferred way of learning. Research suggests that it is important for students on clinical placements to begin the learning process with the preferred learning style and subsequently develop their ability to use other styles and become more balanced learners....... What is unknown is when baccalaureate nursing students are ready to develop the other learning styles, and what facilitates such an expansion in their learning style repertoire? This is important, because students need to develop the abilities to learn both by acting and by deepen their knowledge...... of theory to meet the requirements of the nursing profession. An American study found that operating room students felt confident to adopt new learning styles by the third week of clinical placements. No studies to date have retrieved a similar pattern of readiness to expand learning style repertoire among...

  18. Uncovering the Legionella genus effector repertoire - strength in diversity and numbers

    Science.gov (United States)

    Burstein, David; Amaro, Francisco; Zusman, Tal; Lifshitz, Ziv; Cohen, Ofir; Gilbert, Jack A; Pupko, Tal; Shuman, Howard A; Segal, Gil

    2016-01-01

    Infection by the human pathogen Legionella pneumophila relies on the translocation of ~300 virulence proteins, termed effectors, which manipulate host-cell processes. However, almost no information exists regarding effectors in other Legionella pathogens. Here we sequenced, assembled and characterized the genomes of 38 Legionella species, and predicted their effector repertoire using a previously validated machine-learning approach. This analysis revealed a treasure trove of 5,885 predicted effectors. The effector repertoire of different Legionella species was found to be largely non-overlapping, and only seven core-effectors were shared among all species studied. Species-specific effectors had atypically low GC content, suggesting exogenous acquisition, possibly from their natural protozoan hosts. Furthermore, we detected numerous novel conserved effector domains, and discovered new domain combinations, which allowed inferring yet undescribed effector functions. The effector collection and network of domain architectures described here can serve as a roadmap for future studies of effector function and evolution. PMID:26752266

  19. Finding meaning in first episode psychosis: experience, agency, and the cultural repertoire.

    Science.gov (United States)

    Larsen, John Aggergaard

    2004-12-01

    The article examines individuals' attempts to generate meaning following their experiences with psychosis. The inquiry is based on a person-centered ethnographic study of a Danish mental health community program for early intervention in schizophrenia and involves longitudinal interviews with 15 of its participants. The article takes an existential anthropological perspective emphasizing agency and cultural phenomenology to investigate how individuals draw on resources from the cultural repertoire to make sense of personally disturbing experiences during their psychosis. It is suggested that the concept of "system of explanation" has advantages over, for example, "illness narrative" and "explanatory model" when demonstrating how some individuals engage in the creative analytic and theory-building work of bricolage, selecting, adding, and combining various systems of explanation. Delusions are equally derived from the cultural repertoire but are constructed as dogmatic explanations that are idiosyncratic to the individual who holds them.

  20. The peripheral NK cell repertoire after kidney transplantation is modulated by different immunosuppressive drugs

    Directory of Open Access Journals (Sweden)

    Christine eNeudoerfl

    2013-02-01

    Full Text Available In the context of kidney transplantation, little is known about the involvement of NK cells in the immune reaction leading to either rejection or immunological tolerance under immunosuppression. Therefore, the peripheral NK cell repertoire of patients after kidney transplantation was investigated in order to identify NK cell subsets that may be associated with the individual immune status at the time of their protocol biopsies for histopathological evaluation of the graft. Alterations in the peripheral NK cell repertoire could be correlated to the type of immunosuppression, i.e. calcineurin-inhibitors like CyclosporinA vs. Tacrolimus with or without addition of mTOR inhibitors. Here, we could demonstrate that the NK cell repertoire in peripheral blood of kidney transplant patients differs significantly from healthy individuals. The presence of donor-specific antibodies was associated with reduced numbers of CD56dim NK cells. Moreover, in patients, down-modulation of CD16 and CD6 on CD56dim NK cells was observed with significant differences between CyclosporinA- and Tac-treated patients. Tac-treatment was associated with decreased CD69, HLA-DR and increased CD94/NKG2A expression in CD56dim NK cells indicating that the quality of the immunosuppressive treatment impinges on the peripheral NK cell repertoire. In vitro studies with PBMC of healthy donors showed that this modulation of CD16, CD6, CD69, and HLA-DR could also be induced experimentally. The presence of calcineurin or mTOR inhibitors had also functional consequences regarding degranulation and IFN--production against K562 target cells, respectively. In summary, we postulate that the NK cell composition in peripheral blood of kidney transplanted patients represents an important hallmark of the efficacy of immunosuppression and may be even informative for the immune status after transplantation in terms of rejection vs. drug-induced allograft tolerance. Thus,NK cells can serve as sensors

  1. The self-nonself discrimination and the nature and acquisition of the antibody repertoire.

    Science.gov (United States)

    Coutinho, A

    1980-01-01

    Network ideas are confronted with current hypotheses for the origin of antibody diversity and self-nonself discrimination. The difficulties of reconciling the promethean evolution of the antibody system with "germ line" theories are discussed, as well as the problems of "somatic" hypotheses to explain the completeness of the antibody repertoire. The formal incompatibility of the network theory with ideas basing self-nonself discrimination on the elimination of self-reactive cells is demonstrated, as well as the difficulties of these and other environment-dependent hypotheses for lymphocyte activation, to encompass the internal activity in the immune system. It is argued, on the other hand, that the limitations of the network theory in providing a functional basis for the idiotypic network and in accounting for self-nonself discrimination, can be solved by finding in a complete repertoire of antibody-combining sites the complementary structures to growth receptors on B lymphocytes, and by using these as internal mitogens in the expansion of the precursor cell pools and in the maintenance of the mature steady states. Letting self-nonself discrimination be accounted for by such growth receptors, both the integrity of the antibody repertoire and the internal activity in the system can also be ensured. Moreover, by postulating a germ line origin for the antireceptor antibodies and by accepting idiotypic cross-reactivity between growth receptors and other germ line antibodies, the possibilities are set for a phylogenetically and ontogenically autonomous immune system embodied with the capabilities for self-expansion, diversification and selection of available repertoires. Its promethean characteristics are explained by its completeness, and this is achieved by idiotypic interactions between growth receptors and a limited number of complementary or cross-reactive germ line antibodies, naturally selected on the basis of their structural relationships with growth receptors.

  2. T Cell Phenotype and T Cell Receptor Repertoire in Patients with Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Kostas Patas

    2018-02-01

    Full Text Available While a link between inflammation and the development of neuropsychiatric disorders, including major depressive disorder (MDD is supported by a growing body of evidence, little is known about the contribution of aberrant adaptive immunity in this context. Here, we conducted in-depth characterization of T cell phenotype and T cell receptor (TCR repertoire in MDD. For this cross-sectional case–control study, we recruited antidepressant-free patients with MDD without any somatic or psychiatric comorbidities (n = 20, who were individually matched for sex, age, body mass index, and smoking status to a non-depressed control subject (n = 20. T cell phenotype and repertoire were interrogated using a combination of flow cytometry, gene expression analysis, and next generation sequencing. T cells from MDD patients showed significantly lower surface expression of the chemokine receptors CXCR3 and CCR6, which are known to be central to T cell differentiation and trafficking. In addition, we observed a shift within the CD4+ T cell compartment characterized by a higher frequency of CD4+CD25highCD127low/− cells and higher FOXP3 mRNA expression in purified CD4+ T cells obtained from patients with MDD. Finally, flow cytometry-based TCR Vβ repertoire analysis indicated a less diverse CD4+ T cell repertoire in MDD, which was corroborated by next generation sequencing of the TCR β chain CDR3 region. Overall, these results suggest that T cell phenotype and TCR utilization are skewed on several levels in patients with MDD. Our study identifies putative cellular and molecular signatures of dysregulated adaptive immunity and reinforces the notion that T cells are a pathophysiologically relevant cell population in this disorder.

  3. WORKS FOR CLARINET AND ACCOMPANIMENT IN OLEG NEGRUŢA’S COMPOSITION REPERTOIRE

    OpenAIRE

    MUŞAT SERGHEI; CHICIUC NATALIA

    2015-01-01

    Oleg Negruţa’s composition repertoire for solo instruments with accompaniment, of which clarinet opuses are highlighted, is important for indigenous musical art. In a vast genre complex, it confirms the composer’s constant commitment to the idea of the Bessarabian professional school. In this sense, as relevant works can be considered the three pieces for clarinet and piano: Improvisation, Fantasy on a Theme by Paganini and Elegy. However, this article is meant to offer details in an analytic...

  4. First insights into the vocal repertoire of infant and juvenile Southern white rhinoceros.

    Science.gov (United States)

    Linn, Sabrina N; Boeer, Michael; Scheumann, Marina

    2018-01-01

    Describing vocal repertoires represents an essential step towards gaining an overview about the complexity of acoustic communication in a given species. The analysis of infant vocalisations is essential for understanding the development and usage of species-specific vocalisations, but is often underrepresented, especially in species with long inter-birth intervals such as the white rhinoceros. Thus, this study aimed for the first time to characterise the infant and juvenile vocal repertoire of the Southern white rhinoceros and to relate these findings to the adult vocal repertoire. The behaviour of seven mother-reared white rhinoceros calves (two males, five females) and one hand-reared calf (male), ranging from one month to four years, was simultaneously audio and video-taped at three zoos. Normally reared infants and juveniles uttered four discriminable call types (Whine, Snort, Threat, and Pant) that were produced in different behavioural contexts. All call types were also uttered by the hand-reared calf. Call rates of Whines, but not of the other call types, decreased with age. These findings provide the first evidence that infant and juvenile rhinoceros utter specific call types in distinct contexts, even if they grow up with limited social interaction with conspecifics. By comparing our findings with the current literature on vocalisations of adult white rhinoceros and other solitary rhinoceros species, we discuss to which extent differences in the social lifestyle across species affect acoustic communication in mammals.

  5. Ibrutinib Therapy Increases T Cell Repertoire Diversity in Patients with Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Yin, Qingsong; Sivina, Mariela; Robins, Harlan; Yusko, Erik; Vignali, Marissa; O'Brien, Susan; Keating, Michael J; Ferrajoli, Alessandra; Estrov, Zeev; Jain, Nitin; Wierda, William G; Burger, Jan A

    2017-02-15

    The Bruton's tyrosine kinase inhibitor ibrutinib is a highly effective, new targeted therapy for chronic lymphocytic leukemia (CLL) that thwarts leukemia cell survival, growth, and tissue homing. The effects of ibrutinib treatment on the T cell compartment, which is clonally expanded and thought to support the growth of malignant B cells in CLL, are not fully characterized. Using next-generation sequencing technology, we characterized the diversity of TCRβ-chains in peripheral blood T cells from 15 CLL patients before and after 1 y of ibrutinib therapy. We noted elevated CD4 + and CD8 + T cell numbers and a restricted TCRβ repertoire in all pretreatment samples. After 1 y of ibrutinib therapy, elevated peripheral blood T cell numbers and T cell-related cytokine levels had normalized, and T cell repertoire diversity increased significantly. Dominant TCRβ clones in pretreatment samples declined or became undetectable, and the number of productive unique clones increased significantly during ibrutinib therapy, with the emergence of large numbers of low-frequency TCRβ clones. Importantly, broader TCR repertoire diversity was associated with clinical efficacy and lower rates of infections during ibrutinib therapy. These data demonstrate that ibrutinib therapy increases diversification of the T cell compartment in CLL patients, which contributes to cellular immune reconstitution. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. First insights into the vocal repertoire of infant and juvenile Southern white rhinoceros

    Science.gov (United States)

    Boeer, Michael; Scheumann, Marina

    2018-01-01

    Describing vocal repertoires represents an essential step towards gaining an overview about the complexity of acoustic communication in a given species. The analysis of infant vocalisations is essential for understanding the development and usage of species-specific vocalisations, but is often underrepresented, especially in species with long inter-birth intervals such as the white rhinoceros. Thus, this study aimed for the first time to characterise the infant and juvenile vocal repertoire of the Southern white rhinoceros and to relate these findings to the adult vocal repertoire. The behaviour of seven mother-reared white rhinoceros calves (two males, five females) and one hand-reared calf (male), ranging from one month to four years, was simultaneously audio and video-taped at three zoos. Normally reared infants and juveniles uttered four discriminable call types (Whine, Snort, Threat, and Pant) that were produced in different behavioural contexts. All call types were also uttered by the hand-reared calf. Call rates of Whines, but not of the other call types, decreased with age. These findings provide the first evidence that infant and juvenile rhinoceros utter specific call types in distinct contexts, even if they grow up with limited social interaction with conspecifics. By comparing our findings with the current literature on vocalisations of adult white rhinoceros and other solitary rhinoceros species, we discuss to which extent differences in the social lifestyle across species affect acoustic communication in mammals. PMID:29513670

  7. Immunoglobulin gene repertoire diversification and selection in the stomach – from gastritis to gastric lymphomas

    Directory of Open Access Journals (Sweden)

    Miri eMichaeli

    2014-06-01

    Full Text Available Chronic gastritis is characterized by gastric mucosal inflammation due to autoimmune responses or infection, frequently with Helicobacter pylori. Gastritis with H. pylori background can cause gastric mucosa-associated lymphoid tissue lymphoma (MALT-L, which sometimes further transforms into diffuse large B cell lymphoma (DLBCL. However, gastric DLBCL can also be initiated de novo. The mechanisms underlying transformation into DLBCL are not completely understood. We analyzed immunoglobulin repertoires and clonal trees to investigate whether and how immunoglobulin gene repertoires, clonal diversification and selection in gastritis, gastric MALT-L and DLBCL differ from each other and from normal responses. The two gastritis types (positive or negative for H. pylori had similarly diverse repertoires. MALT-L dominant clones presented higher diversification and longer mutational histories compared with all other conditions. DLBCL dominant clones displayed lower clonal diversification, suggesting the transforming events are triggered by similar responses in different patients. These results are surprising, as we expected to find similarities between the dominant clones of gastritis and MALT-L and between those of MALT-L and DLBCL.

  8. Dance choreography is coordinated with song repertoire in a complex avian display.

    Science.gov (United States)

    Dalziell, Anastasia H; Peters, Richard A; Cockburn, Andrew; Dorland, Alexandra D; Maisey, Alex C; Magrath, Robert D

    2013-06-17

    All human cultures have music and dance, and the two activities are so closely integrated that many languages use just one word to describe both. Recent research points to a deep cognitive connection between music and dance-like movements in humans, fueling speculation that music and dance have coevolved and prompting the need for studies of audiovisual displays in other animals. However, little is known about how nonhuman animals integrate acoustic and movement display components. One striking property of human displays is that performers coordinate dance with music by matching types of dance movements with types of music, as when dancers waltz to waltz music. Here, we show that a bird also temporally coordinates a repertoire of song types with a repertoire of dance-like movements. During displays, male superb lyrebirds (Menura novaehollandiae) sing four different song types, matching each with a unique set of movements and delivering song and dance types in a predictable sequence. Crucially, display movements are both unnecessary for the production of sound and voluntary, because males sometimes sing without dancing. Thus, the coordination of independently produced repertoires of acoustic and movement signals is not a uniquely human trait. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity.

    Directory of Open Access Journals (Sweden)

    Lorenzo Asti

    2016-04-01

    Full Text Available The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high-frequency mutation rate in the genome region that codes for the antibody active site. Eventually, cells that produce antibodies with higher affinity for their cognate antigen are selected and clonally expanded. Here, we propose a new statistical approach based on maximum entropy modeling in which a scoring function related to the binding affinity of antibodies against a specific antigen is inferred from a sample of sequences of the immune repertoire of an individual. We use our inference strategy to infer a statistical model on a data set obtained by sequencing a fairly large portion of the immune repertoire of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6, outperforming other sequence- and structure-based models.

  10. Practical compassions: repertoires of practice and compassion talk in acute mental healthcare.

    Science.gov (United States)

    Brown, Brian; Crawford, Paul; Gilbert, Paul; Gilbert, Jean; Gale, Corinne

    2014-03-01

    This article reports an exploratory study of the concept of compassion in the work of 20 mental health practitioners in a UK Midlands facility. Using notions of practice derived from phenomenology and Bourdieusian sociology and notions of emotional labour we identify two contrasting interpretive repertoires in discussions of compassion. The first, the practical compassion repertoire, evokes the practical, physical and bodily aspects of compassion. It involves organising being with patients, playing games, anticipating disruption and taking them outside for cigarettes. Practitioners described being aware that these practical, bodily activities could lead to patients 'opening up', disclosing their interior concerns and enabling practical, compassionate mental health work to take place. In contrast, the second, organisational repertoire, concerns organisational constraints on compassionate practice. The shortage of staff, the record-keeping and internal processes of quality control were seen as time-greedy and apt to detract from contact with patients. The findings are discussed in relation to Bourdieu and Merleau-Ponty's phenomenological accounts of practice and habit and set in context in the growing interest in placing compassion centrally in healthcare. We also explore how the exercise of compassion in the way our participants describe it can afford the more effective exercise of medical power. © 2013 The Author. Sociology of Health & Illness © 2013 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.

  11. Pervasive and stochastic changes in the TCR repertoire of regulatory T-cell-deficient mice.

    Science.gov (United States)

    Zheng, Lingjie; Sharma, Rahul; Kung, John T; Deshmukh, Umesh S; Jarjour, Wael N; Fu, Shu Man; Ju, Shyr-Te

    2008-04-01

    We hypothesize that regulatory T-cell (Treg)-deficient strains have an altered TCR repertoire in part due to the expansion of autoimmune repertoire by self-antigen. We compared the Vbeta family expression profile between B6 and Treg-lacking B6.Cg-Foxp3(sf)(/Y) (B6.sf) mice using fluorescent anti-Vbeta mAbs and observed no changes. However, while the spectratypes of 20 Vbeta families among B6 mice were highly similar, the Vbeta family spectratypes of B6.sf mice were remarkably different from B6 mice and from each other. Significant spectratype changes in many Vbeta families were also observed in Treg-deficient IL-2 knockout (KO) and IL-2Ralpha KO mice. Such changes were not observed with anti-CD3 mAb-treated B6 mice or B6 CD4+CD25- T cells. TCR transgenic (OT-II.sf) mice displayed dramatic reduction of clonotypic TCR with concomitant increase in T cells bearing non-transgenic Vbeta and Valpha families, including T cells with dual receptors expressing reduced levels of transgenic Valpha and endogenous Valpha. Collectively, the data demonstrate that Treg deficiency allows polyclonal expansion of T cells in a stochastic manner, resulting in widespread changes in the TCR repertoire.

  12. High diversity of the T-cell receptor repertoire of tumor-infiltrating lymphocytes in basal cell carcinoma

    DEFF Research Database (Denmark)

    Omland, Silje H; Hamrouni, Abdelbasset; Gniadecki, Robert

    2017-01-01

    to determine the clonality of TCR and degree of overlap in TCR repertoires between skin resident T-cells and TILs. We found high diversity of the TCR repertoire in BCC and control skin with random V-J gene usage and similar CDR3-length distribution. Lack of TCR repertoire restriction indicates absence of tumor......Whether specific T-cell clones are present in tumor infiltrating lymphocytes (TILs) in BCC is unknown. We employed deep sequencing of mRNA coding for the T-cell receptor (TCR) chains α- and β to characterize the repertoire of TILs in BCC. V and J gene-usage and CDR3 length were computed...

  13. B cell repertoires in HLA-sensitized kidney transplant candidates undergoing desensitization therapy.

    Science.gov (United States)

    Beausang, John F; Fan, H Christina; Sit, Rene; Hutchins, Maria U; Jirage, Kshama; Curtis, Rachael; Hutchins, Edward; Quake, Stephen R; Yabu, Julie M

    2017-01-13

    Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels. Responders to desensitization had a decrease of 5% points or greater in cumulated calculated panel reactive antibody (cPRA) levels, and non-responders had no decrease in cPRA. Dominant B cell clones were not observed in highly sensitized candidates, suggesting that the B cells responsible for sensitization are either not present in peripheral blood or present at comparable levels to other circulating B cells. Candidates that responded to desensitization therapy had pre-treatment repertoires composed of a larger fraction of class-switched (IgG and IgA) isotypes compared to non-responding candidates. After B cell depleting therapy, the proportion of switched isotypes increased and the mutation frequencies of the remaining non-switched isotypes (IgM and IgD) increased in both responders and non-responders, perhaps representing a shift in the repertoire towards memory B cells or plasmablasts. Conversely, after transplantation, non-switched isotypes with fewer mutations increased, suggesting a shift in the repertoire towards naïve B cells. Relative abundance of different B cell isotypes is strongly perturbed by desensitization therapy and transplantation, potentially reflecting changes in the relative

  14. Temporal dynamics of microbial communities in the rhizosphere of two genetically modified (GM) maize hybrids in tropical agrosystems

    NARCIS (Netherlands)

    Cotta, Simone Raposo; Franco Dias, Armando Cavalcante; Marriel, Ivanildo Evodio; Gomes, Eliane Aparecida; van Elsas, Jan Dirk; Seldin, Lucy

    The use of genetically modified (GM) plants still raises concerns about their environmental impact. The present study aimed to evaluate the possible effects of GM maize, in comparison to the parental line, on the structure and abundance of microbial communities in the rhizosphere. Moreover, the

  15. Resequencing of the Phytophthora ramorum genome to characterize genetic variation and population dynamics of the invasive pathogen

    Science.gov (United States)

    Jennifer Yuzon; David M. Rizzo; Mathu Malar C; Sucheta Tripathy; Takao Kasuga

    2017-01-01

    Phytophthora ramorum has spread and diversified throughout California’s northwestern coast since its introduction in the 1990s. Tracking the spread of P. ramorum and the functional response of the pathogen to the environment is of particular interest to managing the epidemic. Using genetic tools such as microsatellite...

  16. Mitochondrial dynamics in the hippocampus is influenced by antidepressant treatment in a genetic rat model of depression

    DEFF Research Database (Denmark)

    Chen, F.; Wegener, Gregers; Madsen, T. M.

    2013-01-01

    Post-mortem, genetic, brain imaging, and peripheral cell studies showed that mitochondria may play an important role in the pathophysiology of depression and effects of antidepressant therapy. Here we investigated whether chronic antidepressant treatment on rats induce changes of the mitochondria...

  17. REPERTOIRE (DIRECTORY).

    Science.gov (United States)

    JOUBERT, MADELEINE

    THIS DIRECTORY DESCRIBES, IN FRENCH, THE STRUCTURE, OBJECTIVES, ADMISSION REQUIREMENTS, AFFILIATIONS, EDUCATIONAL ACTIVITIES, AND PUBLICATIONS OF 62 ADULT EDUCATION ORGANIZATIONS AND INSTITUTIONS SERVING FRENCH-SPEAKING CANADA. IT INCLUDES DATA ON TYPE OF ORGANIZATION OR INSTITUTION, SCOPE OF ACTIVITY, REGION (WHERE SPECIFIED), FINANCIAL SUPPORT,…

  18. Dynamics

    CERN Document Server

    Goodman, Lawrence E

    2001-01-01

    Beginning text presents complete theoretical treatment of mechanical model systems and deals with technological applications. Topics include introduction to calculus of vectors, particle motion, dynamics of particle systems and plane rigid bodies, technical applications in plane motions, theory of mechanical vibrations, and more. Exercises and answers appear in each chapter.

  19. Historical Processes and Contemporary Anthropogenic Activities Influence Genetic Population Dynamics of Nassau Grouper (Epinephelus striatus within The Bahamas

    Directory of Open Access Journals (Sweden)

    Krista D. Sherman

    2017-12-01

    Full Text Available Severe declines of endangered Nassau grouper (Epinephelus striatus across The Bahamas and Caribbean have spurred efforts to improve their fisheries management and population conservation. The Bahamas is reported to hold the majority of fish spawning aggregations for Nassau grouper, however, the status and genetic population structure of fish within the country is largely unknown, presenting a major knowledge gap for their sustainable management. Between August 2014–February 2017, 464 individual Nassau grouper sampled from The Bahamas were genotyped using 15 polymorphic microsatellite loci to establish measures of population structure, genetic diversity and effective population size (Ne. Nassau grouper were characterized by mostly high levels of genetic diversity, but we found no evidence for geographic population structure. Microsatellite analyses revealed weak, but significant genetic differentiation of Nassau grouper throughout the Bahamian archipelago (Global FST 0.00236, p = 0.0001. Temporal analyses of changes in Ne over the last 1,000 generations provide evidence in support of a pronounced historic decline in Bahamian Nassau grouper that appears to pre-date anthropogenic fishing activities. M-ratio results corroborate significant reductions in Ne throughout The Bahamas, with evidence for population bottlenecks in three islands and an active fish spawning aggregation along with apparent signs of inbreeding at two islands. Current estimates of Ne for Nassau grouper are considerably lower compared with historic levels. These findings represent important new contributions to our understanding of the evolutionary history, demographics and genetic connectivity of this endangered species, which are of critical importance for advancing their sustainable management.

  20. Nationwide genetic surveillance of Plasmodium vivax in Papua New Guinea reveals heterogeneous transmission dynamics and routes of migration amongst subdivided populations.

    Science.gov (United States)

    Fola, Abebe A; Nate, Elma; Abby Harrison, G L; Barnadas, Céline; Hetzel, Manuel W; Iga, Jonah; Siba, Peter; Mueller, Ivo; Barry, Alyssa E

    2018-03-01

    The Asia Pacific Leaders in Malaria Alliance (APLMA) have committed to eliminate malaria from the region by 2030. Papua New Guinea (PNG) has the highest malaria burden in the Asia-Pacific region but with the intensification of control efforts since 2005, transmission has been dramatically reduced and Plasmodium vivax is now the dominant malaria infection in some parts of the country. To gain a better understanding of the transmission dynamics and migration patterns of P. vivax in PNG, here we investigate population structure in eight geographically and ecologically distinct regions of the country. A total of 219 P. vivax isolates (16-30 per population) were successfully haplotyped using 10 microsatellite markers. A wide range of genetic diversity (H e =0.37-0.87, R s =3.60-7.58) and significant multilocus linkage disequilibrium (LD) was observed in six of the eight populations (I A S =0.08-0.15 p-value<0.05) reflecting a spectrum of transmission intensities across the country. Genetic differentiation between regions was evident (Jost's D=0.07-0.72), with increasing divergence of populations with geographic distance. Overall, P. vivax isolates clustered into three major genetic populations subdividing the Mainland lowland and coastal regions, the Islands and the Highlands. P. vivax gene flow follows major human migration routes, and there was higher gene flow amongst Mainland parasite populations than among Island populations. The Central Province (samples collected in villages close to the capital city, Port Moresby), acts as a sink for imported infections from the three major endemic areas. These insights into P. vivax transmission dynamics and population networks will inform targeted strategies to contain malaria infections and to prevent the spread of drug resistance in PNG. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Clonal progression during the T cell-dependent B cell antibody response depends on the immunoglobulin DH gene segment repertoire.

    Directory of Open Access Journals (Sweden)

    Ahmad eTrad

    2014-08-01

    Full Text Available The diversity of the third complementarity determining region of the Ig H chain is constrained by natural selection of immunoglobulin diversity (DH sequence. To test the functional significance of this constraint in the context of thymus-dependent (TD immune responses, we immunized BALB/c mice with WT or altered DH sequence with 2-phenyloxazolone-coupled chicken serum albumin (phOx-CSA. We chose this antigen because studies of the humoral immune response to the hapten phOx were instrumental in the development of the current theoretical framework on which our understanding of the forces driving TD responses is based. To allow direct comparison, we used the classic approach of generating monoclonal Ab (mAb from various stages of the immune response to phOx to assess the effect of changing the sequence of the DH on clonal expansion, class switching and affinity maturation, which are hallmarks of TD responses. Compared to WT, TD-induced humoral IgM as well as IgG antibody production in the D-altered D-DFS and D-iD strains were significantly reduced. An increased prevalence of IgM producing hybridomas from late primary, secondary, and tertiary memory responses suggested either impaired class switch recombination (CSR or impaired clonal expansion of class switched B cells with phOx reactivity. Neither of the D-altered strains demonstrated the restriction in the VH/VL repertoire, the elimination of VH1 family-encoded antibodies, the focusing of the distribution of CDR-H3 lengths, or the selection for the normally dominant Ox1 clonotype which all are hallmarks of the anti-phOx response in WT mice. These changes in clonal selection and expansion as well as class switch recombination indicate that the genetic constitution of the DH locus, which has been selected by evolution, can strongly influence the functional outcome of a TD humoral response.

  2. Phenotypic integration and the evolution of signal repertoires: A case study of treefrog acoustic communication.

    Science.gov (United States)

    Reichert, Michael S; Höbel, Gerlinde

    2018-03-01

    Animal signals are inherently complex phenotypes with many interacting parts combining to elicit responses from receivers. The pattern of interrelationships between signal components reflects the extent to which each component is expressed, and responds to selection, either in concert with or independently of others. Furthermore, many species have complex repertoires consisting of multiple signal types used in different contexts, and common morphological and physiological constraints may result in interrelationships extending across the multiple signals in species' repertoires. The evolutionary significance of interrelationships between signal traits can be explored within the framework of phenotypic integration, which offers a suite of quantitative techniques to characterize complex phenotypes. In particular, these techniques allow for the assessment of modularity and integration, which describe, respectively, the extent to which sets of traits covary either independently or jointly. Although signal and repertoire complexity are thought to be major drivers of diversification and social evolution, few studies have explicitly measured the phenotypic integration of signals to investigate the evolution of diverse communication systems. We applied methods from phenotypic integration studies to quantify integration in the two primary vocalization types (advertisement and aggressive calls) in the treefrogs Hyla versicolor , Hyla cinerea, and Dendropsophus ebraccatus . We recorded male calls and calculated standardized phenotypic variance-covariance ( P ) matrices for characteristics within and across call types. We found significant integration across call types, but the strength of integration varied by species and corresponded with the acoustic similarity of the call types within each species. H. versicolor had the most modular advertisement and aggressive calls and the least acoustically similar call types. Additionally, P was robust to changing social competition

  3. Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity.

    Directory of Open Access Journals (Sweden)

    Mathieu Angin

    Full Text Available While modulation of regulatory T cell (Treg function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+ Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region, characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection.

  4. A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the nervous system

    OpenAIRE

    Raimondo, Joseph V.; Joyce, Bradley; Kay, Louise; Schlagheck, Theresa; Newey, Sarah E.; Srinivas, Shankar; Akerman, Colin J.

    2013-01-01

    Within the nervous system, intracellular Cl− and pH regulate fundamental processes including cell proliferation, metabolism, synaptic transmission, and network excitability. Cl− and pH are often co-regulated, and network activity results in the movement of both Cl− and H+. Tools to accurately measure these ions are crucial for understanding their role under physiological and pathological conditions. Although genetically-encoded Cl− and pH sensors have been described previously, these either l...

  5. Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

    DEFF Research Database (Denmark)

    Ostrov, David A; Grant, Barry J; Pompeu, Yuri A

    2012-01-01

    cells, thus causing the equivalent of an alloreactive T-cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir and that were recognized by T cells of hypersensitive patients. The assays that we have established can be applied to test additional...... unclear. Here we show that abacavir can bind within the F pocket of the peptide-binding groove of HLA-B*57:01, thereby altering its specificity. This provides an explanation for HLA-linked idiosyncratic adverse drug reactions, namely that drugs can alter the repertoire of self-peptides presented to T...

  6. Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity

    DEFF Research Database (Denmark)

    Asti, Lorenzo; Uguzzoni, Guido; Marcatili, Paolo

    2016-01-01

    The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high...... of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10-6), outperforming other sequence- and structure-based models....

  7. Changes in the repertoire of natural antibodies caused by immunization with bacterial antigens

    DEFF Research Database (Denmark)

    Shilova, N V; Navakouski, M J; Huflejt, M

    2011-01-01

    The repertoire of natural anti-glycan antibodies in naïve chickens and in chickens immunized with bacteria Burkholderia mallei, Burkholderia pseudomallei, and Francisella tularensis as well as with peptides from an outer membrane protein of B. pseudomallei was studied. A relatively restricted pat...... pattern of natural antibodies (first of all IgY against bacterial cell wall peptidoglycan fragments, L-Rha, and core N-acetyllactosamine) shrank and, moreover, the level of detectable antibodies decreased as a result of immunization....

  8. Genetic variation reveals influence of landscape connectivity on population dynamics and resiliency of western trout in disturbance-prone habitats

    Science.gov (United States)

    Helen M. Neville; R. E. Gresswell; J. B. Dunham

    2012-01-01

    Salmonid fishes have evolved and persisted in dynamic ecosystems (Waples and others 2008) where disturbance events vary in frequency, magnitude, timing, and duration (Gresswell 1999; Dale and others 2001), as well as the specific nature of associated effects (e.g., changes in thermal or flow regimes, geomorphology, or water chemistry; Reeves and others 1995; Benda and...

  9. Repertoire Analysis of Antibody CDR-H3 Loops Suggests Affinity Maturation Does Not Typically Result in Rigidification

    Directory of Open Access Journals (Sweden)

    Jeliazko R. Jeliazkov

    2018-03-01

    Full Text Available Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibody’s antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the complementarity determining region (CDR loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts. However, there were a few exceptions and previous studies were limited to a small handful of cases. Here, we determined the structural flexibility of the CDR-H3 loop for thousands of recent homology models of the human peripheral blood cell antibody repertoire using rigidity theory. We found no clear delineation in the flexibility of naïve and antigen-experienced antibodies. To account for possible sources of error, we additionally analyzed hundreds of human and mouse antibodies in the Protein Data Bank through both rigidity theory and B-factor analysis. By both metrics, we observed only a slight decrease in the CDR-H3 loop flexibility when comparing affinity matured antibodies to naïve antibodies, and the decrease was not as drastic as previously reported. Further analysis, incorporating molecular dynamics simulations, revealed a spectrum of changes in flexibility. Our results suggest that rigidification may be just one of many biophysical mechanisms for increasing affinity.

  10. VH repertoire in progeny of long term lymphoid-cultured cells used to reconstitute immunodeficient mice

    International Nuclear Information System (INIS)

    Denis, K.A.; Timson, L.K.; Witte, O.N.

    1989-01-01

    VH gene utilization in the progeny of long term lymphoid-cultured cells used for reconstitution of severe combined immunodeficient mice under varying conditions was determined. Hybridomas made from the spleens of these animals were evaluated for clonality and donor origin and a panel of 146 independent hybridomas were subsequently examined for VH expression. Hybridomas derived from the spleens of SCID mice reconstituted with fresh cells, used as a control, utilized VH families in proportion to their numerical representation in the genome. However, hybridomas from the spleens of mice reconstituted with long term cultured cells utilized a predominance of the two VH gene families most proximal to JH, characteristic of cells early in B lymphocyte development. Coinjection of thymocytes with cultured fetal liver cells, to provide good levels of T lymphocytes, did not alter this pattern of VH utilization. Irradiation (3 Gy) of the mice before cultured cell injection, which leads to more complete reconstitution of the B cell compartment, was effective in removing this bias in the VH repertoire. Hybridomas derived from these mice expressed their VH genes more in proportion to family size, characteristic of cells later in B lymphocyte development. In this manner, long term lymphoid-cultured cells can be used to study the transitions that occur in VH repertoire expression which appear to be mediated by either B lymphocyte developmental microenvironment or population size

  11. The acoustic repertoire of bottlenose dolphins (Tursiops truncatus) from the southern Gulf of Mexico

    Science.gov (United States)

    Bazua-Duran, Carmen

    2005-04-01

    Bottlenose dolphins live in a variety of habitats of the world's oceans using their acoustic repertoire to communicate and inspect their environment. This work investigates the acoustic repertoire of bottlenose dolphins that inhabit a coastal lagoon of the southern Gulf of Mexico, the Laguna de Terminos and how it may relate to the dolphins' general behavioral state and herd size, and to the general characteristics of the habitat, such as visibility, depth, and sea state. Preliminary results show that bottlenose dolphins produce by far more clicks than whistles in all behavioral states (feeding, resting, social, and travel) and herd sizes, which may correlate with the decreased visibility and shallow depth of the Laguna de Terminos. Additionally, silence was found during all behavioral states, but very seldom in herds of large size. These preliminary results suggest that bottlenose dolphins are choosing when and where to produce their phonations. Therefore, more detailed studies are needed to understand how these animals are using their acoustic sense to communicate and inspect their environment. [Work supported by CONACyT-Gobierno Edo. de Campeche and PAPIIT, UNAM.

  12. The vocal repertoire of the African Penguin (Spheniscus demersus): structure and function of calls.

    Science.gov (United States)

    Favaro, Livio; Ozella, Laura; Pessani, Daniela

    2014-01-01

    The African Penguin (Spheniscus demersus) is a highly social and vocal seabird. However, currently available descriptions of the vocal repertoire of African Penguin are mostly limited to basic descriptions of calls. Here we provide, for the first time, a detailed description of the vocal behaviour of this species by collecting audio and video recordings from a large captive colony. We combine visual examinations of spectrograms with spectral and temporal acoustic analyses to determine vocal categories. Moreover, we used a principal component analysis, followed by signal classification with a discriminant function analysis, for statistical validation of the vocalisation types. In addition, we identified the behavioural contexts in which calls were uttered. The results show that four basic vocalisations can be found in the vocal repertoire of adult African Penguin, namely a contact call emitted by isolated birds, an agonistic call used in aggressive interactions, an ecstatic display song uttered by single birds, and a mutual display song vocalised by pairs, at their nests. Moreover, we identified two distinct vocalisations interpreted as begging calls by nesting chicks (begging peep) and unweaned juveniles (begging moan). Finally, we discussed the importance of specific acoustic parameters in classifying calls and the possible use of the source-filter theory of vocal production to study penguin vocalisations.

  13. The limiting conditional probability distribution in a stochastic model of T cell repertoire maintenance.

    Science.gov (United States)

    Stirk, Emily R; Lythe, Grant; van den Berg, Hugo A; Hurst, Gareth A D; Molina-París, Carmen

    2010-04-01

    The limiting conditional probability distribution (LCD) has been much studied in the field of mathematical biology, particularly in the context of epidemiology and the persistence of epidemics. However, it has not yet been applied to the immune system. One of the characteristic features of the T cell repertoire is its diversity. This diversity declines in old age, whence the concepts of extinction and persistence are also relevant to the immune system. In this paper we model T cell repertoire maintenance by means of a continuous-time birth and death process on the positive integers, where the origin is an absorbing state. We show that eventual extinction is guaranteed. The late-time behaviour of the process before extinction takes place is modelled by the LCD, which we prove always exists for the process studied here. In most cases, analytic expressions for the LCD cannot be computed but the probability distribution may be approximated by means of the stationary probability distributions of two related processes. We show how these approximations are related to the LCD of the original process and use them to study the LCD in two special cases. We also make use of the large N expansion to derive a further approximation to the LCD. The accuracy of the various approximations is then analysed. (c) 2009 Elsevier Inc. All rights reserved.

  14. A role for gut-associated lymphoid tissue in shaping the human B cell repertoire.

    Science.gov (United States)

    Vossenkämper, Anna; Blair, Paul A; Safinia, Niloufar; Fraser, Louise D; Das, Lisa; Sanders, Theodore J; Stagg, Andrew J; Sanderson, Jeremy D; Taylor, Kirstin; Chang, Fuju; Choong, Lee M; D'Cruz, David P; Macdonald, Thomas T; Lombardi, Giovanna; Spencer, Jo

    2013-08-26

    We have tracked the fate of immature human B cells at a critical stage in their development when the mature B cell repertoire is shaped. We show that a major subset of bone marrow emigrant immature human B cells, the transitional 2 (T2) B cells, homes to gut-associated lymphoid tissue (GALT) and that most T2 B cells isolated from human GALT are activated. Activation in GALT is a previously unknown potential fate for immature human B cells. The process of maturation from immature transitional B cell through to mature naive B cell includes the removal of autoreactive cells from the developing repertoire, a process which is known to fail in systemic lupus erythematosus (SLE). We observe that immature B cells in SLE are poorly equipped to access the gut and that gut immune compartments are depleted in SLE. Thus, activation of immature B cells in GALT may function as a checkpoint that protects against autoimmunity. In healthy individuals, this pathway may be involved in generating the vast population of IgA plasma cells and also the enigmatic marginal zone B cell subset that is poorly understood in humans.

  15. Characterizing immunoglobulin repertoire from whole blood by a personal genome sequencer.

    Directory of Open Access Journals (Sweden)

    Fan Gao

    Full Text Available In human immune system, V(DJ recombination produces an enormously large repertoire of immunoglobulins (Ig so that they can tackle different antigens from bacteria, viruses and tumor cells. Several studies have demonstrated the utility of next-generation sequencers such as Roche 454 and Illumina Genome Analyzer to characterize the repertoire of immunoglobulins. However, these techniques typically require separation of B cell population from whole blood and require a few weeks for running the sequencers, so it may not be practical to implement them in clinical settings. Recently, the Ion Torrent personal genome sequencer has emerged as a tabletop personal genome sequencer that can be operated in a time-efficient and cost-effective manner. In this study, we explored the technical feasibility to use multiplex PCR for amplifying V(DJ recombination for IgH, directly from whole blood, then sequence the amplicons by the Ion Torrent sequencer. The whole process including data generation and analysis can be completed in one day. We tested the method in a pilot study on patients with benign, atypical and malignant meningiomas. Despite the noisy data, we were able to compare the samples by their usage frequencies of the V segment, as well as their somatic hypermutation rates. In summary, our study suggested that it is technically feasible to perform clinical monitoring of V(DJ recombination within a day by personal genome sequencers.

  16. The MicroRNA Repertoire of Symbiodinium, the Dinoflagellate Symbiont of Reef-Building Corals

    KAUST Repository

    Baumgarten, Sebastian

    2013-07-01

    Animal and plant genomes produce numerous small RNAs (smRNAs) that regulate gene expression post-transcriptionally affecting metabolism, development, and epigenetic inheritance. In order to characterize the repertoire of endogenous microRNAs and potential gene targets, we conducted smRNA and mRNA expression profiling over nine experimental treatments of cultures from the dinoflagellate Symbiodinium sp. A1, a photosynthetic symbiont of scleractinian corals. We identified a total of 75 novel smRNAs in Symbiodinum sp. A1 that share stringent key features with functional microRNAs from other model organisms. A subset of 38 smRNAs was predicted independently over all nine treatments and their putative gene targets were identified. We found 3,187 animal-like target sites in the 3’UTRs of 12,858 mRNAs and 53 plantlike target sites in 51,917 genes. Furthermore, we identified the core RNAi protein machinery in Symbiodinium. Integration of smRNA and mRNA expression profiling identified a variety of processes that could be under microRNA control, e.g. regulation of translation, DNA modification, and chromatin silencing. Given that Symbiodinium seems to have a paucity of transcription factors and differentially expressed genes, identification and characterization of its smRNA repertoire establishes the possibility of a range of gene regulatory mechanisms in dinoflagellates acting post-transcriptionally.

  17. The natural antibody repertoire of sharks and humans recognizes the potential universe of antigens.

    Science.gov (United States)

    Adelman, Miranda K; Schluter, Samuel F; Marchalonis, John J

    2004-02-01

    In ancestral sharks, a rapid emergence in the evolution of the immune system occurred, giving jawed-vertebrates the necessary components for the combinatorial immune response (CIR). To compare the natural antibody (NAb) repertoires of the most divergent vertebrates with the capacity to produce antibodies, we isolated NAbs to the same set of antigens by affinity chromatography from two species of Carcharhine sharks and from human polyclonal IgG and IgM antibody preparations. The activities of the affinity-purified anti-T-cell receptor (anti-TCR) NAbs were compared with those of monoclonal anti-TCR NAbs that were generated from a systemic lupus erythematosus patient. We report that sharks and humans, representing the evolutionary extremes of vertebrate species sharing the CIR, have NAbs to human TCRs, Igs, the human senescent cell antigen, and to numerous retroviral antigens, indicating that essential features of the combinatorial repertoire and the capacity to recognize the potential universe of antigens is shared among all jawed-vertebrates.

  18. Primer sets for cloning the human repertoire of T cell Receptor Variable regions

    Directory of Open Access Journals (Sweden)

    Santoro Claudio

    2008-08-01

    Full Text Available Abstract Background Amplification and cloning of naïve T cell Receptor (TR repertoires or antigen-specific TR is crucial to shape immune response and to develop immuno-based therapies. TR variable (V regions are encoded by several genes that recombine during T cell development. The cloning of expressed genes as large diverse libraries from natural sources relies upon the availability of primers able to amplify as many V genes as possible. Results Here, we present a list of primers computationally designed on all functional TR V and J genes listed in the IMGT®, the ImMunoGeneTics information system®. The list consists of unambiguous or degenerate primers suitable to theoretically amplify and clone the entire TR repertoire. We show that it is possible to selectively amplify and clone expressed TR V genes in one single RT-PCR step and from as little as 1000 cells. Conclusion This new primer set will facilitate the creation of more diverse TR libraries than has been possible using currently available primer sets.

  19. Primer sets for cloning the human repertoire of T cell Receptor Variable regions.

    Science.gov (United States)

    Boria, Ilenia; Cotella, Diego; Dianzani, Irma; Santoro, Claudio; Sblattero, Daniele

    2008-08-29

    Amplification and cloning of naïve T cell Receptor (TR) repertoires or antigen-specific TR is crucial to shape immune response and to develop immuno-based therapies. TR variable (V) regions are encoded by several genes that recombine during T cell development. The cloning of expressed genes as large diverse libraries from natural sources relies upon the availability of primers able to amplify as many V genes as possible. Here, we present a list of primers computationally designed on all functional TR V and J genes listed in the IMGT, the ImMunoGeneTics information system. The list consists of unambiguous or degenerate primers suitable to theoretically amplify and clone the entire TR repertoire. We show that it is possible to selectively amplify and clone expressed TR V genes in one single RT-PCR step and from as little as 1000 cells. This new primer set will facilitate the creation of more diverse TR libraries than has been possible using currently available primer sets.

  20. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 80; Issue 1. Testing quantum dynamics in genetic information processing ... Keywords. assembly; computation; database search; DNA replication; genetic information; nucleotide base; polymerase enzyme; quantum coherence; quantum mechanics; quantum superposition.

  1. The artiodactyl APOBEC3 innate immune repertoire shows evidence for a multi-functional domain organization that existed in the ancestor of placental mammals

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    Andrésdóttir Valgerdur

    2008-11-01

    Full Text Available Abstract Background APOBEC3 (A3 proteins deaminate DNA cytosines and block the replication of retroviruses and retrotransposons. Each A3 gene encodes a protein with one or two conserved zinc-coordinating motifs (Z1, Z2 or Z3. The presence of one A3 gene in mice (Z2–Z3 and seven in humans, A3A-H (Z1a, Z2a-Z1b, Z2b, Z2c-Z2d, Z2e-Z2f, Z2g-Z1c, Z3, suggests extraordinary evolutionary flexibility. To gain insights into the mechanism and timing of A3 gene expansion and into the functional modularity of these genes, we analyzed the genomic sequences, expressed cDNAs and activities of the full A3 repertoire of three artiodactyl lineages: sheep, cattle and pigs. Results Sheep and cattle have three A3 genes, A3Z1, A3Z2 and A3Z3, whereas pigs only have two, A3Z2 and A3Z3. A comparison between domestic and wild pigs indicated that A3Z1 was deleted in the pig lineage. In all three species, read-through transcription and alternative splicing also produced a catalytically active double domain A3Z2-Z3 protein that had a distinct cytoplasmic localization. Thus, the three A3 genes of sheep and cattle encode four conserved and active proteins. These data, together with phylogenetic analyses, indicated that a similar, functionally modular A3 repertoire existed in the common ancestor of artiodactyls and primates (i.e., the ancestor of placental mammals. This mammalian ancestor therefore possessed the minimal A3 gene set, Z1-Z2-Z3, required to evolve through a remarkable series of eight recombination events into the present day eleven Z domain human repertoire. Conclusion The dynamic recombination-filled history of the mammalian A3 genes is consistent with the modular nature of the locus and a model in which most of these events (especially the expansions were selected by ancient pathogenic retrovirus infections.

  2. Post-embryonic nerve-associated precursors to adult pigment cells: genetic requirements and dynamics of morphogenesis and differentiation.

    Directory of Open Access Journals (Sweden)

    Erine H Budi

    2011-05-01

    Full Text Available The pigment cells of vertebrates serve a variety of functions and generate a stunning variety of patterns. These cells are also implicated in human pathologies including melanoma. Whereas the events of pigment cell development have been studied extensively in the embryo, much less is known about morphogenesis and differentiation of these cells during post-embryonic stages. Previous studies of zebrafish revealed genetically distinct populations of embryonic and adult melanophores, the ectotherm homologue of amniote melanocytes. Here, we use molecular markers, vital labeling, time-lapse imaging, mutational analyses, and transgenesis to identify peripheral nerves as a niche for precursors to adult melanophores that subsequently migrate to the skin to form the adult pigment pattern. We further identify genetic requirements for establishing, maintaining, and recruiting precursors to the adult melanophore lineage and demonstrate novel compensatory behaviors during pattern regulation in mutant backgrounds. Finally, we show that distinct populations of latent precursors having differential regenerative capabilities persist into the adult. These findings provide a foundation for future studies of post-embryonic pigment cell precursors in development, evolution, and neoplasia.

  3. A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development.

    Science.gov (United States)

    Covassin, L D; Siekmann, A F; Kacergis, M C; Laver, E; Moore, J C; Villefranc, J A; Weinstein, B M; Lawson, N D

    2009-05-15

    In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development.

  4. Functional immunomics: microarray analysis of IgG autoantibody repertoires predicts the future response of mice to induced diabetes.

    Science.gov (United States)

    Quintana, Francisco J; Hagedorn, Peter H; Elizur, Gad; Merbl, Yifat; Domany, Eytan; Cohen, Irun R

    2004-10-05

    One's present repertoire of antibodies encodes the history of one's past immunological experience. Can the present autoantibody repertoire be consulted to predict resistance or susceptibility to the future development of an autoimmune disease? Here, we developed an antigen microarray chip and used bioinformatic analysis to study a model of type 1 diabetes developing in nonobese diabetic male mice in which the disease was accelerated and synchronized by exposing the mice to cyclophosphamide at 4 weeks of age. We obtained sera from 19 individual mice, treated the mice to induce cyclophosphamide-accelerated diabetes (CAD), and found, as expected, that 9 mice became severely diabetic, whereas 10 mice permanently resisted diabetes. We again obtained serum from each mouse after CAD induction. We then analyzed, by using rank-order and superparamagnetic clustering, the patterns of antibodies in individual mice to 266 different antigens spotted on the chip. A selected panel of 27 different antigens (10% of the array) revealed a pattern of IgG antibody reactivity in the pre-CAD sera that discriminated between the mice resistant or susceptible to CAD with 100% sensitivity and 82% specificity (P = 0.017). Surprisingly, the set of IgG antibodies that was informative before CAD induction did not separate the resistant and susceptible groups after the onset of CAD; new antigens became critical for post-CAD repertoire discrimination. Thus, at least for a model disease, present antibody repertoires can predict future disease, predictive and diagnostic repertoires can differ, and decisive information about immune system behavior can be mined by bioinformatic technology. Repertoires matter.

  5. New insights into the dynamics between reef corals and their associated dinoflagellate endosymbionts from population genetic studies.

    Science.gov (United States)

    Baums, Iliana B; Devlin-Durante, Meghann K; LaJeunesse, Todd C

    2014-09-01

    The mutualistic symbioses between reef-building corals and micro-algae form the basis of coral reef ecosystems, yet recent environmental changes threaten their survival. Diversity in host-symbiont pairings on the sub-species level could be an unrecognized source of functional variation in response to stress. The Caribbean elkhorn coral, Acropora palmata, associates predominantly with one symbiont species (Symbiodinium 'fitti'), facilitating investigations of individual-level (genotype) interactions. Individual genotypes of both host and symbiont were resolved across the entire species' range. Most colonies of a particular animal genotype were dominated by one symbiont genotype (or strain) that may persist in the host for decades or more. While Symbiodinium are primarily clonal, the occurrence of recombinant genotypes indicates sexual recombination is the source of this genetic variation, and some evidence suggests this happens within the host. When these data are examined at spatial scales spanning the entire distribution of A. palmata, gene flow among animal populations was an order of magnitude greater than among populations of the symbiont. This suggests that independent micro-evolutionary processes created dissimilar population genetic structures between host and symbiont. The lower effective dispersal exhibited by the dinoflagellate raises questions regarding the extent to which populations of host and symbiont can co-evolve during times of rapid and substantial climate change. However, these findings also support a growing body of evidence, suggesting that genotype-by-genotype interactions may provide significant physiological variation, influencing the adaptive potential of symbiotic reef corals to severe selection. © 2014 John Wiley & Sons Ltd.

  6. Expression of parasite genetic variation changes over the course of infection: implications of within-host dynamics for the evolution of virulence.

    Science.gov (United States)

    Clerc, Melanie; Ebert, Dieter; Hall, Matthew D

    2015-04-07

    How infectious disease agents interact with their host changes during the course of infection and can alter the expression of disease-related traits. Yet by measuring parasite life-history traits at one or few moments during infection, studies have overlooked the impact of variable parasite growth trajectories on disease evolution. Here we show that infection-age-specific estimates of host and parasite fitness components can reveal new insight into the evolution of parasites. We do so by characterizing the within-host dynamics over an entire infection period for five genotypes of the castrating bacterial parasite Pasteuria ramosa infecting the crustacean Daphnia magna. Our results reveal that genetic variation for parasite-induced gigantism, host castration and parasite spore loads increases with the age of infection. Driving these patterns appears to be variation in how well the parasite maintains control of host reproduction late in the infection process. We discuss the evolutionary consequences of this finding with regard to natural selection acting on different ages of infection and the mechanism underlying the maintenance of castration efficiency. Our results highlight how elucidating within-host dynamics can shed light on the selective forces that shape infection strategies and the evolution of virulence. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  7. Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer, Loss, and Persistence of Genetic Elements In situ of the Infant Gut.

    Science.gov (United States)

    Porse, Andreas; Gumpert, Heidi; Kubicek-Sutherland, Jessica Z; Karami, Nahid; Adlerberth, Ingegerd; Wold, Agnes E; Andersson, Dan I; Sommer, Morten O A

    2017-01-01

    Elucidating the adaptive strategies and plasticity of bacterial genomes in situ is crucial for understanding the epidemiology and evolution of pathogens threatening human health. While much is known about the evolution of Escherichia coli in controlled laboratory environments, less effort has been made to elucidate the genome dynamics of E. coli in its native settings. Here, we follow the genome dynamics of co-existing E. coli lineages in situ of the infant gut during the first year of life. One E. coli lineage causes a urinary tract infection (UTI) and experiences several alterations of its genomic content during subsequent antibiotic treatment. Interestingly, all isolates of this uropathogenic E. coli strain carried a highly stable plasmid implicated in virulence of diverse pathogenic strains from all over the world. While virulence elements are certainly beneficial during infection scenarios, their role in gut colonization and pathogen persistence is poorly understood. We performed in vivo competitive fitness experiments to assess the role of this highly disseminated virulence plasmid in gut colonization, but found no evidence for a direct benefit of plasmid carriage. Through plasmid stability assays, we demonstrate that this plasmid is maintained in a parasitic manner, by strong first-line inheritance mechanisms, acting on the single-cell level, rather than providing a direct survival advantage in the gut. Investigating the ecology of endemic accessory genetic elements, in their pathogenic hosts and native environment, is of vital importance if we want to understand the evolution and persistence of highly virulent and drug resistant bacterial isolates.

  8. Cultural repertoires and food-related household technology within colonia households under conditions of material hardship

    Directory of Open Access Journals (Sweden)

    Dean Wesley R

    2012-05-01

    Full Text Available Abstract Introduction Mexican-origin women in the U.S. living in colonias (new-destination Mexican-immigrant communities along the Texas-Mexico border suffer from a high incidence of food insecurity and diet-related chronic disease. Understanding environmental factors that influence food-related behaviors among this population will be important to improving the well-being of colonia households. This article focuses on cultural repertoires that enable food choice and the everyday uses of technology in food-related practice by Mexican-immigrant women in colonia households under conditions of material hardship. Findings are presented within a conceptual framework informed by concepts drawn from sociological accounts of technology, food choice, culture, and material hardship. Methods Field notes were provided by teams of promotora-researchers (indigenous community health workers and public-health professionals trained as participant observers. They conducted observations on three separate occasions (two half-days during the week and one weekend day within eight family residences located in colonias near the towns of Alton and San Carlos, Texas. English observations were coded inductively and early observations stressed the importance of technology and material hardship in food-related behavior. These observations were further explored and coded using the qualitative data package Atlas.ti. Results Technology included kitchen implements used in standard and adapted configurations and household infrastructure. Residents employed tools across a range of food-related activities identified as forms of food acquisition, storage, preparation, serving, feeding and eating, cleaning, and waste processing. Material hardships included the quality, quantity, acceptability, and uncertainty dimensions of food insecurity, and insufficient consumption of housing, clothing and medical care. Cultural repertoires for coping with material hardship included reliance on

  9. Rules of song development and their use in vocal interactions by birds with large repertoires

    Directory of Open Access Journals (Sweden)

    Nicole Geberzahn

    2004-06-01

    Full Text Available Songbirds are well known for settling their disputes by vocal signals, and their singing plays a dominant role. Most studies on this issue have concentrated on bird species that develop and use small vocal repertoires. In this article we will go farther and focus on examples of how species with large song repertoires make use of their vocal competence. In particular, we will outline the study of interaction rules which have been elucidated by examining time- and pattern-specific relationships between signals exchanged by territorial neighbors. First we present an inquiry into the rules of song learning and development. In birds with large song repertoires, the ontogeny of such rules proceeds along a number of trajectories which help in understanding the often remarkable accomplishments of adult birds. In both approaches, our model species will be the Common Nightingale Luscinia megarhynchos that has been investigated intensively in the field and in the laboratory.Pássaros canoros são bem conhecidos por resolver suas brigas através de sinais vocais e seu canto tem um papel dominante. A maioria dos estudos sobre este assunto focalizou espécies de aves que desenvolvem e usam repertórios vocais pequenos. Neste artigo iremos mais longe, examinando como espécies com grandes repertórios fazem uso de suas capacidades. Descreveremos particularmente o estudo das regras de interação que foram desvendadas pelo exame das relações temporais e estruturais entre os sinais trocados por vizinhos. Inicialmente, investigamos as regras de aprendizagem e desenvolvimento do canto. Nas aves com grande repertório vocal, a ontogênese dessas regras segue certas trajetórias que ajudam a entender o desempenho dos adultos, geralmente notável. Em ambas abordagens, nossa espécie-modelo será o Rouxinol-comum Luscinia megarhynchos, que foi pesquisado intensamente no campo e no laboratório.

  10. Cultural repertoires and food-related household technology within colonia households under conditions of material hardship.

    Science.gov (United States)

    Dean, Wesley R; Sharkey, Joseph R; Johnson, Cassandra M; St John, Julie

    2012-05-15

    BSTRACT: Mexican-origin women in the U.S. living in colonias (new-destination Mexican-immigrant communities) along the Texas-Mexico border suffer from a high incidence of food insecurity and diet-related chronic disease. Understanding environmental factors that influence food-related behaviors among this population will be important to improving the well-being of colonia households. This article focuses on cultural repertoires that enable food choice and the everyday uses of technology in food-related practice by Mexican-immigrant women in colonia households under conditions of material hardship. Findings are presented within a conceptual framework informed by concepts drawn from sociological accounts of technology, food choice, culture, and material hardship. Field notes were provided by teams of promotora-researchers (indigenous community health workers) and public-health professionals trained as participant observers. They conducted observations on three separate occasions (two half-days during the week and one weekend day) within eight family residences located in colonias near the towns of Alton and San Carlos, Texas. English observations were coded inductively and early observations stressed the importance of technology and material hardship in food-related behavior. These observations were further explored and coded using the qualitative data package Atlas.ti. Technology included kitchen implements used in standard and adapted configurations and household infrastructure. Residents employed tools across a range of food-related activities identified as forms of food acquisition, storage, preparation, serving, feeding and eating, cleaning, and waste processing. Material hardships included the quality, quantity, acceptability, and uncertainty dimensions of food insecurity, and insufficient consumption of housing, clothing and medical care. Cultural repertoires for coping with material hardship included reliance on inexpensive staple foods and dishes, and

  11. Monitoring Forest Dynamics in the Andean Amazon: The Applicability of Breakpoint Detection Methods Using Landsat Time-Series and Genetic Algorithms

    Directory of Open Access Journals (Sweden)

    Fabián Santos

    2017-01-01

    Full Text Available The Andean Amazon is an endangered biodiversity hot spot but its forest dynamics are less studied than those of the Amazon lowland and forests from middle or high latitudes. This is because its landscape variability, complex topography and cloudy conditions constitute a challenging environment for any remote-sensing assessment. Breakpoint detection with Landsat time-series data is an established robust approach for monitoring forest dynamics around the globe but has not been properly evaluated for implementation in the Andean Amazon. We analyzed breakpoint detection-generated forest dynamics in order to determine its limitations when applied to three different study areas located along an altitude gradient in the Andean Amazon in Ecuador. Using all available Landsat imagery for the period 1997–2016, we evaluated different pre-processing approaches, noise reduction techniques, and breakpoint detection algorithms. These procedures were integrated into a complex function called the processing chain generator. Calibration was not straightforward since it required us to define values for 24 parameters. To solve this problem, we implemented a novel approach using genetic algorithms. We calibrated the processing chain generator by applying a stratified training sampling and a reference dataset based on high resolution imagery. After the best calibration solution was found and the processing chain generator executed, we assessed accuracy and found that data gaps, inaccurate co-registration, radiometric variability in sensor calibration, unmasked cloud, and shadows can drastically affect the results, compromising the application of breakpoint detection in mountainous areas of the Andean Amazon. Moreover, since breakpoint detection analysis of landscape variability in the Andean Amazon requires a unique calibration of algorithms, the time required to optimize analysis could complicate its proper implementation and undermine its application for large

  12. Dynamic HIV-1 genetic recombination and genotypic drug resistance among treatment-experienced adults in northern Ghana.

    Science.gov (United States)

    Nii-Trebi, Nicholas Israel; Brandful, James Ashun Mensah; Ibe, Shiro; Sugiura, Wataru; Barnor, Jacob Samson; Bampoh, Patrick Owiredu; Yamaoka, Shoji; Matano, Tetsuro; Yoshimura, Kazuhisa; Ishikawa, Koichi; Ampofo, William Kwabena

    2017-11-01

    There have been hardly any reports on the human immunodeficiency virus type 1 (HIV-1) drug-resistance profile from northern Ghana since antiretroviral therapy (ART) was introduced over a decade ago. This study investigated prevailing HIV-1 subtypes and examined the occurrence of drug resistance in ART-experienced patients in Tamale, the capital of the Northern Region of Ghana. A cross-sectional study was carried out on HIV-infected adult patients receiving first-line ART. HIV viral load (VL) and CD4 + T-cell counts were measured. The pol gene sequences were analysed for genotypic resistance by an in-house HIV-1 drug-resistance test; the prevailing HIV-1 subtypes were analysed in detail.Results/Key findings. A total of 33 subjects were studied. Participants comprised 11 males (33.3 %) and 22 (66.7 %) females, with a median age of 34.5 years [interquartile range (IQR) 30.0-40.3]. The median duration on ART was 12 months (IQR 8.0-24). Of the 24 subjects successfully genotyped, 10 (41.7 %) viruses possessed at least one mutation conferring resistance to nucleoside or non-nucleoside reverse-transcriptase inhibitors (NRTIs/NNRTIs). Two-class drug resistance to NRTI and NNRTI was mostly detected (25 %, 6/24). The most frequent mutations were lamivudine-resistance M184V and efavirenz/nevirapine-resistance K103N. HIV-1 subtype CRF02_AG was predominant (79.2 %). Other HIV-1 subtypes detected were G (8.3 %), A3 (4.2 %) and importantly two (8.3 %) unique HIV-1 recombinant forms with CRF02_AG/A3 mosaic. HIV-1 shows high genetic diversity and on-going viral genetic recombination in the study region. Nearly 42 % of the patients studied harboured a drug-resistant virus. The study underscores the need for continued surveillance of HIV-1 subtype diversity; and of drug-resistance patterns to guide selection of second-line regimens in northern Ghana.

  13. Children show limited movement repertoire when learning a novel motor skill.

    Science.gov (United States)

    Lee, Mei-Hua; Farshchiansadegh, Ali; Ranganathan, Rajiv

    2017-09-27

    Examining age differences in motor learning using real-world tasks is often problematic due to task novelty and biomechanical confounds. Here, we investigated how children and adults acquire a novel motor skill in a virtual environment. Participants of three different age groups (9-year-olds, 12-year-olds, and adults) learned to use their upper body movements to control a cursor on a computer screen. Results showed that 9-year-old and 12-year-old children showed poorer ability to control the cursor at the end of practice. Critically, when we investigated the movement coordination, we found that the lower task performance of children was associated with limited exploration of their movement repertoire. These results reveal the critical role of motor exploration in understanding developmental differences in motor learning. © 2017 John Wiley & Sons Ltd.

  14. WORKS FOR CLARINET AND ACCOMPANIMENT IN OLEG NEGRUŢA’S COMPOSITION REPERTOIRE

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    MUŞAT SERGHEI

    2015-06-01

    Full Text Available Oleg Negruţa’s composition repertoire for solo instruments with accompaniment, of which clarinet opuses are highlighted, is important for indigenous musical art. In a vast genre complex, it confirms the composer’s constant commitment to the idea of the Bessarabian professional school. In this sense, as relevant works can be considered the three pieces for clarinet and piano: Improvisation, Fantasy on a Theme by Paganini and Elegy. However, this article is meant to offer details in an analytical way about Negruţa’s specific language and, moreover, to emphasize the author’s mastery of combining folklore elements with others characteristic ofjazz, both being treated according to the canons of academic music.

  15. Linguistic repertoires of interdisciplinarity in brazilian journals in the area of psychology

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    Mary Jane Paris Spink

    2014-12-01

    Full Text Available This paper is about manners in which linguistic repertoires of interdisciplinarity for dissemination of scientific knowledge are coordinated. It starts with a contextualization about interdisciplinarity and ways in which disciplines are organized for administrative purposes in Brazil. It seeks to answer the question: how these forms of ordering, controlling and coordinating interdisciplinary operate in the dissemination of scientific knowledge? The analysis of the ways of coordinating interdisciplinarity in scientific dissemination was based on the editorial proposals of journals classified as A1, A2 and B1 in the Qualis of the area of Psychology. The conclusion of this analysis is that scientific journals enact interdisciplinarity in different manners because they use various forms of association based on themes, related areas, and theories or theoretical frameworks. We conclude the analysis with a discussion of the implications of the various manners of coordinating knowledge for the dissemination of information for the public at large.

  16. Profiling the repertoire of phenotypes influenced by environmental cues that occur during asexual reproduction.

    Science.gov (United States)

    Dombrovsky, Aviv; Arthaud, Laury; Ledger, Terence N; Tares, Sophie; Robichon, Alain

    2009-11-01

    The aphid Acyrthosiphon pisum population is composed of different morphs, such as winged and wingless parthenogens, males, and sexual females. The combined effect of reduced photoperiodicity and cold in fall triggers the apparition of sexual morphs. In contrast they reproduce asexually in spring and summer. In our current study, we provide evidence that clonal individuals display phenotypic variability within asexual morph categories. We describe that clones sharing the same morphological features, which arose from the same founder mother, constitute a repertoire of variants with distinct behavioral and physiological traits. Our results suggest that the prevailing environmental conditions influence the recruitment of adaptive phenotypes from a cohort of clonal individuals exhibiting considerable molecular diversity. However, we observed that the variability might be reduced or enhanced by external factors, but is never abolished in accordance with a model of stochastically produced phenotypes. This overall mechanism allows the renewal of colonies from a few adapted individuals that survive drastic episodic changes in a fluctuating environment.

  17. Bread, milk and a Tattslotto ticket: the interpretive repertoires of young adult gambling in Australia.

    Science.gov (United States)

    Nekich, Maree Ann; Ohtsuka, Keis

    2016-01-01

    The discourse of Australian young adults who gamble regularly was analysed to explore key dilemmas and challenges of a generation who grew up with the positive and negative impacts of gambling advertisements. Qualitative interviews of seven young recreational gamblers who regularly frequent gaming machine venues were conducted. The discourse that they used to describe their gambling involvement, motivation, development and subjective views were analysed and three central repertoires: 'Culture not self,' 'If it makes you happy,' and 'No problem here!' were identified. The current findings demonstrate the participants' attempts to understand and legitimise their gambling. Further, it was suggested that young adults face a series of dilemmas when deciding whether to gamble and to what extent they gamble. Their discourse highlights the tension between individual agency, societal expectations and familial influence. The respondents primarily gambled for social reasons in a manner which they perceived as culturally acceptable. The importance of harm minimization and public awareness campaigns directed at young adults was also discussed.

  18. Using Existing Response Repertoires to Make Sense of Information System Implementation

    DEFF Research Database (Denmark)

    Jensen, Tina Blegind; Kjærgaard, Annemette Leonhardt

    2010-01-01

    The implementation of information systems (IS) in organizations often triggers new situations in which users experience a disruption of existing work patterns and routines. Sensemaking becomes central in making users’ meanings explicit, serving as a foundation for further actions and interactions...... with the new technology. The purpose of this paper is to study how users make sense of new technologies by building on existing response repertoires. Empirically, we present findings from a study of an Electronic Patient Record (EPR) system implementation in two Danish hospital wards. Our findings illustrate...... to existing literature by providing a detailed account of how users’ early sensemaking of a technology influences their subsequent actions and reactions towards it. Our findings support managers in understanding users’ perceptions of a new technology, helping them in planning and executing the implementation...

  19. Protest Leadership and Repertoire: A Comparative Analysis of Peasant Protest in Hunan in the 1990s

    Directory of Open Access Journals (Sweden)

    Wu Zhang

    2013-01-01

    Full Text Available Based on detailed ethnographic fieldwork, this paper compares two cases of peasant protest against heavy taxes and fees in a northern Hunan county in the 1990s. It argues that peasant protest did not arise spontaneously. Rather, it erupted when leaders emerged who used central policy documents on lowering peasant taxes and fees to mobilise peasants. Protest leaders were articulate and public-spirited peasants who had received political training from the local party-state. Furthermore, the number of leaders, their education level, and their relationship with the local party-state explain why the repertoire and the scope of the two protests varied. Protests led by less educated veteran Communist Party cadres tended to be milder and smaller than those led by better-educated peasants more distant from the local party-state. This paper helps us to understand the process of peasant mobilisation in contemporary China and explains why peasant protest varies across cases.

  20. Structural and Genetic Studies Demonstrate Neurologic Dysfunction in Triosephosphate Isomerase Deficiency Is Associated with Impaired Synaptic Vesicle Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Roland, Bartholomew P.; Zeccola, Alison M.; Larsen, Samantha B.; Amrich, Christopher G.; Talsma, Aaron D.; Stuchul, Kimberly A.; Heroux, Annie; Levitan, Edwin S.; VanDemark, Andrew P.; Palladino, Michael J.; Pallanck, Leo J.

    2016-03-31

    Triosephosphate isomerase (TPI) deficiency is a poorly understood disease characterized by hemolytic anemia, cardiomyopathy, neurologic dysfunction, and early death. TPI deficiency is one of a group of diseases known as glycolytic enzymopathies, but is unique for its severe patient neuropathology and early mortality. The disease is caused by missense mutations and dysfunction in the glycolytic enzyme, TPI. Previous studies have detailed structural and catalytic changes elicited by disease-associated TPI substitutions, and samples of patient erythrocytes have yielded insight into patient hemolytic anemia; however, the neuropathophysiology of this disease remains a mystery. This study combines structural, biochemical, and genetic approaches to demonstrate that perturbations of the TPI dimer interface are sufficient to elicit TPI deficiency neuropathogenesis. The present study demonstrates that neurologic dysfunction resulting from TPI deficiency is characterized by synaptic vesicle dysfunction, and can be attenuated with catalytically inactive TPI. Collectively, our findings are the first to identify, to our knowledge, a functional synaptic defect in TPI deficiency derived from molecular changes in the TPI dimer interface.

  1. 'They don't understand…you cut yourself in order to live.' Interpretative repertoires jointly constructing interactions between adult women who self-harm and professional caregivers.

    Science.gov (United States)

    Lindgren, Britt-Marie; Oster, Inger; Aström, Sture; Hällgren Graneheim, Ulla

    2011-01-01

    The aim of the study was to illuminate interpretative repertoires that jointly construct the interaction between adult women who self-harm and professional caregivers in psychiatric inpatient care. Participant observations and informal interviews were conducted among six women who self-harm and their professional caregivers in two psychiatric inpatient wards, and analysed using the concept of interpretative repertoires from the discipline of discursive psychology. The analysis revealed four interpretative repertoires that jointly constructed the interaction. The professional caregivers used a "fostering repertoire" and a "supportive repertoire" and the women who self-harmed used a "victim repertoire" and an "expert repertoire." The women and the caregivers were positioned and positioned themselves and people around them within and among these interpretative repertoires to make sense of their experiences of the interaction. It was necessary to consider each woman's own life chances and knowledge about herself and her needs. The participants made it clear that it was essential for them to be met with respect as individuals. Professional caregivers need to work in partnership with individuals who self-harm-experts by profession collaborating with experts by experience. Caregivers need to look beyond behavioural symptoms and recognise each individual's possibilities for agency.

  2. Statistical inference of the generation probability of T-cell receptors from sequence repertoires.

    Science.gov (United States)

    Murugan, Anand; Mora, Thierry; Walczak, Aleksandra M; Callan, Curtis G

    2012-10-02

    Stochastic rearrangement of germline V-, D-, and J-genes to create variable coding sequence for certain cell surface receptors is at the origin of immune system diversity. This process, known as "VDJ recombination", is implemented via a series of stochastic molecular events involving gene choices and random nucleotide insertions between, and deletions from, genes. We use large sequence repertoires of the variable CDR3 region of human CD4+ T-cell receptor beta chains to infer the statistical properties of these basic biochemical events. Because any given CDR3 sequence can be produced in multiple ways, the probability distribution of hidden recombination events cannot be inferred directly from the observed sequences; we therefore develop a maximum likelihood inference method to achieve this end. To separate the properties of the molecular rearrangement mechanism from the effects of selection, we focus on nonproductive CDR3 sequences in T-cell DNA. We infer the joint distribution of the various generative events that occur when a new T-cell receptor gene is created. We find a rich picture of correlation (and absence thereof), providing insight into the molecular mechanisms involved. The generative event statistics are consistent between individuals, suggesting a universal biochemical process. Our probabilistic model predicts the generation probability of any specific CDR3 sequence by the primitive recombination process, allowing us to quantify the potential diversity of the T-cell repertoire and to understand why some sequences are shared between individuals. We argue that the use of formal statistical inference methods, of the kind presented in this paper, will be essential for quantitative understanding of the generation and evolution of diversity in the adaptive immune system.

  3. Roaring high and low: composition and possible functions of the Iberian stag's vocal repertoire.

    Directory of Open Access Journals (Sweden)

    Daniela Passilongo

    Full Text Available We provide a detailed description of the rutting vocalisations of free-ranging male Iberian deer (Cervus elaphus hispanicus, Hilzheimer 1909, a geographically isolated and morphologically differentiated subspecies of red deer Cervus elaphus. We combine spectrographic examinations, spectral analyses and automated classifications to identify different call types, and compare the composition of the vocal repertoire with that of other red deer subspecies. Iberian stags give bouts of roars (and more rarely, short series of barks that are typically composed of two different types of calls. Long Common Roars are mostly given at the beginning or at the end of the bout, and are characterised by a high fundamental frequency (F0 resulting in poorly defined formant frequencies but a relatively high amplitude. In contrast, Short Common Roars are typically given in the middle or at the end of the bout, and are characterised by a lower F0 resulting in relatively well defined vocal tract resonances, but low amplitude. While we did not identify entirely Harsh Roars (as described in the Scottish red deer subspecies (Cervus elaphus scoticus, a small percentage of Long Common Roars contained segments of deterministic chaos. We suggest that the evolution of two clearly distinct types of Common Roars may reflect divergent selection pressures favouring either vocal efficiency in high pitched roars or the communication of body size in low-pitched, high spectral density roars highlighting vocal tract resonances. The clear divergence of the Iberian red deer vocal repertoire from those of other documented European red deer populations reinforces the status of this geographical variant as a distinct subspecies.

  4. Contribution of V(H replacement products in mouse antibody repertoire.

    Directory of Open Access Journals (Sweden)

    Lin Huang

    Full Text Available VH replacement occurs through RAG-mediated recombination between the cryptic recombination signal sequence (cRSS near the 3' end of a rearranged VH gene and the 23-bp RSS from an upstream unrearranged VH gene. Due to the location of the cRSS, VH replacement leaves a short stretch of nucleotides from the previously rearranged VH gene at the newly formed V-D junction, which can be used as a marker to identify VH replacement products. To determine the contribution of VH replacement products to mouse antibody repertoire, we developed a Java-based VH Replacement Footprint Analyzer (VHRFA program and analyzed 17,179 mouse IgH gene sequences from the NCBI database to identify VH replacement products. The overall frequency of VH replacement products in these IgH genes is 5.29% based on the identification of pentameric VH replacement footprints at their V-D junctions. The identified VH replacement products are distributed similarly in IgH genes using most families of VH genes, although different families of VH genes are used differentially. The frequencies of VH replacement products are significantly elevated in IgH genes derived from several strains of autoimmune prone mice and in IgH genes encoding autoantibodies. Moreover, the identified VH replacement footprints in IgH genes from autoimmune prone mice or IgH genes encoding autoantibodies preferentially encode positively charged amino acids. These results revealed a significant contribution of VH replacement products to the diversification of antibody repertoire and potentially, to the generation of autoantibodies in mice.

  5. Cloning of the Repertoire of Individual Plasmodium falciparum var Genes Using Transformation Associated Recombination (TAR)

    Science.gov (United States)

    Schmid, Christoph D.; Bühlmann, Tobias; Louis, Edward J.; Beck, Hans-Peter

    2011-01-01

    One of the major virulence factors of the malaria causing parasite is the Plasmodium falciparum encoded erythrocyte membrane protein 1 (PfEMP1). It is translocated to It the membrane of infected erythrocytes and expressed from approximately 60 var genes in a mutually exclusive manner. Switching of var genes allows the parasite to alter functional and antigenic properties of infected erythrocytes, to escape the immune defense and to establish chronic infections. We have developed an efficient method for isolating VAR genes from telomeric and other genome locations by adapting transformation-associated recombination (TAR) cloning, which can then be analyzed and sequenced. For this purpose, three plasmids each containing a homologous sequence representing the upstream regions of the group A, B, and C var genes and a sequence homologous to the conserved acidic terminal segment (ATS) of var genes were generated. Co-transfection with P. falciparum strain ITG2F6 genomic DNA in yeast cells yielded 200 TAR clones. The relative frequencies of clones from each group were not biased. Clones were screened by PCR, as well as Southern blotting, which revealed clones missed by PCR due to sequence mismatches with the primers. Selected clones were transformed into E. coli and further analyzed by RFLP and end sequencing. Physical analysis of 36 clones revealed 27 distinct types potentially representing 50% of the var gene repertoire. Three clones were selected for sequencing and assembled into single var gene containing contigs. This study demonstrates that it is possible to rapidly obtain the repertoire of var genes from P. falciparum within a single set of cloning experiments. This technique can be applied to individual isolates which will provide a detailed picture of the diversity of var genes in the field. This is a powerful tool to overcome the obstacles with cloning and assembly of multi-gene families by simultaneously cloning each member. PMID:21408186

  6. Massively Parallel RNA Sequencing Identifies a Complex Immune Gene Repertoire in the lophotrochozoan Mytilus edulis

    Science.gov (United States)

    Philipp, Eva E. R.; Kraemer, Lars; Melzner, Frank; Poustka, Albert J.; Thieme, Sebastian; Findeisen, Ulrike; Schreiber, Stefan; Rosenstiel, Philip

    2012-01-01

    The marine mussel Mytilus edulis and its closely related sister species are distributed world-wide and play an important role in coastal ecology and economy. The diversification in different species and their hybrids, broad ecological distribution, as well as the filter feeding mode of life has made this genus an attractive model to investigate physiological and molecular adaptations and responses to various biotic and abiotic environmental factors. In the present study we investigated the immune system of Mytilus, which may contribute to the ecological plasticity of this species. We generated a large Mytilus transcriptome database from different tissues of immune challenged and stress treated individuals from the Baltic Sea using 454 pyrosequencing. Phylogenetic comparison of orthologous groups of 23 species demonstrated the basal position of lophotrochozoans within protostomes. The investigation of immune related transcripts revealed a complex repertoire of innate recognition receptors and downstream pathway members including transcripts for 27 toll-like receptors and 524 C1q domain containing transcripts. NOD-like receptors on the other hand were absent. We also found evidence for sophisticated TNF, autophagy and apoptosis systems as well as for cytokines. Gill tissue and hemocytes showed highest expression of putative immune related contigs and are promising tissues for further functional studies. Our results partly contrast with findings of a less complex immune repertoire in ecdysozoan and other lophotrochozoan protostomes. We show that bivalves are interesting candidates to investigate the evolution of the immune system from basal metazoans to deuterostomes and protostomes and provide a basis for future molecular work directed to immune system functioning in Mytilus. PMID:22448234

  7. Next generation sequencing reveals skewing of the T and B cell receptor repertoires in patients with Wiskott Aldrich syndrome

    Directory of Open Access Journals (Sweden)

    Amy E O'Connell

    2014-07-01

    Full Text Available The Wiskott Aldrich syndrome (WAS is due to mutations of the WAS gene encoding for the cytoskeletal WAS protein (WASp, leading to abnormal downstream signaling from the T cell and B cell antigen receptors (TCR, BCR. We hypothesized that the impaired signaling through the TCR and BCR in WAS would subsequently lead to aberrations in the immune repertoire of WAS patients. Using next generation sequencing, the T cell receptor beta (TRB and B cell immunoglobulin heavy chain (IGH repertoires of 8 patients with WAS and 6 controls were sequenced. Clonal expansions were identified within memory CD4+ cells, as well as in total, naïve and memory CD8+ cells from WAS patients. In the B cell compartment, WAS patient IGH repertoires were also clonally expanded and showed skewed usage of IGHV and IGHJ genes, and increased usage of IGHG constant genes, compared with controls. To our knowledge, this is the first study that demonstrates significant abnormalities of the immune repertoire in WAS patients using next generation sequencing.

  8. Identity, small stories and interpretative repertoires in research interviews. An account of market researchers’ discursive positioning strategies

    Directory of Open Access Journals (Sweden)

    Cosmin Toth

    2014-12-01

    Full Text Available My main purpose in this paper is to illustrate how participants in a research interview occasioned conversation make use of two important discursive devices, namely: small stories and interpretative repertoires for positioning during interaction in order to foster certain situated identity claims. The premises I work with in this paper are that identity is a practiced situated accomplishment, that small stories are devices employed frequently for identity work that are no less important than extended autobiographical expositions, and that interpretative repertoires are practiced ways of speaking that allow participants to manage their positions in certain ways. Moreover, I will try to show that positioning by means of small stories and interpretative repertoires should be understood in direct relation with the identities and other membership categories made relevant by the interviewer. When participants’ positions are conflicting or miss-aligned, a more pronounced identity work is employed on the part of the interviewee, sustained by certain repertoires’ management strategies: alternation, nuancing, or rejecting certain repertoires.

  9. Behavioral Cusps: A Person-Centered Concept for Establishing Pivotal Individual, Family, and Community Behaviors and Repertoires

    Science.gov (United States)

    Smith, Garnett J.; McDougall, Dennis; Edelen-Smith, Patricia

    2006-01-01

    Cumulative-hierarchical learning (CHL) and behavior, a premise first introduced by Staats in 1975, describes how higher-level behavioral patterns and structures can emerge from interactions among a set of lower-level actions. Proponents of CHL emphasize the importance of pivotal response interventions, behavior repertoires, generative learning,…

  10. Multilocus Sequence Typing Reveals Relevant Genetic Variation and Different Evolutionary Dynamics among Strains of Xanthomonas arboricola pv. juglandis

    Directory of Open Access Journals (Sweden)

    Marco Scortichini

    2010-11-01

    Full Text Available Forty-five Xanthomonas arboricola pv. juglandis (Xaj strains originating from Juglans regia cultivation in different countries were molecularly typed by means of MultiLocus Sequence Typing (MLST, using acnB, gapA, gyrB and rpoD gene fragments. A total of 2.5 kilobases was used to infer the phylogenetic relationship among the strains and possible recombination events. Haplotype diversity, linkage disequilibrium analysis, selection tests, gene flow estimates and codon adaptation index were also assessed. The dendrograms built by maximum likelihood with concatenated nucleotide and amino acid sequences revealed two major and two minor phylotypes. The same haplotype was found in strains originating from different continents, and different haplotypes were found in strains isolated in the same year from the same location. A recombination breakpoint was detected within the rpoD gene fragment. At the pathovar level, the Xaj populations studied here are clonal and under neutral selection. However, four Xaj strains isolated from walnut fruits with apical necrosis are under diversifying selection, suggesting a possible new adaptation. Gene flow estimates do not support the hypothesis of geographic isolation of the strains, even though the genetic diversity between the strains increases as the geographic distance between them increases. A triplet deletion, causing the absence of valine, was found in the rpoD fragment of all 45 Xaj strains when compared with X. axonopodis pv. citri strain 306. The codon adaptation index was high in all four genes studied, indicating a relevant metabolic activity.

  11. No Adverse Effect of Genetically Modified Antifungal Wheat on Decomposition Dynamics and the Soil Fauna Community – A Field Study

    Science.gov (United States)

    Duc, Caroline; Nentwig, Wolfgang; Lindfeld, Andreas

    2011-01-01

    The cultivation of genetically modified (GM) plants has raised several environmental concerns. One of these concerns regards non-target soil fauna organisms, which play an important role in the decomposition of organic matter and hence are largely exposed to GM plant residues. Soil fauna may be directly affected by transgene products or indirectly by pleiotropic effects such as a modified plant metabolism. Thus, ecosystem services and functioning might be affected negatively. In a litterbag experiment in the field we analysed the decomposition process and the soil fauna community involved. Therefore, we used four experimental GM wheat varieties, two with a race-specific antifungal resistance against powdery mildew (Pm3b) and two with an unspecific antifungal resistance based on the expression of chitinase and glucanase. We compared them with two non-GM isolines and six conventional cereal varieties. To elucidate the mechanisms that cause differences in plant decomposition, structural plant components (i.e. C∶N ratio, lignin, cellulose, hemicellulose) were examined and soil properties, temperature and precipitation were monitored. The most frequent taxa extracted from decaying plant material were mites (Cryptostigmata, Gamasina and Uropodina), springtails (Isotomidae), annelids (Enchytraeidae) and Diptera (Cecidomyiidae larvae). Despite a single significant transgenic/month interaction for Cecidomyiidae larvae, which is probably random, we detected no impact of the GM wheat on the soil fauna community. However, soil fauna differences among conventional cereal varieties were more pronounced than between GM and non-GM wheat. While leaf residue decomposition in GM and non-GM wheat was similar, differences among conventional cereals were evident. Furthermore, sampling date and location were found to greatly influence soil fauna community and decomposition processes. The results give no indication of ecologically relevant adverse effects of antifungal GM wheat on the

  12. No adverse effect of genetically modified antifungal wheat on decomposition dynamics and the soil fauna community--a field study.

    Science.gov (United States)

    Duc, Caroline; Nentwig, Wolfgang; Lindfeld, Andreas

    2011-01-01

    The cultivation of genetically modified (GM) plants has raised several environmental concerns. One of these concerns regards non-target soil fauna organisms, which play an important role in the decomposition of organic matter and hence are largely exposed to GM plant residues. Soil fauna may be directly affected by transgene products or indirectly by pleiotropic effects such as a modified plant metabolism. Thus, ecosystem services and functioning might be affected negatively. In a litterbag experiment in the field we analysed the decomposition process and the soil fauna community involved. Therefore, we used four experimental GM wheat varieties, two with a race-specific antifungal resistance against powdery mildew (Pm3b) and two with an unspecific antifungal resistance based on the expression of chitinase and glucanase. We compared them with two non-GM isolines and six conventional cereal varieties. To elucidate the mechanisms that cause differences in plant decomposition, structural plant components (i.e. C∶N ratio, lignin, cellulose, hemicellulose) were examined and soil properties, temperature and precipitation were monitored. The most frequent taxa extracted from decaying plant material were mites (Cryptostigmata, Gamasina and Uropodina), springtails (Isotomidae), annelids (Enchytraeidae) and Diptera (Cecidomyiidae larvae). Despite a single significant transgenic/month interaction for Cecidomyiidae larvae, which is probably random, we detected no impact of the GM wheat on the soil fauna community. However, soil fauna differences among conventional cereal varieties were more pronounced than between GM and non-GM wheat. While leaf residue decomposition in GM and non-GM wheat was similar, differences among conventional cereals were evident. Furthermore, sampling date and location were found to greatly influence soil fauna community and decomposition processes. The results give no indication of ecologically relevant adverse effects of antifungal GM wheat on the

  13. No adverse effect of genetically modified antifungal wheat on decomposition dynamics and the soil fauna community--a field study.

    Directory of Open Access Journals (Sweden)

    Caroline Duc

    Full Text Available The cultivation of genetically modified (GM plants has raised several environmental concerns. One of these concerns regards non-target soil fauna organisms, which play an important role in the decomposition of organic matter and hence are largely exposed to GM plant residues. Soil fauna may be directly affected by transgene products or indirectly by pleiotropic effects such as a modified plant metabolism. Thus, ecosystem services and functioning might be affected negatively. In a litterbag experiment in the field we analysed the decomposition process and the soil fauna community involved. Therefore, we used four experimental GM wheat varieties, two with a race-specific antifungal resistance against powdery mildew (Pm3b and two with an unspecific antifungal resistance based on the expression of chitinase and glucanase. We compared them with two non-GM isolines and six conventional cereal varieties. To elucidate the mechanisms that cause differences in plant decomposition, structural plant components (i.e. C∶N ratio, lignin, cellulose, hemicellulose were examined and soil properties, temperature and precipitation were monitored. The most frequent taxa extracted from decaying plant material were mites (Cryptostigmata, Gamasina and Uropodina, springtails (Isotomidae, annelids (Enchytraeidae and Diptera (Cecidomyiidae larvae. Despite a single significant transgenic/month interaction for Cecidomyiidae larvae, which is probably random, we detected no impact of the GM wheat on the soil fauna community. However, soil fauna differences among conventional cereal varieties were more pronounced than between GM and non-GM wheat. While leaf residue decomposition in GM and non-GM wheat was similar, differences among conventional cereals were evident. Furthermore, sampling date and location were found to greatly influence soil fauna community and decomposition processes. The results give no indication of ecologically relevant adverse effects of antifungal GM

  14. Genetic characterization of low-pathogenic avian influenza viruses isolated on the Izumi plain in Japan: possible association of dynamic movements of wild birds with AIV evolution.

    Science.gov (United States)

    Nakagawa, Hiroko; Okuya, Kosuke; Kawabata, Toshiko; Matsuu, Aya; Takase, Kozo; Kuwahara, Masakazu; Toda, Shigehisa; Ozawa, Makoto

    2018-04-01

    The Izumi plain in Kagoshima Prefecture, Japan, is an overwintering site of endangered cranes (hooded cranes and white-naped cranes) and of many other migratory birds (including wild ducks) that are considered carriers of avian influenza viruses (AIVs). To assess the risks of a highly pathogenic avian influenza outbreak in the crane populations, we tested various environmental samples for AIVs in this area. In the 2014-2015 winter season, we isolated one AIV of the H6N2 subtype from the cranes' roost water and two AIVs of the H11N9 subtype from a crane fecal sample and a cloacal swab of a dead spot-billed duck. Genetic analysis of these AIV isolates indicated that our H6N2 isolate is genetically close to AIVs isolated from wild birds in Southeast Asian countries, except that the PB1 and NS genes belong to the North American virus lineage. All genes of the two H11N9 isolates are related to AIVs belonging to the Eurasian virus lineage. Notably, in our phylogenetic trees, H11 HA and N9 NA genes showing high sequence similarity to the corresponding genes of isolates from wild birds in South Africa and Spain, respectively, did not cluster in the major groups with recent wild-bird isolates from East Asia. These results suggest that AIVs with viral gene segments derived from various locations and bird species have been brought to the Izumi plain. These findings imply a possible association of dynamic movements of wild birds with AIV evolution.

  15. ClonoCalc and ClonoPlot: immune repertoire analysis from raw files to publication figures with graphical user interface.

    Science.gov (United States)

    Fähnrich, Anke; Krebbel, Moritz; Decker, Normann; Leucker, Martin; Lange, Felix D; Kalies, Kathrin; Möller, Steffen

    2017-03-11

    Next generation sequencing (NGS) technologies enable studies and analyses of the diversity of both T and B cell receptors (TCR and BCR) in human and animal systems to elucidate immune functions in health and disease. Over the last few years, several algorithms and tools have been developed to support respective analyses of raw sequencing data of the immune repertoire. These tools focus on distinct aspects of the data processing and require a strong bioinformatics background. To facilitate the analysis of T and B cell repertoires by less experienced users, software is needed that combines the most common tools for repertoire analysis. We introduce a graphical user interface (GUI) providing a complete analysis pipeline for processing raw NGS data for human and animal TCR and BCR clonotype determination and advanced differential repertoire studies. It provides two applications. ClonoCalc prepares the raw data for downstream analyses. It combines a demultiplexer for barcode splitting and employs MiXCR for paired-end read merging and the extraction of human and animal TCR/BCR sequences. ClonoPlot wraps the R package tcR and further contributes self-developed plots for the descriptive comparative investigation of immune repertoires. This workflow reduces the amount of programming required to perform the respective analyses and supports both communication and training between scientists and technicians, and across scientific disciplines. The Open Source development in Java and R is modular and invites advanced users to extend its functionality. Software and documentation are freely available at https://bitbucket.org/ClonoSuite/clonocalc-plot .

  16. Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study.

    Science.gov (United States)

    de Almeida, Sergio M; Rotta, Indianara; Ribeiro, Clea E; Oliveira, Michelli F; Chaillon, Antoine; de Pereira, Ana Paula; Cunha, Ana Paula; Zonta, Marise; Bents, Joao França; Raboni, Sonia M; Smith, Davey; Letendre, Scott; Ellis, Ronald J

    2017-06-01

    Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

  17. Eye on the B-ALL: B-cell receptor repertoires reveal persistence of numerous B-lymphoblastic leukemia subclones from diagnosis to relapse

    Science.gov (United States)

    Bashford-Rogers, R J M; Nicolaou, K A; Bartram, J; Goulden, N J; Loizou, L; Koumas, L; Chi, J; Hubank, M; Kellam, P; Costeas, P A; Vassiliou, G S

    2016-01-01

    The strongest predictor of relapse in B-cell acute lymphoblastic leukemia (B-ALL) is the level of persistence of tumor cells after initial therapy. The high mutation rate of the B-cell receptor (BCR) locus allows high-resolution tracking of the architecture, evolution and clonal dynamics of B-ALL. Using longitudinal BCR repertoire sequencing, we find that the BCR undergoes an unexpectedly high level of clonal diversification in B-ALL cells through both somatic hypermutation and secondary rearrangements, which can be used for tracking the subclonal composition of the disease and detect minimal residual disease with unprecedented sensitivity. We go on to investigate clonal dynamics of B-ALL using BCR phylogenetic analyses of paired diagnosis-relapse samples and find that large numbers of small leukemic subclones present at diagnosis re-emerge at relapse alongside a dominant clone. Our findings suggest that in all informative relapsed patients, the survival of large numbers of clonogenic cells beyond initial chemotherapy is a surrogate for inherent partial chemoresistance or inadequate therapy, providing an increased opportunity for subsequent emergence of fully resistant clones. These results frame early cytoreduction as an important determinant of long-term outcome. PMID:27211266

  18. Network Approach to Understanding Emotion Dynamics in Relation to Childhood Trauma and Genetic Liability to Psychopathology: Replication of a Prospective Experience Sampling Analysis

    Directory of Open Access Journals (Sweden)

    Laila Hasmi

    2017-11-01

    present findings demonstrate that the network approach may have some value in understanding the relation between established risk factors for mental disorders (particularly GL and the dynamic interplay between emotions. The present finding partially replicates an earlier analysis, suggesting it may be instructive to model negative emotional dynamics as a function of genetic influence.

  19. Studying Air Quality Dynamics using A Linear Genetic Programming Approach over Remotely Sensed Atmospheric Parameters: case study (Cairo, Egypt)

    Science.gov (United States)

    El-Askary, H. M.; Sheta, W.; Prasad, A. K.; Ali, H.; Abdel rahman, M.; El-Desouki, A.; Kafatos, M.

    2011-12-01

    Water Vapor Low Mean, Atmospheric Water Vapor Mean, Mass Concentration Land Mean, Optical Depth Ratio Small Land and Ocean Mean, Small Mode Optical Depth Land and Ocean Mean, Cloud Top Pressure Day Mean, Cloud Top Pressure Mean, Cloud Top Temperature Mean. The suggested linear Genetic approach detected hidden anomalies and relationships that cannot be observed from the conventional statistical methods. A well-established model as an important contribution to show the relationships between particle size and the physical and chemical aerosols properties has been designed. Such coupling will provide insight into the micro physics of the phenomenon. The proposed research will reveal previously uncharacterized yet fundamental relations and dependencies among aerosols, cloud and meteorological related parameters. Moreover, it would aid in filling gaps of missing satellite parameters using other available ones.

  20. A forward-genetic screen and dynamic analysis of lambda phage host-dependencies reveals an extensive interaction network and a new anti-viral strategy.

    Directory of Open Access Journals (Sweden)

    Nathaniel D Maynard

    2010-07-01

    Full Text Available Latently infecting viruses are an important class of virus that plays a key role in viral evolution and human health. Here we report a genome-scale forward-genetics screen for host-dependencies of the latently-infecting bacteriophage lambda. This screen identified 57 Escherichia coli (E. coli genes--over half of which have not been previously associated with infection--that when knocked out inhibited lambda phage's ability to replicate. Our results demonstrate a highly integrated network between lambda and its host, in striking contrast to the results from a similar screen using the lytic-only infecting T7 virus. We then measured the growth of E. coli under normal and infected conditions, using wild-type and knockout strains deficient in one of the identified host genes, and found that genes from the same pathway often exhibited similar growth dynamics. This observation, combined with further computational and experimental analysis, led us to identify a previously unannotated gene, yneJ, as a novel regulator of lamB gene expression. A surprising result of this work was the identification of two highly conserved pathways involved in tRNA thiolation-one pathway is required for efficient lambda replication, while the other has anti-viral properties inhibiting lambda replication. Based on our data, it appears that 2-thiouridine modification of tRNAGlu, tRNAGln, and tRNALys is particularly important for the efficient production of infectious lambda phage particles.

  1. Optimizing the static-dynamic performance of the body-in-white using a modified non-dominated sorting genetic algorithm coupled with grey relational analysis

    Science.gov (United States)

    Wang, Dengfeng; Cai, Kefang

    2018-04-01

    This article presents a hybrid method combining a modified non-dominated sorting genetic algorithm (MNSGA-II) with grey relational analysis (GRA) to improve the static-dynamic performance of a body-in-white (BIW). First, an implicit parametric model of the BIW was built using SFE-CONCEPT software, and then the validity of the implicit parametric model was verified by physical testing. Eight shape design variables were defined for BIW beam structures based on the implicit parametric technology. Subsequently, MNSGA-II was used to determine the optimal combination of the design parameters that can improve the bending stiffness, torsion stiffness and low-order natural frequencies of the BIW without considerable increase in the mass. A set of non-dominated solutions was then obtained in the multi-objective optimization design. Finally, the grey entropy theory and GRA were applied to rank all non-dominated solutions from best to worst to determine the best trade-off solution. The comparison between the GRA and the technique for order of preference by similarity to ideal solution (TOPSIS) illustrated the reliability and rationality of GRA. Moreover, the effectiveness of the hybrid method was verified by the optimal results such that the bending stiffness, torsion stiffness, first order bending and first order torsion natural frequency were improved by 5.46%, 9.30%, 7.32% and 5.73%, respectively, with the mass of the BIW increasing by 1.30%.

  2. Endometrial natural killer (NK) cells reveal a tissue-specific receptor repertoire.

    Science.gov (United States)

    Feyaerts, D; Kuret, T; van Cranenbroek, B; van der Zeeuw-Hingrez, S; van der Heijden, O W H; van der Meer, A; Joosten, I; van der Molen, R G

    2018-02-13

    Is the natural killer (NK) cell receptor repertoire of endometrial NK (eNK) cells tissue-specific? The NK cell receptor (NKR) expression profile in pre-pregnancy endometrium appears to have a unique tissue-specific phenotype, different from that found in NK cells in peripheral blood, suggesting that these cells are finely tuned towards the reception of an allogeneic fetus. NK cells are important for successful pregnancy. After implantation, NK cells encounter extravillous trophoblast cells and regulate trophoblast invasion. NK cell activity is amongst others regulated by C-type lectin heterodimer (CD94/NKG2) and killer cell immunoglobulin-like (KIR) receptors. KIR expression on decidual NK cells is affected by the presence of maternal HLA-C and biased towards KIR2D expression. However, little is known about NKR expression on eNK cells prior to pregnancy. In this study, matched peripheral and menstrual blood (a source of endometrial cells) was obtained from 25 healthy females with regular menstrual cycles. Menstrual blood was collected during the first 36 h of menstruation using a menstrual cup, a non-invasive technique to obtain endometrial cells. KIR and NKG2 receptor expression on eNK cells was characterized by 10-color flow cytometry, and compared to matched pbNK cells of the same female. KIR and HLA-C genotypes were determined by PCR-SSOP techniques. Anti-CMV IgG antibodies in plasma were measured by chemiluminescence immunoassay. KIR expression patterns of eNK cells collected from the same female do not differ over consecutive menstrual cycles. The percentage of NK cells expressing KIR2DL2/L3/S2, KIR2DL3, KIR2DL1, LILRB1 and/or NKG2A was significantly higher in eNK cells compared to pbNK cells, while no significant difference was observed for NKG2C, KIR2DL1/S1, and KIR3DL1. The NKR repertoire of eNK cells was clearly different from pbNK cells, with eNK cells co-expressing more than three NKR simultaneously. In addition, outlier analysis revealed 8 and 15 NKR

  3. Think like a sponge: The genetic signal of sensory cells in sponges.

    Science.gov (United States)

    Mah, Jasmine L; Leys, Sally P

    2017-11-01

    A complex genetic repertoire underlies the apparently simple body plan of sponges. Among the genes present in poriferans are those fundamental to the sensory and nervous systems of other animals. Sponges are dynamic and sensitive animals and it is intuitive to link these genes to behaviour. The proposal that ctenophores are the earliest diverging metazoan has led to the question of whether sponges possess a 'pre-nervous' system or have undergone nervous system loss. Both lines of thought generally assume that the last common ancestor of sponges and eumetazoans possessed the genetic modules that underlie sensory abilities. By corollary extant sponges may possess a sensory cell homologous to one present in the last common ancestor, a hypothesis that has been studied by gene expression. We have performed a meta-analysis of all gene expression studies published to date to explore whether gene expression is indicative of a feature's sensory function. In sponges we find that eumetazoan sensory-neural markers are not particularly expressed in structures with known sensory functions. Instead it is common for these genes to be expressed in cells with no known or uncharacterized sensory function. Indeed, many sensory-neural markers so far studied are expressed during development, perhaps because many are transcription factors. This suggests that the genetic signal of a sponge sensory cell is dissimilar enough to be unrecognizable when compared to a bilaterian sensory or neural cell. It is possible that sensory-neural markers have as yet unknown functions in sponge cells, such as assembling an immunological synapse in the larval globular cell. Furthermore, the expression of sensory-neural markers in non-sensory cells, such as adult and larval epithelial cells, suggest that these cells may have uncharacterized sensory functions. While this does not rule out the co-option of ancestral sensory modules in later evolving groups, a distinct genetic foundation may underlie the

  4. Uncovering the Repertoire of Endogenous Flaviviral Elements in Aedes Mosquito Genomes.

    Science.gov (United States)

    Suzuki, Yasutsugu; Frangeul, Lionel; Dickson, Laura B; Blanc, Hervé; Verdier, Yann; Vinh, Joelle; Lambrechts, Louis; Saleh, Maria-Carla

    2017-08-01

    Endogenous viral elements derived from nonretroviral RNA viruses have been described in various animal genomes. Whether they have a biological function, such as host immune protection against related viruses, is a field of intense study. Here, we investigated the repertoire of endogenous flaviviral elements (EFVEs) in Aedes mosquitoes, the vectors of arboviruses such as dengue and chikungunya viruses. Previous studies identified three EFVEs from Aedes albopictus cell lines and one from Aedes aegypti cell lines. However, an in-depth characterization of EFVEs in wild-type mosquito populations and individual mosquitoes in vivo has not been performed. We detected the full-length DNA sequence of the previously described EFVEs and their respective transcripts in several A. albopictus and A. aegypti populations from geographically distinct areas. However, EFVE-derived proteins were not detected by mass spectrometry. Using deep sequencing, we detected the production of PIWI-interacting RNA-like small RNAs, in an antisense orientation, targeting the EFVEs and their flanking regions in vivo The EFVEs were integrated in repetitive regions of the mosquito genomes, and their flanking sequences varied among mosquito populations. We bioinformatically predicted several new EFVEs from a Vietnamese A. albopictus population and observed variation in the occurrence of those elements among mosquitoes. Phylogenetic analysis of an A. aegypti EFVE suggested that it integrated prior to the global expansion of the species and subsequently diverged among and within populations. The findings of this study together reveal the substantial structural and nucleotide diversity of flaviviral integrations in Aedes genomes. Unraveling this diversity will help to elucidate the potential biological function of these EFVEs. IMPORTANCE Endogenous viral elements (EVEs) are whole or partial viral sequences integrated in host genomes. Interestingly, some EVEs have important functions for host fitness and

  5. Conserved repertoire of orthologous vomeronasal type 1 receptor genes in ruminant species

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    Okamura Hiroaki

    2009-09-01

    Full Text Available Abstract Background In mammals, pheromones play an important role in social and innate reproductive behavior within species. In rodents, vomeronasal receptor type 1 (V1R, which is specifically expressed in the vomeronasal organ, is thought to detect pheromones. The V1R gene repertoire differs dramatically between mammalian species, and the presence of species-specific V1R subfamilies in mouse and rat suggests that V1R plays a profound role in species-specific recognition of pheromones. In ruminants, however, the molecular mechanism(s for pheromone perception is not well understood. Interestingly, goat male pheromone, which can induce out-of-season ovulation in anestrous females, causes the same pheromone response in sheep, and vice versa, suggesting that there may be mechanisms for detecting "inter-species" pheromones among ruminant species. Results We isolated 23 goat and 21 sheep intact V1R genes based on sequence similarity with 32 cow V1R genes in the cow genome database. We found that all of the goat and sheep V1R genes have orthologs in their cross-species counterparts among these three ruminant species and that the sequence identity of V1R orthologous pairs among these ruminants is much higher than that of mouse-rat V1R orthologous pairs. Furthermore, all goat V1Rs examined thus far are expressed not only in the vomeronasal organ but also in the main olfactory epithelium. Conclusion Our results suggest that, compared with rodents, the repertoire of orthologous V1R genes is remarkably conserved among the ruminants cow, sheep and goat. We predict that these orthologous V1Rs can detect the same or closely related chemical compound(s within each orthologous set/pair. Furthermore, all identified goat V1Rs are expressed in the vomeronasal organ and the main olfactory epithelium, suggesting that V1R-mediated ligand information can be detected and processed by both the main and accessory olfactory systems. The fact that ruminant and rodent V1Rs

  6. Sexual repertoires of heterosexuals: implications for HIV/sexually transmitted disease risk and prevention. The ACSF Group, Analyse des Comportements Sexuels en France.

    Science.gov (United States)

    Messiah, A; Blin, P; Fiche, V

    1995-12-01

    To provide a quantitative and population-based analysis of sexual repertoires among heterosexuals. The French National Survey of Sexual Behaviour (ACSF), conducted between September 1991 and February 1992 on a representative sample of the population aged 18-69 years. Sexual practices of the last heterosexual encounter were investigated among 4261 individuals; we measured the combinations of different practices and their correlations with age, and calculated frequencies for the main repertoires and their correlations with the interpartner relationship. Vaginal penetration and caressing were almost systematic, self-masturbation and anal penetration were rare, while mutual masturbation and orogenital practices had intermediate levels of occurrence. Examination of the correlations revealed (1) a very high correlation between practices which are reciprocal or symmetrical, (2) a strong association between genito-manual and genito-oral practices, (3) an association between anal penetration and fellatio, and (4) no clear correlation between any set of practices and vaginal sex or condom use. A small number of repertoires accounted for the vast majority of encounters. Younger people tended to have a more diversified repertoire. Repertoire types and diversity were strongly correlated to the pattern of interpartner relationship, independently of age. Reciprocity seems a standard feature of the heterosexual repertoire. The absence of a negative correlation between vaginal or anal penetration and other practices argues against promotion of the latter as substitute for the former. By contrast, the independence between condom use and any specific repertoire argues for its promotion as a universal means of protection.

  7. Difficulties when assessing birdsong learning programmes under field conditions: a re-evaluation of song repertoire flexibility in the great tit.

    Science.gov (United States)

    Rivera-Gutierrez, Hector F; Pinxten, Rianne; Eens, Marcel

    2011-01-17

    There is a remarkable diversity of song-learning strategies in songbirds. Establishing whether a species is closed- or open-ended is important to be able to interpret functional and evolutionary consequences of variation in repertoire size. Most of our knowledge regarding the timing of vocal learning is based on laboratory studies, despite the fact that these may not always replicate the complex ecological and social interactions experienced by birds in the wild. Given that field studies cannot provide the experimental control of laboratory studies, it may not be surprising that species such as the great tit that were initially assumed to be closed-ended learners have later been suggested to be open-ended learners. By using an established colour-ringed population, by following a standardized recording protocol, and by taking into account the species' song ecology (using only recordings obtained during peak of singing at dawn), we replicated two previous studies to assess song repertoire learning and flexibility in adult wild great tits elicited by social interactions. First, we performed a playback experiment to test repertoire plasticity elicited by novel versus own songs. Additionally, in a longitudinal study, we followed 30 males in two consecutive years and analysed whether new neighbours influenced any change in the repertoire. Contrary to the previous studies, song repertoire size and composition were found to be highly repeatable both between years and after confrontation with a novel song. Our results suggest that great tits are closed-ended learners and that their song repertoire probably does not change during adulthood. Methodological differences that may have led to an underestimation of the repertoires or population differences may explain the discrepancy in results with previous studies. We argue that a rigorous and standardized assessment of the repertoire is essential when studying age- or playback-induced changes in repertoire size and composition

  8. The genome sequence of the commercially cultivated mushroom Agrocybe aegerita reveals a conserved repertoire of fruiting-related genes and a versatile suite of biopolymer-degrading enzymes.

    Science.gov (United States)

    Gupta, Deepak K; Rühl, Martin; Mishra, Bagdevi; Kleofas, Vanessa; Hofrichter, Martin; Herzog, Robert; Pecyna, Marek J; Sharma, Rahul; Kellner, Harald; Hennicke, Florian; Thines, Marco

    2018-01-15

    Agrocybe aegerita is an agaricomycete fungus with typical mushroom features, which is commercially cultivated for its culinary use. In nature, it is a saprotrophic or facultative pathogenic fungus causing a white-rot of hardwood in forests of warm and mild climate. The ease of cultivation and fructification on solidified media as well as its archetypal mushroom fruit body morphology render A. aegerita a well-suited model for investigating mushroom developmental biology. Here, the genome of the species is reported and analysed with respect to carbohydrate active genes and genes known to play a role during fruit body formation. In terms of fruit body development, our analyses revealed a conserved repertoire of fruiting-related genes, which corresponds well to the archetypal fruit body morphology of this mushroom. For some genes involved in fruit body formation, paralogisation was observed, but not all fruit body maturation-associated genes known from other agaricomycetes seem to be conserved in the genome sequence of A. aegerita. In terms of lytic enzymes, our analyses suggest a versatile arsenal of biopolymer-degrading enzymes that likely account for the flexible life style of this species. Regarding the amount of genes encoding CAZymes relevant for lignin degradation, A. aegerita shows more similarity to white-rot fungi than to litter decomposers, including 18 genes coding for unspecific peroxygenases and three dye-decolourising peroxidase genes expanding its lignocellulolytic machinery. The genome resource will be useful for developing strategies towards genetic manipulation of A. aegerita, which will subsequently allow functional genetics approaches to elucidate fundamentals of fruiting and vegetative growth including lignocellulolysis.

  9. Narrative Inquiry for Science Education: Teachers' repertoire-making in the case of environmental curriculum

    Science.gov (United States)

    Hwang, Seyoung

    2011-04-01

    This paper considers how the school science curriculum can be conceptualised in order to address the contingent and complex nature of environmental and sustainability-related knowledge and understanding. A special concern lies in the development of research perspectives and tools for investigating ways, in which teachers are faced with complex and various situations in the sense-making of science-related issues, and subsequent pedagogic issues. Based on an empirical examination of Korean teachers' sense-making of their curricular practice, the paper develops a narrative approach to teachers' perspectives and knowledge by considering the value of stories as sense-making tools for reflective questioning of what is worth teaching, how and why. By employing the idea of 'repertoire', the study regards teachers' stories about their environment-related personal and teaching experiences as offering angles with which to understand teachers' motivation and reflection in curricular development and implementation. Furthermore, three empirical cases present ways in which the nature of knowledge and understanding is recognised and potentially integrated into pedagogies through teachers' narratives. Finally, the paper argues for the need to reconsider the role of the science teacher in addressing environmental and sustainability-related issues, in ways that facilitate teachers' reflexive interpretation of meanings in cultural texts and the construction of pedagogic text.

  10. Fundamental roles of the innate-like repertoire of natural antibodies in immune homeostasis

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    Jaya eVas

    2013-02-01

    Full Text Available The composition of the early immune repertoire is biased with prominent expression of spontaneously arising B-cell clones that produce IgM with recurrent and often autoreactive binding specificities. Amongst these naturally-arising antibodies (NAbs are IgM antibodies that specifically recognize damaged and senescent cells, often via oxidation-associated neo-determinants. These NAbs are present from birth and can be further boosted by apoptotic cell challenge. Recent studies have shown that IgM NAb to apoptotic cells can enhance phagocytic clearance, as well as suppress pro-inflammatory responses induced via Toll-like receptors, and block pathogenic IgG-immune complex (IC-mediated inflammatory responses. Specific antibody effector functions appear to be involved, as these anti-inflammatory properties are dependent on IgM-mediated recruitment of the early recognition factors of complement. Clinical surveys have suggested that anti-AC IgM NAbs may modulate disease activity in some patients with autoimmune disease. In mechanistic studies, anti-AC NAbs were shown to act in dendritic cells by inhibition of the Mitogen Activated Protein Kinase (MAPK pathway, a primary signal transduction pathway that controls inflammatory responses. This immunomodulatory pathway has an absolute requirement for the induction of MAPK Phosphatase-1. Taken together, recent studies have elucidated the novel properties of a class of protective NAbs, which may directly blunt inflammatory responses through a primitive pathway for regulation of the innate immune system.

  11. Analysis of the clonal repertoire of gene-corrected cells in gene therapy.

    Science.gov (United States)

    Paruzynski, Anna; Glimm, Hanno; Schmidt, Manfred; Kalle, Christof von

    2012-01-01

    Gene therapy-based clinical phase I/II studies using integrating retroviral vectors could successfully treat different monogenetic inherited diseases. However, with increased efficiency of this therapy, severe side effects occurred in various gene therapy trials. In all cases, integration of the vector close to or within a proto-oncogene contributed substantially to the development of the malignancies. Thus, the in-depth analysis of integration site patterns is of high importance to uncover potential clonal outgrowth and to assess the safety of gene transfer vectors and gene therapy protocols. The standard and nonrestrictive linear amplification-mediated PCR (nrLAM-PCR) in combination with high-throughput sequencing exhibits technologies that allow to comprehensively analyze the clonal repertoire of gene-corrected cells and to assess the safety of the used vector system at an early stage on the molecular level. It enables clarifying the biological consequences of the vector system on the fate of the transduced cell. Furthermore, the downstream performance of real-time PCR allows a quantitative estimation of the clonality of individual cells and their clonal progeny. Here, we present a guideline that should allow researchers to perform comprehensive integration site analysis in preclinical and clinical studies. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Elucidating the genotype–phenotype map by automatic enumeration and analysis of the phenotypic repertoire

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2015-01-01

    Background: The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. Methods: The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Results: Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Conclusions: Starting with a system’s relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy. PMID:26998346

  13. Elucidating the genotype-phenotype map by automatic enumeration and analysis of the phenotypic repertoire.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Starting with a system's relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy.

  14. Impact of a 3-Months Vegetarian Diet on the Gut Microbiota and Immune Repertoire

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    Chenchen Zhang

    2018-04-01

    Full Text Available The dietary pattern can influence the immune system directly, but may also modulate it indirectly by regulating the gut microbiota. Here, we investigated the effect of a 3-months lacto-ovo-vegetarian diet on the diversity of gut microbiota and the immune system in healthy omnivorous volunteers, using high-throughput sequencing technologies. The short-term vegetarian diet did not have any major effect on the diversity of the immune system and the overall composition of the metagenome. The prevalence of bacterial genera/species with known beneficial effects on the intestine, including butyrate-producers and probiotic species and the balance of autoimmune-related variable genes/families were, however, altered in the short-term vegetarians. A number of bacterial species that are associated with the expression level of IgA, a key immunoglobulin class that protects the gastrointestinal mucosal system, were also identified. Furthermore, a lower diversity of T-cell repertoire and expression level of IgE, as well as a reduced abundance of inflammation-related genes in the gut microbiota were potentially associated with a control group with long-term vegetarians. Thus, the composition and duration of the diet may have an impact on the balance of pro-/anti-inflammatory factors in the gut microbiota and immune system.

  15. Expanding the Repertoire of Optogenetically Targeted Cells with an Enhanced Gene Expression System

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    Kenji F. Tanaka

    2012-08-01

    Full Text Available Optogenetics has been enthusiastically pursued in recent neuroscience research, and the causal relationship between neural activity and behavior is becoming ever more accessible. Here, we established knockin-mediated enhanced gene expression by improved tetracycline-controlled gene induction (KENGE-tet and succeeded in generating transgenic mice expressing a highly light-sensitive channelrhodopsin-2 mutant at levels sufficient to drive the activities of multiple cell types. This method requires two lines of mice: one that controls the pattern of expression and another that determines the protein to be produced. The generation of new lines of either type readily expands the repertoire to choose from. In addition to neurons, we were able to manipulate the activity of nonexcitable glial cells in vivo. This shows that our system is applicable not only to neuroscience but also to any biomedical study that requires understanding of how the activity of a selected population of cells propagates through the intricate organic systems.

  16. Bread, milk and a Tattslotto ticket: the interpretive repertoires of young adult gambling in Australia

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    Maree Ann Nekich

    2016-05-01

    Full Text Available Abstract The discourse of Australian young adults who gamble regularly was analysed to explore key dilemmas and challenges of a generation who grew up with the positive and negative impacts of gambling advertisements. Qualitative interviews of seven young recreational gamblers who regularly frequent gaming machine venues were conducted. The discourse that they used to describe their gambling involvement, motivation, development and subjective views were analysed and three central repertoires: ‘Culture not self,’ ‘If it makes you happy,’ and ‘No problem here!’ were identified. The current findings demonstrate the participants’ attempts to understand and legitimise their gambling. Further, it was suggested that young adults face a series of dilemmas when deciding whether to gamble and to what extent they gamble. Their discourse highlights the tension between individual agency, societal expectations and familial influence. The respondents primarily gambled for social reasons in a manner which they perceived as culturally acceptable. The importance of harm minimization and public awareness campaigns directed at young adults was also discussed.

  17. MicroRNA repertoire for functional genome research in tilapia identified by deep sequencing.

    Science.gov (United States)

    Yan, Biao; Wang, Zhen-Hua; Zhu, Chang-Dong; Guo, Jin-Tao; Zhao, Jin-Liang

    2014-08-01

    The Nile tilapia (Oreochromis niloticus; Cichlidae) is an economically important species in aquaculture and occupies a prominent position in the aquaculture industry. MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression involved in diverse biological and metabolic processes. To increase the repertoire of miRNAs characterized in tilapia, we used the Illumina/Solexa sequencing technology to sequence a small RNA library using pooled RNA sample isolated from the different developmental stages of tilapia. Bioinformatic analyses suggest that 197 conserved and 27 novel miRNAs are expressed in tilapia. Sequence alignments indicate that all tested miRNAs and miRNAs* are highly conserved across many species. In addition, we characterized the tissue expression patterns of five miRNAs using real-time quantitative PCR. We found that miR-1/206, miR-7/9, and miR-122 is abundantly expressed in muscle, brain, and liver, respectively, implying a potential role in the regulation of tissue differentiation or the maintenance of tissue identity. Overall, our results expand the number of tilapia miRNAs, and the discovery of miRNAs in tilapia genome contributes to a better understanding the role of miRNAs in regulating diverse biological processes.

  18. REFLECTIONS ON THE ORNAMENTAL PHENOMENON WITHIN THE REPERTOIRE OF TRADITIONAL VIOLONISTS IN THE HISTORICAL MOLDOVAN FOLK SPACE

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    GRIB VITALIE

    2016-12-01

    Full Text Available The eclectic style in the interpretative manner of the younger generation of traditional violinists, which oft en distorts the aesthetic essence of folklore creations, has determined the need for research, scientifi c reasoning and elaboration of some methods of learning the traditional ornamental instrumental style, which can be general or individual, yet specifi c to the historical Moldovan folk space. To achieve this, we consider important to identify the types of ornaments in traditional instrumental music; to delimit the interpretative particularities of ornaments in literate and folk music; to analyse the ornamentation styles of songs within the repertoire of diff erent traditional violinists, that belong to the folk space investigated in terms of the type of creation. As a model for analysing the particularities of interpreting these ornaments, we select violinists from older generations, whose repertoire and style of execution has not been aff ected by the media and technological progress.

  19. Fundamental characteristics of the immunoglobulin VH repertoire of chickens in comparison with those of humans, mice, and camelids.

    Science.gov (United States)

    Wu, Leeying; Oficjalska, Katarzyna; Lambert, Matthew; Fennell, Brian J; Darmanin-Sheehan, Alfredo; Ní Shúilleabháin, Deirdre; Autin, Bénédicte; Cummins, Emma; Tchistiakova, Lioudmila; Bloom, Laird; Paulsen, Janet; Gill, Davinder; Cunningham, Orla; Finlay, William J J

    2012-01-01

    Examination of 1269 unique naive chicken V(H) sequences showed that the majority of positions in the framework (FW) regions were maintained as germline, with high mutation rates observed in the CDRs. Many FW mutations could be clearly related to the modulation of CDR structure or the V(H)-V(L) interface. CDRs 1 and 2 of the V(H) exhibited frequent mutation in solvent-exposed positions, but conservation of common structural residues also found in human CDRs at the same positions. In comparison with humans and mice, the chicken CDR3 repertoire was skewed toward longer sequences, was dominated by small amino acids (G/S/A/C/T), and had higher cysteine (chicken, 9.4%; human, 1.6%; and mouse, 0.25%) but lower tyrosine content (chicken, 9.2%; human, 16.8%; and mouse 26.4%). A strong correlation (R(2) = 0.97) was observed between increasing CDR3 length and higher cysteine content. This suggests that noncanonical disulfides are strongly favored in chickens, potentially increasing CDR stability and complexity in the topology of the combining site. The probable formation of disulfide bonds between CDR3 and CDR1, FW2, or CDR2 was also observed, as described in camelids. All features of the naive repertoire were fully replicated in the target-selected, phage-displayed repertoire. The isolation of a chicken Fab with four noncanonical cysteines in the V(H) that exhibits 64 nM (K(D)) binding affinity for its target proved these constituents to be part of the humoral response, not artifacts. This study supports the hypothesis that disulfide bond-constrained CDR3s are a structural diversification strategy in the restricted germline v-gene repertoire of chickens.

  20. Low arousing positive affect broadens visual attention and alters the thought-action repertoire while broadened visual attention does not

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    Daniel Thomas Jäger

    2016-10-01

    Full Text Available The Broaden-and-Build Theory states that positive emotions broaden cognition and therefore build personal resources. However, missing theoretical precision regarding the interaction of the cognitive processes involved offers a variety of possible explanations for the mechanisms of broadening and building. In Experiment 1 we tested the causality assumption which states that positive emotions first broaden visual attention which in turn leads to broadened cognition. We examined the effects of a broadened, narrowed or neutral attentional scope of 72 subjects (30 men on their momentary thought-action repertoire. Results showed that there were no significant differences between groups regarding the breadth or the content of the thought-action repertoire. In Experiment 2 we studied the non-causality hypothesis which assumes a non-causal relationship between cognitive processes. We did so by investigating the effects of negative, neutral, and positive affect on the visual attentional scope of 85 subjects (41 men in Experiment 2a, as well as on the thought-action repertoire of 85 participants (42 men in Experiment 2b. Results revealed an attentional broadening effect in Experiment 2a but no differences between groups concerning the breadth of the thought-action repertoire in Experiment 2b. However, a theory driven content analysis showed that positive affect promoted social actions whereas negative affect endorsed resource protecting actions. Thus, our results favor the non-causality assumption. Moreover, results indicate that positive emotions do not target personal resources in general but rather resources associated with social behavior. In conclusion, we argue that the Broaden-and-Build Theory should be refined.

  1. Unsustainable Growth, Hyper-Competition, and Worth in Life Science Research: Narrowing Evaluative Repertoires in Doctoral and Postdoctoral Scientists' Work and Lives.

    Science.gov (United States)

    Fochler, Maximilian; Felt, Ulrike; Müller, Ruth

    There is a crisis of valuation practices in the current academic life sciences, triggered by unsustainable growth and "hyper-competition." Quantitative metrics in evaluating researchers are seen as replacing deeper considerations of the quality and novelty of work, as well as substantive care for the societal implications of research. Junior researchers are frequently mentioned as those most strongly affected by these dynamics. However, their own perceptions of these issues are much less frequently considered. This paper aims at contributing to a better understanding of the interplay between how research is valued and how young researchers learn to live, work and produce knowledge within academia. We thus analyze how PhD students and postdocs in the Austrian life sciences ascribe worth to people, objects and practices as they talk about their own present and future lives in research. We draw on literature from the field of valuation studies and its interest in how actors refer to different forms of valuation to account for their actions. We explore how young researchers are socialized into different valuation practices in different stages of their growing into science. Introducing the concept of "regimes of valuation" we show that PhD students relate to a wider evaluative repertoire while postdocs base their decisions on one dominant regime of valuing research. In conclusion, we discuss the implications of these findings for the epistemic and social development of the life sciences, and for other scientific fields.

  2. From everyday communicative figurations to rigorous audience news repertoires: A mixed method approach to cross-media news consumption

    Directory of Open Access Journals (Sweden)

    Christian Kobbernagel

    2016-06-01

    Full Text Available In the last couple of decades there has been an unprecedented explosion of news media platforms and formats, as a succession of digital and social media have joined the ranks of legacy media. We live in a ‘hybrid media system’ (Chadwick, 2013, in which people build their cross-media news repertoires from the ensemble of old and new media available. This article presents an innovative mixed-method approach with considerable explanatory power to the exploration of patterns of news media consumption. This approach tailors Q-methodology in the direction of a qualitative study of news consumption, in which a card sorting exercise serves to translate the participants’ news media preferences into a form that enables the researcher to undertake a rigorous factor-analytical construction of their news consumption repertoires. This interpretive, factor-analytical procedure, which results in the building of six audience news repertoires in Denmark, also preserves the qualitative thickness of the participants’ verbal accounts of the communicative figurations of their day-in-the-life with the news media.

  3. Kaarel Irdi repertuaaripoliitilised vaated Vanemuise teatri juhina. Kaarel Ird’s Repertoire Policy as Manager of the Vanemuine Theatre

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    Jaak Viller

    2012-04-01

    Full Text Available This article focuses on the meaning of ’repertoire policy’, which in a broader sense usually means the conformity of someone’s creative activities with their main target groups and the interests and expectations of these target groups. Usually, factors inside the theatre also influence repertoire policy (such as contemporary and classical texts, the relationship between local and foreign material, as well as the consideration of the artistic interests and abilities of the directors and actors involved. When analysing the Vanemuine Theatre and its long-standing manager Kaarel Ird (at Vanemuine during the years 1940–1986, a certain aspect stemming from the ideological doctrine of the totalitarian state should be taken into account: the mandatory quota of Soviet drama works (of the Russian and other Soviet nations written after the revolution of 1917, which had to be no less than two-thirds of the plays staged. One of Ird’s more distinguishable accomplishments in the formation of repertoire policy is the rehabilitation of classical Estonian drama and its legacy, which had been ostracised from the stage during the years following the war (1944–1955. Ird justified this with numerous performances and articles as well as in the choice of repertoire at the Vanemuine Theatre, which was very well received by the growing audience. Ird’s own best directed works were based on the legacy of classic Estonian drama (Lydia Koidula, Oskar Luts and others. The other tendency in Ird’s repertoire policy is the attention paid to the Estonian contemporary drama. His role in enthusing writers to create contributions for the drama genre was remarkable, as well as the care taken in order to make their plays reach the stage at Vanemuine Theatre. Something that should be pointed out in Ird’s favour is his explanation – which at the time was not at all self-evident – of the repertoire to the supervisory organs: that contemporary Estonian dramas ought

  4. Broad T-cell receptor repertoire in T-lymphocytes derived from human induced pluripotent stem cells.

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    Chia-Wei Chang

    Full Text Available Human induced pluripotent stem cells (hiPSCs have enormous potential for the treatment of inherited and acquired disorders. Recently, antigen-specific T lymphocytes derived from hiPSCs have been reported. However, T lymphocyte populations with broad T cell receptor (TCR diversity have not been generated. We report that hiPSCs derived from skin biopsy are capable of producing T lymphocyte populations with a broad TCR repertoire. In vitro T cell differentiation follows a similar developmental program as observed in vivo, indicated by sequential expression of CD7, intracellular CD3 and surface CD3. The γδ TCR locus is rearranged first and is followed by rearrangement of the αβ locus. Both γδ and αβ T cells display a diverse TCR repertoire. Upon activation, the cells express CD25, CD69, cytokines (TNF-α, IFN-γ, IL-2 and cytolytic proteins (Perforin and Granzyme-B. These results suggest that most, if not all, mechanisms required to generate functional T cells with a broad TCR repertoire are intact in our in vitro differentiation protocol. These data provide a foundation for production of patient-specific T cells for the treatment of acquired or inherited immune disorders and for cancer immunotherapy.

  5. The effects of a partitioned var gene repertoire of Plasmodium falciparum on antigenic diversity and the acquisition of clinical immunity

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    Arinaminpathy Nimalan

    2008-01-01

    Full Text Available Abstract Background The human malaria parasite Plasmodium falciparum exploits antigenic diversity and within-host antigenic variation to evade the host's immune system. Of particular importance are the highly polymorphic var genes that encode the family of cell surface antigens PfEMP1 (Plasmodium falciparum Erythrocyte Membrane Protein 1. It has recently been shown that in spite of their extreme diversity, however, these genes fall into distinct groups according to chromosomal location or sequence similarity, and that recombination may be confined within these groups. Methods This study presents a mathematical analysis of how recombination hierarchies affect diversity, and, by using simple stochastic simulations, investigates how intra- and inter-genic diversity influence the rate at which individuals acquire clinical immunity. Results The analysis demonstrates that the partitioning of the var gene repertoire has a limiting effect on the total diversity attainable through recombination and that the limiting effect is strongly influenced by the respective sizes of each of the partitions. Furthermore, by associating expression of one of the groups with severe malaria it is demonstrated how a small number of infections can be sufficient to protect against disease despite a seemingly limitless number of possible non-identical repertoires. Conclusion Recombination hierarchies within the var gene repertoire of P. falciparum have a severe effect on strain diversity and the process of acquiring immunity against clinical malaria. Future studies will show how the existence of these recombining groups can offer an evolutionary advantage in spite of their restriction on diversity.

  6. Behavioural repertoire of free-range laying hens indoors and outdoors, and in relation to distance from the shed.

    Science.gov (United States)

    Thuy Diep, A; Larsen, H; Rault, J-L

    2018-04-01

    Access to an outdoor area is believed to allow free-range hens to express a greater behavioural repertoire. However, very little research has been done in this area. We hypothesised that the type and frequency of behaviours would differ between areas that vary in their characteristics and distance from the shed. This preliminary study investigated the behaviour of free-range laying hens in indoor and outdoor areas on one commercial free-range farm, through video recordings and scan sampling of focal hens, with the aim of determining their behavioural repertoire and time budget. While ranging, hens spent most of their time foraging. Indoors, hens preened and rested. Behaviour in the wintergarden showed similarities to both the indoor and outdoor areas, with preening, resting and foraging behaviours. Differences were not in the main behavioural repertoire, but rather in terms of time budget, with access to the range and wintergarden encouraging exploration. There was no difference in the types of behaviours that hens performed in the outdoor range compared with inside the shed, but access to a wintergarden and the outdoor range were favoured by the hens for foraging. © 2018 Australian Veterinary Association.

  7. Genetic algorithms

    Science.gov (United States)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

    Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

  8. On the Origin of Reverse Transcriptase-Using CRISPR-Cas Systems and Their Hyperdiverse, Enigmatic Spacer Repertoires.

    Science.gov (United States)

    Silas, Sukrit; Makarova, Kira S; Shmakov, Sergey; Páez-Espino, David; Mohr, Georg; Liu, Yi; Davison, Michelle; Roux, Simon; Krishnamurthy, Siddharth R; Fu, Becky Xu Hua; Hansen, Loren L; Wang, David; Sullivan, Matthew B; Millard, Andrew; Clokie, Martha R; Bhaya, Devaki; Lambowitz, Alan M; Kyrpides, Nikos C; Koonin, Eugene V; Fire, Andrew Z

    2017-07-11

    Cas1 integrase is the key enzyme of the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas adaptation module that mediates acquisition of spacers derived from foreign DNA by CRISPR arrays. In diverse bacteria, the cas1 gene is fused (or adjacent) to a gene encoding a reverse transcriptase (RT) related to group II intron RTs. An RT-Cas1 fusion protein has been recently shown to enable acquisition of CRISPR spacers from RNA. Phylogenetic analysis of the CRISPR-associated RTs demonstrates monophyly of the RT-Cas1 fusion, and coevolution of the RT and Cas1 domains. Nearly all such RTs are present within type III CRISPR-Cas loci, but their phylogeny does not parallel the CRISPR-Cas type classification, indicating that RT-Cas1 is an autonomous functional module that is disseminated by horizontal gene transfer and can function with diverse type III systems. To compare the sequence pools sampled by RT-Cas1-associated and RT-lacking CRISPR-Cas systems, we obtained samples of a commercially grown cyanobacterium- Arthrospira platensis Sequencing of the CRISPR arrays uncovered a highly diverse population of spacers. Spacer diversity was particularly striking for the RT-Cas1-containing type III-B system, where no saturation was evident even with millions of sequences analyzed. In contrast, analysis of the RT-lacking type III-D system yielded a highly diverse pool but reached a point where fewer novel spacers were recovered as sequencing depth was increased. Matches could be identified for a small fraction of the non-RT-Cas1-associated spacers, and for only a single RT-Cas1-associated spacer. Thus, the principal source(s) of the spacers, particularly the hypervariable spacer repertoire of the RT-associated arrays, remains unknown. IMPORTANCE While the majority of CRISPR-Cas immune systems adapt to foreign genetic elements by capturing segments of invasive DNA, some systems carry reverse transcriptases (RTs) that enable adaptation to RNA molecules. From

  9. Fundamental characteristics of the expressed immunoglobulin VH and VL repertoire in different canine breeds in comparison with those of humans and mice.

    Science.gov (United States)

    Steiniger, Sebastian C J; Dunkle, William E; Bammert, Gary F; Wilson, Thomas L; Krishnan, Abhiram; Dunham, Steven A; Ippolito, Gregory C; Bainbridge, Graeme

    2014-05-01

    Complementarity determining regions (CDR) are responsible for binding antigen and provide substantial diversity to the antibody repertoire, with VH CDR3 of the immunoglobulin variable heavy (VH) domain playing a dominant role. In this study, we examined 1200 unique canine VH and 500 unique variable light (VL) sequences of large and small canine breeds derived from peripheral B cells. Unlike the human and murine repertoire, the canine repertoire is heavily dominated by the Canis lupus familiaris IGHV1 subgroup, evolutionarily closest to the human IGHV3 subgroup. Our studies clearly show that the productive canine repertoire of all analyzed breeds shows similarities to both human and mouse; however, there are distinct differences in terms of VH CDR3 length and amino acid paratope composition. In comparison with the human and murine antibody repertoire, canine VH CDR3 regions are shorter in length than the human counterparts, but longer than the murine VH CDR3. Similar to corresponding human and mouse VH CDR3, the amino acids at the base of the VH CDR3 loop are strictly conserved. For identical CDR positions, there were significant changes in chemical paratope composition. Similar to human and mouse repertoires, the neutral amino acids tyrosine, glycine and serine dominate the canine VH CDR3 interval (comprising 35%) although the interval is nonetheless relatively depleted of tyrosine when compared to human and mouse. Furthermore, canine VH CDR3 displays an overrepresentation of the neutral amino acid threonine and the negatively charged aspartic acid while proline content is similar to that in the human repertoire. In general, the canine repertoire shows a bias towards small, negatively charged amino acids. Overall, this analysis suggests that functional canine therapeutic antibodies can be obtained from human and mouse sequences by methods of speciation and affinity maturation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Cloning of the immunological repertoire in Escherichia coli for generation of monoclonal catalytic antibodies: construction of a heavy chain variable region-specific cDNA library.

    OpenAIRE

    Sastry, L; Alting-Mees, M; Huse, W D; Short, J M; Sorge, J A; Hay, B N; Janda, K D; Benkovic, S J; Lerner, R A

    1989-01-01

    Efficient generation of catalytic antibodies is uniquely dependent on the exact nature of the binding interactions in the antigen-antibody complex. Current methods for generation of monoclonal antibodies do not efficiently survey the immunological repertoire and, therefore, they limit the number of catalysts that can be obtained. We are exploring methods to clone and express the immunological repertoire in Escherichia coli. As the essential first step, we present here a method for the establi...

  11. Genetic Mapping

    Science.gov (United States)

    ... greatly advanced genetics research. The improved quality of genetic data has reduced the time required to identify a ... cases, a matter of months or even weeks. Genetic mapping data generated by the HGP's laboratories is freely accessible ...

  12. Immunoproteomic analysis of the protein repertoire of unsporulated Eimeria tenella oocysts

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    Zhang Zhenchao

    2017-01-01

    Full Text Available The apicomplexan protozoans Eimeria spp. cause coccidioses, the most common intestinal diseases in chickens. Coccidiosis is associated with significant animal welfare issues and has a high economic impact on the poultry industry. Lack of a full understanding of immunogenic molecules and their precise functions involved in the Eimeria life cycles may limit development of effective vaccines and drug therapies. In this study, immunoproteomic approaches were used to define the antigenic protein repertoire from the total proteins of unsporulated Eimeria tenella oocysts. Approximately 101 protein spots were recognized in sera from chickens infected experimentally with E. tenella. Forty-six spots of unsporulated oocysts were excised from preparative gels and identified by matrix-assisted laser desorption ionization time-of-flight MS (MALDI-TOF-MS and MALDI-TOF/TOF-MS. For unsporulated oocysts, 13 known proteins of E. tenella and 17 homologous proteins to other apicomplexan or protozoan parasites were identified using the ‘Mascot’ server. The remaining proteins were searched against the E. tenella protein sequence database using the ‘Mascot in-house’ search engine (version 2.1 in automated mode, and 12 unknown proteins were identified. The amino acid sequences of the unknown proteins were searched using BLAST against non-redundant sequence databases (NCBI, and 9 homologous proteins in unsporulated oocyst were found homologous to proteins of other apicomplexan parasites. These findings may provide useful evidence for understanding parasite biology, pathogenesis, immunogenicity and immune evasion mechanisms of E. tenella.

  13. Identification of Complete Repertoire of Apis florea Odorant Receptors Reveals Complex Orthologous Relationships with Apis mellifera

    Science.gov (United States)

    Karpe, Snehal D.; Jain, Rikesh; Brockmann, Axel; Sowdhamini, Ramanathan

    2016-01-01

    Abstract We developed a computational pipeline for homology based identification of the complete repertoire of olfactory receptor (OR) genes in the Asian honey bee species, Apis florea. Apis florea is phylogenetically the most basal honey bee species and also the most distant sister species to the Western honey bee Apis mellifera, for which all OR genes had been identified before. Using our pipeline, we identified 180 OR genes in A. florea, which is very similar to the number of ORs identified in A. mellifera (177 ORs). Many characteristics of the ORs including gene structure, synteny of tandemly repeated ORs and basic phylogenetic clustering are highly conserved. The composite phylogenetic tree of A. florea and A. mellifera ORs could be divided into 21 clades which are in harmony with the existing Hymenopteran tree. However, we found a few nonorthologous OR relationships between both species as well as independent pseudogenization of ORs suggesting separate evolutionary changes. Particularly, a subgroup of the OR gene clade XI, which had been hypothesized to code cuticular hydrocarbon receptors showed a high number of species-specific ORs. RNAseq analysis detected a total number of 145 OR transcripts in male and 162 in female antennae. Most of the OR genes were highly expressed on the female antennae. However, we detected five distinct male-biased OR genes, out of which three genes (AfOr11, AfOr18, AfOr170P) were shown to be male-biased in A. mellifera, too, thus corroborating a behavioral function in sex-pheromone communication. PMID:27540087

  14. Construction of naïve camelids VHH repertoire in phage display-based library.

    Science.gov (United States)

    Sabir, Jamal S M; Atef, Ahmed; El-Domyati, Fotouh M; Edris, Sherif; Hajrah, Nahid; Alzohairy, Ahmed M; Bahieldin, Ahmed

    2014-04-01

    Camelids have unique antibodies, namely HCAbs (VHH) or commercially named Nanobodies(®) (Nb) that are composed only of a heavy-chain homodimer. As libraries based on immunized camelids are time-consuming, costly and likely redundant for certain antigens, we describe the construction of a naïve camelid VHHs library from blood serum of non-immunized camelids with affinity in the subnanomolar range and suitable for standard immune applications. This approach is rapid and recovers VHH repertoire with the advantages of being more diverse, non-specific and devoid of subpopulations of specific antibodies, which allows the identification of binders for any potential antigen (or pathogen). RNAs from a number of camelids from Saudi Arabia were isolated and cDNAs of the diverse vhh gene were amplified; the resulting amplicons were cloned in the phage display pSEX81 vector. The size of the library was found to be within the required range (10(7)) suitable for subsequent applications in disease diagnosis and treatment. Two hundred clones were randomly selected and the inserted gene library was either estimated for redundancy or sequenced and aligned to the reference camelid vhh gene (acc. No. ADE99145). Results indicated complete non-specificity of this small library in which no single event of redundancy was detected. These results indicate the efficacy of following this approach in order to yield a large and diverse enough gene library to secure the presence of the required version encoding the required antibodies for any target antigen. This work is a first step towards the construction of phage display-based biosensors useful in disease (e.g., TB or tuberculosis) diagnosis and treatment. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  15. ALBUM SUARA (REPERTOIRE KATAK SERASAH Leptobrachium hasseltii TSCHUDI, 1883 DI SITU GUNUNG

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    Sasi Kirono

    2016-07-01

    Full Text Available This study describes the vocal repertoire of forest litter frog Leptobrachium hasseltii from Situgunung Resort, Mount Gede Pangrango National Park. Two types of calls were identified: advertisement call and aggressive call. Each types were represented by two different characteristics thus four types of calls were examined. The kruskall and wallis test was used to test the difference of nine features. Pearson’s correlation test also used to determine the relationship of all call features to air temperature and body size. Dominant frequency of all call types was relatively similar. Advertisement calls type I was emitted in short duration and fewer notes than advertisement call type II. Aggressive call type I and have longer call duration compared to both of advertisement call. However the introductory note of aggressive call type II was more longer than the others. Aggressive call of L. hasseltii tended to be discrete (territorial and encounter and represented two different continuums. This were caused by the extreme differences of both calls in duration and distance between males when emitting calls. Dominan frequencies of all call types inverse correlated with body size of frogs. Most of temporal features of advertisement call type II correlated with body size and only call duration were longer with increasingly air temperature. Interpulse-interval and pulse period were more longer by increasing the body size, while the introductory note, pulse rate and pulse repetition rate were becoming shortened and it could predict male body size to facilitated competition between males, thus serves as mate selection indicator. Key words: advertisement call, agressif call, Leptobrachium hasseltii, Situgunung resort, social interaction

  16. Human Non-linguistic Vocal Repertoire: Call Types and Their Meaning.

    Science.gov (United States)

    Anikin, Andrey; Bååth, Rasmus; Persson, Tomas

    2018-01-01

    Recent research on human nonverbal vocalizations has led to considerable progress in our understanding of vocal communication of emotion. However, in contrast to studies of animal vocalizations, this research has focused mainly on the emotional interpretation of such signals. The repertoire of human nonverbal vocalizations as acoustic types, and the mapping between acoustic and emotional categories, thus remain underexplored. In a cross-linguistic naming task (Experiment 1), verbal categorization of 132 authentic (non-acted) human vocalizations by English-, Swedish- and Russian-speaking participants revealed the same major acoustic types: laugh, cry, scream, moan, and possibly roar and sigh. The association between call type and perceived emotion was systematic but non-redundant: listeners associated every call type with a limited, but in some cases relatively wide, range of emotions. The speed and consistency of naming the call type predicted the speed and consistency of inferring the caller's emotion, suggesting that acoustic and emotional categorizations are closely related. However, participants preferred to name the call type before naming the emotion. Furthermore, nonverbal categorization of the same stimuli in a triad classification task (Experiment 2) was more compatible with classification by call type than by emotion, indicating the former's greater perceptual salience. These results suggest that acoustic categorization may precede attribution of emotion, highlighting the need to distinguish between the overt form of nonverbal signals and their interpretation by the perceiver. Both within- and between-call acoustic variation can then be modeled explicitly, bringing research on human nonverbal vocalizations more in line with the work on animal communication.

  17. Variability and repertoire size of T-cell receptor V alpha gene segments.

    Science.gov (United States)

    Becker, D M; Pattern, P; Chien, Y; Yokota, T; Eshhar, Z; Giedlin, M; Gascoigne, N R; Goodnow, C; Wolf, R; Arai, K

    The immune system of higher organisms is composed largely of two distinct cell types, B lymphocytes and T lymphocytes, each of which is independently capable of recognizing an enormous number of distinct entities through their antigen receptors; surface immunoglobulin in the case of the former, and the T-cell receptor (TCR) in the case of the latter. In both cell types, the genes encoding the antigen receptors consist of multiple gene segments which recombine during maturation to produce many possible peptides. One striking difference between B- and T-cell recognition that has not yet been resolved by the structural data is the fact that T cells generally require a major histocompatibility determinant together with an antigen whereas, in most cases, antibodies recognize antigen alone. Recently, we and others have found that a series of TCR V beta gene sequences show conservation of many of the same residues that are conserved between heavy- and light-chain immunoglobulin V regions, and these V beta sequences are predicted to have an immunoglobulin-like secondary structure. To extend these studies, we have isolated and sequenced eight additional alpha-chain complementary cDNA clones and compared them with published sequences. Analyses of these sequences, reported here, indicate that V alpha regions have many of the characteristics of V beta gene segments but differ in that they almost always occur as cross-hybridizing gene families. We conclude that there may be very different selective pressures operating on V alpha and V beta sequences and that the V alpha repertoire may be considerably larger than that of V beta.

  18. Severity of Acute Infectious Mononucleosis Correlates with Cross-Reactive Influenza CD8 T-Cell Receptor Repertoires.

    Science.gov (United States)

    Aslan, Nuray; Watkin, Levi B; Gil, Anna; Mishra, Rabinarayan; Clark, Fransenio G; Welsh, Raymond M; Ghersi, Dario; Luzuriaga, Katherine; Selin, Liisa K

    2017-12-05

    Fifty years after the discovery of Epstein-Barr virus (EBV), it remains unclear how primary infection with this virus leads to massive CD8 T-cell expansion and acute infectious mononucleosis (AIM) in young adults. AIM can vary greatly in severity, from a mild transient influenza-like illness to a prolonged severe syndrome. We questioned whether expansion of a unique HLA-A2.01-restricted, cross-reactive CD8 T-cell response between influenza virus A-M1 58 (IAV-M1) and EBV BMLF1 280 (EBV-BM) could modulate the immune response to EBV and play a role in determining the severity of AIM in 32 college students. Only ex vivo total IAV-M1 and IAV-M1+EBV-BM cross-reactive tetramer + frequencies directly correlated with AIM severity and were predictive of severe disease. Expansion of specific cross-reactive memory IAV-M1 T-cell receptor (TCR) Vβ repertoires correlated with levels of disease severity. There were unique profiles of qualitatively different functional responses in the cross-reactive and EBV-specific CD8 T-cell responses in each of the three groups studied, severe-AIM patients, mild-AIM patients, and seropositive persistently EBV-infected healthy donors, that may result from differences in TCR repertoire use. IAV-M1 tetramer + cells were functionally cross-reactive in short-term cultures, were associated with the highest disease severity in AIM, and displayed enhanced production of gamma interferon, a cytokine that greatly amplifies immune responses, thus frequently contributing to induction of immunopathology. Altogether, these data link heterologous immunity via CD8 T-cell cross-reactivity to CD8 T-cell repertoire selection, function, and resultant disease severity in a common and important human infection. In particular, it highlights for the first time a direct link between the TCR repertoire with pathogenesis and the diversity of outcomes upon pathogen encounter. IMPORTANCE The pathogenic impact of immune responses that by chance cross-react to unrelated

  19. Genetic privacy.

    Science.gov (United States)

    Sankar, Pamela

    2003-01-01

    During the past 10 years, the number of genetic tests performed more than tripled, and public concern about genetic privacy emerged. The majority of states and the U.S. government have passed regulations protecting genetic information. However, research has shown that concerns about genetic privacy are disproportionate to known instances of information misuse. Beliefs in genetic determinacy explain some of the heightened concern about genetic privacy. Discussion of the debate over genetic testing within families illustrates the most recent response to genetic privacy concerns.

  20. The human skin double-stranded DNA virome: topographical and temporal diversity, genetic enrichment, and dynamic associations with the host microbiome.

    Science.gov (United States)

    Hannigan, Geoffrey D; Meisel, Jacquelyn S; Tyldsley, Amanda S; Zheng, Qi; Hodkinson, Brendan P; SanMiguel, Adam J; Minot, Samuel; Bushman, Frederic D; Grice, Elizabeth A

    2015-10-20

    Viruses make up a major component of the human microbiota but are poorly understood in the skin, our primary barrier to the external environment. Viral communities have the potential to modulate states of cutaneous health and disease. Bacteriophages are known to influence the structure and function of microbial communities through predation and genetic exchange. Human viruses are associated with skin cancers and a multitude of cutaneous manifestations. Despite these important roles, little is known regarding the human skin virome and its interactions with the host microbiome. Here we evaluated the human cutaneous double-stranded DNA virome by metagenomic sequencing of DNA from purified virus-like particles (VLPs). In parallel, we employed metagenomic sequencing of the total skin microbiome to assess covariation and infer interactions with the virome. Samples were collected from 16 subjects at eight body sites over 1 month. In addition to the microenviroment, which is known to partition the bacterial and fungal microbiota, natural skin occlusion was strongly associated with skin virome community composition. Viral contigs were enriched for genes indicative of a temperate phage replication style and also maintained genes encoding potential antibiotic resistance and virulence factors. CRISPR spacers identified in the bacterial DNA sequences provided a record of phage predation and suggest a mechanism to explain spatial partitioning of skin phage communities. Finally, we modeled the structure of bacterial and phage communities together to reveal a complex microbial environment with a Corynebacterium hub. These results reveal the previously underappreciated diversity, encoded functions, and viral-microbial dynamic unique to the human skin virome. To date, most cutaneous microbiome studies have focused on bacterial and fungal communities. Skin viral communities and their relationships with their hosts remain poorly understood despite their potential to modulate states

  1. Longitudinal multiparameter single-cell analysis of macaques immunized with pneumococcal protein-conjugated or unconjugated polysaccharide vaccines reveals distinct antigen specific memory B cell repertoires.

    Directory of Open Access Journals (Sweden)

    Bin Jia

    Full Text Available The efficacy of protein-conjugated pneumococcal polysaccharide vaccines has been well characterized for children. The level of protection conferred by unconjugated polysaccharide vaccines remains less clear, particularly for elderly individuals who have had prior antigenic experience through immunization with unconjugated polysaccharide vaccines or natural exposure to Streptococcus pneumoniae.We compared the magnitude, diversity and genetic biases of antigen-specific memory B cells in two groups of adult cynomolgus macaques that were immunized with a 7-valent conjugated vaccine and boosted after five years with either a 13-valent pneumococcal polysaccharide conjugate vaccine (13vPnC or a 23-valent unconjugated pneumococcal polysaccharide vaccine (23vPS using microengraving (a single-cell analysis method and single-cell RT-PCR.Seven days after boosting, the mean frequency of antigen-specific memory B cells was significantly increased in macaques vaccinated with 13vPnC compared to those receiving 23vPS. The 13vPnC-vaccinated macaques also exhibited a more even distribution of antibody specificities to four polysaccharides in the vaccine (PS4, 6B, 14, 23F that were examined. However, single-cell analysis of the antibody variable region sequences from antigen-specific B cells elicited by unconjugated and conjugated vaccines indicated that both the germline gene segments forming the heavy chains and the average lengths of the Complementary Determining Region 3 (CDR3 were similar.Our results confirm that distinctive differences can manifest between antigen-specific memory B cell repertoires in nonhuman primates immunized with conjugated and unconjugated pneumococcal polysaccharide vaccines. The study also supports the notion that the conjugated vaccines have a favorable profile in terms of both the frequency and breadth of the anamnestic response among antigen-specific memory B cells.

  2. Social and ethical aspects of forensic genetics: A critical review.

    Science.gov (United States)

    Williams, R; Wienroth, M

    2017-07-01

    This review describes the social and ethical responses to the history of innovations in forensic genetics and their application to criminal investigations. Following an outline of the three recurrent social perspectives that have informed these responses (crime management, due process, and genetic surveillance), it goes on to introduce the repertoire of ethical considerations by describing a series of key reports that have shaped subsequent commentaries on forensic DNA profiling and databasing. Four major ethical concerns form the focus of the remainder of the paper (dignity, privacy, justice, and social solidarity), and key features of forensic genetic practice are examined in the light of these concerns. The paper concludes with a discussion of the concept of "proportionality" as a resource for balancing the social and ethical risks and benefits of the use of forensic genetics in support of criminal justice. Copyright © 2017 Central Police University.

  3. On-farm dynamic management of genetic diversity: the impact of seed diffusions and seed saving practices on a population-variety of bread wheat.

    Science.gov (United States)

    Thomas, Mathieu; Demeulenaere, Elise; Dawson, Julie C; Khan, Abdul Rehman; Galic, Nathalie; Jouanne-Pin, Sophie; Remoue, Carine; Bonneuil, Christophe; Goldringer, Isabelle

    2012-12-01

    Since the domestication of crop species, humans have derived specific varieties for particular uses and shaped the genetic diversity of these varieties. Here, using an interdisciplinary approach combining ethnobotany and population genetics, we document the within-variety genetic structure of a population-variety of bread wheat (Triticum aestivum L.) in relation to farmers' practices to decipher their contribution to crop species evolution. Using 19 microsatellites markers, we conducted two complementary graph theory-based methods to analyze population structure and gene flow among 19 sub-populations of a single population-variety [Rouge de Bordeaux (RDB)]. The ethnobotany approach allowed us to determine the RDB history including diffusion and reproduction events. We found that the complex genetic structure among the RDB sub-populations is highly consistent with the structure of the seed diffusion and reproduction network drawn based on the ethnobotanical study. This structure highlighted the key role of the farmer-led seed diffusion through founder effects, selection and genetic drift because of human practices. An important result is that the genetic diversity conserved on farm is complementary to that found in the genebank indicating that both systems are required for a more efficient crop diversity conservation.

  4. Species delimitation, genetic diversity and population historical dynamics of Cycas diannanensis (Cycadaceae occurring sympatrically in the Red River region of China

    Directory of Open Access Journals (Sweden)

    Liu eJian

    2015-09-01

    Full Text Available Delimitating species boundaries could be of critical importance when evaluating the species’ evolving process and providing guidelines for conservation genetics. Here, species delimitation was carried out on three endemic and endangered Cycas species with resembling morphology and overlapped distribution range along the Red River (Yuanjiang in China: Cycas diananensis Z. T. Guan et G. D. Tao, Cycas parvula S. L. Yang and Cycas multiovula D. Y. Wang. A total of 137 individuals from 15 populations were genotyped by using three chloroplastic (psbA-trnH, atpI-atpH and trnL-rps4 and two single copy nuclear (RPB1 and SmHP DNA sequences. Basing on the carefully morphological comparison and cladistic haplotype aggregation (CHA analysis, we propose all the populations as one species, with the rest two incorporated into C. diannanensis. Genetic diversity and structure analysis of the conflated C. diannanensis revealed this species possessed a relative lower genetic diversity than estimates of other Cycas species. The higher genetic diversity among populations and relative lower genetic diversity within populations, as well as obvious genetic differentiation among populations inferred from chloroplastic DNA (cpDNA suggested a recent genetic loss within this protected species. Additionally, a clear genetic structure of C. diannanensis corresponding with geography was detected based on cpDNA, dividing its population ranges into Yuanjiang-Nanhun basin and Ejia-Jiepai basin groups. Demographical history analyses based on combined cpDNA and one nuclear DNA (nDNA SmHP both showed the population size of C. diannanensis began to decrease in Quaternary glaciation with no subsequent expansion, while another nDNA RPB1 revealed a more recent sudden expansion after long-term population size contraction, suggesting its probable bottleneck events in history. Our findings offer grounded views for clarifying species boundaries of C. diannanensis when determining the

  5. Quantitative measurement of pathogen specific human memory T cell repertoire diversity using a CDR3β-specific microarray

    Directory of Open Access Journals (Sweden)

    Gorski Jack

    2007-09-01

    Full Text Available Abstract Background Providing quantitative microarray data that is sensitive to very small differences in target sequence would be a useful tool in any number of venues where a sample can consist of a multiple related sequences present in various abundances. Examples of such applications would include measurement of pseudo species in viral infections and the measurement of species of antibodies or T cell receptors that constitute immune repertoires. Difficulties that must be overcome in such a method would be to account for cross-hybridization and for differences in hybridization efficiencies between the arrayed probes and their corresponding targets. We have used the memory T cell repertoire to an influenza-derived peptide as a test case for developing such a method. Results The arrayed probes were corresponded to a 17 nucleotide TCR-specific region that distinguished sequences differing by as little as a single nucleotide. Hybridization efficiency between highly related Cy5-labeled subject sequences was normalized by including an equimolar mixture of Cy3-labeled synthetic targets representing all 108 arrayed probes. The same synthetic targets were used to measure the degree of cross hybridization between probes. Reconstitution studies found the system sensitive to input ratios as low as 0.5% and accurate in measuring known input percentages (R2 = 0.81, R = 0.90, p 0.05. Conclusion This novel strategy appears to be robust and can be adapted to any situation where complex mixtures of highly similar sequences need to be quantitatively resolved.

  6. Hybridization-based antibody cDNA recovery for the production of recombinant antibodies identified by repertoire sequencing.

    Science.gov (United States)

    Valdés-Alemán, Javier; Téllez-Sosa, Juan; Ovilla-Muñoz, Marbella; Godoy-Lozano, Elizabeth; Velázquez-Ramírez, Daniel; Valdovinos-Torres, Humberto; Gómez-Barreto, Rosa E; Martinez-Barnetche, Jesús

    2014-01-01

    High-throughput sequencing of the antibody repertoire is enabling a thorough analysis of B cell diversity and clonal selection, which may improve the novel antibody discovery process. Theoretically, an adequate bioinformatic analysis could allow identification of candidate antigen-specific antibodies, requiring their recombinant production for experimental validation of their specificity. Gene synthesis is commonly used for the generation of recombinant antibodies identified in silico. Novel strategies that bypass gene synthesis could offer more accessible antibody identification and validation alternatives. We developed a hybridization-based recovery strategy that targets the complementarity-determining region 3 (CDRH3) for the enrichment of cDNA of candidate antigen-specific antibody sequences. Ten clonal groups of interest were identified through bioinformatic analysis of the heavy chain antibody repertoire of mice immunized with hen egg white lysozyme (HEL). cDNA from eight of the targeted clonal groups was recovered efficiently, leading to the generation of recombinant antibodies. One representative heavy chain sequence from each clonal group recovered was paired with previously reported anti-HEL light chains to generate full antibodies, later tested for HEL-binding capacity. The recovery process proposed represents a simple and scalable molecular strategy that could enhance antibody identification and specificity assessment, enabling a more cost-efficient generation of recombinant antibodies.

  7. Urban renewal, migration and memories: The affordances of place-based pedagogies for developing immigrant students’ literate repertoires

    Directory of Open Access Journals (Sweden)

    Barbara Comber

    2013-02-01

    Full Text Available This paper reports on the New literacy demands in the middle years of schooling project in which the affordances of placed-based pedagogy are being explored through teacher inquiries and classroom-based design experiments. The school is located within a large-scale urban renewal project in which houses are being demolished and families relocated. The original school buildings have recently been demolished and replaced by a large ‘Superschool’ which serves a bigger student population from a wider area. Drawing on both quantitative and qualitative data, the teachers reported that the language literacy learning of students (including a majority of students learning English as a second language involved in the project exceeded their expectations. The project provided the motivation for them to develop their oral language repertoires, by involving them in processes such as conducting interviews with adults for their oral histories, through questioning the project manager in regular meetings, and through reporting to their peers and the wider community at school assemblies. At the same time students’ written and multimodal documentation of changes in the neighbourhood and the school grounds extended their literate and semiotic repertoires as they produced books, reports, films, Powerpoints, visual designs and models of structures.

  8. CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors

    Directory of Open Access Journals (Sweden)

    Vanesa Alonso-Camino

    2013-01-01

    Full Text Available A human single-chain variable fragment (scFv antibody library was expressed on the surface of human T cells after transduction with lentiviral vectors (LVs. The repertoire was fused to a first-generation T cell receptor ζ (TCRζ-based chimeric antigen receptor (CAR. We used this library to isolate antibodies termed CARbodies that recognize antigens expressed on the tumor cell surface in a proof-of-principle system. After three rounds of activation-selection there was a clear repertoire restriction, with the emergence dominant clones. The CARbodies were purified from bacterial cultures as soluble and active proteins. Furthermore, to validate its potential application for adoptive cell therapy, human T cells were transduced with a LV encoding a second-generation costimulatory CAR (CARv2 bearing the selected CARbodies. Transduced human primary T cells expressed significant levels of the CARbodies-based CARv2 fusion protein on the cell surface, and importantly could be specifically activated, after stimulation with tumor cells. This approach is a promising tool for the generation of antibodies fully adapted to the display format (CAR and the selection context (cell synapse, which could extend the scope of current adoptive cell therapy strategies with CAR-redirected T cells.

  9. Repertoire Development and the Control of Cytotoxic/Effector Function in Human γδ T Cells

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Urban

    2010-01-01

    Full Text Available T cells develop into two major populations distinguished by their T cell receptor (TCR chains. Cells with the αβ TCR generally express CD4 or CD8 lineage markers and mostly fall into helper or cytotoxic/effector subsets. Cells expressing the alternate γδ TCR in humans generally do not express lineage markers, do not require MHC for antigen presentation, and recognize nonpeptidic antigens. We are interested in the dominant Vγ2Vδ2+ T cell subset in human peripheral blood and the control of effector function in this population. We review the literature on γδ T cell generation and repertoire selection, along with recent work on CD56 expression and defining a cytotoxic/effector lineage within the phosphoantigen-reactive Vγ2Vδ2 cells. A unique mechanism for MHC-independent repertoire selection is linked to the control of effector function that is vital to the role for γδ T cells in tumor surveillance. Better understanding of these mechanisms will improve our ability to exploit this population for tumor immunotherapy.

  10. Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a reengineered phage display system.

    Science.gov (United States)

    Krebber, A; Bornhauser, S; Burmester, J; Honegger, A; Willuda, J; Bosshard, H R; Plückthun, A

    1997-02-14

    A prerequisite for the use of recombinant antibody technologies starting from hybridomas or immune repertoires is the reliable cloning of functional immunoglobulin genes. For this purpose, a standard phage display system was optimized for robustness, vector stability, tight control of scFv-delta geneIII expression, primer usage for PCR amplification of variable region genes, scFv assembly strategy and subsequent directional cloning using a single rare cutting restriction enzyme. This integrated cloning, screening and selection system allowed us to rapidly obtain antigen binding scFvs derived from spleen-cell repertoires of mice immunized with ampicillin as well as from all hybridoma cell lines tested to date. As representative examples, cloning of monoclonal antibodies against a his tag, leucine zippers, the tumor marker EGP-2 and the insecticide DDT is presented. Several hybridomas whose genes could not be cloned in previous experimental setups, but were successfully obtained with the present system, expressed high amounts of aberrant heavy and light chain mRNAs, which were amplified by PCR and greatly exceeded the amount of binding antibody sequences. These contaminating variable region genes were successfully eliminated by employing the optimized phage display system, thus avoiding time consuming sequencing of non-binding scFv genes. To maximize soluble expression of functional scFvs subsequent to cloning, a compatible vector series to simplify modification, detection, multimerization and rapid purification of recombinant antibody fragments was constructed.

  11. Phylogeography of var gene repertoires reveals fine-scale geospatial clustering of Plasmodium falciparum populations in a highly endemic area.

    Science.gov (United States)

    Tessema, Sofonias K; Monk, Stephanie L; Schultz, Mark B; Tavul, Livingstone; Reeder, John C; Siba, Peter M; Mueller, Ivo; Barry, Alyssa E

    2015-01-01

    Plasmodium falciparum malaria is a major global health problem that is being targeted for progressive elimination. Knowledge of local disease transmission patterns in endemic countries is critical to these elimination efforts. To investigate fine-scale patterns of malaria transmission, we have compared repertoires of rapidly evolving var genes in a highly endemic area. A total of 3680 high-quality DBLα-sequences were obtained from 68 P. falciparum isolates from ten villages spread over two distinct catchment areas on the north coast of Papua New Guinea (PNG). Modelling of the extent of var gene diversity in the two parasite populations predicts more than twice as many var gene alleles circulating within each catchment (Mugil = 906; Wosera = 1094) than previously recognized in PNG (Amele = 369). In addition, there were limited levels of var gene sharing between populations, consistent with local parasite population structure. Phylogeographic analyses demonstrate that while neutrally evolving microsatellite markers identified population structure only at the catchment level, var gene repertoires reveal further fine-scale geospatial clustering of parasite isolates. The clustering of parasite isolates by village in Mugil, but not in Wosera was consistent with the physical and cultural isolation of the human populations in the two catchments. The study highlights the microheterogeneity of P. falciparum transmission in highly endemic areas and demonstrates the potential of var genes as markers of local patterns of parasite population structure. © 2014 John Wiley & Sons Ltd.

  12. Understanding B-cell activation and autoantibody repertoire selection in systemic lupus erythematosus: A B-cell immunomics approach.

    Science.gov (United States)

    Tipton, Christopher M; Hom, Jennifer R; Fucile, Christopher F; Rosenberg, Alexander F; Sanz, Inaki

    2018-07-01

    Understanding antibody repertoires and in particular, the properties and fates of B cells expressing potentially pathogenic antibodies is critical to define the mechanisms underlying multiple immunological diseases including autoimmune and allergic conditions as well as transplant rejection. Moreover, an integrated knowledge of the antibody repertoires expressed by B cells and plasma cells (PC) of different functional properties and longevity is essential to develop new therapeutic strategies, better biomarkers for disease segmentation, and new assays to measure restoration of B-cell tolerance or, at least, of normal B-cell homeostasis. Reaching these goals, however, will require a more precise phenotypic, functional and molecular definition of B-cell and PC populations, and a comprehensive analysis of the antigenic reactivity of the antibodies they express. While traditionally hampered by technical and ethical limitations in human experimentation, new technological advances currently enable investigators to address these questions in a comprehensive fashion. In this review, we shall discuss these concepts as they apply to the study of Systemic Lupus Erythematosus. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer, Loss, and Persistence of Genetic Elements In situ of the Infant Gut

    DEFF Research Database (Denmark)

    Porse, Andreas; Gumpert, Heidi; Kubicek-Sutherland, Jessica Z.

    2017-01-01

    made to elucidate the genome dynamics of E. coli in its native settings. Here, we follow the genome dynamics of co-existing E. coli lineages in situ of the infant gut during the first year of life. One E. coli lineage causes a urinary tract infection (UTI) and experiences several alterations of its...

  14. Wild European Apple (Malus sylvestris (L.) Mill.) Population Dynamics: Insight from Genetics and Ecology in the Rhine Valley. Priorities for a Future Conservation Programme

    Science.gov (United States)

    Schnitzler, Annik; Arnold, Claire; Cornille, Amandine; Bachmann, Olivier; Schnitzler, Christophe

    2014-01-01

    The increasing fragmentation of forest habitats and the omnipresence of cultivars potentially threaten the genetic integrity of the European wild apple (Malus sylvestris (L.) Mill). However, the conservation status of this species remains unclear in Europe, other than in Belgium and the Czech Republic, where it has been declared an endangered species. The population density of M. sylvestris is higher in the forests of the upper Rhine Valley (France) than in most European forests, with an unbalanced age-structure, an overrepresentation of adults and a tendency to clump. We characterize here the ecology, age-structure and genetic diversity of wild apple populations in the Rhine Valley. We use these data to highlight links to the history of this species and to propose guidelines for future conservation strategies. In total, 255 individual wild apple trees from six forest stands (five floodplain forests and one forest growing in drier conditions) were analysed in the field, collected and genotyped on the basis of data for 15 microsatellite markers. Genetic analyses showed no escaped cultivars and few hybrids with the cultivated apple. Excluding the hybrids, the genetically “pure” populations displayed high levels of genetic diversity and a weak population structure. Age-structure and ecology studies of wild apple populations identified four categories that were not randomly distributed across the forests, reflecting the history of the Rhine forest over the last century. The Rhine wild apple populations, with their ecological strategies, high genetic diversity, and weak traces of crop-to-wild gene flow associated with the history of these floodplain forests, constitute candidate populations for inclusion in future conservation programmes for European wild apple. PMID:24827575

  15. Wild European apple (Malus sylvestris (L.) Mill.) population dynamics: insight from genetics and ecology in the Rhine Valley. Priorities for a future conservation programme.

    Science.gov (United States)

    Schnitzler, Annik; Arnold, Claire; Cornille, Amandine; Bachmann, Olivier; Schnitzler, Christophe

    2014-01-01

    The increasing fragmentation of forest habitats and the omnipresence of cultivars potentially threaten the genetic integrity of the European wild apple (Malus sylvestris (L.) Mill). However, the conservation status of this species remains unclear in Europe, other than in Belgium and the Czech Republic, where it has been declared an endangered species. The population density of M. sylvestris is higher in the forests of the upper Rhine Valley (France) than in most European forests, with an unbalanced age-structure, an overrepresentation of adults and a tendency to clump. We characterize here the ecology, age-structure and genetic diversity of wild apple populations in the Rhine Valley. We use these data to highlight links to the history of this species and to propose guidelines for future conservation strategies. In total, 255 individual wild apple trees from six forest stands (five floodplain forests and one forest growing in drier conditions) were analysed in the field, collected and genotyped on the basis of data for 15 microsatellite markers. Genetic analyses showed no escaped cultivars and few hybrids with the cultivated apple. Excluding the hybrids, the genetically "pure" populations displayed high levels of genetic diversity and a weak population structure. Age-structure and ecology studies of wild apple populations identified four categories that were not randomly distributed across the forests, reflecting the history of the Rhine forest over the last century. The Rhine wild apple populations, with their ecological strategies, high genetic diversity, and weak traces of crop-to-wild gene flow associated with the history of these floodplain forests, constitute candidate populations for inclusion in future conservation programmes for European wild apple.

  16. Genetic modification and genetic determinism

    Science.gov (United States)

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  17. Accelerating dynamic genetic conservation efforts: Use of FT-IR spectroscopy for the rapid identification of trees resistant to destructive pathogens

    Science.gov (United States)

    C. Villari; R.A. Sniezko; L.E. Rodriguez-Saona; P. Bonello

    2017-01-01

    A strong focus on tree germplasm that can resist threats such as non-native insects and pathogens, or a changing climate, is fundamental for successful genetic conservation efforts. However, the unavailability of tools for rapid screening of tree germplasm for resistance to critical pathogens and insect pests is becoming an increasingly serious bottleneck. Here we...

  18. Genetic diversity and differentiation patterns in Micromeria from the Canary Islands are congruent with multiple colonization dynamics and the establishment of species syngameons.

    Science.gov (United States)

    Curto, M; Puppo, P; Kratschmer, S; Meimberg, H

    2017-08-22

    Especially on islands closer to the mainland, such as the Canary Islands, different lineages that originated by multiple colonization events could have merged by hybridization, which then could have promoted radiation events (Herben et al., J Ecol 93: 572-575, 2005; Saunders and Gibson, J Ecol 93: 649-652, 2005; Caujapé-Castells, Jesters, red queens, boomerangs and surfers: a molecular outlook on the diversity of the Canarian endemic flora, 2011). This is an alternative to the scenario where evolution is mostly driven by drift (Silvertown, J Ecol 92: 168-173, 2004; Silvertown et al., J Ecol 93: 653-657, 2005). In the former case hybridization should be reflected in the genetic structure and diversity patterns of island species. In the present work we investigate Micromeria from the Canary Islands by extensively studying their phylogeographic pattern based on 15 microsatellite loci and 945 samples. These results are interpreted according to the hypotheses outlined above. Genetic structure assessment allowed us to genetically differentiate most Micromeria species and supported their current classification. We found that populations on younger islands were significantly more genetically diverse and less differentiated than those on older islands. Moreover, we found that genetic distance on younger islands was in accordance with an isolation-by-distance pattern, while on the older islands this was not the case. We also found evidence of introgression among species and islands. These results are congruent with a scenario of multiple colonizations during the expansion onto new islands. Hybridization contributes to the grouping of multiple lineages into highly diverse populations. Thus, in our case, islands receive several colonization events from different sources, which are combined into sink populations. This mechanism is in accordance with the surfing syngameon hypothesis. Contrary to the surfing syngameon current form, our results may reflect a slightly different

  19. From Genetics to Genetic Algorithms

    Indian Academy of Sciences (India)

    Genetic algorithms (GAs) are computational optimisation schemes with an ... The algorithms solve optimisation problems ..... Genetic Algorithms in Search, Optimisation and Machine. Learning, Addison-Wesley Publishing Company, Inc. 1989.

  20. From Genetics to Genetic Algorithms

    Indian Academy of Sciences (India)

    artificial genetic system) string feature or ... called the genotype whereas it is called a structure in artificial genetic ... assigned a fitness value based on the cost function. Better ..... way it has produced complex, intelligent living organisms capable of ...

  1. About Genetic Counselors

    Science.gov (United States)

    ... clinical care in many areas of medicine. Assisted Reproductive Technology/Infertility Genetics Cancer Genetics Cardiovascular Genetics Cystic Fibrosis Genetics Fetal Intervention and Therapy Genetics Hematology Genetics Metabolic Genetics ...

  2. The opsin repertoire of the European lancelet: a window into light detection in a basal chordate

    Czech Academy of Sciences Publication Activity Database

    Pantzartzi, Chrysoula; Pergner, Jiří; Kozmiková, Iryna; Kozmik, Zbyněk

    2017-01-01

    Roč. 61, č. 10-12 (2017), s. 763-772 ISSN 0214-6282 R&D Projects: GA ČR GA17-15374S; GA MŠk LO1220; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : Branchiostoma * amphioxus * opsin * expression Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 1.981, year: 2016

  3. Diversity and repertoire of IgW and IgM VH families in the newborn nurse shark.

    Science.gov (United States)

    Rumfelt, Lynn L; Lohr, Rebecca L; Dooley, Helen; Flajnik, Martin F

    2004-05-06

    Adult cartilaginous fish express three immunoglobulin (Ig) isotypes, IgM, IgNAR and IgW. Newborn nurse sharks, Ginglymostoma cirratum, produce 19S (multimeric) IgM and monomeric/dimeric IgM1gj, a germline-joined, IgM-related VH, and very low amounts of 7S (monomeric) IgM and IgNAR proteins. Newborn IgNAR VH mRNAs are diverse in the complementarity-determining region 3 (CDR3) with non-templated nucleotide (N-region) addition, which suggests that, unlike in many other vertebrates, terminal deoxynucleotidyl transferase (TdT) expressed at birth is functional. IgW is present in the lungfish, a bony fish sharing a common ancestor with sharks 460 million years ago, implying that the IgW VH family is as old as the IgM VH family. This nurse shark study examined the IgM and IgW VH repertoire from birth through adult life, and analyzed the phylogenetic relationships of these gene families. IgM and IgW VH cDNA clones isolated from newborn nurse shark primary and secondary lymphoid tissues had highly diverse and unique CDR3 with N-region addition and VDJ gene rearrangement, implicating functional TdT and RAG gene activity. Despite the clear presence of N-region additions, newborn CDR3 were significantly shorter than those of adults. The IgM clones are all included in a conventional VH family that can be classified into five discrete groups, none of which is orthologous to IgM VH genes in other elasmobranchs. In addition, a novel divergent VH family was orthologous to a published monotypic VH horn shark family. IgW VH genes have diverged sufficiently to form three families. IgM and IgW VH serine codons using the potential somatic hypermutation hotspot sequence occur mainly in VH framework 1 (FR1) and CDR1. Phylogenetic analysis of cartilaginous fish and lungfish IgM and IgW demonstrated they form two major ancient gene groups; furthermore, these VH genes generally diversify (duplicate and diverge) within a species. As in ratfish, sandbar and horn sharks, most nurse shark IgM VH

  4. Diversity and repertoire of IgW and IgM VH families in the newborn nurse shark

    Directory of Open Access Journals (Sweden)

    Dooley Helen

    2004-05-01

    Full Text Available Abstract Background Adult cartilaginous fish express three immunoglobulin (Ig isotypes, IgM, IgNAR and IgW. Newborn nurse sharks, Ginglymostoma cirratum, produce 19S (multimeric IgM and monomeric/dimeric IgM1gj, a germline-joined, IgM-related VH, and very low amounts of 7S (monomeric IgM and IgNAR proteins. Newborn IgNAR VH mRNAs are diverse in the complementarity-determining region 3 (CDR3 with non-templated nucleotide (N-region addition, which suggests that, unlike in many other vertebrates, terminal deoxynucleotidyl transferase (TdT expressed at birth is functional. IgW is present in the lungfish, a bony fish sharing a common ancestor with sharks 460 million years ago, implying that the IgW VH family is as old as the IgM VH family. This nurse shark study examined the IgM and IgW VH repertoire from birth through adult life, and analyzed the phylogenetic relationships of these gene families. Results IgM and IgW VH cDNA clones isolated from newborn nurse shark primary and secondary lymphoid tissues had highly diverse and unique CDR3 with N-region addition and VDJ gene rearrangement, implicating functional TdT and RAG gene activity. Despite the clear presence of N-region additions, newborn CDR3 were significantly shorter than those of adults. The IgM clones are all included in a conventional VH family that can be classified into five discrete groups, none of which is orthologous to IgM VH genes in other elasmobranchs. In addition, a novel divergent VH family was orthologous to a published monotypic VH horn shark family. IgW VH genes have diverged sufficiently to form three families. IgM and IgW VH serine codons using the potential somatic hypermutation hotspot sequence occur mainly in VH framework 1 (FR1 and CDR1. Phylogenetic analysis of cartilaginous fish and lungfish IgM and IgW demonstrated they form two major ancient gene groups; furthermore, these VH genes generally diversify (duplicate and diverge within a species. Conclusion As in ratfish

  5. Different Somatic Hypermutation Levels among Antibody Subclasses Disclosed by a New Next-Generation Sequencing-Based Antibody Repertoire Analysis

    Directory of Open Access Journals (Sweden)

    Kazutaka Kitaura

    2017-05-01

    Full Text Available A diverse antibody repertoire is primarily generated by the rearrangement of V, D, and J genes and subsequent somatic hypermutation (SHM. Class-switch recombination (CSR produces various isotypes and subclasses with different functional properties. Although antibody isotypes and subclasses are considered to be produced by both direct and sequential CSR, it is still not fully understood how SHMs accumulate during the process in which antibody subclasses are generated. Here, we developed a new next-generation sequencing (NGS-based antibody repertoire analysis capable of identifying all antibody isotype and subclass genes and used it to examine the peripheral blood mononuclear cells of 12 healthy individuals. Using a total of 5,480,040 sequences, we compared percentage frequency of variable (V, junctional (J sequence, and a combination of V and J, diversity, length, and amino acid compositions of CDR3, SHM, and shared clones in the IgM, IgD, IgG3, IgG1, IgG2, IgG4, IgA1, IgE, and IgA2 genes. The usage and diversity were similar among the immunoglobulin (Ig subclasses. Clonally related sequences sharing identical V, D, J, and CDR3 amino acid sequences were frequently found within multiple Ig subclasses, especially between IgG1 and IgG2 or IgA1 and IgA2. SHM occurred most frequently in IgG4, while IgG3 genes were the least mutated among all IgG subclasses. The shared clones had almost the same SHM levels among Ig subclasses, while subclass-specific clones had different levels of SHM dependent on the genomic location. Given the sequential CSR, these results suggest that CSR occurs sequentially over multiple subclasses in the order corresponding to the genomic location of IGHCs, but CSR is likely to occur more quickly than SHMs accumulate within Ig genes under physiological conditions. NGS-based antibody repertoire analysis should provide critical information on how various antibodies are generated in the immune system.

  6. Transcription Factor Repertoire of Necrotrophic Fungal Phytopathogen Ascochyta rabiei: Predominance of MYB Transcription Factors As Potential Regulators of Secretome

    Directory of Open Access Journals (Sweden)

    Sandhya Verma

    2017-06-01

    Full Text Available Transcription factors (TFs are the key players in gene expression and their study is highly significant for shedding light on the molecular mechanisms and evolutionary history of organisms. During host–pathogen interaction, extensive reprogramming of gene expression facilitated by TFs is likely to occur in both host and pathogen. To date, the knowledge about TF repertoire in filamentous fungi is in infancy. The necrotrophic fungus Ascochyta rabiei, that causes destructive Ascochyta blight (AB disease of chickpea (Cicer arietinum, demands more comprehensive study for better understanding of Ascochyta-legume pathosystem. In the present study, we performed the genome-wide identification and analysis of TFs in A. rabiei. Taking advantage of A. rabiei genome sequence, we used a bioinformatic approach to predict the TF repertoire of A. rabiei. For identification and classification of A. rabiei TFs, we designed a comprehensive pipeline using a combination of BLAST and InterProScan software. A total of 381 A. rabiei TFs were predicted and divided into 32 fungal specific families of TFs. The gene structure, domain organization and phylogenetic analysis of abundant families of A. rabiei TFs were also carried out. Comparative study of A. rabiei TFs with that of other necrotrophic, biotrophic, hemibiotrophic, symbiotic, and saprotrophic fungi was performed. It suggested presence of both conserved as well as unique features among them. Moreover, cis-acting elements on promoter sequences of earlier predicted A. rabiei secretome were also identified. With the help of published A. rabiei transcriptome data, the differential expression of TF and secretory protein coding genes was analyzed. Furthermore, comprehensive expression analysis of few selected A. rabiei TFs using quantitative real-time polymerase chain reaction revealed variety of expression patterns during host colonization. These genes were expressed in at least one of the time points tested post

  7. Synthetic alienation of microbial organisms by using genetic code engineering: Why and how?

    Science.gov (United States)

    Kubyshkin, Vladimir; Budisa, Nediljko

    2017-08-01

    The main goal of synthetic biology (SB) is the creation of biodiversity applicable for biotechnological needs, while xenobiology (XB) aims to expand the framework of natural chemistries with the non-natural building blocks in living cells to accomplish artificial biodiversity. Protein and proteome engineering, which overcome limitation of the canonical amino acid repertoire of 20 (+2) prescribed by the genetic code by using non-canonic amino acids (ncAAs), is one of the main focuses of XB research. Ideally, estranging the genetic code from its current form via systematic introduction of ncAAs should enable the development of bio-containment mechanisms in synthetic cells potentially endowing them with a "genetic firewall" i.e. orthogonality which prevents genetic information transfer to natural systems. Despite rapid progress over the past two decades, it is not yet possible to completely alienate an organism that would use and maintain different genetic code associations permanently. In order to engineer robust bio-contained life forms, the chemical logic behind the amino acid repertoire establishment should be considered. Starting from recent proposal of Hartman and Smith about the genetic code establishment in the RNA world, here the authors mapped possible biotechnological invasion points for engineering of bio-contained synthetic cells equipped with non-canonical functionalities. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. City of Uruk 3000 B.C. : using genetic algorithms, dynamic planning and crowd simulation to re-enact everyday life of ancient Sumerians

    OpenAIRE

    Trescak, Tomas; Bogdanovych, Anton; Simoff, Simeon

    2014-01-01

    Virtual reality reconstructions of ancient historical sites have become a valuable technique for popularising science and visualising expert knowledge to general audiences. Most such reconstructions only re-create buildings and artefacts and place them in the context of the virtual environment, but what is often missing in such simulations is the ability to see how ancient people lived their daily life in these environments. Our presented case study shows how the use of genetic algorithms and...

  9. Across-environment genetic correlations and the frequency of selective environments shape the evolutionary dynamics of growth rate in Impatiens capensis.

    Science.gov (United States)

    Stinchcombe, John R; Izem, Rima; Heschel, M Shane; McGoey, Brechann V; Schmitt, Johanna

    2010-10-01

    Trade-offs can exist within and across environments, and constrain evolutionary trajectories. To examine the effects of competition and resource availability on trade-offs, we grew individuals of recombinant inbred lines of Impatiens capensis in a factorial combination of five densities with two light environments (full light and neutral shade) and used a Bayesian logistic growth analysis to estimate intrinsic growth rates. To estimate across-environment constraints, we developed a variance decomposition approach to principal components analysis, which accounted for sample size, model-fitting, and within-RIL variation prior to eigenanalysis. We detected negative across-environment genetic covariances in intrinsic growth rates, although only under full-light. To evaluate the potential importance of these covariances, we surveyed natural populations of I. capensis to measure the frequency of different density environments across space and time. We combined our empirical estimates of across-environment genetic variance-covariance matrices and frequency of selective environments with hypothetical (yet realistic) selection gradients to project evolutionary responses in multiple density environments. Selection in common environments can lead to correlated responses to selection in rare environments that oppose and counteract direct selection in those rare environments. Our results highlight the importance of considering both the frequency of selective environments and the across-environment genetic covariances in traits simultaneously. © 2010 The Author(s). Journal compilation © 2010 The Society for the Study of Evolution.

  10. Mining Naïve Rabbit Antibody Repertoires by Phage Display for Monoclonal Antibodies of Therapeutic Utility.

    Science.gov (United States)

    Peng, Haiyong; Nerreter, Thomas; Chang, Jing; Qi, Junpeng; Li, Xiuling; Karunadharma, Pabalu; Martinez, Gustavo J; Fallahi, Mohammad; Soden, Jo; Freeth, Jim; Beerli, Roger R; Grawunder, Ulf; Hudecek, Michael; Rader, Christoph

    2017-09-15

    Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity. Moreover, ROR1- and ROR2-targeting rabbit mAbs demonstrated therapeutic utility as components of chimeric antigen receptor-engineered T cells, further corroborating the value of the naïve rabbit antibody library as a rich and virtually unlimited source of rabbit mAbs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. A diverse host thrombospondin-type-1 repeat protein repertoire promotes symbiont colonization during establishment of cnidarian-dinoflagellate symbiosis.

    Science.gov (United States)

    Neubauer, Emilie-Fleur; Poole, Angela Z; Neubauer, Philipp; Detournay, Olivier; Tan, Kenneth; Davy, Simon K; Weis, Virginia M

    2017-05-08

    The mutualistic endosymbiosis between cnidarians and dinoflagellates is mediated by complex inter-partner signaling events, where the host cnidarian innate immune system plays a crucial role in recognition and regulation of symbionts. To date, little is known about the diversity of thrombospondin-type-1 repeat (TSR) domain proteins in basal metazoans or their potential role in regulation of cnidarian-dinoflagellate mutualisms. We reveal a large and diverse repertoire of TSR proteins in seven anthozoan species, and show that in the model sea anemone Aiptasia pallida the TSR domain promotes colonization of the host by the symbiotic dinoflagellate Symbiodinium minutum . Blocking TSR domains led to decreased colonization success, while adding exogenous TSRs resulted in a 'super colonization'. Furthermore, gene expression of TSR proteins was highest at early time-points during symbiosis establishment. Our work characterizes the diversity of cnidarian TSR proteins and provides evidence that these proteins play an important role in the establishment of cnidarian-dinoflagellate symbiosis.

  12. The repertoire of olfactory C family G protein-coupled receptors in zebrafish: candidate chemosensory receptors for amino acids

    Directory of Open Access Journals (Sweden)

    Ngai John

    2006-12-01

    Full Text Available Abstract Background Vertebrate odorant receptors comprise at least three types of G protein-coupled receptors (GPCRs: the OR, V1R, and V2R/V2R-like receptors, the latter group belonging to the C family of GPCRs. These receptor families are thought to receive chemosensory information from a wide spectrum of odorant and pheromonal cues that influence critical animal behaviors such as feeding, reproduction and other social interactions. Results Using genome database mining and other informatics approaches, we identified and characterized the repertoire of 54 intact "V2R-like" olfactory C family GPCRs in the zebrafish. Phylogenetic analysis – which also included a set of 34 C family GPCRs from fugu – places the fish olfactory receptors in three major groups, which are related to but clearly distinct from other C family GPCRs, including the calcium sensing receptor, metabotropic glutamate receptors, GABA-B receptor, T1R taste receptors, and the major group of V2R vomeronasal receptor families. Interestingly, an analysis of sequence conservation and selective pressure in the zebrafish receptors revealed the retention of a conserved sequence motif previously shown to be required for ligand binding in other amino acid receptors. Conclusion Based on our findings, we propose that the repertoire of zebrafish olfactory C family GPCRs has evolved to allow the detection and discrimination of a spectrum of amino acid and/or amino acid-based compounds, which are potent olfactory cues in fish. Furthermore, as the major groups of fish receptors and mammalian V2R receptors appear to have diverged significantly from a common ancestral gene(s, these receptors likely mediate chemosensation of different classes of chemical structures by their respective organisms.

  13. miRNA Repertoires of Demosponges Stylissa carteri and Xestospongia testudinaria

    KAUST Repository

    Liew, Yi Jin

    2016-02-12

    MicroRNAs (miRNAs) are small regulatory RNAs that are involved in many biological process in eukaryotes. They play a crucial role in modulating genetic expression of their targets, which makes them integral components of transcriptional regulatory networks. As sponges (phylum Porifera) are commonly considered the most basal metazoan, the in-depth capture of miRNAs from these organisms provides additional clues to the evolution of miRNA families in metazoans. Here, we identified the core proteins involved in the biogenesis of miRNAs, and obtained evidence for bona fide miRNA sequences for two marine sponges Stylissa carteri and Xestospongia testudinaria (11 and 19 respectively). Our analysis identified several miRNAs that are conserved amongst demosponges, and revealed that all of the novel miRNAs identified in these two species are specific to the class Demospongiae.

  14. miRNA Repertoires of Demosponges Stylissa carteri and Xestospongia testudinaria

    KAUST Repository

    Liew, Yi Jin; Ryu, Tae Woo; Aranda, Manuel; Ravasi, Timothy

    2016-01-01

    MicroRNAs (miRNAs) are small regulatory RNAs that are involved in many biological process in eukaryotes. They play a crucial role in modulating genetic expression of their targets, which makes them integral components of transcriptional regulatory networks. As sponges (phylum Porifera) are commonly considered the most basal metazoan, the in-depth capture of miRNAs from these organisms provides additional clues to the evolution of miRNA families in metazoans. Here, we identified the core proteins involved in the biogenesis of miRNAs, and obtained evidence for bona fide miRNA sequences for two marine sponges Stylissa carteri and Xestospongia testudinaria (11 and 19 respectively). Our analysis identified several miRNAs that are conserved amongst demosponges, and revealed that all of the novel miRNAs identified in these two species are specific to the class Demospongiae.

  15. Analysis of the HLA-DR peptidome from human dendritic cells reveals high affinity repertoires and nonconventional pathways of peptide generation

    NARCIS (Netherlands)

    Ciudad, M Teresa; Sorvillo, Nicoletta; van Alphen, Floris P.J.; Catalán, Diego; Meijer, Sander; Voorberg, Jan; Jaraquemada, Dolores

    Dendritic cells (DCs) are the major professional APCs of the immune system; however, their MHC-II-associated peptide repertoires have been hard to analyze, mostly because of their scarce presence in blood and tissues. In vitro matured human monocyte-derived DCs (MoDCs) are widely used as

  16. "Nobody Told Me They Didn't Speak English!": Teacher Language Views and Student Linguistic Repertoires in Hutterite Colony Schools in Canada

    Science.gov (United States)

    Sterzuk, Andrea; Nelson, Cynthia A.

    2016-01-01

    This article presents a qualitative study of five monolingual teachers' understandings of the linguistic repertoires of their multilingual students. These teachers deliver the Saskatchewan provincial curricula in English to Hutterite colony students who are users of three languages: (a) spoken Hutterisch as a home and community language, (b)…

  17. Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study.

    Directory of Open Access Journals (Sweden)

    Christopher Vollmers

    2015-10-01

    Full Text Available It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation.In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412 that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without. We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient's net state of immunosuppression (correlation with tacrolimus level, r = -0.867, 95% CI -0.968 to -0.523, p = 0.0014, as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9% and a specificity of 82.0% (95% CI 72.1% to 89.1% (cell-free donor-derived DNA as noninvasive gold standard. To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several criteria including the

  18. Slow and fast dynamics model of a Malaria with Sickle-Cell genetic disease with multi-stage infections of the mosquitoes population

    Science.gov (United States)

    Dewi Siawanta, Shanti; Adi-Kusumo, Fajar; Irwan Endrayanto, Aluicius

    2018-03-01

    Malaria, which is caused by Plasmodium, is a common disease in tropical areas. There are three types of Plasmodium i.e. Plasmodium Vivax, Plasmodium Malariae, and Plasmodium Falciparum. The most dangerous cases of the Malaria are mainly caused by the Plasmodium Falciparum. One of the important characteristics for the Plasmodium infection is due to the immunity of erythrocyte that contains HbS (Haemoglobin Sickle-cell) genes. The individuals who has the HbS gene has better immunity against the disease. In this paper, we consider a model that shows the spread of malaria involving the interaction between the mosquitos population, the human who has HbS genes population and the human with normal gene population. We do some analytical and numerical simulation to study the basic reproduction ratio and the slow-fast dynamics of the phase-portrait. The slow dynamics in our model represents the response of the human population with HbS gene to the Malaria disease while the fast dynamics show the response of the human population with the normal gene to the disease. The slow and fast dynamics phenomena are due to the fact that the population of the individuals who have HbS gene is much smaller than the individuals who has normal genes.

  19. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies

    Directory of Open Access Journals (Sweden)

    Specht Günther

    2010-03-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. Description eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle, security aspects (by using database technology and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs. It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. Conclusions The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

  20. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies.

    Science.gov (United States)

    Weissensteiner, Hansi; Schönherr, Sebastian; Specht, Günther; Kronenberg, Florian; Brandstätter, Anita

    2010-03-09

    Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

  1. Genetic modification and genetic determinism

    Directory of Open Access Journals (Sweden)

    Vorhaus Daniel B

    2006-06-01

    Full Text Available Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  2. Fragile Cities: a Critical Perspective on the Repertoire for New Urban Humanitarian Interventions

    Directory of Open Access Journals (Sweden)

    Manoela Miklos

    Full Text Available Abstract At the end of the 1990s, researchers involved in the debate on the new wars introduced discussion about the urban dimension of contemporary conflicts into the International Relations discipline. The innovative debate about urban fragility is one of the many lines of inquiry that emerge within the framework of the relationship between cities and contemporary conflicts. This paper seeks to demonstrate that the concept of ‘fragile city’ offers a new and relevant analytical framework for understanding contemporary urban violence and inequality. Moreover, this same concept could also be instrumental in making fragile cities the new locus of international humanitarianism. The notion of fragile city emerges to describe new emergency situations more closely linked to urban contexts than to national dynamics, as previously described in the literature on fragile states. The concept of fragile city is a groundbreaking tool for understanding the human consequences of inequality in urban settings, but might also be used as a rhetorical vehicle for the reproduction of old dynamics and the inauguration of new intervention practices in urban areas that were previously inaccessible to humanitarian action, especially cities in Latin America.

  3. Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative.

    Science.gov (United States)

    Sun, Baoguo; Meng, Jun; Xiang, Ting; Zhang, Lei; Deng, Liuxiang; Chen, Yan; Luo, Haoxuan; Yang, Zhangbin; Chen, Zexiong; Zhang, Shijun

    2016-03-01

    The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vβ-chain complementarity-determining region 3 (TCRVβCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVβCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (PSimpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL-OHC-induced animals may be due to the promotion of the Ds values of the TCRVβCDR3 repertoire.

  4. Genetic Engineering

    Science.gov (United States)

    Phillips, John

    1973-01-01

    Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)

  5. Genetic Romanticism

    DEFF Research Database (Denmark)

    Tupasela, Aaro

    2016-01-01

    inheritance as a way to unify populations within politically and geographically bounded areas. Thus, new genetics have contributed to the development of genetic romanticisms, whereby populations (human, plant, and animal) can be delineated and mobilized through scientific and medical practices to represent...

  6. Virus encoded MHC-like decoys diversify the inhibitory KIR repertoire.

    Directory of Open Access Journals (Sweden)

    Paola Carrillo-Bustamante

    Full Text Available Natural killer (NK cells are circulating lymphocytes that play an important role in the control of viral infections and tumors. Their functions are regulated by several activating and inhibitory receptors. A subset of these receptors in human NK cells are the killer immunoglobulin-like receptors (KIRs, which interact with the highly polymorphic MHC class I molecules. One important function of NK cells is to detect cells that have down-regulated MHC expression (missing-self. Because MHC molecules have non polymorphic regions, their expression could have been monitored with a limited set of monomorphic receptors. Surprisingly, the KIR family has a remarkable genetic diversity, the function of which remains poorly understood. The mouse cytomegalovirus (MCMV is able to evade NK cell responses by coding "decoy" molecules that mimic MHC class I. This interaction was suggested to have driven the evolution of novel NK cell receptors. Inspired by the MCMV system, we develop an agent-based model of a host population infected with viruses that are able to evolve MHC down-regulation and decoy molecules. Our simulations show that specific recognition of MHC class I molecules by inhibitory KIRs provides excellent protection against viruses evolving decoys, and that the diversity of inhibitory KIRs will subsequently evolve as a result of the required discrimination between host MHC molecules and decoy molecules.

  7. Mapping cellular hierarchy by single-cell analysis of the cell surface repertoire.

    Science.gov (United States)

    Guo, Guoji; Luc, Sidinh; Marco, Eugenio; Lin, Ta-Wei; Peng, Cong; Kerenyi, Marc A; Beyaz, Semir; Kim, Woojin; Xu, Jian; Das, Partha Pratim; Neff, Tobias; Zou, Keyong; Yuan, Guo-Cheng; Orkin, Stuart H

    2013-10-03

    Stem cell differentiation pathways are most often studied at the population level, whereas critical decisions are executed at the level of single cells. We have established a highly multiplexed, quantitative PCR assay to profile in an unbiased manner a panel of all commonly used cell surface markers (280 genes) from individual cells. With this method, we analyzed over 1,500 single cells throughout the mouse hematopoietic system and illustrate its utility for revealing important biological insights. The comprehensive single cell data set permits mapping of the mouse hematopoietic stem cell differentiation hierarchy by computational lineage progression analysis. Further profiling of 180 intracellular regulators enabled construction of a genetic network to assign the earliest differentiation event during hematopoietic lineage specification. Analysis of acute myeloid leukemia elicited by MLL-AF9 uncovered a distinct cellular hierarchy containing two independent self-renewing lineages with different clonal activities. The strategy has broad applicability in other cellular systems. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Functional Repertoire of Antibiotic Resistance Genes in Antibiotic Manufacturing Effluents and Receiving Freshwater Sediments

    Science.gov (United States)

    González-Plaza, Juan J.; Šimatović, Ana; Milaković, Milena; Bielen, Ana; Wichmann, Fabienne; Udiković-Kolić, Nikolina

    2018-01-01

    Environments polluted by direct discharges of effluents from antibiotic manufacturing are important reservoirs for antibiotic resistance genes (ARGs), which could potentially be transferred to human pathogens. However, our knowledge about the identity and diversity of ARGs in such polluted environments remains limited. We applied functional metagenomics to explore the resistome of two Croatian antibiotic manufacturing effluents and sediments collected upstream of and at the effluent discharge sites. Metagenomic libraries built from an azithromycin-production site were screened for resistance to macrolide antibiotics, whereas the libraries from a site producing veterinary antibiotics were screened for resistance to sulfonamides, tetracyclines, trimethoprim, and beta-lactams. Functional analysis of eight libraries identified a total of 82 unique, often clinically relevant ARGs, which were frequently found in clusters and flanked by mobile genetic elements. The majority of macrolide resistance genes identified from matrices exposed to high levels of macrolides were similar to known genes encoding ribosomal protection proteins, macrolide phosphotransferases, and transporters. Potentially novel macrolide resistance genes included one most similar to a 23S rRNA methyltransferase from Clostridium and another, derived from upstream unpolluted sediment, to a GTPase HflX from Emergencia. In libraries deriving from sediments exposed to lower levels of veterinary antibiotics, we found 8 potentially novel ARGs, including dihydrofolate reductases and beta-lactamases from classes A, B, and D. In addition, we detected 7 potentially novel ARGs in upstream sediment, including thymidylate synthases, dihydrofolate reductases, and class D beta-lactamase. Taken together, in addition to finding known gene types, we report the discovery of novel and diverse ARGs in antibiotic-polluted industrial effluents and sediments, providing a qualitative basis for monitoring the dispersal of ARGs

  9. Functional Repertoire of Antibiotic Resistance Genes in Antibiotic Manufacturing Effluents and Receiving Freshwater Sediments

    Directory of Open Access Journals (Sweden)

    Juan J. González-Plaza

    2018-01-01

    Full Text Available Environments polluted by direct discharges of effluents from antibiotic manufacturing are important reservoirs for antibiotic resistance genes (ARGs, which could potentially be transferred to human pathogens. However, our knowledge about the identity and diversity of ARGs in such polluted environments remains limited. We applied functional metagenomics to explore the resistome of two Croatian antibiotic manufacturing effluents and sediments collected upstream of and at the effluent discharge sites. Metagenomic libraries built from an azithromycin-production site were screened for resistance to macrolide antibiotics, whereas the libraries from a site producing veterinary antibiotics were screened for resistance to sulfonamides, tetracyclines, trimethoprim, and beta-lactams. Functional analysis of eight libraries identified a total of 82 unique, often clinically relevant ARGs, which were frequently found in clusters and flanked by mobile genetic elements. The majority of macrolide resistance genes identified from matrices exposed to high levels of macrolides were similar to known genes encoding ribosomal protection proteins, macrolide phosphotransferases, and transporters. Potentially novel macrolide resistance genes included one most similar to a 23S rRNA methyltransferase from Clostridium and another, derived from upstream unpolluted sediment, to a GTPase HflX from Emergencia. In libraries deriving from sediments exposed to lower levels of veterinary antibiotics, we found 8 potentially novel ARGs, including dihydrofolate reductases and beta-lactamases from classes A, B, and D. In addition, we detected 7 potentially novel ARGs in upstream sediment, including thymidylate synthases, dihydrofolate reductases, and class D beta-lactamase. Taken together, in addition to finding known gene types, we report the discovery of novel and diverse ARGs in antibiotic-polluted industrial effluents and sediments, providing a qualitative basis for monitoring the

  10. The scavenger receptor repertoire in six cnidarian species and its putative role in cnidarian-dinoflagellate symbiosis

    Directory of Open Access Journals (Sweden)

    Emilie F. Neubauer

    2016-11-01

    Full Text Available Many cnidarians engage in a mutualism with endosymbiotic photosynthetic dinoflagellates that forms the basis of the coral reef ecosystem. Interpartner interaction and regulation includes involvement of the host innate immune system. Basal metazoans, including cnidarians have diverse and complex innate immune repertoires that are just beginning to be described. Scavenger receptors (SR are a diverse superfamily of innate immunity genes that recognize a broad array of microbial ligands and participate in phagocytosis of invading microbes. The superfamily includes subclades named SR-A through SR-I that are categorized based on the arrangement of sequence domains including the scavenger receptor cysteine rich (SRCR, the C-type lectin (CTLD and the CD36 domains. Previous functional and gene expression studies on cnidarian-dinoflagellate symbiosis have implicated SR-like proteins in interpartner communication and regulation. In this study, we characterized the SR repertoire from a combination of genomic and transcriptomic resources from six cnidarian species in the Class Anthozoa. We combined these bioinformatic analyses with functional experiments using the SR inhibitor fucoidan to explore a role for SRs in cnidarian symbiosis and immunity. Bioinformatic searches revealed a large diversity of SR-like genes that resembled SR-As, SR-Bs, SR-Es and SR-Is. SRCRs, CTLDs and CD36 domains were identified in multiple sequences in combinations that were highly homologous to vertebrate SRs as well as in proteins with novel domain combinations. Phylogenetic analyses of CD36 domains of the SR-B-like sequences from a diversity of metazoans grouped cnidarian with bilaterian sequences separate from other basal metazoans. All cnidarian sequences grouped together with moderate support in a subclade separately from bilaterian sequences. Functional experiments were carried out on the sea anemone Aiptasia pallida that engages in a symbiosis with Symbiodinium minutum

  11. Role of genomic typing in taxonomy, evolutionary genetics, and microbial epidemiology.

    NARCIS (Netherlands)

    Belkum, van A.; Struelens, M.; Visser, de J.A.G.M.; Verburgh, H.; Tibayrenc., M.

    2001-01-01

    Currently, genetic typing of microorganisms is widely used in several major fields of microbiological research. Taxonomy, research aimed at elucidation of evolutionary dynamics or phylogenetic relationships, population genetics of microorganisms, and microbial epidemiology all rely on genetic typing

  12. Fluctuating fitness shapes the clone-size distribution of immune repertoires.

    Science.gov (United States)

    Desponds, Jonathan; Mora, Thierry; Walczak, Aleksandra M

    2016-01-12

    The adaptive immune system relies on the diversity of receptors expressed on the surface of B- and T cells to protect the organism from a vast amount of pathogenic threats. The proliferation and degradation dynamics of different cell types (B cells, T cells, naive, memory) is governed by a variety of antigenic and environmental signals, yet the observed clone sizes follow a universal power-law distribution. Guided by this reproducibility we propose effective models of somatic evolution where cell fate depends on an effective fitness. This fitness is determined by growth factors acting either on clones of cells with the same receptor responding to specific antigens, or directly on single cells with no regard for clones. We identify fluctuations in the fitness acting specifically on clones as the essential ingredient leading to the observed distributions. Combining our models with experiments, we characterize the scale of fluctuations in antigenic environments and we provide tools to identify the relevant growth signals in different tissues and organisms. Our results generalize to any evolving population in a fluctuating environment.

  13. Evolutionary genetics

    National Research Council Canada - National Science Library

    Maynard Smith, John

    1989-01-01

    .... It differs from other textbooks of population genetics in applying the basic theory to topics, such as social behaviour, molecular evolution, reiterated DNA, and sex, which are the main subjects...

  14. Genetic Discrimination

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  15. Arthropod Genetics.

    Science.gov (United States)

    Zumwalde, Sharon

    2000-01-01

    Introduces an activity on arthropod genetics that involves phenotype and genotype identification of the creature and the construction process. Includes a list of required materials and directions to build a model arthropod. (YDS)

  16. The Individual and Population Genetics of Antibody Immunity.

    Science.gov (United States)

    Watson, Corey T; Glanville, Jacob; Marasco, Wayne A

    2017-07-01

    Antibodies (Abs) produced by immunoglobulin (IG) genes are the most diverse proteins expressed in humans. While part of this diversity is generated by recombination during B-cell development and mutations during affinity maturation, the germ-line IG loci are also diverse across human populations and ethnicities. Recently, proof-of-concept studies have demonstrated genotype-phenotype correlations between specific IG germ-line variants and the quality of Ab responses during vaccination and disease. However, the functional consequences of IG genetic variation in Ab function and immunological outcomes remain underexplored. In this opinion article, we outline interconnections between IG genomic diversity and Ab-expressed repertoires and structure. We further propose a strategy for integrating IG genotyping with functional Ab profiling data as a means to better predict and optimize humoral responses in genetically diverse human populations, with immediate implications for personalized medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Desktop Genetics

    OpenAIRE

    Hough, Soren H; Ajetunmobi, Ayokunmi; Brody, Leigh; Humphryes-Kirilov, Neil; Perello, Edward

    2016-01-01

    Desktop Genetics is a bioinformatics company building a gene-editing platform for personalized medicine. The company works with scientists around the world to design and execute state-of-the-art clustered regularly interspaced short palindromic repeats (CRISPR) experiments. Desktop Genetics feeds the lessons learned about experimental intent, single-guide RNA design and data from international genomics projects into a novel CRISPR artificial intelligence system. We believe that machine learni...

  18. Dynamic Gaming Platform (DGP)

    Science.gov (United States)

    2009-04-01

    GAMING PLATFORM (DGP) Lockheed Martin Corporation...YYYY) APR 09 2. REPORT TYPE Final 3. DATES COVERED (From - To) Jul 07 – Mar 09 4. TITLE AND SUBTITLE DYNAMIC GAMING PLATFORM (DGP) 5a...CMU Carnegie Mellon University DGP Dynamic Gaming Platform GA Genetic Algorithm IARPA Intelligence Advanced Research Projects Activity LM ATL Lockheed Martin Advanced Technology Laboratories PAINT ProActive INTelligence

  19. Chromosome translocations: the dynamics of embryos preimplantation genetic diagnosis%染色体易位-胚胎植入前诊断的研究进展

    Institute of Scientific and Technical Information of China (English)

    范俊梅; Cram David; 刘忠宇; 李娜; 姚元庆

    2015-01-01

    染色体易位携带者有较高的发生不良妊娠结局的风险,主要源自高概率的非均衡配子.对于染色体易位的携带者,进行胚胎植入前遗传学诊断(preimplantation genetic diagnosis,PGD)可以改善妊娠结局.目前,临床应用的非平衡易位诊断的方法主要有比较基因组杂交微阵列(comparative genomic hybridization array,array CGH)、单核苷酸多态性微阵列(single nucleotide polymorphism array,SNP array)和二代测序(next generation sequencing,NGS);荧光原位杂交(fluorescence in situ hybridization,FISH),能够区分平衡易位和正常胚胎,可能实现的技术有NGS.此外,平衡易位的诊断是否有必要开展尚存在争议.

  20. Dynamic role and importance of surrogate species for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms.

    Science.gov (United States)

    Wach, Michael; Hellmich, Richard L; Layton, Raymond; Romeis, Jörg; Gadaleta, Patricia G

    2016-08-01

    Surrogate species have a long history of use in research and regulatory settings to understand the potentially harmful effects of toxic substances including pesticides. More recently, surrogate species have been used to evaluate the potential effects of proteins contained in genetically engineered insect resistant (GEIR) crops. Species commonly used in GEIR crop testing include beneficial organisms such as honeybees, arthropod predators, and parasitoids. The choice of appropriate surrogates is influenced by scientific factors such as the knowledge of the mode of action and the spectrum of activity as well as societal factors such as protection goals that assign value to certain ecosystem services such as pollination or pest control. The primary reasons for using surrogates include the inability to test all possible organisms, the restrictions on using certain organisms in testing (e.g., rare, threatened, or endangered species), and the ability to achieve greater sensitivity and statistical power by using laboratory testing of certain species. The acceptance of surrogate species data can allow results from one region to be applied or "transported" for use in another region. On the basis of over a decade of using surrogate species to evaluate potential effects of GEIR crops, it appears that the current surrogates have worked well to predict effects of GEIR crops that have been developed (Carstens et al. GM Crops Food 5:1-5, 2014), and it is expected that they should work well to predict effects of future GEIR crops based on similar technologies.

  1. Strategies for the structural analysis of multi-protein complexes: lessons from the 3D-Repertoire project.

    Science.gov (United States)

    Collinet, B; Friberg, A; Brooks, M A; van den Elzen, T; Henriot, V; Dziembowski, A; Graille, M; Durand, D; Leulliot, N; Saint André, C; Lazar, N; Sattler, M; Séraphin, B; van Tilbeurgh, H

    2011-08-01

    Structural studies of multi-protein complexes, whether by X-ray diffraction, scattering, NMR spectroscopy or electron microscopy, require stringent quality control of the component samples. The inability to produce 'keystone' subunits in a soluble and correctly folded form is a serious impediment to the reconstitution of the complexes. Co-expression of the components offers a valuable alternative to the expression of single proteins as a route to obtain sufficient amounts of the sample of interest. Even in cases where milligram-scale quantities of purified complex of interest become available, there is still no guarantee that good quality crystals can be obtained. At this step, protein engineering of one or more components of the complex is frequently required to improve solubility, yield or the ability to crystallize the sample. Subsequent characterization of these constructs may be performed by solution techniques such as Small Angle X-ray Scattering and Nuclear Magnetic Resonance to identify 'well behaved' complexes. Herein, we recount our experiences gained at protein production and complex assembly during the European 3D Repertoire project (3DR). The goal of this consortium was to obtain structural information on multi-protein complexes from yeast by combining crystallography, electron microscopy, NMR and in silico modeling methods. We present here representative set case studies of complexes that were produced and analyzed within the 3DR project. Our experience provides useful insight into strategies that are more generally applicable for structural analysis of protein complexes. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. The effect of intracellular trafficking of CD1d on the formation of TCR repertoire of NKT cells.

    Science.gov (United States)

    Shin, Jung Hoon; Park, Se-Ho

    2014-05-01

    CD1 molecules belong to non-polymorphic MHC class I-like proteins and present lipid antigens to T cells. Five different CD1 genes (CD1a-e) have been identified and classified into two groups. Group 1 include CD1a-c and present pathogenic lipid antigens to αβ T cells reminiscence of peptide antigen presentation by MHC-I molecules. CD1d is the only member of Group 2 and presents foreign and self lipid antigens to a specialized subset of αβ T cells, NKT cells. NKT cells are involved in diverse immune responses through prompt and massive production of cytokines. CD1d-dependent NKT cells are categorized upon the usage of their T cell receptors. A major subtype of NKT cells (type I) is invariant NKT cells which utilize invariant Vα14-Jα18 TCR alpha chain in mouse. The remaining NKT cells (type II) utilize diverse TCR alpha chains. Engineered CD1d molecules with modified intracellular trafficking produce either type I or type II NKT cell-defects suggesting the lipid antigens for each subtypes of NKT cells are processed/generated in different intracellular compartments. Since the usage of TCR by a T cell is the result of antigen-driven selection, the intracellular metabolic pathways of lipid antigen are a key in forming the functional NKT cell repertoire.

  3. Genomic and transcriptomic insights into the cytochrome P450 monooxygenase gene repertoire in the rice pest brown planthopper, Nilaparvata lugens.

    Science.gov (United States)

    Lao, Shu-Hua; Huang, Xiao-Hui; Huang, Hai-Jian; Liu, Cheng-Wen; Zhang, Chuan-Xi; Bao, Yan-Yuan

    2015-11-01

    The cytochrome P450 monooxygenase (P450) gene family is one of the most abundant eukaryotic gene families that encode detoxification enzymes. In this study, we identified an abundance of P450 gene repertoire through genome- and transcriptome-wide analysis in the brown planthopper (Nilaparvata lugens), the most destructive rice pest in Asia. Detailed gene information including the exon-intron organization, size, transcription orientation and distribution in the genome revealed that many P450 loci were closely situated on the same scaffold, indicating frequent occurrence of gene duplications. Insecticide-response expression profiling revealed that imidacloprid significantly increased NlCYP6CS1v2, NLCYP4CE1v2, NlCYP4DE1, NlCYP417A1v2 and NlCYP439A1 expression; while triazophos and deltamethrin notably enhanced NlCYP303A1 expression. Expression analysis at the developmental stage showed the egg-, nymph-, male- and female-specific expression patterns of N. lugens P450 genes. These novel findings will be helpful for clarifying the P450 functions in physiological processes including development, reproduction and insecticide resistance in this insect species. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Genome sequencing and comparative genomics reveal a repertoire of putative pathogenicity genes in chilli anthracnose fungus Colletotrichum truncatum.

    Science.gov (United States)

    Rao, Soumya; Nandineni, Madhusudan R

    2017-01-01

    Colletotrichum truncatum, a major fungal phytopathogen, causes the anthracnose disease on an economically important spice crop chilli (Capsicum annuum), resulting in huge economic losses in tropical and sub-tropical countries. It follows a subcuticular intramural infection strategy on chilli with a short, asymptomatic, endophytic phase, which contrasts with the intracellular hemibiotrophic lifestyle adopted by most of the Colletotrichum species. However, little is known about the molecular determinants and the mechanism of pathogenicity in this fungus. A high quality whole genome sequence and gene annotation based on transcriptome data of an Indian isolate of C. truncatum from chilli has been obtained. Analysis of the genome sequence revealed a rich repertoire of pathogenicity genes in C. truncatum encoding secreted proteins, effectors, plant cell wall degrading enzymes, secondary metabolism associated proteins, with potential roles in the host-specific infection strategy, placing it next only to the Fusarium species. The size of genome assembly, number of predicted genes and some of the functional categories were similar to other sequenced Colletotrichum species. The comparative genomic analyses with other species and related fungi identified some unique genes and certain highly expanded gene families of CAZymes, proteases and secondary metabolism associated genes in the genome of C. truncatum. The draft genome assembly and functional annotation of potential pathogenicity genes of C. truncatum provide an important genomic resource for understanding the biology and lifestyle of this important phytopathogen and will pave the way for designing efficient disease control regimens.

  5. J. Genet. classic 101

    Indian Academy of Sciences (India)

    Journal of Genetics, Vol. 85, No. 2, August 2006. 101. Page 2. J. Genet. classic. 102. Journal of Genetics, Vol. 85, No. 2, August 2006. Page 3. J. Genet. classic. Journal of Genetics, Vol. 85, No. 2, August 2006. 103. Page 4. J. Genet. classic. 104. Journal of Genetics, Vol. 85, No. 2, August 2006. Page 5. J. Genet. classic.

  6. J. Genet. classic 37

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 84, No. 1, April 2005. 37. Page 2. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 38. Page 3. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 39. Page 4. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 40. Page 5. J. Genet. classic. Journal of ...

  7. Cognitive radio resource allocation based on coupled chaotic genetic algorithm

    International Nuclear Information System (INIS)

    Zu Yun-Xiao; Zhou Jie; Zeng Chang-Chang

    2010-01-01

    A coupled chaotic genetic algorithm for cognitive radio resource allocation which is based on genetic algorithm and coupled Logistic map is proposed. A fitness function for cognitive radio resource allocation is provided. Simulations are conducted for cognitive radio resource allocation by using the coupled chaotic genetic algorithm, simple genetic algorithm and dynamic allocation algorithm respectively. The simulation results show that, compared with simple genetic and dynamic allocation algorithm, coupled chaotic genetic algorithm reduces the total transmission power and bit error rate in cognitive radio system, and has faster convergence speed

  8. Genetic diversity of canine olfactory receptors

    Directory of Open Access Journals (Sweden)

    Hitte Christophe

    2009-01-01

    Full Text Available Abstract Background Evolution has resulted in large repertoires of olfactory receptor (OR genes, forming the largest gene families in mammalian genomes. Knowledge of the genetic diversity of olfactory receptors is essential if we are to understand the differences in olfactory sensory capability between individuals. Canine breeds constitute an attractive model system for such investigations. Results We sequenced 109 OR genes considered representative of the whole OR canine repertoire, which consists of more than 800 genes, in a cohort of 48 dogs of six different breeds. SNP frequency showed the overall level of polymorphism to be high. However, the distribution of SNP was highly heterogeneous among OR genes. More than 50% of OR genes were found to harbour a large number of SNP, whereas the rest were devoid of SNP or only slightly polymorphic. Heterogeneity was also observed across breeds, with 25% of the SNP breed-specific. Linkage disequilibrium within OR genes and OR clusters suggested a gene conversion process, consistent with a mean level of polymorphism higher than that observed for introns and intergenic sequences. A large proportion (47% of SNP induced amino-acid changes and the Ka/Ks ratio calculated for all alleles with a complete ORF indicated a low selective constraint with respect to the high level of redundancy of the olfactory combinatory code and an ongoing pseudogenisation process, which affects dog breeds differently. Conclusion Our demonstration of a high overall level of polymorphism, likely to modify the ligand-binding capacity of receptors distributed differently within the six breeds tested, is the first step towards understanding why Labrador Retrievers and German Shepherd Dogs have a much greater potential for use as sniffer dogs than Pekingese dogs or Greyhounds. Furthermore, the heterogeneity in OR polymorphism observed raises questions as to why, in a context in which most OR genes are highly polymorphic, a subset of

  9. Genome dynamics, genetic complexity and macroevolution Dinámica del genoma, complejidad genética y macroevolución

    Directory of Open Access Journals (Sweden)

    MILTON GALLARDO

    2003-12-01

    Full Text Available Genome data analysis indicates that the major evolutionary transitions have been driven by substantial increases in genomic complexity. These increases, accounting for novelty in evolution, have proceeded mainly by gene duplication. This idea, advanced by Ohno (1968, remains current in the study of several organisms whose genomes have been sequenced. Maize, yeast, and humans contain more paralogons than would be expected to occur by chance, and this supports the contention that gene families were not formed de novo, but by large-scale DNA duplications. Lineage hybridization emerges as an efficient and widespread mechanism to create evolutionary novelty by recruiting redundant genes to new roles. Lateral gene transfer indicates a chimeric composition of prokaryote genomes. This peculiar manner of inheritance blurs the edges of phylogenetic lineages and suggests that the anastomosing and dichotomization of branches play key roles in determining the shape of the tree of life. Adaptive mutations have also enlarged the genetic framework of evolutionary thought by incorporating a new mechanism of gene formation. Moreover, developmental biology has provided solid grounds for understanding organisms as consisting of onto- and epigenetically organized modules. Rapid and drastic changes brought about by the study of developmental genes have discredited the notions that adaptation is achieved exclusively by stepwise allele replacement within populations, and that macroevolutionary change is extrapolated microevolution. Apparently, a broadening, if not a remodeling of the genetic framework in which we understand phylogeny and the evolution of morphological complexity, is emerging through the study of comparative genomicsEl análisis genómico comparado indica que las principales transiciones evolutivas se deben a un aumento de la complejidad genómica. Estos incrementos que dan cuenta de las novedades evolutivas se han originado principalmente por

  10. Effect of the Winter Wheat Cheyenne 5A Substituted Chromosome on Dynamics of Abscisic Acid and Cytokinins in Freezing-Sensitive Chinese Spring Genetic Background

    Science.gov (United States)

    Kalapos, Balázs; Novák, Aliz; Dobrev, Petre; Vítámvás, Pavel; Marincs, Ferenc; Galiba, Gábor; Vanková, Radomira

    2017-01-01

    The effect of short- and long-term cold treatment on the abscisic acid (ABA) and cytokinin (CK) metabolism, and their main biosynthesis- and signaling-related genes were investigated in freezing-sensitive and freezing-tolerant wheat genotypes. Varieties Cheyenne and Chinese Spring substituted with the 5A Cheyenne chromosome, which represented freezing-tolerant genotypes, were compared with the freezing-sensitive Chinese Spring. Hormone levels and gene expression data indicated that the short- and long-term cold treatments are associated with specific regulation of the accumulation of cold-protective proteins and phytohormone levels, as well as the expression profiles of the hormone-related genes. The significant differences were observed between the genotypes, and between their leaf and crown tissues, too. The level of dehydrins, including WCS120 protein, and expression of WCS120 gene were considerably higher in the freezing-tolerant genotypes after 21 days of cold treatment. Expression of Cor14b and CBF14, cold-responsive regulator genes, was increased by cold treatment in all genotypes, to higher extent in freezing-tolerant genotypes. Cluster analysis revealed that the tolerant genotypes had a similar response to cold treatment, regarding expression of the ABA and CK metabolic genes, as well as hormone levels in leaves. As far as hormone levels in crowns are concerned, however, the strongly freezing-tolerant Cheyenne variety clustered separately from the Chinese Spring and the substitution line, which were more similar to each other after both 1 and 21 days of cold treatment than to Cheyenne. Based on these results we concluded that the 5A chromosome of wheat might have both a direct and an indirect impact on the phytohormone-dependent cold-induced freezing tolerance. Based on the gene expression data, novel genetic markers could be developed, which may be used to determine the freezing tolerance level in a wide range of wheat varieties. PMID:29238355

  11. A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4+ T cell receptor repertoire clonality.

    Science.gov (United States)

    Zhu, Wei; Germain, Claire; Liu, Zheng; Sebastian, Yinong; Devi, Priyanka; Knockaert, Samantha; Brohawn, Philip; Lehmann, Kim; Damotte, Diane; Validire, Pierre; Yao, Yihong; Valge-Archer, Viia; Hammond, Scott A; Dieu-Nosjean, Marie-Caroline; Higgs, Brandon W

    2015-12-01

    T and B cell receptor (TCR and BCR, respectively) Vβ or immunoglobulin heavy chain complementarity-determining region 3 sequencing allows monitoring of repertoire changes through recognition, clonal expansion, affinity maturation, and T or B cell activation in response to antigen. TCR and BCR repertoire analysis can advance understanding of antitumor immune responses in the tumor microenvironment. TCR and BCR repertoires of sorted CD4 + , CD8 + or CD19 + cells in tumor, non-tumoral distant tissue (NT), and peripheral compartments (blood/draining lymph node [P]) from 47 non-small cell lung cancer (NSCLC) patients (age median = 68 y) were sequenced. The clonotype spectra were assessed among different tissues and correlated with clinical and immunological parameters. In all tissues, CD4 + and CD8 + TCR repertoires had greater clonality relative to CD19 + BCR. CD4 + T cells exhibited greater clonality in NT compared to tumor ( p = 0.002) and P ( p 68). Younger patients exhibited greater CD4 + T cell diversity in P compared to older patients ( p = 0.05), and greater CD4 + T cell clonality in tumor relative to P ( p cell clonality in tumor and P, respectively (both p = 0.05), correlated with high density of tumor-associated tertiary lymphoid structure (TLS) B cells, a biomarker of higher overall survival in NSCLC. Results indicate distinct adaptive immune responses in NSCLC, where peripheral T cell diversity is modulated by age, and tumor T cell clonal expansion is favored by the presence of TLSs in the tumor microenvironment.

  12. Sequence-Based Discovery Demonstrates That Fixed Light Chain Human Transgenic Rats Produce a Diverse Repertoire of Antigen-Specific Antibodies

    Directory of Open Access Journals (Sweden)

    Katherine E. Harris

    2018-04-01

    Full Text Available We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1. This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest.

  13. Mouse lysozyme-M knockout mice reveal how the self-determinant hierarchy shapes the T cell repertoire against this circulating self antigen in wild-type mice

    NARCIS (Netherlands)

    Sinha, Pratima; Chi, Howard H.; Kim, Hong R.; Clausen, Björn E.; Pederson, Brian; Sercarz, Eli E.; Forster, Irmgard; Moudgil, Kamal D.

    2004-01-01

    We have studied T cell tolerance to defined determinants within ML-M using wild-type (WT; ML-M+/+) and LysMcre (ML-M-/-) C3H (H-2(k)) mice to determine the relative contribution of ML-M-derived epitopes vs those from other self Ags in selection of the ML-M-specific T cell repertoire. ML-M was

  14. Impact of clonal competition for peptide-MHC complexes on the CD8[superscript +] T-cell repertoire selection in a persistent viral infection

    Energy Technology Data Exchange (ETDEWEB)

    Wynn, Katherine K.; Fulton, Zara; Cooper, Leanne; Silins, Sharon L.; Gras, Stephanie; Archbold, Julia K.; Tynan, Fleur E.; Miles, John J.; McCluskey, James; Burrows, Scott R.; Rossjohn, Jamie; Khanna, Rajiv (Monash); (Queensland Inst. of Med. Rsrch.); (Melbourne)

    2008-04-29

    CD8{sup +} T-cell responses to persistent viral infections are characterized by the accumulation of an oligoclonal T-cell repertoire and a reduction in the naive T-cell pool. However, the precise mechanism for this phenomenon remains elusive. Here we show that human cytomegalovirus (HCMV)-specific CD8{sup +} T cells recognizing distinct epitopes from the pp65 protein and restricted through an identical HLA class I allele (HLA B*3508) exhibited either a highly conserved public T-cell repertoire or a private, diverse T-cell response, which was uniquely altered in each donor following in vitro antigen exposure. Selection of a public T-cell receptor (TCR) was coincident with an atypical major histocompatibility complex (MHC)-peptide structure, in that the epitope adopted a helical conformation that bulged from the peptide-binding groove, while a diverse TCR profile was observed in response to the epitope that formed a flatter, more 'featureless' landscape. Clonotypes with biased TCR usage demonstrated more efficient recognition of virus-infected cells, a greater CD8 dependency, and were more terminally differentiated in their phenotype when compared with the T cells expressing diverse TCR. These findings provide new insights into our understanding on how the biology of antigen presentation in addition to the structural features of the pMHC-I might shape the T-cell repertoire and its phenotype.

  15. Genetic GIScience

    DEFF Research Database (Denmark)

    Jacquez, Geoffrey; Sabel, Clive E; Shi, Chen

    2015-01-01

    The exposome, defined as the totality of an individual's exposures over the life course, is a seminal concept in the environmental health sciences. Although inherently geographic, the exposome as yet is unfamiliar to many geographers. This article proposes a place-based synthesis, genetic...... geographic information science (genetic GIScience), that is founded on the exposome, genome+, and behavome. It provides an improved understanding of human health in relation to biology (the genome+), environmental exposures (the exposome), and their social, societal, and behavioral determinants (the behavome......). Genetic GIScience poses three key needs: first, a mathematical foundation for emergent theory; second, process-based models that bridge biological and geographic scales; third, biologically plausible estimates of space?time disease lags. Compartmental models are a possible solution; this article develops...

  16. Desktop Genetics.

    Science.gov (United States)

    Hough, Soren H; Ajetunmobi, Ayokunmi; Brody, Leigh; Humphryes-Kirilov, Neil; Perello, Edward

    2016-11-01

    Desktop Genetics is a bioinformatics company building a gene-editing platform for personalized medicine. The company works with scientists around the world to design and execute state-of-the-art clustered regularly interspaced short palindromic repeats (CRISPR) experiments. Desktop Genetics feeds the lessons learned about experimental intent, single-guide RNA design and data from international genomics projects into a novel CRISPR artificial intelligence system. We believe that machine learning techniques can transform this information into a cognitive therapeutic development tool that will revolutionize medicine.

  17. Genetic programming theory and practice XII

    CERN Document Server

    Riolo, Rick; Kotanchek, Mark

    2015-01-01

    These contributions, written by the foremost international researchers and practitioners of Genetic Programming (GP), explore the synergy between theoretical and empirical results on real-world problems, producing a comprehensive view of the state of the art in GP. Topics in this volume include: gene expression regulation, novel genetic models for glaucoma, inheritable epigenetics, combinators in genetic programming, sequential symbolic regression, system dynamics, sliding window symbolic regression, large feature problems, alignment in the error space, HUMIE winners, Boolean multiplexer funct

  18. Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection.

    Science.gov (United States)

    Coutinho, A; Caramalho, I; Seixas, E; Demengeot, J

    2005-01-01

    The seminal work of Le Douarin and colleagues (Ohki et al. 1987; Ohki et al. 1988; Salaun et al. 1990; Coutinho et al. 1993) first demonstrated that peripheral tissue-specific tolerance is centrally established in the thymus, by epithelial stromal cells (TEC). Subsequent experiments have shown that TEC-tolerance is dominant and mediated by CD4 regulatory T cells (Treg) that are generated intrathymically by recognition of antigens expressed on TECs (Modigliani et al. 1995; Modigliani et al. 1996a). From these and other observations, in 1996 Modigliani and colleagues derived a general model for the establishment and maintenance of natural tolerance (MM96) (Modigliani et al. 1996b), with two central propositions: (1) T cell receptor (TCR)-dependent sorting of emergent repertoires generates TEC-specific Treg displaying the highest TCR self-affinities below deletion thresholds, thus isolating repertoires undergoing positive and negative selection; (2) Treg are intrathymically committed (and activated) for a unique differentiative pathway with regulatory effector functions. The model explained the embryonic/perinatal time window of natural tolerance acquisition, by developmental programs determining (1) TCR multireactivity, (2) the cellular composition in the thymic stroma (relative abundance of epithelial vs hemopoietic cells), and (3) the dynamics of peripheral lymphocyte pools, built by accumulation of recent thymic emigrants (RTE) that remain recruitable to regulatory functions. We discuss here the MM96 in the light of recent results demonstrating the promiscuous expression of tissue-specific antigens by medullary TECs (Derbinski et al. 2001; Anderson et al. 2002; Gotter et al. 2004) and indicating that Treg represent a unique differentiative pathway (Fontenot et al. 2003; Hori et al. 2003; Khattri et al. 2003), which is adopted by CD4 T cells with high avidity for TEC-antigens (Bensinger et al. 2001; Jordan et al. 2001; Apostolou et al. 2002). In the likelihood that

  19. Selfish genetic elements, genetic conflict, and evolutionary innovation.

    Science.gov (United States)

    Werren, John H

    2011-06-28

    Genomes are vulnerable to selfish genetic elements (SGEs), which enhance their own transmission relative to the rest of an individual's genome but are neutral or harmful to the individual as a whole. As a result, genetic conflict occurs between SGEs and other genetic elements in the genome. There is growing evidence that SGEs, and the resulting genetic conflict, are an important motor for evolutionary change and innovation. In this review, the kinds of SGEs and their evolutionary consequences are described, including how these elements shape basic biological features, such as genome structure and gene regulation, evolution of new genes, origin of new species, and mechanisms of sex determination and development. The dynamics of SGEs are also considered, including possible "evolutionary functions" of SGEs.

  20. Spectratyping analysis of the islet-reactive T cell repertoire in diabetic NOD Igμnull mice after polyclonal B cell reconstitution

    Directory of Open Access Journals (Sweden)

    Sercarz Eli E

    2011-07-01

    Full Text Available Abstract Background Non Obese Diabetic mice lacking B cells (NOD.Igμnull mice do not develop diabetes despite their susceptible background. Upon reconstitution of B cells using a chimera approach, animals start developing diabetes at 20 weeks of age. Methods We have used the spectratyping technique to follow the T cell receptor (TCR V beta repertoire of NOD.Igμnull mice following B cell reconstitution. This technique provides an unbiased approach to understand the kinetics of TCR expansion. We have also analyzed the TCR repertoire of reconstituted animals receiving cyclophosphamide treatment and following tissue transplants to identify common aggressive clonotypes. Results We found that B cell reconstitution of NOD.Igμnull mice induces a polyclonal TCR repertoire in the pancreas 10 weeks later, gradually diversifying to encompass most BV families. Interestingly, these clonotypic BV expansions are mainly confined to the pancreas and are absent from pancreatic lymph nodes or spleens. Cyclophosphamide-induced diabetes at 10 weeks post-B cell reconstitution reorganized the predominant TCR repertoires by removing potential regulatory clonotypes (BV1, BV8 and BV11 and increasing the frequency of others (BV4, BV5S2, BV9, BV16-20. These same clonotypes are more frequently present in neonatal pancreatic transplants under the kidney capsule of B-cell reconstituted diabetic NOD.Igμnull mice, suggesting their higher invasiveness. Phenotypic analysis of the pancreas-infiltrating lymphocytes during diabetes onset in B cell reconstituted animals show a predominance of CD19+ B cells with a B:T lymphocyte ratio of 4:1. In contrast, in other lymphoid organs (pancreatic lymph nodes and spleens analyzed by FACS, the B:T ratio was 1:1. Lymphocytes infiltrating the pancreas secrete large amounts of IL-6 and are of Th1 phenotype after CD3-CD28 stimulation in vitro. Conclusions Diabetes in NOD.Igμnull mice appears to be caused by a polyclonal repertoire of T cell

  1. On the Origin of Reverse Transcriptase-Using CRISPR-Cas Systems and Their Hyperdiverse, Enigmatic Spacer Repertoires

    Directory of Open Access Journals (Sweden)

    Sukrit Silas

    2017-07-01

    Full Text Available Cas1 integrase is the key enzyme of the clustered regularly interspaced short palindromic repeat (CRISPR-Cas adaptation module that mediates acquisition of spacers derived from foreign DNA by CRISPR arrays. In diverse bacteria, the cas1 gene is fused (or adjacent to a gene encoding a reverse transcriptase (RT related to group II intron RTs. An RT-Cas1 fusion protein has been recently shown to enable acquisition of CRISPR spacers from RNA. Phylogenetic analysis of the CRISPR-associated RTs demonstrates monophyly of the RT-Cas1 fusion, and coevolution of the RT and Cas1 domains. Nearly all such RTs are present within type III CRISPR-Cas loci, but their phylogeny does not parallel the CRISPR-Cas type classification, indicating that RT-Cas1 is an autonomous functional module that is disseminated by horizontal gene transfer and can function with diverse type III systems. To compare the sequence pools sampled by RT-Cas1-associated and RT-lacking CRISPR-Cas systems, we obtained samples of a commercially grown cyanobacterium—Arthrospira platensis. Sequencing of the CRISPR arrays uncovered a highly diverse population of spacers. Spacer diversity was particularly striking for the RT-Cas1-containing type III-B system, where no saturation was evident even with millions of sequences analyzed. In contrast, analysis of the RT-lacking type III-D system yielded a highly diverse pool but reached a point where fewer novel spacers were recovered as sequencing depth was increased. Matches could be identified for a small fraction of the non-RT-Cas1-associated spacers, and for only a single RT-Cas1-associated spacer. Thus, the principal source(s of the spacers, particularly the hypervariable spacer repertoire of the RT-associated arrays, remains unknown.

  2. Characterization of the repertoire diversity of the Plasmodium falciparum stevor multigene family in laboratory and field isolates

    Directory of Open Access Journals (Sweden)

    Holder Anthony A

    2009-06-01

    Full Text Available Abstract Background The evasion of host immune response by the human malaria parasite Plasmodium falciparum has been linked to expression of a range of variable antigens on the infected erythrocyte surface. Several genes are potentially involved in this process with the var, rif and stevor multigene families being the most likely candidates and coding for rapidly evolving proteins. The high sequence diversity of proteins encoded by these gene families may have evolved as an immune evasion strategy that enables the parasite to establish long lasting chronic infections. Previous findings have shown that the hypervariable region (HVR of STEVOR has significant sequence diversity both within as well as across different P. falciparum lines. However, these studies did not address whether or not there are ancestral stevor that can be found in different parasites. Methods DNA and RNA sequences analysis as well as phylogenetic approaches were used to analyse the stevor sequence repertoire and diversity in laboratory lines and Kilifi (Kenya fresh isolates. Results Conserved stevor genes were identified in different P. falciparum isolates from different global locations. Consistent with previous studies, the HVR of the stevor gene family was found to be highly divergent both within and between isolates. Importantly phylogenetic analysis shows some clustering of stevor sequences both within a single parasite clone as well as across different parasite isolates. Conclusion This indicates that the ancestral P. falciparum parasite genome already contained multiple stevor genes that have subsequently diversified further within the different P. falciparum populations. It also confirms that STEVOR is under strong selection pressure.

  3. Repertoire of bovine miRNA and miRNA-like small regulatory RNAs expressed upon viral infection.

    Directory of Open Access Journals (Sweden)

    Evgeny A Glazov

    Full Text Available MicroRNA (miRNA and other types of small regulatory RNAs play a crucial role in the regulation of gene expression in eukaryotes. Several distinct classes of small regulatory RNAs have been discovered in recent years. To extend the repertoire of small RNAs characterized in mammals and to examine relationship between host miRNA expression and viral infection we used Illumina's ultrahigh throughput sequencing approach. We sequenced three small RNA libraries prepared from cell line derived from the adult bovine kidney under normal conditions and upon infection of the cell line with Bovine herpesvirus 1. We used a bioinformatics approach to distinguish authentic mature miRNA sequences from other classes of small RNAs and short RNA fragments represented in the sequencing data. Using this approach we detected 219 out of 356 known bovine miRNAs and 115 respective miRNA* sequences. In addition we identified five new bovine orthologs of known mammalian miRNAs and discovered 268 new cow miRNAs many of which are not identifiable in other mammalian genomes and thus might be specific to the ruminant lineage. In addition we found seven new bovine mirtron candidates. We also discovered 10 small nucleolar RNA (snoRNA loci that give rise to small RNA with possible miRNA-like function. Results presented in this study extend our knowledge of the biology and evolution of small regulatory RNAs in mammals and illuminate mechanisms of small RNA biogenesis and function. New miRNA sequences and the original sequencing data have been submitted to miRNA repository (miRBase and NCBI GEO archive respectively. We envisage that these resources will facilitate functional annotation of the bovine genome and promote further functional and comparative genomics studies of small regulatory RNA in mammals.

  4. T cell receptor sequencing of early-stage breast cancer tumors identifies altered clonal structure of the T cell repertoire.

    Science.gov (United States)

    Beausang, John F; Wheeler, Amanda J; Chan, Natalie H; Hanft, Violet R; Dirbas, Frederick M; Jeffrey, Stefanie S; Quake, Stephen R

    2017-11-28

    Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T cell beta-chain repertoire in 16 patients with early-stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing ∼2.5-fold greater density of T cells and higher clonality compared with normal breast. The clonal structure of T cells in blood and normal breast is more similar than between blood and tumor, and could be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T cell sequences overlap between tissue and blood from the same patient, including ∼50% of T cells between tumor and normal breast. Both tumor and normal breast contain high-abundance "enriched" sequences that are absent or of low abundance in the other tissue. Many of these T cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T cells in both tumor and normal breast. Enriched T cell sequences are typically unique to each patient, but a subset is shared between many different patients. We show that many of these are commonly generated sequences, and thus unlikely to play an important role in the tumor microenvironment. Copyright © 2017 the Author(s). Published by PNAS.

  5. Ancestral and derived attributes of the dlx gene repertoire, cluster structure and expression patterns in an African cichlid fish

    Directory of Open Access Journals (Sweden)

    Renz Adina J

    2011-01-01

    Full Text Available Abstract Background Cichlid fishes have undergone rapid, expansive evolutionary radiations that are manifested in the diversification of their trophic morphologies, tooth patterning and coloration. Understanding the molecular mechanisms that underlie the cichlids' unique patterns of evolution requires a thorough examination of genes that pattern the neural crest, from which these diverse phenotypes are derived. Among those genes, the homeobox-containing Dlx gene family is of particular interest since it is involved in the patterning of the brain, jaws and teeth. Results In this study, we characterized the dlx genes of an African cichlid fish, Astatotilapia burtoni, to provide a baseline to later allow cross-species comparison within Cichlidae. We identified seven dlx paralogs (dlx1a, -2a, -4a, -3b, -4b, -5a and -6a, whose orthologies were validated with molecular phylogenetic trees. The intergenic regions of three dlx gene clusters (dlx1a-2a, dlx3b-4b, and dlx5a-6a were amplified with long PCR. Intensive cross-species comparison revealed a number of conserved non-coding elements (CNEs that are shared with other percomorph fishes. This analysis highlighted additional lineage-specific gains/losses of CNEs in different teleost fish lineages and a novel CNE that had previously not been identified. Our gene expression analyses revealed overlapping but distinct expression of dlx orthologs in the developing brain and pharyngeal arches. Notably, four of the seven A. burtoni dlx genes, dlx2a, dlx3b, dlx4a and dlx5a, were expressed in the developing pharyngeal teeth. Conclusion This comparative study of the dlx genes of A. burtoni has deepened our knowledge of the diversity of the Dlx gene family, in terms of gene repertoire, expression patterns and non-coding elements. We have identified possible cichlid lineage-specific changes, including losses of a subset of dlx expression domains in the pharyngeal teeth, which will be the targets of future functional

  6. The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea

    Directory of Open Access Journals (Sweden)

    Zamanian Mostafa

    2011-12-01

    Full Text Available Abstract Background G protein-coupled receptors (GPCRs constitute one of the largest groupings of eukaryotic proteins, and represent a particularly lucrative set of pharmaceutical targets. They play an important role in eukaryotic signal transduction and physiology, mediating cellular responses to a diverse range of extracellular stimuli. The phylum Platyhelminthes is of considerable medical and biological importance, housing major pathogens as well as established model organisms. The recent availability of genomic data for the human blood fluke Schistosoma mansoni and the model planarian Schmidtea mediterranea paves the way for the first comprehensive effort to identify and analyze GPCRs in this important phylum. Results Application of a novel transmembrane-oriented approach to receptor mining led to the discovery of 117 S. mansoni GPCRs, representing all of the major families; 105 Rhodopsin, 2 Glutamate, 3 Adhesion, 2 Secretin and 5 Frizzled. Similarly, 418 Rhodopsin, 9 Glutamate, 21 Adhesion, 1 Secretin and 11 Frizzled S. mediterranea receptors were identified. Among these, we report the identification of novel receptor groupings, including a large and highly-diverged Platyhelminth-specific Rhodopsin subfamily, a planarian-specific Adhesion-like family, and atypical Glutamate-like receptors. Phylogenetic analysis was carried out following extensive gene curation. Support vector machines (SVMs were trained and used for ligand-based classification of full-length Rhodopsin GPCRs, complementing phylogenetic and homology-based classification. Conclusions Genome-wide investigation of GPCRs in two platyhelminth genomes reveals an extensive and complex receptor signaling repertoire with many unique features. This work provides important sequence and functional leads for understanding basic flatworm receptor biology, and sheds light on a lucrative set of anthelmintic drug targets.

  7. New Genetics

    Science.gov (United States)

    ... of the booklet. » more Chapter 1: How Genes Work Covers DNA, RNA, transcription, RNA splicing, translation, ribosomes, antibiotics, genetic diseases, gene chips. » more Chapter 2: RNA and DNA Revealed: New Roles, New Rules Covers microRNAs, RNAi, epigenetics, telomeres, mtDNA, recombinant DNA. » ...

  8. Genetic effects

    International Nuclear Information System (INIS)

    Kato, Hiroo

    1975-01-01

    In 1948-1953 a large scale field survey was conducted to investigate the possible genetic effects of A-bomb radiation on over 70,000 pregnancy terminations in the cities of Hiroshima and Nagasaki. The indices of possible genetic effect including sex ratio, birth weight, frequency of malformation, stillbirth, neonatal death, deaths within 9 months and anthropometric measurements at 9 months of age for these children were investigated in relation to their parent's exposure status to the A-bomb. There were no detectable genetic effects in this sample, except for a slight change in sex ratio which was in the direction to be expected if exposure had induced sex-linked lethal mutations. However, continued study of the sex ratio, based upon birth certificates in Hiroshima and Nagasaki for 1954-1962, did not confirm the earlier trend. Mortality in these children of A-bomb survivors is being followed using a cohort of 54,000 subjects. No clearly significant effect of parental exposure on survival of the children has been demonstrated up to 1972 (age 17 on the average). On the basis of the regression data, the minimal genetic doubling dose of this type of radiation for mutations resulting in death is estimated at 46 rem for the father and 125 rem for the mother. (auth.)

  9. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  10. Genetic Recombination

    Science.gov (United States)

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  11. Genetic analysis

    NARCIS (Netherlands)

    Koornneef, M.; Alonso-Blanco, C.; Stam, P.

    2006-01-01

    The Mendelian analysis of genetic variation, available as induced mutants or as natural variation, requires a number of steps that are described in this chapter. These include the determination of the number of genes involved in the observed trait's variation, the determination of dominance

  12. Molecular genetics

    International Nuclear Information System (INIS)

    Parkinson, D.R.; Krontiris, T.G.

    1986-01-01

    In this chapter the authors review new findings concerning the molecular genetics of malignant melanoma in the context of other information obtained from clinical, epidemiologic, and cytogenetic studies in this malignancy. These new molecular approaches promise to provide a more complete understanding of the mechanisms involved in the development of melanoma, thereby suggesting new methods for its treatment and prevention

  13. J. Genet. classic 235

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 83, No. 3, December 2004. 235. Page 2. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 236. Page 3. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 237. Page 4. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 238. Page 5 ...

  14. Genetic effects

    International Nuclear Information System (INIS)

    Bender, M.A.; Abrahamson, S.; Denniston, C.; Schull, W.J.

    1989-01-01

    In this chapter, we present a comprehensive analysis of the major classes of genetic diseases that would be increased as a result of an increased gonadal radiation exposure to a human population. The risk analysis takes on two major forms: the increase in genetic disease that would be observed in the immediate offspring of the exposed population, and the subsequent transmission of the newly induced mutations through future generations. The major classes of genetic disease will be induced at different frequencies, and will also impact differentially in terms of survivability and fertility on the affected individuals and their descendants. Some classes of disease will be expected to persist for only a few generations at most. Other types of genetic disease will persist through a longer period. The classes of genetic diseases studied are: dominant gene mutation, X-linked gene mutation, chromosome disorders and multifactorial disorders which involve the interaction of many mutant genes and environmental factors. For each of these classes we have derived the general equations of mutation induction for the male and female germ cells of critical importance in the mutation process. The frequency of induced mutations will be determined initially by the dose received, the type of radiation and, to some extent at high dose, by the manner in which the dose is received. We have used the modeling analyses to predict the outcomes for two nuclear power plant accident scenarios, the first in which the population receives a chronic dose of 0.1 Gy (10 rad) over a 50-year period, the second in which an equivalent population receives an acute dose of 2 Gy. In both cases the analyses are projected over a period of five generations

  15. Genetic variations in the dynamics of dry matter accumulation, nitrogen assimilation and translocation in new T. aestivum L. varieties. I. Dynamics of dry matter accumulation. Grain yield and structural elements of yield

    International Nuclear Information System (INIS)

    Kostadin, K.; Nonkova, M.; Penchev, E.

    1999-01-01

    The genotype peculiarities in the translocation dynamics of dry matter in relation to wheat yield were studied under vegetation-laboratory and field conditions. The new wheat varieties Enola, Karat and Svilena created at the Institute for Wheat and Sunflower 'Dobroudja' have a high production potential due to their high intensity of dry matter accumulation in grain during the second half of maturation. It was established that in the standard variety Pliska the intensity of dry matter accumulation in reproductive parts was higher during heading-grain filling and then sharply decreased during maturation. This variety was characterized with high translocation of vegetation mass eventually leading to grain yield decrease. Significant genotype variations were established in the vegetation mass translocation in the respective parts during the stages of development. The contribution of the individual organs concerning carbohydrate reutilization to grain was mainly due to stems. An especially important peculiarity of the leaves of cv. Svilena was established: they ensured over 30 of grain yield at optimal nutrition. The complex evaluation of the new varieties revealed their high plasticity, the cultivar Karat showing the best characteristics. Refs. 13 (author)

  16. Genetically programmed chiral organoborane synthesis

    Science.gov (United States)

    Kan, S. B. Jennifer; Huang, Xiongyi; Gumulya, Yosephine; Chen, Kai; Arnold, Frances H.

    2017-12-01

    Recent advances in enzyme engineering and design have expanded nature’s catalytic repertoire to functions that are new to biology. However, only a subset of these engineered enzymes can function in living systems. Finding enzymatic pathways that form chemical bonds that are not found in biology is particularly difficult in the cellular environment, as this depends on the discovery not only of new enzyme activities, but also of reagents that are both sufficiently reactive for the desired transformation and stable in vivo. Here we report the discovery, evolution and generalization of a fully genetically encoded platform for producing chiral organoboranes in bacteria. Escherichia coli cells harbouring wild-type cytochrome c from Rhodothermus marinus (Rma cyt c) were found to form carbon-boron bonds in the presence of borane-Lewis base complexes, through carbene insertion into boron-hydrogen bonds. Directed evolution of Rma cyt c in the bacterial catalyst provided access to 16 novel chiral organoboranes. The catalyst is suitable for gram-scale biosynthesis, providing up to 15,300 turnovers, a turnover frequency of 6,100 h-1, a 99:1 enantiomeric ratio and 100% chemoselectivity. The enantiopreference of the biocatalyst could also be tuned to provide either enantiomer of the organoborane products. Evolved in the context of whole-cell catalysts, the proteins were more active in the whole-cell system than in purified forms. This study establishes a DNA-encoded and readily engineered bacterial platform for borylation; engineering can be accomplished at a pace that rivals the development of chemical synthetic methods, with the ability to achieve turnovers that are two orders of magnitude (over 400-fold) greater than those of known chiral catalysts for the same class of transformation. This tunable method for manipulating boron in cells could expand the scope of boron chemistry in living systems.

  17. Trust repertoires for collaboration

    DEFF Research Database (Denmark)

    Fuglsang, Lars

    This case study analyses the role of trust in a public private innovation network that involved a private consultancy company as a facilitator. We know that collaboration is a important for innovation, and that collaboration across organizational boundaries is not a trivial issue. But we know very...... little about how such processes develop and how trust, understood as “confident positive expectations” (Lewicki et al. 1998) to collaborative activities, arises out of collaboration. The paper contributes by showing how trust and collaboration are intertwined. The main finding is that a facilitator can...

  18. Genetic effects

    International Nuclear Information System (INIS)

    Abrahamson, S.; Bender, M.; Denniston, C.; Schull, W.

    1985-01-01

    Modeling analyses are used to predict the outcomes for two nuclear power plant accident scenarios, the first in which the population received a chronic dose of 0.1 Gy (10 rad) over a 50 year period, the second in which an equivalent population receives acute dose of 2 Gy. In both cases the analyses are projected over a period of five generations. The risk analysis takes on two major forms: the increase in genetic disease that would be observed in the immediate offspring of the exposed population, and the subsequent transmission of the newly induced mutations through future generations. The classes of genetic diseases studied are: dominant gene mutation, X-linked gene mutation, chromosome disorders and multifactorial disorders which involve the interaction of many mutant genes and environmental factors. 28 references, 3 figures, 5 tables

  19. Supernatural T cells: genetic modification of T cells for cancer therapy.

    Science.gov (United States)

    Kershaw, Michael H; Teng, Michele W L; Smyth, Mark J; Darcy, Phillip K

    2005-12-01

    Immunotherapy is receiving much attention as a means of treating cancer, but complete, durable responses remain rare for most malignancies. The natural immune system seems to have limitations and deficiencies that might affect its ability to control malignant disease. An alternative to relying on endogenous components in the immune repertoire is to generate lymphocytes with abilities that are greater than those of natural T cells, through genetic modification to produce 'supernatural' T cells. This Review describes how such T cells can circumvent many of the barriers that are inherent in the tumour microenvironment while optimizing T-cell specificity, activation, homing and antitumour function.

  20. Cancer Genetics Services Directory

    Science.gov (United States)

    ... Services Directory Cancer Prevention Overview Research NCI Cancer Genetics Services Directory This directory lists professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, ...

  1. A predictive model of muscle excitations based on muscle modularity for a large repertoire of human locomotion conditions

    Directory of Open Access Journals (Sweden)

    Jose eGonzalez-Vargas

    2015-09-01

    Full Text Available Humans can efficiently walk across a large variety of terrains and locomotion conditions with little or no mental effort. It has been hypothesized that the nervous system simplifies neuromuscular control by using muscle synergies, thus organizing multi-muscle activity into a small number of coordinative co-activation modules. In the present study we investigated how muscle modularity is structured across a large repertoire of locomotion conditions including five different speeds and five different ground elevations. For this we have used the non-negative matrix factorization technique in order to explain EMG experimental data with a low-dimensional set of four motor components. In this context each motor components is composed of a non-negative factor and the associated muscle weightings. Furthermore, we have investigated if the proposed descriptive analysis of muscle modularity could be translated into a predictive model that could: 1 Estimate how motor components modulate across locomotion speeds and ground elevations. This implies not only estimating the non-negative factors temporal characteristics, but also the associated muscle weighting variations. 2 Estimate how the resulting muscle excitations modulate across novel locomotion conditions and subjects.The results showed three major distinctive features of muscle modularity: 1 the number of motor components was preserved across all locomotion conditions, 2 the non-negative factors were consistent in shape and timing across all locomotion conditions, and 3 the muscle weightings were modulated as distinctive functions of locomotion speed and ground elevation. Results also showed that the developed predictive model was able to reproduce well the muscle modularity of un-modeled data, i.e. novel subjects and conditions. Muscle weightings were reconstructed with a cross-correlation factor greater than 70% and a root mean square error less than 0.10. Furthermore, the generated muscle excitations

  2. Molecular fingerprinting of complex grass allergoids: size assessments reveal new insights in epitope repertoires and functional capacities.

    Science.gov (United States)

    Starchenka, S; Bell, A J; Mwange, J; Skinner, M A; Heath, M D

    2017-01-01

    that modification allows shorter-course therapy options as a result of providing an IgG epitope repertoire important for efficacy. Additionally, the work paves the way to help further develop methods for standardising allergoid platforms.

  3. Complex Genetics of Behavior: BXDs in the Automated Home-Cage.

    Science.gov (United States)

    Loos, Maarten; Verhage, Matthijs; Spijker, Sabine; Smit, August B

    2017-01-01

    This chapter describes a use case for the genetic dissection and automated analysis of complex behavioral traits using the genetically diverse panel of BXD mouse recombinant inbred strains. Strains of the BXD resource differ widely in terms of gene and protein expression in the brain, as well as in their behavioral repertoire. A large mouse resource opens the possibility for gene finding studies underlying distinct behavioral phenotypes, however, such a resource poses a challenge in behavioral phenotyping. To address the specifics of large-scale screening we describe how to investigate: (1) how to assess mouse behavior systematically in addressing a large genetic cohort, (2) how to dissect automation-derived longitudinal mouse behavior into quantitative parameters, and (3) how to map these quantitative traits to the genome, deriving loci underlying aspects of behavior.

  4. Next-Generation DNA Sequencing of VH/VL Repertoires: A Primer and Guide to Applications in Single-Domain Antibody Discovery.

    Science.gov (United States)

    Henry, Kevin A

    2018-01-01

    Immunogenetic analyses of expressed antibody repertoires are becoming increasingly common experimental investigations and are critical to furthering our understanding of autoimmunity, infectious disease, and cancer. Next-generation DNA sequencing (NGS) technologies have now made it possible to interrogate antibody repertoires to unprecedented depths, typically by sequencing of cDNAs encoding immunoglobulin variable domains. In this chapter, we describe simple, fast, and reliable methods for producing and sequencing multiplex PCR amplicons derived from the variable regions (V H , V H H or V L ) of rearranged immunoglobulin heavy and light chain genes using the Illumina MiSeq platform. We include complete protocols and primer sets for amplicon sequencing of V H /V H H/V L repertoires directly from human, mouse, and llama lymphocytes as well as from phage-displayed V H /V H H/V L libraries; these can be easily be adapted to other types of amplicons with little modification. The resulting amplicons are diverse and representative, even using as few as 10 3 input B cells, and their generation is relatively inexpensive, requiring no special equipment and only a limited set of primers. In the absence of heavy-light chain pairing, single-domain antibodies are uniquely amenable to NGS analyses. We present a number of applications of NGS technology useful in discovery of single-domain antibodies from phage display libraries, including: (i) assessment of library functionality; (ii) confirmation of desired library randomization; (iii) estimation of library diversity; and (iv) monitoring the progress of panning experiments. While the case studies presented here are of phage-displayed single-domain antibody libraries, the principles extend to other types of in vitro display libraries.

  5. Genomes of the most dangerous epidemic bacteria have a virulence repertoire characterized by fewer genes but more toxin-antitoxin modules.

    Directory of Open Access Journals (Sweden)

    Kalliopi Georgiades

    2011-03-01

    Full Text Available We conducted a comparative genomic study based on a neutral approach to identify genome specificities associated with the virulence capacity of pathogenic bacteria. We also determined whether virulence is dictated by rules, or if it is the result of individual evolutionary histories. We systematically compared the genomes of the 12 most dangerous pandemic bacteria for humans ("bad bugs" to their closest non-epidemic related species ("controls".We found several significantly different features in the "bad bugs", one of which was a smaller genome that likely resulted from a degraded recombination and repair system. The 10 Cluster of Orthologous Group (COG functional categories revealed a significantly smaller number of genes in the "bad bugs", which lacked mostly transcription, signal transduction mechanisms, cell motility, energy production and conversion, and metabolic and regulatory functions. A few genes were identified as virulence factors, including secretion system proteins. Five "bad bugs" showed a greater number of poly (A tails compared to the controls, whereas an elevated number of poly (A tails was found to be strongly correlated to a low GC% content. The "bad bugs" had fewer tandem repeat sequences compared to controls. Moreover, the results obtained from a principal component analysis (PCA showed that the "bad bugs" had surprisingly more toxin-antitoxin modules than did the controls.We conclude that pathogenic capacity is not the result of "virulence factors" but is the outcome of a virulent gene repertoire resulting from reduced genome repertoires. Toxin-antitoxin systems could participate in the virulence repertoire, but they may have developed independently of selfish evolution.

  6. Antigenic Fingerprinting following Primary RSV Infection in Young Children Identifies Novel Antigenic Sites and Reveals Unlinked Evolution of Human Antibody Repertoires to Fusion and Attachment Glycoproteins.

    Directory of Open Access Journals (Sweden)

    Sandra Fuentes

    2016-04-01

    Full Text Available Respiratory Syncytial Virus (RSV is the major cause of pneumonia among infants. Here we elucidated the antibody repertoire following primary RSV infection and traced its evolution through adolescence and adulthood. Whole genome-fragment phage display libraries (GFPDL expressing linear and conformational epitopes in the RSV fusion protein (F and attachment protein (G were used for unbiased epitope profiling of infant sera prior to and following RSV infection. F-GFPDL analyses demonstrated modest changes in the anti-F epitope repertoires post-RSV infection, while G-GFPDL analyses revealed 100-fold increase in number of bound phages. The G-reactive epitopes spanned the N- and C-terminus of the G ectodomain, along with increased reactivity to the central conserved domain (CCD. Panels of F and G antigenic sites were synthesized to evaluate sera from young children (<2 yr, adolescents (14-18 yr and adults (30-45 yr in SPR real-time kinetics assays. A steady increase in RSV-F epitope repertoires from young children to adults was observed using peptides and F proteins. Importantly, several novel epitopes were identified in pre-fusion F and an immunodominant epitope in the F-p27. In all age groups, antibody binding to pre-fusion F was 2-3 folds higher than to post-fusion form. For RSV-G, antibody responses were high following early RSV infection in children, but declined significantly in adults, using either G proteins or peptides. This study identified unlinked evolution of anti-F and anti G responses and supportive evidence for immune pressure driven evolution of RSV-G. These findings could help development of effective countermeasures including vaccines.

  7. Local Chromatin Features Including PU.1 and IKAROS Binding and H3K4 Methylation Shape the Repertoire of Immunoglobulin Kappa Genes Chosen for V(DJ Recombination

    Directory of Open Access Journals (Sweden)

    Louise S. Matheson

    2017-11-01

    Full Text Available V(DJ recombination is essential for the generation of diverse antigen receptor (AgR repertoires. In B cells, immunoglobulin kappa (Igκ light chain recombination follows immunoglobulin heavy chain (Igh recombination. We recently developed the DNA-based VDJ-seq assay for the unbiased quantitation of Igh VH and DH repertoires. Integration of VDJ-seq data with genome-wide datasets revealed that two chromatin states at the recombination signal sequence (RSS of VH genes are highly predictive of recombination in mouse pro-B cells. It is unknown whether local chromatin states contribute to Vκ gene choice during Igκ recombination. Here we adapt VDJ-seq to profile the Igκ VκJκ repertoire and present a comprehensive readout in mouse pre-B cells, revealing highly variable Vκ gene usage. Integration with genome-wide datasets for histone modifications, DNase hypersensitivity, transcription factor binding and germline transcription identified PU.1 binding at the RSS, which was unimportant for Igh, as highly predictive of whether a Vκ gene will recombine or not, suggesting that it plays a binary, all-or-nothing role, priming genes for recombination. Thereafter, the frequency with which these genes recombine was shaped both by the presence and level of enrichment of several other chromatin features, including H3K4 methylation and IKAROS binding. Moreover, in contrast to the Igh locus, the chromatin landscape of the promoter, as well as of the RSS, contributes to Vκ gene recombination. Thus, multiple facets of local chromatin features explain much of the variation in Vκ gene usage. Together, these findings reveal shared and divergent roles for epigenetic features and transcription factors in AgR V(DJ recombination and provide avenues for further investigation of chromatin signatures that may underpin V(DJ-mediated chromosomal translocations.

  8. Implications of recurrent disturbance for genetic diversity.

    Science.gov (United States)

    Davies, Ian D; Cary, Geoffrey J; Landguth, Erin L; Lindenmayer, David B; Banks, Sam C

    2016-02-01

    Exploring interactions between ecological disturbance, species' abundances and community composition provides critical insights for ecological dynamics. While disturbance is also potentially an important driver of landscape genetic patterns, the mechanisms by which these patterns may arise by selective and neutral processes are not well-understood. We used simulation to evaluate the relative importance of disturbance regime components, and their interaction with demographic and dispersal processes, on the distribution of genetic diversity across landscapes. We investigated genetic impacts of variation in key components of disturbance regimes and spatial patterns that are likely to respond to climate change and land management, including disturbance size, frequency, and severity. The influence of disturbance was mediated by dispersal distance and, to a limited extent, by birth rate. Nevertheless, all three disturbance regime components strongly influenced spatial and temporal patterns of genetic diversity within subpopulations, and were associated with changes in genetic structure. Furthermore, disturbance-induced changes in temporal population dynamics and the spatial distribution of populations across the landscape resulted in disrupted isolation by distance patterns among populations. Our results show that forecast changes in disturbance regimes have the potential to cause major changes to the distribution of genetic diversity within and among populations. We highlight likely scenarios under which future changes to disturbance size, severity, or frequency will have the strongest impacts on population genetic patterns. In addition, our results have implications for the inference of biological processes from genetic data, because the effects of dispersal on genetic patterns were strongly mediated by disturbance regimes.

  9. Strategies for interpersonal and public communication in social movements. Transformations in informal networks and repertoires in the era of social Web

    Directory of Open Access Journals (Sweden)

    Rocío Ortiz Galindo

    2016-07-01

    Full Text Available This work aims to advance in the theoretical analysis of the field of communication and social movements. The article studies the new changes that have emerged in the social Web era. We will review some of the principal works of the literature to observe the communicative strategies in these collectives, which are able to influence in the social change. We will differentiate the area of interpersonal communication (the informal networks and the public communication (the repertoires of collective action. We will use this classification to analyze the communicative strategies which have born in the social cybermovements, in the ICT age.

  10. [Genetics of congenital heart diseases].

    Science.gov (United States)

    Bonnet, Damien

    2017-06-01

    Developmental genetics of congenital heart diseases has evolved from analysis of serial slices in embryos towards molecular genetics of cardiac morphogenesis with a dynamic view of cardiac development. Genetics of congenital heart diseases has also changed from formal genetic analysis of familial recurrences or population-based analysis to screening for mutations in candidates genes identified in animal models. Close cooperation between molecular embryologists, pathologists involved in heart development and pediatric cardiologists is crucial for further increase of knowledge in the field of cardiac morphogenesis and genetics of cardiac defects. The genetic model for congenital heart disease has to be revised to favor a polygenic origin rather than a monogenic one. The main mechanism is altered genic dosage that can account for heart diseases in chromosomal anomalies as well as in point mutations in syndromic and isolated congenital heart diseases. The use of big data grouping information from cardiac development, interactions between genes and proteins, epigenetic factors such as chromatin remodeling or DNA methylation is the current source for improving our knowledge in the field and to give clues for future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Colony structure in a plant-ant: behavioural, chemical and genetic study of polydomy in Cataulacus mckeyi (Myrmicinae).

    Science.gov (United States)

    Debout, Gabriel; Provost, Erick; Renucci, Marielle; Tirard, Alain; Schatz, Bertrand; McKey, Doyle

    2003-10-01

    Social organisation of colonies of obligate plant-ants can affect their interaction with myrmecophyte hosts and with other ants competing for the resources they offer. An important parameter of social organisation is whether nest sites of a colony include one or several host individuals. We determined colony boundaries in a plant-ant associated with the rainforest understorey tree Leonardoxa africana subsp. africana, found in coastal forests of Cameroon (Central Africa). This myrmecophyte is strictly associated with two ants, Petalomyrmex phylax and Cataulacus mckeyi. Plants provide food and nesting sites for P. phylax, which protects young leaves against insect herbivores. This mutualism is often parasitised by C. mckeyi, which uses but does not protect the host. The presence of C. mckeyi on a tree excludes the mutualistic ant. Because Petalomyrmex-occupied trees are better protected,